2003 June 30 Monday
C. Elegans Life Extension Genes Identified

A mutation in the gene daf-2 in the worm Caenorhabditis elegans (generallly referred to as C. elegans) doubles life expectancy by turning on a large number of other genes which serve a variety of functions.

Tracing all the genetic changes that flow from a single mutation, UCSF scientists have identified the kinds of genes and systems in the body that ultimately allow a doubling of life span in the roundworm, C. elegans. Humans share many of these genes, and the researchers think the new findings offer clues to increasing human youthfulness and longevity as well.

Using DNA microarray technology, the researchers found that the single life-extending mutation -- a change in the gene known as daf-2 -- exerts its influence through antimicrobial and metabolic genes, through genes controlling the cellular stress response, and by dampening the activity of specific life-shortening genes.

"This study tells us that there are many genes that affect life span, each on its own having only a small effect," said Cynthia Kenyon, PhD, UCSF professor of biochemistry and senior author on a paper in Nature reporting the research.. "The beauty of the daf-2 gene is that it can bring all of these genes together into a common regulatory circuit. This allows it to produce these enormous effects on lifespan." Kenyon is also director of the Hillblom Center for the Biology of Aging at UCSF's Mission Bay campus.

Lead author on the paper is Coleen Murphy, PhD, a postdoctoral scientist in Kenyon's lab.

By partially disabling one gene at a time, either in daf-2 mutants or in wild-type worms, through a technique known as RNA interference, the scientists were able to discover that no single gene by itself determines lifespan. Of the key genes, each can increase life span by 10 to 30 percent, the research shows. But when daf-2 engages the whole army of genes, they can produce huge changes in lifespan.

Because any individual gene appears to have a relatively small effect on life span, identifying the key players would have been difficult in a standard genetic screen, the scientists say, underscoring the power of DNA microarray analysis for teasing apart complex systems.

Kenyon's team discovered ten years ago that a single mutation in the daf-2 gene, which encodes a hormone receptor similar to the human receptors for the hormones insulin and IGF-1, doubled the worms' life span. The same or related hormone pathways have since been shown to affect life span in fruit flies and mice, and therefore are likely to control life span in humans as well. Her lab found that daf-2 affects lifespan through a second gene, known as daf-16, whose function was known to control the expression of other genes.

But the finding left unanswered just how longevity is achieved. What are the genes that daf-16 regulates? The new research shows that several key systems are involved. Many of the genes that affect lifespan code for antioxidant proteins, the researchers found; others code for proteins called chaperones that help repair or degrade damaged proteins. This is especially interesting, Kenyon says, because many diseases of aging involve oxidative damage or protein aggregation.

Other longevity genes found active in the long-lived mutants make proteins that help ward off bacterial infections, the researchers found. Kenyon's lab showed earlier that infections are the likely cause of death for the worm; recent research from others has shown that the long-lived animals are known to be resistant to bacterial infection. The current study shows that without these genes activated, the long-lived worms die sooner. In humans, too, infections pose a serious health problem for the aged.

"Maybe one day we will be able to tweak the insulin/IGF-1 systems in humans to produce many of the same benefits that we see in the worm," Kenyon says.

The scientists also found longevity genes affecting lipid transport and energy metabolism, as well as a host with unknown functions.

"The diversity of these life span gene functions is just remarkable" said Kenyon.

The long-lived worms, as well as mice with similar changes in the same genes, also are disease resistant, and the study suggests possible mechanisms for this finding. The antimicrobial response could protect against infections, and the antioxidant response can protect against diseases that involve oxidative damage. Many researchers suspect stroke and a number of neurological diseases in humans are hastened by oxidative damage.

Earlier this year, Kenyon's lab showed in C. elegans that the damage-repairing chaperone proteins not only increase lifespan, but also delay the onset of protein-aggregation diseases similar to Huntington's disease.

"The marvelous thing about this new study is that it provides an explanation not only for the remarkable longevity of these animals, but also for their ability to stay healthy so long," Kenyon says.

"They just turn up the expression of many, many different genes, each of which helps out in its own way. The consequences are stunning, and if we can figure out a way to copy these effects in humans, we might all be able to live very healthy long lives," she adds.

Co-authors on the Nature paper are Cornelia Bargmann, PhD, professor of anatomy and Howard Hughes Medical Institute investigator at UCSF; Steven McCaroll, a graduate student; Hao Li, PhD, UCSF assistant professor of biochemistry; and Andrew Fraser and Ravi Kamath at the Welcome CRC Institute and Department of Genetics, University of Cambridge.

You might be thinking, if a single mutation in a single gene can increase life expectancy why doesn't this mutation exist naturally? The most likely explanation is that the mutation in daf-2 somehow decreases reproductive fitness. In other words, it exerts some effect that decreases the number of viable offspring that a C. elegans organism will produce in at least some environments.

One reason why upregulation of repair and other systems might be selected against is that there are energy costs and other costs to making and operating enzymes. Just increasing the amount of a particular type enzyme in a cell has the effect of taking up room that would otherwise be used for other enzymes that serve other purposes. A cell that has more repair enzymes floating around in it can do a better job of repairing itself but at the cost of not being able to do some other functions as well.

An organism has to first survive in the short term in order to even be around to grow old in the long term. If a mutation helps short term early life survival enough to allow the organism to reproduce where it otherwise wouldn't have lived long enough to reproduce then that mutation will tend to be selected for. We can see in a large number of design trade-offs in cells that natural selection has acted to put limits to how much of a cell's metabolism is dedicated to dealing with longer term threats.

Research into genetic variations that influence life expectancy is certainly valuable because it produces a better understanding of the aging process and may point the way toward therapies that will slow or, in some cases, even reverse some changes that cause aging. Drugs will eventually be developed that will intervene in gene expression regulatory mechanism to turn up expression of genes for repair, antioxidant, immune, and other systems related to longevity. But keep in mind that there are limits to how much can be accomplished by turning up existing biological subsystems that extend because all of these systems have the effect of only slowing the process of aging. They do not reverse the process of aging.

The really radical anti-aging therapies of the future will use Strategies for Engineered Negligible Senescence (SENS) to rejuvenate cells and whole organisms by repairing and replacing cells and organs that existing human genes do not know how to repair or replace.

By Randall Parker 2003 June 30 05:05 PM  Aging Reversal
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2003 June 29 Sunday
Mandarin Language Uses More Of The Brain Than English

Dr. Sophie Scott of the University College London and colleagues have discovered that English and Mandarin language speakers use their brains in different ways to decode language.

They found that the left temporal lobe, which is located by the left temple, becomes active when English speakers hear English.

...

However, they found that both their left and right temporal lobes become active when they hear Mandarin.

"People who speak different sorts of languages use their brains to decode speech in different ways," said Dr Scott.

Two questions immediately arise in my mind in response to these results:

  • By causing more language processing to take place on the right side of the brain does the use of Mandarin versus English exert subtle effects on how people think about the world?
  • Did the need to speak Mandarin exert any kind of natural selection effect on genes coding for mental characteristics in humans in those areas where it has been spoken for a long time? For instance, did it select for a greater integration between the two halves of the brain in order to be able to process tones and integrate them with the brain's language center?l

People have been arguing for a long time whether the language one speaks is responsible for at least some of the conceptual model which one uses to make sense of the world. I'm reminded of Samuel Delaney's Babel 17 in which a character learns a more precise alien language and by doing so has the way she looks at life altered.

Locked into English, Rydra awakens to a certain reality - she is trapped in a strange restraining web. In desperation she switches in her thoughts to the language Babel-17, which she has partially mastered: "She looked down at the - not 'webbing' but rather a three particle vowel differential, each part of which defined one stress of the three-way tie, so that the weakest points in the mesh were identified when the total sound of the differential reached its lowest point." The perspective afforded by the new language enables her to see the weakness of the webbing: "By breaking the threads at these points, she realized, the whole web would unravel". Switching to another language creates another reality: Rydra is able to free herself."

Now, Delaney's novel is kinda nuts and hard slogging to get thru. If I went back and read it now I'd probably not even like it as much as I did way back when. But while the exact effects that Babel-17 had on the characters in his book may have little in common with the differences caused by thinking in different human languages the idea that the structure of a language has effects on how we think seems a lot more plausble. That two languages can differ so much in their intellectual demands that the effects of hearing them causes a large visible difference in brain scans certainly makes much more plausible the idea that differences between human languages can cause significant differences in cognitive processing.

For example, given that parsing the sounds of Mandarin language into something intelligible causes both sides of the brain to light up does that make it more likely that a Mandarin speaker will access different kinds of memories (textual vs emotional vs visual and so on) from both sides of the brain than a person who interprets spoken language on only one side of the brain? My point here is not to argue that doing so will enhance total cognitive performance. I'm just thinking that something about how people reason about reality (e.g. whether they tend to think spatially or whether they tend to connect melodies to textual memories) will be different if they use both versus one side of the brain to interpret language.

Also, if more of the mind is used to process language then that raises the possibility that less of the mind is available for other purposes. Whatever area of the right temporal lobe that processes language sounds in Mandarin speakers is not available to do whatever that part of the brain tends to do in English speakers. Did this create an extra selective pressure in evolution among Chinese that caused some other part of the brain to be bigger to accomodate the greater need for brain area to do language processing?

By Randall Parker 2003 June 29 11:01 PM  Brain Performance
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Human Stem Cell Growth Signals Save Damaged Rat Neurons

Stem cells isolated from human embryos were injected into rats suffering from neuronal damage caused by a virus. The stem cells helped recover movement by releasing growth factors that helped the damaged neurons to recover.

In their experiments, spearheaded and majorly funded by the private organization Project ALS, the scientists first infected rats with a virus (Sindbis) they developed that selectively destroys nerve cells that control muscles in the hind limbs. Lou Gehrig's disease, also known as ALS or amyotrophic lateral sclerosis, is similarly marked by a gradual loss of the nerves that control muscles, although its cause is unknown.

One-third of the animals then received transplants of human embryonic germ cells, which are capable of becoming any cell type, into their spinal fluid. The other rats served as controls and received either hamster kidney cells or human cells that don't have stem cell properties.

Twelve weeks later, the 15 paralyzed rats that got human stem cells partially recovered control of their hind limbs. Moreover, their hind limbs were 40 percent stronger than control animals'. By 24 weeks, 11 of the 15 turned over at least three seconds faster when placed on their backs than before getting the human cells. Control rats did not improve, on average, over the 24 weeks of the study.

In paralyzed rats, Kerr and his team found that most of the implanted human cells migrated into the spinal cord, and many became cells of the nervous system -- astrocytes, neurons and even motor neurons -- while in uninjured animals the transplanted cells just sat on the spinal cord's outer surface. However, even in injured animals, only about four human cells per rat became motor neurons that actually extended out of the spinal cord and into muscle, potentially creating a circuit that could control movement.

"We saw some physical recovery, and we saw human stem cells that had become motor neurons, but it turns out that the two observations weren't related," says Kerr. "We saw functional recovery that wasn't due to new neurons, and we had no idea how that could be possible."

Kerr then discovered that the rats' own neurons were healthier in animals that received human stem cells. In subsequent laboratory experiments, Kerr found that the human stem cells produced copious amounts of two key growth signals. These were transforming growth factor-alpha (TGF-alpha), which promotes neurons' survival, and brain derived neurotrophic factor (BDNF), which strengthens their connections to other neurons. When the scientists blocked these two signals in the laboratory, the stem cells' beneficial effects disappeared.

"Even before motor neurons die, connecting neurons peel back as if they sense a sinking ship," says Kerr. "Simply keeping a neuron alive can't improve physical abilities if it's not connected to other neurons. It must be part of a circuit.

"In some ways our results reduce stem cells to the non-glamorous role of protein factories, but the cells still do some amazing, glamorous things we can't explain," he adds. "For example, the white matter that surrounds the spinal cord was thought to be an impenetrable barrier to axon growth, but some of the transplanted cells not only migrated into the spinal cord, but also sent axons back out. It is just incredible."

This is the second study to come out in the last couple of weeks that showed a beneficial effect from stem cells where the stem cells worked their benefit by releasing compounds that transformed other existing cells. The other was the use of bone marrow stem cells to restore insulin production to existing pancreatic cells. These are surprising results.

These two sets of results suggest that in addition to serving as a supply of new cells to replace damaged or lost cells a normal function of stem cells may be to supply signals to encourage growth and change of cell type in existing non-stem cells.

These results also make me think that the therapeutic value of stem cells as growth factor delivery vehicles could be enhanced by genetic engineering. If stem cells are needed to deliver a particular growth factor or set of growth factors then their effects might be able to be enhanced by genetically engineering them to produce more of whichever growth factors are needed for a specific therapeutic purpose. Damaged neurons need different growth factors than damaged pancreatic cells for instance. So it makes sense to use gene therapy to program stem cells to produce the exact growth factors needed for each purpose.

By Randall Parker 2003 June 29 09:18 PM  Biotech Therapies
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Protein Identified Which Signals Stem Cells To Become Muscle Cells

A protein named Wnt serves as a molecular signal to instruct CD45+ adult muscle stem cells to become muscle cells.

OTTAWA, ON (June 26, 2003) - A research team from the Ottawa Health Research Institute (OHRI), led by Dr. Michael Rudnicki, has published a groundbreaking study that demonstrates how a novel population of adult stem cells resident in muscle tissue plays an important role in muscle regeneration.

For the first time, the research also identifies details of the molecular signals that direct these adult stem cells to form new muscle, offering hope for millions of people with neuromuscular disorders.

The Rudnicki team's findings are published in the June 27 issue of the prestigious scientific journal Cell.

This landmark research shows that a class of adult muscle stem cells, called CD45+ cells, play a natural role in regeneration when they receive signals in the form of a secreted protein known as Wnt. Wnt proteins are secreted in response to tissue damage and act to trigger the stem cells to divide and then develop into highly specialized muscle cells.

"Why is this important?" asks Dr. Rudnicki, who is a Professor of Medicine at the University of Ottawa. "A central question in the application of stem cells to repair damage has been 'what are the switches that trigger the stem cells to make new tissue of a specific type?' Now that this question has been answered for muscle tissue, we can exploit this knowledge to potentially benefit people with neuromuscular diseases such as muscular dystrophy or diseases that involve muscle wasting such as multiple sclerosis, ALS, and cancer." However, he cautions, clinical applications are still some time away.

A focus of future research will be to develop drugs that target the Wnt signaling pathway as new treatments for neuromuscular diseases and muscle injury.

The ability to instruct stem cells to become muscle cells also has future application in therapies to reverse the effects of aging. Aging humans lose muscle cells from the heart and from muscles throughout the body. While the ability to do this is still some years away the ability to send in cells to serve as replacements will be a valuable rejuvenation therapy.

The fact that muscle cells die will eventually even be exploitable to enhance human muscles. Any form of genetic engineering that has the effect of increasing efficiency or capacity of muscles will be deliverable by adding genetic modifications to stem cells. The fact that older muscle cells have died basically will provide an opening to bring in new cells which will have enhanced functionality.

By Randall Parker 2003 June 29 07:32 PM  Aging Reversal
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2003 June 27 Friday
Bone Replacement Grown With Polymer Scaffolding

Whitaker Foundation and University of Toronto researcher Molly Shoichet has developed a polymer scaffolding that looks like bone which bone marrow cells can infuse into and then grow bone that replaces the slowing dissolving scaffolding.

The new bone grows naturally without the addition of chemical growth stimulants, said Whitaker investigator Molly Shoichet, Ph.D., of the University of Toronto. The innovation is in the design of the synthetic scaffold that provides a framework for the growing tissue.

The design mimics the structure of natural bone so faithfully that some experts in the field cannot distinguish between the two when shown micrographs of each side-by-side, Shoichet said. The research was published in the June 15 issue of the Journal of Biomedical Materials Research Part A.

"The structure is very open and porous," she said. "There are large interconnections between the pores separated by struts, rather than solid walls."

Into this spongy matrix, the researchers drizzle bone marrow cells, which can differentiate into osteoblasts, the strong, mineral-like cells of mature bone. The marrow cells take up residence in the scaffold and begin growing and multiplying. As they mature, the scaffold itself dissolves.

"You don't need growth factors to get the cells into the scaffold," Shoichet said. "The cells almost fall through it and get stuck along the way."

The scaffold, developed with coinvestigator John Davies of the University of Toronto, is made of poly(lactide-co-glycolide), a polymer used in sutures. The polymer is processed in a unique way to yield the open, sponge-like structure with pores more than 10 times larger than those that result from conventional processing.

Animal studies show that the scaffold provides an intricate framework for dense new bone growth while it slowly dissolves. In rabbits, strong new bone completely replaced the scaffold in about eight weeks.

This discovery has been licensed to Bonetec Corp. for marketing as OsteofoamTM.

By Randall Parker 2003 June 27 02:16 PM  Biotech Organ Replacement
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2003 June 26 Thursday
Low Cost Biomass Hydrogen Catalyst Discovered

Researchers at the University of Wisconsin in Madison have discovered a much lower cost catalyst for producing hydrogen from organic matter.

MADISON – It is thousands of times less expensive than platinum and works nearly as well.

Writing this week in the journal Science (June 27) University of Wisconsin-Madison chemical and biological engineers report the discovery of a nickel-tin catalyst that can replace the precious metal platinum in a new, environmentally sustainable, greenhouse-gas-neutral, low-temperature process for making hydrogen fuel from plants.

The new catalyst, together with a second innovation that purifies hydrogen for use in hydrogen fuel cells, offers new opportunities toward the transition of a world economy based on fossil fuels to one based on hydrogen produced from renewable resources.

James Dumesic, a professor of chemical and biological engineering, and graduate students George Huber and John Shabaker describe testing more than 300 materials to find a nickel-tin-aluminum combination that reacts with biomass-derived oxygenated hydrocarbons to produce hydrogen and carbon dioxide without producing large amounts of unwanted methane.

"Platinum is very effective but it's also very expensive," says Dumesic. "It's also problematic for large-scale power production because platinum is already in demand for use as anode and cathode materials in hydrogen fuel cells. We knew nickel was very active, but it allowed reaction to continue beyond hydrogen producing methane. We found that adding tin to what's known as a Raney-Nickel catalyst decreased the rate of methane formation without compromising the rate of hydrogen production."

Dumesic, research scientist Randy Cortright (now at Virent Energy Systems) and graduate student Rupali Davda first reported the catalytic reforming process for hydrogen production in the Aug. 29, 2002 issue of the journal Nature.

The simple, single-step process employs temperature, pressure and a catalyst to convert hydrocarbons such as glucose, the same energy source used by most plants and animals, into hydrogen, carbon dioxide, and gaseous alkanes with hydrogen constituting 50 percent of the products. More refined molecules such as ethylene glycol and methanol are almost completely converted to hydrogen and carbon dioxide. Because plants grown as fuel crops absorb the carbon dioxide released by the system, the process is greenhouse-gas neutral.

Platinum is too expensive.

The precious metal platinum (Pt) is well known to be an excellent catalyst in a number of chemical reactions. It is one component in a car's catalytic converter, for example, that helps remove toxins from automobile exhaust. Yet, platinum is rare and very expensive, costing more than $17 per gram (about $8,000 per pound).

Catalytic platinum (Pt) and nickel (Ni) stand out from other metals (such as copper or iron) because they process reaction molecules much faster. But pure nickel, unlike platinum, recombines the hydrogen product with carbon atoms to make methane, a common greenhouse gas. Dumesic and his colleagues tested over 300 catalysts to find one that could compete with platinum and perform in the APR process. Using a specially designed reactor that can test 48 samples at one time, the team finally found a match in a modified version of what researchers call a Raneynickel catalyst, named after Murray Raney, who first patented the alloy in 1927.

Raney-nickel is a porous catalyst made of about 90 percent nickel (Ni) and 10 percent aluminum (Al). While Raney-nickel proved somewhat effective at separating hydrogen from biomass-derived molecules, the researchers improved the material's effectiveness by adding more tin (Sn), which stops the production of methane and instead generates more hydrogen. Relative to other catalysts, the Raney-NiSn can perform for long time periods (at least 48 hours) and at lower temperatures (roughly 225 degrees Celsius).

According to Dumesic, a substitute for platinum catalysts is essential for the success of hydrogen technology. "We had to find a substitute for platinum in our APR process for production of hydrogen, since platinum is rare and also employed in the anode and cathode materials of hydrogen fuel cells to be used in products such as cars or portable computers," he said.

While this is an important advance by itself it does not make biomass a viable major energy source. The problem with growing crops for biomass is that it takes energy to make and transport the fertilizer, run tractors, run irrigation equipment, harvest, transport, and so on. It remains to be seen whether there is a crop that will yield enough biomass energy to make it worthwhile.

This catalyst may be useful on smaller scales in places where there is already a great amount of biomass waste being produced. For instance, the processing of existing crops produces biomass waste. Equipment to convert that biomass waste into useful hydrogen energy could be installed next to agricultural product processing facilities if this new catalyst turns out to work well in industrial use. Still, all the existing biomass waste is not sufficient as an energy source to replace much of the currently consumed fossil fuels.

Other enabling technologies such as fuel cells need to mature ot make hydrogen a more useful energy source once it has been produced. Those advances will come with time. What strikes me as less certain is whether biomass will ever become a major energy source for producing hydrogen. Plants have to be planted, tended, harvested, and processed. They are vulnerable to insects and droughts. They do not convert most of the light that hits them into stored chemical energy.

There are competing approaches that may be cheaper in the longer run. Advances in nanotechnology will eventually yield photovoltaic materials that will be cheap to produce. Then the electricity from the photovoltaics will could be used to run hydrolysis reactions to produce hydrogen from water. Also, some materials may be found that can absorb light to drive a direct catalysis reaction to produce hydrogen from water without first producing electricity. Such materials would probably be more efficient than plants at converting sunlight to energy and would even be able to do so all year around (albeit at lower rates during the shorter days of the year).

Update: Some Tufts researchers have also recently discovered a way to reduce the amount of precious metals used as catalysts to make hydrogen.

"A lot of people have spent a lot of time studying the properties of gold and platinum nanoparticles that are used to catalyze the reaction of carbon monoxide with water to make hydrogen and carbon dioxide," said Maria Flytzani-Stephanopoulos, professor of chemical and biological engineering at Tufts and the lead researcher of the project. "We find that for this reaction over a cerium oxide catalyst carrying the gold or platinum, metal nanoparticles are not important. Only a tiny amount of the precious metal in non metallic form is needed to create the active catalyst. Our finding will help researchers find a cost-effective way to produce clean energy from fuel cells in the near future"

She and her two colleagues, doctoral student Qi Fu and research professor Howard Saltsburg, were funded by a $300,000 three-year grant from the National Science Foundation, and have filed a provisional patent for their research. Their cutting-edge work in catalytic fuel processing to generate hydrogen for fuel cell applications is one of the major undertakings at Tufts' Science and Technology Center at the University's Medford campus.

The Tufts researchers' article is based on the "water-gas shift" reaction they use to make hydrogen from water and carbon monoxide over cerium oxide loaded with gold or platinum. Typically, a loading of 1-10 weight percent of gold or other precious metals is used to make an effective catalyst. But the Tufts team discovered that, after stripping the gold with a cyanide solution, the catalyst was just as active with a slight amount of the gold remaining – one-tenth the normal amount used.

According to Flytzani-Stephanopoulos, "This finding is significant because it shows that metallic nanoparticles are mere 'spectator species' for some reactions, such as the water-gas shift. The phenomenon may be more general, since we show that it also holds for platinum and may also hold true for other metals and metal oxide supports, such as titanium and iron oxide."

She adds, "It opens the way for new catalyst designs so more hydrogen can be produced with less precious metal. This can pave the way for cost-effective clean energy production from fuel cells in the near future."

By Randall Parker 2003 June 26 05:52 PM  Energy Biomass
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2003 June 25 Wednesday
Leroy Hood: $1000 Personal DNA Sequencing In 10 Years

Speaking at the Biotechnology Industry Organization (BIO) Convention 2003 in Washington DC Leroy Hood, president of the Institute for Systems Biology in Seattle, predicts personal genome sequencing for under $1000 within 10 years.

Within about 10 years, advances in nanotechnology and other predictive models will allow the fast and cheap sequencing of individuals' genomes, Hood said, which in turn will lead to advances in predictive medicine. As scientists are able to look at 30,000 or more genes for each patient, doctors could use such genome sequences to predict what health problems the individual patient is likely to face, he said.

"I think we will have an instrumentation that could well bring sequencing of the human genome ... down to a 20-minute process and do it for under $1,000," Hood said. "This changes the way we think about predictive medicine."

Suppose the 10 year goal for reducing DNA sequencing costs is achieved. Will the ability to get one's own DNA sequenced be useful? Francis Collins, director of the National Human Genome Research Institute at the U.S. National Institutes of Health, is promoting the goal of identifyng all the genetic risk factors for major diseases in 7 or 8 years.

Collins called on the biotechnology and medical communities to identify the risk factors for all major common diseases in the next seven to eight years.

Once we can cheaply sequence each person's DNA then genetic variations that increase the risk of side effects from taking specific drugs will be identified for a large number of drugs. Combine the ability to guide drug choice with the ability to more accurately predict the risk of developing various illnesses and it will become possible to devise low-risk strategies for reducing the risk of developing heart disease, cancer, and other diseases.

Once DNA sequencing is cheap and the risk factors are all identified the big pay-off will come from the development of treatments that cancel out and eliminate the risks that particular genetic variations cause. Drugs, gene therapy, and other approaches will be developed to reduce or eliminate specific risk factors. A great deal gets written about the potential ways that individual genetic privacy needs to be protected in order to prevent discrimination against people who have genetic risk factors for diseases. But individual genetic risk profiles offer far more potential for benefit than harm.

Look at it this way: if one person is a risk for a variety of illnesses due to genetic risk factors and another person has little in the way of genetic risks then who is in a better position to benefit from the knowledge of their genetic risk profile? The person who has the risks needs to know about them in order to act to somehow mitigate some of those risks. The person who doesn't have the genetic risks benefits far less from being told they do not have the risks because the knowledge really doesn't help them do anything to protect their health.

Someone who has a genetic endowment that'll keep them alive til age 95 even if they smoke and eat junk food is far less in need of biotechnological advances that are designed to deal with genetically-caused health risks. Someone who has a genetic variation that puts then at enormous risk of getting heart disease or cancer by age 55 is in desperate need of the treatments that will be designed to cancel out genetic risks. The good news is that leading figures in biotechnology and science are increasingly of the opinion that the day is not far off when we will each individually begin to benefit from detailed knowledge of our individual genetic make-ups.

By Randall Parker 2003 June 25 06:04 PM  Biotech Advance Rates
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UK Government Proposes Genetic Screening Of All Newborns

The British government is considering the possibility of collecting DNA samples from all newborn babies born in Britain.

All babies born in Britain could have their DNA stored in a national databank for their future medical treatment as part of a £50m genetics initiative published yesterday.

At this point the proposal has been made only to refer the matter to a commission to study the idea and make a report in a year and a half.

· Asking the Human Genetics Commission to consider the case for screening babies at birth, and storing their genetic profiles, to provide doctors with the knowledge to individually tailor their healthcare - and to report by the end of 2004.

The British government is obviously thinking in terms of having genetic profiles as standard information that every doctor will have on every patient. It makes perfect sense for doctors to have such detailed information. Early testing will identify genetic metabolic disorders that must be treated from a very early stage. They will also identify risk factors for future diseases and provide guidance for preventive measures for those at special risk. Plus, eventually most drugs will have identified for them specific genetic profiles which contraindicate their use or which indicate specific dosing regimens. From a medical standpoint genetic profiles will become so powerful that to not routinely use them will eventually come to be seen as malpractice.

The British government, as operators of a national health care system, see the collection of genetic data by the government as a logical step. The national health care system will greatly benefit and patients will benefit. From purely a medical effectiveness standpoint the decision seems a no-brainer for them. Plus, the database of genetic profiles, cross-referenced with health and other records would provide a bonanza of information for medical researchers. Absent a large public outcry I expect the British will implement their proposal. If there is too much political opposition to this proposal in the short term that will probably only delay its eventual implementaiton. As more desireable medical uses of genetic profiles are discovered the British public will gradually become more supportive of the idea that all doctors should have genetic informatoin available on every patient.

As part of a set of proposals on genetics-related issues the British government also is proposing the outlawing of secret collection of DNA without consent.

The new law of DNA theft is intended to stop people from secretly collecting genetic material from "dental floss in dustbins" or from hair on a comb. It will protect celebrities and those involved in unwelcome paternity tests.

Alistair Kent, director of the Genetic Interest Group, raises an obvious and reasonable objection to this proposal:

"While this may be necessary to protect celebrities from prying newspapers, criminalising desperate fathers trying to prove their paternity may not be the best approach."

In the long run genetic privacy will be impossible to protect. Once cheap compact DNA sequencing machines built using nanopore technology become widely available (my guess is in 10 to 20 years) it will become too easy for a single person to get a DNA sample and test it without any help.

By Randall Parker 2003 June 25 02:49 AM  Biotech Society
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Evolution Of Color Eyesight Led To Loss Of Pheromone Response

University of Michigan evolutionary biologist Jianzhi “George” Zhang argues that the development of the ability to see colors in our primate ancestors led to the loss of the ability to respond to sexual pheromones.

Zhang believes that a significant gene duplication made the difference and that it happened sometime between 23 million years ago and the split of the New World and Old World primates about 35 million years ago. An ancestor of the Old World primates (humans, chimps, gorillas, orangutans, gibbons, baboons and guerezas) developed a second copy of the red/green color-vision gene, which resides on the X chromosome. Female New World monkeys have full color vision because females have two X chromosomes that harbor both red and green color vision genes. But males only have one X chromosome, so New World males have only one copy of either the red or green gene, and that leaves them color-blind. After the red/green gene duplication in the Old World family however, even the males got color vision too.

Once humans could see in color the visual inspection of a potential mate yielded far more useful information and at a greater distance than was the case with scents. As a result of natural selection color-seeing primates came to have neuronal wiring that caused them to place much more importantce on appearance in mate choice. In Zhang's view it is therefore not coincidental that around the time human males developed the ability to see color humans also lost the ability to respond to pheromones:

To test their idea, Zhang’s team zeroed in on a human gene called TRP2, which makes an ion channel that is unique to the pheromone signaling pathway. They found that in humans and Old World primates, this gene suffered a mutation just over 23 million years ago that rendered it dysfunctional. But because we could use color vision for mating, it didn’t hurt us. In turn, the pheromone receptor genes that rely on this ion channel fell into disuse, and in a random fashion, mutated to a dysfunctional state because they haven’t experienced any pressure from natural selection. Zhang calls this process “evolutionary deterioration.”

The FuturePundit blog focuses on the future. This report is about events that took place tens of millions of years ago in our our evolutionary past. So how does this discovery about the history of human sexual evolution figure into the human future? In a couple of ways:

  • It will eventually become possible to fix the genes involved in the pheromone pathway and make humans have a sexual reaction to pheromones.
  • Drugs will be able to be developed that will work like pheromones. It is likely that by taking apart the steps of the pheromone signalling pathway in primate species which still have functioning pheromone systems it will be possible to identify portions of the pathway that still work in humans because they are far enough downstream that they have been preserved for other uses. Drugs aimed at enzymes and genes in the downstream portion of the pheromone response may be able to elicit a pheromone reaction in humans.

Many changes that happened in our evolutionary past will not be lost to us forever once it becomes possible to do genetic engineering to ourselves and our progeny. If we want to recover lost functionality or behavioral tendencies it will eventually become possible to do so. I would go so far as to predict that there will eventually be cultish groups who will pursue biological nostalgia fads to make themselves more authentic and less modern by giving themselves features associated with our pre-human ancestors. These faddists of the future will use biological technology to take the back-to-nature movement to a whole 'nuther level.

By Randall Parker 2003 June 25 01:04 AM  Biological Mind
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2003 June 23 Monday
Device Maintains External Liver Cells For Blood Filtration

Researchers from the University of Pittsburgh McGowan Institute for Regenerative Medicine have developed a device for growing liver tissue outside of the body to use as a blood filtering device that is analogous to a kidney dialysis device. This device has been used on 8 people so far.

Growing functioning liver tissue in a fist-sized device that works in a way similar to kidney dialysis has kept patients in liver failure alive until donor organs have become available, according to Jörg Gerlach, M.D., Ph.D., professor of surgery at the University of Pittsburgh School of Medicine. "We have treated eight patients in acute liver failure - some of whom were in a coma - who were able to be bridged to transplant," said Dr. Gerlach, who also is a faculty member of the university's McGowan Institute.

Dr. Gerlach and his colleagues have been able to grow functioning liver tissue from human liver stem cells derived from organs that had been deemed unsuitable for transplant because of damage or underlying disease. Such cells have been shown to proliferate and form liver-like tissues in bioreactors, and persist in culture for many weeks.

About 25 million Americans - one in 10 - have liver disease, according to the American Liver Foundation. More than 43,000 people die of liver disease yearly. Annual hospitalization costs exceed $8 billion. Dr. Gerlach's bioreactor could have an impact for the sickest of these patients, who often do not survive the wait for transplantation or become too sick to qualify for a transplant.

Once the ability to grow replacement livers is developed then one future application for this type of device would be to give a person time to live while a replacement liver was grown from his own cells in an artificial vat.

By Randall Parker 2003 June 23 10:04 PM  Biotech Organ Replacement
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Bone Marrow Stem Cells Cure Diabetes In Mice

A research team at the Robarts Research Institute in London Ontario Canada led by Dr Mickie Bhatia has successfully used bone marrow stem cells to regenerate damaged pancreases in diabetic mice to cure their diabetes.

The scientists injected bone marrow stem cells into diabetic mice, who were cured or back to normal within seven to 14 days.

But the "most amazing" finding, said Bhatia, is that the stem cells triggered the rodents' damaged pancreases to regenerate on their own.

Here's the surprising part: the stem cells did not integrate into the pancreases of these mice. Instead they somehow triggered the pancreatic cells to become insulin-producing cells. Bhatia's group is now searching for molecules that the bone marrow stem cells might have released to induce the pancreatic cells to repair the damage to the pancreas.

The repair happened quite quickly.

When the researchers injected stem cells into mice with pancreatic damage, the organs were stimulated to repair themselves within 17 days.

Type I diabetes takes literally decades off life expectancy. The greater range of swings in blood sugar that diabetics experience causes their bodies to develop degenerative diseases of old age more rapidly. A human version of this treatment would be very beneficial. If molecular signals are released by the stem cells and can be identified then just those chemicals could be used as therapeutic agents to cure diabetes.

Update: A vaccine that stops the auto-immune response that causes type I diabetes is showing great promise.

Diamyd Medical's phase II trial was conducted on 47 diabetes patients with the GAD‑based vaccine at the UMAS hospital in Malmoe, Sweden, and St. Gorans Hospital in Stockholm, Sweden. The patients were randomly divided into four groups of approximately 12 patients per group. Each patient received one injection of the vaccine, followed by at least one boost injection four weeks later. Nine patients in every group received the active drug; three received placebo. The groups received different doses of the vaccine, ranging from 4 micrograms to 500 micrograms per dose.

All patients visited the hospitals 10 times during this six-month study. Detailed clinical, immunological and neurological investigations showed no safety concerns at the administered dose levels. The study results show that the diabetes vaccine could significantly protect the patient's ability to secrete insulin, both when fasting and after meals.

The GAD vaccine originated at UCLA from an unexpected convergence of studies in neurobiology and immunology. In the late 1980s, the laboratory of Dr. Allan Tobin, who now directs the UCLA Brain Research Institute, was involved in isolating genes that were thought to be important in brain development and neurological diseases.

Working with Tobin, graduate students Kaufman and Mark Erlander isolated the gene that makes a protein called "GAD," which creates an important neurotransmitter in the brain. At that time, it was known that although GAD was made primarily in the brain, it was also made in the pancreas in the cells that secreted insulin.

Several years later, Kaufman and Tobin realized that the autoimmune response that causes type I diabetes may be due to the immune system attacking the GAD protein in the insulin-producing cells in the pancreas. With this knowledge, they developed a GAD diagnostic test for identifying individuals who were developing type I diabetes based on antibodies in their blood that recognized GAD.

Kaufman, in his own laboratory at the UCLA Department of Molecular and Medical Pharmacology, along with Dr. Jide Tian, of the same department, searched for ways to help the immune system tolerate the GAD protein, which would circumvent or inhibit the autoimmune attack.

The team reported in the journal Nature in 1993 that when young, diabetes-prone mice were treated with a small amount of the GAD protein, their immune systems learned to tolerate the protein. The autoimmune response that leads to type I diabetes never developed in these mice as they grew older.

In another study published by Nature-Medicine in 1996, the UCLA team developed the GAD vaccine to inhibit the autoimmune response after it had already begun to attack the insulin‑producing cells. Kaufman and Tian showed that even after the type I diabetes disease process had started in diabetes-prone mice, its progression could be inhibited by the GAD vaccine.

According to Tian, the GAD vaccine activated T-cells (a type of white blood cell or immune defense cell) that recognized GAD. The T-cells traveled to the pancreas and, recognizing the GAD protein, released calming substances called "anti-inflammatory" cytokines, which suppressed the immune cells that were killing the insulin-producing cells.

"The beauty of this vaccine is that it just affected one small part of the immune system — without broadly inhibiting the function of the entire immune system," Tian said.

For people who already have type I (the kind that comes when one is young) diabetes this is probably a necessary treatment in addition to a treatment that will get the pancreas producing insulin again. Otherwise a pancreas that starts producing insulin will likely come under auto-immune attack again.

Update: Also see a January 2004 report that reports how infection of mice with lymphocytic choriomeningitis virus (LCMV) in the early stages of diabetes stops the autoimmune response.

Viruses can both cause and prevent autoimmune disease. In order to understand this dualism, Matthias von Herrath and colleagues from the La Jolla Institute for Allergy and Immunology in California exposed prediabetic mice to viral infections. In the January 2 issue of the Journal of Clinical Investigation the authors report that infection with lymphocytic choriomeningitis virus (LCMV) during the prediabetic period completely abolished the diabetic process in two distinct mouse models.

This protection against the development of type 1 diabetes correlated with a reduced number of autoaggressive CD8 T cells in pancreatic islets. Increased production of the chemokine CXCL-10 in pancreatic lymph nodes redirected cells of the immune response away from the b cells. Once in the pancreatic lymph node, CD8 lymphocytes underwent increased apoptosis, which was directly dependent on TNF-a and indirectly on IFN-g production. The data indicate that proinflammatory cytokines and chemokines induced by viral infection can influence ongoing autoaggressive processes beneficially at the preclinical stage if produced at the correct time, location, and level. Therefore viruses that do not directly destroy b cells may actually enhance the course of autoimmune diabetes.

By Randall Parker 2003 June 23 07:56 PM  Biotech Therapies
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Most Surveillance Cameras In NYC Privately Owned

Most video surveillance cameras in New York City are privately owned.

The use of surveillance cameras erupted into a major issue in 1998 when the New York Civil Liberties Union (NYCLU) mapped the city and concluded that there were 2,400 surveillance cameras in Manhattan alone, a number that Mr. Brown believes has tripled.

Former NYCLU head Norman Siegel said that 89 percent of the cameras were privately owned and 11 percent publicly owned.

There is an important implication of this report: efforts to restrict the use of surveillance cameras by governments will have little effect upon the rate of growth of the use of surveillance cameras in general, This pattern of many times more privately than publicly owned security cameras probably holds throughout the United States and likely in a number of other countries as well. One factor that may make international comparisons difficult is differing patterns of public versus private ownership of port facilities, airports, bus and train stations, and other facilities where cameras could be used for security purposes.

As it now stands there does not appear to be substantial public opposition to government operation of surveillance cameras. Therefore my guess is that even government operation of surveillance cameras will continue to expand quite rapidly.

Some private organizations that operate surveillance cameras are not conventional commercial interests. For instance, the apparently private foundation Surf Life Saving Queensland wants to install surveillance cameras to prevent drownings.

CIVIL libertarians and naturalists have vowed to fight plans to install surveillance cameras at a Sunshine Coast nudist beach.

There is some irony in the notion that nudists on a public beach do not want to have their privacy invaded.

From a government police agency's perspective the proliferation of private security cameras makes their jobs easier. If privately owned and operated cameras are positioned to record public approaches to privately owned establishments and then a crime is committed in an area the private cameras will often be useful in police investigations. This form of usefulness is becoming increasingly common as private video surveillance cameras proliferate. To take just one recent example, police in Melbourne Australia are looking thru footage from a hotel's video footage even though the murder case they are investigating didn't happen in the hotel whose camera might have caught the crime.

As Moran's family began planning his funeral, police were examining footage from a surveillance camera on a hotel near the murder scene at North Essendon.

As video surveillance systems fall in price and increase in capabilities their use will grow by orders of magnitude. We may reach a point where most stores, hotels, bus stations, airports, and other public places operate multiple cameras. The cost of data storage capacity will fall so far and become so miniaturized that much more of the images recorded by surveillance cameras will be recorded and retained for longer periods of time.

What is really going to drive the push toward pervasive monitoring by video cameras is the spread of WiFi (Wireless Fidelity) internet access networks. The island nation of Niue has the first nationwide WiFi network.

ALOFI, Niue, The South Pacific -- The Internet Users Society – Niue (IUS-N), today announced that it has launched the world’s first free nation-wide WiFi Internet access service on the Polynesian island-nation of Niue. This new free wireless service which can be accessed by all Niue residents, tourists, government offices and business travelers, is being provided at no cost to the public or local government.

The number of areas covered by WiFi networks looks set to grow rapidly.

Today, IDC predicts that by 2006, 3 billion cell phones will be in use, and 50 percent of Internet users will be mobile. Gartner Dataquest estimates that by 2007, nearly 120,000 Wi-Fi hotspots will exist worldwide, with Asia accounting for about a third of these.

Using WiFi-enabled webcams and cellphone cameras an increasing number of people are going to send still images and motion video pictures of wherever they are to wherever they want to send them.Video surveillance is no longer going to be the done mainly by police, public transportation agencies, and private businesses. The general public is going to be in on it. The depiction of the surveillance society of David Brin's Earth science fiction novel is looking more prophetic every day.

By Randall Parker 2003 June 23 06:51 PM  Surveillance Cameras
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2003 June 22 Sunday
Transcranial Magnetic Stimulation Of Brain Unleashes Creative Abilities

Allan Snyder, director of Centre for the Mind at the University of Sydney is using transcranial magnetic stimulation (TMS) to slow down or speed up various parts of the brain and by doing so appears to be able to unlock savant intellectual abilities dormant in many minds.

As remarkable as the cat-drawing lesson was, it was just a hint of Snyder's work and its implications for the study of cognition. He has used TMS dozens of times on university students, measuring its effect on their ability to draw, to proofread and to perform difficult mathematical functions like identifying prime numbers by sight. Hooked up to the machine, 40 percent of test subjects exhibited extraordinary, and newfound, mental skills. That Snyder was able to induce these remarkable feats in a controlled, repeatable experiment is more than just a great party trick; it's a breakthrough that may lead to a revolution in the way we understand the limits of our own intelligence -- and the functioning of the human brain in general.

Snyderr claims TMS can rapidly improve drawing abilitiies

Professor Allan Snyder and colleague Elaine Mulcahy say tests on 17 volunteers show their device can improve drawing skills within 15 minutes.

Some scientists think he may be on to something important.

In a 1999 paper, Snyder and his colleague John Mitchell challenged the compulsive-practice explanation for savant abilities, arguing that the same skills are biologically latent in all of us. "Everyone in the world was skeptical," says Vilayanur Ramachandran, director of the Center for Brain and Cognition at the University of California at San Diego. "Snyder deserves credit for making it clear that savant abilities might be extremely important for understanding aspects of human nature and creativity."

Others think he has not published enough big rigorous studies on the phenomenon to be able to judge it.

"I wrote a comment two or three years ago in Nature, on his theory on autism and early information processing. I never commented on his TMS stuff and the reason is I'm a little bit skeptical. And there's no data so far available supporting his claims," said Professor Niels Birbaumer, of the University of Tubingen, Germany.

For some more relevant reading see Darold A. Treffert's articles on savants which include his own comments on the results of studies of TMS which he calls repetitive transcranial magnetic stimulation (rTMS)

By Randall Parker 2003 June 22 01:38 PM  Biological Mind
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2003 June 20 Friday
Study on Differences in Female, Male Sexuality

While heterosexual males are chiefly aroused by females heterosexual females are aroused by males and females.

June 12, 2003

Study on Differences in Female, Male Sexuality

EVANSTON, Ill. --- Three decades of research on men’s sexual arousal show patterns that clearly track sexual orientation -- gay men overwhelmingly become sexually aroused by images of men and heterosexual men by images of women. In other words, men’s sexual arousal patterns seem obvious.

But a new Northwestern University study boosts the relatively limited research on women’s sexuality with a surprisingly different finding regarding women’s sexual arousal.

In contrast to men, both heterosexual and lesbian women tend to become sexually aroused by both male and female erotica, and, thus, have a bisexual arousal pattern.

“These findings likely represent a fundamental difference between men’s and women’s brains and have important implications for understanding how sexual orientation development differs between men and women,” said J. Michael Bailey, professor and chair of psychology at Northwestern and senior researcher of the study “A Sex Difference in the Specificity of Sexual Arousal.” The study is forthcoming in the journal Psychological Science.

Bailey’s main research focus has been on the genetics and environment of sexual orientation, and he is one of the principal investigators of a widely cited study that concludes that genes influence male homosexuality.

As in many areas of sexuality, research on women’s sexual arousal patterns has lagged far behind men’s, but the scant research on the subject does hint that, compared with men, women’s sexual arousal patterns may be less tightly connected to their sexual orientation.

The Northwestern study strongly suggests this is true. The Northwestern researchers measured the psychological and physiological sexual arousal in homosexual and heterosexual men and women as they watched erotic films. There were three types of erotic films: those featuring only men, those featuring only women and those featuring male and female couples. As with previous research, the researchers found that men responded consistent with their sexual orientations. In contrast, both homosexual and heterosexual women showed a bisexual pattern of psychological as well as genital arousal. That is, heterosexual women were just as sexually aroused by watching female stimuli as by watching male stimuli, even though they prefer having sex with men rather than women.

“In fact, the large majority of women in contemporary Western societies have sex exclusively with men,” said Meredith Chivers, a Ph.D. candidate in clinical psychology at Northwestern University and a psychology intern at the Centre for Addiction and Mental Health and the study’s first author. “But I have long suspected that women’s sexuality is very different from men’s, and this study scientifically demonstrates one way this is so.”

The study’s results mesh with current research showing that women’s sexuality demonstrates increased flexibility relative to men in other areas besides sexual orientation, according to Chivers.

“Taken together, these results suggest that women’s sexuality differs from men and emphasize the need for researchers to develop a model of the development and organization of female sexuality independent from models of male sexuality,” she said.

The study’s four authors include Bailey and three graduate students in Northwestern’s psychology department, Chivers, Gerulf Rieger and Elizabeth Latty.

“Since most women seem capable of sexual arousal to both sexes, why do they choose one or the other?” Bailey asked. “Probably for reasons other than sexual arousal.”

Sexual arousal is the emotional and physical response to sexual stimuli, including erotica or actual people. It has been known since the early 1960s that homosexual and heterosexual men respond in specific but opposite ways to sexual stimuli depicting men and women. Films provoke the greatest sexual response, and films of men having sex with men or of women having sex with women provoke the largest differences between homosexual and heterosexual men. That is because the same-sex films offer clear-cut results, whereas watching heterosexual sex could be exciting to both homosexual and heterosexual men, but for different reasons.

Typically, men experience genital arousal and psychological sexual arousal when they watch films depicting their preferred sex, but not when they watch films depicting the other sex. Men’s specific pattern of sexual arousal is such a reliable fact that genital arousal can be used to assess men’s sexual preferences. Even gay men who deny their own homosexuality will become more sexually aroused by male sexual stimuli than by female stimuli.

“The fact that women’s sexual arousal patterns are not all predicted by their sexual orientations suggests that men’s and women’s minds and brains are very different,” Bailey said.

To rule out the possibility that the differences between men’s and women’s genital sexual arousal patterns might be due to the different ways that genital arousal is measured in men and women, the Northwestern researchers identified a subset of subjects: postoperative transsexuals who began life as men but had surgery to construct artificial vaginas.

In a sense, those transsexuals have the brains of men but the genitals of women. Their psychological and genital arousal patterns matched those of men -- those who like men were more aroused by male stimuli and those who like women were more aroused by the female stimuli -- even though their genital arousal was measured in the same way women’s was.

“This shows that the sex difference that we found is real and almost certainly due to a sex difference in the brain,” said Bailey.

You can download the full paper A Sex Difference in the Specificity of Sexual Arousal as a 494 kb PDF. From the full paper:

The sex difference reported here has important implications for future conceptualizations of women’s sexuality. Sexual arousal, especially genital sexual arousal, is likely to play a much smaller role in women’s sexual orientation development than it does in men’s. Female sexuality, in general, may be more motivated by extrinsic factors, such as the desire to create or maintain a romantic relationship, than intrinsic factors, such as genital sexual arousal (Baumeister, Catanese, & Vohs, 2001). This basic sex difference in the role of sexual arousal processes highlights the need to use distinct models when investigating the development and expression of female or male sexuality.

Bailey has information about his areas of research interest. Also, he has a book out that, by reports from people whose judgement I trust, is an excellent examination of the types of transsexuality: The Man Who Would Be Queen: The Science of Gender-Bending and Transsexualism.

You might be wonder what does all this have to do with the future? I think a great deal. Some day 2 or 3 or, at the very most, 4 decades from now it will become possible to do large scale germ line genetic engineering to give offspring different genetic endowments that change how their minds will develop. The extent to which various aspects of human behavior are found to have a firm biological basis is a strong indicator of how much changes in genetic endowments will be able to change mental qualities in human offspring.

In my opinion, this latest result is more evidence that differences in how genes are regulated during embryonic and early life development probably cause male and female brains to develop in such a way to cause them to have different sexual natures and likely causes different forms of male and female heterosexuality, bisexuality, homosexuality, and transsexuality.

Update: There is an on-going blogosphere discussion of various aspects of Bailey's research on sexuality. See Charles Murtaugh's post as a good starting point.

Also, the Chronicle of Higher Education has an article on Bailey and the reactions to his research on sexuality.

But his latest work has created a bigger buzz than most scholars hope to enjoy in their entire careers. Not only does he identify a set of interests and behaviors he says can be used to tell whether a man is gay, he ties homosexuality to transsexualism. The book is receiving praise and damnation in equal measures, and the controversy is quickly making the author one of the most talked-about sex and gender researchers in academe.

By Randall Parker 2003 June 20 03:57 PM  Brain Sex Differences
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Shyness In Babies Detectable By MRI Brain Amygdala Scans

Functional Magnetic Resonance (fMRI) brain scans done on adults show patterns in adult brain activity that correlate with shyness of those same people as toddlers.

A key area in the brains of people who displayed an inhibited temperament as toddlers shows a greater response to new faces than does the same brain area in adults who were uninhibited early in life, according to a study by researchers from Massachusetts General Hospital (MGH). The imaging studies of the amygdala – a part of the brain that responds to events requiring extra vigilance – appear in the June 20 issue of Science.

"Our findings both support the theory that differences in temperament are related to differences in amygdala function, something earlier technology could not prove, and show that the footprint of temperamental differences observed when people are younger persist and can be measured when they get older," says Carl Schwartz, MD, director of the developmental psychopathology lab in the MGH Psychiatric Neuroscience Program, the paper's first author. "In a way, this research is the neuroscientist's version of the 'Seven-Up' movies," he adds, referring to a well-known series of British documentaries that have revisited a group of people every seven years for more than 40 years.

In psychological terms, temperament refers to a stable emotional and behavioral profile that is observed in infancy and partially controlled by genetic factors. One of the most carefully studied temperamental measures relates to a child's typical response to unfamiliar people, objects and situations. It usually is described with terms such as shyness versus sociability, caution versus boldness, or withdrawal versus approach. The two extremes of this measurement define types of children called inhibited and uninhibited by Jerome Kagan, PhD, professor of Psychology at Harvard University, a co-author of the current study.

The study participants were 22 young adults who, as children, had participated in Kagan's earlier research. Thirteen of the participants had been determined to be inhibited as infants, and nine were categorized as uninhibited. In the first phase of the current study, functional MR images (fMRI) were taken while participants viewed a random series of six faces that were presented several times. In the test phase, participants viewed a larger number of faces, some of which were totally new and some that were repeated from the first phase. All of the faces that the participants viewed had expressions that were neutral and not characterized by any emotion.

While some increase in amygdala response to strange faces is normal, the inhibited participants showed a significantly greater response to the unfamiliar faces than did the uninhibited participants. Two of the inhibited participants previously had been diagnosed with the anxiety disorder social phobia, but even when their results were removed from analysis, the inhibited groups showed much greater amygdala response.

"It's been theorized that the behavioral differences that characterize inhibited and uninhibited children may relate to the amygdala's response to novelty, and our study supports that concept," says Schwartz, who is assistant professor of Psychiatry at Harvard Medical School. "This was a modest study that needs to be confirmed in a larger population, something we are hoping to receive the resources to carry out."

The researchers also note that the current findings could complicate the interpretation of psychiatric imaging studies. Schwartz notes, "There are many imaging studies that have compared people with anxiety disorders such as panic disorder and social phobia to normal controls and found increased amygdalar activity.

While the conventional interpretation of such studies is to regard these differences as markers of the illness, our results suggest that this brain activity may in fact be a marker for the continued influence of temperamental risk factors persisting from infancy."

"These findings may reflect a difference in vulnerability that can be compensated for or exacerbated by environment and experience," says Scott Rauch, MD, MGH director of psychiatric neuroimaging, another co-author of the Science paper.

Two year old babies already have distinct recognizeable differences in their reactions to new situations.

"Inhibited children in the second year of life don't like novelty, don't like unknown situations," Schwartz said in a telephone interview. "It is broader than shyness ... It is about being more vigilant about things that are new

The differences in the temperament of babies are easily observable.

"A grad student made a little R2D2 robot," Schwartz said. "The uninhibited toddlers would walk up and poke the robot in the eye and say 'duh.' The inhibited child would freeze or even run to his mother."

There are long term behavior differences between inhibited and uninhibited children.

These temperaments are widely thought to be inborn, and each carries risks. Uninhibited children can become aggressive and antisocial in adolescence and adulthood, while inhibited children are more prone to anxiety disorders.

Anxiety is more common among inhibited people.

The findings may help to start sorting out the nature-versus-nurture debate. About one-third of "inhibited" children end up with social anxiety disorder, versus only 9 percent of "uninhibited" ones.

If these differences in temperament which are evident from such an early age are at least partially genetically based then eventually it will become possible to do genetic engineering to create babies with different temperaments.

Early amygdala differences persist for decades.

Dr Schwartz said: "It's been theorised that the behavioural differences that characterise inhibited and uninhibited children may relate to the amygdala's response to novelty, and our study supports that concept. Now we're suggesting that the same link continues through life. We found that individual differences in temperament are associated with persistent differences in the response of the amygdala after more than 20 years of development and life experience."

By Randall Parker 2003 June 20 11:31 AM  Brain Development
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2003 June 19 Thursday
Carbon Nanotube Fibers Tougher, Stronger Than Steel Or Spider Silk

Nanotechnology researchers at the University of Texas at Dallas and at Trinity College in Dublin Ireland have developed nanotube fibers that are stronger and tougher than any known synthetic or natural fiber.

The nanotube threads, created by Ray Baughman and colleagues at the University of Texas, Dallas, and Trinity College, Dublin, have a toughness of 570 Joules per gram. This is three times greater than the toughest natural material, spider silk.

These fibers are 20 times tougher than steel and 17 times tougher than Kevlar.

Now the researchers report they have spun nanotubes into fibers more than 300 feet long; the fibers have the strength of spider silk and more than three times its shock-absorbing toughness. That makes the fibers more than 17 times tougher than the Kevlar used in military flak jackets.

These fibers are both tougher and stronger than steel.

The fibres have twice the stiffness and strength and 20 times the toughness of the same weight and length of steel wire.

The current methods for producing nanotubes still cost many orders of magnitude more than existing materials and the method used to make these fibers is slow and costly as well.

They placed single-walled nanotubes in a rotating bath of aqueous polyvinyl alcohol, yielding gelatinous fibres, which were then coagulated, washed in an acetone bath, dried and reeled up.

This result does far more to demonstrate the performance potential of nanotubes than it does to lower costs. What is most needed to advance the use of nanotubes in materials applications are better methods for making them much more cheaply. While their process may scale well for converting nanotubes to fibers their process does not make the expensive nanotubes that are one of the materials which the process uses.

"We are currently making our fibres on the laboratory scale, producing hundreds of metres of fibre per run," added Baughman. "This basic fibre-spinning process is amenable to upscaling, which will involve increasing the spinning rate and going from single filament to multifilament spinning."

The nanotubes used in these experiments are incredibly expensive.

So far, the biggest hurdle to sewing futuristic nanotube clothes is the $500-per-gram cost of the nanotubes.

The ability of the fibers to function as sensors, electronic circuits, and even energy storage devices creates all sorts of possibilities for unusual clothing.

Or, pushing the envelope of imagination, think of a bulletproof shirt that plays MP3's and receives cellphone calls. (A more realistic potential application would be lightweight body armor that would also provide electrical power for a soldier's radio and other equipment.)

Frankly, I do not see what Kenneth Chang of The New York Times finds so unrealistic about clothing that would play music and take phone calls. Once the costs come down far enough one can easily imagine while people would want to wear clothes that provided so many capabilities. Here's another one: how about embedded temperature sensors that would respond to the change in outside and skin temperature to open and close openings in the cloth to change the level of insulation that one's clothes provide?

These fibers can be used for energy storage.

Baughman and his coworkers have already fashioned the fibers into electricity-storage devices called supercapacitors, which they incorporated into ordinary cloth.

It is likely that the energy storage density of this material is not high enough to get very excited about or they would have more strongly emphasised that part of their results. The discovery of much higher capacity electrical storage materials would enable the widespread use of electric-powered cars and also address the demand for much greater storage capacity for portable electronic devices.

There are many potential uses for incredibly strong textiles.

Baughman and coworkers propose a number of applications for the tough fibrous materials, including safety harnesses and explosion-proof blankets for aircraft cargo areas. In addition, the combination of electronic and mechanical properties may be used to make textiles that serve as sensors, electronic interconnects, and electromagnetic shielding.

Aeorspace, automotive, buildings, bridges, and countless other areas would benefit from much stronger materials. Once nanotubes can be manufactured cheaply they are going to replace existing materials in a large variety of uses and will enable the design of many products that can only be imagined today.

Spacecraft design could be completely revolutionized by advances in nanotechnology. Of course greater strength in materials would allow a reduction in the amount of materials used. But nanomaterials holds out the promise of further weight reduction thru their ability to be structural materials while simultaneously functioning as sensors, electronic circuits, mechanical actuators and other mechanical devices.

Beyond merely being strong, nanotubes will likely be important for another part of the spacecraft weight-loss plan: materials that can serve more than just one function. "We used to build structures that were just dumb, dead-weight holders for active parts such as sensors, processors, and instruments," Marzwell explains. "Now we don't need that. The holder can be an integral, active part of the system."

Imagine that the body of a spacecraft could also store power, removing the need for heavy batteries. Or that surfaces could bend themselves, doing away with separate actuators. Or that circuitry could be embedded directly into the body of the spacecraft. When materials can be designed on the molecular scale, such holistic structures become possible.

Advances in nanotech fabrication techniques will do more to advance the state of the art in aerospace design and manufacture than anything else happening in the aerospace industry today.

By Randall Parker 2003 June 19 12:07 AM  Materials Advances
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2003 June 17 Tuesday
Anxiety, Bipolar Depression Genes Discovered

A couple of interesting reports just out have identified additional genes with variants that are linked to mental disorders. A research team at the University of California at San Diego has identified a genetic variation of the GRK3 gene that may be responsible for 10% of all cases of bipolar disorder (aka manic depression).

Published in the June 16, 2003 issue of the journal Molecular Psychiatry, the findings indicate that a mutation in a gene that regulates sensitivity to brain neurotransmitters such as dopamine, causes bipolar disorder in as many as 10 percent of bipolar cases. The mutation in this gene, G protein receptorkinase 3 (GRK3), occurs in a portion of the gene called the promoter, that regulates when the gene is turned on.

The research team hypothesizes that this mutation causes the individual to become hypersensitive to dopamine, leading to the mood extremes that characterize biopolar disorder.

A complex and variable illness, bipolar disorder is thought to be caused by multiple genes. Although previous research has suggested candidate genes or general DNA regions where faulty genes may reside, the UCSD study is the first to pinpoint a precise gene involved in the disease.

Also known as manic depression, bipolar disorder is characterized by extreme mood states alternating between euphoric peaks and terrible depression. Current treatments help many who suffer from bipolar disorder, but physicians estimate that one-third to one-half of the 1 million bipolar patients worldwide receive little benefit from existing therapies.

The UCSD scientists used amphetamines in rats to mimic the effect of the manic phase of bipolar disorder and found that GRK3 was upregulated by the administration of amphetamines.

In a parallel study, Kelsoe and collaborators Bob Niculescu, David Segal and Ron Kuczenski, used DNA micro arrays, also called gene chips, to look at 8,000 genes from rats treated with amphetamine so as to mimic the mania of bipolar disorder. This relatively new technology allows scientists to track the expression – the turning on and off – of thousands of genes in a single, high-speed test.

“GRK3 had the largest change in levels of expression, indicating that it played a substantial role in the brain’s response to dopamine and possibly other neurotransmitters,” Kelsoe said. He added that “this was one of the most exhilarating moments for all of us involved. We had the positional piece from the linkage studies, and then the expression data which identified the same gene. We call this convergent functional genomics – identifying a gene based on both its position on a chromosome and on its function.”

One obvious use for this result would be to look at the people who have bipolar disorder due to the GRK3 variant and see if the best drugs for treating them are different than the drugs that work best for people who have bipolar disorder for other reasons. Every time a new genetic variation is linked to some mental disease then drug treatment regimes can be tested for that subset of people suffering from the disorder who have that variation. In the longer run new drugs can be developed that specifically target expression of the gene which is found to be playing a role in the disease.

A gene that codes for the human serotonin transporter has been found to be linked to anxiety. People with a tendency toward anxiety are more likely to abuse drugs and hence one version of serotonin transporter may contribute to drug abuse.

Researchers found that one version of the human serotonin transporter gene (5HTT-LPR) was strongly associated with anxious personalities. Individuals with this gene variant were the sort who find social interaction stressful and may take refuge in substance abuse.

But wait, that is not the only genetic variation that contributes to drug abuse. In a separate result a variation of the D4 dopamine receptor gene has also been found to be linked to a personality trait that contributes to drug abuse.

And a version of the gene for a receptor of the neurotransmitter dopamine - the D4 receptor - was associated with having a more outgoing personality. It is well-established that both these personality traits are more likely to lead to substance misuse.

Leave aside the focus on drug abuse in the reports on these last two results. Here we are seeing the identification of more genetic variations that contribute to personality. There are certainly dozens and perhaps even hundreds more such variants waiting to be found. As DNA sequence assaying technology continues to advance to make it easier and cheaper to test for DNA variations the rate at which personality influencing genetic variations will be found will continue to accelerate.

As each new genetic variant that influences behavior is identified there are predictably people such as one Dr Jonathan Chick who rush forth to proclaim that we still have free will.

He said: "There is no genetic condition that completely removes free will with respect to drinking or smoking.

Well, how does he know there is no genetic condition that at least in some individuals does not make their compulsion to smoke so strong as to be uncontrollable? There are people who have other kinds of completely uncontrollable compulsions. Some bite their lips. Some bang their heads against walls. People with Tourette's can't keep from blurting out all sorts of random thoughts. It is not inconceivable that there are people who have uncontrollable compulsions to smoke. However, whether there are or not is besides the point when it comes to the question of free will because we already know that there are other biochemical conditons which are probably genetically based which cause some people to have uncontrollable compulsions.

There are limits to free will. We are going to learn of many more genetic variations that tilt the odds in various ways to change group average behavior. This fact is disturbing to many. Heck, it is disturbing to me. But if we do not accept it we will do a poor job of dealing with all the implications.

By Randall Parker 2003 June 17 04:37 PM  Brain Genetics
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Natural Life Criminal Sentences And Life Extension

Daniel Bergner has an Op-Ed in The New York Times about the trend toward natural life sentences for criminals.

Across the country, at least 31,000 state and federal inmates are serving terms of natural life. That means they have been put away forever, without opportunity for parole. Except in the most unusual circumstances, we need never think of them again. And though national support for capital punishment may be softening, this does not mean that fewer people will be sentenced to die in prison. A decade ago, according to the Criminal Justice Institute, the number of natural lifers was about 12,000. Then, 31 states had adopted the sentence; now, 46 have chosen the safety of permanence and the luxury of not thinking.

Bergner happens to be opposed to the practice of natural life criminal sentences and it sounds like he's opposed to capital punishment too. But let us put aside the question of whether natural life is a fair or necessary criminal sentence under current circumstances. The natural life sentence is the more problematic when we look decades into the future. Once someone is dead (assuming we do not immediately cryogenically freeze them) we do not face any future decisions on what to do with that person. But as biotechnology advances the existence of long-serving inmates will present us with a number of problems.

One set of questions will come from the development of rejuvenating life extension therapies. I share the view of Aubrey de Grey that it will be possible to develop Strategies for Engineered Negligible Senescence (SENS) that will allow us to become young again and to stay young more or less indefinitely. Well, the first question that will arise with natural life prisoners is whether they should be eligible to receive treatments that cause aging to slow down to a negligible rate. If such treatments are withheld from prisoners serving natural life sentences then the effect will be to sentence them to slow death from old age. But if they are given such treatments then they would be faced with the prospect of effectively "unnatural life" prison sentences that could literally last for centuries (provided the human race lasts that long and the imprisoning government continues to exist - two big ifs).

Bergner describes the case of Wilbert Rideau who has been serving a prison term for over 40 years for grisly murders but who many prison officials think has changed so much that he is not a threat to anyone. Well, certainly there are older convicts who are no longer dangerous. Some people go thru intellectual and emotional growth, reflect upon who they were, and make profound changes in how they look at life. But some become less dangerous as they age simply because their hormone levels decline, their energy declines, and they just have less energy available with which to be aggressive. Suppose those latter types of people, sentenced to natural life terms, are made young again. In at least some cases the effect will be to make them very dangerous once again. Even if they are kept imprisoned they will become more dangerous to fellow inmates and to guards. Should they be made youthful again if that will make them more dangerous?

Another set of questions will come from the development of permanently mind-altering therapies. Eventually we will discover how to identify and manipulate biological factors that contribute to criminal behavior. Should someone serving a natural life sentence be told that they can receive therapies that will reverse the aging process only if they consent to alterations in their brains that make them less dangerous? Should those serving natural life sentences be given the option to have their minds altered as a condition of parole?

The development of rejuvenation therapies and the development of techniques to alter brains to change behavioral tendencies will each present us with basic questions about criminal justice. The death of criminals from old age will no longer be inevitable. The mellowing of violent youth with age will similarly no longer be a process that we can rely upon. Some will become less dangerous because of changes they go thru in their thinking. But what should we do with long-serving prisoners who are "bad to the bone" once aging becomes fully reversible?

By Randall Parker 2003 June 17 01:42 PM  Bioethics Debate
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2003 June 16 Monday
Emotions Overrule Logic To Cause Us To Punish

If your anterior insula gets the better of your dorsolateral prefrontal cortex then you are probably going to punish someone.

The study focused on an example of decision-making called the ultimatum game, in which two strangers meet and have a chance to split $10. One person is designated the "proposer" and offers some portion of the money to the "receiver." If the receiver accepts the offer, both collect the money as proposed; if the receiver rejects the offer, neither receive anything. The game is played with the explicit stipulation that it is a one-time interaction.

Standard economic theory suggests that the proposer should always offer $1 or some minimal amount and that the receiver should always accept, preferring to receive $1 than nothing. Many previous studies, however, have shown that people often reject what they see as unfair offers, foregoing profit and denying a windfall for the other player.

In their study, the Princeton researchers asked people to play the ultimatum game while the receiver's brain was being scanned by functional magnetic resonance imaging, a technology that allows researchers to see what brain areas are active at all moments during the study. They found that the more unfair the offer, the more activity they saw in an area called the anterior insula, which is associated with disgust and other negative emotions.

Another brain area, the dorsolateral prefrontal cortex, which is associated with working memory and deliberative thought, also responded to unfair offers. When the researchers averaged the results from 19 subjects, who each played 10 rounds of the game with different proposers, they found that the activity of the emotion area exceeded that of the deliberative area in cases when the subjects rejected the offers. The reverse was true when they accepted offers.

"It is not only telling us that there is an emotional response but that there seems to be a competition between these different considerations or ways of processing the situation," said Jonathan Cohen, who directs Princeton's Center for the Study of Brain, Mind and Behavior and is a co-author of the study.

During the study, receivers rejected unfair offers about half the time, which is consistent with many published studies, said Alan Sanfey, the lead author of the study. "When we explain the game to people they often ask, 'So why would I ever reject an offer? What's the trick?' And we say, 'There's no trick; if you reject an offer you don't get any money; if you accept the offer, you get it.' And they say 'OK.' And yet when they get in there and receive an unfair offer, oftentimes they reject it. There's an element of feeling a little betrayed."

"Both the field of economics and the field of decision making have, for a long time, resisted talking about emotions," said Sanfey, a postdoctoral researcher. "Now we can show biologically that emotions are not just important in a tangential way, in that making a decision makes you feel a certain way; they are important in a primary way because a sufficiently negative emotion can induce you to make certain decisions that would seem to go against your self interest."

My guess is that this behavior is a product of natural selection because the impulse to punish people was usually played out against people with whom one would have longer term dealings. If people knew from previous experience that a person would punish people who were perceived to have acted unfairly then it was less likely that the people in a tribe or village would act unfairly toward that person. Emotions essentially were designed to provide a reward in terms of emotional satisfaction under circumstances where the act of punishing exacted an immediate objective cost on the punisher. Therefore emotions were really designed to cause us to act in our longer term self interest. Of course emotions were not flawless in their guidance in ancient times. Emotions are probably even less perfect guides to action in modern environments because we have not evolved to be adaptive to the kinds of environments we can create.

What does this have to do with the future? First of all, we are no longer in the environment we evolved in because we increasingly create our own environments. Will we create environments that are compatible with our nature? Also, the biological basis of human nature throws a light on what we might modify to become something different in the future. Germline genetic engineering will eventually produce humans who are, on average, different in how their minds work than humans now living. What problems lie in the future that are a consequence of our nature? See my previous post Altruistic Punishment And Genetic Engineering Of The Mind.

By Randall Parker 2003 June 16 05:07 PM  Brain Altruism
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2003 June 15 Sunday
New Diseases Jumping Into Humans At Faster Rate

The Washington Post reports on the view of many infectious disease experts that the rate at which pathogens are jumping from other species into humans is increasing.

"Influenza is a zoonotic disease. HIV is a zoonotic disease. Monkeypox. SARS," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "You can go on and on."

The increasing pace is being caused by a confluence of factors that bring people into contact with a greater diversity of creatures than ever before, experts say.

Many reasons are cited for this. There are more humans. Humans are pushing into more parts of the globe. There are farming and marketing practices (e.g. the live animal markets in South China) that increase the chance of contact between humans and other species. When a disease does jump into a single human its odds of spreading into other humans is increased by faster and more widely used modern transportation. Contaminated food is spread more widely by modern transportation as well. Humans keep and trade in exotic pets.

The article mentions in passing that smallpox may have originally jumped into humans from camels. There is an interesting story behind that. Camelpox has been found to be genetically closest to human smallpox of all the known pox viruses. There is a real possibility that camelpox could mutate in a way that would allow it to jump into humans.

All the comparisons showed that camelpox and smallpox are genetically closer to each other than to any other virus. The authors speculate that the two viruses evolved from a common ancestor, possibly a rodent virus, probably after the advent of intensive agriculture about 7,000 years ago.

Gubser and Smith say the growth in the percentage of people who are "immunologically naïve" for orthopoxviruses increases the danger that these viruses will emerge or re-emerge as a threat to human health. In addition, the growth in the number of people whose immunity is suppressed by HIV infection poses a risk that the orthopoxviruses such as camelpox will jump species and adapt to humans.

There is a new theory just published about the origins of HIV. HIV may have been created by an exchange of genetic material between two Simian Immunodeficiency Viruses (SIVs).

A genetic study of SIV - the Aids-like virus that infects monkeys - suggests that HIV - the virus that causes Aids in humans - came about through the combination of two viruses in chimpanzees.

HIV may have been created by recombination of DNA from viruses that infect red-capped mangabeys and spot-nosed monkeys

In some ways, SIVcpz was found to resemble SIVrcm, a virus endemic in red-capped mangabeys.

But in other respects it closely matched another form of the virus, SIVgsn, which is found in the spot-nosed monkey.

It is possible that HIV was created by keeping primates of different species in close proximity in captivity.

"The genetics does not tell you how it arose," he said. "If you ask me to put money on it I think SIVcpz arose when monkeys and chimps were kept together in captivity. We know Asian rhesus monkeys caught SIV from African monkeys in captivity."

If this theory becomes well known and achieves some degree of acceptance one could easily imagine animal rights activists citing it as an argument against zoos.

By Randall Parker 2003 June 15 12:56 PM  Dangers Natural Bio
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2003 June 14 Saturday
Industry Continues To Advance DNA Assaying Technologies

The Scientist has published their annual review of the burgeoning microfluidics industry which includes a description of the 451 Life Sciences DNA sequencing technology. (free registration required)

Multiplexed amplification and sequencing reactions take place in the 75- picoliter wells of the company's high-density (~300,000 well) PicoTiter™ plates. Sequencing is accomplished with synthesis reactions, which produce light that is captured by the instrument's detection system. The current configuration will support resequencing of many strains of viruses and bacteria, and ultimately the de novo sequencing of bacterial and viral genomes.

454 Life Sciences' goal is to cut orders of magnitude of time off the sequencing of an entire genome.

As a majority-owned subsidiary of CuraGen, 454 Life Sciences follows CuraGen's tradition of innovative, industrialized, high-throughput solutions to bio-product development bottlenecks. As CuraGen's focus is on genomics-based pharmaceutical development to address unmet medical needs, 454 Life Sciences' mission is to develop and commercialize instrument systems to conduct whole genome analysis in a massively parallel fashion. Together, engineers and scientists from both companies are actively working together to develop and refine technology that can analyze entire genomes in days, instead of years, thus addressing bottlenecks currently impeding product development across the life sciences industry. In essence, CuraGen receives the benefits from being the "first user" of 454 Life Sciences' instruments and technology.

The Scientist also has published an article on 4 highly parallel approaches to whole genome Single Nucleotide Polymorphism (SNP) testing. The approach followed by Affymetrix illustrates how rapidly the rate of SNP testing is accelerating.

In 1999, the Santa Clara, Calif.-based company released its GeneChip HuSNP™, capable of profiling 1,200 SNPs simultaneously. Now its GeneChip Mapping10K Array (in early access) genotypes 10,000 SNPs per assay. By the end of the year, Affymetrix expects to begin offering early access to next-generation products that can genotype 100,000 SNPs per assay across multiple arrays.

Another company mentioned in the second article is Illumina which clams their Sentrix™ 96 multi-array matrix enables parallel processing of up to 150,000 SNPs

BeadArray fiber bundle arrays contain nearly 50,000 individual, light-conducting fiber strands which are chemically etched to create a microscopic well at the end of each strand. Each bead in the array con-tains multiple copies of covalently attached oligonucleotide probes, and up to 1,500 unique probe sequences are represented in each array, with approximately 30-fold redundancy of each bead type.

Note the use of bundles of large numbers of optical fibers. It illustrates how communications and electronics technologies are being used in biological instrumentation systems because they are of the right scale to do what is being attempted: make things smaller in order to make them more sensitive, faster, more parallel, and cheaper.

What is perhaps most encouraging about these reports is that the story of advances in DNA sequencing and SNP assaying is increasingly a story about industrial technology developers than about academic researchers. All the assaying systems described in these articles are made by companies, not university research groups (though it would not be surprising if university research groups collaborate with some of them in their development). The development of much cheaper and faster DNA assaying tools is not a distant prospect waiting on unpredictable advances in basic science. Rather, it is happening now as dozens of companies refine existing products and roll out new products that offer dramatic improvements over previous generation products that are just a couple of years old.

By Randall Parker 2003 June 14 01:03 PM  Biotech Advance Rates
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2003 June 12 Thursday
Multiphoton Microscopy Allows 3-D Live Tissue Imaging

Optical biopsies on horizon using noninvasive biomedical imaging technique developed by Cornell-Harvard group.

Diagnoses of cancers and neurodegenerative diseases, such as Alzheimer's disease, are two applications suggested by the researchers in their report in Proceedings of the National Academy of Sciences (PNAS , June 10, 2003), "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation." The researchers predict that it should be possible to obtain endoscopic and laparoscopic images of tissues at the cellular level from deep within living animals, or even human patients, thus enabling a new form of optical biopsy.

The researchers have demonstrated the new imaging technique by making live-tissue intrinsic fluorescence scans of autopsy samples from the brains of patients with Alzheimer's disease and by imaging mammary gland tumors in mice that serve as models of human cancer. Side-by-side comparison with conventional medical biopsy images of thin embalmed sections of the same organs reveals that the new method provides at least equal information, and in some cases contains additional diagnostic details not found in the conventional biopsies, which require invasive surgery.

Another advantage of live-tissue intrinsic emission imaging, the researchers say, is that the scans can be made through the surface of intact organs or body systems. By comparison, histopathology studies generally are performed on biopsy samples removed from subjects, then "fixed" or embalmed and stained with labeling chemicals, which involves extended time delays.The Cornell-Harvard team incorporated a technology into the new imaging procedure called multiphoton microscopy, invented in 1989 by Watt W. Webb, Cornell's S.B. Eckert Professor of Engineering and professor of applied physics, and Winfried Denk, now director of the Max-Planck-Institut für Medizinische Forschung Biomedizinische Optik, Germany.

Biological imaging technology has already gone thru dramatic advances with the development of CAT scanners, MRI scanners, and other scanning technologies. The general trend toward easier and more detailed 3 dimensional imaging of living biological tissue shows no sign of stopping.

The use of multiphoton microscopy can be enhanced by use of quantum dots. The use of shock waves in photonic crystals to shift light frequencies may provide a useful method to produce the light needed for this kind of imaging.

What I think is kinda funny about these advances is that they are starting to make science fiction TV shows set a few centuries into the future look backward in comparison. Dr. McCoy's medical tricorder has not yet been equalled. But can anyone doubt that within a few decades real medical science will be far more advanced than 22nd, 23rd, and 24th century fictional Star Trek Federation technology?

By Randall Parker 2003 June 12 03:44 PM  Biotech Assay Tools
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Microfluidic Pump May Work As Insulin Delivery System

C.J. Zhong of Binghamton University has developed a microfluidic pump with no moving parts.

An assistant professor of chemistry at Binghamton since 1998, Zhong refers to the invention as a "pumpless pump" because it lacks mechanical parts. The pumping device is the size of a computer chip and could be fabricated at a scale comparable to an adult's fingernail. The device comprises a detector, a column filled with moving liquid, and an injector. The pumping action is achieved when a wire sends an electrical voltage to two immiscible fluids in a tiny column, perhaps as small as the diameter of a hair. Applying opposite charges to each side of the column causes the fluids to oscillate, thereby simulating the action of a pump. In some ways, the tiny system works like a thermostat: it takes a small sample, analyzes it, and tells other components how to act in response.

Zhong's device has significant potential in the treatment of diabetes because it is small enough to be inserted into and remain in the body where it would conduct microfluidic analysis, constantly measuring the need for insulin and, then, delivering precise amounts of insulin at the appropriate times. Because the detector would remain constantly at work, the device could eliminate the need for regular blood tests. Moreover, because less time would have passed between infusions of insulin, it is likely that insulin levels could be better maintained, without soaring and surging as dramatically as they sometimes do with present day treatment strategies. While his device is not an "artificial pancreas," Zhong says that it could well prove to be an integral part of a system that could someday become just that.

Diabetics are not the only ones who will benefit from the tiny pumping device, developed by Zhong and his research team of undergraduate and graduate students and a post-doctoral researcher. Any small, closed environment could benefit from tiny equipment that requires little fuel and produces no waste, he said.

Zhong sees the use of microfluidics to automate and shrink down the size of science laboratory equipment as offering substantial advantages.

Making lab equipment smaller and more efficient is one of Zhong's chief research goals. It's a goal he sees as highly achievable.

"Look at the computer," he said. "Twenty years ago, it was huge. Now it's tiny." He eventually hopes to create what he calls a "lab on a chip," by shrinking down all of the equipment in a chemistry lab to the size of computer chips. Smaller equipment not only uses fewer resources, he said, but creates less waste.

While microfluidics will provide much better methods to do drug delivery this will not be the source of the greatest benefits from microfluidics. The absolutely revolutionary benefit from microfluidics will be that it will speed up the rate of advance of basic biological science. The biggest problem holding back medical advance is not a need for better ways to deliver drugs or to monitor a person's body for signs of disease. Our biggest problem is that we do not know enough about how genes and cells and organisms operate. We need more automated, faster, and cheaper ways to take apart biological systems to understand how they work in much greater detail. The greatest promise of microfluidics is that it will be able to lower costs, speed up experiments, and make experiments far more sensitive.

A lot of people wonder why, after decades of trying, we still do not have a general cure for cancer. The reason is pretty simple: we do not have tools that are sophisticated enough to understand cancer and normal cells well enough to be able to target cancer cells with enough selectivity. Microfluidics will provide much better tools for taking apart biological systems whether the purpose is to study cancer, the aging process, or any other biological problem.

By Randall Parker 2003 June 12 03:14 PM  Biotech Advance Rates
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Sensors On Vehicles Will Detect Traffic Congestion Levels

In the San Francisco Bay area of California commuters put an electronic device - essentially a form of radio frequency ID or RFID - on their cars that allows them to automatically pay tolls. Those devices are going to be detected by antennas that will be installed on literally hundreds of millions of Bay Area freeways in order to track how quickly cars move from one sensing antenna to the next one. This will be done to measure and report traffic congestion and traffic speeds in real time.

Using small electronic antennas under overpasses and on signs, the system will calculate freeway speeds by tracking drivers' FasTrak units -- devices that pay bridge tolls electronically.

As a FasTrak device passes by one of 150 roadside sensors, an electronic signature will be entered into a government database and then scanned repeatedly as the vehicle passes other sensors

Note the pattern here. An electronic ID device tracking is adopted for one uncontroversial purpose and goes into widespread use. Then new uses are proposed. Unless a large public outcry ensues the tracking devices are checked for at more locations and for more purposes. The cost of collecting data to track the movement of people and things will steadily decline and the collected data will be put to a steadily increasing number of uses.

There are safeguards in this use of FasTrak to prevent highway sensors from reporting the identity of the individual vehicles whose speeds are being measured. But I bet those safeguards could be lifted with just a firmware revision to prevent the scrambling and encryption of the vehicle identities.

By Randall Parker 2003 June 12 01:48 PM  Surveillance Society
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2003 June 11 Wednesday
Selective Blocking Of Mutant Genes Demonstrated

University of Iowa graduate student Victor Miller and other researchers have demonstrated the ability to selectively turn off a copy of a gene that differs by only a single nucleotide from other copies of the same gene in the same cell.

Turning off a mutant gene while keeping the normal gene active would be particularly useful in therapies aimed at treating so-called dominantly inherited diseases. In these diseases, a single mutant copy of a gene inherited from either parent dominates the normal gene by producing a protein that is toxic to cells. Thus, a successful therapy must remove or suppress the disease-gene rather than simply add a corrected version. At the same time, the normal gene may be essential, so it is important to be able to silence the disease-causing gene without affecting the normal copy. Many neurodegenerative conditions, including Huntington's disease (HD), are dominantly inherited. The HD gene also is an example of a normal gene that appears to be essential for normal function.

Working in cell culture, the UI researchers used the relatively new technology known as RNA interference to silence a mutant gene that causes the neurodegenerative condition called Machado-Joseph disease (or Spinocerebellar Ataxia Type 3), while leaving the normal gene alone.

Machado-Joseph disease (MJD), Huntington's disease and at least seven other neurodegenerative disorders all are caused by the same type of genetic mutation. The genetic defect in these diseases produces a mutated protein with an abnormally long stretch of a repeated amino acid. The mutant protein in each of these conditions is prone to clump together, forming aggregates, which appear to damage brain tissue. Other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, also are characterized by a tendency for proteins to misfold or clump in the brain. The UI team studies Machado-Joseph disease because it is a good model for investigating these types of neurodegenerative diseases.

Initial attempts to silence the mutant MJD gene by targeting the RNA interference to the repeat-expansion mutation failed. So the UI researchers focused on a single sequence difference, also known as a single nucleotide polymorphism (SNP), which occurs just next to the mutated sequence in about 70 percent of mutant MJD genes.

"When we tried to target the mutation itself, the interfering RNA was not able to distinguish the mutant gene from the normal gene and both copies were suppressed," said Henry Paulson, M.D., Ph.D., UI assistant professor of neurology and principle investigator of the study. "Then we noticed that there was a single nucleotide polymorphism in the mutant MJD gene that comes right after the mutation in most cases. We targeted that single nucleotide variation with RNA interference and that approach was able to distinguish the mutant from the normal and only knock down the mutant gene."

Paulson added that the discovery that RNA interference could distinguish between genes on the basis of a single nucleotide polymorphism was very exciting because every person's DNA differs mostly on the basis of these unique single letter variations in the genetic code. Thus it might be possible to use RNA interference to target unique single nucleotide polymorphisms associated with specific genes in order to manipulate those genes.

"Even when one cannot target a disease-causing mutation, it may still be possible to target the mutant gene on the basis of a SNP associated with that gene," Paulson said.

The research team also used RNA interference to target an actual disease-causing mutation due to a single base pair change in a gene. Tau is an important cellular protein that is mutated in some inherited dementias that are somewhat similar to Alzheimer's disease. The UI researchers directed RNA interference against a specific mutation in the Tau gene that is known to cause dementia in people. Again, the approach was successful in silencing only the mutant gene and not the normal gene.

This result is important because it is harder to replace a gene in a cell than it is to add another gene. Picture a cell that has two different variants of the same gene. Most cells have at least 2 copies of almost every gene (a notable exception being the genes that are on the X chromosome in males). Some people have genetic diseases that are the result of a dominant mutation. When a harmful mutation is dominant only one of the two copies of a gene has to have the mutation in order for the mutation to have harmful effects. The ability to effectively turn off the expression of just the harmful copy would be very valuable. This report provides evidence that even a point mutation of a single nucleotide in the DNA sequence of a gene (called a Single Nucleotide Polymorphism or SNP) provides enough of a difference to be targetted by RNA interference therapies.

To make RNA interference useful for many genetic disorders what is needed is a gene therapy that will cause copies of the interfering RNA sequence to be present in cells for a long time. To do that what is needed is the ability to add DNA to a cell that would persist and continually be used to make interfering RNA. The big enabling technologies needed are mini-chromosomes and a mechanism for delivering mini-chromsomes into large numbers of cells of a target cell type (e.g. into all the neurons in a brain). If a very small mini-chromosome could be added to a cell that expressed a sequence that could do RNA interference against the harmful variation of a gene then it would be possible to prevent the harmful gene from causing problems.

By Randall Parker 2003 June 11 03:01 PM  Biotech Manipulations
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Identical Twins Live Longer Than Fraternal Twins

Clones, er, I mean identical twins, live longer.

Zaretsky analyzed the responses and found one factor - social communication between twin partners - that was highly correlated with longer life in identical but not fraternal twins. Other types of social interaction, including active membership in church or community groups or close relationships with other relatives or friends, did not preferentially benefit identical or fraternal twins.

"Clearly, identical twins who communicated frequently survived longer than those who did not," he said. "This was not true of fraternal twins, whether they communicated or not."

In line with the Scandinavian studies, he found that the median life span of identical twins is 82 years - that is, half live more and half live less - versus 80.5 years for fraternal twins.

Interestingly, identical twins exhibited healthier behavior, which also contributed to their longevity. More of them exercised and fewer smoked in comparison with fraternal twins.

Zaretsky noted that exercise at all levels above the lowest level of exercise increased longevity.

"This indicates that a moderate amount of exercise is highly beneficial for health, and that highly vigorous exercise is not more beneficial than moderate exercise," he said.

What is going on here? Do they give each other better advice because they understand each other better? Or do they just feel better knowing that someone else so thoroughly understands them and can empathize with them? My guess is that the longer life is due to a reduction in stress caused by knowing someone who more deeply understands and sympathises. This reduces stress and stress reduction would definitely raise average life expectancy.

This result suggests a politically incorrect idea: Once the technology of cloning is perfected clones will live longer than non-clones. You can imagine just how unbearably snobbish that knowledge will make some class conscious clones in the future: "Oh you singletons, without fellow clones to talk to how ever can you bear to live your lonely wretched lives?" This will of course lead to gangs of resentful marginalized singleton youth roaming around looking for clones to beat up on.

By Randall Parker 2003 June 11 02:42 AM  Biotech Society
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2003 June 10 Tuesday
Composite Compounds Promote Repair Of Teeth

A class of composite materials helps in the repair of natural teeth.

"Smart materials" invented at the National Institute of Standards and Technology (NIST) soon may be available that stimulate repair of defective teeth. Laboratory studies show that these composites, made of amorphous (loosely structured) calcium phosphate embedded in polymers, can promote re-growth of natural tooth structures efficiently. In the presence of saliva-like solutions, the material releases calcium and phosphate ions, forming a crystalline calcium phosphate similar to the mineral found naturally in teeth and bone. Developed through a long-standing partnership between NIST and the American Dental Association (ADA), these bioactive, biocompatible materials are described in a forthcoming paper in the NIST Journal of Research.

Plans are being made for clinical trials, and several companies have expressed interest in licensing the patented material once a production-ready form is available. Initial applications include adhesive cements that minimize the decay that often occurs under orthodontic braces. The material also can be used as an anti-cavity liner underneath conventional fillings and possibly in root canal therapy.

NIST and ADA scientists continue to enhance the material's physicochemical and mechanical properties and remineralizing behavior, thereby extending its dental and even orthopedic applications. For example, the researchers found that adding silica and zirconia to the material during processing stabilizes the amorphous calcium phosphate against premature internal formation of crystals, thereby achieving sustained release of calcium and phosphate over a longer period of time.

What would be handy would be a way to use this material to cause a gradual repair of cracks and pits and small chipped off areas.

By Randall Parker 2003 June 10 03:31 PM  Biotech Teeth And Gums
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2003 June 09 Monday
Epigenetic Factors Reverse Nucleus Cancer State

Transfer of a cell nucleus from a cancer cell to a normal cell does not turn the normal cell into a cancer cell.

Nuclei removed from mouse brain tumor cells and transplanted into mouse eggs whose own nuclei have been removed, give rise to cloned embryos with normal tissues, even though the mutations causing the cancer are still present. This research, from scientists at St. Jude Children's Research Hospital, appears in the June 1 issue of Cancer Research.

The finding demonstrates that the cancerous state can be reversed by reprogramming the genetic material underlying the cancer, according to James Morgan, Ph.D., a member of the St. Jude Department of Developmental Neurobiology, and lead author of the study. The findings also indicate that genetic mutations alone are not always sufficient to cause a cell to become cancerous.

“Specifically, it shows that so-called epigenetic factors are key elements in the development and maintenance of tumors,” Morgan said.

Epigenetic factors are those that influence the cell’s behavior. Examples include environmental effects and chemical modification.

“The concept of epigenetic factors having a role in cancer is already largely accepted,” Morgan said. “In fact, it’s already known that epigenetic alterations of chromosomes can cause certain rare forms of cancer. And some anti-cancer agents actually target epigenetic changes. But this is the first formal proof of the theory in a living animal.”

Unlike mutations, epigenetic modifications of DNA are potentially reversible molecular events that cause changes in gene expression. Some genes that help prevent the development of cancer (e.g., tumor suppressor genes) can be targets of epigenetic factors. The inactivation of such a gene might make the DNA more vulnerable to developing a cancer-causing mutation.

A cell is an incredibly complex state machine. The transition of a cell into a cancerous state may require (at least in some cases) more than just a set of mutations in the nucleus. The challenge is going to be to figure out what it is about an egg cell that allows it to turn the nucleus from a cancerous cell back into a non-cancerous state.

The epigenetic state that is producing this effect might be enzymes that methylate (attach methyl groups to) nuclear DNA. Or it might be molecules that bind to DNA at sites in the nucleus where binding will shut down replication. Or possibly the key might not be something that is in the egg cells. The key could be that the egg cell cytoplasm is missing some compounds that are necessary to maintain rapid cell division. Those compounds might even be essential for telling the nucleus to make enzymes that make more of those compounds. There are just a lot of imaginable ways that the epigenetic state difference might be working to convert a cancerous nucleus back into a non-cancerous state.

Note that they transferred the nuclei from cancer cells into eggs, not into regular cells. An egg has only half the normal amount of DNA that a normal cell has since it has only one member of each pair of chromosomes. An egg's epigenetic state is very different from that of adult cells. It is so different that it is possible in some species to put adult non-cancerous cell nucleuses into eggs to make embryos. This doesn't work every time but it can be used to clone animals.

It would be interesting to know whether this transfer of a cancer cell nucleus into a different type of cell has ever been tried with non-egg cells as targets.

Update: Providing what may be a clue to how a nucleus could be shifted back to a non-cancerous state, a sey of recent papers point to an important role for methylation in cancer development. (free registration at The Scientist site required)

Minna's team has gone on to characterize RASSF1 expression in more than 1,000 tumor samples. "I would say that after p53, it's the most frequently inactivated tumor suppressor gene," says Minna. Some already have begun to link RASSF1A status with prognosis. "Several studies have now shown that the presence of RASSF1A methylation confers worse prognosis on non-small-cell lung cancer patients," he says.5

What will be interesting to see is whether epigenetic changes such as methylation are being caused by mutations elsewhere in the genome.

By Randall Parker 2003 June 09 02:58 AM  Biotech Manipulations
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Medical Transcripts And Personal Medical Privacy

The San Francisco Chronicle has an interesting piece on the practice of hospitals and other health care providers sending medical charts out to be read and typed into computers. Many medical transcriptionists in the US work in their homes doing the work. But an increasing number of medical records are being sent to India to be entered into computer format.

Last month, for example, India celebrated World Medical Transcription Week. "India has become the favorite country for outsourcing in the U.S.," Prasenjit Ganguly, vice president of the country's largest medical transcription service,

This passing around of hard copy medical records into homes and even to other countries certainly does not inspire confidence that medical privacy is being well protected. While the advance of electronic communications makes it easier to send records abroad to be translated in the longer run technology will probably eventually eliminate the need for human medical transcriptionists entirely. Scanning software ought to eventually be able to read many paper charts. Also, voice translation software ought to be able to transcribe video records made by doctors. But eventually all data entry on medical charts will be done directly into encoded digital form. Even voice records should be translated into properly spelled words just as doctors speak into a recording device.

Advanced integration of test equipment and lab results with medical computer databases should entirely eliminate the paper copies of test results. Increasing portions of medical records will never even be generated as hard copy in the first place.

So my FuturePundit forecast on medical record privacy is in the short term even greater distribution of written medical records to distant countries for data entry. But in the longer term all human medical transcriptionist work will be entirely eliminated.

Will the end of hard copy medical records increase medical privacy? Or will medical records be sent between health care providers, insurers, and other organizations more rapidly and in larger quantities? Will increasing numbers of workers of those organizations will be able to more quickly and easily look up details of your medical history? Will the result be that so many medical records are accessible by any one person that a black market in medical record information will become easier to develop since a single worker in a hospital chain or insurance company will be able to sell the records of many people to interested parties?

By Randall Parker 2003 June 09 01:18 AM  Surveillance Society
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2003 June 05 Thursday
Altruistic Punishment And Genetic Engineering Of The Mind

One of the recurring themes on FuturePundit is that the greatest danger from human genetic engineering will come from genetic engineering of the mind. We will develop the ability to create minds that will be dangerous or simply not compatible with the kind of societies that most of us prefer to live in. At one extreme, imagine genetically engineered minds devoid of conscience or empathy and at the same time highly calculating and ruthless in the pursuit of their own desires. Or, at a different extreme, imagine minds that so desired to fit in and to serve that they'd make ideal members of a communist collective ruled over by personalities genetically engineered to lead the masses.

The Debate About Genetic Engineering As A Threat To Human Nature

A number of commentators voice worries about human genetic engineering. Others consider those worries exaggerated in part because they think human genetic engineering is unlikely. Let me state up front that I think human genetic engineering is inevitable and that it will become a widespread practice. Furthermore, just because one believes that some specific objections voiced by particular worriers seem naive or unlikely does not discredit the very idea of being concerned about the consequences. It will eventually become possible to use genetic engineering to raise intelligence, to alter personality and to change the behavioral tendencies of our progeny. Whatever alterations parents or governments choose to make to future progeny will have profound effects upon human society. It would be irresponsible to simply dismiss the fears of those who are frightened by this prospect.

Some of those who are opposed to the practice of human genetic engineering are afraid that something vital about human nature will be lost by genetic engineering. Some are afraid that humans will be genetically engineered to be perpetually happy and that this happiness will somehow leave humans spiritually impoverished and devoid of the capacity to understand the deeper meaning of life. Curiously, such critics rarely seem to offer examples of how humans could be made less able to respect the rights of others. I suspect this particular danger from genetic engineering is not cited more often because the idea that humans can be made to have wildly different moral capacities and behavioral tendencies undermines the religious view of humans as moral actors possessed of consciences and capable of judging right from wrong according to some universal God-given standard. Well, the day is approaching within 10 or 20 years when it will become possible to do genetic engineering of offspring in such a way that they will have different behavioral tendencies and different innate conceptions of right and wrong. Therefore we can not afford to continue to avert our gaze from the biological basis of conscience, of the tendency to form moral judgements, and of the biological foundations of human values and normative beliefs. These basic attributes of human nature already vary considerably between humans. Genetic engineering will make these attributes more mutable in ways that constitute a substantial potential threat to the continuation of human civilization.

It seems likely that there are many genes in the human population which have variations that cause people to differ in their personality characteristics. Therefore the large number of different combinations of genetic variations found in human populations contribute to the large variety of personalities and behavioral tendencies also found among humans. Because of the genetic variations that are so largely responsible for the existing variety of personalities it should be possible to use only currently existing genetic variations to create a human population which is much different in average behavioral tendencies from existing human populations. A large change in the average of human behavior could be accomplished just by increasing the frequency of some genetic variations while decreasing the frequency of other variations which influence cognitive processes. Because there are already fairly extreme outliers in behavior and personality in the human population and since in at least some cases part of the reason for their extreme desires and behaviors is genetic it probably will not be necessary to create new genes or new variations of existing genes to do embryonic genetic engineering to create humans that differ considerably from the vast majority of existing humans. To get a sense of just how radically the human population could be altered without developing new genes or new genetic variations one has to look no further than the behavioral differences already existing in the human population.

Psychopaths Demonstrate The Danger Of Existing Extreme Human Outliers

Consider more extreme deviations from the human norm. One of the worst forms of deviations from human norms of behavior is found in psychopaths.

"The murdering psychopaths showed a much more positive association to violence. Psychopaths who were not murderers had a much more negative view of violence," Gray explained.

Unrestrained by the guilt that most humans would feel from harming others psychopaths do not even appear to have memory associations that categorize violence as unpleasant.

Normally, when shown a word on the screen, people take longer to figure out which button to press when non-related words -- such as "violent" and "pleasant" -- are on the same button, Snowden said.

However, psychopathic murderers responded differently, and completed the test "as if they do not associate violence and unpleasant," Snowden said.

Will it some day be possible to genetically engineer violent psychopaths? Why not? After all, a number of non-human predator species enjoy killing and in some species in some circumstances they even kill members of their own species. Surely these behavioral traits are somehow coded for by the genomes of these species. It may well be that there are genetic variations which influence personality that predispose the existing psychopaths to be psychopaths.

You might argue that very few people will want to choose genetic variations for their children that would increase the odds that the children will be psychopaths. True enough. But these outliers in human behavior and human cognition demonstrate just how far existing human nature extends without the use of genetic engineering. Genetic engineering will make it possible to create humans whose emotional make-up will differ substantially from what we see in most humans today.

Could Subtle Changes In Personalities Cause Huge Societal Changes?

Are there changes in human nature that at first glance might strike people as less extreme and less threatening than the creation of psychopaths and yet that could still cause huge problems for the healthy functioning of human societies? Are there changes in personality and in behavioral tendencies that people might want to give their offpsring that would have profound and negative consequences if a sufficiently large percentage of the populace opted to do genetic modification of embryos to cause personality changes in their offspring?

An accurate answer to those questions would give us a better idea of whether the ability to do genetic engineering in the embryonic stage of our future progeny could lead to disastrous consequences for the future of human civilization. One way to attempt to answer these questions is to look for evidence of characteristics of human nature that are beneficial for society, which may be genetically based, which are not equally shared by all humans, and for which we could imagine reasons why at least some prospective parents would want to modify those characteristics in their future offspring. This brings us to the topic of altruistic punishment.

A Study Of Altruistic Punishment

Ernst Fehr of the University of Zurich and Simon Gächter of the University of St. Gallen in Switzerland published an interesting study "Altruistic punishment in humans" in the January 2002 issue of Nature. This study has occasioned a great deal of discussion about the implications it holds for human nature. Fehr and Gachter showed that many people will pay to punish those who do not cooperate even though the punishers derive no other benefit from punishing aside from the satisfaction of carrying out the punishment.

In an investment game with shared profits, players punish those who do not contribute to the group's good, despite the personal cost. The emotional satisfaction of dispensing justice seems to spur them on: "People say, 'I like to punish'," says Ernst Fehr of the University of Zurich.

The punishment was doled out to people who the punishers knew they would not play again. The ability to dole out punishment caused people to cooperate to mutual benefit.

Investment climbed to four times the previous level as the threat of punishment encouraged cooperation.

Researchers said that anger was the reason the players handed out punishment, even though it cost them money to do so.

"At the end of the experiment, people told us they were very angry about the free-riders," said Fehr. "Our hypothesis is that negative emotions are the driving force behind the punishment."

These people doled out punishment at cost to themselves even though one rule of the game was that players never played with other players more than once. The punishment therefore did not benefit the punisher by causing the punished person to be more cooperative toward the punisher in future rounds of the game.

In a separate series of games that Fehr and Gachter conducted where it was not possible to inflict punishment the amount of cooperation quickly declined. However, in game series where it was possible to inflict punishment on non-cooperating free riders the amount of cooperation rose in successive rounds even though each person played a completely new set of people in each round.

"It's a very important force for establishing large-scale cooperation," Dr. Fehr said in a telephone interview. "Every citizen is a little policeman in a sense. There are so many social norms that we follow almost unconsciously, and they are enforced by the moral outrage we expect if we were to violate them."

People expected to be punished based on their previous experience and they adjusted their behavior accordingly. This expectation that others would punish them even though others had nothing to gain from doling out punishment was key to increasing cooperation in successive rounds of games.

You can read the full paper "Altruistic punishment in humans" in PDF format.

Altruistic punishment took place frequently. In the ten sessions, subjects punished other group members a total of 1,270 times; 84.3% of the subjects punished at least once, 34.3% punished more than five times during the six periods, and 9.3% punished even more than ten times. Punishment also followed a clear pattern. Most (74.2%) acts of punishment were imposed on defectors (that is, below-average contributors) and were executed by cooperators (that is, above-average contributors), and punishment of the defectors was harsh (Fig. 1). For example, if a subject invested 14±20 MUs less than the average investment of the other members during periods 5 and 6, the total group expenditures for punishing this subject were almost 10 MUs. Moreover, the more a subject's investment fell short of the average investment of the other three group members, the more the subject was punished. The pattern and strength of punishment was also stable across time (Fig. 1). A Wilcoxon signed rank test of punishment in periods 1±4 versus periods 5 and 6, with 10 matched observations, yields z = -1.07, P = 0.285 (two-tailed). The same test for periods 1±5 versus period 6 yields z = 0.178, P = 0.859 (two-tailed).

Note that the most enthusiastic cooperators were also the ones most likely to punish. Those people who most enjoyed working in a cooperating group also had the strongest drive to make others cooperate as well. It may be that the anger that came from observing free rider behavior came as a response of being denied the joy humans experience from working in a cooperating team. Are there genetic variations that make people feel greater or lesser amounts of pleasure from working in cooperating groups? If there are (and this seems likely to be the case) then imagine how much human societies would change if a substantial portion of the population chose to give their offspring genetic variations that increased or decreased their desire to work in cooperating groups or to punish those who didn't.

The chain of cause and effect that leads to the infliction of punishment probably has a few different parts that are each separately variable from person to person. The participants in this study were motivated by anger. But in order to feel anger they first had to perceive unfairness. In order to do that they had to believe that people in a group have an obligation to cooperate for joint benefit. This desire to work together is an important human desire. Is there a genetic basis for just this desire? Well, look at other species. Some like to work together in groups. Others prefer solitary existences. Surely there must be a genetic basis for this inter-species difference in behavior.

The participants also had to be willing to act on their anger, pay a price for that action, and to act even when they stood to gain nothing personally from acting. It is likely that different groups of genes and genetic variations separately influence different parts or stages of the response that leads to infliction of punishment. Though it is not clear just what those parts are.

Is Altrustic Punishment The Result Of A Lack Of Discernment?

Cooperation is encouraged by the ability of people to reward each other for cooperating. But what Fehr and Gachter found was that the ability to punish non-cooperators encouraged cooperation and, crucially, that most people are willing to incur costs in order to punish non-cooperators. Those who elected to pay to punish must have derived satisfaction from the ability to punish those who angered them by acting in what the punishers saw as an unfairly selfish manner.

Why would altruistic punishment be selected for by evolution? One possible explanation is that the behavior that was selected for caused benefit to those who had the trait in ancient environments but that in modern environments the trait frequently causes humans to engage in altruistic punishment. In this view we are seeing it because humans are living under conditions which are far from the conditions in which we evolved. It is quite possible that historically humans were far more likely to benefit from punishing those who did not cooperate with any group they were members of because people were members of fewer groups and for longer periods of time per group. Anyone who was punished was almost always someone with whom the punisher would have future dealings. Therefore humans may not have been under enough selective pressure to become more discerning about whom to punish. There wasn't as great of a need to be able to accurately judge when the costs of inflicting punishment would be a net benefit to the punisher because of the longer term nature of most relationships. Therefore the willingness to mete out punishment to noncooperators probably didn't need to be complex enough to make humans draw distinctions between people they would or would not have future dealings with.

If you think that humans do not have traits that are expressed in ways that show insufficient use of cognitive processes to discern the appropriateness of emotional responses then consider sexual jealousy in human males. It was probably selected for in men so that men would have a motive to prevent their women from mating with someone else. A man unknowingly who raised another man's child wasted his own precious resources and decreased his reproductive fitness. Emotional responses that decrease the likelihood of that happening were selected for. But in the modern era sexual jealousy happens in men who are in relationships with women who are incapable of having children or unwilling to do so. So why should jealousy happen under those circumstances? Because the emotional response of jealousy was never selected for to use a cognitive process that is sufficiently discerning to be able to take into account mating that did not have the possibility of causing reproduction. That kind of mating is far more common today than it was in our evolutionary past when our traits were selected for. Also, people who are not going to reproduce are not going to pass along a greater or lesser tendency toward sexual jealousy and therefore there is not much of a mechanism available to even select for a more complex sexual jealousy response in the modern world.

Not everyone in the Fehr and Gächter study meted out punishments. There are, broadly speaking, two possible major reasons why some did not pay to punish. Some people may simply be less easily roused to punish uncooperative people in general. Some step in the process leading to the act of punishment may be harder to stimulate in them. Another possibility is that some may be far more discerning (either for genetic or environmental/educational reasons) in evaluating when paying to punish is worth it to them. It is likely that both of these factors cause differences in how people respond to non-cooperators and that genetic variability has an effect on both factors.

Change The Desire To Punish Free Riders Or The Ability To Discern One's Interests?

How does all this matter to the genetic engineering of offspring? Suppose genetic variations will be discovered that affect how easily people become angered by uncooperative behavior. Imagine that some people choose to give their offspring genetic variations that decrease their tendency to be angered by noncooperation. It is possible to conceive of plausible reasons why some people will make these choices for their progeny. Parents might decide they want their children to go thru life feeling less anger about perceived injustices in their lives. If that happened then future generations would be less inclined than current generations to enforce cooperation. The consequences for how human societies functioned would be profound.

It is also possible that there are genetic variations that make a person more able to evaluate whether paying to punish someone is worth it. One can easily imagine why a parent would want to make their children more capable of subtle discernment of where their real interests lie. This ability would give their kids an edge in dealing with other people in business negotiations and in other settings. But that enhanced capacity to discern where one's own interests lie might come at the expense of making society function less well as a whole - at least in some respects. In a society where people get less riled up when they are able to more accurately calculate their own self-interest then there would be less altruistic punishment doled out. This would effectively lower the amount of informal policing of norms in a society. Therefore those who would go unpunished would, as a consequence, be more willing to be uncooperative and to free load off the efforts of others. Again, the consequences would be profound and problematic.

The More General Desire To Punish Perceived Unfairness

Avoidance of cooperation in working toward a group goal is just one way that individuals can cause problems for others in a group. People can also take the possessions of others, hurt others, and deceive others for a variety of reasons. These other types of perceived unfair behavior are all also capable of eliciting an anger response and a desire to punish.

The desire to punish perceived unfairness is important. That desire causes behavior that is altruistic and that is necessary to maintain cooperation between members of groups. The desire to punish the unfair among us probably motivates police officers, prosecutors, soldiers, government and corporate whistleblowers, and a great many others as well. Imagine a society where either a smaller percentage of the population would ever feel angry enough to perform altruistic punishment or where those who did feel the desire didn't feel it as strongly and didn't act on it as often. The resulting society might have more crime for a number of reasons. Law enforcement personnel might be less motivated. Fewer would be willing to work at the most challenging law enforcement jobs since job satisfaction from meting out punishment would be felt to a much lesser extent. Witnesses to crimes would be less motivated to come forward to testify or to intervene to stop a crime. An assortment of other behaviors would change in ways that reduced restraints on law-breakers.

But the effects would not be limited to law enforcement. Members of groups punish each other in an assortment of ways in a variety of environments including businesses, volunteer groups, militaries, and families. Imagine every kind of situation where you've wanted to punish someone for something they did. Genetic engineering that affected that desire would change human behavior in all of those situations.

A person making a purely selfish economic calculation would probably not choose to punish unfairness in cases where the bulk of the benefits of meting out the punishment would flow to other people. Witnesses to crimes, to unfair acts in the workplace, and to unfair behavior in general are frequently in the position where they have little at stake and yet often are willing to intervene or testify or otherwise pay a price to prevent or punish unfairness that is not directly aimed at them personally.

Another possible consequence of a reduction in the desire to perform altruistic punishment might be that governments would be more likely to abuse a small fraction of the populace. The rest of the populace would be less inclined to get angry about it and to make sacrifices to protest and oppose such government actions. Therefore governments would be less constrained. On the margin a large number of decisions would be made differently in ways that would make a society function less well and a society whose populace was less motivated to dole out altruistic punishment might well become less free as a consequence.

Fehr and Gachter have uncovered a human behavior that is most likely the product of natural selection. The fact that people desire to punish others even though they have to pay to mete out the punishment suggests that the punishment behavior is deeply built into human minds. This desire to punish those who are viewed as unfair is probably an essential element of human nature needed to maintain a civilized society.

Fairness In Real Life Situations Is Harder To Judge And Open To Dispute

The desire to mete out justice is problematic because determining what is fair is difficult and open to dispute. Fehr and Gachter defined the rules of simple games that their experimental subjects played. The actions of each of the players were easy for the other players to understand. There was no uncertainty as to the number of players, the actions taken, or their ramifications. There was no dispute as to the legitimacy or interpretation of the game rules. There was no need for reference to events of previous days, months, years, or centuries. By contrast, real human societies have all these complications and much more.

In real life situations disagreements over what is fair and over what are the relevant facts in a given situation make many acts of punishment itself seem unfair to those receiving it or to observers. One reason people differ on whether any particular act of punishment is justified is that people can be and frequently are misled by others or by their own flawed cognitive processes into reaching false conclusions about who did what and why. The desire to punish unfairness can occur in situations where the real facts of the matter do not justify the response. Also, some react with to perceived unfairness with what others see as excessive anger and their response can seem a disproportionate act of punishment compared to the original act that evoked the perception of unfairness. It is easy to see how that can get out of hand. For instance, if members of a nation, religion, or other grouping become convinced that they have been on the receiving end of a great injustice (e.g. the famous Nazi myth about being stabbed in the back by Jews in World War I which contributed to World War II) this sort of belief can be used to motivate them to commit all manner of violent acts individually and collectively. But incorrect beliefs about unfair treatment and excessive responses to perceived unfairness are common well below the level of grand historical events. Such beliefs can be found everywhere in school playgrounds, work places, and marriages. Surely, the impulse to punish unfairness is not an unmitigated benefit to the human race.

Still, in spite of all the problems that arise from the desire to punish a bigger problem would occur if people had a weaker desire to punish the unfairness of others. Societies absolutely need cooperation and the ability and desire to inflict punishment are essential to the maintenance of a sufficient degree of cooperation to make societies function well.

We Need To Understand The Genetic Basis Of Human Nature

The most important missing element in research on the intersection between economics and psychology is the genetic link. But at this point in time it is hard to make that connnection. The cost of DNA sequencing is still in the millions of dollars per person. It is too expensive to find connections between genetic variations and variations in behavior. Surely progress along that front is being made. But it would be far easier to do if every experiment on human behavior could include complete DNA sequence information on each study participant. Then genetic variations could be compared with behavioral differences. The inability to effectively control for genetic differences when doing experiments is one of the biggest factors holding back the advance of a more accurate social and psychological science of human nature.

Science is starting to supply us with information about how genetic variations affect human nature. The coming abililty to do make use of this information when doing germ line genetic engineering will cause a huge conflict between the desires of parents to give their offspring characteristics that the parents prefer versus the interests of the larger society on how members of future generations act toward the rest of us. The ability to affect how and when future generations will act in altruistic fashions will be politically far more contentious than current issues such as abortion or embryonic stem cell therapy.

The problem with allowing parents alone to decide on what future generations will be like is that we all have to live with the consequences of their decisions. Currently the effects of decisions that people make over who to mate with can not be easily measured or predicted. Also, currently there are limits to how much a difference each person can make in the genetic make-up of their progeny because they can only pass down what they have. What is going to change is that much of the uncertainty will be eliminated and the degree of control on the outcome will rise enormously. This will allow much larger changes in distribution of behavioral tendencies in populations. Averages and extremes will shift in ways that we can only begin to guess at today.

If one wants to have a relevant debate about the dangers of genetic engineering of humans then the central issue must be genetic engineering of the mind. The biggest benefits and greatest dangers come from the decisions people make when they start genetically engineering the minds of future generations.

Update: See Kenneth Silber's essay on Tech Central Station entitled Genetic Paradoxes.

And yet, it is precisely such automatons that would be most readily manipulated by genetic engineering. Genetic engineering's conservative critics seem to believe both that humans are beings of depth and complexity, and that humans can be transformed by science with relative ease. These positions are in considerable tension with each other. Could it be that conservatives who worry about genetic engineering actually regard dignity as an illusion that must be protected from scientific probing?

Silber sees contradictions with the conservative critique of genetic engineering by Leon Kass, Bill McKibben et.al. that are similar to the problems I see in their arguments. If there is something irreducibly magic about being humans then we can't possibly genetically engineer humans who are missing the magic elements. Are we just going to reduce human dignity and make life less meaningful if we genetically engineer people? Or are we going to gain the ability to change human nature? Also, when people talk about "human nature" it is only sensible to mean charactertistics of the mind. Are there characteristics of the mind that are inherent to human nature that will be changeable some day with genetic engineering? I think so. Others differ.

There are others who are attacking the conservative critique who also seem quite wrong to me. Charles Murtaugh recently made an argument in a recent article on Tech Central Station arguing it is all so complex we may never figure it out.

When the trait is complex, and the genetics are complex, their interaction may well never be unraveled.

But to illustrate his point Charles uses an example where the womb environment differences between lab mouse strains turned out to be important. But the scientists investigating did find the factor that accounted for a developmental difference even though the genetic difference between the strains operated by changing the womb environment in a way that changed behavior. The mechanism of action was seemingly obscure and yet it was identified. The cause did not remain unknowable. Well, I'm reminded of a quote spoken by the character Yama-Dharma the Death God in Roger Zelazny's Lord of Light:

"It is the difference between the unknown and the unknowable, between science and fantasy - it is a matter of essence. The four points of the compass be logic, knowledge, wisdom and the unknown. Some do bow in that final direction. Others advance upon it. To bow before the one is to lose sight of the three. I may submit to the unknown, but never to the unknowable. The man who bows in that final direction is either a saint or a fool. I have no use for either."

(You can see the chapter context here)

Yes, we will figure out what all the genes do and how they interact with each other and with the environment. Long before we understand what they all do we will understand what many of them do and how differences between them create differences in personality, intelligence, and behavior. We will be able to figure that out by sequencing millions of people and comparing their genetic sequences and their mental qualities (as well as medical histories and assorted other things about them).

Aside: For more on how it will become possible to do massive comparisons of genetic sequences see reports on efforts to drive down the costs of DNA sequencing by many orders of magnitude in my Biotech Advance Rates archive.

What annoys me about the arguments by Steven Pinker, Charles Murtaugh, Kenneth Silber, and Amy Greenwood (see my pleasant debate with Amy in the comments section of this post) is the way they try to down play the fears of the spiritual conservatives of the Kass school of bioethics (no, there is no such formal school but close enough) by arguing that it will not even be possible to abuse biotechnology to create intelligent creatures that are far from the human norm. They sound like Officer Barbrady of South Park: "Move along folks. Nothing to see here".

An argument that it will be hard to develop the knowledge needed to do germ line genetic engineering is not an argument that it will never happen. Even if it takes 20 years (as Amy estimates for single location genetic changes to fix genetic diseases - see the comments of this post) to develop the ability to do germline genetic engineering, well, 20 years is not all that long a time. Humans seem to have a tendency to think that 20 years into the past is more real than 20 years into the future because they can remember back 20 years. But while we can not go back in a time machine 20 years into the past most of us now alive will slowly but surely travel in the unidirectional time machine of this universe to 20 years in the future (at least barring global thermonuclear war or a massive asteroid strike). We will live in that day when we will have the ability to do a great many more things with biotechnology than we can now. Even if germline genetic engineering to change many genetic locations to affect a complex trait such as the mind is 30 year out it will happen. It is real kids. It is coming. We are moving along into a future where many more things will become possible.

Another argument these folks make is that so many genetic variations are involved in causing different types of minds that we will not be able to manage to make changes complex enough to change the desired traits while also avoiding undesireable side effects. But this is an argument that the task is difficult, not that it is impossible. We are gaining the ability to manage more complex processes all the time. Our tools for understanding and modelling complex processes continue to improve and in all likelihood will continue to do so. We will eventually gain the ability to genetically engineer offspring to intentionally cause them to have minds which will be substantially different than what their minds would have been like had they just gotten the unmodified genes of their parents. We ought to discuss what problems may arise as a consequence of this inevitable development and what we will need to do to try to avoid the dangers that unwise and malicious uses of these technologies will make possible.

By Randall Parker 2003 June 05 05:57 PM  Brain Altruism
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Draft: Altruistic Punishment And Genetic Engineering Of The Mind

One of the recurring themes on FuturePundit is that the greatest danger from human genetic engineering will come from the ability to create minds that will be dangerous or simply not compatible with the kind of societies that most of us prefer to live in. At one extreme, imagine genetically engineered minds devoid of conscience or empathy and at the same time highly calculating and ruthless in the pursuit of their own desires. Or, at a different extreme, imagine minds that so desired to fit in and to serve that they'd make ideal members of a communist collective ruled over by personalities genetically engineered to lead the masses.

The Debate About Genetic Engineering As A Threat To Human Nature

A number of commentators voice worries about human genetic engineering. Those who are opposed to the practice are afraid that something vital about human nature will be lost by genetic engineering. Some are afraid that humans will be genetically engineered to be perpetually happy and that that this happiness will somehow leave humans spiritually impoverished and deviod of the capacity to understand the deeper meaning of life. Curiously, such critics rarely seem to offer examples of how humans could be made less able to respect the rights of others. I suspect this particular danger from genetic engineering is not cited more often because the idea that humans can be made to have wildly different moral capacities and behavioral tendencies undermines the model of humans as moral actors possessed of consciences and capable of judging right from wrong according to some universal God-given standard. Well, the day is approaching in 10 or 20 years time when it will become possible to do genetic engineering of offspring in such a way that they will have different behavioral tendencies and different innate conceptions of right and wrong. Therefore we can not afford to continue to avert our gaze from the biological basis of conscience, of the tendency to form moral judgements, and of the biological foundations of human values and normative beliefs. These basic attributes of human nature already vary considerably between humans already. Genetic engineering will make these attributes more mutable in ways that constitute a substantial potential threat to the continuation of human civilization.

It seems mostly likely that there are many genes which have variations in the human population that cause people to differ in their personality characteristics. Therefore the large number of different combinations of genetic variations found in human populations contribute to the large variety of personalities and behavioral tendencies also found among humans. Because of this large existing variety of personalities one could in theory create a human population much different in average behavioral tendencies from other human population without introducing either new genes or any new genetic variations that are not already found in humans. A large change in the average of human behavior could be accomplished just by increasing the frequency of some genetic variations while decreasing the frequency of other variations which influence cognitive processes. Because there are already fairly extreme outliers in behavior and personality in the human population and since in at least some cases part of the reason for their extreme desires and behaviors is genetic it will probably not be necessary to create new genes or new variations of existing genes to use in genetic engineering that would create humans that differ considerably from the vast majority of existing humans. To get a sense of just how radically the human population could be altered without developing new genes or new genetic variations one has to look no further than the most extreme differences already existing in the existing human population.

Psychopaths Demonstrate The Danger Of Existing Extreme Human Outliers

Consider more extreme deviations from the human norm. One of the worst form of deviations from human norms of behavior is found in psychopaths.

"The murdering psychopaths showed a much more positive association to violence. Psychopaths who were not murderers had a much more negative view of violence," Gray explained.

Unrestrained by the guilt that most humans would feel from harming others psychopaths do not even appear to have memory associations that categorize violence as unpleasant.

Normally, when shown a word on the screen, people take longer to figure out which button to press when non-related words -- such as "violent" and "pleasant" -- are on the same button, Snowden said.

However, psychopathic murderers responded differently, and completed the test "as if they do not associate violence and unpleasant," Snowden said.

Will it some day be possible to genetically engineer violent psychopaths? Why not? After all, a number of non-human predator species enjoy killing and in some species in some circumstances they even kill members of their own species. Surely these behavioral traits are somehow coded for by the genomes of these species. It may well be that there are genetic variations which influence personality that predispose the existing psychopaths to be psychopaths.

You might argue that very few people will want to choose genetic variations for their children that would increase the odds that the children will be psychopaths. True enough. But these outliers in human behavior and human cognition demonstrate just how far existing human nature extends without the use of genetic engineering. Genetic engineering will make it possible to create humans whose emotional make-up will differ substantially from what we see in most humans today.

Subtle Changes In Personalities Could Cause Huge Societal Changes?

Are there changes in human nature that at first glance might strike people as less extreme and less threatening than the creation of psychopaths that could still cause huge problems for the healthy functioning of human societies? Are there changes in personality and in behavioral tendencies that people might want to give their offpsring that would have profound and negative consequences if a sufficiently large percentage of the populace opted to do genetic modification of embryos?

An accurate answer to those questions would give us a better idea of whether the ability to do genetic engineering in the embryonic stage of our future progeny could lead to disastrous consequences for the future of human civilization. One way to attempt to answer these questions is to look for evidence of characteristics of human nature that are beneficial for society, which may be genetically based, which are not equally shared by all humans, and for which we could imagine why reasons at least some prospective parents would want to modify those characteristics in their future offspring. This brings us to the topic of altruistic punishment.

A Study Of Altruistic Punishment

Ernst Fehr of the University of Zurich and Simon Gächter of the University of St. Gallen in Switzerland published an interesting study "Altruistic punishment in humans" in the January 2002 issue of Nature. This study has occasioned a great deal of discussion about the implications it holds for human nature. Fehr and Gachter showed that many people will pay to punish those who do not cooperate even though the the punishers derive no other benefit from punishing aside from the satisfaction of carrying out the punishment.

In an investment game with shared profits, players punish those who do not contribute to the group's good, despite the personal cost. The emotional satisfaction of dispensing justice seems to spur them on: "People say, 'I like to punish'," says Ernst Fehr of the University of Zurich.

The punishment was doled out to people who the punishers knew they would not play again. The ability to dole out punishment caused people to cooperate to mutual benefit.

Investment climbed to four times the previous level as the threat of punishment encouraged cooperation.

Researchers said that anger was the reason the players handed out punishment, even though it cost them money to do so.

"At the end of the experiment, people told us they were very angry about the free-riders," said Fehr. "Our hypothesis is that negative emotions are the driving force behind the punishment."

These people doled out punishment at cost to themselves even though one rule of the game was that players never played with other players more than once. The punishment therefore did not benefit the punisher by causing the punished person to be more cooperative toward the punisher in future rounds of the game.

In a separate series of games that Fehr and Gachter conducted where it was not possible to inflict punishment the amount of cooperation quickly declined. However, in game series where it was possible to inflict punishment on non-cooperating free riders the amount of cooperation rose in successive rounds even though each person played a completely new set of people in each round.

"It's a very important force for establishing large-scale cooperation," Dr. Fehr said in a telephone interview. "Every citizen is a little policeman in a sense. There are so many social norms that we follow almost unconsciously, and they are enforced by the moral outrage we expect if we were to violate them."

People expected to be punished based on their previous experience and they adjusted their behavior accordingly. This expectation that others would punish them even though others had nothing to gain from doling out punishment was key to increasing cooperation in successive rounds of games.

You can read the full paper in PDF format.

Altruistic punishment took place frequently. In the ten sessions, subjects punished other group members a total of 1,270 times; 84.3% of the subjects punished at least once, 34.3% punished more than five times during the six periods, and 9.3% punished even more than ten times. Punishment also followed a clear pattern. Most (74.2%) acts of punishment were imposed on defectors (that is, below-average contributors) and were executed by cooperators (that is, above-average contributors), and punishment of the defectors was harsh (Fig. 1). For example, if a subject invested 14±20 MUs less than the average investment of the other members during periods 5 and 6, the total group expenditures for punishing this subject were almost 10 MUs. Moreover, the more a subject's investment fell short of the average investment of the other three group members, the more the subject was punished. The pattern and strength of punishment was also stable across time (Fig. 1). A Wilcoxon signed rank test of punishment in periods 1±4 versus periods 5 and 6, with 10 matched observations, yields z = -1.07, P = 0.285 (two-tailed). The same test for periods 1±5 versus period 6 yields z = 0.178, P = 0.859 (two-tailed).

Note that the most enthusiastic cooperators were also the ones most likely to punish. Those people who most enjoyed working in a cooperating group also had the strongest drive to make others cooperate as well. It may be that the anger that came from observing free rider behavior came as a response of being denied the joy humans experience from working in a cooperating team. Are there genetic variations that make people feel greater or lesser amounts of pleasure from working in cooperating groups? If there are (and this seems likely to be the case) then imagine how much human societies would change if a substantial portion of the population chose to give their offspring genetic variations that increased or decreased their desire to work in cooperating groups or to punish those who didn't.

There are probably a few different parts of the chain of cause and effect that lead to the infliction of punishment that are each separately variable from person to person. The participants in this study were motivated by anger. But in order to feel anger they first had to perceive unfairness. In order to do that they had to believe that people in a group have an obligation to cooperate for joint benefit. This desire to work together is an important human desire. Is there a genetic basis for just this desire? Well, look at other species. Some like to work together in groups. Others prefer solitary existences. Surely there must be a genetic basis for this inter-species difference in behavior.

The participants also had to be willing to act on their anger, pay a price for that action, and to act even when they standed to gain nothing personally from acting. Genetics likely separately influences a few parts of the response here. Though it is not clear just what those parts are.

Is Altrustic Punishment The Result Of A Lack Of Discernment?

Cooperation is encouraged by the ability of people to reward each other for cooperating. But what Fehr and Gachter found was that the ability to punish non-cooperators encouraged cooperation and, most important, most people are willing sacrifice to be able to punish non-cooperators. Those who elected to pay to punish must have derived satisfaction from the ability to punish those who angered them by acting in what the punishers saw as an unfairly selfish manner.

Why would altruistic punishment be selected for by evolution? One possible explanation is that in reality it was not selected for. In this view we are seeing it because humans are living under conditions which are far from the conditions in which we evolved. It is quite possible that historically humans were far more likely to benefit from punishing those who did not cooperate with any group they were part of because people were members of fewer groups and for longer periods of time per group. Anyone who was punished was someone who the punisher would have future dealing with. Therefore humans may not have been under enough selective pressure to become more discerning about who to mete punishment to. There wasn't as great of a need to be able to accurately judge when the costs of inflicting punishment would be a net benefit to the punisher. The willingness to mete out punishment to noncooperators probably didn't need to be complex enough to make humans draw distinctions between people they would or would not have future dealings with.

If you think that humans do not have traits that are expressed in ways that show insufficient use of cognitive processes to discern the appropriateness of an emotional response then consider sexual jealousy in human males. It was probably selected for in men so that men would have a motive to prevent their women from mating with someone else. A man unknowingly raising another man's child is wasting his own resources. Emotional responses that decrease the likelihood of that happening were selected for. But sexual jealousy happens in men who are in relationships with women who are incapable of having children. Why is that? Because the emotional response of jealousy was never selected for to use a cognitive process that is sufficiently discerning to be able to take into account mating with women that did not have the possibility to causing reproduction. That kind of mating is far more common today than it was in our evolutionary past. Also, people who are not going to reproduce are not going to pass along a greater or lesser tendency toward sexual jealousy and therefore there is not much of a mechanism available to even select for a more complex sexual jealousy response in the modern world.

Not everyone in the Fehr and Gächter study meted out punishments. There are, broadly speaking, two possible major reasons why some did not pay to punish. Some people may simply be less easily roused to punish uncooperative people in general. Some step in the process leading to the act of punishment may be harder to stimulate in them. Another possibility is that some may be far more discerning (either for genetic or environmental/educational reasons) in evaluating when paying to punish is worth it to them. It is likely that both of these factors cause differences in how people respond to non-cooperators and that genetic variability has an effect on both factors.

Change The Desire To Punish Free Riders Or The Ability To Discern One's Interests?

How does all this matter to the genetic engineering of offspring? Suppose genetic variations are discovered that affect how easily people become angered by a lack of cooperation in general. Imagine that some people choose to give their offspring genetic variations that decrease their tendency to be angered by noncooperation. Parents might decide they want their children to go thru life feeling less anger about perceived injustices in their lives. If that happened then future generations would less inclined than current generations to enforce cooperation. The results for human societies would be profound.

There is also the possibility that there are genetic variations that make a person more able to evaluate whether paying to punish someone is worth it. One can easily imagine why a parent would want to make their children more capable of subtle discernment of where their real interests lie. This ability would give their kids an edge in dealing with other people in business negotiations and in other settings. But that enhanced capacity to discern where one's own interests lie might come at the expense of making society function less well as a whole. In a society where people get less riled up when they are able to more accurately calculate their own self-interest then there would be less altruistic punishment doled out. This would effectively lower the amount of informal policing of norms in a society. Therefore people in general would be more willing to be uncooperative and to free load off the efforts of others. Again, the consequences would be profound and problematic.

The More General Desire To Punish Perceived Unfairness

A reluctance to cooperate in working toward a group goal is just one way that individuals can cause problems for others in a group. People can take the possessions of others, hurt others, and deceive others for a variety of reasons. These other types of perceived unfair behavior are all capable of eliciting an anger response and a desire to punish.

The desire to punish perceived unfairness is important. It causes behavior that is altruistic and that is necessary to maintain cooperation between members of groups. The desire to punish the unfair among us probably motivates police officers, prosecutors, soldiers, government and corporate whistleblowers, and a great many others as well. Imagine a society where either a smaller percentage of the population would feel angry enough to do punishment or where those who did it wouldn't want to do it as much. The resulting society might have more crime for a number of reasons. Llaw enforcement personnel might be less motivated. Fewer would be willing to work at the most challenging law enforcement jobs since one form of job satisfaction would be felt to a much lesser extent. Witnesses to crimes would be less motivated to come forward to testify or to intervene to stop a crime. An assortment of other behaviors should change in ways that reduced restraints on law-breakers.

A person making a purely selfish economic calculation would probably not choose to punish unfairness in cases where the bulk of the benefits of meting out the punishment would flow to other people. Witnesses to crimes, to unfair acts in the workplace, and to unfair behavior in general are frequently in the position where they have little at stake involving people they do not know often are willing to intervene or testify or otherwise pay a price to prevent or punish unfairness that is not directly aimed at them personally.

Another possible consequence of a reduction in the desire to perform altruistic punishment might be that governments would be more likely to abuse a small fraction of the populace because the rest of the populace would be less inclined to get angry about it and to make sacrifices to protest and oppose the government. On the margin a large number of decisions would be made differently in ways that would make a society function less well and a society whose populace was less motivated to dole out altruistic punishment might well become less free as a consequence.

Fehr and Gachter have uncovered a human behavior that is most likely the product of natural selection. The fact that people desire to punish others even though they have to pay to mete out the punishment suggests that the punishment behavior is deeply built into human minds. This desire to punish those who are viewed as unfair is probably an essential element of human nature needed to maintain a civilized society.

Fairness In Real Life Situations Is Harder To Judge And Open To Dispute

The desire to mete out justice is problematic because determining what is fair is difficult and open to dispute. Fehr and Gachter defined the rules of simple games that their experimental subjects played. The actions of each of the players were easy for the other players to understand. There was no uncertainty as to the number of players, the actions taken, or their ramifications. There was no dispute as to the legitimacy or interpretation of the game rules. There was no need for reference to events of previous days, months, years, or centuries. By contrast, real human societies have all these complications and much more.

In real life situations disagreements over what is fair and over what are the relevant facts in a given situation make punishment itself to often be seen as unfair. People can be and frequently are misled by others or by their own flawed cognitive processes into reaching false conclusions about who did what and why. The desire to punish unfairness can occur in situations where the real facts of the matter do not justify the response. Also, once the desire to punish becomes strong enough the response can become disproportionate to the original act that evoked the feeling of perceived unfairness. It is easy to see how that can get out of hand. For instance, if members of a nation, religion, or other grouping become convinced that they have been on the receiving end of a great injustice (e.g. the famous Nazi myth about being stabbed in the back by Jews in World War I which contributed to World War II) this can belief can be used to motivate them to commit all manner of violent acts individually and collectively. But incorrect beliefs in unfair treatment are just as common in school playgrounds, work places, and marriages. Surely, the impulse to punish unfairness is not an unmitigated benefit to the human race.

Still, in spite of all the problems that arise from the desire to punish a bigger problem would occur if people had a weaker desire to punish the unfairness of others. Societies absolutely need cooperation and the ability and desire to inflict punishment are essential to the maintenance of a sufficient degree of cooperation to make societies function well.

We Need To Understand The Genetic Basis Of Human Nature

The most important missing element in research on the intersection between economics and psychology is the genetic link. But at this point in time it is hard to make that connnection. The cost of DNA sequencing is still in the millions of dollars per person. It is too expensive to find connections between genetic variations and variations in behavior. Surely progress along that front is being made. But it would be far easier to do every experiment on human behavior could include complete DNA sequence information on each study participant. Then genetic variations could be compared with behavioral differences. The inability to effectively control for genetic differences when doing experiments is one of the biggest factors holding back the advance of a more accurate social and psychological science of human nature.

Once science starts to supply us with information about how genetic variations affect human nature the coming abililty to do germ line genetic engineering will cause a huge conflict between the desires of parents to give their offspring characteristics that the parents prefer versus the interests of the larger society in how members of future generations toward the rest of us. The ability to affect how and when future generations will act in altruistic fashions will be politically far more contentious than current issues such as abortion or embryonic stem cell therapy.

The problem with allowing parents alone to decide on what future generations will be like is that we all have to live with the consequences of their decisions. Currently the effects of decisions that people make over who to mate with can not be easily measured or predicted. Also, currently there are limits to how much a difference each person can make in the genetic make-up of their progeny because they can only pass down what they have. What is going to change is that much of the uncertainty will be eliminated and the degree of control on the outcome will rise enormously. This will allow much larger changes in distribution of behavioral tendencies in populations. Averages and extremes will shift in ways that we can only begin to guess at today.

If one wants to have a relevant debate about the dangers of genetic engineering of humans then the central issue must be genetic engineering of the mind. The biggest benefits and greatest dangers come from what people decide tol do to genetically engineer the minds of future generations.

By Randall Parker 2003 June 05 05:57 PM  Dangers Mind Engineering
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2003 June 03 Tuesday
Brain Aging Studied With Gene Microarrays

The level of expression of many genes changes as the brains of rats age.

A study in rats matching the activity of 146 genes with brain aging and impaired learning and memory produces a new picture of brain aging and cognitive impairment. The research, by scientists at the University of Kentucky, uses powerful new gene microarray technology in a novel way to match gene activity with actual behavioral and cognitive performance over time, resulting in the identification of this wide range of aging- and cognition-related genes (ACRGs). Importantly, the changes in gene activity had mostly begun in the mid-life of the rats, suggesting that changes in gene activity in the brain in early adulthood might set off cellular or biological changes that could affect how the brain works later in life.

The report (embargoed for release until May 7, 2003, at 5 p.m. ET) appears in the May 2003 issue of The Journal of Neuroscience. It provides more information on genes already linked to aging, including some involved in inflammation and oxidative stress, and also describes additional areas in which gene activity might play a role in brain aging. These include declines in energy metabolism in cells and changes in the activity of neurons (nerve cells) in the brain and their ability to make new connections with each other. In addition, other areas in which genes appear to play an influential role involve increases in cellular calcium levels which could trigger cell death, cholesterol synthesis (also implicated in Alzheimer's disease in other research), iron metabolism and the breakdown of the insulating myelin sheaths that when intact facilitate efficient communication among neurons.

Note that this study does not explain why energy metabolism declines. Is the decline caused by damage to the genes that code for proteins involved in energy metabolism? Does junk accumulate in the cells and crowd out the space which would otherwise be used for energy metabolism? Does the circulatory system decline in its ability to deliver the nutrients needed to feed the machinery of energy metabolism in the mitochondria. Or it could be that the energy metabolism be getting down-regulated because there is too much oxidative stress on the aged cells for other reasons (e.g. accumulated junk in the cells could be reacting with compounds in the cell to create free radicals). There might be a regulatory mechanism in cells to down-regulate energy metabolism when there is a lot of oxidative stress so that the cell no longer has to handle the additional free radical stress caused by high levels of energy metabolism. There are a lot of other possibilities. Some of those possibilities are a lot more likely than others and there are obvious experiments that could be tried to test them.

One obvious avenue of investigation would be experiments to try to introduce replacement genes for the mitochondrial genes involved in energy metabolism. If the replacement genes helped then one explanation for declining energy production might be accumulated damage to mitochondrial DNA.

The study was conducted by a team led by Philip W. Landfield, Ph.D., and colleagues Eric M. Blalock, Kuey-Chu Chen, Keith Sharrow, Thomas C. Foster, and Nada M. Porter at the University of Kentucky, Lexington, and James P. Herman at the University of Cincinnati, Ohio. It was supported primarily by the National Institute on Aging (NIA). Additional support was provided by the National Institute of Mental Health (NIMH). Both are parts of the National Institutes of Health at the U.S. Department of Health and Human Services.

"Gene microarrays, which can measure activity of thousands of genes simultaneously, provide the most advanced genomics technology. This has allowed us to do what no other study has done before – use large numbers of microarrays to relate genes and behavior over the lifespan of the animals on a scale that can identify most of the important players," says Landfield. "The good news is that we have a new, more comprehensive model of brain aging at the genetic level; the downside is that this model shows just how very complex that process may be." "This study makes it very clear that it is not a single gene or even several genes that are responsible for brain aging. Here, we are presented a picture of age-related changes in multiple cellular pathways and systems which interact with one another to change the brain's structure and how it functions," notes Brad Wise, Ph.D., Program Director, Fundamental Neuroscience, NIA.

This fellow's phrasing is unfortunate and can leave readers with a misimpression of the meaning of these results. Just because the expression of a large number of genes changes as we age does not mean that all those genes are contributing to the process of aging. The expression of many of those genes may be changing in order to compensate for changes that aging is causing. The changing of the gene expression might simply be symptoms rather than causes of aging. This is why gene microarray studies to study changes in gene expression by themselves provide only a very incomplete picture of what causes aging.

The microarrays do not provide an indication of what is causing each gene to be turned on or off in the cells in the sample. The biggest missing element in this kind of study is a way to measure what molecules are turning each gene on and off and, in turn, what molecules are regulating those molecules. Gene arrays do not show the chains of cause-and-effect that are responsible for the levels of gene expression that they measure.

In the study, young, middle-aged, and aged rats were trained on two memory tasks, learning to navigate a water maze and remembering familiar objects in their cages. After training, the scientists examined the brain tissue of the rats, specifically the hippocampus, an area associated with memory and cognition. RNA (ribonucleic acid, which carries out the DNA's instructions for making proteins) was isolated from each rat and selectively bound to a separate chip containing over 8,700 fragments of genes to generate gene expression, or activity, profiles. One important step was further refining of the analyses to reduce false positives and false negatives while statistically assessing changes in gene activity. The researchers then homed in on genes that changed with aging and, finally, on genes involved in age-related changes in the performance of the rats on the two memory tests. Ultimately, they zeroed in on 146 ACRGs (aging- and cognition-related genes), which were then assigned to functional categories representing different cellular processes in the brain. A complete listing of the genes and what they do appears in the original journal article.

Offering one model of brain aging, the researchers suggest that loss of neuronal processes and the compromise of their insulating myelin sheaths may trigger brain inflammation, eventually leading to loss of the cells' function. The changes in gene expression for the most part were seen in mid-life, before cognition was impaired, suggesting that changes in gene activity in the brain in early adulthood might initiate cellular or biological changes that could lead to functional changes later in life.

An increase in the expression of genes that are involved in inflammation responses is characteristic of other aged cell types that have been studied with gene microarrays. I think these guys are just guessing that the inflammation might be causing the loss of myelin sheath. My guess is that the inflammation is causing a number of other problems in neurons as well.

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The NIA leads the Federal effort to support and conduct basic, clinical, and social and behavioral studies on aging and on age-related memory change and dementia. It supports the Alzheimer's Disease Education and Referral (ADEAR) Center, which provides information on research on age-related memory change and Alzheimer's disease. ADEAR's website can be viewed at www.alzheimers.org. ADEAR may also be contacted at 1-800-438-4380. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA's general information website www.nia.nih.gov.

What we need are experiments that try a variety of interventions to find ways for aged cells to be repaired. As mentioned above, genes could be introduced to try to replace mitochondrial genes that are more susceptible to damage. Also, genes that code for “xenohydrolases” could be introduced in animal models to see if clearing out the accumulated junk in neurons would allow them to function more like younger cells. A number of other approaches are possible. What we need, as Aubrey de Grey explains, is a shift toward more of an engineering mindset to develop tools and techniques that can undo the damage caused by aging (PDF file).

If you want to get up to speed on the most radical thinking on how to stop and reverse human aging then take the time to read all of Aubrey de Grey's publications on Strategies for Engineered Negligible Senescence.

By Randall Parker 2003 June 03 03:49 PM  Aging Reversal
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2003 June 02 Monday
Bill McKibben Thinks Genetically Improved Children Will Be Robots

Bill McKibben, author of the book Enough argues that a genetically engineered children would be more akin to robots than to humans with free will.

But I've tried also to raise a deeper set of issues: the meaning of a human life will disappear if we make these changes. To understand what I mean, imagine yourself an 'improved' child. Is your intelligence your own? Is your mood your own, or the result of some protein pumped out by your cells in response to a particular stretch of commercial DNA added by your parents before your birth? Would your accomplishments, your hopes, your dreams mean anything in the way we reckon it now in such a world? Or would you be more akin to a robot?

Here is my problem with that argument in a nutshell: there are aleady people walking around who have genetic variations that make them far more prone to be happy or sad than the average person. Do these people have free wills? There are also people walking around who have genetic variations that make them brilliant. They can sit down and as easily read and understand a math book on real analysis or complex analysis or topology like most people can read a junk novel. Are these brilliant people lacking in free will?

Most of the genetic variations that parents will first try to give their offspring via fetal gene therapy will be genetic variations that will be identified in the already existing human population. The reason is simple: it will be far easier to figure out what the existing genetic variations do than to design and test new genetic variations. But whether a person inherits a genetic variation from parents or from genetic engineering if it is a naturally occurring genetic variation then will the person be any more or less human? If so, why?

To argue that the introduction of an existing variation into a particular fetus will rob that fetus of free will one would have to be willing to accept the idea that there are existing humans walking around with the same variation who have either only partial conscious control over what they do or no control at all.

I'm personally willing to consider the idea that some people have compulsions and desires that are so strong that they can not control themselves. I'm also willing to consider the idea that there may be genetic variations that effectively prevent a person from developing much of a conscience or empathy toward others. But if such variations already naturally exist in the genetic code of some humans then is this an argument against genetic engineering of children in general? Or is it perhaps an argument against allowing people to have progeny that possess those variations which give them uncontrollable impulses?

If there are genetic variations that, for instance, make people more violent or devoid of any sense of fairness does it matter whether those genetic variations are passed down by sexual reproduction or fetal genetic engineering? If so, why?

McKibben does get one thing right:

A political debate is coming, therefore – a political debate on what it means to be a human being.

But that debate is not just a political debate. It is a debate about the scientific basis for human nature. Scientifiic discoveries will demonstrate a great many ways in which genes influence personality, desires, conscience, compassion, empathy, intelligence, and other mental attributes. Our practical problem will be that there are many naturally occurring combinations of the extent to which people possess each of these human attributes. One person might have a strong conscience, out-going personality and enormous spatial intelligence with less verbal intelligence. Another person might have less of a conscience but more compassion and more verbal reasoning and yet less spatial ability. When all these things become controllable using genetic engineering we will be faced with the question of whether some combinations of attributes will cause us problems if too large a fraction of humanity possesses them.

By Randall Parker 2003 June 02 04:10 PM  Biotech Society
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2003 June 01 Sunday
Steven Pinker Says Human Genetic Engineering Unlikely

Steven Pinker, author of The Blank Slate: The Modern Denial of Human Nature (see some reviews here), has written an essay arguing that genetic enhancement of humans is too unlikely to worry about.

Why are technological predictions usually wrong? Many futurologists write as if current progress can be extrapolated indefinitely-committing the fallacy of climbing trees to get to the moon. They routinely underestimate how much has to go right for a development to change our lives. It takes more than a single ''eureka!'' It takes a large number of more boring discoveries, together with the psychological and sociological imponderables that make people adopt some invention en masse. Who could have predicted that the videophones of the 1960s would sink like a stone while the text messaging of the 1990s would become a teenage craze?

I find all of his arguments on this subject to be questionable and am surprised to read them coming from such an able mind.

Pinker is right that linear trends can not be extrapolated indefintely. But the problem with his argument is that the rate of biotechnological advance is more likely to accelerate than decelerate. See the FuturePundit Biotech Advance Rates archive for some of the reasons why.

Pinker argues that since many traits such as personality and IQ are due to complex interactions between multiple genes it will be very difficult to puzzle out how changes to genes will affect traits of the mind. Well, there are several billion people in the world and therefore many existing combinations of genetic variations already existing in the human population. Once it becomes cheap and fast to sequence the DNA of each person then it will become possible to sequence the DNA of millions of people and do a massive comparison of mental traits (e.g. IQ, personality tests, and various facts from life histories such as arrest records, mental illnesses, and involvement in various hobbies and forms of recreation) and genetic variations to tease out complex relationships between genetic variations.

Scientists are gaining the ability with computers to collect and analyse absolutely massive amounts of data. The ability of scientists to study interactions in complex systems will only become greater with time. The complexity of human biology will not prevent scientists from figuring it out in enormous detail.

Then Pinker comes to the fact that while identical twins are a lot more like each other mentally than they are like fraternal twins they can still differ in significant ways. Environment still matters. To Pinker's way of thinking this is somehow supposed to be a disincentive to human genetic engineering. But think about it from a prospective parent's position. Given two sets of genetic combinations if one set dramatically increases the odds of getting a child with a certain personality type as compared to the other combination even if the outcome is not guaranteed parents may elect to go with the combination that tilts the odds. Right now some people are choosing to try the Microsort service for sex selection of offspring even though the outcome is less than 100% guaranteed to be successful. Also, by opting for a route that includes the use of IVF they may be increasing the risk of birth defects in their children. Yet they are doing so along with many others who are using IVF to start pregnancies.

Pinker tries to argue that most people will be turned off by the idea of reproducing via unnatural means. This is a curious argument to make in an age when some women schedule the date to hormonally induce labor or to have a Caesarean section because a chosen date is more convenient than waiting for natural processes to bring the pregnancy to an end. Pinker points to in vitro fertilization as a procedure that people resort to only when they are unable to reproduce in the more conventional way. But there are already couples using it in order to have babies to use as donors of tissue to treat another child for a genetic disorder. The utilitarian attitude that couples bring to such a decision ought to give pause to anyone who thinks the wider public will not embrace biotechnological manipulations of early stage fetuses.

Also, and more importantly, there are already a growing number of people reproducing using artificial means in place of sexual relations because they want to select the sex of their offspring (again, see the Microsort service for details). They are using artificial means to control If it becomes possible to control more characteristics besides sex is there any reason to suppose that no portion of the populace will be attracted to "unnatural" interventions when it becomes possible to have them? For instance, many genetic variations that contribute to intelligence will be found and most will be found to not have severe side effects. Why won't many prospective parents be attracted to the idea of providing those genetic variations for their offspring?

We live in an era when millions of women terminate pregnancies every year using the rather unnatural procedure of abortion. We live in an era when millions of people undergo an increasing assortment of plastic surgery procedures, take recreational drugs, use drugs to alter their moods to treat mental illness, and give drugs to their kids to make them concentrate better in school. Where is the popular fear of the biologically unnatural? For cosmetic purposes Isolagen now offers (at least in assorted Western countries where it has approval - it is current seeking FDA approval) a service to take a person's cells, grow them outside of their body, and then to inject those cells back into locations under facial skin in order to provide a more enduring facial enhancement than is provided by collagen shots. An affluent public does not shrink from the latest appearance-enhancing biotechnology. Why will they shrink from biotechnology used on humans for other purposes?

Pinker also argues that since people are repulsed by genetically engineered soybeans they will not opt to have genetically engineered children. Well, 74% of the US soybean crop is genetically engineered to be resistant to the Roundup pesticide. If revulsion was such a big problem how could all this soybean be getting sold and consumed? Again, where is the big revulsion to biotechnology that provides the basis for his expectation that people will not opt to genetically enhance their offspring?

It is my estimation we are within at the very most 20 years of the time when a large assortment of gene therapies will be available to genetically enhance fetuses. Once it becomes possible there will be a stampede for genetic enhancement. Gene therapy will have a very positive image with the public when a large assortment of gene therapies to cure illnesses and to enhance performance of adults become available. The public, accustomed to having gene therapy done on themselves for benefical purposes as adults, will not shrink from considering gene therapy options when planning to have children.

By Randall Parker 2003 June 01 09:14 PM  Biotech Society
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Brain Protein Tangles Cause Memory Loss With Age

The tangled up pieces of protein fragments (known as neurofibrillary tangles) seen in Alzheimer's Disease patients also occur to a lesser extent in aging brains in people who do not develop Alzheimer's.

The researchers found tangles in all of the brains. However, the number of tangles was higher in those with mild cognitive impairment.

The researchers also found a direct link between the number of tangles and scores from memory tests carried out on the eight people before they died.

You might see this as bad news. Our brains are accumulating protein tangles that are causing cognitive decline as we age. Well, the cognitive decline is already happening regardless of its cause. But if you look at this latest research in the right light it is good news. Why? A lot of money and effort are going into discovering the causes of Alzheimer's and how to treat it. These latest results suggest that those future treatments developed for Alzheimer's which work by ridding the brain of neurofibrillary tangles will probably be of benefit to us all regardless of whether we are going to develop Alzheimer's.

Neurofibrillary tangles are far from the only harmful compounds that accumulate in the body as we age. One key class of therapies designed to repair and reverse the effects of aging throughout the body will be the development of techniques for the removal of assorted classes of junk that accumulate within cells. One place in cells where junk or waste accumulates as cells age are the lysosomes. Lysosomes are intracellular organelles that specialize in breaking down cellular waste. But some forms of waste (notably lipofuscin - which is actually an assortment of different kinds of compounds) can not be broken down by lysosomal enzymes and hence these forms of waste accumulate. Lipofuscin and other accumulating forms of waste are suspected of contributing to the formation of a number of degenerative diseases of old age.

University of Cambridge biogeronotologist Aubrey de Grey has proposed the development of cellular rejuvenation therapies using gene therapy to transfer bacterial or fungal enzymes into cells to break down lipofuscin and other accumulated cellular waste products. (PDF file)

Here I consider the feasibility of a hitherto unexplored approach to this problem: augmentation of the lysosomal catabolic machinery with “xenohydrolases”, enzymes identified in other organisms that can degrade material that our existing apparatus cannot. Such enzymes should only need to break down a small minority of the molecular structures present in these aggregates to have a substantial effect because by doing so they will create and/or expose previously inaccessible substrates for enzymes we already have. Lysosomal function seems to be impaired by such aggregates [7], but not abolished, indicating that new hydrolases are continually (albeit ineffectively) targeted to aggregate-laden lysosomes.

The neurofibrillary tangles which are linked to cognitive impairment may also be accumulating in lysosomes. Therefore therapies aimed at introducing “xenohydrolases” (xeno in this context referring to enzymes whose genes are transferred from other species) may also be able to be adapted to work against neurofibrillary tangles.

The development of gene therapies that give cells the ability to synthesize enzymes that can "throw out the trash" promises to extend longevity, make cells throughout the body to perform in more youthful ways, and to contribute to the eventual ability to reverse aging and make aging humans young again. Gene therapies to break down toxic accumulated waste in cells will play an essential part in efforts to achieve Engineered Negligible Senescence. If you want to read more about Engineered Negligible Senescence and the coming ability to make aged humans young again then check out the FuturePundit Aging Reversal archive. Also, see the Strategies for Engineered Negligible Senescence (SENS) web site.

By Randall Parker 2003 June 01 02:53 PM  Aging Reversal
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Gene Therapy Grows Inner Ear Hair Cells In Guinea Pigs

Age and exposure to loud noises can damage the inner ear cochlea hair cells that grow the fine cilia hair that are used to measure sounds. Recently some scientists at the University of Michigan have succeeded in using gene therapy delivered by adenovirus vector into the cochlea to add a gene called Math1 to cells in that area that stimulates those cells to become hair cells. Math1 gene theapy has resulted in the growth of hair cells in the cochlea and nerves were detected growing toward those hair cells.

Gene therapy grows new auditory hair cells in mammals ANN ARBOR, MI – University of Michigan scientists have used gene therapy to grow new auditory hair cells in adult guinea pigs – a discovery that could lead to new treatments for human deafness and age-related hearing loss.

Healthy hair cells are vital to the ability to hear, but aging, infection, certain medications and exposure to loud noises can damage or destroy hair cells causing sensorineural hearing loss – a condition affecting over 30 million Americans. Since the discovery, in the late 1980s, that birds can spontaneously regenerate damaged hair cells, scientists have been trying to find a way to induce the replacement of lost hair cells in mammals.

U-M scientists have now accomplished this goal by inserting a gene called Math1 into non-sensory epithelial cells lining the inner ear. Results from the study will be published in the June 1 issue of the Journal of Neuroscience.

"We found that non-sensory epithelial cells in adult guinea pig cochlea can generate new sensory hair cells following the expression of Math1," says Yehoash Raphael, Ph.D., an associate professor of otolaryngology in the U-M Medical School, who directed the study. "We also found that some of these hair cells can attract the growth of new fibers from auditory neurons."

In a normal ear, vibrations from sound waves striking the eardrum are transferred to fluid inside a snail-shaped bony organ called the cochlea, which is the auditory component of the inner ear. When cochlear fluid moves, it stimulates movement in thousands of tiny projections on hair cells lining the inside of the cochlea. Moving hair cells initiate electrical signals, which are picked up by auditory nerve fibers and carried to an area of the brain called the auditory cortex. If hair cells are damaged or missing, electrical signals are not generated and hearing is impaired.

"During the embryonic stage of an animal's development, hair cells and supporting cells have a common origin. Cells that express Math1 are fated to become hair cells, while Math1 expression is inhibited in the remaining non-sensory cells," Raphael says.

"After embryonic development, hair cell production ceases. Unlike other epithelial cells in the skin or gut, epithelia in the inner ear contain no stem cells, so there is no source for renewal," Raphael explains. "That's the main reason why hair cell loss is permanent. When we over-expressed Math1 in non-sensory cells of the mature cochlea, however, we found that it causes them to transdifferentiate or change their personality to become hair cells."

"We knew that transdifferentiation of supporting cells was a major source of new hair cell development in birds," Raphael says. "But there was no proof it would work in mammals. We started gene therapy experiments in 1994 and it took us seven years to develop a successful method of introducing the gene into the non-sensory cochlear epithelium."

Dr. Kohei Kawamoto, Ph.D., a former U-M research fellow who performed the laboratory experiments, used an adenovirus as a vector to deliver the Math1 gene to inner ear epithelial cells. Kawamoto injected the Math1 vector into inner ear fluid of 14 adult guinea pigs. The same procedure, but without the transfer of the Math1 gene, was performed on 12 matched control animals.

Thirty to 60 days after inoculation, U-M scientists used scanning electron microscopes to examine inner ears from both sets of animals. In experimental guinea pigs that received the Math1 gene, scientists found new hair cells growing in areas where hair cells are typically absent. No new hair cells were found in the control animals.

"The inner ear is an ideal target for gene therapy, because it is closed – not sealed, but nicely isolated," Raphael says. "As long as the amount you inoculate is small, the spread to other organs is minimal, and the risk of systemic toxicity is almost zero."

Because the total amount of fluid in the inner ear of a guinea pig is so small, the mechanical impact of injecting the viral vector fluid into the cochlear fluid damaged some of the hair cells in experimental animals. "While this is a concern, we believe the micro-injection technology can be improved to prevent this mechanical trauma," Raphael says. "The human cochlea is larger than a guinea pig cochlea and may better tolerate the inoculation. Also, profoundly deaf human candidates for this gene transfer approach would likely have severe pre-existing hair cell loss to begin with, so the risk of mechanically-induced side effects would be somewhat less troubling."

One of the most surprising results of the study was the discovery of long, slender nerve fibers growing toward some of the newly formed hair cells. "This suggests that these hair cells can provide signals to attract axons and that neurons can respond to these signals," Raphael says.

In the next stage of research, Raphael will determine whether the guinea pig hair cells are functional and able to transmit sound signals to auditory neurons. He also plans to test the procedure in aging animals and in animals that are completely deaf.

"This is just the beginning," Raphael says. "It is really just a proof of the principle to show that, with proper gene therapy, these non-sensory cells have the competence to become hair cells."

The research was funded by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health and supported by GenVec, Inc. GenVec provided its proprietary adenovector technology to deliver the atonal gene, Math1. Raphael was an occasional consultant to GenVec, but has no significant financial interest in the company.

First author on the paper was Kohei Kawamoto, Ph.D., a former U-M research fellow who is now at Kansai Medical University in Osaka, Japan. Co-authors on the paper include Douglas E. Brough, Ph.D., director of vector sciences at GenVec, Inc.; Shin-Ichi Ishimoto, Ph.D., a former U-M research fellow; and Ryosei Minoda, Ph.D., a post-doctoral fellow in the U-M Medical School.

This result demonstrates how gene therapy can be used to repair one kind of damage caused by injury and aging. It will take several years to turn this into a safe and useful human gene therapy. However, it seems likely that within 10 or at most 20 years deafness caused by cochlea hair cell death will be a curable disorder.

By Randall Parker 2003 June 01 01:27 AM  Biotech Therapies
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