2005 March 30 Wednesday
Planet Earth Is Overdue For The 62 Million Year Extinction Cycle

Some European environmentalists like to worry about genetically modified foods. A larger group of people like to worry about global warming. FuturePundit, far more focused on risks to his own life, is worried we don't have the means to produce large numbers of vaccine shots in response to a dangerous flu strain (like the Avian influenza that might currently be spreading in North Korea). Well, these are bush league catastrophe worries. You want to have a heftier and more manly worry? Time to sink your teeth into a massive recurring pattern of extinction that has been happening once every 62 million years for over 500 million years and which is currently overdue!

BERKELEY, CA – A detailed and extensive new analysis of the fossil records of marine animals over the past 542 million years has yielded a stunning surprise. Biodiversity appears to rise and fall in mysterious cycles of 62 million years for which science has no satisfactory explanation. The analysis, performed by researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley, has withstood thorough testing so that confidence in the results is above 99-percent.

Think about a massive die-off of most of the species on planet Earth that would make environmentalist fears of human-inflicted damage to the environment seem puny in comparison. We are talking about a die-off that would make a first class Hollywood disaster movie. Heck, it could even be made into a series of movies and civilization progressively collapses as our stars fight their way toward the few areas where humans are managing to hang on.

Muller and Rohde have entertained many hypotheses for what might have caused the die-off. But their theorizing is still at the stage of hunches. Either periodic passage of the solar system through molecular clouds or periodic massive volcanic eruptions could be behind the massive die-offs.

Muller and Rohde have been working on this study for nearly two years, and first discovered the 62 million year biodiversity cycle in November, 2003. They spent the next year trying to either knock it down or explain it. Despite examining 14 possible geophysical and astronomical causes of the cycles, no clear explanation emerged. Muller and Rohde each has his own favorite guess.

Muller suspects there is an astrophysical driving mechanism behind the 62 million year periodicity.

“Comets could be perturbed from the Oort cloud by the periodic passage of the solar system through molecular clouds, Galactic arms, or some other structure with strong gravitational influence,” Muller said. “But there is no evidence even suggesting that such a structure exists.”

Rohde prefers a geophysical driver, possibly massive volcanic eruptions triggered by the rise of plumes to the earth’s surface. Plumes are upwellings of hot material from near the earth’s core that some scientists believe have the potential to reoccur on a periodic basis.

“My hunch, far from proven,” Rohde said, “is that every 62 million years the earth is releasing a burst of heat in the form of a plume formation event, and that when those plumes reach the surface they result in a major episode of flood volcanism. Such volcanism certainly has the potential to cause extinctions, but, right now there isn't enough geologic evidence to know whether flood basalts or plumes have been recurring at the right frequency.”

We also have a 140 million year cycle to worry about.

Muller and Rohde also found a second, less pronounced diversity cycle of 140 million years.

"The 140 million year cycle is also strong, but we see only four oscillations in our 542 million year record,” Muller said. “This means there is some chance that it could be accidental, rather than driven by some external mechanism."

If it is real, the 140 million year fossil diversity cycle could be tied to a reported 140 million year cycle in Ice Ages. Said Rohde, "It is also possible that this 140 million year fossil diversity cycle is driven by passage through the arms of the Milky Way galaxy".

John Alroy is skeptical of the Muller and Rohde analysis.

John Alroy coordinates the Paleobiology Database at the National Center for Ecological Analysis and Synthesis in Santa Barbara, California. He is skeptical about the accuracy of Rohde and Muller's statistical analysis. He does, however, applaud their exhaustive search for the cycle's cause.

The bad news is if Rohde and Muller are correct then we are overdue for the next big die-off.

Their research has shown that every 62 million years - plus or minus 3m years - creatures are wiped from the planet's surface in massive numbers.

And given that the last great extinction occurred 65m years ago, when dinosaurs and thousands of other creatures abruptly disappeared, the study suggests humanity faces a fairly pressing danger. Even worse, scientists have no idea about its source.

I am hoping that Muller's explanation turns out to be correct. Why? Muller's astrophysical mechanism would be easier to defend against. Suppose this mechanism could be proven to be at work in the waves of extinctions. We could develop a number of methods for deflecting asteroids and comets. The key to such a defense system would be early detection of incoming objects. We would need many great space telescopes constantly scanning the sky looking for an approaching cloud of rocks headed our way. Then space lasers or particle beams could deflect incoming objects or automated nuclear-powered spaceships could be sent out to intercept and nudge them away from a collision with Earth.

Rohde's massive volcanic eruption mechanism would be a lot more difficult to defend against. It is unlikely we could stop a massive eruption. If we knew where the eruption was coming we could move away from it. But we'd be left with the need to find ways to clean up the polluted atmosphere more rapidly in order to prevent a long period of freezing darkness. Perhaps if we knew a massive eruption was coming in advance we could build tens of thousands of nuclear reactors and use their power to run massive air filtration systems on the atmosphere. One year's output of the US economy would pay for the construction of 10,000 $1 billion dollar 1 Gigawatt nuclear reactors. How much air filtration could be done with 10,000 Gigawatts of electric power?

The human race is still at a stage of development where it is vulnerable to natural disasters. We are much more vulnerable than we need to be. Even with our current level of technology we could be doing a lot of fairly cheap stuff to reduce our risks from a few natural threats. For example, a price that is in the range of hundreds of millions of dollars per year we could construct an impressive set of satellite and ground-based stations for detecting 99.9+% of asteroids long before they could threaten Earth. A similar sized expenditure for vaccine technology development would lead to vaccine production techniques that would greatly lower the risks of a big human die-off from natural strains of influenza and probably from some other naturally occurring pathogens as well.

Looking about 50 or 100 years into the future I do not expect either asteroids or naturally occurring pathogens to still have the potential to kill millions of people. Our technologies will be so advanced and our accumulated wealth so great that the cost of defending against both these threats will be so low that the defenses against these threats will be created even without a strong political consensus in support of building the needed defenses. At some point in the 21st century our greater threat of extinction will come from our own technologies in the hands of the most malicious and reckless members of humanity.

By Randall Parker 2005 March 30 02:32 PM  Dangers Natural General
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2005 March 29 Tuesday
Response To Obesity Epidemic Should Be Urgent Priority

Jane Brody of the New York Times asks an important question about the growing incidence of obesity.

I can't understand why we still don't have a national initiative to control what is fast emerging as the most serious and costly health problem in America: excess weight. Are our schools, our parents, our national leaders blind to what is happening - a health crisis that looms even larger than our former and current smoking habits?

Brody is right. Obesity is causing more damage than smoking does. Brody is reacting to a new book Diabesity : The Obesity-Diabetes Epidemic That Threatens America--And What We Must Do To Stop It by pediatric endocrinologist Francine R. Kaufman MD. Brody says type II diabetes is rapidly growing.

In just over a decade, she noted, the prevalence of diabetes nearly doubled in the American adult population: to 8.7 percent in 2002, from 4.9 percent in 1990. Furthermore, an estimated one-third of Americans with Type 2 diabetes don't even know they have it because the disease is hard to spot until it causes a medical crisis.

Type II diabetes is the type where the body becomes insensitive to insulin. It accelerates a variety of degenerative diseases (heart disease, kidney failure, stroke, peripheral vascular diseases that lead to amputations, blindness, and much more) just as type I diabetes does.

Obesity does a lot more harm beyond causing type II diabetes. Obesity causes neural cell loss in the temporal lobe and is a risk factor for dementia. Rudolph Liebel of Columbia University and other researchers have found that fat cells release over 2 dozen compounds that cause harmful changes the body. The more fatty tissue you have the more of those compounds are excreted into the bloodstream. Increased obesity may even lead to decreasing life expectancies.

Kaufman and Brody blame fast food for this state of affairs. But fast food is in large part the result of advances in agriculture that made the production of starches incredibly cheap. Measures to change grade school and high school cafeteria menus are certainly called for. Kids should be taught to avoid foods that increase obesity. Parents should be discouraged from keeping junk food around the house. Junk food vending machines should be removed from schools and places of employment. But while all these obvious measures will help my guess is they will make only a small dent on the problem.

One problem mentioned by Brody is that lots of kids can not safely bike to school or play outside afterward. Part of the danger here is the distance between schools and homes and the heavy road traffic that makes bicycling too risky. But neighborhoods made dangerous by criminals also contribute to obesity. However, part of the problem in many instances is irrational fear on the part of parents. Child kidnappings and other crimes against children more rare than news reports lead many to believe. Parents who imagine a larger threat than exists keep their kids indoors more than is necessary. Still, longer prison terms for pedophiles and child kidnappers and a generally harder line toward criminal activity would probably create conditions more conducive to good health of all children.

Our biggest problem is that we are not evolutionarily adapted to the environments we have created. We could build bike trails, lock up criminals for even longer periods of time, and make other changes to suburban and urban enviroments to make it easier safer to get exercise in our daily routines. But many of the changes would be expensive to implement and have little popular support. For most communities the needed zoning ordinance changes that would enable, for example, bike trails or pedestrian trails would had to have been implemented decades ago. The communities have already been built. There is no room for sidewalks and trails. Schools have already been built surrounded by very busy streets and highways.

A more basic problem is that today food is cheap but we evolved under conditions where calorie deficiency malnutriton was very common. So we are designed to eat too much. As biotechnology advances food prices will rise more slowly than inflation. So food will become cheaper still. Access to food will become even easier. Its preparation will become ever more automated. Blaming this on McDonalds and Carls Jr really misses the bigger technological picture.

Programs and proposals to encourage weight loss also ignore history: The long running torrent of diet books, talk show discussions, and commercial weight loss companies produce lots of yo yo dieters whose weight goes up and down many times. Sustained weight loss is the exception for dieters.

Brody mentions lots of ideas for her idea of a national initiative to control obesity. But she ignores the one obvious option that will eventually provide more benefit than everything else she mentions: the development pf appetite suppressing treatments. We need an increase in funding for research to develop therapies that suppress appetite and cause fat cells to burn off their stored fat. The appetite suppressants will be the best solution. Eventually we will even have gene therapies that permanently adjust metabolism so that appetite declines when a person begins to become overweight. A few billion dollars per year spent funding research into the mechanisms of appetite control would pay back orders of magnitude in avoided diseases, greater physical and mental vigor, and longer healthier lives.

By Randall Parker 2005 March 29 12:16 PM  Aging Population Problems
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2005 March 27 Sunday
Donald Sadoway: Solid State Batteries Could Double Or Triple Capacity

MIT battery researcher Donald Sadoway says there is still room to improve lithium ion batteries but solid-state could double or triple capacity over the best existing commerical batteries.

I have cells operating at about 300 watts per kilogram, which is double what lithium ion is doing today. I think there's plenty of room at the top here. We're not banging up against the ceiling yet.

Where will the next big leap come from? Solid-state batteries. We think the next improvement will come from eliminating any liquid from the battery. We think that there are opportunities for looking at multilayer thin-film laminate with no liquid, a polymer as the electrolyte separator. You're looking at something that's similar to a potato chip bag, a polymer web coated with a different layer of chemistry. We can make that by the square mile -- it's not difficult to do. We're talking about a doubling or tripling of the capacity of today's batteries, as opposed to a 20% or 30% improvement.

Sadoway also says that the fuel cell fad starting in the 1990s caused a shift of government research funding away from batteries toward fuel cells. But he says that even before the fuel cell fad the government was putting little into battery research funding.

I think the US government's focus on fuel cells and hydrogen research is a mistake. We could achieve some major gains in energy efficiency much sooner if battery research was ramped up. Hybrid vehicles are becoming popular now whereas hydrogen fuel cell vehicles are probably decades into the future. Hybrids avoid the need to totally replace the existing infrastructure for delivering energy for transportation.

Batteries could also serve as an important enabling technology for both wind and solar energy by providing a way for energy generated at peak times to be used when the wind doesn't blow and the sun does not shine. Battery technologies pushed forward now could first find large scale use in hybrid vehicles. Then as wind and solar photovoltaics become cheaper the battery technology will already be available to enable their more rapid adoption.

By Randall Parker 2005 March 27 10:48 PM  Energy Policy
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2005 March 25 Friday
Caterpillar Cells May Accelerate Flu Vaccine Production

Caterpillar cells and genetically engineered bacilovirus might provide a better means to make influenza vaccines.

BALTIMORE, MD -- March 21, 2005 -- Using a strategy involving a genetically modified baculovirus and caterpillar cells scientists from Protein Sciences Corporation have been able to speed up a key step in the development of an experimental cell-based influenza vaccine. They report their findings today at the 2005 American Society for Microbiology Biodefense Research Meeting.

"The bird flu may become the next flu pandemic strain. It could happen at any time," says Keyang Wang, a scientist at Protein Sciences Corp. and a researcher on the study. "The most effective method to control such an outbreak is the widespread use of a vaccine. The traditional egg-based method requires 3 to 6 months to develop the vaccine. With our cell-based method, the time from receipt of the virus strain to the final vaccine product would be shortened to approximately 1 to 2 months."

Wang is absolutely correct to state that the current chicked egg-based method for manufacturing vaccine takes a long time. Plus, it can not easily be scaled up quickly. Should a big killer influenza strain break out into human populations existing vaccine manufacturers would be hard pressed to produce billions of doses of influenza vaccine. My guess is they would be able to satisfy only a small fraction of the demand for vaccine.

The existing approach for making vaccines in eggs might not work with a killer avian influenza strain. The egg embryos might be killed by the virus before much vaccine could be produced.

Today's flu vaccines are prepared in fertilized chicken eggs. The eggshell is punctured, and the influenza virus is injected into the fluid surrounding the embryo. The egg is then resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine. In addition to the long development time, another drawback to this method is the possibility that an avian influenza virus would be lethal to embryos in the eggs.

The vaccine strategy pursued by Protein Sciences, known commercially as FluBlok, does not rely on whole vaccine virus. It uses a purified concentration of a key molecule on the surface of the virus, called hemagglutinin, to elicit an immune response against that specific strain of the virus.

Wang and his colleagues have developed a methodology for rapidly producing and purifying hemagglutinin from an influenza virus. They extract the genes responsible for the production of hemagglutinin from the virus and insert them into a baculovirus. Caterpillar cells are then infected with the virus and begin to produce the hemagglutinin.

The FluBlok vaccine has recently finished phase II clinical trials, where it has established safety and the ability to elicit a strong antibody response in humans.

"Since all the media used here are chemically stable and commercially available, the process can be easily scaled up for commercial manufacture," says Wang. "New FluBlok vaccines can be developed quickly and safely to address late appearing influenza viruses and to reduce the impact of a potential flu pandemic."

It is interesting to note that this vaccine is being developed by a commercial company. The US government and other governments have been slow to respond to the need for vaccines that can be manufactured more rapidly and for which manufacturing can more easily be scaled up. Both capabilities are needed in order to produce large numbers of vaccine doses should a major killer influenza strain become established in human populations. With that thought in mind it is worth looking at more of what Protein Sciences has to say for itself.

The FluBlØk™ vaccine may even provide more protection than current commercially available vaccines.

FluBlØk™, derived from Recombinant hemagglutinin (rHA) is a patented replacement vaccine for the current licensed vaccines that are produced in eggs using 40-year old technology. FluBlØk™ consists of three rHA proteins corresponding to the flu strains selected by the World Health Organization and the Center for Disease Control for each year's vaccine. These proteins are produced in serum free insect cells and formulated in PBS without preservatives or adjuvants. Clinical trials have shown safety and efficacy in healthy adults and the elderly population:

  • Several Phase I and II trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) involving over 600 subjects demonstrated safety and efficacy as reported in four published studies in the Journal of Infectious Diseases. A significantly higher percentage of elderly subjects receiving a higher dose of our vaccine develop protective antibody titers compared to the licensed vaccine.

If this vaccine lives up to its claims it will both work better and be faster and easier to manufacture.

This vaccine is made using a virus to infect caterpillar cells grown in culture.

There are many advantages of using the baculovirus expression system, including: high expression levels, limitless size of the expressed protein, efficient cleavage of signal peptides and processing of the protein, post-translational modifications and simultaneous expression of multiple genes. In addition to these advantages, expressed proteins are correctly folded and biologically active. Human clinical studies have demonstrated that proteins produced in the baculovirus expression system can be safely administered to humans. Because the cells die during the manufacturing process, the BEVS system is uniquely able to produce proteins from genes of unknown function.

If you page down to the bottom of that list link you'll see a graphical chart comparing how this vaccine production method compares to several other vaccine production methods in terms of speed, cost, glycosylation (coating of virus antigen proteins with sugars that would be found on them naturally), folding (vaccine proteins have folded 3 dimensional shapes that need to be duplicated), and ease of FDA approval.

I wish these folks luck in their attempts to bring their vaccine to market. We'd all be better off with an influenza vaccine that can be made more rapidly and cheaply and which even elicit a stronger immune response. This vaccine may even save many of our lives some day.

By Randall Parker 2005 March 25 04:30 PM  Dangers Natural Bio
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2005 March 23 Wednesday
Chick Embryos Turn Human Bone Marrow Stem Cells Into Neurons

Cells taken from human bone marrow and transplanted into chicken embryos in place of chicken spinal cord nerves were converted into nerve cells.

The Norwegian team used a micro-surgery technique to cut out a small section of the developing spinal cord within the chicken egg.

Human haematopoietic stem cells (hHSCs) from bone marrow were then implanted into the damaged area.

The eggs were incubated before the embryos were removed, and spinal cord slices containing human cells dissected out and analysed.

These neurons were found to be very functional and even have the ability to send signals to other neurons.

Put human haematopoietic stem cells into the right environment and they will become neurons.

Senior researcher Joel C. Glover, of the Institute of Basic Medical Science at the University of Oslo, in Norway said, "We found that bone marrow stem cells did make neurons in the environment of the regenerating embryonic [chick] spinal cord."

There are a number of types of neurons. While the news reports on this study do not say what types of neurons were produced I'm going to guess that they were cholinergic. Parkinson's Disease sufferers need dopaminergic neurons. However, getting the bone marrow stem cells to turn into any kind of neuron is probably the bigger obstacle to get past than getting them to turn into a particular type of neuron. So this result is good news for Parkinson's sufferers.

One obvious next step is to try to discover which compounds in the chick spinal cord area are stimulating the bone marrow cells to turn into neurons.

The key to the success of this model lies in as-yet-unidentified compounds within the quickly developing "microenvironment" of the embryonic spinal cord, said Paul Sanberg, a professor of neurosurgery and director of the University of South Florida's Center for Aging and Brain Repair.

Sanberg, an expert in this kind of research, believes that if scientists can identify those compounds, they might then be able to use them as a kind of cellular fertilizer -- encouraging adult stem cells to generate into human neurons.

Sanberg also commented that since chicken eggs are used on a massive scale to make vaccines (notably influenza vaccine - and that method is too slow to handle deadly pandemics btw) that the infrastructure and considerable experience already exists for using chicken embryos to make suitable cell types for therapeutic purposes.

The ability to take an adult stem cell type and turn it into a differentiated cell type which it does not normally become is strongly suggestive that adult stem cells can be made quite pliable if only scientists can discover the right combinations and concentrations of growth factors to change them. I've always expected this to be the case. But the question has always been just how hard will the search turn out to be to discover the compounds and techniques for converting adult stem cells into a larger range of cell types? Perhaps experiments with chick embryos will provide the means to more rapidly discover how to change the differentiation state of adult stem cells.

While the use of human embryonic stem cells (hESCs) remains morally objectionable in some quarters it is important to note that the use of hESCs may still be a faster approach for the development of some forms of cell therapies. However, even if hESC research is slowed by political opposition it is my very strong expectation that for any therapy that can be developed using hESCs eventually a way will be found to provide an equivalent therapy using adult stem cells instead.

One other point is too often missed in the adult versus embryonic stem cell debate: A larger research effort (meaning more money) would accelerate either of these approaches. I wish as much effort would go into pushing for increased stem cell research funding (even if that funding would come with strings attached with regard to use of hESCs) as currently goes into arguing about hESC research. Lots of questions about stem cells can be answered with research into animal models and lots of progress can be made with adult stem cell research.

By Randall Parker 2005 March 23 12:00 PM  Biotech Organ Replacement
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2005 March 22 Tuesday
Nanoscale Silica May Be Key To Hydrogen Storage

Will the hydrogen storage problem be solved sooner than expected?

LOS ANGELES – Researchers at the Department of Energy's Pacific Northwest National Laboratory are taking a new approach to "filling up" a fuel cell car with a nanoscale solid, hydrogen storage material. Their discovery could hasten a day when our vehicles will run on hydrogen-powered, environmentally friendly fuel cells instead of gasoline engines.

The challenge, of course, is how to store and carry hydrogen. Whatever the method, it needs to be no heavier and take up no more space than a traditional gas tank but provide enough hydrogen to power the vehicle for 300 miles before refueling.

One approach is to find a solid chemical material that can hold and then release hydrogen as needed. Recently, PNNL researchers Tom Autrey and Anna Gutowska found a way to release hydrogen from a solid compound almost 100 times faster than was previously possible.

These researchers used silica in combination with ammonia borane to accelerate the release of hydrogen from ammonia borane.

The PNNL team used a nanoscale mesoporous silica material as scaffolding for ammonia borane to achieve a high rate of hydrogen release at a lower temperature than is found at the conventional scale. A lower temperature reaction, 80 degrees Celsius (170 degrees Fahrenheit), or below, is important because additional energy is not required to maintain the reaction.

To transform the ammonia borane to a nanomaterial, scientists dissolve the solid compound in a solvent and then add the solution to the mesoporous support material.

Capillary action of the porous material pulls the ammonia borane into the pores of the support. When the solvent is removed, nanosized pores filled with ammonia borane are left. Each pore is about 6.5 nanometers in diameter.

The nanoscience approach to using ammonia borane as a storage material exceeds DOE's weight and volume storage goals for 2010. As a bonus, it also avoids the volatile chemicals produced at the bulk scale.

"We found no detectable borazine, which is harmful to fuel cells, produced by the reaction in the mesoporous materials," said Autrey.

Hydrogen storage faces a few problems. Getting hydrogen out of a storage medium is just one of them. Another problem is the stage when the hydrogen is stored. Some hydrogen storage methods either require energy be expended continuously to keep hydrogen cold or the storage mechanism is too risky for cars due to accidents and equipment failure. But there is an even earlier step problem that must be solved: How to get the hydrogen into a storage medium quickly, easily, and cheaply? These researchers think they can extend their work on this material to solve the initial storage problem as well.

Based on computational thermodynamic analysis, researchers believe the process may eventually be designed to be reversible, which would allow the storage material to be regenerated and provide a sustainable hydrogen storage compound with a longer lifetime. A patent is pending on this process for hydrogen storage.

It is hard to predict when the economy may shift to hydrogen or to batteries for transportation because it is hard to predict when bright scientists and engineers will come up with solutions to the many problems holding back various energy storage approaches.

By Randall Parker 2005 March 22 05:18 PM  Nanotech For Energy Tech
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European Obesity Rates Surpassing American Levels

People are porking out all over.

The proportion of overweight or obese men is higher in some European countries than it is in the United States, experts said yesterday in an analysis of Europeans' expanding girth.

The International Obesity Task Force estimated that Finland, Germany, Greece, Cyprus, the Czech Republic, Slovakia and Malta have exceeded the United States figure of 67% for overweight or obese males.

Some snobbish Englishmen told me years ago that Americans were lazy and had no self-restraint and that American obesity rates were a disgrace to the country. I've heard this from continental Europeans as well. I tried to explain to them that obesity is the inevitable result of tens of thousands of years of human evolutionary history where humans were calorie deficient most of the time combined with a high level of automation of manual labor, cheap food, and high living standards. Their societies were just not as far along down the road of making humans ill-adapted to their environment because they had lower living standards. They were all ill-disposed toward my argument. Well, all you snobs: Your cultures are not immune to obesity.

In the short run (5-15 years) I expect obesity to worsen in all the industrialized and industrializing countries and for human health to suffer as a result. But in the medium run we will have drugs to control appetite and prevent obesity. In the longer run we will have gene therapies that will reprogram our bodies to adapt us to the unnatural environments that we have created for ourselves. Note that by "unnatural" I'm not trying to imply these modern environments are innately bad. The problem is simply that we evolved to be adapted to other kinds of environments. Those other environments have plenty to be said against them (e.g. lots of diseases and temperature extremes that are stressful). We just need to adjust our bodies to be compatible with our technologies.

By Randall Parker 2005 March 22 01:54 PM  Trends Health
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Stimulaton Of Primate Brains Show Many Complex Behaviors Are Innate

The set of behaviors that are thought to be innate rather than learned continues to expand.

Vanderbilt researchers, writing this week in the Proceedings of the National Academy of Sciences Online Early Edition, report that they can elicit these complex behaviors by stimulating specific areas in the brain of a small nocturnal primate called the Galago or bush baby (Otolemur garnetti). Their results provide significant new support for the proposition that all primate brains, including our own, contain such a repertoire of innate complex behaviors.

"We have now seen this feature in the brain of an Old World monkey and New World prosimian. The fact that it appears in the brains of two such divergent primates suggests that this form of organization evolved very early in the development of primates. That, in turn, suggests that it is characteristic of all primate brains, including the human brain," says Jon Kaas, the head of the research group, Distinguished Professor of Psychology at Vanderbilt University and investigator at the Vanderbilt Kennedy Center for Research on Human Development.

"These results explain why certain behaviors – such as defensive and aggressive movements, smiling and grasping food – are so similar around the world. It is because the instructions for these movements are built-in and not learned," he adds.

Over the last 20 years, neuroscientists have identified an area called the primary motor cortex, which, when stimulated, triggers simple muscle movements. The fact that they were able to produce only motions by single muscles and other simple movements reinforced the idea that only simple movements were hard-wired into primate brain circuitry.

Then, last year Michael Graziano at Princeton University pointed out that previous stimulation experiments in the motor cortex – the area that controls bodily motions – had been done using very short electrical pulses that last less than a half-second. He further suggested that longer pulses might stimulate more complicated motions. Working with alert macaques, he and his colleagues found that applying such long-duration signals did in fact elicit several of these complex behaviors, much as they had predicted.

Kaas and his colleagues, research assistant professor Iwona Stepniewska and doctoral student Pei-Chun Fang, decided to follow the Princeton researchers' lead and try long-duration stimuli in the simpler brain of the Galago. When they did, they also found that this type of stimuli triggered complex behaviors. In fact, they were able to stimulate a larger number of complex movements than the Princeton group had reported, including aggressive facial patterns, defensive forelimb movements, and hand-to-mouth and reaching-and-grasping movements.

The Princeton researchers stimulated areas in the motor cortex. The Vanderbilt researchers found that they could also elicit these behaviors by stimulating a nearby area of the brain called the posterior parietal cortex. This area is heavily interconnected with the motor cortex and had previously been associated with transforming data from the eyes and other senses into a spatial map of the surrounding environment. The new findings reveal that this brain area also plays an important role in complex, innate behaviors.

If a behavior is innate then some day it will become genetically reprogrammable. The reprogramming will be easier to do in embryos than in fully developed humans. A lot of the genetic coding that controls behavior does so by controlling development. Just what choices people will make once they can control the genetic coding of their offspring is one of the most important questions of the 21st century.

Even before offspring genetic engineering becomes possible the discoveries of more genetic causes of human behavior is going to lead to massive rethinks in how we approach child rearing, teaching, criminal justice, decisions about reproduction, and many other aspects of human life. Should a person who is genetically prone to violence be seen as morally responsible for his actions? Is that a reason not to imprison him? Or will people put their own safety first (which is what I'm guessing) and demand that if a violent guy can't help himself should he be jailed for a longer period of time? Also, if he can be identified as violent while still in childhood should be he isolated before he first murders or rapes?

By Randall Parker 2005 March 22 01:20 PM  Brain Innate
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2005 March 20 Sunday
Antioxidant Supplements Helpful Or Harmful?

Many studies have been published with conflicting and confusing results on whether long term use of assorted antioxidants is beneficial or detrimental to human health. In the latest chapter in the search for antioxidant regimens that might slow the rate of aging vitamin E supplementation has been found to raise the risk of heart failure for a coronary high risk group of older people.

Eva Lonn, M.D., of the Population Health Research Institute and McMaster University, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada, and colleagues conducted a study to evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. The randomized, double-blind, placebo-controlled trial ( Heart Outcomes Prevention Evaluation [HOPE] ) was initially conducted between December 21, 1993, and April 15, 1999, and included patients at least 55 years old with vascular disease or diabetes mellitus. This trial was extended ( HOPE-The Ongoing Outcomes [HOPE-TOO] ) to between April 16, 1999, and May 26, 2003.

...

The researchers found: "In the HOPE and HOPE-TOO trials, the daily administration of 400 IU of natural source vitamin E for a median of 7.0 years had no clear impact on fatal and nonfatal cancers, major cardiovascular events, or deaths. We observed an increase in the risk of heart failure, which is of concern. Although this adverse effect of vitamin E was unexpected and cannot be confirmed at this time by other trials, our data are internally consistent. Therefore, a meta-analysis of heart failure events including all completed large vitamin E trials is strongly recommended."

Sounds either neutral or bad for vitamin E supplementation, right? Well, this study got a lot of (mostly negative) press. However, there still tons of studies that show benefits from vitamin supplementation. Also it is very likely that there is an optimal level of dosage of vitamin E which might be lower than the 400 IU of alpha tocopherol used in this trial. For example,

Simin Nikbin Meydani of Tufts University in Boston says that lower doses of vitamin E might offer health benefits without adding risks. In her tests ... older people developed fewer respiratory infections while taking half the amount of the vitamin E they received in Lonn's study.

She notes that many of the people in the new study were on medication for heart disease. "Maybe vitamin E increases degradation of some of the drugs these people take," she suggests.

Also, from a dim faded old memory of mine I recall a study on vitamin E and old folks which found that smaller amounts of vitamin E boosted immune response whereas larger doses decreased immune response. This is not surprising. Antioxidants quench free radicals. Some free radicals are harmful and so quenching them is good. But the body also uses free radicals for intercellular and intracellular communication. Quenching those free radicals will prevent needed signals from getting through and that is certainly going to be harmful. Denman Harman MD, the guy who first proposed the free radical theory of aging way back in 1954, said in an interview (sorry, I can no longer find it on the web) that excess antioxidant supplementation will make one feel mentally and physically sluggish and that he discovered this effect on himself many years ago.

One unanswered question about antioxidant supplementation is what is the optimal dose for each antioxidant that would do more quenching of bad free radicals than it did of good free radicals? Another important question is at what absolute doses and ratios of doses of antioxidants do the antioxidants become oxidants? You see, many antioxidants neutralize free radicals by becoming free radicals themselves. Then other antioxidants quench those radicals to turn them back into antioxidants once again. In theory one could have, for example, so much vitamin E in one's body that other compounds (e.g. vitamin C) will be comparatively too rare in the body to recycle vitamin E back into its antioxidant state. So balance between antioxidants is probably very important. Does supplementation with just vitamin E upset some balance? Is one better off eating foods that have lots of different vitamins and other antioxidant compounds rather than take supplements? I wish I knew exact and detailed answers to alll these questions.

While the HOPE and HOPE-TOO trials on vitamin E, heart disease, and cancer were getting a lot of press a potentially more important study on antioxidants, genetics, and cancer risk attracted very little attention. But, hey, lucky you read me! So now pay close attention to a report with important implications for nutrigenomics. Whether selenium, vitamin E, and lycopene lower the risk of aggressive prostate cancer may depend on which genetic variation you have for the antioxidant enzyme manganese superoxide dismutatase (MnSOD).

PHILADELPHIA – Greater levels of selenium, vitamin E and the tomato nutrient lycopene have been shown to reduce prostate cancer in one out of every four Caucasian males -- those who inherit a specific genetic variation that's particularly sensitive to oxidative stress.

Conversely, if carriers of this genetic variant have low levels of these vitamins and minerals, their risk of aggressive prostate increases substantially, as great as 10-fold, over their cohorts who maintain higher levels of these nutrients.

These results, published in the March 15 issue of the journal Cancer Research, were based on the analysis of 567 men diagnosed with prostate cancer between 1982 and 1995, and 764 cancer-free men from the Physicians Health Study (PHS).

"This large prospective study provides further evidence that oxidative stress may be one of the important mechanisms for prostate cancer development and progression, and adequate intake of antioxidants, such as selenium, lycopene and vitamin E, may help prevent prostate cancer," said Haojie Li, M.D., Ph.D., a researcher at the Brigham and Women's Hospital and Harvard Medical School.

Destructive molecules known as "free radicals" have been shown to team up with oxygen in the human body resulting in oxidative stress and what some scientists believe is an assortment of age-related ailments. As a result, many believe that consumption of antioxidants can slow that process.

"Our study, as well as many other epidemiological studies, encourages dietary intake of nutrients such as lycopene from tomato products, or supplements for vitamin E and selenium to reduce risk of prostate cancer," said Li.

The initial goal of the PHS study was to assess the effect of aspirin and beta carotene on men's health. Since blood samples collected in 1982 were available from many of the study's participants, the research team decided to review variants for the gene that codes for manganese superoxide dismutatase (MnSOD), an important enzyme that works as an antioxidant in human cells to defend against disease. The MnSOD gene is passed from parents to offspring in one of three forms: VV, VA or AA.

"Compared with men with the MnSOD VV or VA genotype, people with the AA genotype seem to be more sensitive to the antioxidant status," said Li. "Men with the AA genotype are more susceptible to prostate cancer if their antioxidant levels are low."

People with the AA genotype for MnSOD will derive more benefit from antioxdant supplementation than those with other MnSOD phenotypes.

The study's results found that a quarter of the men in the study carried the MnSOD AA genotype, half carried the VA genotype, and the remaining quarter carried the VV genotype.

The results indicated that the VA and VV men were at equivalent risk for developing prostate cancer across all levels of antioxidants in their blood. Compared to MnSOD VV or VA carriers with low selenium – those men in the lowest quartile of the study group – MnSOD AA males had an 89 percent greater risk for developing aggressive prostate cancer if blood levels for selenium were low.

On the other hand, MnSOD AA carriers with high selenium – those men in the highest quartile – had a 65 percent lower risk than the MnSOD VV or VA males who maintained low levels of selenium.

"The levels of selenium in the highest quartile of these men are not abnormally high," Li said. "Our range is neither extremely high nor extremely low."

While similar trends were observed for lycopene and vitamin E when tested independently, the contrast in relative risk was most pronounced for the men who had high blood levels for all three antioxidants combined.

"Among men with the MnSOD AA genotype, we observed a 10-fold difference in risk for aggressive prostate cancer, when comparing men with high versus low levels of antioxidants combined," said Li. "In contrast, among men with the VV or VA genotype, the prostate cancer risk was only weakly altered by these antioxidant levels."

Similar interactions between dietary antioxidants and the variations in the MnSOD gene have previously been linked to risk for breast cancer.

So should you take vitamin E and selenium and eat lots of tomato products to get the lycopene? The answer probably depends on your genes. Here is a demonstration that nutrigenomics (the use of genetic information to customize diets) clearly is going to become very beneficial. Some people may derive a net harm from vitamin E supplementation whereas others may derive a net benefit. Big studies like the HOPE-TOO trial that do not examine genetic differences between study participants are going to miss the existence of genetic subgroups that are experiencing even greater harm or greater benefit than what appears to be the case when all the study participants are looked at as a single aggregate.

We need advances in gene sequencing technologies that drive down costs by orders of magnitude so that personal DNA sequencing becomes a reality. With detailed knowledge of all our genetic variations we can choose much more optimal custom diets and supplement regimens.

By Randall Parker 2005 March 20 07:27 PM  Aging Diet Studies
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American Electric Utilities Planning New Nuclear Reactors

The high cost of natural gas is making nuclear power more attractive. The New York Times reports that nuclear power plant operators Entergy, Exelon, and Dominion have applied for approval for sites where nuclear reactors might be constructed and Duke Power has informed the Nuclear Regulatory Commission it plans to apply for a reactor license. None of the new reactors are expected to be radical departures from previous designs.

On the drawing boards are all kinds of exotic designs, using graphite and helium, or plutonium and molten sodium, and making hydrogen rather than electricity. But the experts generally agree that if a reactor is ordered soon, its design changes will be evolutionary, not revolutionary.

The utilities are not ready for a giant technology leap; they want a plant that does what the existing ones do, but slightly better. So if new orders materialize in the next five years, it will be the mechanics and engineers who will get to show what they have learned. The physicists will have to wait.

The Westinghouse AP1000 is considered typical of the new reactors that incorporate many improvements.

Westinghouse is one of the companies trying to market a reactor, the AP1000, with more modest technical goals. It has an output of a little over 1,000 megawatts with what is called a passive approach to safety. It requires only half as many safety-related valves, 83 percent less safety-related pipe and one-third fewer pumps.

Unfortunately the article does not provide cost estimates. However, two GE reactors are under construction at Yenliao, Taiwan and an Areva European Pressurized Water Reactor (EPR) is under construction at Olkiluoto, Finland. I can't find any total reactor cost information on it in Areva's press releases (anyone who wants to look through those press releases go here) but Areva claims that the new reactor in Finland will provide cheaper power than previous nuclear reactors.

With a capacity of about 1600 MWe, the EPR has a number of major innovative features making it safer and more competitive. The electricity generated is 10% cheaper than that generated in the nuclear reactors currently in operation. It uses 15% less uranium to generate the same amount of electricity and so produces less spent fuel. Maintenance operations are simpler and therefore shorter, increasing availability to over 90%.

But what is the total cost of the Finnish project? Anyone know?

Even if we leave aside the hard-to-calculate clean-up costs it is hard to find good information on the real costs of nuclear electric power for new reactors today as compared to natural gas and coal. If anyone has some good sources for comparative costs please post them in the comments. One complicating factor on clean-up costs is that old reactors are being kept in operation for longer htan originally planned and hence their clean-up can be amortized over a longer than expected operating life. Double the life of a reactor and the effect is to greatly decrease clean-up as a fraction of total costs.

The Taiwan project has a total cost of $6.5 billion (presumably US dollars).

The Lungmen (Dragon Gate) nuclear project is Taipower's fourth and largest single investment in a broad building programme. Pressed by demand and the country's uncomfortable exposure to foreign fossil fuel supply disruption risk, Taipower is determined to proceed. This is despite unprecedented protests against its plans and the total price tag of an estimated $6.5 billion. Its opponents, mostly from the site area and opposition parties, are equally determined to stop what they see as an unnecessary investment with very high risks.

...

The project involves a 2,700MW plant consisting of two 1,350MW units at Yenliao, on the north eastern tip of Taiwan, near the capital Taipei. The advanced boiling water reactor technology marks a departure from the utility's three existing nuclear plants, which are smaller units completed in the late 1970s and early 1980s. US technology, however, will be a common thread from the first to the fourth plant. The units will come on-line in 2004 and 2005.

Does 2,700MW of reactor capacity for $6.5 billion strike anyone as pricey? I've read previously that Westinghouse's 1,100 MW AP1000 reactors might cost $1 billion each. But perhaps that figure is a price for a smaller subset for the reactor itself and not including the electric generators and surrounding complex? How to compare nuclear electric power costs to fossil fuel electric power costs?

By Randall Parker 2005 March 20 01:03 PM  Energy Nuclear
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2005 March 17 Thursday
Every Other Day Fasting May Reduce Cancer Risk

Every other day fasting seems to provide mice with much of the known health benefits that calorie restriction diets are known to provide.

An apple a day keeps the doctor away, but could eating an apple every other day be better?

A new study by researchers at the University of California, Berkeley, raises such a possibility. It shows that healthy mice given only 5 percent fewer calories than mice allowed to eat freely experienced a significant reduction in cell proliferation in several tissues, considered an indicator for cancer risk. The key was that the mice eating 5 percent fewer calories were fed intermittently, or three days a week.

What is encouraging about the findings is that the reduction in cell proliferation from that intermittent feeding regimen was only slightly less than that of a more severe 33 percent reduction in calories. Until now, scientists have been certain only of a link between a more substantial calorie reduction and a reduction in the rate of cell proliferation.

The results of the study are scheduled to appear in the May 2005 issue of the American Journal of Physiology-Endocrinology and Metabolism, but are now available online.

"Cell proliferation is really the key to the modern epidemic of cancer," said Marc Hellerstein, professor of human nutrition in the Department of Nutritional Sciences and Toxicology at UC Berkeley's College of Natural Resources. Hellerstein is principal investigator of the study.

Cancer is essentially the uncontrolled division of cells, and its development typically requires the presence of multiple mutations. "Normally, a cell will try to fix any damage that has occurred to its DNA," said Hellerstein, "But, if it divides before it has a chance to fix the damage, then that damage becomes memorialized as a mutation in the offspring cells. Slowing down the rate of cell proliferation essentially buys time for the cells to repair genetic damage."

Cell proliferation contributes to carcinogenesis in a number of other ways, as well, collectively termed "cancer promotion."

Studies over the past 70 years have established that substantial calorie reduction - up to 50 percent in some studies - not only can reduce the rate of cell proliferation, it can extend the maximum life span of a variety of organisms, including rats, flies, worms and yeast. The results can be dramatic, with 30 to 70 percent increases in life span reported in the studies.

"Significant caloric restriction is the one and only thing that has been scientifically proven to extend life span," said Hellerstein, who has a joint appointment at UC San Francisco. He noted that while exercise and good nutrition can prevent premature death by disease, they have not been shown to extend a maximum life span.

Cutting calories has also been shown to reduce the development of cancer, enhance insulin sensitivity and lower the risk of heart disease.

The 5% reduction in calories used for mice translates into about 100 calories per day for humans. Many obese people overeat by about that amount and have little luck dieting to avoid those extra 100 calories. This brings into question the practicality of implementing this research in human diets.

Can some of the benefits of calorie restriction really be achieved by fasting every other day? To prove that this experiment would need to be run on mice and rats for years in order to find out whether this regimen increases their life expectancies and if so by how much.

Another question: Would one derive more benefit from even longer periods of fasting and eating? A week on and a week off perhaps? Or just 2 days fasting alternated with 2 days eating?

The researchers conducted several trials with a control group of mice that ate "ad lib," or freely. They compared the control group with mice that ate 5 percent fewer calories but were fed three times a week with mice that were given 33 percent fewer calories. Trial periods ranged from two weeks to three months.

As expected, the researchers found that mice on the 33 percent reduced calorie diet exhibited significantly decreased proliferation rates for skin, breast and T (lymphocyte) cells. The greatest effect was seen after one month on the regimen, when proliferation of skin cells registered only 61 percent of that for mice fed freely.

The surprising finding came with the results of the more modest 5 percent reduced calorie diet that was fed intermittently. Mice in this group had skin cell division rates that were 81 percent of those for mice fed freely.

Fasting every other day may decrease the chances of breast cancer the most. But I can not imagine many women being willing to fast every other day for weeks, months, and years on end.

In all cases, division rates for breast cells were reduced the most. Mice with the lowest calorie diet had breast cell proliferation results that were only 11 percent of those for the control group mice, and mice fed intermittently had results that were 37 percent of those for the control group.

The researchers said this may be partly related to the reduction in estrogen, which stimulates breast cell division. Tests revealed that the estrus cycle stopped for mice on the lowest calorie diet. The mice fed intermittently, on the other hand, continued to cycle regularly.

Results of the refeeding trials indicated that any weight lost during the calorie restriction period was regained once a normal feeding pattern was resumed.

Every other day fasting was tried on a small pilot study of humans.

A recent pilot study of 16 non-obese adults by researchers at the Pennington Biomedical Research Center in Louisiana found that eating only every other day was feasible when the participants successfully followed an alternate-day fasting regimen for three weeks. However, the people also reported feeling hungry and irritable on their fasting days.

The authors of the pilot study said that adding a small meal, fulfilling no more than 20 percent of the day's caloric needs, might just take the edge off and make the feeding pattern more palatable.

Would even shorter fasting periods provide any benefit? It would be interesting to see if any benefit could be derived by eating very day but having at least 12 hour stretches every day when no food is consumed. That might be more achievable. Don't eat before bedtime and then entirely skip breakfast and make lunch be the first meal of the day.

Even if intermittent fasting is eventually shown to deliver real human health benefits (and I expect it will) few people are going to be up for fasting every other day. Though perhaps more people could manage to do intermittent fasting than can manage to stay on a calorie restriction diet.

However, once safe appetite suppressant drugs are developed fasting could become a lot easier and may become popular as a method to slow aging and lower the risk of degenerative diseases. Appetite suppressants that could work for differing lengths of time would be handy. One could take an appetite suppressant for 12 hours or 24 hours depending on your fasting regime.

Another approach that may eventualy obviate the need for fasting is a class of drugs called calorie restriction mimetics. The idea behind calorie restriction mimetics (which are the subject of active research in a number of labs) is that they'll fool your metabolism into thinking you haven't eaten. Then your cells would throw themselves into the same state they go into when they are not getting as much calories. Appetite suppressants would remain useful for anyone who is overweight. But the benefit of fasting would be delivered by a separate calorie restriction mimetic drug.

Update: A previous study found that rodents genetically engineered to have less fat in fat cells lived longer without calorie restriction. This is not surprising because fat cells appear to excrete pro-inflammatory compounds. In fact. Rudolph Liebel of Columbia University says adipose fat cells excrete at least 25 hormones and other signalling compounds including adiponectin and resistin. The fatter you get the bigger the problem you'll have with accumulated damage from chronic inflammation. If we can develop treatments that prevent fat cells from converting excess calories into fat then we may be able to get many of the benefits of calorie restriction.

Also, see my previous post which reports that rodents which were made to skip meals had lower blood insulin and their brains were more resistant to damage from neurotoxins. Being skinny is good. Skipping meals is good too.

By Randall Parker 2005 March 17 02:05 PM  Aging Diet Cancer Studies
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Exploding Obesity May Reduce Average Life Expectancies

A group of researchers including well known names Jay Olshansky and Leonard Hayflick are arguing that average American life expectancy may drop due to rising rates of obesity.

Over the next few decades, life expectancy for the average American could decline by as much as 5 years unless aggressive efforts are made to slow rising rates of obesity, according to a team of scientists supported in part by the National Institute on Aging (NIA), a component of the National Institutes of Health (NIH) of the Department of Health and Human Services (DHHS).

The U.S. could be facing its first sustained drop in life expectancy in the modern era, the researchers say, but this decline is not inevitable if Americans — particularly younger ones — trim their waistlines or if other improvements outweigh the impact of obesity. The new report in the March 17, 2005 issue of The New England Journal of Medicine appears little more than a year after the DHHS unveiled a new national education campaign and research strategy to combat obesity and excessive weight.

The new analysis, by S. Jay Olshansky, PhD, of the University of Illinois at Chicago, Leonard Hayflick, Ph.D., of the University of California, San Francisco, Robert N. Butler, M.D., of the International Longevity Center in New York, and others* suggests that the methods used to establish life expectancy projections, which have long been based on historic trends, need to be reassessed. This reevaluation is particularly important, they say, as obesity rates surge in today’s children and young adults.

“Forecasting life expectancy by extrapolating from the past is like forecasting the weather on the basis of its history,” Olshansky and his colleagues write. “Looking out the window, we see a threatening storm — obesity —that will, if unchecked, have a negative effect on life expectancy.”

Note this is not a new idea. Other researchers have made this suggestion. In fact, this expectation is extremely obvious. We know in increasing detail the ways that obesity changes metabolism for the worse.

My reaction: This is a sort of "if all is is equal" sort of study. It is a really big and improbable "If" in my view: If we do not develop drugs and gene therapies and other treatments to reverse the epidemic of obesity and if we develop no ways to reverse the metabolic damage caused by obesity and if we do not develop new rejuvenation therapies then, yes, life expectancies will decline. But of course we are going to develop all of those things. 50 years from now obesity will be a rarety. Rejuvenation therapies will be cheaply and widely available. Life expectancies will be rising rapidly.

In fact, one National Institute of Aging scientist states the obvious in the press release for this study:

Unlike historic life expectancy forecasts, which rely on past mortality trends, the Olshansky group bases their projection on an analysis of body mass indexes and other factors that could potentially affect the health and well-being of the current generation of children and young adults, some of whom began having weight problems very early in life. The authors say that unless steps are taken to curb excessive weight gain, younger Americans will likely face a greater risk of mortality throughout life than previous generations.

“This work paints a disturbing portrait of the potential effect that life styles of baby boomers and the next generation could have on life expectancy,” says Richard M. Suzman, Ph.D., Associate Director of the NIA for Behavioral and Social Research. Indeed, Suzman notes, obesity may already have had an effect. The sharp increase of obesity among people now in their 60s, he suggests, may be one explanation why the gains in U.S. life expectancy at older ages have been less than those of other developed countries in recent years.

“But it is critical to note that the reduced life expectancy forecast by the study is not inevitable, and there is room for optimism,” Suzman says. “Government and private sector efforts are mobilizing against obesity, and increased education, improved medical treatments, and reduced smoking can tip the balance in favor of reduced mortality and continued improvements in life expectancy.”

I do not expect education to help much. What we need is gene therapy to reprogram human metabolism to maintain a skinny body weight. Staying at an ideal weight should be and eventually will be made effortless. The big unknown here is just how fast will effective appetite suppressant drugs be developed? We should treat obesity research as an urgent matter deserving greater research efforts just as cancer and heart disease research are treated. Lowering the incidence of obesity would lower the incidence of heart disease, cancer, and a great many other diseases.

My guess is that obesity is still going to be lowering life expectancies for the next 10 years but certainly not 30 years from now. Just how soon the obesity problem will be solved remains to be seen. My guess is it will be solved in 20 years or less. We could solve it faster with more research money though.

Here is the abstract for the article.

As for why I'm an optimist about future human life expectancies start here to learn about rejuvenation therapies and Strategies for Engineered Negligible Senescence (SENS). Then read here for more on rejuvenation.

By Randall Parker 2005 March 17 12:09 PM  Aging Studies
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2005 March 16 Wednesday
Twins Study Finds Adult Religiosity Heritable

University of Minnesota at Minneapolis psychology graduate student Laura Koenig and other U Minn researchers have found in a twins study that religiousness becomes more genetically determined as we age. (same article here)

Environmental factors, like attending religious ceremonies with family, affect our religiousness as children, but genes most likely keep us attending and believing as we become adults.

A study published in the current issue of Journal of Personality studied adult male monozygotic (MZ) and dizygotic (DZ) twins to find that difference in religiousness are influenced by both genes and environment. But during the transition from adolescence to adulthood, genetic factors increase in importance while shared environmental factors decrease. Environmental factors (i.e. parenting and family life) influence a child’s religiousness, but their effects decline with the transition into adulthood. An analysis of self-reported religiousness showed that MZ twins maintained their religious similarity over time, while the DZ twins became more dissimilar. “These correlations suggest low genetic and high environmental influences when the twins were young but a larger genetic influence as the twins age” the authors state.

Participants for this study were 169 MZ and 104 DZ male twin pairs from Minnesota. Religiousness was tested using self-report of nine items that measured the centrality of religion in their lives. The twins graded the frequency in which they partook in religious activities such as reading scripture or other religious material and the importance of religious faith in daily life.

If any of the Minnesota researchers see this then what would be extremely interesting would be to collect fertility data on these men. Are the more religious men reproducing at higher rates than the less religious? Are genes for religiosity being selected for? I'm guessing the answer is Yes!

The questioning was conducted on male twins in their early 30s.

The twins, all male and in their early 30s, were asked how often they currently went to religious services, prayed, and discussed religious teachings. This was compared with when they were growing up and living with their families. Then, each participant answered the same questions regarding their mother, father, and their twin.

One of the biggest unanswered questions about the human race's future is what choices will people make once they can control the genetically controlled attributes of their offspring. Will people choose to make their children be more or less spiritual than they are? My guess is that the mild to moderately religious may choose to make their kids even more religious while those who are not religious at all will choose genetic variants that ensure their children will not be religious. Therefore the mildly religious and the people who are lukewarm to religious belief will become a smaller fraction of society while the emphatically religious and the emphatically not religious both increase in number.

Will splits over questions of religious belief widen in the future due to widening genetic divergences between the religious and non-religious? If so it will fit into a larger pattern that I'm predicting: "Children Of The Future May Be More Genetically Determined".

Also see my previous posts "On Religious Belief And Germ Line Engineering" and "Genetically Engineered Minds And Religious Experience" and "Serotonin Receptor Concentration Varies Inversely With Spirituality"

By Randall Parker 2005 March 16 04:07 PM  Brain Spirituality
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2005 March 14 Monday
Rats May Experience Cravings When Put In Drug Withdrawal Environment

When rats are returned to the environment where they withdrew from an addictive drug the brain circuitry that recalls drug withdrawal memories was activated.

François Frenois, PhD, of Université Victor Segalen Bordeaux 2 in France, and colleagues analyzed the brains of rats that had been addicted to morphine, denied access to the drug, and then re-exposed to the environment where withdrawal was experienced.

“This paper defines regions of the brain that are important for memories of withdrawal in rats, providing new insight into the development of new treatments for withdrawal syndromes in humans,” said Eric Nestler of the University of Texas Southwestern Medical Center at Dallas.

Frenois and his team compared the neural pathways activated during both the initial formation and subsequent retrieval of withdrawal memories. They analyzed the activity of a gene called c-fos, an indicator of stress and adaptation. Drugs and other stimuli can trigger c-fos expression and alter long-term brain function—even if used only once. In this study, the stimuli used were a precipitated withdrawal from morphine (implanted as pellets under the rats' skin) or an environment previously associated with withdrawal.

Being reminded of the withdrawal episode caused rats to reactivate circuitry in ways analogous to how the brain functioned while going through withdrawal.

The team found that re-exposure to an environment associated with withdrawal reactivated part of the withdrawal neural circuitry, which can drive behavioral changes causing drug relapse. Addiction, the authors say, is a chronic, recurrent disorder involving motivation, emotion, and memory. Frenois and his team say their work is an important step in helping to determine how specific environments associated with drug withdrawal might encourage drug seeking.

There are two obvious ways this knowledge could be utilized. First off, a drug that prevents memory formation could be used during addictive drug withdrawal in order to prevent a person from being able to later recall the experience of withdrawal. Then there would be no chance of cravings for the addictive drug from being intensified by remembering the withdrawal experience. This is a pretty drastic measure. But if it would help a person stay off something really damaging like methamphetamine it might be worth it to some people.

Less radically, a person about to go through withdrawal could be put in an environment very unlike any environment that person usually spends time in. That way the odds of encountering environmental cues that would recall the withdrawal episode could be decreased. The challenge then would be to figure how to construct an environment that would be least likely to be recalled by a later set of environmental stimuli. One difficulty in developing such an environment is that movies and TV shows present a much larger set of environments than most people would encounter in their own lives. Perhaps sensory deprivation environments would be best. But then just turning out the lights to go to bed might serve as a trigger to recall withdrawal. Total inability to recall withdrawal would be a far more certain method to prevent reactivation of the withdrawal response in the brain.

In the future withdrawal will be greatly helped by a number of therapies that are in the pipeline. Vaccines that cause the immune system to attack and destroy addictive drugs will reduce the satisfaction from using addictive drugs. Also, gene therapies and cell therapies will modify the brain to make it less prone to craving a drug in the first place.

By Randall Parker 2005 March 14 02:35 PM  Brain Addiction
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2005 March 12 Saturday
Methuselah Mouse Prize Fund Reaches $1 Million

Donations for the Methuselah Mouse Prize to extend the lives of mice have reached a commitment level of one million US dollars.

In a move that will push the Methuselah Foundation’s M Prize over the $1 million mark, Dr. William Haseltine, biotech pioneer of Human Genome Sciences fame, has joined the Three Hundred, a group of individuals who pledge to donate $1000 per year to the M Prize for the next 25 years. “I am delighted that my decision to join the Three Hundred has pushed the prize fund over its first one million dollars, which I trust is only the first of many millions,” said Dr. Haseltine of his decision. “There’s nothing to compare with this effort, and it has already contributed significantly to the awareness that regenerative medicine is a near term reality, not an IF.”

Dr. William Haseltine’s stature as the father of regenerative medicine - for his research in the field of biomedical genomics - is matched by his reputation as a creative and successful businessman. His commitment to the prize speaks to both its scientific integrity and its viability as a model for encouraging research into the science of curing aging.

“The Methuselah Foundation’s M Prize has sparked the public’s interest in regenerative biomedicine,” said Dr. Haseltine. “Encouraging researchers to compete for the most dramatic advances in the science of slowing, even reversing aging, is a revolutionary new model that is making its mark.”

Methuselah Foundation chairman Aubrey de Grey is very happy that this fund-raising milestone for the mouse longevity extension prize has been reached.

“That’s good news for those of us who are already alive,” says Dr. Aubrey de Grey, Cambridge biogerontologist and Chairman of the Methuselah Foundation. “If we are to bring about real regenerative therapies that will benefit not just future generations, but those of us who are alive today, we must encourage scientists to work on the problem of aging,” said de Grey. “The M Prize is a catalyst for research into this field. The defeat of aging is foreseeable, if we take the steps to make it happen.”

The idea behind the prize is similar to that behind the Ansari X Prize. The X Prize demonstrated that prize money can provide big incentives for people to extend the boundaries of what is possible. The M Prize is attracting scientists enticed by the idea that they could simultaneously do scientifically and medically valuable research while also possibly making themselves rich. What's not to like about that?

The Methuselah Foundation is in fact running two prize competitions for mouse life extension:

- a "Longevity Prize" (LP) for the oldest-ever Mus musculus;
- a "Rejuvenation Prize" (RP) for the best-ever late-onset intervention.

You can read the details of the eligibility for each prize and how the sizes of the awards are calculated at that link.

Aubrey de Grey believes aging can be stopped and reversed using what he calls Strategies for Engineered Negligible Senescence (SENS). FuturePundit agrees! You can read interviews of Aubrey about SENS here and here.

About the Methuselah Foundation.

The Methuselah Foundation is a non-profit 501c(3) organization of professional and non-professional volunteers who are dedicated to raising the awareness of the potential for near-term science-based aging interventions using modern technologies. With the map of the human genome and the power of supercomputers to guide them, competitors for monetary prizes sponsored by the Foundation are racing to be the first to develop real anti-aging therapies.

Click here to donate.

Update The Methuselah Mouse Prize reached the half million dollar mark in September 2004. So the prize appears to be averaging about $100,000 per month in donations. Obviously the idea of a prize aimed at finding ways to extend life and avoid aging is appealing to a lot of people who want to avoid growing old, weak, and sickly. My guess is that prospect of all the physical changes associated with aging (such as physical disablement, urinary incontinence, benigh prostate hyperplasia, metastatic bone cancer, colostomy bags, macular degeneration leading to blindness, the muscle wasting of sarcopenia, loss of teeth, a declining ability to maintain balance, a declining ability to handle very cold or hot weather, a reduction in coordination, knee pain, back pain, broken bones, emphysema, decline in hearing ability, and cognitive decline) are just not popular outside of the President's Council on Bioethics.

By Randall Parker 2005 March 12 02:44 PM  Worthy Causes
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2005 March 11 Friday
Should We Fear Transhumanism And Identity Copying?

On the Marginal Revolution blog Alex Tabarrok and Tyler Cowen are debating transhumanism. Tyler discusses how much will people be willing to genetically engineer their children when doing so makes the children be less like their parents.

Most people want their children to look like themselves, and to some extent to think like themselves.  We invest many thousands of dollars and many months of our time to acculturate our children.  Now let's say your children could be one percent happier throughout their lives, but this would mean they were totally unlike you, the parent.  In fact your children would be turned into highly intelligent velociraptors and flown to another planet to live among their own kind.  How many of us would choose this option?  I can think of a few responses:

1. Transhumanism will bring improvements of more than one percent; we should forget about identity and let everyone become healthier and happier.  What's wrong with uploads?

2. Governments should not restrict transhumanist innovation.  Let people and their children choose their degrees of identity continuity for themselves.  (Isn't there a collective action problem here?  Everyone wants a more competitive kid but at the end humanity is very different.)

As for the idea of making kids 1% happier: It will become trivially easier to genetically engineer offspring to feel happier: give them genes that make their minds feel happy even in the face of adversity. I do not think that large physical changes in shape or other non-cognitive body changes will be needed to make happier people. I do not even think that IQ boosting will be needed to do that. My guess is that genetic engineering for happiness will be aimed at directly enhancing the feeling of happiness independent of other characteristics that might also be changed in offspring.

Regarding uploads: the ability to copy one's mind into a synthetic brain will cause some severe problems. One can easily imagine a sort of arms race between different identities competing for influence. Some will try to acquire wealth in order to get the computing capacity needed to create many copies of their brains. Competition for resources will probably become much greater when copies of sentient entities can be made quickly.

Uploads are also problematic because a person could be copied against their will and then the copy could be modified to be more compliant and willing to work for some cause that the original mind would reject as immoral. Imagine a great weapons scientist kidnapped and copied in order that some country or group could have many copies of an extremely talented scientist to work for their cause. The world would become a much more dangerous place.

Even without uploads the potential exists to some day infect a person (or an entire population) with a virus that changes personality and motivation. This capability would be attractive to governments, business interests, and people in relationships. Not sure if he loves you? Genetically reengineer him to make him more committed to long term relationships.

Alex Tabarrok expects the transhumanist change between generations be fairly small and unlikely to produce much opposition.

Transhumanism will never make as large a difference between a single generation as does immigration.

...

Fortunately, change across a single generation is likely to be small so parents will say yes even though 5 or 6 or 10 generations down the line the changes will be dramatic.  It's because of this wedge effect that Fukuyama is so worried about relatively small changes today and it's precisely for this reason that his opposition has no hope of success in a free society.

I disagree with Alex regarding the potential rate of change across generations. The rate of biotechnological advance is going to accelerate by orders of magnitude because biotechnology will increasingly be driven by the same technologies that drive computer technology advances. For example, microfluidics devices will be fabricated using some of the same technologies used to create semiconductors and microfluidics devices in all likelihood will have lots of semiconductor gates and analog electronic circuits built into them.

We will have all the existing genetic variations in humans to choose for offspring. But we will also have the genetic variations for similar proteins in thousands of other species to investigate to look for variations that yield some desired quality. Plus, as we come to understand the genetic signalling system regulating cell growth, differentiation, and other functions of the cell lots of obvious ways to modify genes to create desired effects will jump out at us.

My guess is that in 30 or 40 years time a person planning to have an offspring will be able to choose from millions and perhaps even tens of millions of well understood and functionally significant genetic variations. Personality type, assorted behavioral tendencies, intelligence, and many physical characteristics that determine abilities and esthetic qualities will be selectable. Combinations of genetic alleles to code for physical appearances and cognitive characteristics that have yet to naturally occur in humans will be available to put in offspring. Download "Alligator Boy".

The ability of people to introduce huge number of genetic changes from one generation to the next is not the biggest reason to be worried about what sorts of semihumans or transhumans might be created (though that will be problematic). I think the real problem with big changes in sentient beings (either through genetic enhancement to create transhumans or human-machine interfaces that create cyborgs or uplifting other species - see David Brin's science fiction novel Startide Rising and the sequels) is the potential to create intelligent minds that do not have some of the emotional and ethical structures that cause human societies to function.

For example, the tendency to dole out altruistic punishment could some day be genetically engineered out of offspring. Think about people who report crimes they witnessed being perpetrated against others or who take the time as witnesses to step forward and volunteer to testify in a criminal trial. Imagine that the genetic variations that code for the rewards brains deliver to themselves for doing acts of altruistic punishment were just edited out when some people designed the genomes for their offspring. Well, that'd lead to a decrease in the rate of criminals being caught and of punishment of non-criminal abuses of people.

Tyler wonders whether the rate of change across generations should be slowed so that older generations do not lose the way of life they've had due to radical differences in their offspring.

So work backwards to transhumanism. We cannot and should not ban it, but to what extent should we regulate/tax/patent/subsidize it? We don't know until we determine the value of identity at the margin. The Icelanders -- all 279,000 of them -- are not crazy to insist on some language skills for their immigrants; they would otherwise be overwhelmed and lose their way of life. The fact that their customs are changing each generation anyway -- and often quite radically -- is beside the point. Nor is it relevant that many Icelanders emigrate to the U.S.

Imagine, for example, the first genetically engineered generation is made to be, on average, so averse to killiing animals that they all oppose fox hunts. This just happened in England without the use of genetic engineering to produce the inter-generational change in attitudes. With genetic engineering we can expect successive generations to have far greater changes in values than we are witnessing in the West due to effects of industrialization.

Alex discusses whether competition and fear will drive the spread of transhumanist changes to ourselves and our offpsring.

When the demand for a change in personal identity is strong it can have important external effects.  You may not want to be a velociraptor but if I change what choice do you have?  Or you may simply have a preference (atavistic and irrational perhaps but still a preference) for human beings as they are now.

Tyler makes the mistake, however, of jumping from such and such preferences are important and real to such and such preferences justify regulation/taxation/subsidization etc.

Certainly some day the awareness of some parents that other parents are starting to genetically enhance the intelligence or motivation of their offspring will cause many in the first group of parents to follow the lead of the second group simply in order to keep their own kids competitive.

Transhumanism is going to present a problem to libertarians: On the one hand libertarians will tend to favor a laissez faire approach to regulation of offspring genetic engineering. On the other hand genetic engineering will easily be able to produce offspring that like to follow orders and that dislike those who are not like them in some way. If some fraction of society decides to use genetic engineering to produce offspring that are more communist or more totalitarian in attitude or extremely religious and hostile to non-believers or criminal then libertarians are going to have to decide whether highly coercive government intervention in the short run is worth tolerating in order to prevent far larger rights violations in the longer run.

By Randall Parker 2005 March 11 02:31 AM  Transhumans Posthumans
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2005 March 10 Thursday
More Signs Bird Flu Is Spreading Between Humans

The World Health Organization is reporting cases where multiple members of families are testing positive for bird flu. When multiple infections occur in the same family that raises the threatening possibility that the bird flu is mutating into a form that is more capable of human-to-human transmission. The development of that capability could ignite a deadly worldwide bird flu pandemic which could potentially kill tens of millions of people. Some of the bird influenza cases being found in Vietnamese families are strongly suggestive that human-to-human transmission is taking place.

Since the family members are infected with identical or closely related H5N1, distinguishing between a common source and human transmission is heavily dependent on onset dates. Most cases show symptoms 2-4 days after exposure. Therefore, cases involving a common source will develop symptoms at about the same time. If the transmission is from one family member to another, there will be a longer time lag and the onset dates will be bimodal.

As noted above, the latest familial cluster from Thai Binh has a 7 day differential between onset dates suggesting the sister was infected by her brother.

Since primary caregivers for sick family member are most often female another sign of human-to-human transmission is the higher rate of infection of females in cases where multiple family members are diagnosed with bird flu.

However, another way to demonstrate human-to-human transmission in these other familial clusters is to simply compare the gender distribution of the primary cases relative to the secondary. There were 13 index cases in the 12 clusters (in one cluster cousins developed symptoms at the same time). There were 6 females and 7 males indicating the risk to both sexes was similar. In contrast, 11 of the 14 secondaries were female.

Why should we be alarmed by these reports? Karl Nicholson, a professor of infectious diseases at University of Leicester in Britain who currently working on bird flu vaccine development says bird flu has a very high mortality rate.

Based on the current recognized cases of the illness, it seems to have an 80% mortality rate, says Nicholson.

Imagine a virus with such a high mortality rate mutating to become easily transmissible between humans.

However, the mortality rate from bird flu may be overstated due to cases that are not diagnosed.

The World Health Organization said Tuesday that seven Vietnamese patients who initially tested negative for bird flu have been found to be carrying the virus after their samples were retested.

All seven, who were first tested in January, have since recovered, said WHO regional spokesman Peter Cordingley.

Still, even if some of the current estimate for bird flu mortality rate is overstated it is very unlikely to be overstated by, say, a full order of magnitude.

A recent case with a Vietnamese male nurse is another possible case of human-to-human bird flu transmission.

A 26-year-old male nurse from northern Vietnam who provided bedside care for a 21-year-old bird flu patient now in critical condition has himself tested positive for H5N1 avian influenza, according to media reports from the region.

It is possible the nurse was exposed to the patient's blood or mucus. It is not clear that the nurse got the virus from the patient and even if he did it is not clear that the virus was transmitted by a route that would mean the virus has developed greater ability to move between people.

Whether or not these cases indicate the avian flu is now more able to spread between humans the virus is still over there moving through duck, chicken, and other bird populations. It may still mutate into a massive killer pandemic.

Should the bird flu break out into the general population keep in mind that in my past posts I've listed things we ought to do to reduce our risks of getting the flu in the case of a killer pandemic. If I don't turn out to be one of the early victims when the pandemic starts I'll colllect together all those items and you all can then read my comprehensive list of things you ought to do and ought not do.

One thing you ought to do now: Tell your government to accelerate the development of better flu vaccine production technologies so that when a killer pandemic eventually shows up in the human population we will be able to more quickly and massively manufacture vaccines.

By Randall Parker 2005 March 10 01:37 PM  Dangers Natural Bio
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2005 March 08 Tuesday
Mild Cognitive Decline In Old Age Sign Of More Severe Brain Disease

Slowing of minds in old people is a sign that a more serious brain disorder is developing.

CHICAGO - Mild cognitive impairment in older people is not a normal part of growing old but rather appears to be an indicator of Alzheimer's disease or cerebral vascular disease, according to a study published in the March 8 issue of the journal, Neurology.

"The study shows that mild cognitive impairment is often the earliest clinical manifestation of one or both of two common age-related neurologic diseases," said Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center and the principal author of the paper. "From a clinical standpoint, even mild loss of cognitive function in older people should not be viewed as normal, but as an indication of a disease process," said Bennett.

This is the first study involving a large number of subjects who were followed until they developed mild cognitive impairment or dementia, and then died. The study involved examining brain tissue from 180 people, including 37 with mild cognitive impairment, 60 without cognitive impairment, and the rest with dementia. All were Catholic nuns, priest or brothers who agreed to participate in the National Institute on Aging (NIA) funded Religious Orders Study. Since 1993 more than 1000 persons have agreed to annual clinical evaluations and to donate their brains to the Rush investigators at the time of death.

Study participants took tests of memory, language, attention and other cognitive abilities each year to document their clinical status. The diagnosis of mild cognitive impairment (MCI) was made when impaired performance on these tests was not severe enough to warrant a diagnosis of dementia. After death, the investigators measured the amount of Alzheimer's disease pathology and cerebral infarcts (strokes) through brain autopsy. Of the 37 individuals with MCI, more than half (23) met pathologic criteria for Alzheimer's disease, and nearly a third (12) had cerebral infarcts (this include five with both). Less than a quarter (9) did not have either pathology.

"Because most people with mild cognitive impairment progress to dementia, it has been difficult to obtain brain tissue from persons who die while they still have the condition," said Bennett. "We now know that both clinically and pathologically, mild cognitive impairment patients are in the middle in terms of the disease process for Alzheimer's disease and cerebral vascular disease," said Bennett.

One positive finding from the study is that one-third (60) of the total study participants with an average age of 85 did not experience cognitive decline over several years of follow-up. Yet, about half of these persons had significant Alzheimer's disease pathology and nearly a quarter had cerebral vascular disease. "It is likely that these individuals have some type of 'reserve' capacity in their brains that allows them to escape the loss of memory despite the accumulation of pathology," said Bennett.

Bennett and his colleagues are involved in another NIA funded study at Rush, the Memory and Aging Project, trying to identify what keeps these individuals from becoming impaired. "Preventing the accumulation of disease pathology is a common approach to disease prevention," said Bennett. "Another way to prevent loss of cognition is to identify factors that protect us from becoming forgetful despite this pathology.

"From a public health perspective, the number of people with cognitive loss due to Alzheimer's disease and cerebral vascular disease is probably much larger than current estimates," said Bennett. He hopes that these data provide additional impetus to research efforts to develop treatments and, ultimately, prevention for these common diseases of aging.

On the downside if you live into your 80s the odds of suffering from cognitive declines are very high. Your odds of living into your 80s are going to rise with future advances in biotechnology and biomedical science. So most of us should see this report as describing the likely future of our brains - barring the development of treatments that prevent these diseases.

Treatments for Alzheimer's Disease and for cerebral vascular disease would benefit much larger numbers of people than current estimates of disease incidence would suggest. Therefore the value of developing treatments for these diseases is even greater that previous estimates would lead one to believe. A great increase in biomedical science funding would pay very rich dividends.

You gotta ask yourself: Do you want your brain to rot? Well, do you?

By Randall Parker 2005 March 08 12:41 PM  Brain Aging
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2005 March 06 Sunday
Stanford Prof Plans Mouse With Human Brain Cells

Adult stem cell researcher Irving Weissman, M.D. of the Stanford School of Medicine wants to develop mice that have a lot of human neurons in their brains.

So Stanford asked where it should draw the line. It is the first university in the nation to tackle the philosophical question: When does a chimera stop being an animal and start becoming a person, suggesting that research should end? The report foreshadows the release of guidelines on stem-cell research, including chimeras, by the National Academy of Sciences this spring.

``We concluded that if we see any signs of human brain structures . . . or if the mouse shows human-like behaviors, like improved memory or problem-solving, it's time to stop,'' said law and genetics Professor Henry T. Greely, director of the Center for Law and the Biosciences and leader of the committee.

``We think if he takes appropriate caution -- including stopping at each step along the way, to see what's happening -- the research is ethical,'' he said.

What I find especially interesting about this report is the reticence to see animals made smarter. What is their motivation for this restriction? Is it that they do not want lab animals made intelligent because then experimentation on them would become too much like experimentation on sentient humans?

Or do they object more generally to modification of other species to make them become as smart as humans? If the latter, what are their reasons for opposing this move? Certainly one can think of reasons to oppose such a development. The human race could find its existence threatened if we genetically engineered some predator species to be as smart as we are. Imagine smart lions and tigers with no empathy for the human species hunting us down to eat. For that matter, imagine genetically engineered human psychopaths with no empathy for the human species. They already occur naturally in smaller numbers. Will some people ever choose to use biotechnology to produce offspring with little or no empathy?

Or is the objection to making smart mice with human neurons just the creepiness factor? Are the committee members either creeped out by that notion or afraid the public will be? In the longer run discoveries of which genetic variations raise intelligence will point to ways to increase the intelligence of mice without the need to use human neurons. Higher intelligence will be achievable in mice by use of genetic engineering to change the sequences of existing mouse genes.

Weissman's motivation here is that he wants better animal models of human diseases. He is not initially aiming to create mice that have 100% human nerve cell brains. He just needs enough human neuronal cells in the brains of a mouse model to recreate manifestations of human neurological disorders such as Lou Gehrig's disease (a.k.a. Amyotrophic Lateral Sclerosis or ALS), schizophrenia, stroke, and other neurological disorders. The ability to replicate human diseases outside of humans is an enormously valuable approach to investigating the mechanism that cause diseases and to test potential therapeutic approaches for treating and curing diseases.

For some interesting insights and an overview of the state of stem cell research see Weissman's July 14, 2004 testimony on adult stem cell research to the US Senatoe Committee on Commerce, Science, & Transportation.

On the subject of cross-species hybrids the US Patent Office has just rejected an attempt to patent the idea of creating a human-animal chimera hybrid.

The U.S. Patent and Trademark Office rejected the claim, saying the hybrid -- designed for use in medical research but not yet created -- would be too closely related to a human to be patentable.

Paradoxically, the rejection was a victory of sorts for the inventor, Stuart Newman of New York Medical College in Valhalla, N.Y. An opponent of patents on living things, he had no intention of making the creatures. His goal was to set a legal precedent that would keep others from profiting from any similar "inventions."

Newman does not want to see people create chimeras. So he is trying to reduce the business incentive for doing so. However, I do not believe the question of whether to create chimeras is going to be decided based on expected return on investment. Some potential projects hold sufficient allure that even absent a large chance of profit there are wealthy people who will attempt them once attempts to do so become cheap enough. For examples of this phenomenon look at the groups (some of them driven by spiritual beliefs) that are trying to clone humans. Or how about people who build airplanes and other devices for the challenge and for the fame that sometimes results.

I think the development of smarter animals and the development of chimeras are both inevitable. These developments can be delayed by regulations and restrictions on government funding. But the expense and difficulty of attempting these efforts will eventually drop to the point that the barriers in the way of attempts to do these things will fall so low that they will happen. The streets find their own uses for technology.

Update: Michael J. Fox is helping to get the broad public ready for future talking mice.

Supporters of stem cell research at Stanford University include the actor Michael J Fox, who suffers from Parkinson's disease. Fox provided the voice for Stuart Little, Hollywood's version of the "human mouse'', who talks, has human parents and lives in a New York apartment.

I picture a Back To The Future sequel where talking mice go along for a ride in a Delorean.

Update II: Also see my previous post Human-Mouse Hybrid Creation Debated.

By Randall Parker 2005 March 06 03:34 PM  Biotech Hybrids
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2005 March 05 Saturday
Nicholas Eberstadt On Russia's Unfolding Demographic Disaster

Nicholas Eberstadt paints a bleak picture of Russia's demographic future.

On New Year's Day 1992—one week after the dissolution of the Soviet Union—Russia's population was estimated to be 148.7 million. As of mid 2004, according to the Russian State Statistics Committee (Goskomstat), the Russian Federation's population was 143.8 million. During its first eleven and a half years of post-Communist independence, Russia's population had apparently declined by almost five million people, or over 3 percent.

In proportional terms, this was by no means the largest population loss recorded during that period. According to estimates and projections by the U.N. Bureau of the Census, over a dozen states with a million people or more experienced a population decline between mid 1992 and mid 2004, 11 of these amounting to drops of 3.1 percent or more. Unlike some of these drops, however—Bosnia, for example, whose population total fell almost 10 percent—Russia's decline could not be explained by war or violent upheaval. In other places, population decline was due entirely to emigration (Armenia, Kazakhstan), or nearly so (Georgia). Russia, by contrast, had absorbed a substantial net influx of migrants during those years—a total net addition of over 5.5 million newcomers was tabulated between the territory's Soviet-era January 1989 census and its October 2002 population count.

Despite the mitigating impact of immigration, Russia's post-Communist population decline was larger in absolute terms than any other country's over the past decade. Furthermore, continuing population decline—at a decidedly faster tempo—is envisioned for Russia for as far as demographers care to project into the future. The only question is how steep the downward path will be. The U.S. Census Bureau, for example, offers the relatively optimistic projection of a "mere" 14 million person drop in Russia's population between 2000 and 2025—an average net decline of about 560,000 persons a year. The U.N. Population Division's (UNPD) "medium variant" projection, by contrast, suggests a drop of more than 21 million over that same quarter century—about 840,000 persons a year for the period as a whole.

To maintain their current population Russian women need to bear more children than the 2.1 often cited in industrialized countries as replacement level reproduction.

Consider Russia's current fertility patterns. In a society with the Russian Federation's present survival patterns, women must bear an average of about 2.33 children per lifetime to assure population stability over successive generations. In the late Soviet era, Russian fertility levels were near replacement: The country's total fertility rate (TFR) fluctuated near two births per woman from the mid 1960s through the mid 1980s. But with the collapse of the Soviet Union, the Russian fertility rate likewise collapsed, plummeting from 2.19 births per woman in 1986-87 to 1.17 in 1999. Moreover, extreme subreplacement fertility is not peculiar to certain regions of Russia today; to the contrary, it prevails across almost the entire territorial expanse of the Federation.

Since 2001, there have been some indications of a resurgence of fertility in the Russian Federation. For the year 2002, according to Goskomstat, the country's total fertility rate has risen to 1.32.

The number of children that has to be born just to maintain population stability is surprisingly high. That reflects high rates of infant mortality and mortality at later stages of development as well as the surprisingly high rate of infertility.

A combination of scarred reproductive tracts from lots of abortions (really, I am not making this up) and a high rate of sexually transmitted infections (STIs - in other venues referred to as sexually transmitted diseases or STDs) are causing low Russian fertility rates.

According to some recent reports, however, 13 percent of Russia's married couples of childbearing age are infertile—nearly twice the 7 percent for the United States in 1995 as reported by the National Center for Health Statistics. Other Russian sources point to an even greater prevalence of infertility today, with numbers ranging as high as 30 percent of all males and females of childbearing age.

If the Russian leadership wanted to increase child births in Russia then good place to start would be a tax on abortions (and a tax on vodka) that would be used to pay for subsidies to supply birth control pills. Also, the article provides an estimate that as many as 15% of college students may have current STIs. Wow. Rather than test everyone for infections it might make more economic sense to simultaneously give all late teen and early twenties Russians (or whatever age range would be indicated as optimal by testing of population samples) a course of antibiotic treatment to wipe out the STI infections. Russia could really benefit from development of vaccines for syphilis, gonorrhea, and the like.

Russia is also suffering from declining marriage rates and rising divorce rates. Plus, the death rate from injury (including accidents, murders, suicides) is very high.

For men under 65 years of age, Russia's death rate from injury and poisoning is currently over four times as high as Finland's, the nation with the worst rate in the EU. Russia's violent death rate for men under 65 is nearly six times as high as Belgium's, over nine times as high as Israel's, and over a dozen times that of the United Kingdom. As is well known, men are more likely than women to die violent deaths—but in a gruesome crossover, these death rates for Russian women are now higher than for most western European men.

Russian male life expectancy is below 60 years. Alcoholism is one of the reasons for this.

Low life expectancy exacts a large economic toll. A doctor or engineer or manager who gets degenerative diseases decades sooner than a Japanese or an American becomes less productive as the diseases progress and then of course stops producing altogether if death comes when that same person would still have years left to work in a more successful society. The bad habits of binge drinking and higher rates of infectious diseases exact tolls on productivity as well. Esiimates for HIV infection rates in the Russian population range as high as 2%.

Russia's biggest problem is public health. The Russian government ought to elevate public health measures ahead of a lot of other competing uses of government money. If spent wisely, money spent on public health measures (e.g. vigorous tracing and treatment of people exposed to STIs) could pay big economic dividends.

What is most amazing to me is that the Russians are letting this disaster unfold. Think about it. As the core of the USSR the Russians put men into space, developed ICBMs, and built massive dams and other scientific and engineering projects. By some measures theirs is not a primitive society. Yet look at what is going on there. The trends in Russia illustrate the substantial differences in cultures and characteristics that still separate the different peoples of the world.

Read the whole article.

By Randall Parker 2005 March 05 09:05 PM  Trends Demographic
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2005 March 04 Friday
Index And Ring Finger Lengths Partially Predict Violent Tendencies

Higher prenatal testosterone has already been found to be correlated with a higher ratio of ring finger length to index finger length. Now University of Alberta researchers Peter Hurd and Allison Bailey have shown that the higher ring finger to index finger ratio is correlated with physically aggressive behavior in men.

Dr. Peter Hurd initially thought the idea was "a pile of hooey", but he changed his mind when he saw the data.

Hurd and his graduate student Allison Bailey have shown that a man's index finger length relative to ring finger length can predict how inclined that man is to be physically aggressive. Women do not show a similar effect.

A psychologist at the University of Alberta, Hurd said that it has been known for more than a century that the length of the index finger relative to the ring finger differs between men and women. More recently, researchers have found a direct correlation between finger lengths and the amount of testosterone that a fetus is exposed to in the womb. The shorter the index finger relative to the ring finger, the higher the amount of prenatal testosterone, and--as Hurd and Bailey have now shown--the more likely he will be physically aggressive throughout his life.

"More than anything, I think the findings reinforce and underline that a large part of our personalities and our traits are determined while we're still in the womb," said Hurd.

Hurd and Bailey's research, published this March in Biological Psychology, was determined from surveys and hand measurements of 300 U of A undergraduates.

In their study, they found there were no correlations between finger lengths and people who are prone to exhibit verbally aggressive, angry, or hostile behaviors, but there was to physically aggressive behavior.

Hurd is conducting ongoing research in this area, including a study that involves measuring hockey players' finger lengths and cross referencing the results with each player's penalty minutes. He also has a similar study showing that men with more feminine finger ratios are more prone to depression; a paper on this will be published later this year in Personality and Individual Differences.

"Finger lengths explain about five per cent of the variation in these personality measures, so research like this won't allow you to draw conclusions about specific people. For example, you wouldn't want to screen people for certain jobs based on their finger lengths," Hurd said. "But finger length can you tell you a little bit about where personality comes from, and that's what we are continuing to explore."

Every year that goes by more of human behavior is going to be pinned down to biological causes. Mechanisms of operation of each cause will be worked out down at the molecular level. This is going to be quite the challenge to mainstream Western liberal thought and to at least some schools of Christian theology (though perhaps not to those who believe in predestination) as the ghost is shown to have progressively less operating leeway within the machine.

Are you a male that is worried you have too much testosterone that is making you too aggressive? Get married and have kids and your blood testosterone will go down. On the other hand, if you want that aggressive edge and really good visual-spatial abilities then either eschew marriage or wear a testosterone patch. Not that I'm advocating hormone dosing...

By Randall Parker 2005 March 04 08:59 AM  Brain Violence
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2005 March 02 Wednesday
Are The Benefits Of Global Warning Underestimated?

Benny Peiser, a social anthropologist at Liverpool John Moores University in England, argues that global warming may bring more benefits than costs.

A large number of studies show that urban populations in the USA and Europe have successfully adapted to recurrent extreme weather events and heatwaves. People who used to be much more weather-sensitive only 30 or 40 years ago have become less susceptible to extreme climate conditions and heatwaves due to improved medical care, increased access to air conditioning, and biophysical and societal adaptations (4).

These studies essentially falsify the contention that future warming will lead to a significant increase of heat-related mortality rates. In fact, some of Britain's leading medical experts have calculated that a rise of the average temperature by two degrees Celsius over the next 50 years would increase heat-related deaths in Britain by about 2,000 - but would reduce cold-related deaths by about 20,000 (5). In other words, the decrease in the number of cold-related deaths would be much more significant (by a factor of 10) than the heat-related deaths due to rising temperatures. The potentially huge health benefits of moderate temperature increases have been confirmed by other researchers. They estimate that a warming of 2.5 degree Celsius would lower the annual death rate by 40,000 in the USA alone while reducing medical cost by almost $20 billion per year (6).

Very cold temperatures stress old tired hearts just as very hot temperatures do. If that is the biggest reason for the expected lowered annual death rates then my guess is that the dip in death rates would be temporary as a bunch of old folks got their day of reckoning shifted out by a couple of years. Eventually their aged and weak hearts are going to kill them anyway.

As for people becoming less susceptible to the weather: Yes, this is definitely the case in industrialized countries. This trend has gone so far as to help catalyze a massive shift in the American population southward (and a similar trend is discernible in Europe though on a smaller scale). People can better handle the hot summers of the Carolinas, Georgia, Florida, Alabama, Mississippi, Louisiana, and Texas because they have air conditioning. Growing numbers of people live in Palm Springs California all year around (as compared to the previous practice of only wintering there) again because of affordable air conditioning. It is worth noting that the decline in climate-related deaths in America has happened in parallel with the shift of populations into areas with more extreme weather conditions.

The thrust of Peiser's argument is that global warming gloomsters tend to tally up only the costs of warming and not any of the benefits. I think he is right about that. Parts of the world that are extremely cold in winters will become more livable as the world warms. Finland, for example, might derive a big net benefit from global warming. Russians in Siberia might find it an improvement as well. Also, while weather patterns and, in particular, rainfall patterns will shift it is not clear to me that this will lead to a net decrease in agricultural production. Certainly growing seasons will get longer.

Though I think Peiser goes too far in his argument here:

Given the accelerated economic growth and technological progress in the developing world, successful adaptation to increasing or decreasing temperatures will become a universal feature in the not too distant future.

The bulk of population increase in the next 50 years will take place in what some call "developing countries". The problem is that a great many of those countries are not developing. Africa in particular comes to mind as the basket case of the world. Africa is glaringly failing to develop economically. Hotter temperatures are not going to be ameliorated in Africa with air conditioning. Also, India's rate of economic development is lagging China's and Burma/Myanmar is not a poster child for economic development (though that might change as China's influence there gradually turns the place into a virtual colony of China).

But suppose improbably that all the less developed countries could miraculously follow China's pattern of economic development and a few billion more people could afford to buy air conditioners. Such a massive increase in buying power would cause an enormous increase in fossil fuel burning and an atmospheric carbon dioxide (CO2) rise that would be greater than the current pessimistic climate forecasts. If we could even find the fossil fuels to burn we'd face an environmental disaster. Air conditioning the whole world with fossil fuels does not strike me as a realistic option.

If fossil fuel use is restricted by regulatory regimes aimed at reducing CO2 then the higher costs of air conditioning in the summer and heating in the winter will reduce the use of heaters and air conditioners and lead to more weather-related deaths in industrialized countries. But while those deaths will rise other deaths from heat will likely be avoided less developed countries which are mostly closer to the equator than the industrialized countries.

What we need are technologies that provide cheaper and less polluting energy. If we had those technologies we would not need to spend so much time arguing about green house gasses and climate projections. Rather than saddle the industrialized economies with very high taxes on fossil fuels to reduce energy use with a resulting slowing of economic growth why not launch a Manhattan Project to develop new energy sources?

Nobelist Richard Smalley points out that if we only had a cheap way to collect it the solar energy hitting the Earth is enormous.

By the year 2050, the current world population of 6.5 billion is expected to increase to a possible 10 billion. According to Smalley, the energy required to maintain this population will theoretically more than double from the 14 Terawatts used per day in 2003 to 30-60 Terawatts in 2050.

In his argument, Smalley showed that 165,000 TW of energy from the sun hits the earth's surface every day. "We only need 20 to completely sum up the world's energy needs," Smalley said.

Solar satellites anyone?

Smalley thinks "Peak Oil" is coming and maybe soon.

Because right now, we have 6-and-a-half billion people on the planet of which about only 1 billion are really consuming energy at a significant rate. Those other 5-and-a-half billion people are going to, there's no way to stop it. We don't want to stop it, consume energy. By the middle of the century, at least a factor of two more energy will be produced every day. Right now it's about 200 million barrels of oil every day are burnt up one way or another. Either as oil or as gas or as coal or other energy sources.

By mid-century we're going to need at least 400. Where's that going to come from? Well if it has to come from oil, and the way that we're used to getting it, the low cost we're usually getting it, it's not by any means certain there will be that oil there. In fact, we may peak within the next couple of years or the next 10 years. By mid-century we will have peaked, so where are the billions of people on the planet going to have their primary energy coming from? Where?

Note that China is going to add another billion to the set of people who use energy at a significant rate.

Smalley calls for $10 billon per year to be spent on a Manhattan Project to develop new energy sources.

Smalley believes that nuclear fission power is the only realistic energy alternative to fossil fuels but only in very stable societies that can safeguard it properly. (note that this is from 1996 and so his "next century" is the 21st century)

Right now, I believe there really is only one alternative that could really apply to the energy needs of the entire planet. That alternative is nuclear—nuclear fission in particular, not nuclear fusion.

"I believe that the United States, Europe, and Japan are stable enough societies that they could generate all their power by nuclear fission and provide the necessary stewardship to make the planet safe...

"It would be very nice to have an alternative to fossil fuels—an alternative to nuclear fission—that would be capable of providing energy for what will probably be 10-15 billion people in the middle of this next century. I believe that if this alternative exists, it has to be solar. Right now we do not even have a solar technology that is even laughably close to being able to handle—for example—80% of all the world's energy production. If you don't do 80%, you're not touching the problem. And if you don't provide energy technology that is economically cheaper than the alternatives, it won't be adopted at all.

"Where is that solar technology going to come from? [It will come] not just from improving solar cells, but from something totally new. On a cloudy day in New York, can take most of the photons that hit on cheap collectors and store it in some useful form of energy—like hydrogen or electric charge. When you think about the physics that controls that, you're rapidly led to the conclusion that the physics which makes this possible happen within a little, 1 nm cubic box....

"I don't know what that solar technology is going to be, but I'll bet you that it's nanotechnology."

One really big advantage that would come from solar cells built using nanotechnology is that they would be safe enough for the whole world to use. We ought to be developing better nuclear reactors (e.g. pebble bed modular reactors) for the developed countries and doing nanotechnology research into photovoltaic cells to make photovoltaics orders of magnitude cheaper.

We need to start working seriously on alternatives to fossil fuels.

By Randall Parker 2005 March 02 10:47 AM  Climate Trends
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