2002 October 31 Thursday
HapMap Genetic Variation Mapping Project Begins

It is now believed that in most people genetic variations vary in groups. By looking at a relatively small number of locations in the genome it should be possible to predict (albeit with less than complete certainty) what genetic variations will be found between the tested locations (these ranges are called Haplotypes). To map out and identify the marker locations from which other locations can be predicted an ambitious 3 year $100 million dollar international project is attempting to collect analyze the DNA of several hundred humans. This project is known as the HapMap project:

Genetic information is physically inscribed in a linear molecule called deoxyribonucleic acid (DNA). DNA is composed of four chemicals, called bases, which are represented by the four letters of the genetic code: A, T, C and G. The Human Genome Project determined the order, or sequence, of the 3 billion A’s, T’s, C’s and G’s that make up the human genome. The order of genetic letters is as important to the proper functioning of the body as the order of letters in a word is to understanding its meaning. When a letter in a word changes, the word’s meaning can be lost or altered. Variation in a DNA base sequence – when one genetic letter is replaced by another – may similarly change the meaning.

More than 2.8 million examples of these substitutions of genetic letters – called single nucleotide polymorphisms or SNPs (pronounced snips) – are already known and described in a public database called dbSNP (http://www.ncbi.nlm.nih.gov/SNP/), operated by NIH. The major source of this public SNP catalog was work done by The SNP Consortium (TSC), a collaborative genomics effort of major pharmaceutical companies, the Wellcome Trust and academic centers.

The human genome is thought to contain at least 10 million SNPs, about one in every 300 bases. Theoretically, researchers could hunt for genes using a map listing all 10 million SNPs, but there are major practical drawbacks to that approach.

Instead, the HapMap will find the chunks into which the genome is organized, each of which may contain dozens of SNPs. Researchers then only need to detect a few tag SNPs to identify that unique chunk or block of genome and to know all of the SNPs associated with that one piece. This strategy works because genetic variation among individuals is organized in "DNA neighborhoods," called haplotype blocks. SNP variants that lie close to each other along the DNA molecule form a haplotype block and tend to be inherited together. SNP variants that are far from each other along the DNA molecule tend to be in different haplotype blocks and are less likely to be inherited together.

"Essentially, the HapMap is a very powerful shortcut that represents enormous long-term savings in studies of complex disease," said David Bentley, Ph.D., of the UK's Wellcome Trust Sanger Institute.

Since all humans descended from a common set of ancestors that lived in Africa about 100,000 years ago, there have been relatively few generations in human history compared to older species. As a result, the human haplotype blocks have remained largely intact and provide an unbroken thread that connects all people to a common past and to each other. Recent research indicates that about 65 to 85 percent of the human genome may be organized into haplotype blocks that are 10,000 bases or larger.

The exact pattern of SNP variants within a given haplotype block differs among individuals. Some SNP variants and haplotype patterns are found in some people in just a few populations. However, most populations share common SNP variants and haplotype patterns, most of which were inherited from the common ancestor population. Frequencies of these SNP variants and haplotype patterns may be similar or different among populations. For example, the gene for blood type is variable in all human populations, but some populations have higher frequencies of one blood type, such as O, while others have higher frequencies of another, such as AB. For this reason, the HapMap consortium needs to include samples from a few geographically separated populations to find the SNP variants that are common in any of the populations.

Charles Rotimi, Ph.D., leader of the Howard University group collecting the blood samples in Nigeria, said, "We need to be inclusive in the populations that we study to maximize the chance that all people will eventually benefit from this international research effort."

Because of the block pattern of haplotypes, it will be possible to identify just a few SNP variants in each block to uniquely mark, or tag, that haplotype. As a result, researchers will need to study only about 300,000 to 600,000 tag SNPs, out of the 10,000,000 SNPs that exist, to efficiently identify the haplotypes in the human genome. It is the haplotype blocks, and the tag SNPs that identify them, that will form the HapMap.

By Randall Parker 2002 October 31 10:38 PM  Biotech Advance Rates
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Development Of Memory In Human Babies

When humans are born their brains are not capable of forming recallable memories. The sequence of the development of mental capabilities is being studied more closely:

Six-month-olds have a memory span of no more than about 24 hours, which gradually expands to up to a month by 9 months. In the new study, 13-month-old babies could not remember events they had witnessed and mimicked four months earlier -- a task that came easily to their elders, ages 21 months and 28 months.

The findings support the view that at 9 months, two key areas of the brain involved in learning and memory are not yet fully mature. These are the hippocampus, a region where memories are first processed before being transferred to the cerebral cortex for permanent storage, and the frontal cortex. This large anterior area of the brain is involved in reasoning, planning, abstract thought and other complex cognitive processes in addition to motor functions, such as speech, handwriting, drawing, walking, reaching and grasping.

By Randall Parker 2002 October 31 09:49 PM  Brain Memory
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Will Functional MRI Read Thoughts Some Day?

U Penn scientist Daniel Langleben is developing the fMRI as a lie detector and expects within 50 years it will be possible to read minds. His collaborator Ruben Gur can already detect whether a person recognizes another person.

Ruben Gur, a neuropsychologist at the University of Pennsylvania, says new kinds of brain scans can reveal when a person recognizes a familiar face, no matter how hard he or she tries to conceal it.

The scanning machine, called a functional MRI, takes pictures that highlight specific parts of the brain activated during certain tasks. Telltale parts of your brain "light up," he said, when you are presented with a face you have seen before.

By Randall Parker 2002 October 31 10:27 AM  Biological Mind
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2002 October 30 Wednesday
Depression Tied To Hippocampal Stem Cells

Since this story is written for the layman they use the term "cell birth". But what is really happening is that adult stem cells in the hippocampus divide. One cell remains an adult stem cell and stays in the hippocampus. The other travels up into the brain and converts itself into a nerve cell. Well, this process is probably happening in order to form new memories, possibly new reflexes, and to replace damaged cells that die. Suppression of this process may either cause depression or possibly it doesn't cause the initial depression but does prolong it. Anti-depressants are known to stimulate hippocampal adult stem cells to divide and so the thinking is that this stimulation may be one of the ways that anti-depressant drugs relieve depression. There are now many scientists pursuing this line of thought and looking for drugs that will more quickly stimulate hippocampal adult stem cells to divide.

Stress, which plays a key role in triggering depression, suppresses neurogenesis in the hippocampus.

Antidepressants, on the other hand, encourage the birth of new brain cells.

Animals must take antidepressants for two or three weeks before they bump up the birth rate of brain cells, and the cells take another two weeks to start functioning. That's consistent with the lag time antidepressants show before they lift moods in people.

If an antidepressant is given during a period of chronic stress, it prevents the decline in neurogenesis that normally occurs.

You can also fiind the previous article here.

In a related report stress hampers learning ability in female rats but Prozac prevents stress's effects:

Shors and her research team, Benedetta Leuner, Jacqueline Falduto and Sabrina Mendolia, studied adult female rats treated with the antidepressant Prozac and a control group that received no treatment. They found that after a stressful event, learning was impaired in the control group but not in the group treated with Prozac. The researchers also found that only chronic treatment with Prozac was effective, which is consistent with reported efficacy of Prozac in patients with depression and other mental disorders.

"Importantly," Shors pointed out, "unstressed females treated with Prozac did not differ from unstressed, untreated females, indicating that Prozac itself did not affect learning."

Shors noted that males and females differ in their responses to stressful experiences. The researchers have found that exposure to a stressful experience that impairs new learning in females actually enhances new learning in males.

These results also suggest a reason why depression is more common in old folks: their adult stem cells are also aged and very likely not as able to divide and differentiate into nerve cells. In order to rejuvenate people and make their bodies young again it will be essential to rejuvenate the adult stem cells in various adult stem cell reservoirs throughout the body. If hippocampal adult stem cells could be rejuvenated it might be possible to reduce the incidence of depression, improve memory, and even to raise intelligence. Since the demand for more effective anti-depressant treatments is so large this theory about hippocampal adult stem cells having a role in prolonging depression may cause depression researchers to develop methods to rejuvenate hippocampal adult stem cells. Hence attempts to develop more advanced anti-depressant treatments may contribute to the development of anti-aging therapies.

By Randall Parker 2002 October 30 04:45 PM  Brain Emotions
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Nucleic Acid-Triggered Catalytic Drug Release

I'm reproducing this press release in full here because it describes such an incredibly promising technique for treating a large assortment of diseases. The ability to target drugs to activate in only the cell types that express a particular gene would allow great specificity of delivery.

You can find the original copy here and the the Science Daily copy here.

Tailor-made Cancer Drugs: Wave of the Future? Washington University chemist offers radical new strategy in fight against cancer.

[St. Louis, MO., 10-27-02]

By Carolyn Jones Otten

Today, even the best cancer treatments kill about as many healthy cells as they do cancer cells but John-Stephen A. Taylor, Ph.D., professor of chemistry at Washington University in St. Louis, has a plan to improve that ratio. Over the last several years, Taylor has begun to lay the conceptual and experimental groundwork for a radical new strategy for chemotherapy -- one that turns existing drugs into medicinal "smart bombs," if you will.

All DNA is formed of three basic components: a phosphate and a sugar, which combine to form the sides of the double helix "ladder," and a base that forms the ladder's "rungs." All variances in DNA, including cancerous mutations, are the result of unique sequencing of the four types of bases, denoted A, G, C and T.

Taylor's approach, described as "nucleic acid-triggered catalytic drug release," is essentially a sophisticated drug releasing system, one that is able to recognize and use cancerous sequences as triggering mechanisms for the very drugs that fight them.

"The beauty of this system is that it could use already-approved FDA drugs," Taylor explained. "So all I have to worry about is getting FDA approval on the general releasing mechanism, and then I can incorporate whatever anticancer drugs are currently on the market."

Taylor discussed his work at the 40th annual New Horizons in Science Briefing, a function of the Council for the Advancement of Science Writing. He spoke Oct. 27, 2002 at Washington University in St. Louis, which hosted the event.

Guiding drugs to their 'parking spot'

In nucleic acids, Nature has already determined the rules of base pairing -- A binds with T and G pairs with C -- a system called "Watson-Crick base-pairing," named for the discoverers of the double helix. Recent advances in biotechnology have given doctors the ability to profile a patient's genetic information, taken during a biopsy, using something called a DNA chip, which can identify unique or uniquely overexpressed messenger RNA (mRNA). Messenger RNA is a single-stranded RNA molecule that encodes information to make a protein, using the same bases as DNA except that U replaces T. Taylor's idea is to employ this information as a genetic roadmap, guiding drug components to where they should "park" amongst the millions of base pair "spaces."

Taylor's system is built on three components: a "prodrug," or a dormant form of a drug; a catalyst that activates the prodrug; and a nucleic acid triggering sequence, designed to match and interlock with a unique or uniquely overexpressed strand of RNA in cancerous cells. The RNA binding drug components will be fashioned out of Peptide Nucleic Acid (PNA), which is identical to DNA, but replaces the sugar backbone with a "peptide" or protein backbone. The benefit is that a single strand of RNA actually binds tighter to a strand of PNA than it does to itself.

So, the prodrug and the catalytic components each contain a PNA strand that is complementary to the cancer cell's mRNA, allowing them to bind right next to one another in the cancer cell. This close proximity enables a chemical reaction to occur between them, resulting in the release of a cytotoxic drug which kills the cancer cell. Although the medication might encounter healthy cells in its travels, it would not harm them because the RNA triggering sequence would not be present, or else present in a much lower amount, and the drug could not be released.

This new "rational" design doesn't stop there -- it could be the answer to all sorts of viral diseases such as AIDS, hepatitis and herpes, and could even help guard against new biologically engineered viruses that we haven't yet imagined.

"Here's my vision of the future," Taylor said. "You go to a doctor's office and take a biopsy, which is then run through a DNA chip analysis machine allowing the appropriated triggering sequence to be identified. This information is then passed to an automated synthesis machine and, iIdeally, the catalytic and prodrug components can be synthesized and administered to you within hours."

In related work, Taylor said he will be using overexpressed RNA sequences to help target drugs in research with Washington University colleague Karen Wooley, Ph.D., associate professor of chemistry, and other collaborators. The group hopes to splice Taylor's RNA-docking molecules to Wooley's new breed of nanoparticles for on-the-mark, stay-put delivery of diagnostic and disease-fighting agents.


Contact: Gerry Everding, Office of Public Affairs, Washington University in St. Louis, (314) 935-6375; gerry_everding@aismail.wustl.edu

You can find Dr. Taylor's web page here.

By Randall Parker 2002 October 30 01:03 PM  Biotech Therapies
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Calorie Restriction Slows Heart Genetic Aging

Calorie Restriction (CR) is the only known consistent reliable way to extend life expectancy of a large variety of animals using wild type strains of animals (ie leaving aside in-bred lab strains that have special health problems). This latest result is not surprising but does suggest that CR's benefit may lie in its ability to reduce accumulation of genetic damage.

The hearts of mice on the low-calorie diets showed nearly 20% fewer age-related genetic changes and also appeared to have less DNA damage than those of mice on regular diets. Restricting calories also inhibited potentially disease-causing changes in the immune system, and suppressed apoptosis, or programmed cell death.

Its not too late to benefit.

Numerous studies on animals have shown nutritious diets low in calories can result in significant health benefits, slow ageing and extend longevity. In some cases, the life-spans of animals in experiments have been increased by as much as a third. Even when calorie intake was not restricted until middle age, the life-span of mice increased by 20 per cent.

Eat less, live longer:

"Based on our finding, it appears that if people reduce their current calorie intake between 20 and 40% -- even starting in middle age -- they may delay the development of heart disease or possibly even prevent it," professor of genetics Tomas Prolla, PhD, tells WebMD.

By Randall Parker 2002 October 30 12:27 PM  Aging Reversal
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Cal Tech Chemical Lab On A Silicon Chip

The research group of California Institute of Technology biophysicist Stephen Quake has built a silicon chip that can function as a mini chemistry lab:

To show what such a device is capable of, Quake's team have made an array in which 3,574 microvalves can separate an injected fluid into 1,000 tiny chambers in a 25x40 grid. Each chamber contains just a quarter of a billionth of a litre of liquid. If all the chambers were full, they'd contain less than a hundredth of a raindrop. Each chamber can be individually emptied.

This is from the research paper's abstract.

Microfluidic Large-Scale Integration

Todd Thorsen,1 Sebastian J. Maerkl,1 Stephen R. Quake 2*

We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.

The Quake group's web site at Cal Tech has all sorts of interesting information. You can read the PDF reprints of their published papers here There is a list of the group's major areas of research here. One of the projects is a miniaturized DNA sequencing device:

Novel DNA Sequencing Techniques

Marc Unger

The current paradigm in DNA sequence determination is Sanger Dideoxy sequencing by electrophoresis on polyacrylamide gels. This has limitations both in terms of speed (running a gel takes several hours) and read frame (a maximum of approximately 500 base pairs may be sequenced at one time). In order to surpass these limitations, we are developing novel a DNA sequencing technology based on microfabricated flow channels and single molecule fluorescence detection. Both microfabrication and single molecule detection have advanced to the point where straightforward techniques are readily available in the literature, and the equipment required can be purchased off-the-shelf. Work to date has focussed on microchannel preparation and calibrating our optical detection system. The picture below is a fluorescence image of single dye molecules (tetramethylrhodamine isothiocyanate) on a glass coverslip, at a magnification of approximately 1000x on your screen. Our microchannels are also working quite well - fabrication is now reliable, reproducible, and fairly easy. We are now beginning work on the chemistry of attaching molecules to the surfaces of the flow channels.

By Randall Parker 2002 October 30 12:05 AM  Biotech Advance Rates
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2002 October 29 Tuesday
US Department of Genetic Identification

Annalee Newitz attended a guest lecture that Craig Venter presented to an biology class at Woods Hole's Marine Biological Laboratory. She managed to get in some questions to Venter about his new venture to do DNA sequencing for anyone with enough money to pay for it. His answers raise some troubling issues.

"What if you sequence my genome and find out that I have some genes with interesting and unique properties?" I asked. "Who will own that data?" Looking at the floor with a half-smile, Venter evasively replied, "Well, you'd get a copy of the data." Did he mean I'd be licensing the data from him, the way I license Windows XP? I asked for clarification. Finally, after much hedging, Venter explained that the genomic data he gathered would be in a public database but that "probably it will belong to the nonprofit organization." So I'd be paying him to sequence my genome, but I wouldn't own the data.

At the end of his lecture Venter unveiled one of the real goals of his new work. We stared at a PowerPoint slide that displayed the image of a card that looked a lot like a driver's license. Only it was issued by the "US Department of Genetic Identification," an imaginary government agency that Venter predicted would exist in the future. This agency would use the biotech Venter's lab is developing to sequence your genome on the cheap and associate its unique code with an ID card the moment you were born. In the future, not only Venter but also the government will have a chance to own your genomic data. As an aside, Venter noted that policy makers ought to create genetic antidiscrimination laws to go along with genetic identity tracking.

Once there are multiple companies offering DNA sequencing services it seems inevitable that some will offer the option of their destroying their copy of your DNA sequence once they have finished sequencing it. In the long run personal DNA sequencing machines will provide a way to avoid allowing a company to know your DNA sequence in the first place. But at the same time those future portable cheap DNA sequencing machines will open up the possibility of someone grabbing some dandruff flakes or saliva drippings from another person and then sequencing that other person's DNA.

Then there is this possibility of governments wanting to take a DNA "fingerprint" of all people. It seems inevitable that some governments will implement such a scheme as described above. Is this a bad thing? Most identity faking is done for malicious and criminal reasons after all. Will the result be a more or less free society?

By Randall Parker 2002 October 29 11:54 AM  Biotech Society
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2002 October 28 Monday
Sequenom Searching For SNP Disease Risk Factors

Wired News writer David Ewing Duncan paid a visit to Sequenom of San Diego to become the first person to be tested for all known genetic markers that are thought to contribute to diseases. While a couple of risk factors for high blood pressure and heart problems were uncovered his genetic screening results came out looking favorable for a longer than average life.

Toni Schuh, CEO of Sequenom, told Genomics & Proteonomics magazine that Sequenom is rapidly scaling up its ability to the number of genetic markers it is watching in a large group of people to try to identify genetic variations that contribute to disease:

“We are doing large-scale genetics discovery studies to find the genes that harbor the predisposition to disease and to nail down the variations in these genes that turn them into risk genes. A year ago if a geneticist wanted to do this, he would have 400 to 800 microsatellite markers to cover the entire human genome. Two years ago, if somebody had these 400 markers to do a study on 500 people, that was considered a big genetic study. We have 11,000 people in our healthy population now and our total base of DNA markers is more than 100,000. The dramatic change in scale in terms of markers is 100 times more than a few years ago. That’s the very significant inflection point in the power of pharmacogenetics and medical genetics in general,” says Schuh.

Update: On that previous link it is claimed that 4 million SNPs have been discovered so far and there may be millions more that have not yet been discovered. The article reports on many biotech instrumentation companies which are rapidly introducing new products that further accelerate and automate the process of DNA assaying.

While Sequenom doesn't have as many SNPs identified as Perlegen Sequenom is offering 2 million SNP assays to its customers.

At the end of last year, Sequenom Inc., San Diego, completed a portfolio of 400,000 different working SNP assays, which is now available to their customers on its recently launched Web site, www.realSNP.com. The site is named as such “because the SNPs are real,” says Charles Cantor, chief scientific officer at Sequenom. The Web site contains information on how to run the assays, as well as information on population frequency of SNPs in various populations. Sequenom continues to design SNP assays for every SNP in the public domain, so the RealSNP.com Web site currently has more than 2 million designed assays. “And we know from past experience that about 90% of those will work the first time they’re tried without any optimization,” says Cantor.

We are on the edge of an explosion in the number of known genetic risk factors for diseases.

By Randall Parker 2002 October 28 11:57 PM  Biotech Advance Rates
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Perlegen finds 1.7 million SNPs

Perlegen, a two year old spin-off of Affymetrix, has announced that it has compared the DNA sequences of 50 people and identified all the Single Nucleotide Polymorphisms (singe genetic letter differences) found in that group of people. Perlegen is keeping that information to itself to use business deals with pharmaceutical companies to identify which genetic variations cause adverse drug reactions:

Yet there was only a muted celebration a few weeks ago, when Perlegen's scientists decided they'd found the last of the 1,717,015 SNPs that biotech firms have been seeking since the human genome was sequenced in 2000.

"We cracked a single bottle of cheap champagne," quipped Perlegen chief scientist David Cox.

Two simple reasons explain Perlegen's restraint.

Although the company claims to have found just about every SNP in creation, the scientific community hasn't the proof. Perlegen won't publish its SNP map. Instead it will try to recoup its investment by helping drug firms use these subtle genetic variations to determine why some people react badly to medicines -- or get sick in the first place.

Perlegen will also use this data to look for genetic variations that predispose people to get various illnesses. Perlegen has just announced a large collaborative effort to search for genetic variations that are risk factors for type 2 diabetes.

Perlegen will use human genetic variations (single nucleotide polymorphisms or SNPs) it has discovered and its high-density oligonucleotide array-based SNP genotyping capability to assist researchers from around the world in intensifying their search for genes involved in a disease that affects approximately 15 million people in the United States and millions more around the world. The study includes geneticists at the University of Michigan, the University of Southern California, the National Public Health Institute of Finland, and the National Human Genome Research Institute in Bethesda, Maryland. During the past nine years, by studying the DNA of type 2 diabetes patients and their families, the FUSION group (Finland-United States Investigation Of Non-insulin-dependent diabetes mellitus genetics) has narrowed its search for the genes that play a causal role in the disease to certain areas of the human genome. An area of particularly high interest falls on the long arm of chromosome 6. Now, with help from Perlegen's scientists and the company's innovative genotyping technology, the FUSION group hopes to discover the gene or genes in that region.

What I find curious about their approach is that they used only 50 people as DNA sample donors. Surely it is not possible to find all the genetic variations that matter by looking at just 50 people. There are genetic sequence variations that show up in less than 2% of the population and hence one would expect one would need DNA from more than 50 people to identify all the SNPs that matter. Likely they took this approach for cost reasons. Most medically important SNPs are in the 1.7 million they identified and this is a cost effective way to search for most medically significant SNPs.

Update: Perlegen can identify all the unique sequences (or only out of the 1.7 million SNPs they've mapped?) in an individual's genoome in 10 days:

In theory, that goal is within reach, because researchers can now scan the entire genome to look for DNA variants of interest. Perlegen Sciences, a closely held company in Mountain View, Calif., recently announced that it can parse a person's genome in about ten days using so-called DNA chips--an astounding advance, given that it took an international army of scientists all of the 1990s to create the first draft of the human genome.

Update: Keep in mind that just as DNA sequencing technology advanced to make SNP detection faster and cheaper for Perlegen's recent work it will continue to advance and SNP detection costs will probably fall by orders of magnitude in the next ten years. Many more research groups and companies will be able to collect of SNP maps of larger groups of people for less money in the future. A company that seeks to make money off of SNP maps of smaller groups of people had better find useful SNP variations fairly quickly if they want to make a profit off their information. Collecting that information will only become cheaper going forward. If you want to get a sense of just how rapidly biotech assay tools are going to advance then read the FuturePundit Biotech Advance Rates archive.

By Randall Parker 2002 October 28 11:22 PM  Biotech Advance Rates
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Anti-Doping Agencies Versus Athletes And Biotech

Advances in biotechnology are going to make it harder to detect new ways to enhance athletic performance:

Following another conference in October, the U.S. Anti Doping Agency announced it had a urine-based test for the use of recombinant erythropoietin, also known as EPO, that would allow for extensive out-of-competition testing.

Arne Ljunggvist, chairman of WADA's health, medical and research committee, said he expected to have tests in place by the 2004 Olympics for many more kinds of oxygen downloaders, which boost the volume or increase the efficiency of oxygen-carrying hemoglobin in the blood.

"We're getting the tests before the products are out there," said Frank Shorter, chairman of the board of the U.S. Anti Doping Agency.

While the World Anti-Doping Agency and USADA officials sound confident in this article about their ability to stay ahead in their ability to detect new techniques for athletic performance enhancement the job of detection is going to become increasingly difficult. story Blood and urine testing will not be able to detect many of the types of gene therapy that will be developed for athletes.

One future detection technique will be to take tissue samples from various locations on an athlete, have the DNA in those samples sequenced, and verify that the athlete has the same single known DNA sequence at all the tested locations. Then analyse (using knowledge that scientists do not yet have but will in a decade or two) the genetic athletic potential of each athlete. With that knowledge analyse an athlete's performance and look for signs that athletes are exceeding their genetic potential. The problem with that approach is that the genetic potential is affected by accidential influences during development that could make some organ bigger or smaller or otherwise different than the genes alone would normally expect to make it. Still, variations above expected genetic limits would provide reason to look at an athlete more closely.

When gene therapies for athletic performance enhancement become available will it be possible to find positive proof against a suspected beneficiary of a prohibited gene therapy? If one knows exactly where the gene therapy must have been delivered then a biopsy if the tissue could be taken and a genetic analysis could be performed on the biopsy. That sounds easy enough in theory but there are practical complications that may make that very difficult. The first complication is that many locations that may undergo gene therapy will be deep inside a person's body. Athletes are going to be understandably reluctant to have needles stuck deep into them to retrieve a tissue sample.

Even if it becomes possible to go fishing for tissue samples deep in a person's body its still not going to be easy to find tissue that provides the proof that the athlete is benefitting from gene therapy. The next complication here is that some gene therapies may need to modify only a very small fraction of the cells in an organ in order to provide an athletic enhancement. Worse yet, a gene therapy could be delivered to some other part of the body in order to provide an unsuspected supplemental location to enhance some organ's functionality. Imagine issue placed in leg veins or along the intestines in order to provide a larger capacity to make a hormone that increases athletic performance. How would one know where to go looking? It could be like finding a needle in a haystack.

One way to try to narrow a search to find cells in an athlete's body which have undergone gene therapy would be to implant mini-sensors at various locations in the body and then have the athlete exercise while the sensors are being monitored. A distributed set of sensors might be able to detect an unexpected gradient of hormone or waste product concentrations. For instance, a sensor in a vein returning blood from the lower body might detect higher concentrations of a hormone than are found in an artery headed for the extremities.

But what is the point of all these games? The article above quotes Jon Entine to the effect that the prohibited pharmaceutical interventions are levelling the playing field between those who are lucky to have genes that are great for athletics and those who are not so lucky. There is some merit in his argument. As it stands now most types of sports at the Olympic level amounts to a competition between those at the genetic extreme in various combinations of abilities. While a willingness to devote a lot of effort to training was essential for the top Olympic athletes most people would never have a chance of reaching the Olympics becaues they just don't have a sufficiently favorable combination of genetic variations.

Olympic sports officials and officials on some other types of sports can ban the use of pharmaceuticals and of gene therapy to increase performance. For some types of enhancements the sports organizations will find methods to detect the enhancements at least some of the time. But in the longer term atttempts to enforce these sorts of prohibitions will run up against an even greater challenge: children will be born who have had their genes changed before or shortly after conception. How will these sorts of modifications be detected? If they are detected will the exclusion of such people from various sports competitions be considered acceptable? My expectation is that if amateur sports organizations attempt to practice such exclusion then new amateur sports organizations will form to allow the genetically enhanced to compete with each other. The public wil tune in and attend the competitions of the genetically enhanced. In this view the World Anti-Doping Agency and the U.S. Anti-Doping Agency are engaged in a rearguard fight to extend the twilight of the old regime of the genetically lucky few who compete only against each other.

By Randall Parker 2002 October 28 12:04 AM  Biotech Athletics
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2002 October 26 Saturday
Paper discusses circuitry for quantum computing

One thing about the future is certain: Computers are going to increase in speed by orders of magnitude. If you click thru to this URL you can also find a link there to the original paper in Physical Review Letters.

In order to implement quantum information technology, it will be necessary to prepare, manipulate and measure the fragile quantum state of a system. "The first steps in this field have mostly focused on the study of single qubits,” Nori said. “But constructing a large quantum computer will mean scaling up to very many qubits, and controlling the connectivity between them. These are two of the major stumbling blocks to achieving practical quantum computing and we believe our method can efficiently solve these two central problems. In addition, a series of operations are proposed for achieving efficient quantum computations.

“We have proposed a way to solve a central problem in quantum computing – how to select two qubits, among very many, and make them interact with each other, even though they might not be nearest neighbors, as well as how to perform efficient quantum computing operations with them,” Nori said.

By Randall Parker 2002 October 26 09:54 PM  Computing Advances
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2002 October 25 Friday
UCLA Geneticists Find Location of Major Gene in ADHD

The region they've narrowed the search to is also linked to autism. However, since they haven't yet narrowed the search to a single gene it is not yet proven that the same gene is involved in both disorders. However, what is important here is that the search for a major genetic contributor to ADHD is getting close to a culprit:

UCLA Neuropsychiatric Institute researchers have localized a region on chromosome 16 that is likely to contain a risk gene for Attention Deficit Hyperactivity Disorder, the most prevalent childhood-onset psychiatric disorder.

Their research, published in the October edition of the American Journal of Human Genetics, suggests that the suspected risk gene may contribute as much as 30 percent of the underlying genetic cause of ADHD and may also be involved in a separate childhood onset disorder, autism.

Pinpointing a gene with a major role in ADHD will help researchers and clinicians better understand the biology of this disorder and likely lead to the development of improved diagnosis, treatment and early intervention.

"We know there are about 35,000 genes in the human genome. By highlighting this region on chromosome 16, we have narrowed our search for a risk gene underlying ADHD to some 100 to 150 genes," said Susan Smalley, principal investigator of the study and co-director of the Center for Neurobehavioral Genetics at the UCLA Neuropsychiatric Institute.

Once it becomes possible to control whether progeny get the genes that contribute to mental disorders it will become possible to totally eliminate a large variety of mental disorders from some future generation. This will result in an intergenerational difference in attitudes as the average younger person will be brighter and happier than any previous generation.

By Randall Parker 2002 October 25 03:00 PM  Brain Genetics
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Chromosome Twin Sisters Used To Repair DNA Damage

Each cell gets on average 20,000 mutations per day on its chromosomes. There are a number of repair mechanisms for dealing with this damage. These Israeli scientists have demonstrated a long hypothesized repair mechanism. Since chromosomes come in pairs it is possible for a cell to repair one chromosome by copying the equivalent section of the other member of its pair:

The other last-resort repair system was hypothesized by scientists in the 1960s yet was never proved until the current study. This system, which relies on the help of “sister chromosomes,” enables the cell to repair genetic damage without the risk of creating mutations. (During the process of cell division, each chromosome - the structure in the nucleus that contains DNA - gives rise to two identical “sister” chromosomes. These move on to the two separate cells created from the dividing cell.)

According to this theory, if one of the sister chromosomes is damaged, the other can serve as a back-up system of sorts. The damaged genetic information can be restored precisely using the corresponding DNA segment from the other, identical chromosome. That segment detaches itself from the intact “sister” chromosome and moves over to the defective chromosome, helping to repair the damage. The gap created in the donor chromosome is refilled by using the segment from its remaining intact DNA strand (DNA consists of two matching strands) as a template. Both chromosomes end up with a complete, undamaged genetic segment.

In the new study, Prof. Zvi Livneh, head of the Biological Chemistry Department at the Weizmann Institute of Science, has for the first time observed this repair mechanism in action. Furthermore, Livneh and his team, which consisted of graduate students Ala Berdichevsky and Lior Izhar, also showed that the repair mechanism based on a genetic “donation” from the sister chromosome is unusually common: it is responsible for 85% of last-resort repairs – those performed by alternative repair systems when the major, “all-or-nothing” repair mechanism fails. The second last-resort system – the relatively inaccurate repair mechanism that allows the creation of mutations – is responsible only for some 15% of repairs.

Keep in mind the limitations of this repair technique. First of all, it doesn't work on males for X chromosomes since males have only one X chromosome. Also, the copied section may be different than what it replaces because there is considerable genetic variation between the chromosomes people get from each parent. Its possible that by doing the copy a harmful mutation that was silent on one chromososome could get copied to the other so that then two copies of the harmful mutation would exist in the same cell. Still, the vast bulk of the time when this repair mechanism is used the result is beneficial.

It is conceivable that some day this repair mechanism could be hijacked by gene therapy delivery mechanisms to replace sections of a chromosome with new and improved genetic code. The gene therapy could cause a piece of chromosome to be recognized as damaged, a mini-chromosome could be introduced that looked like the matching pair member so that the replacement DNA would be copied from the new mini-chromosome. So this latest research result may eventually be useful for genetically-based treatments.

By Randall Parker 2002 October 25 01:10 PM  Biotech Manipulations
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2002 October 24 Thursday
Quantum NOT gate demonstrated

The article says this technique might be useful for quantum cryptography:

Quantum computation has moved another step closer with the first demonstration of a quantum NOT gate. Although it is impossible to build perfect logic gates for quantum bits of information, a team led by Francesco De Martini of the University of Rome "La Sapienza" and INFM in Italy has achieved almost the maximum theoretical fidelity with its device (F De Martini et al 2002 Nature 419 815).

By Randall Parker 2002 October 24 01:59 PM  Computing Advances
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Huntington's Treatment Works In Mice

It is not clear from this report what technique they used to shut down the Huntington's gene. If they genetically engineered the mice to make the gene able to be shut down by pharmaceutical means then this result is only useful for studying the disease. But if they developed a drug that could shut down the regular regulatory region for this gene then the technique might be closer to a treatment usable on humans. If anyone knows exactly what they did do tell. Still, the fact that the toxic protein will clear out if the cell can be made to stop making it is good news for Huntington's patients:

Researchers have devised a clever genetic technique in mice that can regulate the production of the abnormal protein that causes Huntington's disease.

Ai Yamamoto, a researcher at Memorial Sloan-Kettering Cancer Center, created an animal model that exhibits all the signs of the lethal disease: brain damage and impaired movement. When the mutant gene is shut off, toxic protein deposits clear out and the animal improves substantially. Yamamoto presented her findings last week at the American Neurological Association's annual meeting in Manhattan.

By Randall Parker 2002 October 24 01:36 PM  Biotech Therapies
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Rate Of Biotech Medicine Advance Accelerating

This rate of new product development will increase even further as the ability to manipulate genes increases. Advances in the power of the technological tools will lower the cost of new product development and enable new types of products to be developed:

A record number of biotech medicines has reached the final stage of clinical trials, positioning the industry to produce as many products in the next few years as it has during the past 20.

Data compiled by the Pharmaceutical Research and Manufacturers of America show that of 371 biotech medicines now undergoing commercial tests, 116 have reached Phase III clinical trials -- the last step before the U.S. Food and Drug Administration decides whether they are safe and effective enough to sell to consumers.

This is the original press release from the Pharmaceutical Research and Manufacturers of America that probably inspired the San Francisco Chronicle article:

371 Biotechnology Medicines IN Testing Offer Hope of New Treatments for Nearly 200 Diseases

October 21, 2002


Washington, D.C. – More than 250 million people have already benefited from medicines and vaccines developed through biotechnology, and a new survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) identifies 371 more biotechnology medicines in the pipeline. Nearly 200 diseases are being targeted by this research conducted by 144 companies and the National Cancer Institute.

These new medicines – all of which are in human clinical trials or are awaiting FDA approval –include 178 new medicines for cancer, 47 for infectious diseases, 26 for autoimmune diseases, 22 for neurologic disorders, and 21 for HIV/AIDS and related conditions.

Approved biotechnology medicines already treat or help prevent heart attacks, stroke, multiple sclerosis, leukemia, hepatitis, rheumatoid arthritis, breast cancer, diabetes, congestive heart failure, lymphoma, kidney cancer, cystic fibrosis and other diseases.

"These medicines are the result of extensive efforts to understand the human genome and penetrate the molecular basis of disease," said PhRMA President Alan F. Holmer. "The cutting-edge medicines in development – many of which attack or prevent disease in fundamentally different ways – offer hope to patients with diseases for which we have no cures."

Among the new biotechnology medicines in development are an epidermal growth factor inhibitor that targets and blocks signaling pathways used to promote the growth and survival of cancer cells; monoclonal antibodies – or laboratory-made versions of one of the body’s own weapons against disease – that target asthma, Crohn’s disease, rheumatoid arthritis, lupus, various types of cancer, and other diseases; and therapeutic vaccines, designed to jump start the immune system to fight such diseases as AIDS, diabetes, and several types of cancer.

Researchers are also pursuing antisense medicines – which interfere with the signaling process that triggers disease pathways for AIDS, several types of cancer, Crohn’s disease, heart disease, and psoriasis, and gene therapies, which augment normal gene functions or replace or inactivate disease-causing genes, for hemophilia, several cancers, cystic fibrosis, heart disease, and other diseases.

PhRMA represents the country’s leading research-based pharmaceutical and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. The industry invested more than $30 billion in 2001 in discovering and developing new medicines. PhRMA companies are leading the way in the search for new cures.

By Randall Parker 2002 October 24 12:19 PM  Biotech Advance Rates
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2002 October 23 Wednesday
Dust Discs To Discover Planets Around Other Stars

Planets create characteristic dust patterns around stars:

The new technique, pioneered by University of Rochester astronomer Alice Quillen and graduate student Stephen Thorndike and described in the current issue of The Astrophysical Journal Letters, instead is based on studies of patterns in dust discs associated with planet-bearing stars.

By Randall Parker 2002 October 23 10:56 PM  Space Exploration
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2002 October 22 Tuesday
Boeing Bird Of Prey Stealth Aircraft Unveiled

The Seattle Post Intelligencer has the best zoomable higher resolution images if the Bird Of Prey.

Aviation Week's Aviation Now web site has a picture of it from above though not at high res.

This article has no pictures but it has more basic information about the aircraft. Sounds like this was a one off technology prototype testbed aircraft. It was built for a mere $67 million dollars and the program supposedly ended in 1999. It will be displayed at the U.S. Air Force Museum at Wright-Patterson Air Force Base in Dayton, Ohio:

Bird of Prey

First flight: Fall 1996

Wingspan: About 23 feet

Length: 47 feet

Weight: 7,400 pounds

Height: 9 feet, 3 inches

Engine: Pratt & Whitney JT15D-5C turbofan

Thrust: 3,190 pounds

Maximum speed: About 300 mph

Maximum altitude: 20,000 feet

More basic info here.

Update: On the Boeing web site you can find more images and streaming video here. Popular Science also has Bird Of Prey images here.

By Randall Parker 2002 October 22 01:10 PM  Airplanes and Spacecraft
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Brain Tumor Causes Pedophilia

This is evidence that there is a part of the brain that is involved in moral enforcement:

The sudden and uncontrollable paedophilia exhibited by a 40-year-old man was caused by an egg-sized brain tumour, his doctors have told a scientific conference. And once the tumour had been removed, his sex-obsession disappeared.

The cancer was located in the right lobe of the orbifrontal cortex, which is known to be tied to judgment, impulse control and social behaviour. But neurologists Russell Swerdlow and Jeffrey Burns, of the University of Virginia at Charlottesville, believe it is the first reported case linking damage to the region with paedophilia.

Did this guy have this behavior as a result of the tumor's increasing the amount of pleasure he felt for forbidden activities? Or did the tumor disable a part of the brain that enforces moral constraint? Either way there is an important lesson here for future human genetic engineering: It will be possible some day to genetically engineer humans who do not feel as much constraint to respect the rights of others. Genetic engineering will make possible the design of minds that have a different set of desires than the typical range of desires seen in fairly normal law-abiding humans today.

Some day in the future it will become possible to genetically engineer a mind to find obesity or an old age appearance to be attractive. Or a person's tastes could be changed to find sweets to be repulsive or bitter taste to be yummy. So there will ways to make changes that will result in people whose tastes are, at least by our standards, extremely weird and even repugnant. These odd changes in tastes can create problems if, for instance, a fraction of the human race is made to like color schemes and designs that the rest of us think are disgusting. Imagine the political fights that could result over zoning ordinances or the appearance of public parks.

But the real danger from mind engineering comes from the ability to fiddle with the parts of the mind that involve moral constraints and intense desires that involve other humans. A mind could be engineered to feel no remorse at killing someone or to feel joy from beating and dominating others physically. A mind could be made to derive pleasure from deception, hurting others physically, and insulting others. Minds can be thought of as complex computer programs. Using the terminology of programming then modification of moral programming and modification of programming of desires that are controlled by moral programming are the greatest future potential dangers from genetic engineering.

A lot of attention is being paid to ethical arguments about choosing the sex of children or about selecting sperm and eggs that have higher intelligence. In terms of the potential danger to society these issues are small potatoes next to the issue of changing the genetic code in ways that affect moral and desire programming.

By Randall Parker 2002 October 22 12:50 PM  Biological Mind
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2002 October 21 Monday
Human Genes Put Into Pig Sperm

A new method for putting genes into an animal species by gene therapy on sperm has been tested in pigs:

Genetically-modified animals can be created simply by washing sperm, swishing it in a centrifuge with an additional gene, and using the altered sperm for artificial insemination, say Italian researchers.

Marialuisa Lavitrano's team at the University of Milan-Bicocca in Milan have demonstrated how well the simple method works by creating pigs that could one day provide rejection-free organs for transplantation into people. The technique worked 25 times more efficiently than the standard way of engineering animals.

Pigs are being used because genetically modified pigs are excellent candidates as methods to grow replacement human organs:

"In the U.S., every 18 minutes a person dies on the waiting list for organ transplants without receiving one. Every 18 minutes is a lot. Xenotransplation could really be a solution," lead researcher Marialuisa Lavitrano, an immunologist and pathologist at the University of Milan-Bicocca, told United Press International.

This sperm-based technique also is relatively cheap and about 14 to 114 times more effective at implanting genes in pigs than the direct injection of DNA, the most common way of making genetically engineered animals.

This method is cheaper and has a higher success rate than gene injection:

Ninety-three piglets were born after the researchers tinkered with the pig sperm, and 57 percent of them contained the human gene, suggesting the sperm soaked it up from the solution. When researchers injected sperm with the gene, only 4 percent of the piglets born had the gene inside them.

These researchers are pursuing the development of this technique in order to be able to transplant a large number of human genes into pigs. Their goal is to create pigs which would contain internal organs that would be sufficiently compatible both physiologically and immunologically to allow transplantation into humans. My guess is that this technique alone will not be sufficient to do the amount of genetic engineering that will be required to achieve this ambitious goal. It may be necessary to both remove and add genes in order to create pigs with all the desired biological qualities. Also, the process of adding the sheer number of required genes may end up causing harmful mutations in the sperm chromosomes. Still, its a great piece of research.

There is another obvious purpose that this technique might eventually be used for: human progeny genetic engineering. Human sperm could be treated using the same technique in order to put desired genes into human progeny. Of course, the technique might require a much greater degree of refinement in order to prevent harmful mutations. One potential risk is the possibility that any gene transplanted into sperm chromosomes could get incorporated into the middle of an existing gene. That could cause harmful genetic defects in progeny that would manifest at birth or at a later time in life.

Update: This story from CNN confirms that deletion and modification of existing genes are also necessary to make pigs suitable for xenotransplantation:

"You can add a gene, but you cannot alter or remove a gene using this technique," said Prather. It is known that some other genes will have to be altered or removed in order to create animals for the xenotransplantation of organs, he said.

By Randall Parker 2002 October 21 06:55 PM  Biotech Organ Replacement
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Detect Nukes Smuggled Into Cities?

Writing in Wired Steven Johnson has written an article about efforts underway to detect nuclear weapons in vehicles being driven into cities:

Then there's the more pressing issue: How easy would it be to subvert the network? After the scanning demo in Massachusetts, I sit down in a conference room with Callerame, and he walks me through the physics of concealment. High atomic-weight materials like lead can block gamma radiation, but the large quantities of lead that would be needed would show up on other scanning devices. Callerame's solution is to combine radiation sensors with advanced X-ray technologies, like the backscatter system that produced the startling image of the Mercedes. "I still think you're going to have to X-ray these things," Callerame says. "If you run only a radiation detector and somebody shields their source well enough, you may not pick it up. On the other hand, if you're simultaneously doing X-ray imaging, you'll see this big blob in the middle of the cargo, which would be a dead giveaway of something being clandestinely brought in." He shows me printouts of scans done at a demo in Washington, where they concealed the radioactive material in a container of lead the size of a bowling ball. In the image, the lead container pops out immediately, a bright-white circular shape in the middle of translucent grays. "Now, I should mention, even though we wrapped the cesium in this lead casing, we still managed to pick up the gamma radiation. It's just easier when you do the two in combination."

But a ship carrying a nuke could make it into a harbor and blow up before its cargo was scanned.

By Randall Parker 2002 October 21 12:23 PM  Dangers Tech Terrorism
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Gene Vaccines Accelerating Vaccine Development

The article discusses why gene vaccines are cheaper, faster to develop, usable for more purposes, and capable of being delivered in more ways than standard vaccines. Gene vaccines may even help slow aging:

Gene vaccines hold special promise as weapons against diseases too complex or dangerous for traditional immunology. Already, they've proven successful in hundreds of animal trials against bioweapons like anthrax and the plague, as well as against pandemics like malaria and TB, which claim millions of lives each year. In July, Oxford scientist Adrian Hill began testing a gene-based malaria vaccine on hundreds of at-risk people in Gambia.

Closer to home, a gene vaccine against melanoma has completed three rounds of clinical trials on humans and appears ready to be submitted to the FDA for final approval. When injected directly into cancerous tumors, the vaccine, called Allovectin-7, causes proteins to grow on the tumor's surface — which in turn stimulates the immune system. The drug's manufacturer, Vical, is reviewing data from the experiments in hopes of presenting them to the FDA.

By Randall Parker 2002 October 21 11:34 AM  Biotech Advance Rates
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2002 October 19 Saturday
Keeping Brain Cells Alive Longer In Vitro

Imagine scaling this up to an even longer period of time and even more cells. Eventually they'll have the ability to keep Spock's brain alive:

A way of keeping slices of living brain tissue alive for weeks has developed by a biotech company. This will allow drug developers to study the effect of chemicals on entire neural networks, not just individual cells.

"We are building stripped-down mini-brains, if you will, directly on a chip," says Miro Pastrnak, business development director of Tensor Biosciences of Irvine, California.

By Randall Parker 2002 October 19 06:00 PM  Biotech Advance Rates
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Brain Gets Sex Orientation Before Genitals

The SRY gene is widely considered as the gene for determining sexual identity. See for instance this page about the role of the SRY gene in determining sexual identity. Also, see this page:

By its structure, the SRY gene is a 1,0 kb one exon gene located just centromeric to the pseudoautosomal region of Yp functioning as the dominant inducer of testis development. This gene comprises a single exon that encodes a 203- amino acid protein. The middle third of the protein represents the HMG (high-mobility group) domain specifically binging to a target nucleotide sequence 5’-AACAAAG-3’ characterising it as a transcription regualtor protein. Although its function is not entirely known, this gene is obviously the first initiator of male sexual differentiation 13, 19, 37, 42.

However, a UCLA team led by Eric Vilain has discovered differences in genetic expression that happen before the SRY gene becomes active during development. It is possible that male-female brain differences start developing before SRY starts changing genitals development:

"But in a study of mice, a team at the University of California, Los Angeles, has now found that males and females show differences in the expression of no fewer than 50 genes well before SRY switches on," according to the magazine.

Eric Vilain, the head of the UCLA team, said three of the genes are dominant in females and four in males, but they still need to determine whether the genes influence brain sexuality in mice and whether the same thing occurs in humans.

You can find the same article here.

Eric Vilain's home page at UCLA provides some more details about his lab's work:

Sex determination orients development toward sexually dimorphic individuals, male or female. In mammals, male sex determination is triggered by a primary signal, encoded by the testis determining factor SRY, localized on the Y chromosome. Subsequently, a complex network of genes, most of them still unknown, is regulated and leads to male sexual differentiation. We have discovered new molecular and cellular mechanisms of sex determination during fetal development. In particular, we have provided strong evidence supporting SRY as the testis determining gene, and identified regulatory mechanisms of transcription of DAX1, another sex determining gene. We have also recently identified human WNT-4, a signalling molecule responsible, when duplicated, for XY sex reversal in mammals. A new concept is now emerging: normal sexual development is highly dependent on strict gene dosage at all major steps of the sex determination pathway.

One possibility this opens up is the ability to separately control genital and brain sexual differentiation. Some day there will be people who have male minds in female bodies and vice versa. They will be more like the opposite sex in their thinking than is the case with homosexuals.

By Randall Parker 2002 October 19 02:14 PM  Brain Development
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2002 October 18 Friday
Father's Increasing Age Raises Birth Defect Risk

This result argues for the development of an effective male contraceptive that would shut off spermatogenesis until a man is ready to father children. Note that as sperm progenitor cells go thru each cell division there is a risk of error during the duplication process. So a way to shut down the process until real functioning sperm are needed could greatly reduce the rate at which harmful mutations accumulate:

Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35. Until now, the only evidence for paternal age effects has come from determining how many children with these diseases are born to fathers of various ages.

To obtain the first genetic explanation for these effects, the scientists studied sperm from about 60 men of various ages and looked for two genetic changes responsible for 99 percent of the cases of Apert syndrome. They found that men over 50 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations were not more common in blood samples as men aged.

The scientists say it's likely that the number of cell divisions that go into making a sperm plays a large role in the link between Apert syndrome and paternal age, and represents a fundamental difference between how aging egg and sperm can impact the health of a child.

By Randall Parker 2002 October 18 05:55 PM  Biotech Reproduction
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2002 October 15 Tuesday
Nanotech batteries 100x more powerful

What the article doesn't say is whether this approach can be used to build larger batteries that would have higher power density than existing conventional large batteries. My guess is that the answer is Yes but it is not clear. Anyone know? Prototype devices are expected in 3 years:

All batteries consist of two electrodes, an anode and a cathode, and an electrolyte solution. UF researchers have created both nano-anodes and nano-cathodes, or anodes and cathodes measured on the scale of billionths of a meter. They've shown in tests that these electrodes are as much as 100 times more powerful than traditional ones.

The electrodes also have a unique and promising structure.

"The UF progress is very significant," said Bruce Dunn, a professor of materials science and engineering at the University of California-Los Angeles, the lead institution in the project. "(Martin's) work, the fabrication and testing of nano-dimensional cathodes and anodes, represents the key elements of his concentric tube battery approach, which represents a novel three-dimensional configuration."

Martin and his colleagues create the nano-electrodes using a technique he pioneered called template synthesis. This involves filling millions of tiny "nanoscopic" holes in a centimeter-sized plastic or ceramic template with a solution that contains the chemical components that make up the electrode. After the solution hardens, the researchers remove the template, leaving only the electrodes. The next challenge is to find a way to put together the nano-anode and nano-cathode with a nano-electrolyte and other components.

"We've proposed a totally new design for a battery where all the components are nanomaterials, and we have succeeded in making nearly all of these components," Martin said. "We have not yet developed the technologies to assemble these components, and that's what we're working on."

Robbie Sides, a UF doctoral student in chemistry and one of the researchers in Martin's lab, said UF's nano-anodes and nano-cathodes are not only more powerful than traditional ones, they're also hardier. Lithium-ion battery electrodes might sustain an average of 500 charges and discharges before wearing out, he said. In tests done by another UF chemistry doctoral student on Martin's team, the nano-electrodes sustained as many as 1,400 charges.

By Randall Parker 2002 October 15 06:45 PM  Nanotech Advances
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Redheads Need More Anesthesia

It would also be interesting to test pain sensitivity for milder pain without using anesthesia. One also wonders whether redheads have different levels of sensitivity to hot and cold or other differences in sensations. From a genetic engineering perspective it might be desireable to give your kids a different variation of the gene for melanocortin-1 receptor and then add red-headedness genetic variation just to the melanocytes of the hair after birth. Though we shouldn't rule out the possibility of unknown advantages to this mutation that manifest in other ways:

Ten red-haired women between 19 and 40 years of age and ten more with dark hair were given a commonly-used inhaled anaesthetic in the study. After each dose of the anaesthetic, the women were given a standard electric shock.

The process was repeated until the women said they felt no pain. Their reflexes were also monitored to assess the effectiveness of the painkiller. The researchers found that red heads required 20 per cent more aesthetic to dull the pain.

A smaller group of blondes was tested and found to have the same pain sensitivity as brunettes:

The sun triggers a hormone that in turn triggers the production of melanin to form a tan. Redheads seldom tan easily because they have a defective receptor for that hormone — a quirk with this “melanocortin-1 receptor” that also leaves their hair red. Without its intended receptor to dock in, the melanin-producing hormone may cross-react with a related receptor on brain cells that influences pain sensitivity, Sessler explained.

By Randall Parker 2002 October 15 06:27 PM  Biological Mind
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Overcoming Fear Has Biochemical Basis

Blocking the LVGCC channels can prevent extinction of fear :

In a discovery with implications for treatment of anxiety disorders, UCLA Neuropsychiatric Institute investigators have identified a distinct molecular process in the brain involved in overcoming fear. The findings will be published in the Oct. 15 edition of the Journal of Neuroscience. The study of how mice acquire, express and extinguish conditional fear shows for the first time that L-type voltage-gated calcium channels (LVGCCs) -- one of hundreds of varieties of electrical switches found in brain cells -- are required to overcome fear but play no role in becoming fearful or expressing fear. The findings suggest that it may be possible to identify the cells, synapses and molecular pathways specific to extinguishing fear, and to the treatment of human anxiety disorders.

"Brain plasticity, or the ability of the central nervous system to modify cellular connections, has long been recognized as a key component to learning and memory," said Dr. Mark Barad, the UCLA Neuropsychiatric Institute's Tennenbaum Family Center faculty scholar and an assistant professor in-residence of psychiatry at the David Geffen School of Medicine at UCLA. "The discovery of a distinct molecular process in overcoming fear bodes well for development of new drugs that can make psychotherapy, or talk therapy, easier and more effective in treating anxiety disorders. More broadly, the findings also suggest that distinct molecular processes may be involved in the expression and treatment of other psychiatric disorders."

Both the acquisition and extinction of conditional fear are forms of active learning. The acquisition of conditional fear requires a unique pairing of an initially neutral conditional stimulus with an aversive unconditional stimulus. In this research, the conditional stimulus was a tone and the unconditional stimulus was a mild foot shock.

If blocking LVGCC will prevent one from overcoming fear then would a design of LVGCC that opens at a lower threshold of stimulation result in a personality that overcomes fear more easily? Will it become possible to genetically engineer personality types that are more fearless? Will people choose such personality types for their children when it becomes possible to do so?

By Randall Parker 2002 October 15 10:48 AM  Biological Mind
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2002 October 14 Monday
Thymus Teaches T Cells Not To Attack Self

Some Harvard University researchers have found a key piece of the puzzle about how the body prevents the immune system from attacking the self. One can easily imagine how a deficiency of one kind of protein in the thymus could cause an auto-immune disorder when T cells encounter the same protein in some organ of the body:

Building on work of other groups, first author Mark Anderson, a research fellow in medicine at Joslin; Emily Venanzi, a Harvard Medical School graduate student in immunology; Christophe Benoist, a professor of medicine at Joslin; Mathis, and colleagues, reported that a small network of thymic cells -- the medullary epithelial cells -- expresses hundreds of genes usually associated with organs such as the pancreas, brain, and liver.

"No one would think you would encounter your big toe protein in the thymus, but in fact proteins from the eye, the liver, from all over the place are specifically expressed in a small population of stromal cells in the thymus," said Benoist.

A majority of these expressed proteins are used by the peripheral organs to tell T cells to stay away. Indeed, the researchers believe the proteins are used in the thymus to foreshadow the very self-antigens that the T cells will encounter once they travel out into the body.

"There is a foretelling of these proteins in the thymus, which is why we call it an immunological self-shadow," said Mathis.

In a critical step, the Joslin team discovered that the transcription factor aire plays a critical role in producing these self-shadow proteins in the thymus (hence its name, which is formed from two letters in each word of autoimmune regulator). Mutant mice lacking aire exhibited in their thymus only a fraction of the peripheral self-proteins found in the thymus of normal mice. And the mutants exhibited widespread autoimmunity. In fact, their condition was reminiscent of a condition found in humans carrying a defective AIRE gene, autoimmune polyglandular syndrome.

It is not yet clear how the shadow proteins educate developing T cells inside the thymus, though Benoist suspects the processes are similar to those used to eliminate T cells that react to ubiquitous or circulating proteins. Nor is it clear how aire controls the expression of so many shadow proteins. One possibility is that it works by binding to other transcription factors.

"It is going to be interesting to figure out what the mechanism really is," Mathis said. While novel, the mechanism is probably only one of many that the immune system uses to educate peripheral T cells about the self-vs.-foreign distinction.

"It is very dangerous for the immune system to have self-reactive T cells," Anderson said. "It takes advantage of any mechanism to get rid of these cells. So there is a whole net of mechanisms."

A better understanding of the role of the thymus in prevention of auto-immune response will open up avenues for the development of therapies to treat auto-immune disorders. Also, it may become possible to add cells or do gene therapy to the thymus in order to teach immune cells not to attack transplanted organs. Plus, this information may even turn out to be useful for inducing immune responses against cancers and infectious diseases.

By Randall Parker 2002 October 14 10:38 AM  Biotech Immunology
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2002 October 13 Sunday
Details on Parkinson's Disease Gene Therapy

Science Daily's published press release from Thomas Jefferson University has the most detail of the reports I've seen so far.

According to Dr. Oshinsky and Jia Luo, M.D., research associate at Jefferson Medical College of Thomas Jefferson University, in Parkinson's, a portion of the brain called the subthalamic nucleus is overactive. These cells produce glutamate, an excitatory neurotransmitter, or chemical message carrier, into another region called the substantia nigra, which is important for the coordination of movement and where the brain chemical dopamine is made. Parkinson's is caused by the deterioration of dopamine-producing nerve cells.

The researchers - including scientists from Jefferson, the University of Auckland, New Zealand, and Cornell University - took their cues from work with deep brain stimulation, where brain cells in the subthalamic nucleus are stimulated at a high frequency as a treatment for late-stage Parkinson's. This treatment prevents overactivity in the substantia nigra.

The team, led by Matthew During, M.D., formerly of Jefferson Medical College of Thomas Jefferson University and now at the University of Auckland, decided that instead of turning off the neurons in the subthalamic nucleus, they would attempt to change the neurons from excitatory to inhibitory, which would then contain the inhibitory chemical messenger GABA.

The team used an adeno-associated virus to carry the gene for an enzyme, glutamic acid decarboxylase (GAD), into brain cells in rats that were made Parkinsonian. They saw a dramatic difference in the behavior and physiology of the Parkinsonian rats treated with the GAD-carrying virus compared to the Parkinsonian rats that did not receive the treatment.

Three weeks after the gene transfer, Dr. Luo made Parkinson's lesions on one side of the brains of rats that had the gene therapy. The researchers then performed various behavioral tests to see if the gene therapy could protect against the development of classic Parkinson's symptoms. One test showed that nearly 70 percent of the animals with Parkinson's lesions and the GAD gene therapy had no Parkinson's symptoms when they received chemicals that mimicked dopamine in the brain. Normally, animals with Parkinson's are hypersensitive to dopamine, and actually respond to it by running around in circles over and over. The test result was a "very strong behavioral measure showing this is a good treatment for Parkinson's," Dr. Oshinsky says.

If anyone wants to find Jefferson Medical College of Philadelphia PA then click here for contact information. Though possibly the Department of Neurology might be what you are looking for. Jefferson's Farber Institute for Neurosciences looks like it might be the place for Parkinson's treatment.

By Randall Parker 2002 October 13 01:11 PM  Biotech Therapies
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2002 October 12 Saturday
More on Regime Stability, IQ, Personality

Razib at Gene Expression has responded to me here about my post on whether progeny genetic engineering for intelligence and personality will happen more rapidly in the US or China.

I'd like to clarify a few points. First of all, I do not see cloning as an essential technology for IQ enhancement and certainly not for personality change. Granted, one could take someone who has a very high IQ and a preferred personality type and clone that person and make many people with similar IQ and personality. The big advantage of cloning is that one doesn't have to identify the particular genetic variations that contribute to making a particular IQ level or personality type. Just find someone with the desired characteristics and clone him (or her).

However, there are many disadvantages to cloning (leaving aside the fact that we do not yet know how to do human cloning). The first is that identical clones are no improvement over whoever it is that is being cloned. Granted, one can choose people to clone who have highly desired qualities (looks, athletic skills, intelligence, personality, disease resistance, etc) and therefore those clones can have more of those desired qualities than the population at large. Still, each of us are all walking around with many harmful mutations and there is no single ideal person to clone. Another really big disadvantage with cloning is that whether in China, America, or elsewhere, the vast majority of parents really do want to have kids that have mostly the parents' DNA. If you can tell people that they can have kids that are built mostly from their own DNA but with, say, some DNA changes for health reasons and also their choice of changes for brain characteristics then that will have a lot more appeal than offering them cell to implant in the woman's uterus that has the qualities of some person that is not closely related to them. Children still need to be raised and it is unlikely that the Chinese government will start running large scale cloned baby group homes to raise cloned babies. It seems more reasonable to expect that even 20 or 30 years from now the vast bulk of children will be born to the women who will then proceed to raise them and that the bulk of those children will have more genetically in common with their mothers than with the population at large. Therefore, it seems to me that the way forward will be by tinkering with parental DNA to make small numbers of changes that the parents decide they definitely want their children to have.

Now we come to the question of non-democratic regime stability in a genetically engineered future. For the purpose of argument let us accept the Lynn & Vanhanen figures for average IQ per nation. I'm no expert in psychometrics to even be able to judge the quality of the data upon which their estimates are based. But for the moment assume the figures are fairly accurate. Well, is the average IQ difference between China and America large enough to really make a difference in regime control? I think a 7 or 9 point IQ difference is not as big as what will happen the future if one country rapidly embraces genetic engineering for IQ enhancement while another country lags in adopting it. Suppose genetic engineering becomes widespread and China's average IQ goes up by 30 points. It's not like the IQ scale is linear in its effects. Higher IQ causes qualitative differences in how people think. People with higher intelligence can think with concepts that are quite beyond the reach of lesser minds.

But genetic engineering of the mind will not be done only for intelligence. It will be done for personality too. It seems very likely that there are personality types that are harder or easier to rule by a repressive regime. There may also be intelligence characteristics (e.g. inquisitiveness) that make one have a greater independence of mind, a lesser willingness to accept orders, a greater desire to feel unconstrained, and a lesser desire to bow to peer pressure. The really huge wildcard for the future is that we do not know what personality characteristics people will choose once they can choose personality characteristics. As I've stated previously, the biggest danger from human genetic engineered may come from the ability to do personality type selection.

Personality engineering is the really a triple edged sword here. It will become possible to genetically engineer truly psychopathic personalities that will feel no loyalty to either free societies or to autocratic regimes. It will also be possible to genetically engineer personalities that are very obedient and easy to rule undemocratically. Imagine incredibly altruistic and, at the same time, easily intimidated personality types. But it will also become possible to genetically engineer very independent personalities that have strong consciences that are constructed to make them easily trainable to be strongly resistant to tyranny and supportive of freedom for all.

By Randall Parker 2002 October 12 11:22 PM  Biotech Society
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Will The Chinese Genetically Enhance More Quickly?

Razib from Gene Expression has brought up a topic that I've occasionally wondered about: whether the Chinese will advance more rapidly thru genetic engineering due having less philosophical or ethical opposition to the idea:

My opinion is that because the Han people tend not to be encumbered by the same ethical limitations due to individual rights they will make great advances in human genetic engineering. I even think they'll tailor soldiers-and create something of an army of clones [1].

Ethical considerations aside, there are reason to expect progeny genetic engineering will be widely used in the USA before the same happens in China. We have to consider the economic environment, the regulatory environment, and the motives and knowledge of the prospective parents.

The first economic consideration is the higher living standards in America. Initial technologies for genetically enhancing progeny will be very expensive. There are more people in the US who will be able to afford them than in China. Also, since there is a lot more money available for research and for venture capital start-ups in America most of the work currently being done to develop faster, cheaper DNA sequencing machines, gene therapy, and other relevant technologies is happening in the USA. So the first businesses that start up to offer progeny genetic engineering services will probably be started in the USA. Of course higher US regulatory barriers could easily cancel out that advantage.

At first glance the regulatory advantage appears to be in China's court. The Chinese government probably will not stand in the way of initial attempts to provide genetic enhancements to create higher IQ children. But there is one reason why this may not turn out to be the case: High IQ people are harder to politically control. Also, if Chinese parents decide they want to have children with more aggressive personalities the mainland Chinese regime may see these personality types as an additional threat to autocratic regime stability. By contrast, higher IQs and more assertive personalities pose less of a threat to the US political system (anyone want to speculate about what the US political system would be like with higher IQ and more assertive people?). So will the Chinese leaders choose regime stability over competitive edge? It is possible.

Then we come to the prospective parents. Currently the US has an advantage in the amount of knowledge available to its citizens. That advantage is shrinking as more mainland Chinese gain access to the internet. If only a quarter of Chinese parents get access to the same amount of knowledge as Americans have access to then they will have roughly the same total number of people who can make informed choices. The other issue here is incentives facing the parents. Will American or Chinese parents feel more incentive to have brighter kids? On one hand the ethical issues (of a neo-Luddite sort that I think ridiculous - but they exist in the minds of many) will weigh more heavily in the minds of American parents. At the same time, the practice of competing with others is more deeply rooted in American culture. SUV driving Yuppies will be faced with the prospect that their kids won't be able to get into the same quality colleges as they attended because the Joneses and Smiths down the road are genetically engineering their kids (via trips to other countries with more lax regulatory regimes). At that point the attitudes of the Suburban moms toward genetically engineering their own kids may shift in favor of being able to use this new kind of advantage because this advantage will be seen as having far greater value than foreign language immersion with the au pairs, Suzuki piano lessons, or getting the kids into the top local expensive private schools (which will be raising their standards anyhow when brighter genetically engineered kids start applying.

The competitive forces in the US favor the choice to genetically engineer at the personal level. Once the competitive urges of suburbanites come to the fore it will take only one overwhelming Congressional vote to dissolve the regulatory obstacles. You can bet that the US national security establishment will line up with the ambitious suburbanites to support greater freedom of progeny genetic engineering. Then the American per capita GDP advantage will do the rest.

Okay Razib, what do you think of this argument?

By Randall Parker 2002 October 12 03:45 PM  Biotech Society
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The Future Prospects For Climate Engineering

Razib from Gene Expression has beaten me to posting about this Scientific American article on the proposed use of phytoplankton to take CO2 out of the atmosphere in order to prevent global warming:

Working from this theory, Green Sea Venture postulates that fertilizing 16 million square miles of the Southern Ocean with 8.1 million tons of iron would zero out the world contribution to atmospheric CO2 increases from burning fossil fuel--2.2 gigatons of carbon per year. "The potential of the oceans is so great that we ought to do the experiments that allow us to decide whether or not it is a worthwhile undertaking for climate control," says Lee Rice, president of the company. "But the scientific data are not conclusive." No one has yet been able to measure how much carbon sinks into the deep ocean, because the detritus sinks slowly. So that is the focus of an, as-yet-unscheduled, 5,000 square mile fertilization experiment, which the company would help fund. "In addition," says Rice, "there is a real gap between the scientific clarity and how to do this practically, since you do need to verify how much carbon has been sequestered in order to get paid." His investors, he asserts, are willing to wait for science's judgment about whether commercial activity is warranted.

However, I want to post on this because I want to use it as a jumping off point to talk about an issue that I think is worth thinking about: future prospects for climate engineering. The most dramatic experiments made in climate engineering have been with the attempts to control hurricanes in Project Stormfury:

It was on the heels of Hurricane Camille barreling into the Gulf Coast regions of Mississippi and Alabama when Hurricane Debby was seeded on a couple of occasions over the two day period of August 19-20, 1969. Each time the storm was seeded, sustained winds were reduced significantly.

The first time, winds dropped 31 percent while the second time, they only dropped 15 percent. The apparent success with Debby helped fuel new projects, and improvements in technology. In particular, Hurricane Hunter aircraft, which went up dramatically during the 1970s.

Ultimately though, Project Stormfury was cancelled in 1980 since the team was unable to clearly ascertain whether or not the seeding efforts were really causing storms to weaken, or the systems just became victims of the environment around them. Nevertheless, the work done did bear some fruit as forecasters and scientists alike were able to learn a great deal from their research, and it has helped them improved forecasting accuracy.

The NOAA web site has a graphical depiction of Project Stormfury Hypothesis. Here's another article on Project Stormfury. My own take on the skepticism expressed in the article is that science is all about experimentation. If an attempt at cloud seeding was attempted on a much larger scale (say bump up the seeding by a couple of orders of magnitude) using today's technology then the seeding approach could be much more thoroughly tested.

Some people are going to oppose climate engineering because, for reasons that are religious in character, they believe that humans do not have the right to intervene in nature to cause climate scale changes. Others will oppose it out of fear of unintended consequences. However, even if we reject the sort of moral philosophy that views natures as something that should not be tampered with and even if we may some day know enough to be able to predict all major consequences there will still be another argument against climate engineering: any intentional shift in weather that causes changes in one place will cause changes throughout the world. As a consequence of those changes (no matter how large or small) there are bound to be winners and losers throughout the world as well. For instance, a slight increase or decrease in rainfall in other countries will either increase flooding or lead to a reduction of crop yields.

Of course industrialization is already causing small scale climate changes around the world. Greenhouse gases are only one of the ways that this is happening. Agriculture and cities change how much dust gets generated and, as was demonstrated by the airline shutdown in America after the 9/11 attacks, jet contrails change temperature ranges. Many other examples can be cited. But these activities are carried out for reasons other than intentional climate change and most governments support the right of their own peoples to carry out these various climate-changing activities. Few human activities are currently carried out for the sole purpose of climate change (cloud seeding for rain being the only one I can think of). So people will still draw a distinction between intentional and unintentional climate change.

One might be able to argue that climate engineering to dampen the energy of hurricanes would cause changes that are smaller than the changes we are already causing. However, unless the dampening down will reduce the hurricane into a mild storm the danger is that the hurricane might change course and in doing so cause damage to different towns and cities. The problem is that while the total amount of damage may be less the people who suffer it will claim they have a right not to have artificially induced damage inflicted on them as a consequence of reducing a much larger amount of damage elsewhere.

So does that mean that climate engineering is beyond the realm of political feasibility? I can see one reason why the vast bulk of the population of many countries may decide to support it: to reverse a sudden, large, and painful change in the climate. I've previously posted a link on ParaPundit.com about the possibility that the Atlantic Conveyor that brings heat up from the Gulf Stream to keep the North Atlantic and Europe much warmer could stop running if the salinity of the north Atlantic drops too low (and as you can see by clicking thru it is dropping).

It is not clear at this point that human greenhouse gas emissions are what are behind the changes in the north Atlantic salinity. We must bear in mind that large climate variations happen naturally. The Atlantic Conveyor may stop running and start running for reasons unrelated to human activity. Still, if it did stop running lots of people would decide that human activities at least contributed to the event and hence they would conclude that the event was "unnatural" (ignoring that humans are part of nature and that it is false to believe that consciousness and sentience makes us unnatural). The ability to label a large and sudden climate change as "unnatural" would open the door widespread support for an unnatural intervention to get the Conveyor running again.

It is my view that any large sudden change in climate will be labeled as unnatural. Never mind that large sudden changes in climate happen for natural reasons (ie not as a consequence of activities carried out by humans). Human impacts on the world are large enough that any large climate change can plausibly be blamed on human activity. The objections to climate engineering therefore are easier to overcome because in many cases climate engineering can be portrayed as an attempt to reverse what humanity has caused. This makes the future prospects for climate engineering much more likely that they might seem at first glance.

By Randall Parker 2002 October 12 02:57 PM  Engineering Large Scale
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2002 October 11 Friday
Personal DNA Sequencing Affordability

This article projects it will take at least 5 years before personal DNA sequencing is affordable:

US Genomics in Massachusetts has developed a machine that scans a single DNA molecule 200,000 bases long in milliseconds. For now, it untangles the DNA and scans the molecule by picking out fluorescent tags located every 1000 base pairs or so.

But chief executive Eugene Chan says the company expects to be able to read sequences one base at a time in three or four years. "Our goal is to sequence the genome instantaneously," he says.

Blonde or brunette

Other firms, such as Texas-based VisiGen Biotechnologies and British company Solexa of Essex are also trying the single-molecule approach. The consensus is that it will take at least five years before sequencing technology reaches the point where it's fast and cheap enough to make personal genomics feasible. What's more, it also has to be highly accurate.

You can find my previous post about Solexa here and one about nanopore technology for rapid DNA sequencing here. Also, once personal DNA sequencing becomes cheap the mating dance will change. and also personal DNA privacy will become impossible to protect.

By Randall Parker 2002 October 11 07:43 PM  Biotech Advance Rates
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Implantable Microchips to deliver drugs

The idea here is not just to have better control of the rate of deliver. A lot of large biological macromolecules can not be taken orally. In order to avoid the need for injection this approach puts the drug delivery system inside the body:

A small onboard processor, packaged with the drug-holding chip, choreographs how each of the 400 wells opens at precisely the right moment over a period of, say, six months. In the case of the MicroCHIPS prototype, the processor is an off-the-shelf model similar to those that power handheld calculators. The whole drug-delivery system finishes up as an implantable device no bigger than a cardiac pacemaker. After being implanted, blood vessels grow around the chip, allowing the medication to diffuse straight into the capillary network.

More advanced models will sense drug levels and will use a radio transmitter to return the information to a receiving device outside the body.

By Randall Parker 2002 October 11 01:11 AM  Cyborg Tech
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2002 October 10 Thursday
Kevin Warwick On Our Cyborg Future

UK Reading University professor Kevin Warwick foresees a day when brain implants send signals between humans rendering spoken speech obsolete:

His ideas get weirder. Warwick looks forward to the day when implants might allow the body’s functions like heart rate, blood pressure and temperature to be monitored in real time. His most bizarre vision: the world of 2050 dominated by cyborgs, their brains all linked to a global network, sharing access to a common super-intelligence. Network police could be summoned at the mere thought of crime.

This reminds me of the 1967 paranoid classic movie The President's Analyst which has a great part where Coburn's character is kidnapped by The Phone Company because The Phone Company wants him to convince the President to allow The Phone Company to implant chips in everyone's brains that will allow them to dial a phone number just by thinking it.

By Randall Parker 2002 October 10 06:57 PM  Cyborg Tech
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Mutation for redheads is of recent origin

In evolutionary terms a mutation that arose only 20,000 years ago is pretty recent. If this is correct then the pheomelanin variation of melanin that produces red hair is pretty new.

According to the most recent estimates, the first red hair sprouted just 20,000 years ago, long after the advent of modern homo sapiens.

Well, whether your hair has (or had) eumelanin for brown and black hair or pheomelanin for yellow and red hair some day gene therapy or cell therapy will make it possible to turn gray hair back to a youthful color. Women wanting a different color will even be able to choose which type of melanin and in what quantity they want to have. Probably some adult stem cells will be able to be converted into youthful melanocytes and melanosomes:

Research suggests that we may be able to reverse the graying process in the future. Tobin's group, for instance, has determined that the dormant melanocytes and melanosomes in gray hair follicles can be coaxed into creating melanin again

By Randall Parker 2002 October 10 03:13 PM  Human Population Genetics
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Microtiter Plates Next DNA Sequencing Cost Reduction?

Genome Therapeutics Corp. has won an NIH grant to try to reduce DNA sequencing costs by an order of magnitude:

Reflecting a commitment to delivering high-quality genomics services, the commercial services division of Genome Therapeutics Corp. (Nasdaq: GENE), GenomeVision(TM) Services, has received a $1.6 million grant from the National Human Genome Research Institute (NHGRI) for the advanced development of genomic technologies. As the only commercial sequencing center in the federally-funded Human Genome Project and a major participant in the Rat Genome Project, GenomeVision Services has continually worked to advance its own technologies and practices in order to help streamline critical parts of the genome sequencing process, such as sample preparation and DNA analysis.

This is a refinement of current techniques:

The goal of this two-year grant, which is separate from previous awards from the NHGRI, is to achieve a five to ten-fold reduction in the sequencing costs for large-scale genomic sequencing projects. Specifically, GenomeVision Services is working to reduce the minimum amount of DNA needed, from microliters to nanoliters, for standard instruments to perform analysis using microtiter plates. In addition to plates that use smaller sample amounts, GenomeVision Services is also developing plates that allow the removal of contaminants while still enabling the retrieval of the DNA in the sample for additional analysis. Genome Therapeutics retains all rights to the microtiter plates, which are available for licensing.

By Randall Parker 2002 October 10 02:18 PM  Biotech Advance Rates
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First Human Parkinsons Gene Therapy Trial To Start

This is exciting:

The first human clinical trial of a gene therapy treatment for Parkinson's disease is set to begin in the US, following successful results in animals.

By Randall Parker 2002 October 10 11:59 AM  Biotech Therapies
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Microbial Fuel Cell To Run On Kitchen Scraps

This reminds me of the fusion reactor that took scraps in the Back To The Future movie. This one produces hydrogen gas to run a fuel cell.

Although such "microbial fuel cells" (MFCs) have been developed in the past, they have always proved extremely inefficient and expensive. Now Chris Melhuish and technologists at the University of the West of England (UWE) in Bristol have come up with a simplified MFC that costs as little as £10 to make.

By Randall Parker 2002 October 10 08:42 AM  Energy Tech
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2002 October 09 Wednesday
Ray Kurzweil on Sensors In Our Brains

Here's a report from EE Times of Kurzweil's comments at the Fall Sensors Expo

BOSTON — Using deliberately provocative predictions, speech-recognition pioneer Ray Kurzweil said that by 2030 nanosensors could be injected into the human bloodstream, implanted microchips could amplify or supplant some brain functions, and individuals could share memories and inner experiences by "beaming" them electronically to others.

The NY Times also reported on Kurzweil's speech:

"We're limited to 100 trillion connections," said Mr. Kurzweil, alluding to current estimates of the processing power in the human brain. "I don't know about you, but I find that quite limiting."

You can go to Kurzweil's site and watch the AI Ramona perform.

By Randall Parker 2002 October 09 11:41 AM  Cyborg Tech
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Color Controllable LED Light Sources

LED light sources will make it possible to dial the up your preferred color mix. Want to wake up to a reddish tinge? No problem. If the cost trend for LED light sources continues then the days of incandescent and flourescent bulbs are numbered:

The best white LEDs on the market emit 25 lm/W, which is almost twice as efficient as an equivalent tungsten-filament light bulb, but barely a third as good as a fluorescent tube. To become competitive, the devices need to reach 80 lm/W. To rule the world, 150 lm/W is probably required. If progress continues at the rate of the past 30 years, this will be reached by 2010. That is a big if, but the efficiency of blue and UVLEDs should improve dramatically as better ways are found to build them.

By Randall Parker 2002 October 09 10:11 AM  Materials Advances
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2002 October 08 Tuesday
Proposed Huge Boeing Pelican Aircraft

Its payload would be more than an order of magnitude greater than that of a C-5 Galaxy.

This article has comparisons to other existing aircraft as well:

The Boeing Co.'s proposed Pelican transport aircraft would dwarf the largest plane now flying, the Russian-built Antonov An225.

The An225 has a 290-foot wingspan, which would be more than 200 feet shorter than the Pelican's preliminary wingspan design of 500 feet. It is 275 feet long, compared to the Pelican's projected length of more than 300 feet. And its cargo-hauling capacity, 275.5 tons, would be only a fraction of the Pelican's as-designed 1,400-ton payload.

The Daily Telegraph has an artist's rendering here.

The Pelican will be designed to fly 50 feet above the ocean, using the buoyant aerodynamic effect of flying close to the water to provide its maximum economic range.

The BBC says Boeing hasn't yet committed to building it.

Here's the best article on the prospects for the Pelican.

Update: Some additional clarification from the Pelican Program Manager.

Other than cruising at low altitude above water, the Pelican has little in common with historical Russian wing-in-ground-effect (WIG) aircraft. The Russian WIGs were designed primarily for short range, sea-based military missions. With beefy structure and ample propulsion systems for water operations, they were no more efficient than modern subsonic transports, despite their lower speed.

The advent of computer-based flight controls permits the Pelican to be land-based, so that it can be much lighter and aerodynamically cleaner than earlier WIGs. It appears, remarkably, that land-based WIGs differ little from aircraft optimized for conventional cruising altitudes. This permits a dual-mode aircraft to provide substantial operational benefits in the long-range transport of cargo.

Advanced flight control systems also provide ample maneuverability while automatically maintaining safe clearance from the water.

— Blaine K. Rawdon, Pelican Program Manager, San Pedro, Calif.

Pelican would fly on a cushion of air.

Riding on top of a cushion of air, the Pelican would experience 70 percent less drag than a normal plane, allowing it to travel further while using the same amount of fuel. The wing-in-ground effect occurs at an altitude equivalent to 10 percent to 25 percent of the wing’s width at the point where it joins the fuselage. The phenomenon increases the ratio of lift to drag for a wing.

"It’s an effect that provides extraordinary range and efficiency," says John Skorupa, senior manager of strategic development for Boeing Advanced Airlift and Tankers. "With a payload of 1.5 million pounds, the Pelican could fly 10,000 nautical miles over water and 6,500 nautical miles over land.

By Randall Parker 2002 October 08 07:38 PM  Airplanes and Spacecraft
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2002 October 07 Monday
Heart-lung bypass machines used to rest organs

As shown in this article about Children's Hospital in Boston heart-lung bypass machines are used as a way to allow tired organs to rest:

As he drove back to Children's in the dark, he ordered Jordan placed on a special heart-lung bypass machine that would give her heart a rest - and keep her alive - while doctors figured out what to do.

It was an emergency, and the cost - $3,600 a day - did not enter his mind. ''We try to do things as efficiently as we can,'' he said, ''but I am not prepared to cut corners in a life-and-death situation.''

By Randall Parker 2002 October 07 11:11 AM  Cyborg Tech
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Genetic Privacy And Medical Insurance

Scientists are gradually identifying the many genetic variations that affect health risks. As the number of known variations increases and as the cost of genetic testing falls an increasing number of people will decide to undergo genetic testing to learn more about their health risks. It seems likely that genetic variations will be found that influence the risks for almost all diseases.

When individuals can learn much more about their personal genetic risks for a variety of illnesses they will in many cases respond by making different choices for medical insurance. Many of those faced with greater genetic risks will respond by trying to buy more medical insurance and those faced with fewer risks tend to buy less medical insurance. This will cause a large change in the medical insurance industry regardless of what regulatory changes are adopted in response. These changes will happen in any country that has private medical insurance. While the life insurance industry will also face changes the scope of this essay will restricted to medical insurance.

Logically speaking there are 4 main scenarios for knowledge about genetically derived health risks as they affect medical insurance:

• First, the individual and the insurance company both know very little about the individual's DNA sequence. This describes most of history up until this point.

• Second, only the insurance company knows the health risk information from an individual's DNA.

• Third, only individuals know their own genetic health risks.

• Fourth, both the individual and the insurance company know the individual's genetic health risks.

The first possibility describes where things have stood for most of the history of medical insurance up till now. However, since there are already a number of testable genetic health risk factors this has already begun to change in the direction of the other 3 choices.

The advantage of the first possibility is it literally makes medical insurance possible. The medical insurance industry and applicants have nearly equal ignorance of the health risks of medical insurance applicants. Everyone has a motive to buy medical insurance because no one knows whether they might fall ill. This provides the revenue to pay for those who do develop an illness.

The second logical possibility is unlikely to happen much in practice. Once personal DNA sequencing becomes affordable its likely that individuals will choose to have themselves tested. However, it is conceivable that some people won't want to know what their DNA sequence is or what risks they face from their DNA sequence. At the same time an insurance company, if allowed by regulatory agencies, might in the future insist on a tissue sample for DNA testing as part of an application for medical insurance. That way the medical insurance company can create a more accurate picture of the applicant's health risks. This possibility puts an individual who has an excellent low risk genetic profile at a disadvantage vis a vis an insurance company because the company can charge him a premium that is average for all people even though he's at below average risk and he will not know that in theory he ought to qualify for a lower rate.

The eventual debate will be between the third and fourth possibilities. Should insurance companies be allowed to know the genetically caused health risks of insurance applicants? That question looks set to become the cause of a large political battle in many nations. As genetic testing becomes cheaper and as it advances to cover a larger number of genetic locations most people will have their DNA tested in order to learn about their genetically caused health risks. So the most important question in the debate about medical insurance is going to boil down to the question of whether medical insurance providers will have the right to find out the medically important genetic variations of each applicant as part of the application for medical insurance. The insurance companies will want this information to decide whether to grant coverage and if so what premiums to charge and terms to offer.

When Genetic Testing Becomes Cheap Can The Insurance System Survive?

What happens when many genetic risk factors become known and genetic testing becomes cheap and widely available? This will change the decisions that individuals make about their medical insurance. The insurance industry will be greatly affected by this change regardless of whether it is allowed access to the genetic test results of individual medical insurance applicants. Lets look at the two mostly likely scenarios.

If only insurance buyers know their genetic risks the rates will rise for all.

If a government passes legislation that denies insurance companies access to the results of genetic disease susceptibility tests then individuals will still get tested and find out their genetic risks. People at greater risk will tend to buy more insurance and people at lesser risk will tend to buy less insurance. So the people who will cost the insurance companies to the most will rush to get lots of coverage and therefore will cost the medical insurance companies more than they do now. At the same time the people who face the least risk will spend less on medical insurance. So medical insurance companies will get less money from a group that currently pays in more than they draw out in benefits. The result is that with rates kept the same the revenue for the insurance companies will drop while their costs will rise.

Employer provided health plans will suffer similar problems. Someone who knows they have a greater genetic health risk will choose jobs that have fancier medical insurance plans. People at low risk will be more willing to be self-employed and buy their own medical insurance with more limited plans with higher deductibles and lower premiums. Such low risk people will also be more willing to take jobs that come with less or no medical insurance.

The general trend therefore will be that high risk individuals will tend to buy more insurance while the low risk individuals will tend to buy less. If current premium levels were kept the same then the total amount of revenue flowing to the insurance companies would decrease while their outlays would increase (since high risk people would tend to have more insurance than is they do now on average). The insurance companies would have to raise rates across the board in order to survive. Under this scenario some customers will be priced out of the market.

If both sides know the genetic risks the rates will rise for some and fall for others.

If the insurance companies are allowed to know genetic profile of each insurance applicant and are allowed to set rates based on genetic risk profiles then people with greater risk of illness (especially for illnesses that are expensive to treat) will have to pay higher medical insurance premiums. Under this scenario the lower risk people will pay less for the same amount of coverage than they would under the scenario where the medical insurance companies are allowed to know the genetic risks of applicants. More low risk people would buy coverage under this scenario because their premiums will be more affordable.

Of course, the rates for really high risk people will be too high for many of them to afford. In some cases the insurance companies will decide they will not even offer coverage.

How much will insurance rates change?

An insurance system only works because people don't know how much risk they face. If risks can be accurately calculated for groups but not for individuals then insurance works. Lots of people pay in since all payers think they are at risk. To the extent that any payers can learn they are at less risk they become less willing to pay in. If they can know that they are at no risk at all for a particular threat they would have no need to buy any insurance to deal with that threat.

Just how much insurance rates (and even the availability of insurance) will change depends on how much health risks can be calculated from genetic information. It also depends on how much the knowledge of the health risks can be used to reduce those risks.

Conditional Medical Insurance

Just because some people will turn out to have high risks for certain illnesses will not necessarily be a reason for an insurance company to deny them coverage. In some cases there will be ways to manage the increased risks. For high risk depending on the nature of the risk there are alternatives that insurance companies may offer:

  • Some high risk people will be offered accident coverage only.
  • Other high risk people will be offered medical insurance that has exemptions where their highest risk illnesses are not covered. This will be similar to pre-existing illness exemptions on some policies available today.
  • Required periodic testing for specific disorders as a condition for issuance of a policy for high risk individuals for disorders. There may be an increased premium to cover the testing and to treat the disease should it arise.
  • Required preventative treatments as a condition for issuance and continuation of a policy. It is highly likely that, for instance, a variety of compounds will be found that reduce the risk of some types of cancers (eg by up-regulating liver detoxification enzymes) and some of those compounds may work especially well in people who are at heightened risk for the disorders. Gene therapies will be developed that can reduce risks as well. So someone with, for instance, a higher risk for colon cancer might be required to undergo colon gene therapy to make the colon cells less likely to become cancerous.
  • Required dietary and other lifestyle changes. The problem with this type of requirement is that it can be hard to enforce. So unless an insurance company has a way to monitor compliance this approach is not likely to be used. Still, in some cases blood tests will be capable of detecting noncompliance with medical insurance terms. One might be required to get periodic blood or other testing to detect whether a particular type of food has been consumed.
Anyone have a crystal ball?

It seems difficult to predict exactly how medical insurance will change. It depends on how much genetic variations contribute to health risks, how quickly treatments come along that can cancel out the harmful effects of high risk variations, how expensive those treatments will be, how rapidly the genetic tests become available, and how various factions mobilize to fight over this issue in each political jurisdiction.

There is a bright side: knowledge of how genetic variations contribute to disease incidence will greatly accelerate the rate of advance of biomedical science and technology. Much more effective treatments will be developed for all illnesses. Gene therapy will eventually allow parents to change their progeny's genes so that future generations will have fewer genetically caused health risks.

By Randall Parker 2002 October 07 10:57 AM  Biotech Privacy
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Genetic testing leads to insurance denial

This is on the cusp of becoming a very big political issue:

Early this year, a healthy 28-year-old Livonia, Mich., mother became what is believed to be one of the first people in the country to be denied life insurance because of her genes. An underwriter refused to issue her a policy in part because she has a gene indicating a good chance of developing breast or ovarian cancer. The woman fears further discrimination and does not want her name in the newspaper.

By Randall Parker 2002 October 07 10:10 AM  Biotech Society
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2002 October 06 Sunday
Henry Jenkins: Love Online

Henry Jenkins, director of the Program in Comparative Media Studies at MIT, has written an essay in Technology Review about his son's experiences as an adolescent developing relationships with girls he has met online:

They may have met online but they communicated through every available channel. Their initial exchange of photographs produced enormous anxiety as they struggled to decide what frozen image or images should anchor their more fluid online identities. In choosing, my son attempted to negotiate between what he thought would be desirable to another 15 year old and what wouldn’t alienate her conservative parents.

The photographs were followed by other tangible objects, shipped between Nebraska and Massachusetts. These objects were cherished because they had achieved the physical intimacy still denied the geographically isolated teens. Henry sent her, for example, the imprint of his lips, stained in red wine on stationery. In some cases, they individually staged rituals they could not perform together. Henry preserved a red rose he purchased for himself the day she first agreed to go steady. Even in an age of instant communication, they still sent handwritten notes. These two teens longed for the concrete, for being together in the same space, for things materially passed from person to person.

Of course, as technology advances the distance that a relationship can progress online will similarly advance. Next stop will be live video feeds. Even that is possible already, albeit limited by a rather low frame rate and/or resolution. Remotely controlled prosthetic sex toys can't be very far behind. Anyone know whether primitive remote controlled prosthetics have reached the consumer market yet?

By Randall Parker 2002 October 06 06:31 PM  Comm Tech Society
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2002 October 05 Saturday
Anti-satellite Warfare Could Ruin Low Earth Orbit?

According to Joel Primack writing in the Bulletin of the Atomic Scientists a really big dust-up in low Earth orbit caused by anti-satellite weapons could render LEO unusable for satellites:

But in reality, space does not clear after an explosion near our planet. The fragments continue circling the Earth, their orbits crossing those of other objects. Paint chips, lost bolts, pieces of exploded rockets—all have already become tiny satellites, traveling at about 27,000 kilometers per hour, 10 times faster than a high-powered rifle bullet. A marble traveling at such speed would hit with the energy of a one-ton safe dropped from a three-story building. Anything it strikes will be destroyed and only increase the debris.

With enough orbiting debris, pieces will begin to hit other pieces, fragmenting them into more pieces, which will in turn hit more pieces, setting off a chain reaction of destruction that will leave a lethal halo around the Earth. To operate a satellite within this cloud of millions of tiny missiles would be impossible: no more Hubble Space Telescopes or International Space Stations. Even communications and GPS satellites in higher orbits would be endangered. Every person who cares about the human future in space should also realize that weaponizing space will jeopardize the possibility of space exploration.

To a scientist whose research has benefited enormously from space observations, these prospects are horrifying. Many of the important astronomical satellites are in low Earth orbit (from the lowest practical orbits—about 300 kilometers—to about 2,000 kilometers above the Earth). The Cosmic Background Explorer, which operated from 1989 to 1994, is at 900 kilometers and the Hubble Space Telescope is at about 600 kilometers.

In addition, most Earth-observing satellites are also in low Earth orbit, both those that study changes in climate and vegetation and those for military surveillance. Low orbits permit the highest-resolution imaging, and are also easiest to reach with existing launch vehicles.

Unfortunately it is probably impossible for treaties to prevent the inevitable development of anti-satellite weapons. US adversaries such as China see US military satellites as high priority targets in any future conflict with the US. The history of arms control treaty cheating (eg the massive Soviet biological weapons program) suggests that only countries that want to obey treaties will do so - especially among the less democratic and less open nations.

What would be interesting to know is whether any low cost techniques could be developed for doing clean-up after massive amounts of small fragments were released into LEO. Could one make, for instance, large very thin sheets unfolded and moved around in orbit (perhaps using solar wind?) to try to get fragments to collide with them? Every collision - even if the collisions punch right thru the thin sheets - is going to rob a fragment of momentum. Rob of them of enough momentum and they will fall out of orbit.

By Randall Parker 2002 October 05 03:57 PM  Airplanes and Spacecraft
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2002 October 04 Friday
Initial sheep artificial lung tests successful

The tests were done for a short period of time. Researcher Robert Bartlett next intends to repeat the tests for 30 day periods and hopes to try the first human tests in a year or two.

In early tests, sheep with damaged lungs were either put on standard therapy — the mechanical ventilator — or given the artificial lung plus a ventilator. All the sheep with the artificial lung survived, while some on the ventilator alone died, Bartlett says.

Additionally, the sheep using the device had only minimal use for the ventilator, suggesting that “it provided nearly 100 percent of their normal lung function,” he says.

Importantly, there were no deleterious effects. “The only problem was a sheep falling asleep and knocking it over,” he says with a smile.

By Randall Parker 2002 October 04 01:42 AM  Cyborg Tech
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Artificial liver phase I tests in humans

One of uses for artificial organs will be to provide a patient with a way to stay alive while waiting for a new organ to be grow from the patient's own cells. Though the initial use of the artificial liver described below will be to keep patients alive while they wait for a suitable donor liver:

BERLIN – Four years after the first American clinical trial of an experimental artificial liver system began at the University of Michigan Health System, its leader says he is encouraged by the results thus far. And, he's optimistic about the system's potential to help more liver-failure patients stay alive until they receive a liver transplant, or recover without a transplant.

Already, says Robert Bartlett, M.D., 20 desperately ill patients at the U-M Health System have used the device in a phase I trial. Six patients went on to receive a transplant, three of whom are still alive. Two other patients recovered liver function without needing a transplant. Data on the first nine U-M patients were published last August in the journal Surgery; Bartlett discussed the full group at a meeting this week in Germany.

Results from Germany, where the system was invented, and from the three other American hospitals now testing it, also give Bartlett hope. In all, the system appears safe, able to reduce blood toxins, and able to reverse coma and shock.

The system, called albumin dialysis, uses special filters and proteins to remove toxic substances from the blood while sparing helpful compounds.

Bartlett spoke about the status of the albumin dialysis approach to liver support in the keynote and summary addresses at the Fourth International Symposium on Albumin Dialysis in Liver Disease this week in Rostock, Germany.

By Randall Parker 2002 October 04 01:12 AM  Cyborg Tech
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Umbilical cords as sources of stem cells

A scientist at Oklahoma State is working on growing blood vessels from umbilical cord stem cells:

Sundar Madihally has already found a way to turn stem cells from umbilical cords into endothelial cells, which line the inside of blood vessels.

Within five years, he hopes to create a process that will make blood vessels in large quantities. He plans to patent the idea.

His next project will be to turn the CD34 positive stem cells into tissue for livers and heart valves.

People who are about to have a baby who want to plan way ahead for their baby's future could take the umbilical cord and store cells from it as a future stem cell source. My guess is that the cells would be frozen for long term storage and, while most cells would die, enough would survive being frozen for decades to eventually be usable as stem cells.

Ideally, Madihally said, stem cells would come from umbilical cord blood stored by families, so the blood has the same genetic makeup as the patient.

However, it may well turn out that this technique will never be practically useful. By the time someone born now would be old enough to need umbilical stem cells it is likely other techniques will be available for growing compatible organs from one's own regular cells.

Lots of other tissue growing research is actively being pursued:

One of Madihally's undergraduate students is trying to grow teeth. Other researchers in Cleveland are creating bone and cartilage. A doctor in Philadelphia was able insert stem cells into a baby in the womb and cure the baby's immune deficiency disease, commonly known as the "bubble boy syndrome," before birth.

By Randall Parker 2002 October 04 12:58 AM  Biotech Organ Replacement
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2002 October 02 Wednesday
Athletic Genetic Manipulation To Be Banned

Learn a new acronym if you don't already know it: World Anti-Doping Agency or WADA. Sounds like something out of an Austin Powers movie. Well, WADA and the International Olympic Committee are banning genetic therapy to enhance athletic performance:

Lungs designed to saturate oxygen for endurance running; arms custom-built for golf, tennis, baseball-pitching, or javelin-throwing; knees constructed for skiing; sprinters, perhaps, with cells cloned from cheetahs, and rugby-players ditto, but additionally modified with cells from the fighting Miuras of the Spanish bullring? Jonah Lomu would look like Ronnie Corbett.

Science fiction? Sport does not believe so, as evidenced by the decision by the World Anti-Doping Agency and International Olympic Committee to add genetic manipulation to the list of offences under their rules.

There is no end to the number of ways that genetic engineering will enhance athletic performance:

'Designer knees' for downhill skiers or 'super arms' for tennis players have moved from science-fiction novels to the agency agenda as it fears genetic engineering could become the biggest threat to the future of sports. However, the anti-doping authorities are already playing catch-up and genetic doping could prove hard to rein in.

This article predicts genetically engineered athletes within 10 years:

"It's within the grasp of any graduate-level student in molecular biology," said Dr. Ted Friedmann, director of the gene therapy program at the University of California at San Diego and a member of the World Anti-Doping Agency's health and research committee.

"He or she could give you at least four different ways to do it. They could also tell you how to improve oxygen transportation or tell you how to engineer faster and stronger athletes. That, combined with the existence of huge amounts of money in sport and the pressures to excel, all suggests something will be done in this direction.

Gene therapy to enhance athletic performance will be much harder to detect. It could be injected directing into an organ and the effects could be limited to just that organ. So how to detect it? Take samples from every organ? Seems impractical.

Gene Therapy Will Still Become Widely Used For Athletic Purposes

Gene Screening For Recruitment: There is another way that genetic technology will change athletics: genetic screening to choose the most promising athletes for training and recruitment. This will be done for reasons other than pure performance potential. Proneness to injuries and ability to heal from injuries will surely be found to have strong genetic components. So an NFL football club faced with a difficult choice may well opt for the fellow who is less likely to be sidelined by injuries.

Repair That Improves Function: Another conflict will arise over the question of gene therapy for injury repair. It is inevitable that some gene therapy will be developed that will, for instance, repair a ligament that makes it even better than new. Many people in the general public will decide that if their ligament was weak enough to get injured in the first place why not apply a treatment that will make it stronger. Will an organization like the IOC allow athletes to do the same? if they do then injured athletes who have been treated and healed will be more capable than those who haven't yet suffered injuries.

Pro Sports and Ratings: I predict that there will be professional sports organizations that decide to allow it. Look at pro wrestling which is a sport that is as much about entertainment as it is about physical prowess. Also, look at the circuits travelled by former Olympic skaters. The audiences just want to see a beautiful show. The injuries experienced by pro skaters in their 30s or 40s will be dealt with using the latest in genetic therapy. The ability to pull in crowds and have good TV ratings will outweigh the sorts of concerns that motivate the managers of Olympic sports.

Ballet and Gene Therapy: There are occupations that are similar to athletics in that they place special demands on the body and cause much higher rates of career-threatening injuries. The best example is ballet. Injuries to muscles, ligaments, and tendons are frequent occurrences and too often career ending. I expect gene therapy to improve ligaments and tendons will become very common among ballet dancers.

Genetically Engineered Children: The IOC has banned gene therapy for athletic enhancement. But what happens when inevitably someone uses genetic engineering techniques to choose genes for their children before the children are even conceived? Are all such children to be banned from Olympic sports and other amateur sports? Parents may enhance their children by using genetic variations found elsewhere in the human population which they themselves do not possess. In these cases it will not even be possible to detect this sort of genetic engineering unless genetic samples are taken from the official parents and compared to the genetic sequence of the athlete.

By Randall Parker 2002 October 02 04:14 PM  Biotech Athletics
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Nuffield: Use Genetic Info In Criminal Sentencing

There is another big issue that the Nuffield Council on Bioethics tackles in their latest report: The use of genetic information about convicted offenders in court sentencing decisions. Here from the PDF report summary is the relevant excerpt:

We conclude that, with regard to the sentencing of convicted offenders, the criminal law should be receptive to whatever valid psychiatric and behavioural evidence is available. The taking into account of genetic factors would depend on the degree to which such evidence is convincing and relevant. Credible evidence of influence and a robust test for the genetic factor in question would be essential: the weight to be accorded to such information would be determined by the judge (paragraph 14.32). Currently, environmental, social and psychiatric assessments may be taken into account by judges in determining appropriate sentences. These must also be supported by valid, accurate and reliable evidence. It would be unwise to assume that genetics will not be able to assist in determining degrees of blame, even if the ‘all-or-nothing’ question of responsibility is not affected by genetic factors themselves. Such a role would not compromise basic assumptions as to responsibility.

Exchanges between genetics and the criminal law are at present not very productive given the uncertain nature of the evidence. This is likely to change. We recommend that the criminal justice system should be open to new insights from disciplines that it has not necessarily considered in the past. The regular exchange of ideas in this area between researchers in behavioural genetics, criminologists and lawyers could be an effective means of ensuring that legal concepts of responsibility are assessed against current evidence from the behavioural and medical sciences (paragraph 14.33).

I find their position on this issue surprising in light of their opposition to the use of genetic technology to boost the IQ of offspring. Some day the genetic factors that play a role in mental development will be understood. On one hand they argue that we aren't supposed to try to make any changes in our offspring. On the other hand we are supposed to treat criminals differently depending on which genes they have. I find this inconsistent.

Lets consider some reasons for and against the use of genetic information in criminal sentencing. First of all, genetic factors will be useful in predicting the odds of recidivism. Will a given convict violate the law again? It may never be possible to predict with absolute accuracy for every single convict whether the convict will continue with criminal behavior. But decisions are made all the time based on probabilities and most people find this to be a reasonable thing to do. Judges routinely give longer sentences to criminals who are expected to pose greater threats in the future. It has long been standard to use knowledge of motives and circumstances to try to guess who has committed an act they are unlikely to repeat (eg the murder of a lover found unexpectedly with a spouse or the accidental killing of someone in a fight where the other fighter falls into an object that kills them) and who has committed an act that demonstrates a tendency toward a repeated pattern of behavior (eg a mugger who kills in order to make it easier to get stolen goods or in order to prevent his victims from reporting him). Genetic information will just increase the accuracy of the probabilities used. But there are arguments that can be made for and against the use of this information and those arguments include:

  • Science can better predict who will be a recidivist. Longer jail terms for those with criminal genetic tendenices and shorter sentences for those without such tendencies may lower the crime rate without increasing the total prison population.
  • Sentencing someone to longer sentences have genetic tendencies toward violence means effectively condemning someone for crimes they haven't even committed yet.
  • If someone knows they don't have genetic variations that mark them as crime-prone then they may use this knowledge in their calculations of whether to commit a crime. They may be more likely to commit a crime because they know that if caught and convicted they will face a lighter sentence. Of course, this population group is more easily deterred in the first place. So the danger here might not be that great.
  • The more decisions are made based on guesses about recidivism the less the decisions will be based on punishment. The public at large believes criminals should be punished. If some people are let off lightly because they don't have criminal tendencies in their genes the public may see this as unfair.
By Randall Parker 2002 October 02 02:13 PM  Biotech Society
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2002 October 01 Tuesday
UK Group Opposes Selecting For High IQ Genes

A British think tank has come out in opposition to selection higher IQ children:

The selection of babies with genes linked to high IQ should be banned, along with the abortion of embryos predicted to have below average intelligence, according to a report published today.

The Nuffield Council on Bioethics, an independent think tank, makes the call in its study, Genetics and human behaviour. This weighs up ethical, legal and social issues raised by the search for genes that influence intelligence, violence, personality traits and sexual orientation.

Note that this group is not arguing against abortion in general. They are also not arguing against artificial insemination. They are arguing against using techniques to select for mental characteristics that are genetically determined when this is done to boost abilities.

The behavioural genetics part of the Nuffield Bioethics website is here

Here is the report Summary And Recommendations as a 115.4 Kb PDF.

Here is the Full Report as a 2.5 MB PDF.

These people do raise some valid concerns. For instance, I fully share this concern from page 9 of the summary:

Medicalisation is an issue that affects many areas of life, not just behavioural genetics. In the case of behavioural traits, since research into genetic influences is at an early stage, it is not possible to say whether medicalisation will be likely, or whether it will have, on balance, positive or negative implications. However, examples of the deleterious effects of medicalisation in other areas suggest the need for awareness of potential problems. We conclude that research in behavioural genetics has the potential to contribute to the existing phenomenon of medicalisation. Deleterious effects that should be borne in mind include shifting the boundary between normal variation and disorder further away from the extremes of variation; reducing social tolerance of previously ‘normal’ behavioural traits; and the routine selection of genetic or medical interventions without adequate consideration being given to environmental interventions and other options (paragraph 13.23).

Medicalisation has led to Ritalin Nation - at least here in America. I suspect too many people are being treated as suffering from mental conditions.

However, the idea that we should not change genes that are within the "normal" range of variations is highly problematic. What if it turns out that a large fraction of the population carries genetic variations that predispose them to depression? Do we tell them, sorry, you have to pass these genes along to your children? Just what counts as a therapy versus an enhancement is in the eyes of the beholder to a very large extent. This is especially the case with behaviour and personality characteristics. Here is a relevant excerpt from summary pages 10-11:

The way to distinguish between those interventions which count as ‘therapies’ and those which count as ‘enhancements’ is by reference to the condition that is to be altered: therapies aim to treat, cure or prevent diseases and to alleviate pathological conditions which place someone outside the normal range, whereas enhancements aim to improve already healthy systems and to advance capacities which already fall within the normal range. This distinction is often used to justify a distinction between interventions which merit public support and those which do not. The suggestion is that there is a duty to ensure that our fellow citizens receive therapies, but no duty to ensure that they receive enhancements. The distinction between therapy and enhancement is not straightforward and requires qualification, but the principle which associates it with that between public and private provision is a useful starting-point in this area.

The term "behavioural" misses the extent to which mental life is to a large extent internal. Yes, mental life does affect behaviour. But there are lots of people living lives of inner torment while putting on a different face with those they come into contact.

On page 11 of the summary one begins to see what values are driving their position on this issue:

It is difficult to adjudicate in the abstract between these egalitarian and libertarian positions. It is only once some effective intervention is under consideration that the costs and benefits of full public availability versus limited private availability for a privileged few can be assessed seriously. We believe that equality of opportunity is a fundamental social value which is especially damaged where a society is divided into groups that are likely to perpetuate inequalities across generations. We recommend, therefore, that any genetic interventions to enhance traits in the normal range should be evaluated with this consideration in mind (paragraph 13.48).

What do they mean by equality of opportunity in this context? When they talk about inequalities across generations it is clear they are referring to equality of outcomes. Their position appears to be a back door acknowledgment that people differ in innate abilities and that those differences lead to differences in outcomes. I think they are really arguing that people should not be allowed to make their children more intellectually able than other children because to do so would allow those smarter children to be more successful. The absolute level of success will be greater for these genetically selected children (which seems good to me) but that means greater success relative to others (which is bad in the eyes of socialists everywhere). So equality of opportunity is really a polite way of saying equality of ability for the purpose of equality of outcomes.

But if they really advocate equality of opportunity and are concerned that genetic selection for higher intelligence will give some people greater ability to achieve more favorable outcomes for themselves they ought to stop and notice that this is already the case. Suppose prospective parents can test several fertilized embryos and choose the one that will result in higher intelligence for their kid where otherwise the odds would be quite high that they'd have a below average kid. In that case aren't the parents choosing to produce a child whose earnings and achievement potential will not be so far below the best and the brightest?

The curious thing about this is that if the less bright people choose to use biotech to boost the intelligence of their children then they reduce the economic inequality of the next generation. But if more bright parents do the same then they will increase the economic inequality in the next generation.

If the writers of this report want a narrower range of economic outcomes in future generations then they really could advocate the use of genetic engineering techniques to do this. Simply require all parents to have children of equal intelligence. No, I am not advocating that. But it would certainly result in greater equality of opportunity and outcomes.

What we see here in this report is the working out from a fundamentally Leftist position on ethics and economics an assertion about what should or should not be allowed to be done with genetic engineering. However, they try very hard to cloak this position inside of the rhetoric of unconditional agape love (pages 14 to 15 in the summary):

At present, parents accept their children as they find them in an attitude of ‘natural humility’ to the unchosen results of procreation. This attitude is an important feature of parental love, the love that parents owe to their children as individuals in their own right; for this is a love that does not have to be earned and is not dependent on a child having characteristics that the parents hoped for. Parental love which includes this element of natural humility is, therefore, incompatible with the will to control. It is not compatible with attempts to interfere in the life of a child except where the interference is in the child’s own interest. Equally, it is not compatible with the practice of prenatal selection which seeks to identify, as a basis for choice, genetic predispositions for enhanced abilities or special character traits. For this is an attempt to determine the kind of child one will have – which is precisely not the unconditional, loving acceptance of whatever child one turns out to have.

Oh come on already. To be consistent an argument for natural humility toward the results of procreation would be an argument against any attempts to intervene for any reason before birth. Of course they are not arguing that. They only invoke this argument for characteristics of the brain. At the same time they bring up the child's best interests. How is it not in the child's best interests to be smarter? Can they argue that parents will love smarter children less? Why? The key argument in their summary report is where they talk about different forms of equality. The rest of it is window dressing.

By Randall Parker 2002 October 01 11:22 PM  Biotech Society
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NYTBR reviews Gregory Stock's Redesigning Humans

In an article entitled 'Redesigning Humans': Taking Charge of Our Own Heredity writer Gina Maranto (herself author of Quest for Perfection: The Drive to Breed Better Human Beings) reviews Redesigning Humans: Our Inevitable Genetic Future by Gregory Stock.

Gregory Stock is an optimist about the effects of genetic engineering of offspring. Maranto makes clear that she is more worried than Stock about what humans will do with the ability to genetically modify future generations:

But even if evolution could be steered in a positive direction, why presume that humans have the wisdom to do so? ''Redesigning Humans'' is an act of both boosterism and reductionism. It admits but then ignores the enormous complexity of biological systems; it places biology firmly above social, ecological and economic considerations; and it reduces concepts like success in life to the purely physical, as if health and longevity were the only issues that mattered. Isn't it pretty to think so?

It is perfectly legitimate to have such concerns. Surely any technology can be put to uses that are dangerous. However, what is lacking in the vast bulk of the more pessimistic writings about human genetic engineering is any real analysis of exactly which types of genetically engineered characteristics would pose great threats to civilization. What real dangers to civilization might arise as a result of genetic engineering? The stereotype some critics cite (and an old theme in science fiction) is of clone armies willing to obey the orders of their masters. However, even that stereotype is typically presented without a precise description of which personality characteristics, engineered into human fetuses, would lead to that dystopian future.

Genetically Engineered Dangerous Personality Types Are Greatest Potential Danger in Human Genetic Future

The ability to control personality type of offspring poses the largest potential danger of human genetic engineering. But here we have to be precise. Not all imaginable personality types are a threat to civilization. Many people will choose personality types for their offspring that are unlike the personality characteristics that they themselves possess. However, there are many different personalities that one will be able to choose for a child that might simply make them happier or less socially awkward while not in any way making them into people who are greater dangers to the rest of us.

Why do most of us choose to respect the rights of others? Why don't we all do so all of the time? Obviously, details of our personal experiences during upbringing play a role in determining just how fair or how compassionate each person wants to be or is able to be. But there is plenty of evidence (e.g, from comparative studies of twins raised apart) that biology plays a big role in causing differences in human behavior. For instance, men and women have radically different rates of commission of most types of crime. Another example is roid rage. Its caused by steroids that body builders take and it demonstrates how hormones can boost the propensity to commit violent acts.

Its clear that biochemistry can affect personality and behavior. Since that is the case ways will be found to manipulate biochemical states of the brain thru much genetic manipulations. Most drugs that alter mental state have to be taken continuously to maintain a different mental state. By contrast, genetic manipulations will create enduring changes in metal state because the genes are there throughout a person's life. So genetic engineering will allow permanent changes in offspring personality and in behavioral tendencies.

If, for some reason, a small number of people decided they wanted to genetically engineer their kids to be lacking in empathy, compassion, and conscience we'd face the risk of genetically engineered psychopaths living among us. This might even be done by tyrants who want to create progeny who will rule as they do. Imagine someone like Saddam Hussein choosing to make sure his kids are absolutely brutal and manipulative by genetic design.

Human Genetic Engineering Opponents Rarely Articulate Greatest Danger

In most diatribes against human genetic engineering there is a lack of specificity as to what forms of genetic engineering would be most threatening to human civilization. I see this lack of specificity in part a result of a reluctance to accept the degree to which human personality types will turn out to be determined by genetic variations. After all what other types of genetic changes to humans have the potential to causes problems for society at large on the scale the cognitive genetic engineering will be able to cause? Lots of people are really tall or really short with assorted colors of skin, hair, and eyes. Some people are thin and others naturally more muscular or heavy set. Most of these differences are not absolute obstacles to the maintenance of human civilizations. It seems obvious to me that variations in physical shape are not as important as differences in goes on in human minds.

Let us illustrate that last point by looking at lions and tigers. Imagine someone genetically engineered lions to be as smart as humans. Imagine the lions could even talk. Would you want to have lions living in your neighborhood if they still had strong instincts that caused them to look at all other species (including humans!) as something to hunt down and eat? I hope your answer is "NO!".

To acknowledge the key role of genetics in personality formation forces one to confront a number of derivative admissions about the nature of us each personally (what, I'm genetically fated to be [fill in something you don't like about yourself here]?) and also about why some people are more dysfunctional and socially pathological. One result of this unwillingness to accept the genetics-personality link is this rather sterile and unproductive debate about the dangers posed by human genetic engineering.

In future posts I will explore some of the dangers that we will face when genetic engineering gives us the ability to finely control progeny personality types and behavioral characteristics. When we gain the ability to determine progeny personality types we will no longer be able to afford to ignore these dangers.

Aside: to be fair, I haven't read Maranto's book and so I can't say whether she addresses these dangers there.

By Randall Parker 2002 October 01 07:39 PM  Dangers Mind Engineering
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Choosing which chromosomes to pass along

When a couple decides to have a child they are uncertain what the child will look liike, what sort of personality the child will have, or even whether the child will have inherited genetic defects. The biggest reason for this uncertainty is that each person donates half of their genetic complement to their children but they do not control which half they donate.

We can donate many different subsets of our genes to our progeny

The human genome is made up of 23 pairs of chromosomes. One of each pair came from the mother and the other came from the father. Lets call each member of each pair A and B where the A chromosomes are from your mother and the B chromosomes are from your father. So you have chromosome pair 1 and it has members 1A and 1B (1A from your mother and 1B from your father) and the same for the other pairs, 2A and 2B, 3A and 3B, and so on. Well, when you have a child you could donate all your A chromosomes or all your B. Or you could also donate all your B chromosomes. But you could also donate just 1 of your As with 22 Bs or 2 of your As with 21 Bs. So how many possibility combinations can you donate? The number is is 2 to the 23rd power or 8,388,608 unique combinations.

Well, it still takes two people to produce a child and your mate can also donate just as many different combinations. The total possible combinations of genetically distinct children you can have from different chromosome pairings is 8,388,608 times 8,388,608. That's 2 to the 46th power or over 7 to the 13th power or over 70 trillion combinations. This is why two children of the same parents can be so different from each other. In fact, while it is extremely unlikely to happen it is possible for two siblings to have no chromosomes in common. For instance, one sibling could get the A chromosomes of each parent and the other could get the B chromosomes of each parent.

Cross-overs between chromosomes create even more combinations

Controlling chromosome donations

Right now it is difficult and expensive to control which chromosomes get passed along and it is only practical for a single chromosome and only then in extreme cases. Typically it is done to assure that a child will not carry some genetic defect that each parent possesses or to make the child genetically compatible with an existing child which needs a cell donor to treat a genetic disease.

Since the meaning of most genetic differences is not understood at all even if we today had the ability to control which of each chromosome pair we wanted to pass along we wouldn't have any reason to try. We simply don't know enough to choose one chromosome over another except in rather exceptional situations.

Chromosome donation control makes some men more attractive mates

So how will control of which chromosomes get passed to offspring affect mate choice? Well, this will be good news for some men who might otherwise be passed over when females are selecting mates.

Some sperm donors become more attractive with chromosome donation control as well

Our control of chromosome donation will change the human race

By Randall Parker 2002 October 01 04:37 PM  Biotech Reproduction
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Disappearing blondes story was a hoax

So where did the story originate?

Reports to that effect had appeared in recent days on CNN and ABC News and in the London Daily Mail, among others. But WHO said it has never conducted research on the topic.

WHO "has no knowledge of how these news reports originated but would like to stress that we have no opinion on the future existence of blonds," it said in a statement released at United Nations headquarters in New York.

To reiterate what I said previously: When genetic engineering makes it possible to choose progeny hair color the world is going to have many more blondes than it does now. At the same time people will become taller, better looking, with straighter whiter teeth, more perfect looking skin, and any other features that are widely desired. The average girl next door will look as good as the sexiest Sports Illustrated Swimsuit Issue women.

By Randall Parker 2002 October 01 04:03 PM  Biotech Society
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The Coming Era of Nutritional Genomics

Some experts dispute whether we know enough about how various genetic variants work to start dispensing dietary advice based on the results of genetic tests. However, companies are starting offer such services. The NY Times has published an article which is mostly on this field known as nutritional genomics or nutrigenomics (free registration required):

Sciona, a British company, is selling customized dietary advice for about $200. The company tests for 19 variations in nine genes. Six genes are involved in removing toxins from the bodies. Consumers who have variations that the company says slow this process are advised, for instance, to avoid well-done red meats, which have higher levels of certain toxins.

Another test is for the gene that produces Mthfr, an enzyme involved in using folic acid, an important vitamin. People with a less efficient version of this gene are told to eat more liver, broccoli and other foods rich in the vitamin.

Personal genetic profiles will allow individualized advice about diet, exercise, drug choices, and medical testing regimens. People who have poor toxin processing enzymes will know what toxins to avoid exposure to and even what drugs to take to enhance toxin processing. Eventually it is likely that such people will even opt for gene therapy or liver replacement. Said liver will be grown from one's own stem cells after those stem cells have been genetically engineered to enhance their toxin processing. One can even imagine diet books written for different genetic groups.

By Randall Parker 2002 October 01 01:32 PM  Biotech Assay Services
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Radio waves to correct farsightedness

Some day in the future everyone will have perfect eyesight. Some Johns Hopkins scientists have just moved us closer to that day:

Surgeons at Johns Hopkins' Wilmer Eye Institute are now offering conductive keratoplasty, or CK, to correct low-level farsightedness in selected patients over age 40.

The procedure, approved in April by the U.S. Food and Drug Administration, is the first non-laser treatment for hyperopia, a condition in which people can see objects far away but have trouble focusing on those nearby. It is an outpatient surgery performed under local anesthesia in just a few minutes.

Unlike laser treatments, which use light waves as an energy source, CK uses radiofrequency waves, a form of electromagnetic energy, to re-shape the peripheral cornea. The energy is similar in some respects to the microwaves that power CB radios and cell phones.

CK employs a pen-shaped instrument with a tip as thin as a human hair that releases the radiofrequency energy. The tip is applied in a circular pattern on the outer layer of the front of the eyeball to shrink small areas of tissue. The result is a constrictive band of tissue, similar to a tightened belt, that increases the overall curvature of the cornea.

"Nearly 95 percent of patients with low to moderate ranges of farsightedness achieve normal or near-normal vision after the procedure," says Terrence P. O'Brien, M.D., medical director of the Wilmer Laser Vision Center in Lutherville, Md.

By Randall Parker 2002 October 01 11:04 AM  Biotech Therapies
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