2003 January 31 Friday
Telomere Length Indicates Mortality Risk

There has been considerable debate for years as to whether the shortening of telomere length that happens each time cells divide is linked to mortality. Skeptics have argued that people were dying of other factors before telomeres became short enough to become a rate-limiting factor on longevity. However, recent research by Richard Cawthon has found a correlation between telomere length and longevity in humans.

Dr. Richard M. Cawthon and his colleagues at the University of Utah in Salt Lake City discovered that initially healthy people older than 60 with shorter telomeres--snippets of genetic material that cap chromosomes--are more likely to die than people of the same age with longer caps at the end of the chromosomes, which are long strings of coiled DNA found in cells.

Risk of death from both infection and heart disease was higher for those with shorter telomeres.

In all, 101 donors died. People with shorter telomeres showed an 86 percent higher death rate. They ran a threefold higher risk of dying from heart disease and an eight-fold higher risk of death from infectious disease, almost entirely pneumonia.

The higher rate of death from infection involved only a small fraction of the total set of people in the study. Most people die from things other than infection. Still, the results may demonstrate that the immune system requires a lot of cell replication to handle pathogens and over the years immune cells may have their telomeres wear down a lot as a result.

Telomere length matters for cells that have to divide. Heart muscle cells do not normally divide. Also, while regular muscle has a type of muscle stem cell that can generate replacement muscle cells the heart muscle does not have stem cells closely associated with them (at least not to my knowledge). Therefore the higher heart disease death rate for people with shorter telomeres brings up the question of why. Is it that people with shorter telomeres can't easily grow new blood vessels to keep the heart muscle cells well fed? Or do stem cells come from other parts of the body travel to the heart to form replacements for damaged and dead heart muscle cells?

The reduction in the ability of immune cells to rapidly divide is probably what causes the big increase in mortality from infection.

This was associated with a 3.18-fold increase in risk of death from heart disease for those in the bottom half of telomere length, to an 8.54-fold increased risk of death from infectious diseases for people in the bottom quartile of telomere length.

A blood test for telomeres could make longevity predictions more accurate. The implications of these results is dramatic for medical insurance and life insurance.

The test, which can produce a result in less than six hours from one drop of blood, could revolutionise the life insurance and health industries.

That means higher insurance rates for people with shorter telomeres or even denial of coverage while those with longer telomeres would get lower rates. Are you curious to find out for yourself how short or long your telomeres are?

There are even more subtle effects that could flow from a more accurate way of predicting longevity. Suppose you are an administrator for a defined benefit pension plan. You could reasonably argue that people with longer telomeres should have to work longer than people with shorter telomeres to earn a given level of benefits once retired.

Why do telomeres get short as we age? Why don't cells just turn on their telomerase enzymes and grow their telomeres? Once telomeres get short enough they prevent cells from dividing. Why would cells be designed to get to a point where they can no longer divide? One theory is that shortening of telomeres prevents old cells which are accumulating damage from becoming cancerous.

Judith Campisi of the Lawrence Berkeley Laboratory has a more sophisticated version of the popular theory that cellular aging evolved in part as a defense against cancer.

Epidemiologists and practicing physicians have long noted that cancer rates soar in people over 50, an observation usually attributed to the build-up of deleterious genetic mutations with age. But Dr. Campisi puts at least part of the blame on the accumulation of cells with a senescent phenotype, which hang around in certain tissues long after they've undergone changes in morphology, behavior and function. They secrete many different molecules, some of which appear to have a "field effect" that promotes malignant changes in nearby cells.

Support for this idea comes from a series of experiments in which preneoplastic epithelial cells were grown either on a lawn of presenescent stromal cells or one where 10-15% of cells were senescent. Dr. Campisi and her colleagues saw significantly more premalignant changes in cells exposed to senescent neighbors. The investigators obtained similar results in nude mice, where they observed a direct relationship between exposure to senescent cells and the size and number of tumors that developed. In mice, a neoplastic mutation was needed as a starting point for oncogenesis; after that, senescence appeared to drive tumor development.

Dr. Campisi speculates that cellular senescence evolved as a cancer suppression mechanism at a time when the life expectancy for humans was far shorter than it is today. Now that people live so much longer, senescence may be an example of antagonistic pleiotropy: a trait selected to optimize fitness early in life turns out to have unselected deleterious effects later on. Although this may sound like depressing news, Dr. Campisi sees it differently. She believes that additional research will discover small molecules that can counteract damaging secretions from old cells that have overstayed their welcome.

An implication of Campisi's work is to make aging rejuvenation harder to do. The senescent cells need to either be induced to die or somehow (drugs or gene therapy perhaps) induced to not secrete the kinds of molecules that they make that drive tumor development. A lot of cancers show up in organs. One way to get rid of the senescent cells that are driving tumor development is to get rid of the organs that contain them. So one more radical strategy for reducing the risk of cancer would be to grow replacements for those organs that posed the greatest cancer risk for each individual.

Short telomeres can cause all sorts of problems.

BOSTON - Scientists at Dana-Farber Cancer Institute and their colleagues have found that much of the widespread damage that the rare genetic disease ataxia telangiectasia, or AT, wreaks on the body results from the progressive shortening of telomeres, the structures that cap the ends of a cell's chromosomes.

In genetically altered mice, the researchers found that the shortening of telomeres led to a "crisis" that disrupted chromosomes "like a hand grenade thrown into the cell," as one scientist put it. The resulting cellular chaos was manifested throughout the rodents' bodies by the loss of reparative stem cells that different organs normally have in reserve, producing symptoms of premature aging such as hair loss and slow wound healing, and early death.

The report by Kwok-Kin Wong, MD, PhD, and Ronald A. DePinho, MD, of Dana-Farber and their collaborators was posted by Nature today on its website as an advance online publication, and it will appear in a forthcoming print issue of the journal.

"There are significant implications for humans" in the discovery, said DePinho, whose laboratory has made a number of fundamental findings about telomeres and their role in aging, cancer and problems like liver cirrhosis. "It suggests that much of the problems in AT are related to eroding telomeres. It provides us with a point of attack." For example, it might be possible someday to restore telomere function with drugs and potentially reduce some of the ravages of the disease, DePinho says.

Short telomeres are harmful in all sorts of ways. Long telomeres are a cancer risk.

Aside from perhaps providing for a new blood test to predict longevity does this latest result provide any sort of guide for the development of anti-aging treatments? To put it another way: Does it make sense to try to develop treatments that will lengthen telomeres? One potential risk of such treatments is cancer. The cells that have short telomeres are probably more at risk of becoming cancerous than cells in the same body that have longer telomeres (cells in the same body and cell type will not all have the same telomere length). Whether telomere lengthening would be a net benefit is hard to know and would probably depend on each individual's risk factors.

If a therapy (probably a gene therapy though not necessarily) to lengthen telomeres is delivered in the body then many different cells will get their telomeres lengthened. Some of the cells will be ones which have accumulated mutations that put them at risk for becoming cancerous. This argues against generalized therapies to lengthen telomeres throughout the body.

One less risky approach is to develop the ability to make high quality rejuvenated cells with lengthened telomeres outside of the body and then to deliver those cells back into the body as cell therapies. Cells taken out of the body could be treated to increase telomere length. A further step would be needed in order to reduce the risk of cancer due to accumulation of mutations. Individual cells whose telomeres were lengthened could be grown up into much larger numbers of cells. From that larger number of cells some could be sacrificed to do integrity testing of the genes that are most crucial for prevention of cancer. In other words the DNA could be sequenced or otherwise checked for mutations - especially in genes that regulate cell division. Cell lines that were found to have no mutations in crucial areas could then be further developed to eventually be injected back into the body to provide rejuvenated cells of the desired type.

In order to do the most thorough possible testing to screen out harmful mutations the development of much faster and cheaper DNA sequencing technology is needed. See the FuturePundit category archive for Biotech Advance Rates for a number of posts on the development of technologies that promise to reduce the cost of DNA sequencing by orders of magnitude.

Gene therapy to cell lines would also be helpful. There are naturally occurring genetic variations that increase the risk of cancer. More genetic risk factors for cancer will be found with time. Gene therapy to cell lines could be done to change cancer risk factor genes of cells to versions that make the cells less likely to turn cancerous.

In summary, short telomeres are probably a mortality risk. But telomere lengthening will bring risks as well as benefits. Development of therapies that increase telomere length for cells in the body (i.e. in situ therapies) might be beneficial for some portion of the population. The benefit would be greater if the therapy could be targeted to specific cell types. It would be greater still if it could be applied to cells outside of the body which are then carefully screened and treated in order to reduce the cancer risk before the cells are returned to the body. Telomere lengthening is unlikely to be applied systemically to increase telomere lengths for all the cells in the body or for all people.

Update: Illustrating the importance of short telomeres as a way to prevent cancer some scientists have recently discovered a regulatory site that controls telomerase expression. The suspicion is that this site gets mutated to enable the growth of cancers. They hope their finding can be used to develop a drug that will turn off telomerase in cancer cells.

The scientists, whose findings are reported in the journal Cancer Research, believe that a drug that targets the gene and the way it is packaged could switch off telomerase in cancerous cells.

Because telomerase is active in about 85-90 percent of cancers, a drug that blocks its production could potentially be effective against many different types of cancer.

From the BBC report Professor Robert Newbold of Brunel University and lead researcher for this study says blocking the expression of telomerase could stop cancer growth.

"Now we understand more fully how tumours activate telomerase we can begin to develop drugs that target this process to restore mortality to cancer cells and stop them from growing and dividing indefinitely."

By Randall Parker 2003 January 31 09:29 PM  Aging Reversal
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US To Rejoin International Fusion Energy Effort

Speaking at the Princeton Plasma Physics Laboratory Spencer Abraham announced the United States will rejoin an international consortium to build a fusion reactor.

On Thursday, U.S. Energy Secretary Spencer Abraham announced at PPPL that the United States is joining negotiations with Canada, Japan, China, the European Union and the Russian Federation for the construction and operation of a major international magnetic fusion research project, known as the International Thermonuclear Experimental Reactor, or ITER.

The proposed design will produce more energy than it uses.

ITER has been designed to confine a plasma of deuterium and tritium for times of up to 500 seconds, and to produce 10 times as much fusion power as is used to create and maintain the plasma.

Secretary Abraham draws an optimistic picture for fusion energy's future.

Despite fusion's long research history and unresolved fate, Abraham said the Bush administration still thinks it should remain a major goal in U.S. long-term energy plans. Fusion promises to produce "no troublesome emissions," he said. "It is safe, and has few, if any, proliferation concerns. It creates no long-term waste problems and runs on fuel readily available to all nations. Moreover, fusion plants could produce hydrogen ... to power hundred of millions of hydrogen fuel cell vehicles in the U.S. and abroad."

This is nothing to get excited about in the short term. We are still looking at the 2040s before fusion could become a major source of energy.

The project's goal is to prove the technical feasibility of fusion energy. It should put scientists one step away from a demonstration fusion power plant, which physicists believe could be achieved in 35 years.

My guess is that by the time fusion energy's technological problems are solved solar cells built with nanotech combined with nanotech hydrogen storage materials will already have displaced fossil fuel as the primary energy source. But fusion will be useful for Mars colonies where less sunlight reaches.

By Randall Parker 2003 January 31 04:31 PM  Energy Nuclear
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Richard Dawkins On What Is Biologically Natural

Richard Dawkins argues that genes are analogous to software subroutines. They are not any more naturally a part of the species they are found in than a particular subroutine is of any program that uses it. Dawkins suggests that a more rational response to the prospect of genes moved across species is rigorous safety testing.

What, then, of the widespread gut hostility, amounting to revulsion, against all such “transgenic” imports? This is based on the misconception that it is somehow “unnatural” to splice a fish gene, which was only ever “meant” to work in a fish, into the alien environment of a tomato cell. Surely an antifreeze gene from a fish must come with a fishy “flavour”. Surely some of its fishiness must rub off. Yet nobody thinks that a square-root subroutine carries a “financial flavour” with it when you paste it into a rocket guidance system. The very idea of “flavour” in this sense is not just wrong but profoundly and interestingly wrong. It is a cheerful thought, by the way, that most young people today understand computer software far better than their elders, and they should grasp the point instantly. The present Luddism over genetic engineering may die a natural death as the computer-illiterate generation is superseded.

Genetic engineering for agricultural purposes is more widely feared in Europe and the UK than in the United States. Americans tend to view technology more in terms of benefits than in terms of potential threats. Also, Third Worlders for whom hunger is a real concern are far more eager to use genetically engineered plants and animals. The known threat of hunger is weighed against potential mostly theoretical threats of gene transfer between species and its not surprising that they decide to put dealing with the real threat ahead of dealing with a potential threat that may not turn out to be justified.

There is a school of thought that holds that humans are simply not wise enough to interfere with the basic mechanisms of life. Part of the motive for this view is a feeling that life is somehow holy and that to mess with it is akin to biting the apple in the Garden of Eden or of perhaps of trying to steal fire from the gods. This view is held even by people who are not religious in any conventional sense. In Europeam cultures where Christianity has lost much of its force this might be due to historical resonances of pre-Christian pagan ideas about nature.

As compared to other potentially dangerous technologies the big difference with biological engineering is that life forms can replicate. A harmful mistake has the potential to spread over the world. Depending on the species being genetically engineered it may be difficult or even impossible to stop it once the mistake is uncovered. For some types of plants controlling them once released might not be that difficult. They might not compete well in the wild absent farmer-provided weed control and fertilized fields. This danger is even less a threat for a big land animal species. After all, humans have hunted quite a few animal species to extinction. Imagine if some wild pigs were breeding that carried genes that were discovered to be dangerous. Lots of hunters would positively relish the prospects of hunting down all the pigs to kill them with full official approval. Hunting to save humanity? What could be more fun for a hunter than to take on that sacred challlenge?

As new generations grow up with different experiences will people gradually come to see genetic engineering as natural? While most efforts to move a gene from one species to another for agricultural purposes are not going to create ecological disasters there are types of genetic engineering that could. Most people simply don't know enough science to be able to begin to guess which types of genetic engineering might pose a threat. Therefore if people come to accept genetic engineering and rigorous safety testing they will have to place their safety into the hands of experts whose competence and prudence they will have to take more or less on faith.

By Randall Parker 2003 January 31 03:45 PM  Bioethics Debate
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MIT Institute for Soldier Nanotechnologies Opening Soon

The MIT Institute for Soldier Nanotechnologies will offically open April 2003.

Researchers are working to develop sensor patches and reactive coating that could respond to chemical and biological agents with antidotes or determine whether a soldier is dehydrated and adjust accordingly. They are trying to make soft materials rigid, to recycle water from a soldier's body, and to create "intelligent" fabric by weaving computer and communications technology into a uniform.

See a previous post for more details on this project.

By Randall Parker 2003 January 31 12:41 PM  Nanotech Advances
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Fuel Cells First Big Use To Be Stationary Power Sources

The engineering problems in fuel cell development are easier to solve for fuel cells as stationary electric power generators than for transportation. Fuel cells in vehicles have additional design requirements such as low weight and ability to handle vibrations. Therefore fuel cells will first be widely used for electric power generation.

"We really see fuel cells starting to be viable by the generators toward the end of the decade. We're past science and we're into engineering," said Greg Romney, vice president of fuel cells and fuel processing at Chevron Technology Venture Co.'s Houston headquarters. "We're not there yet in terms of entering the market with real products. Some foreign markets may develop first because (the demand for and cost of) electricity is higher."

Decreasing costs for smaller turbine electric generators has led to the growth of the use of turbines by companies to generate their own electricity instead of buying from electric utilities. The advent of cost effective fuel cell electricity generators that convert natural gas to electricity with greater efficiency than turbines can achieve will surely accelerate that trend. So one consequence of the development of fuel cell technology will be a reducing in the centralization of electricity generation combined with the growth in the distribution of natural gas to more end-points.

The article argues that fuel cells will first be used in more developed countries because the technological infrastructure and natural gas availability exists to support their use. But in developing countries the ability to generate reliable electricity to fund, for instance, software development and services technology parks will make fuel cell electric generators attractive where reliable natural gas supply can be arranged.

By Randall Parker 2003 January 31 10:04 AM  Energy Electric Generators
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2003 January 30 Thursday
Alteon ALT-711 Anti-Aging Drug

As people age chemical bonds built using glucose molecules connect proteins to each other in ways that are harmful. The resulting compounds are called Advanced Glycosylation End-products or AGEs. This is a bit confusing since AGE the chemical bond sounds like age which is how old something is. As we age we get more AGEs. The neat thing about AGEs is that they are a type of bond that is fairly easily reversible by a whole class of chemical compounds. A company called Alteon has been developing an AGE-breaker drug called ALT-711 for several years. They've had trouble getting funded in part because some in the pharmaceutical industry fear that if ALT-711 gets approved for market it will be very easy for competitors to see that it works and then to rapidly to develop other drugs from the same class of chemicals to compete with it.

A lot of anti-aging enthusiasts have wanted to take ALT-711 for years in hopes that it would generally break AGE bonds throughout the body and by doing so reverse one aspect of aging. While Alteon's low level of funding has slowed its development of ALT-711 it has recently been able to complete a phase IIa trial of ALT-711 with promising results.

Alteon has announced positive results for its developmental agent, ALT-711, from a preliminary analysis of the phase IIa DIAMOND trial in diastolic heart failure. The first 17 patients in the trial, who received ALT-711 for 16 weeks, experienced a statistically significant reduction in left ventricular mass, and the drug had a positive effect on their quality of life.

The results of ALT-711 trials for other medical conditions, importantly including high blood pressure, will be announced in the first half of 2003.

But the real tests of the drug's potential are still to come. Alteon says the results of clinical trials testing ALT-711 in 450 patients with high blood pressure will be available in the first half of this year. Data on another 180 patients with a thickening of the heart's left ventricle will be available at the same time.

Alteon is developing ALT-711 for a wide range of conditions related to aging.

These compounds have an impact on a fundamental pathological process caused by protein-glucose complexes called Advanced Glycosylation End-products (A.G.E.s). The formation and crosslinking of A.G.E.s lead to a loss of flexibility and function in body tissues, organs and vessels and have been shown to be a causative factor in many age-related diseases and diabetic complications. Alteon is initially developing therapies for cardiovascular and kidney diseases in older or diabetic individuals.

The ability to break the AGE bonds may provide many benefits to the aging body. In addition to improving the cardiovascular system it might make skin less wrinkly and possibly it might make kinks in muscles (if there's some medical term for this I'd be curious to know it) less likely to happen. Connective tissue might become more supple and older folks might regain some of the ability to stretch more easily like when they were younger. The awareness that AGE breakers could deliver these kinds of benefits has kept anti-aging enthusiasts as a sort of cheering section for Alteon's progress over the years.

Anti-aging enthusiasts want to see ALT-711 to be approved for just one disorder so that it is available on the market. In the United States once a drug is approved doctors who are willing to do so can prescribe it for off-label uses (i.e. for purposes other than why the US Food and Drug Administration approved it). Alteon will probably not try to get the ALT-711 approved for its broad anti-aging effects. The FDA would be reluctant to approve a drug for that purpose and it would be hard (and rather more expensive) to design a clincal trial that would demonstrate that a drug had broad anti-aging effects. Alteon is smart to pursue ALT-711 approval for a really big market such as high blood pressure treatment. However, once its approved for a single purpose such as for high blood pressure treatment expect to see hard core anti-aging enthusiasts go shopping around for doctors willing to prescribe it for off-label uses.

By Randall Parker 2003 January 30 09:48 AM  Aging Reversal
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2003 January 27 Monday
Bioethics and the Inevitability of Biotechnical Advances

The Winter 2003 issue of The Public Interest has some essays in response to the US President’s Council on Bioethics report entitled Human Cloning and Human Dignity: An Ethical Inquiry. The head of the commission, Leon Kass, provides comments along with Diana Schaub, William A. Galston, and J. Bottum. The most interesting essay of the lot is written by Charles Murray and is entitled An opportunity lost.

If in 1939, when we already had the physics for the atom bomb, we didn’t yet have a Hitler, it is quite possible that many physicists would have said, “Take this cup from our lips. We don’t want to spend the next five years building an atom bomb.” Yet biotechnology is different. The scientists in the field do not see themselves as engaged in the work of the devil; they see themselves as bringing incalculable benefits to mankind. They do not see Leon Kass and other members of the President’s Council as people who are trying to hold back and ponder at greater lengths extremely difficult moral questions. They see them as troglodytes.

Furthermore, hundreds of billions of dollars are to be made in biotechnology. If you take a group of scientists who think they are doing the Lord’s work (even if most of them are not religious) and if there are hundreds of billions of dollars to be made, I promise you, it will happen. It may not happen in the United States if we pass certain laws, but it will happen.

In this respect, there are a variety of ways in which the council’s report, much as I admire its tone and spirit, represents a missed opportunity. For once we realize that the development of this technology is inevitable, then our approach becomes quite different from the council’s. Most importantly, we would take steps to make sure that the United States remains the center of this research, that the top scientists in the world are socialized here, and that the best graduate students come here to learn how to do it. At least then the science would develop within an ethos of moral responsibility. Such will not happen if the center of research is in China, or if it is done under cover in Barbados.

I agree with Murray that the biotech advances to perfect human reproductive cloning and therapeutic cloning will happen somewhere. These technologies will then become available in many countries regardless of what biotechnologies the United States government decides to prohibit within US borders.

What are needed are more practical arguments about likely effects of the use of various coming biotechnologies. For instance, reproductive cloning that produces many identical copies could make conventional police work much harder to do. Also, cloning that produces many identical copies could result in clones that feel like they share much in common distinct from the larger society. This could have effects similar to what is seen in societies where the widespread practice of cousin marriage creates family bonds that reduce loyalty toward the larger society in ways that make good government impossible to achieve.

Some who are opposed to therapeutic cloning take that position because they view that an embryo as a human life that it is entitled to all the legal protections granted to fully formed human. They haven't yet succeeded in winning that argument on the abortion issue. Now advances in biotechnology have made status of early stage embryos relevant to the development of new therapeutic treatments as well. That debate has such emotive force that its acting rather like a black hole in the realm of bioethical debate. There are a lot of other relevant observations, such as Charles Murray's argument about the inevitability of the biotechnical advances that will make treatments based on therapeutic cloning a reality, that are not getting the hearing they deserve.

Banning all kinds of human cloning will not eliminate the greatest dangers that likely biotechnological advances will pose to humanity. The cloning issue is simply not the most important bioethics issue if we look at it from the standpoint of threat to society and threat to the existence of the human race. We should be more concerned about sexual selection technologies creating imbalances between the sexes (the use of ultrasound for selective abortion is already having dramatic effect in sex ratios in China and India), the use of personality engineering to create everything from psychopaths to obedient drones, and the potential for genetically engineered bioweapons to kill or harm large portions of the human population.

Legal approaches are not even the most productive avenue of pursuit to reduce the incidence of therapeutic cloning. The opponents of therapeutic cloning ought to admit to themselves that it is going to happen no matter what law they manage to get the US Congress to pass. If they care strongly about minimizing the use of therapeutic cloning then the wisest course of action would be to lobby for increased funding to accelerate the development of alternative technological approaches.

By Randall Parker 2003 January 27 03:14 PM  Biotech Society
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Neurofeedback Trains Minds To Improve Memory

If you don't want to look at gory pictures as a way to improve your memory there is a less disturbing technique available.

Scientists believe they may have found a way to improve our memory by as much as 10%.

Researchers at Imperial College London have used a technique called neurofeedback to train people to remember more clearly.

It works by showing people their own brainwaves on a computer screen, and teaching them how to control them.

By Randall Parker 2003 January 27 10:10 AM  Brain Memory
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2003 January 26 Sunday
Cloning, Biotech, and the Future of the Family

Stanley Kurtz argues reproductive cloning will undermine the two parent family.

Of course, a single women can have a child now, but not without facing some human complications. A woman can go to a sperm bank, but that means discomfort over the father's anonymity. More often, a Murphy Brown will have her child by a man she knows. She will get pregnant by him secretly, or on condition that he will decline to press his rights as a father. But cloning will liberate human vanity to allow at least some among us to produce a child wholly in their own image, and thus free of any legal or emotional complications related to the existence of a second parent.

Some day the technologies involved in doing reproductive cloning will mature to the point where it is no more risky than conventional reproduction in terms of rate of undesireable complications in offspring. At that point health concerns about offspring will not be reason enough to ban reproductive cloning. Kurtz is arguing that many women will opt to clone themselves rather than find someone to marry to have children with. Of course some women today can't even find a suitable mate and so their only choices are reproduction outside marriage or no reproduction at all. Kurtz further argues that since cloning makes it easier to forgo marriage it should be banned as a threat to a vital institution. I think this is an argument that deserves to be taken seriously.

I'd like to place that argument in a larger context of other technologies existing and forthcoming which will affect the attractiveness of marriage and conventional sex as a way to conceive offspring. Biotechnological advances will make it possible to use a large array of different reproductive choices which are not possible today and these technologies will bring with them many advantages for prospective parents. Also, some existing choices will become more desireable when biotech allows one to have greater knowledge of and control of their outcomes.

Certainly there are downsides to using a sperm bank. Kurtz doesn't address those downsides with sufficient detail. Why would a woman prefer (as some are doing today) to, say, pick up a guy in a bar for a one night stand as a way to conceive a child? After all, the father in that case is going to be no more involved in the upbringing of the child than is the case with sperm bank sperm. The most notable advantage of the bar pick-up over the sperm bank donor is that a woman can evaluate the physical appearance, personality, intelligence, and status of the guy in the bar. Women can form an intuitive judgement of men they meet in person. Still, there is a limit to how much one can learn from fast casual social interactions. To have even greater knowledge of potential mates some women think back on all the men they've known in their past and seek out one with desireable qualities for a brief affair for the purpose of getting pregnant. Others who want to conceive a child try to bed a celebrity who has desired qualities. Again, the advantage over a sperm bank is the ability to evaluate the man directly in greater detail.

Some sperm banks provide biographical info about donors including academic achievements, occupation, and other indicators of status, intellect and personality. Plus, they provide general descriptions of physical appearance. Still, there are many qualities of a person that are not captured by the measures that even the most sophisticated sperm banks currently provide.

The big advantage shared in common by the bar pick-ups, brief affairs, celebrity one night stands, and sperm bank sperm is that they all allow a woman to choose a reproductive mate who they wouldn't be able to get into a long-term child-raising commitment. Basically, any one woman's choice of marriage mates is much smaller than her choice of reproductive mates.

Advances in biotechnology will provide more new reproductive options aside from reproductive cloning. Many of those will allow women better choices in terms of DNA quality than they will be able to get thru marriage. If Kurtz wants to extend his argument into an opposition to all biotechnological advances that decrease the attractiveness of reproduction within marriage then he's going to have a long list of biotech advances to fight against. One big advance will be the ability to know in much greater detail what is contained in the DNA of potential mates. Sperm banks will be able to provide detailed lists of genetically determined and influenced qualities in each of their donors. This will make sperm bank donors a more attractive option to many women. The degree of uncertainty about donors will be greatly reduced. In the process some donors will be found to have many qualities that women want.

The attractiveness of men that women can not get married to but with whom they can have brief relationships with will similarly be increased. When the cost of DNA sequencing drops far enough and DNA sequencing technology becomes available to the masses then women will be able to surreptitiously check the DNA sequences of boyfriends and even of one night stands. Imagine a woman having sex with a man in a one night stand. When DNA sequencing devices become cheap enough and fast enough she could leave immediately after sex, get a sperm sample from within herself (after all, this is done in rape cases) and then do a quick test on the genes that the guy has. If she likes what she sees she can let herself get pregnant either immediately or later with some sperm she saved.

Conventional sexual reproduction suffers from one big drawback: one can't control which half of one's genes and which half of one's partner's genes (or one's sperm donor's genes) one will pass along to offspring. With cloning one knows with far greater precision what one is passing along because one is passing along the almost exact replica (not exact because some mutations might have occurred in the cell that is cloned) of one's own genes. Howver, advances in biotech will eventually allow control over which of each pair of chromosomes one uses in making one's progeny. So at some point in the future it will be possible for a woman to choose a sperm donor and then to even choose which chromosome of each pair to use from that sperm donor. This will be further extended to allow chromosomes to be chosen from more than one donor. If one donor meets a woman's ideal for most chromosomes and another donor meets the woman's ideal for the rest of the chromosomes then different subsets will be able to be extracted from two different males to make the ideal donor sperm. This ability to decrease the uncertainty associated with reproduction will make reproduction more attractive to the risk averse. Given a stronger chance of a desireable outcome more will choose to reproduce.

Cloning will also eventually be just a starting point for genetic engineering. Suppose one decides to clone oneself. Well, do you have any biological qualities that you wish were different? For instance, suppose you have allergies or asthma. Wouldn't it be nice to edit your DNA to make your clone not be prone to developing those conditions? If you don't feel a need to have an exact clone (which most people wouldn't since they are already satisfied with donating only half their DNA to their offspring) then all sorts of improvements become possible. Want your offspring to avoid the need for braces that you had to wear for a few years? Edit the part of your genes that controls teeth development. Also, there are people walking around who appear to be immune to cavities and there is probably some discoverable genetic reason for that. So why not introduce genetic variations that increase the resistance to dental caries? Also, how many males will want their offspring to suffer male pattern baldness? There will be an incredibly large number of ways to improve on one's genetic endowment. Many cloners will be tempted by the sort of Cloning Plus option to improve on their own design.

The ability to genetically enhance one's clone will be a greater incentive to choose cloning. For instance, women who have a genetic predisposition to depression or anxiety and who suffer terribly from it might be reluctant to have an exact clone of themselves because they wouldn't want to have offspring who will suffer similarly. However, if offered the ability to create someone almost identical to themselves but who would be free from depression and anxiety some will find that an attractive idea.

So far most of the debate has been about women who decide to have children without a father actively involved in the process of raising the children. This is in part because only women have wombs and in part because women on average like having children more than men do. While its hard to say whether people will eventually genetically engineer their male offspring to have a greater desire for babies it seems more likely that advances in biotech will eventually lead to the creation of artificial wombs. For wealthy men who are so inclined this will eliminate their reliance on women for reproduction.

All of the technological advances discussed here will provide incentives for having children outside the institution of marriage. While some people would choose to have children within marriage even while using these technologies any of the choices that would leave one member of a couple contributing nothing to the genetic endowment of progeny will in most cases cause that person to see little reason to involve themselves in the raising of such a child. Also, some women who can't find a suitable marriage mate who currently are electing not to have offspring at all will find single parenthood much more attractive if they can be guaranteed to have a child that will have all the qualities that they highly desire.

The net effect of all of these reproductive technologies appears to be to increase the incentives for single parenthood. Granted that the social science literature shows single parenthood is correlated with a large array of social pathologies such as higher crimie rate of the children, less educational attainment, etc. (a separate debate is the question of how much of that is the result of single parenthood and how much is caused by the same factor(s) - genetic or environmental - that cause single parenthood?). Will reproductive biotech's encouragement of single motherhood then result in greater social pathology? Not necessarily. The reason for this is that the kinds of children being born will be different on average in intelligence and personality than children being born today. What these offspring will be like will depend largely on the choices that the mothers make. If women choose genetic variations that increase intelligence while also choosing personality characteristics that tend to make one more studious, law-abiding and hard-working then the result may well be a far more civilized society. The actual result depends greatly on which mental characteristics women choose for their offspring.

We should probably be more worried about the results of the use of reproductive technologies in male-dominated societies. In male-dominated societies the choices made for offspring mental characteristics will tend to be quite different than those made in societies that grant women greater power. My guess is that males will favor aggressiveness in offspring more than females will. (though I could be wrong about that) The great unknown in all of this discussion is just what sorts of mental characteristics will people in different societies choose once they have the ability to control offspring mental characteristics. Personality genetic engineering is the area of human genetic engineering that we should be most concerned about.

By Randall Parker 2003 January 26 12:52 PM  Biotech Society
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2003 January 25 Saturday
Mouse Gene Linked To Anxiety, Aggression

A gene that affects serotonin neuron function in mice has been identified. (my bold emphasis added below)

"We have now shown that Pet-1 is required specifically for fetal development of serotonin neurons," says Deneris. In mice missing this gene, most serotonin neurons fail to be generated in the fetus and the ones that remain are defective. This leads to very low serotonin levels throughout the developing brain, which in turn results in altered behavior in adults. "This is the first gene shown to impact adult emotional behavior through specific control of fetal serotonin neuron development."

Deneris and his colleagues employed sensitive tests of aggression and anxiety to compare the behavior of the knockout mice to wild type mice. One such aggression test measures a mouse's response time to an intruder mouse entering its territory. The Pet-1 knockout mice attacked intruders much more quickly and more often than wild type mice. In fact, knockout mice often would not engage in normal exploratory behavior directed toward the intruder before attacking it. Excessive anxiety-like behavior was evident in another test, measuring the amount of time a mouse spends in open unprotected areas of a test chamber compared to closed protected areas. Unlike normal mice, which will enter and explore an unprotected portion of the test chamber, the Pet-1 knockout mice avoided this area all together, indicating abnormal anxiety-like behavior.

The human and mouse serotonin systems share many anatomical and functional features, and the same Pet-1 gene is present in the human genome. Therefore, Deneris' discovery creates the first animal model for gaining a greater understanding of the causes of abnormal anxiety and aggression brought about through defective early serotonin neuron development. Deneris also sees this knockout mouse being used as a model for screening new drugs that can treat both aggression and anxiety. "If in fact particular genetic variants of Pet-1 are associated with excessive anxiety or violent activity in humans, then tests to detect these variants might be useful for early diagnosis of people who may be at risk for developing these abnormal behaviors," Deneris says. His lab plans more studies in mice to see how the gene affects sleep-wake patterns, learning and memory, and sexual behavior – all functions controlled in part by serotonin.

It seems likely that within 20 or at most 30 years all the genes that influence behavior and mental state will be identified. Work in animal models will lead to the identification of genes that are important in the brain. Declining costs of DNA sequencing will ensure that all the genetic variations will be identified. Once sequencing costs drop low enough large groups of people with different variations will be able to be compared to see if and how they differ in behavior, personality, and intelligence. This will accelerate efforts to identify which variations are important. The most important variations will tend to be found first because they will cause the most dramatic and easily measurable differences within groups.

It will take much longer to learn how all of the mind-influencing genes work in every detail. But long before we understand everything about the brain's function we will at least be able to identify which genes and genomic regulatory areas (i.e. regulatory areas of the genome which affect when and how each gene is expressed) come in multiple versions where the different versions cause humans to differ from each other in how their minds work.

Far more than space, the mind is the final frontier. That we are on the threshold of answering basic questions about the mind seems remarkable. For centuries humans have wondered and argued about human nature. Many have puzzled over why they have felt compelled to do things that were harmful to themselves or to others. They've battled their emotions or wallowed in them. Why is one person shy or another person easily irritated or easily distracted? Why is one person seemingly perpetually happy while another is perpetually sad? Noone has known the answers to these questions. While all the details of how the mind functions will take decades to fully understand we will know many practical consequences of a large number of genetic variations long before that. This information will be useful for a assortment of purposes.

The ability to analyse an individuals's DNA to check for specific variations will be used to speed the diagnosis of mental illness and to choose the most effective treatment. For instance, depression will likely be found to have many different genetic causes. Guided by the knowledge of which genes and which variations of those genes are contributing to a specific case of depression a doctor will be able to choose drugs which have been found most effective in treating patients with that particular contributing set of genetic variations. To do this it will not even be necessary to understand why specific drugs work best with specific genetic variations (though that knowledge will be helpful when it comes). Also, the identification of genetic variations that contribute to depression will serve as a guide for the development of drugs that target the proteins that those genes code for.

The mouse gene in this latest report is linked to aggression. Consider what it will mean for the criminal justice system when someone can be tested for genetic factors that contribute to aggressiveness. If genetic variations become routinely available in criminal trials will judges decide to give longer prison sentences to those who have a genetic propensity toward repeated acts of violence? Or will defense attorneys successfully argue that defendants with genetic variations that are linked to violence can't be held responsible because "their genes made them do it"? Another possibility is that if a convict has a genetic variation that makes him more hostile and if a drug is available that targets that genetic variation to suppress its effects on behavior then a condition of parole might be to require the convict to take the drug that suppresses the aggression-enhancing genetic variation. Advances in neurobiology will at least partially undermine the Western notion of free will and will change our view of individual responsibility.

By Randall Parker 2003 January 25 04:47 PM  Brain Genetics
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2003 January 24 Friday
Clue For Life Extension By Calorie Restriction Found

Even though the rodents ate more food than normal mice they had less fat and lived longer.

Clever genetic detective work may have pinpointed the reason why a near-starvation diet prolongs the life of many animals.

Ronald Kahn at Harvard Medical School in Boston, US, and his colleagues have been able to extend the lifespan of mice by 18 per cent by blocking the rodent's accumulation of fat in specific cells. This suggests that leanness - and not necessarily diet - promotes longevity in "calorie restricted" animals.

The experiment was done by knocking out (ie disabling or removing) a gene that codes for the insulin receptor found on fat cells. Without this receptor the fat cells had no way of being told by insulin to pick up sugar from the blood. Hence the fat cells couldn't get the raw materials they needed in order to be able to make and store fat. The consequence was a substantial boost in life expectancy.

As a consequence of this modification, they cut off the fuel supply that enables the body to lay down fat.

These "Firko" (fat-specific insulin receptor knock-out) mice ate normal diets but had reduced fat mass and lived 18 per cent longer on average than normal mice. Even when they were made to overeat, they stayed lean.

While calorie restriction (CR) typically boosts life even more (30% in some cases) this result tends to suggest that one mechanism by which CR works is by reducing the amount of stored fat. Recent research results on the risks of intra-abdominal fat suggests a number of mechanisms by which a reduction in fat will increase life expectancy.

Reducing intra-abdominal, or visceral, fat is important because in addition to increasing the risk of cardiovascular disease and diabetes, among other conditions, such fat can raise insulin levels, which promotes the growth of cancer cells.

People with high levels of intra-abdominal fat may not even know it, McTiernan said, because it is hidden, deposited around the internal organs within the abdomen. "Most women don't know about intra-abdominal fat, but they should, since it is the most clinically significant type of fat and it's where women tend to store fat after menopause."

Although it is known that so-called "apple-shaped" people who store their fat around the stomach are at higher risk for conditions such as diabetes, hypertension and stroke than "pear-shaped" people who store their fat in their buttocks and thighs, visceral obesity is not necessarily correlated with body shape, McTiernan said. The only accurate way to determine the presence and extent of intra-abdominal fat is with imaging procedures such as CT or MRI scans.

By Randall Parker 2003 January 24 01:36 AM  Aging Reversal
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Lithium Nitride Sets New Hydrogen Storage Record

The material has drawbacks because it requires either a higher temperature or low pressure to cause the hydrogen to release. But this result is important because it identifies a class of compounds that are worth investigating for hydrogen storage potential.

The researchers have found a material that can store and quickly release large amounts of hydrogen. Lithium nitride can store 11.4 percent of its own weight in hydrogen, which is 50 percent more than magnesium hydride, the previous best hydrogen storage material. Other metal hydrides generally store only 2 to 4 percent of their weight.

By Randall Parker 2003 January 24 12:52 AM  Energy Tech
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2003 January 22 Wednesday
Modified Printers Used For Tissue Engineering

Scientists at the Medical University of South Carolina are using inkjet printers to lay down cells and gels to make 3 dimensional cell structures.

Three-dimensional tubes of living tissue have been printed using modified desktop printers filled with suspensions of cells instead of ink. The work is a first step towards printing complex tissues or even entire organs.

"This could have the same kind of impact that Gutenberg's press did," claims tissue engineer Vladimir Mironov of the Medical University of South Carolina.

One enabling technology for this work came from Thomas Boland of Clemson University who developed the idea of printing biomaterials on surfaces.

1. Protein Printing
The research involves deposition of proteins in patterns or arrays using the protein printer, a device developed in the laboratory. Protein printing allows high throughput, fully automated deposition of a variety of biomolecules such as DNA , proteins, antibodies or drugs onto polymeric supports such as petri-dishes or tissue engineering scaffolds. Currently, the device is used to analyze 300,000 potential anti cancer drugs for their ability to prevent angiogenesis.

2. Cell Printing
Cell printing is the extension of protein printing to entire cells. The cell printer developed in the laboratory is fully automated and allows to deposit live cells with 500 nm precision on to supports such as tissue engineering scaffolds. Current research includes the deposition of enothelial cells for in vitro tube formation, single cell microculture and single cancer cell characterization.

An important enabling technology for this work is the thermoreversible gel which is also delivered by a printer cartridge over each cell layer to provide a structure to allow build-up of a 3 dimensional structure.

Called a stimuli-sensitive polymer, the material is designed to change immediately from a liquid into a gel in response to stimulus, such as an increase in temperature. This feature would enable physicians to inject the mixture of the polymer and a medicinal solution directly into a specific target in the body, where it would warm and instantly gel.

"Stimuli-sensitive gels show promise for the effective treatment of inoperable tumors," said Anna Gutowska, senior research scientist at PNNL and lead developer of the gel. "While much more research remains to be done before this becomes an accepted medical procedure, we are very excited about its potential."

Gutowska has spent many years developing biocompatible gels for drug delivery, cartilage repair and other medical applications. This latest work appears to be an outgrowth of her previous collaboration with MUSC researchers to use a gel as a scaffolding for the growth of cartilage.

In related research, PNNL is collaborating with the Medical University of South Carolina to test a biodegradable version of the polymer gel to support repair of articular cartilage—the durable type of cartilage that provides cushion between knee joints and other joints in the body.

Once injured, articular cartilage doesn't heal well, or typically at all on its own. Consequently, more than one million cartilage repair surgeries are conducted annually. However, there are limitations to the effectiveness of these surgeries because physicians have been unable to spur growth of articular cartilage inside the body.

To try to encourage growth and healing, cartilage cells, called chondrocytes, are extracted from a different site within the body for cultivation in the laboratory. Not only does this create another defect at the removal site, but physicians have been unable to cultivate chondrocytes with all the properties required to generate articular cartilage. Rather, a weaker, less durable type called fibrocartilage forms.

Through a two-year, DOE-funded project, Gutowska and collaborators at the Medical University of South Carolina are developing two components to support the successful repair of articular cartilage. The first is a three-dimensional cell culture system to support the in-laboratory growth of chondrocytes that retain the properties necessary for articular cartilage repair. A patent recently was issued for this technology.

The second component is a biodegradable polymer gel that can be injected into the defect to serve as a temporary synthetic "scaffold" to support growth of the injected chondrocytes. Testing of the biodegradable gel currently is taking place at the Medical University of South Carolina.

The idea of using common inkjet printers for laying down biomaterials and even living cells demonstrates how advances in other technological fields provide mature technologies for use in bioengineering. Also, the development of the thermosensitive biocompatible gel demonstrates that bioengineering involves a lot more than just the understanding and manipulation of cells.

By Randall Parker 2003 January 22 07:59 PM  Biotech Manipulations
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2003 January 21 Tuesday
Restrict Dangerous Scientific Information?

A recent conference organised by the US National Academies of Sciences was held to debate the question of whether restrictions should be made on the publication of research that terrorists could use.

Several speakers at the conference urged that leaders in science sit down and talk with national security officials to outline what information it would make sense to keep confidential.

"Rational and well-conceived restrictions do remain necessary," Mitch Wallerstein said, a former assistant secretary of defense now at the MacArthur Foundation in Chicago.

Mr Wallerstein said universities should be more careful about who they admit and grant access to research, while the Government should look more carefully at who is granted visas.

The opposing argument is that scientists need to be able to show each other their research and to discuss their research in order to advance.

"Science is inherently a social activity," John Marburger, director of the White House Office of Science and Technology Policy, told the conference.

The problem, of course, is that there are people with malevolent intentions reading and listening to what scientists are telling each other.

Various agencies of the United States government have been putting security restrictions on research that they fund. Many researchers are resisting the new restrictions.

Before 9/11 and the anthrax attacks, most biologists would never have considered withholding results from publication. Outside of private companies and defence-related projects, the free exchange of information is a cornerstone of scientific culture. So the steps taken by the Bush administration have come as a shock to many researchers.

"For scientific openness, this has been an earthquake, an avalanche and a tidal wave rolled into one," says Steven Aftergood, who monitors government secrecy at the Federation of American Scientists in Washington DC.

Some universities are turning down grants that come with restrictions on prior review before publication of research and on the nationality of researchers. However, not all universities are balking at the new funding rules.

But the National Security Agency refused to budge from a requirement that any foreigners working on a planned project at MIT's Artificial Intelligence Laboratory be screened by the government in advance, forcing the school to turn down the money in September, Powell said.

About half of graduate students in the physical sciences and engineering come from abroad.

Lets entertain some hypotheticals. Suppose every pathogen known to humanity has its DNA sequence published on the web. Suppose nanotechnology advances far enough that affordable (lets say under $1 million and hence affordable by any decent sized international terrorist organization or rogue state) devices are developed for sale on the open market that can generate any DNA sequence and perhaps by using an existing bacteria place that sequence into an organism that then becomes the desired pathogen. The ability to make any pathogen will be available. A large body of scientific research may be available at some point in the future on how to modify pathogens to make them more virulent, to make them have a longer period of contagiousness for the host.

Suppose information is discovered to allow a pathogen to be bioengineered to have mild symptoms that mimic the symptoms of a mild cold for a couple of weeks before the host finally becomes seriously ill. Suppose other information is discovered that makes it easy to know how to modify pathogens in other ways that increase their usefulness to biological terrorists. At that point how do we stop some suicidal cult from killing a large fraction of the human population as part of their own plan to cross over to, say, rejoin with the alien spirits calling to them from a passing comet?

Suppose some research project investigating how well various devices can detect smuggled bombs discovers a way of packing a bomb that makes it impossible for existing detection devices to detect. If that method of packing is not known to terrorists and is unlikely to be discovered by them then should the scientists publish that part of their results?

Or suppose at some point in the future scientific research gets published that shows how to use then available nanotech to construct a small fusion bomb that doesn't require a fission trigger. Are we supposed to just say that the need for scientists to talk to each other trumps all other considerations?

The concern about where the graduate students in American universities come from is a valid one. Saddam's best weapons makers were educated in America. Should anyone of any ideological or religious persuasion from any country on Earth be allowed to come to the United States or other Western countries for advanced scientific and technical education?

By Randall Parker 2003 January 21 01:18 PM  Dangers Tech General
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Nanotech To Enable New Types Of WMD

Nanotechnology will make it possible to develop new kinds of weapons of mass destruction.

Nanotechnology has the potential to create entirely new weapons. Fourth-generation nuclear weapons are new types of nuclear explosives that would use inertial confinement fusion (ICF) facilities.

The defining technical characteristic of fourth-generation nuclear weapons is the triggering - by some advanced technology such as a superlaser - of a relatively small thermonuclear explosion in which a deuterium-tritium mixture is burnt in a device whose weight and size are not much larger than a few kilograms. Since the yield of these warheads could go from a fraction of a ton to many tens of tons of high-explosive equivalent, their delivery by precision-guided munitions or other means will dramatically increase the fire-power of those who possess them - without crossing the threshold of using kiloton-to-megaton nuclear weapons, and therefore without breaking the taboo against the first-use of WMD. Moreover, since these new weapons will use no (or very little) fissionable materials, they are expected to produce virtually no radioactive fallout.

The problem this poses is that as nanotech manufacturing equipment becomes available for purchase many more groups and countries will be able to make weapons that are currently beyond their technical ability to build. The ability to build nuclear weapons with little or no fissionable materials will remove another obstacle. Countries that are now struggling to buy and build uranium and plutonium enrichment facilities (e.g. Iraq, Iran, North Korea, and perhaps Libya) will suddenly find that the size of that problem will shrink by orders of magnitude.

The threats posed by the spread of WMD into the hands of more governments and to terrorist organizations will grow enormously as technology advances throughout the 21st century.

By Randall Parker 2003 January 21 08:55 AM  Dangers Nanotech
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2003 January 19 Sunday
Easier DNA Sequence Detection Method Developed

Researchers at The Scripts Research Institute have developed a new method for detecting specific DNA sequences.

Now TSRI Ph.D. graduate and current research associate Alan Saghatelian, TSRI graduate student Desiree Thayer, research associate Kevin Guckian, and Professor Reza Ghadiri in the Department of Chemistry have designed a non-PCR method for detecting specific sequences of nucleic acid that may have advantages over PCR, especially in such situations as field work and point-of-care medicine where the technology could be used by non-specialists. The new method is exquisitely sensitive and quite fast, according to Ghadiri, detecting as minute a sample as 10 femtomoles of DNA in less than three minutes. The method makes use of a detection system based on an inhibitor–DNA–enzyme complex. Specifically, the complex is composed of an enzyme, a single-stranded piece of DNA covalently attached to the enzyme, and, at the end of this DNA strand, an "intramolecular" inhibitor. The complex is able to "detect" pieces of DNA that are complimentary to its single strand of DNA. When complimentary DNA is not present, the single strand of DNA in the complex is flexible enough that it can loop around, allowing the inhibitor to occupy the binding site of the enzyme. But when complimentary DNA is present, the complimentary DNA forms a duplex with the complex's single strand—straightening out the DNA—and the inhibitor at the end on this duplex can no longer occupy the enzyme's binding site, enabling the enzyme to cleave its substrate. Ghadiri and his colleagues selected a fluorophoric substrate so that this cleavage releases energy in the form of easily detected fluorescence, signaling the presence of complimentary DNA. The sensitivity of the method comes from the fact that the system is self-amplifying. Any one molecule of DNA that hybridizes to one complex turns on that one enzyme, which can then do multiple turnovers of the substrate.

This is not a general sequencing method. Its designed to detect specific sequences of DNA. Its advantage over the existing polymerase chain reaction method is the potential ability to build devices that use it that do not require a trained technician. This will lower costs and allow use in a larger range of settings.

Its not clear from the press release what this technique's limitations might be. Could a partially matching fragment cause the method to report a match? Is it sensitive down to the level of a single nucleotide polymorphism (SNP) difference? It would be a lot more useful medically if it was. Eventually specific SNPs will be linked to medically useful factors such as drug sensitivities and incompatibilities. At that point what would be needed is the ability of a doctor to test for a specific SNP in order to choose the best drug treatment.

By Randall Parker 2003 January 19 04:21 PM  Biotech Assay Tools
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Bush May Announce Nuclear Rocket Trip To Mars

President Bush may announce an aggressive project for a nuclear powered spaceship to make a manned mission to Mars.

President George Bush may announce the plan, named Project Prometheus, at his State of the Union address on January 28, according to a report in the Los Angeles Times. It would commit the US to the exploration of Mars as a priority and herald the development of a nuclear-powered propulsion system. The first voyage could take place as soon as 2010.

"We're talking about doing something on a very aggressive schedule to not only develop the capabilities for nuclear propulsion and power generation but to have a mission using the new technology within this decade," said Nasa administrator Sean O'Keefe.

The most gratifying aspect of this proposal is the underlying attitude at NASA that is driving the nuclear propulsion approach. NASA has spent the last couple of decades trying to patch up yesterday's technology (the loser space shuttle) rather than try to make technological leaps that would make space exploration more affordable and feasible. Now NASA wants to work on enabling technologies.

The new rocket proposal also represents a significant change at the agency, which has typically been driven by a quest to get somewhere -- the moon, Mars or the outer planets in the solar system -- and then developed the technologies to do so.

Instead, O'Keefe has begun shifting the agency's focus to developing so-called "enabling technologies" to carry out missions whatever they might be.

NASA is now denying that Project Prometheus will be announced in the President's State of the Union address. But NASA may be backpedalling in order to allow the President to make the official announcement.

"At this point I can't say what they plan beyond what we announced in the 2003 budget," Savage said.

"O'Keefe didn't say that there would be announcement in the State of the Union concerning NASA. He doesn't know what's going to be in the State of the Union and certainly wouldn't get out in front of the President," Savage responded to SPACE.com.

This is not as sudden a decision as it might seem. NASA decided to reactivate its nuclear propulsion program a year ago.

ALBUQUERQUE, NEW MEXICO – For the first time in a decade, NASA has been given the go-ahead to say the “N” word – nuclear power for space.

The White House-backed NASA budget for fiscal year 2003 includes a major nuclear systems initiative that sets the stage for faster trip times by spacecraft exploring the solar system and powering human outposts on distant worlds.

If a nuclear propulsion program is going to be used to go somewhere the logical first stop is obviously Mars. Serious discussions in NASA of a nuclear propulsion mission to Mars were reported by Space.com to have started back in 2000.

In the past few months, several NASA notables, including associate administrators Joe Rothenberg and Gary Payton, have mentioned publicly that nuclear power in space transportation deserves a closer look. The comments indicate that if public relations efforts can gain acceptance for the possibility, future interplanetary missions may include nuclear-power options.

The NASA proposal is not for a rocket that a series of nuclear explosions made behind a shield on the back of the spacecraft (ala Niven and Pournelle's Footfall). Rather, the idea is to use a nuclear reactor to heat hydrogen propellant and then expel it behind the spacecraft at a high velocity.

In NTP, a compact lightweight nuclear reactor heats hydrogen propellants to a high temperature, e.g., 3000 K. Because the molecular weight of hydrogen is almost a factor of 10 smaller than the molecular weight of hydrogen/oxygen combustion products, the exhaust velocity of hot hydrogen propellant is much greater than that of hydrogen/oxygen. A NTP engine can achieve a hydrogen exhaust velocity of 10 kilometers/sec. and a maximum Delta-V increase in rocket velocity of ~22 kilometers/sec.

Also see this previous post in nuclear powered spaceships.

Update: Bruce Moomaw has written a follow-up article in SpaceDaily.com claiming that Peter Pae of the Los Angeles Times confused talk of a Nuclear Electric Propulsion system for space probes with a much more expensive and longer term development effort needed to build a Nuclear Thermal Propulsion system for a human trip to Mars program.

Peter Pae, in his Times article, seems to have been completely confused by O'Keefe's references to the fact that such a vastly larger nuclear-rocket system could indeed send a manned ship to Mars in only a couple of months, and so falsely connected them to O'Keefe's simultaneously declared indications that the Bush Administration does intend to considerably increase the current spending level on the NEP program while renaming it "Prometheus".

At this point it sounds like Bush will not announce a Mars mission or even the development of a nuclear propulsion system for a Mars effort. Instead the Bush Administration is going to increase funding for a nuclear propulsion system more suited for space probes. This will allow the development of much more ambitious unmanned space exploration missions. But its not going to enable the development of a spacecraft that can make a faster trip to Mars.

Update II: Bill Emrich of NASA Marshall Space Flight Center is proposing a way to make a fusion reactor (as compared to the fission reactor designs proposed for NTP and NEP designs mentioned above) for spacecraft propulsion.

Emrich is proposing a bold solution. He wants to use microwaves to heat the plasma to 600 million kelvin, triggering a different kind of fusion reaction that generates not neutrons but charged alpha particles - helium nuclei. These can then be fired from a magnetic nozzle to push the craft along.

If NASA wants to advance the state of technology for doing manned spaceflight then the development of more advanced propulsion systems should be at the top of its list of priorities. If it was up to me I'd axe the International Space Station and the Shuttle and take all the money being spent on them and spend that money on the development of nuclear fission and fusion propulsion systems. In the short term less would be accomplished in space. We'd have fewer news events with video of astronauts floating around in and outside of space structures. But NASA is accomplishing very little in either science or in technological advance with its current efforts. Rather than spend so much doing so little with yesterday's technologies NASA ought to take bigger steps and choose long term payoffs over short-term photo-ops.

By Randall Parker 2003 January 19 09:59 AM  Space Exploration
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2003 January 17 Friday
Tethers As Orbital Space Debris Cleaners

It is very expensive to launch propellants into orbit. So it would be prohibitively expensive for a spacecraft to move around in orbit to pick up space junk. Similarly, it would be too expensive to give each launched satellite enough propellant to deorbit itself at the end of its service life. However, a propellant-free way of moving objects around in orbit very slowly is under development. How a long tether propulsion system moves around in orbit:

It works as a thruster because a magnetic field exerts a force on the current-carrying wire. When electrical current flows through a through a tether connected to a spacecraft, the force exerted on the tether by the magnetic field raises or lowers the orbit of the satellite, depending on the direction the current is flowing. The current is extracted from the magnetic field of the Earth's ionosphere by the tether.

"The working principle of electrodynamic tethers is not new, but the application to space transportation will be revolutionary," said Les Johnson, principal investigator of the ProSEDS experiment. "Imagine driving your car and never having to stop for gas - that's what a tether does for a spacecraft in low-Earth orbit. Tether propulsion requires no fuel, is completely reusable and environmentally clean, and provides all these features at low cost."

There are a lot of small fragments flying around in low earth orbit. The number of fragments is growing in number and as they do they collide more often with satellites. Those collisions break pieces off of satellites and hence create new fragments that in turn can collide with still other satellites. Joseph Carroll of Tether Applications has proposed the use of space tethers as a cost effective way to collect up loose fragments in orbit.

His plan is to equip the tether with a roving sheepdog, a small vehicle that is released near a piece of debris to fly around it looking for a suitable point to latch onto. Once attached, it returns to the tether with its prize in tow. The tether then heads for another piece of junk and sets the sheepdog loose again. "A single tether could be reused up to 100 times, capturing a piece of junk many times its own mass each time, " he says.

The NASA ProSEDS project will soon test the first tether propulsion system.

The Propulsive Small Expendable Deployer system - called ProSEDS - is a tether-based propulsion experiment that draws power from the space environment around Earth, allowing the transfer of energy from the Earth to the spacecraft.

Inexpensive and reusable, ProSEDS technology has the potential to turn orbiting, in-space tethers into "space tugboats" -- replacing heavy, costly, traditional chemical propulsion and enabling a variety of space-based missions, such as the fuel-free raising and lowering of satellite orbits.

The flight of ProSEDS, scheduled for early in 2003, will mark the first time a tether system is used for propulsion. To be launched from the Cape Canaveral Air Force Station, Fla., ProSEDS will fly aboard an Air Force Delta II rocket and demonstrate an electrodynamic tether's ability to generate significant thrust.

"We achieved an important milestone with our tests in November," said ProSEDS project manager Leslie Curtis of the Marshall Space Flight Center's Space Transportation Directorate. "Using a vacuum chamber to represent the space environment, we successfully simulated the first 16 hours of the experiment's initial flight."

In orbit, ProSEDS will deploy from a Delta-II second stage a 3.1-mile-long (5 kilometers), ultra-thin bare-wire tether connected with a 6.2-mile-long (10 kilometers) non-conducting tether. The interaction of the bare-wire tether with the Earth's magnetic field and the ionosphere will produce thrust, thus lowering the altitude of the stage.

Although the mission could last as long as three weeks, the first day is the most critical, because the primary objective of demonstrating thrust with the tether should be achieved during the experiment's first 24 hours.

Tethers also look like a promising way to deorbit old satellites.

The Terminator Tether™ (TT) system will provide a lower mass and more reliable means of bringing old satellites out of orbit. The TT system will be a small package bolted onto the satellite. When the end of the satellite's useful life is reached, the TT system will deploy a several-kilometer length of conducting tether from the satellite. Because the satellite and tether are moving at great speed across the Earth's magnetic field, a voltage will be induced along the tether. This voltage will cause a current to flow along the tether. At the ends of the tether, the current will be transmitted to the thin space plasma present in low-Earth orbit.

The current flowing through the tether will cause power to be dissipated in the resistance of the metal in the tether. This power has to come from somewhere, and it comes out of the orbital energy of the satellite. As a result, the orbit of the satellite decays, and this decay can be very rapid. Calculations indicate that a tether massing as little as 2% of the satellite mass can bring a satellite out of some orbits in just a few weeks (compared to centuries without the Terminator Tether™).

The Tethers Unlimited Inc. Terminator Tether™does not require any propellant.

The Terminator Tether™ is a small device that uses electrodynamic tether drag to deorbit a spacecraft. Because it uses passive electromagnetic interactions with the Earth's magnetic field to lower the orbit of the spacecraft, it requires neither propellant nor power. Thus it can achieve autonomous deorbit of a spacecraft with very low mass requirements.

The tether is necessary because parking old satellites in "graveyard" orbits eventually results in the generation of smaller and more dangerous pieces of space debris as micrometeorites collide with the satellites.

Some organizations are currently planning on boosting their satellites to higher, "graveyard" orbits at the end of their missions. This also requires that the satellite's power, propulsion, and guidance be working at the end of the satellite's mission. Moreover, it doesn't really solve the problem - it just delays it, somewhat like a toxic waste dump. Recent studies have shown that satellites left in a higher graveyard orbit will slowly break apart as micrometeorites hit them, and the smaller fragments will filter back down to lower altitudes [2]. Thus satellites boosted to higher disposal orbits will eventually endanger operational satellites. Moreover, once the old satellites fragment into smaller particles, it will be nearly impossible to clean up the debris. Consequently, it will be much more cost effective in the long run to deal with the problem properly from the start, and deorbit all old spacecraft, rather than leaving them as a problem for our children to deal with.

Tethers are not going to exert a lot of force. Orbits will change only very slowly. But there's no rush when the cargos are under automated controls and there are no living passengers.

By Randall Parker 2003 January 17 07:22 PM  Space Exploration
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2003 January 16 Thursday
Researcher: Stem Cell Funding Restrictions Not An Obstacle

Dr. Evan Snyder, a top Harvard University stem cell researcher who is in the process of moving to the Burnham Institute in La Jolla California, was interviewed by the San Francisco Chronicle about the current state and prospects for stem cell research. Snyder believes current US government restrictions on stem cell research funding are not yet holding back progress in the field.

Q. Does the Bush administration's policy, and the governmental financing restrictions, allow the field to move forward?

A. It's not so dire at this particular point because so much fundamental work needs to be done. Any scientists who say they have been paralyzed in their research because of the Bush administration is really being disingenuous.

There is so much fundamental work we still need to do before we even know if these edicts are restrictive or not.

This confirms an argument I've made previously: there is so much information needed about how cells differentiate that is best worked out using animal models (primarily mice but other species as well) that few scientists have much need to work with human embyronic stem cells at this point. So why all the debate? Scientists who want to rush more directly into trying experimental therapies on humans are going to object to that line of argument. Those latter scientists think they can develop useful therapies without understanding the details of how stem cells differentiate. They basically want to develop a technology without understanding the underlying science of how it works. This is not an argument that is easily dismissed. There have been many successful medical treatments whose underlying mechanisms of action were unknown for many decades after they entered widespread use.

Snyder's argument therefore is correct as far as the advance of developmental biology is concerned. How cells differentiate and how to manipulate cells to differentiate in different ways and to de-differentiate (i.e. to become less specialised) can be worked out using animal models. Most of what is learned with animal models will turn out to be directly applicable to human developmental biology. Also, the knowledge that will come from animal model research will eventually make it possible to create stem cell therapies for all possible applications without using embryonic stem cells. But scientists who are approaching the use of stem cells with more of an engineering mindset want to develop useful therapies well ahead of the advance of the underlying science. These scientists may well be able to develop many useful therapies using embryonic stem cells without waiting for the science to be worked out first. Therefore the debate about the use of human embryonic stem cells will continue.

By Randall Parker 2003 January 16 10:43 AM  Bioethics Debate
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2003 January 15 Wednesday
Genetically Engineering Pigs for Xenotransplantation

One of the problems holding back the use of other species to grow organs for transplant into humans is the presence of retroviruses in their genomes that could activate in humans and cause a devastating infection. There is even a risk that such an infection could turn out to be transmissable to other humans. This problem has so far ruled out the use of other primate species as a source of organ transplants in spite of their greater genetic similarity to humans than is the case with other types of species. However, a type of miniature pig (mini for a pig still means 250 pounds when fully grown) that has been found to not have viable retroviruses. In particular it doesn't have viable Porcine Endogenous Retrovirus or PERV. For this reason this pig breed has attracted the attention of researchers who want to develop pigs as a source of replacement organs.

One obstacle to the use of pigs is an enzyme that pigs have called a-1,3-galactosyltransferase or GGTA1. GGTA1 puts a sugar of surface of cell membrane proteins that causes human immune systems to recognize those proteins as foreign and to vigorously and rapidly attack them. Some scientists have recently created a pig that lacks this problematic enzyme.

AUCKLAND, NZ, January 13, 2003 -- In a session today at the annual meeting of the International Embryo Transfer Society (IETS), Randall Prather, Ph.D., Distinguished Professor of Reproductive Biotechnology at the University of Missouri-Columbia, announced the successful cloning of the first miniature swine with both copies of a specific gene "knocked out" of its DNA. The ultimate goal of this research, which is being conducted in partnership with Immerge BioTherapeutics, Inc (a BioTransplant Incorporated (Nasdaq:BTRN)/Novartis Pharma AG (NYSE:NYS) joint venture company), is to develop a herd of miniature swine that can be used as a safe source for human transplantation, a process known as xenotransplantation.

"The fact that we have been able to clone this particular strain of miniature swine with both copies of the gene that produces GGTA1 knocked out is a very exciting step for the field of xenotransplantation," said Dr. Prather, a researcher in MU's College of Agriculture, Food and Natural Resources. "Organs from regular swine are too large for human transplant, and this particular strain of miniature swine has been refined for years solely for its potential use in humans."

New options for organ sources are desperately needed to treat the rapidly increasing number of critically ill people on the transplant waiting list (more than 80,000 in the U.S. alone). Researchers have targeted the pig as the best potential candidate for an alternative organ source because of the similarity between human and pig organs and the relative ease of breeding. However, the massive rejection response mounted by the human immune system has been a major hurdle in this research.

A key player in this rejection process is the gene called a-1,3-galactosyltransferase or GGTA1 that produces a sugar molecule. When a foreign organ is introduced, human antibodies attach to the sugar molecule on the surface of pig cells produced from the action of the GGTA1 molecule, thus killing the organ. With both copies of this gene eliminated, the antibodies cannot attach, halting the early rejection process.

Dr. Robert Hawley and scientists at Immerge, in collaboration with Dr. Kenth Gustafsson, first identified the gene that produces GGTA1 and eliminated, or knocked it out, of the DNA of the cells from the miniature swine. This genetic material was then sent to Dr. Prather's lab, where Dr. Liangxue Lai and colleagues implanted it into an egg that had its DNA eliminated. The egg was stimulated to begin dividing and was later implanted into a sow. Prather and Immerge announced in January 2002 in the journal Science that they had successfully cloned the world's first single knock-out miniature swine. The genetic material from these swine was then re-engineered with the aim of knocking out the second copy of this critical gene. These cells were then subjected to another round of nuclear transfer cloning, leading to the birth of the double knock-out piglet on November 18, 2002.

The presence of the sugar on pig organs has provoked such a strong immune reaction in primates that it has not been possible keep pig organs alive in primates for more than a few hours. However, with the removal of this sugar it will likely be possible to test organs for other immune incompatibilities. It may well turn out that there are many other causes of immune incompatibility and it may require a series of cycles of testing, genetic modification of pig genomes, and then recloning to create pigs that are more immunologically compatible. It is difficult to say at this point how many iterations of genetic engineering modiifications, cloning, and testing will be required to make pigs that are immunologically compatible with humans. The process could take several years or even as long as a couple of decades.

Each cycle of genetic modification, growth of clone pigs, and testing takes years.

Researchers said many issues must be resolved before the promise of transplanting pig organs becomes a reality. They predict it will be at least two or three years before the transplants can be tested in humans, and then only if they can show that the transplanted organs survive in primates for more than six months without requiring such severe suppression of the immune system as to pose a danger to patients.

Another approach would be to use human stem cells to develop into organs in pigs or another species. That way the resulting organ would be more likely to be immunologically compatible with a human recipient. However, then one runs into ethical problems (see the previous post on mini human kidneys grown in mice) because of the methods used to get stem cells that are in the proper genetic regulatory state to be able to become the desired type of organ. Some scientists still think the use of human stem cells will be what wins the race in the long run but others say that the use of pigs will produce useful transplantable organs before a technique utilising human stem cells does.

On the bright side the competition between different technological approaches increases the odds that at least one approach will succeed in producing transplantable organs in 10 or 15 years.

Update: A friend raises an excellent point that I've not seen raised before in discussions about xenotransplantation: xenotransplant organs from a species which has a shorter lifespan than humans (which pretty much describes all species that are candidates for use as xenotransplant organ sources) will probably not last as long as organs grown from human stem cells. Pigs in the wild have a life expectancy of about 25 years and some of their organs will be fairly aged by the time they die. This doesn't seem like a major obstacle to the use of pig organs though. Suppose pig organ transplanted into a human will last 20 years. Someone getting a pig organ transplant in 2010 would have until 2030 to come up with a replacement. By that time it seems very likely that the growth of replacement organs from human stem cells will be possible.

In the longer run the genetic variations that make organs wear out more or less quickly will become identified. DNA sequence comparisons of shorter and longer lived humans will be done once the cost of DNA sequencing drops by orders of magnitude. This will lead to the identification of all genetic variations that affect longevity. This information will be used to do gene therapy treatments to human stem cells to make organs grown from them last for much longer periods of time. Also, entirely new genetic changes will be developed to make organs last far longer than any human's organs can last naturally.

By Randall Parker 2003 January 15 01:45 PM  Biotech Organ Replacement
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Shift Emerges In Debate On Therapeutic Cloning

Some ethicists are drawing an ethical line at the point where the cells in an embryo start to organize into some sort of 3 dimensional shape.

Cynthia Cohen, senior research fellow at the Kennedy Institute of Ethics at Georgetown University and member of a national Episcopal task force on ethics and genetics, said the moral status of the embryo "arouses the most vehement discussion" when she addresses church and civic groups.

Cohen said she believes, as do many scientists and religious leaders, that "very early embryos" -- those younger than 14 days -- cannot be considered human because cells have not formed a single, individualized entity.

The argument of ethicists who make the 14 day distinction is that cells that are not yet organized 3 dimensionally into shapes haven't really started to create a life. They argue therefore that it is ethical to take cells from an embryo that is less than 2 weeks old and starting doing things to those cells to induce them to change into a more differentiated (i.e. specialized, less general purpose) state in order to grow organs or to make non-embyronic stem cells for stem cell therapeutic uses.

If the 14 day dividing point was legally adopted this would not move us that much closer to being able to grow replacement organs. Cells from the first two weeks of embryo development would not immediately be usable for, say, growing organs. As was demonstrated recently with mini human kidneys grown in mice it is not until the later stages of embryo development (7-8 weks in the case of kidney progenitor cells) that cells change into progenitor cells that are suitable for growing organs. Without the larger developing embryo to use as a context that interacts with organ progenitor cells to bring them to the point where they are readly to become organs scientists would have to figure out how to make early embryo cells turn into cells that are for growing particular organ types. That may turn out to be a fairly difficult problem to solve.

The strong opponents of therapeutic cloning in the United States are not going to find the 14 day development point an acceptable boundary for the last point to which human embryos can be grown to for the purpose of extracting cells for therapeutic cloning. In cloning an adult cell nucleus is placed in an unfertilized egg in place of the egg's nucleus. This is done to make the regulatory state of the adult nucleus (which has a full genetic complement whereas the egg has only half a genetic complement and normally gets the other half by fertilization by a sperm) revert back into the state close to that of a freshly fertilised egg.

Any technique is going to elicit religiously motivated ethical objections as long as the technique causes a nucleus to revert to the state that is the same as that of a freshly fertilized egg's nucleus. If one could get an adult nucleus to convert directly into the genetic state of an organi progenitor cell (e.g. the genetic state of a kidney progenitor cell between the 7th and 8th week of embryonic development) then one would effectively avoid the main ethical objection raised against the technique of therapeutic cloning.

By Randall Parker 2003 January 15 02:23 AM  Biotech Organ Replacement
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2003 January 13 Monday
Emerging World Changing Technologies

MIT's Technology Review has an article entitled 10 Emerging Technologies That Will Change The World. Here is the summary list of the 10 technologies.

Technologies pinpointed to change the future include glycomics, injectable tissue engineering, molecular imaging, grid computing, wireless sensor networks, software assurance, quantum cryptography, nanoimprint lithography, nano solar energy and mechatronics. For each technology, Technology Review has profiled one researcher or research team whose work exemplifies the field’s possibilities.

Molecular imaging will be greatly helped by quantum dots. Nanotech for solar is important because nanotech manufacturing techniques show promise for huge reductions in manufacturing costs. The biggest factor holding back the widespread use of solar photovoltaics is their cost (yes, energy storage is another problem but nanotech fabrication techniques for batteries and fuel cells will similarly reduce their costs).

Wireless sensor networks have implications for privacy that science fiction writer David Brin has fleshed out in both his non-fiction book The Transparent Society: Will Technology Force Us to Choose Between Privacy and Freedom? and in his fun fiction read Earth. Brin argues advancing technology will make the use of surveillance technologies ubiquitous and that our choice is between just letting only the government watch everyone or letting everyone use surveillance technologies to watch everyone else. I think he's right about this and agree with him that the latter option is preferable.

Here is the more detailed description of each of the technologies. In particular, nanoimprint lithography sounds especially promising as a way to make nanotech device manufacture affordable.

Right now everybody is talking about nanotechnology, but the commercialization of nanotechnology critically depends upon our ability to manufacture,” says Princeton University electrical engineer Stephen Chou.

A mechanism just slightly more sophisticated than a printing press could be the answer, Chou believes. Simply by stamping a hard mold into a soft material, he can faithfully imprint features smaller than 10 nanometers across. Last summer, in a dramatic demonstration of the potential of the technique, Chou showed that he could make nano features directly in silicon and metal. By flashing the solid with a powerful laser, he melted the surface just long enough to press in the mold and imprint the desired features.

Although Chou was not the first researcher to employ the imprinting technique, which some call soft lithography, his demonstrations have set the bar for nanofabrication, says John Rogers, a chemist at Lucent Technologies’ Bell Labs. “The kind of revolution that he has achieved is quite remarkable in terms of speed, area of patterning, and the smallest-size features that are possible. It’s leading edge,” says Rogers. Ultimately, nanoimprinting could become the method of choice for cheap and easy fabrication of nano features in such products as optical components for communications and gene chips for diagnostic screening. Indeed, NanoOpto, Chou’s startup in Somerset, NJ, is already shipping nanoimprinted optical-networking components. And Chou has fashioned gene chips that rely on nano channels imprinted in glass to straighten flowing DNA molecules, thereby speeding genetic tests.

Nanotechnology's big challenge is how to manufacture nanotech devices. Sounds like Chou's technique may be useful for fabrication of a wide range of nanotech devices notably including nanopore DNA sequencers. If Chou's technology only enables the construction of nanopore DNA sequencing devices that alone will make his technology extremely worthwhile. The ability to cheaply do full personal DNA sequencing would allow the collection of data on each person's DNA sequence. As a consequence the efforts to run down what each sequence variation does will be accelerated enormously. In addition to providing valuable information about the causes of almost all types of diseases detailed personal DNA sequence information will affect everything from mating choices to medical insurance to privacy.

There are other approaches to nanotech fabrication involving the use of proteins and biological systems to make nanotech structures that might turn out to be equally or even more promising for nanotech manufacturing in the longer run.

One item that I think should have been on the list is microfluidics. The ability to miniaturize chemical, biochemical, and molecular biological experiments will greatly accelerate the rate of advance of biotechnologies and of chemistry as well.

In terms of life extension and rejuvenation the most important technology on the list is injectable tissue engineering. What is especially needed there is the ability to make youthful non-embryonic stem cells to replenish various non-embryonic stem cell reservoirs in the body. One big challenge to achieve that goal is to understand for each non-embryonic stem cell type exactly what regulatory state its genes are in to make it be differentiated into its particular stem cell type. Non-embryonic stem cells are not pluripotent (i.e. they can not become all cell types) because they are in the various parts of the body to make new cells of particular types that each part needs. It is hard to say just how long it will take to develop sufficient control of cellular genetic regulation to be able to make exactly the kinds of non-embryonic stem cells that are desired for each reservoir type.

Another application of tissue engineering is for the growth of replacement organs. This too will be used for life extension and rejuvenation. Though in cases where injectable stem cells will do the job the stem cells will be preferred because stem cell therapy is a lot easier than surgery.

Another important technology emerging technology that went unmentioned in the MIT list is gene therapy. For many cell types one can't simply replace them when you get older (e.g. your brain!). The ability to do repair in situ is essential. Gene therapy will make this possible many years before nanotech repair bots become workable.

By Randall Parker 2003 January 13 02:03 PM  Biotech Advance Rates
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2003 January 10 Friday
How To Detect Terrorist Weapons Of Mass Destruction?

Aracor has developed a system that uses X-rays to look for hidden nuclear materials.

The system they developed produces high-energy X-rays that can penetrate cargo containers and common shielding materials. If the X-rays hit uranium or plutonium they induce fission reactions, splitting their nuclei into smaller fragments. In the process, neutrons are emitted that can pass through shielding materials and be picked up by a neutron detector outside.

If this system becomes deployed at every point of entry into the United States and every single piece of cargo or vehicle is examined with it it still won't prevent nuclear bombs from being smuggled into the United States.

SUNNYVALE, CA – October 2002 – Advanced Research and Applications Corporation (ARACOR), a leading manufacturer of x-ray imaging systems, announces that it has signed a Cooperative Research and Development Agreement ("CRADA") to develop and deploy technology that can detect special nuclear materials and nuclear weapons concealed within sea cargo containers or trucks. Under this CRADA, ARACOR will work with the Idaho National Engineering and Environmental Laboratory and the Los Alamos National Laboratory to optimize and deploy a new nuclear materials detection system.

"Presently, Customs inspectors are equipped with small radiation sensors ("radiation pagers") to detect the presence of special nuclear materials and radioactive isotopes. These sensors provide the first layer of defense against the nuclear materials threat," explained ARACOR’s President, Dr. R. A. Armistead. "However, to further enhance Custom’s capabilities for the interdiction of nuclear materials illicitly entering the U.S., we are using an active detection approach involving photoneutron and photofission reactions that can only be produced in fissile materials. If this new active nuclear detection technology is deployed on our Eagle® inspection system, it will be possible to automatically detect nuclear materials while routine x-ray inspections of the cargo are being conducted," Armistead added.

The Eagle is a self-contained mobile x-ray inspection system designed for inspecting cargo containers, vehicles and rail cars. This high-performance system provides a cargo penetration capability equivalent to 300 mm of steel and can form an image of a cargo container or truck in less than a minute.

Here's the problem in a nutshell: Detection systems have to succeed before the weapon reaches a high population density area. A ship has to come into a harbor and to be off-loaded in order for its cargo to be examined. Well, Ahmed the A-bomb Attacker is just going to install a remote control device or a GPS detected that will cause the nuclear bomb in some ship's cargo to go off once the ship reaches the harbor of some major US port city. That would allow them to blow up San Diego, San Francisco, Seattle, New York City, Boston, New Orleans and many other US cities. So I do not see how this detection system helps all that much.

A more clever attacker could develop a large long-range torpedo that could carry a nuclear bomb and then release it from a ship many miles off-shore with a guidance system that would deliver the bomb into a harbor before detonating. A similar approach would be to use a small surface boat that had an automatic guidance system that would keep it moving toward a port. The boat could even be made up to have a dummy at the helm so that the boat would appear to have a pilot. The boat could even use a camera feeding a video signal to a remote that had electronic means of controlling the boat.

It is extremely difficult to prevent a nuclear attack by a small group once that group gets a workable nuclear weapon. If a group has enough money and brains they can figure out any number of ways to delivering the weapon with a high probability of success.

Looking at likely technological trends for the next 30 or 40 years its hard to see how advances defensive systems can keep pace with the development of new ways to manufacture and deliver weapons of mass destruction (WMD). Advances in nanotechnology, biotechnology and other fields will make it feasible for people with less resources and skills to develop WMD. As a result,as technology advances smaller and smaller groups will be able to develop WMD. A steadily increasing number of people will be able to develop WMD. What must we to do to prevent terrorist attacks that kill tens or hundreds of millions?

The only detection system that would have a chance of stopping terrorist WMD weapons before they reach their targets would have to be absolutely monumental in scope. Ships would need to dock in automated ports in extremely low population density areas. Then their cargo could be unloaded and examined to check for WMD. All originating ports would need weapons detection systems and extensive video and other sensor systems to prevent WMD from being placed on ships headed outbound. All ships would need extensive monitoring systems on-board to prevent the addition of WMD while in transit. Major coastal population areas would require embedded passive sensor systems offshore and automated underwater, surface, airborne mobile platforms that did constant patrols looking for approaching ships and underwater craft.

Detection of WMD on approaching aircraft, ships, boats, and underwater craft is not an adequate method of defense. Another approach (and keep in mind I'm not advocating any approach; just trying to illustrate the scope of the effort required to defend against easily buildable WMD) would be to prevent WMD development by extensively monitoring the actions of every person on the planet. Once artificial intelligence is achieved this might be possible to do. Stationary and mobile monitoring of the scope required would generate so much sensor data that it could only be done if artificially intelligent computers were doing the work.

There's an even more radical approach possible for defense against WMD development by increasing numbers of governments and non-governmental organisations: genetically engineer the personalities of some or all of the human race to make them less dangerous. People could be made to be less hostile and angry or perhaps to be more empathetic and more kind and benevolent. That may well turn out to be the only approach that will work well enough to prevent catastrophic terrorism.

Technology is a way to do things. The tools of technology can be applied for good or ill. Each person must decide what to use technologies for. As technologies become more advanced the number of things that each person will be able to do will steadily increase. The problem is that technologies can more easily destroy than they can protect. Therefore, as technologies become more advanced the risk that even a very small number of hostile peope pose eventually becomes enormous. This is the biggest political problem that the human race faces in the 21st century.

By Randall Parker 2003 January 10 04:18 PM  Dangers Tech General
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2003 January 09 Thursday
US Army Funding Nanotech For Infantry Protection

The US Army is funding the MIT Institute for Soldier Nanotechnologies (ISN) to develop all the supersoldier gadgets that Hollywood shows in movies.

Jan. 6, 2002 – In the not-too-distant future, American soldiers may wear Kevlar vests that will protect against biological agents as well as stop bullets. With the flick of a switch, the sleeves of their uniform may stiffen into anti-shrapnel armor or a medical splint. They may carry night-vision contacts lenses, while a patch on their shoulder or helmet signals their position to their commander.

The article doesn't name the type of material that comes incredibly stiff when a magnetic field is applied but they are probably referring to magneto-rheological fluids.

Interesting excerpts from the MIT ISN web site FAQ answers:

The ISN’s role is one of basic and applied research. The primary goal is to create an expansive array of innovations in nanoscience and nanotechnology in a variety of survivability-related areas that will be harvested by the industrial partners for future Army application. The research will integrate a wide range of functions, including multithreat protection against ballistics, sensory attack, chemical and biological agents; climate control (cooling, heating, and insulating), possible chameleon-like garments; biomedical monitoring; and load management. The objective is to enable a revolutionary advance in soldier survivability through the development of novel materials for integration into the future warrior systems.

The focus of the ISN is soldier survivability. The intent is to improve the ability of the soldier to perform their mission in the battlespace where somebody is actively trying to locate and kill them. The first of the research areas, listed above, looks at both ballistic and directed energy protection of the soldier. Mechanically Active Materials simultaneously looks at mechanical actuators for armour or exoskeletal support (either for load carrying systems or wound compresses and splints), and pressure/motion sensors to monitor the soldier. Signature and Detection Management looks at active camouflage and sensor systems to detect enemy rangefinding or target designation probes. The Soldier Medical Technology thrust focuses attention of soldier triage and automatic "first aid" for a wounded or disabled soldier. The final two areas are crosscutting areas intended to provide enabling technologies for the other thrust areas.

From the results of current DoD sponsored nanoscience research a number of potential applications have been developed. One is a semi-permeable membrane with molecular scale pores that open to allow passage of water but remain closed to other molecules. This would have application to water filtration and purification systems or for chemical/biological protective clothing. Molecular scale rotors on a 3d grid array so that they can pivot and block off high intensity laser light – a molecular scale Venetian blind – to protect soldier eyes from laser blinding or to act as high-speed switches in opto-electronic circuits. Nanoparticles of gold in solution, linked together by strands of DNA that are specifically encoded to respond to the DNA of biological agents, that produce dramatic optical colour changes to allow reliable field detection of biological warfare agents at very low sample sizes, or rapid, reliable screening for such diseases as flu, strep etc. Nanoporous antenna ground planes that reflect all electromagnetic energy with very low absorption, to increase the net transmission power of cell-phones and small radios. Nanoporous electrodes for batteries to increase power density and efficiency – this list grows longer every day.

Super soldiers must be able to leap tall walls with a single bound.

Thomas even spoke of soldiers being able to leap over 20-foot walls by "building up energy storage in shoes." Thomas went on to note that MIT researchers have recently created "world-record actuator materials" that are "better than human muscles."

One of the most intriguing ideas mentioned is to make optical bar codes visible only to one's own troops in order to reduce friendly fire casualties.

On the battlefield or on patrol, soldiers risk being separated from their own troops. They need a way to distinguish their side from the enemy. So scientists at the Massachusetts Institute of Technology’s (MIT) Institute for Soldier Nanotechnologies (in partnership with the U.S. Army) set out to create a fabric that carried an optical bar code, visible only to someone wearing special goggles.

By Randall Parker 2003 January 09 12:04 AM  Nanotech Advances
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2003 January 08 Wednesday
The Growing Market For Donor Eggs

The first article cites the example of ads run in a student newspaper offering Stanford female students $50,000 for egg donation.

The use of egg donors is increasing at nearly 20 percent annually, as more women delay childbearing to the point where their own eggs are in trouble. (If human cloning, which relies on ripe eggs, becomes a reality, it will call for even more donors.) Though some years off, new technology might help. Scientists are finding ways to ripen eggs in test tubes rather than in women's bodies, eliminating the risk of ovary-stimulating drugs. And frozen egg technology will enable women to store their own eggs for later use–rather than look to vulnerable students in search of tuition payments.

This article doesn't explain why most egg sources are cheaper than the Stanford example.

In the United States, prices vary greatly from clinic to clinic, but you should expect to pay between $15,000 and $20,000 for one donor egg or embryo in vitro fertilization (IVF) cycle. This includes the cost of compensation for the donor (usually about $5,000) and one cycle of IVF (usually between $12,000 and $17,000). If your insurance policy doesn't cover this treatment, you'll have to pay the entire cost up front.

Someone who was considering using donor eggs who looked into this market tells me there is a large price premium on higher IQ donor eggs. It is not a coincidence that the advertisement offering such a high price for donor eggs was run in a Stanford newspaper. In order to get into Stanford one has to be exceptionally bright. The Ivy League students get higher price offers to be egg donors as well. The growing use of donor eggs is driving up the price. That $50,000 price is literally a multiple of what it was a few years ago for top quality eggs.

Donor eggs are not a panacea for aging women. Their bodies are less able to support a pregnancy.

However, these successful pregnancies do not come risk free for older women. Even among women in their 50s who had passed a rigorous physical, the study found a 20 percent risk of gestational or pregnancy induced diabetes and a 35 percent risk of preeclampsia or pregnancy related high blood pressure.

The use of donor eggs is not always reported as such.

They make it look easy -- the celebrities who are regularly featured on tabloid covers, appearing to have almost effortlessly had a baby or two when they're beyond their 20s or 30s.

"These are women who are in their 40s, often late 40s, and the tabloids are saying they just had twins. And what they don't say is that these women used donor eggs," says Dr. Michael P. Diamond, director of reproductive endocrinology and infertility at Wayne State University, Detroit Medical Center and Hutzel Hospital.

In the long run technologies for viable creating eggs from cells and the genome of the mother-to-be will be developed. Eventually it will be possible to manipulate adult fully differentiated cells to make them do meiotic cell division to produce eggs. It will even become possible to grow new ovaries from stem cells just as it will become possible to grow other types of replacement organs from stem cells. It is likely that in many cases (depending on each woman's willingness to do so) these techniques will be done in conjunction with gene therapy that fixes any harmful mutations that one doesn't want to pass along to offspring. There will even be gene therapy to modify genetic sequences to produce changes that are enhancements such as higher intelligence or changes in appearance.

By Randall Parker 2003 January 08 12:30 AM  Biotech Reproduction
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2003 January 06 Monday
Stem Cells, Regenerative Medicine And Rejuvenation

Will it some day be possible to be rejuvenated, to become physically young once again? Yes. Barring an asteroid strike, nanotech goo, robot revolt, or biowar that wipes out the human race the day will come when bodies can be restored to a youthful state. Not only is this day coming but it is coming in this century. Many of us may live to see it. Stem cells topics to cover: - stem cells - embryonic and adult - cloning - what the clone egg does to the nucleus - youthful stem cells outcompete older stem cells - stem cell reseeding as method for rejuvenation and restoration of youthfulness - engineered negligible senescence - The cow experiment is important for a number of reasons. Should you care about stem cell research progress? Yes. Why? Stem cells are great. Stem cell reservoir reseeding will be one of the major rejuvenation therapies for turning back the aging clock so that some day we can become young again. The younger readers may not yet appreciate what a drag it is getting old: poorer eyesight, less endurance, poorer memory, more aches, easier to get kinks in muscles, less ability to bounce back from a night of debauched partying, you name it. As we get older there are more things that we could do when we were younger that we become less able to as we get older.

Current investigations include the evaluation of stem cells to treat incontinence in animal models. In research to date stem cell tissue engineering has been used to restore deficient urethral sphincter muscles in animal models. "These findings are exciting on many levels. First this is the first time that stem cell tissue engineering has been used to restore deficient sphincter muscles. Secondly, it lays the foundation for further investigation into methods of using stem cells to treat stress urinary incontinence," said Michael Chancellor, M.D., Professor of Urology and Gynecology. Chancellor and his colleagues have isolated muscle-derived stem cells (MDSC) from normal rats, transduced them with a reporter gene and injected the stem cells into allogenic denervated proximal urethral sphincters. After two weeks, they prepared urethral muscle strips from normal, denervated and denervated-MDSC injected rats. Fast twitch muscle contractions were recorded after electrical field stimulation. The amplitude of fast twitch muscle contractions decreased in denervated sphincters, and improved in denervated sphincters injected with MDSC by approximately 88 percent. Histological evaluation revealed the formation of new skeletal muscle fiber at the urethral sphincter injection sites.

By Randall Parker 2003 January 06 11:48 AM  Aging Reversal
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UK Genetic Census To Search For Disease Causes

The U.K. Biobank in Great Britain is going to track the health of hundreds of thousands of participants for years and then determine their genetic differences to look for genetic variations that contribute to disease.

For 10 years, they will be followed through their national health care records, which will be copied into the Biobank. The data will be anonymous, but not completely, to allow for updates by doctors or new questionnaires. By 2014, 40,175 are expected to fall ill with diabetes, heart disease, stroke or cancer. Another 6,200 are expected to have Parkinson's, dementia, rheumatoid arthritis or hip fractures. The DNA of these people will be read and compared, and any normal gene variants, the one-nucleotide differences in DNA that make one person's biology different from another's, will be tagged for study.

The cost of DNA sequencing is going to continue to fall and will fall by many orders of magnitude. It makes sense to start collecting samples and medical histories now and start tracking people for many years. Then when the cost of sequencing falls far enough it will be possible to cheaply determine the entire sequence of every person in the study and compare the data to the health histories of the participants.

However, the study is not ambitious enough. Genetics affects behavioral and personality characteristics and of course an assortment of physical performance characteristics. A really ambitious study would not just collect a representative cross-section of the population. It would also collect samples from people who have either excelled or stood out for being unique in a variety of ways. To look for genetic factors that contribute to various forms of excellence such people as Nobel Prize winners in every category, champion chess players, Olympic medal winners in every category of sport, and any others who have excelled in some measure of extreme accomplishment should be included. At the same time, people who have been maladaptive and dangerous to self or others in extreme ways (eg serial killers, self-mutilators, gambling addicts, drug addicts, and those who suffer from obsessive compuslive disorders) should be sought out for participation.

Another useful way to make the study more ambitious would be to collect more types of measureable information about each participant. For instance, personality tests, psychometric tests, and other tests of mental qualities could be done on volunteers. Also, a wide array of physical tests of coordination, endurance, and of bodily and mental responses to stresses (eg heat, cold, loud noise, being spun around) could be measured. Opinion tests on politics and even on personal preferences in food, colors, music, and other subjects could be done. In a similar vein, a detailed questionaire about hobbies and habits would yield useful information when compared against genetic sequences.

For far too long countless social science studies have been done where genetic factors were not controlled for as variables. What is needed is a massive set of test data collected on a large group of people where genetics can be controlled for along with as many other measurable qualities of people that can be imagined. This could revolutionize the social sciences. A study involviing hundreds of thousands of people that has genetic contribution to physical diseases as its main focus, as laudable as that may be, is lacking in ambition.

By Randall Parker 2003 January 06 01:19 AM  Human Population Genetics
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NASA Researchers Build Nanostructures With Proteins

NASA announces the use of genetic engineering to customize a protein to make it more useful for nanostructure construction.

Scientists from NASA's Ames Research Center, Moffett Field, CA, have invented a biological method to make structures that could be used to produce electronics 10 to 100 times smaller than today's components.

As part of their new method, the scientists genetically engineered proteins from "extremophile" microbes to grow onto semiconductor materials.

The microbes' environments are "extreme" to us -- near-boiling, acidic hot springs -- but just right for the biological organisms to grow mesh-like structures, known as "chaperonins," presumably for their accompanying role.

"We took a gene from a single-celled organism, Sulfolobus shibatae, which lives in near-boiling acid mud, and changed the gene to add instructions that describe how to make a protein that sticks to gold or semiconductors," said Andrew McMillan, a leader of the project.

"What is novel in our work," he continued, "is that we designed this protein so that when it self-assembles into a two-dimensional lattice or template, it also is able to capture metal and semiconductor particles at specific locations on the template surface."

The genetically engineered proteins form lattice-like structures that act as templates, and particles of gold or semiconductor material (cadmium selenide/zinc sulfide) stick to them. According to McMillan, the minute pieces that adhere to the protein lattice are "quantum dots" that are about one to 10 nanometers across. Today's standard computer chips have features that are roughly 130 nanometers apart.

The proteins can be used to make highly patterned structures.

"The cage-like chaperonin provides an ideal structure that we envisioned as being a vessel or container to use to organize nanophase materials," McMillan told nanotechweb.org. "The higher-order crystalline structures that these protein-cages can be induced to form closely resemble similar patterns that the electronics industry uses, namely in the formation of precise, regular arrays of materials on substrates."

From the abstract of the published research paper.

Here, we fabricated nanoscale ordered arrays of metal and semiconductor quantum dots by binding preformed nanoparticles onto crystalline protein templates made from genetically engineered hollow double-ring structures called chaperonins. Using structural information as a guide, a thermostable recombinant chaperonin subunit was modified to assemble into chaperonins with either 3 nm or 9 nm apical pores surrounded by chemically reactive thiols.

Eric Smalley in Technology Research News has interviewed other researchers in the field who provide important qualifiers on the usefulness of the research.

Proteins are particularly useful because researchers can modify their structures in precise locations without significantly altering their folding behavior, said Zhang. "This tailor-made approach will have tremendous impact on the growth of nanotechnology and nanobiotechnology," he said. "However, much effort is still needed to reduce the high cost of production and [improve the] stability of proteins in their complexes," said Zhang.

Proteins are obviously going to turn out to be important tools for creating nanostructures. Biotechnology is probably going contribute more to nanotechnology than vice versa for some years to come. A huge number of types of proteins already exist which perform an enormous variety of molecule-level transformations Also, the machinery whereby cells synthesize proteins can be used to make whatever modified and customized proteins look like they might be useful. The techniques exist to change DNA sequences. So customized genes can be used to make customized proteins.

By Randall Parker 2003 January 06 12:04 AM  Nanotech Advances
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2003 January 05 Sunday
Cloning a Threat to Criminal Investigations

One argument against cloning is that it makes personal identification much more difficult. Picture a future in which cloning is used by cults who, say, want to enjoy the company of as many copies of the perfect maximal leader as is possible. Suppose someone committed a murder and multiple witnesses saw him do it. Well, suppose the description of the murderer matches that of the dozens of clones of the leader of the local commune of a religious clone cult of Chaelians which is led by living god Chael. How can the particular clone be identified if they all look the same and all deny committing the murder or knowing who did it?

Worse yet, suppose the Chaelian cult has enemies in another cloning cult led by rival human god Shael. Shael (who has been kind enough to incarnate here on Earth so that humanity can be saved by his infinite wisdom), managed to get a bit of tissue from Chael 20 yearrs ago before Shael and Chael split over an argument involving preferential access to love slaves. Well, Shael (being, after all, a million year old soul who takes a long term view of things) could have arranged to clone Chael and to bring up his secret clone Achael to hate his genetic clone father (perhaps a bit of genetic engineering of neural stem cells to tweak Achael's personality helped with the indoctrination into Shaelianism while allowing Achael to show up on normal genetic tests as pure Chaelian). Achael might have been the person who was seen murdering the victim. The murder victim, btw, was the investment advisor that did work for the Chael commune. This muddies the waters quite well. Either the investment advisor was killed by the Chaelians to cover up rumoured large scale tax fraud or he was killed by the Shaelians to discredit the Chaelians and to bring attention to the questionable financial transactions of the perfidious Chaelians.

There is a fairly consistent rate internationally for the birth of monozygotic (ie identical) twins of about 4 monozygotic twins per 1000 births. The use of reproductive biotechnology increases the rate of twin births but not of identical twin births. Also, aging increases only the rate of non-identical twin births. Cloning is the first technology to come down the pike that has prospects of increasing the birth rate of genetically identical humans.

The correct identification of suspected criminals is already highly problematic. DNA testing of suspects and of convicted criminals has set many free in the face of eyewitness accounts that fingered them as the culprits. This and the evidence of cognitive science research demonstrates that human memory is very faulty and highly suggestible. The need to accurately determine identity has been sharpened by the growing problem of identity theft. The need to quickly and accurately identify people has led to proposals to develop biometric identity databases. Biometric databases are variously derided as threats to liberty or hailed as vital tools to protect liberty.

But an official of the American Civil Liberties Union, while declining to comment on any particular biometric system, said "it's a fact of life" that data bases and "privacy-invading technology" inevitably are used for new purposes and inevitably are abused.

Networks that ID individuals by fingerprint, the iris of the eye, facial features, or voice "enable the ethical user to assert his identity in multiple applications and protect privacy at the same time," Oliver Tattan told United Press International in a phone interview from Dublin. "Voice is the least accurate so far," he said. "Iris is quite good, but there aren't as many vendors and not as much experience with it. Finger is the most mature technology. "

Fortunately, some types of biometric data differ between genetically identical twins. For example, fingerprints are different in identical twins and presumably will be in clones as well (though one can imagine some biotech development that could produce identical fingerprints in clones). However, visual identification or tissue samples for DNA will be the only available information in many criminal cases. Therefore, from a law enforcement standpoint cloning is highly problematic.

Twins already pose the same set of problems that clones would pose in terms of risk of misidentification or inability to identify who did something. Clones that are born decades apart will be less of a problem for visual identification given that they will look to be very different physical ages. However, in the case where only DNA evidence is available multiple living clones are going to be a problem just as much as twins are. Though if one clone was really old or young one may be able to rule out a clone based on physical inability to commit a crime.

Single clones of already dead people will not pose an identification problem except in the most extreme and unlikely case where some biometric database doesn't delete or mark an entry for a deceased person and then their clone eventually allows a sample to be taken for a DNA test to, say, gain access to a bank lockbox that contains precious jewels or other valuables. However, if the death of a person could be kept secret a clone could be grown and used without the biometric data for the original being erased. Still, it seems unlikely that such subterfuge could be maintained for a long enough time to make it worthwhile. Plus, cloning is not useful for creating matches for all types of biometric data. A really secure facility is going to use multiple types of biometric data and some of those types will not be the same for clones.

One way to try to reduce the complications introduced by having so many genetically identical people walking around would be to require cloners to use gene therapy to introduce a unique genetic signature into each clone. The genetic signature would serve as something analogous to a serial number so that all clones would be genetically unique. The DNA sequence that would contain the signature could be placed in a part of the geneome that is not used for any purpose. However, that would not solve the visual identification problem that the Chaelian-Shaelian murder scenario illustrates above.

The ability to easily identify each person uniquely in a large number of settings is an essential element in efforts to maintain law and order in any human society. One problem posed by cloning is that it can make that task much harder to perform and to reduce the frequency with which it can be done correctly. This will inevitably provide incentive for abuse by those with nefarious intentions.

For an unserious look at the Raelian cloning controversy see my StoryPundit post on Raelian cloning, the Ferengi, and the purpose of Star Trek.

By Randall Parker 2003 January 05 04:37 PM  Biotech Society
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Smart Materials Survey

Mechanical Engineering magazine has an interesting survey of a large variety of smart materials. The article covers such diverse materials as magneto-rheological fluids which become more viscous when a magnetic field is applied and piezoelectric materials that will be able to generate electricity from normal equipment vibrations. The article describes an electroactive flexible polymer one of whose neater applications is to translate the mechanical energy of a shoe hitting the ground into enough electrical energy to power a cell phone.

The system also can be used to generate electricity, by applying mechanical energy to the polymer. The film can be made to push the positive charge away from the negative, raising the voltage between the two electrodes, Pelrine said. SRI had one project to put such a device in the heel of a shoe, to generate power when a person is walking. Von Guggenberg estimated that enough electricity could be generated to power a cell phone—about one to two watts of power per step.

Another cool application under development is a biodegradable shape memory polymer that could be used to form a suture when doing endoscopic surgery.

By Randall Parker 2003 January 05 10:59 AM  Materials Advances
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Legal Right To Use Reproductive Technologies?

Findlaw columnist Julie Hilden suggests there may be a constitutional right to use a wide array of reproductive technologies.

Indeed, so far, the Supreme Court has supported broad reproductive rights. In Skinner v. Oklahoma, it declared a right to procreate when it barred a state from sterilizing a prisoner. In Griswold v. Connecticut, it struck down a ban on contraception. In Roe v. Wade and Planned Parenthood v. Casey, it held unconstitutional laws that unduly restrict abortion.

Roe and Casey are often discussed as decisions involving bodily privacy and a woman's right to choose. Yet Griswold involves not privacy, but a drugstore purchase. Moreover, its holding not only the right of a woman, but the right of a couple to choose when -- and when not to -- reproduce. And the right to choose implicated in Skinner was a man's right to choose, not a woman's.

Thus, taken together, these decisions arguably suggest a broad right of parental choice -- one that applies to men and couples, as well as individual women, and to issues of reproductive choice, in the lab, the doctor's office, or the drugstore. Based on these precedents, if a state were, for example, to ban safe, perfected methods of in vitro fertilization (IVF), the Court would probably strike down the ban.

Suppose cloning becomes perfected and that a cloned baby has no greater risk of being defective than a baby made by regular (dare I say classical?) sexual reproduction. Would the United States Supreme Court find that there is a legal right to clone under those circumstances? What would be the argument against it? One argument against its legality is that the clone children would suffer from psychological trauma. While I think such a claim is questionable even if we grant it some credence is that a reason to outlaw reproductive cloning. We already allow people to reproduce under circumstances (eg extreme poverty, with a history of recurrent drug abuse, with a history of repeated criminal activity) which certainly do not bode well for the offspring. It seems like a weak reason to outlaw the practice of cloning in order to avoid some unproven psychological trauma when rather messed people are regularly having children whose experiences with their parents are likely to be far more traumatic to the children.

Cloning, in any case, is likely to appeal to only a very small portion of the population. One factor that will limit its popularity is that most people want a partner to help them raise their children. That partner is likely to be far more dedicated to raising the children if the children also have some of the partner's DNA. The biggest factor limiting the spread of cloning then is the need to get a partner to feel a personal bond to the children.

Cloning is a solution to some infertility problems. The biggest appeal of cloning is likely to be its ability to create an offspring under circumstances where some biological problem is preventing fertilization of an egg. Advances in other reproductive techniques will in time provide other solutions to infertility problems.

Another big appeal of cloning is that it will allow people of exceptional mental abilities to have children who are just as smart as the parents. Very bright couples frequently have children who are not as smart as the parents. One reason for this may be that both parents have only one copy of a dominant IQ-boosting variant of some gene and one copy (on the other chromosome of each chromosome pair) of a lower IQ version of the same gene. When each parent passes on genes to offspring there is one chance in 4 that neither parent will donate the smart version of the gene to their offspring. By contrast, cloning will assure that if a parent has a dominant IQ-boosting version of a gene then the offspring will too.

As reproductive biotechnology advances methods will be developed to control which of each chromosome pair one will pass on to one's offspring. Therefore it will be possible to avoid passing on the "dumber" version of a gene if you also happen to have the "smarter" version of the same gene. For most people the ability to control which half of one's genetic complement one passes on to one's children will provide a greater benefit in terms of optimizing one's childrens' abilities than cloning will. The reason is simple: one will be able to pick and choose the best of the genetic complement of two people and hence in many cases produce offspring who are better (by whatever criteria the parents care to use when selecting genes to pass along) than the parents. Therefore the ability to control whch subset of one's genetic complement one will pass on to offpsring will also reduce the demand for reproductive cloning.

More generally, the ability to genetically engineer one's children will provide an additional reason not to have offspring that are genetic clones. We will be able to use gene therapy to modify the genes we give to our offspring. This will provide the ability to make offspring that are better looking, smarter, with a better personality, with greater disease resistance, and with other appealing qualities. By contrast, simple cloning,. while limiting the downside risk, also limits the upside potential. Given the choice between having a clone who roughly equals the parent in abilities and having a child who is genetically enhanced many will opt for the non-clone superkid.

This ability to make changes in the DNA of our offspring will lead to potential uses of genetic engineering that will result in humans who have innate qualities (eg a total lack of empathy or the lack of a conscience) that make them dangerous to society. Once it becomes possible to control the personality characteristics of offspring it is unlikely that the US Supreme Court will decide that there is an unlimited right to reproductive choice. Once biotechnology advances far enough that it provides a way to make extemely dangerous children the legislatures and highest courts of Western nations will decide that the public interest overrides reproductive freedom.

By Randall Parker 2003 January 05 08:22 AM  Bioethics Reproduction
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2003 January 04 Saturday
Consolidated Memories Are Erasable In Rats

45 day old memories in rats were called up by an environmental stimulus and then erased.

In the Neuron article, Dr. Nader and his colleague from New York University extended this work to the part of the memory system that contributes to mediating conscious or declarative memories, called the hippocampus. They conditioned rats to fear the environment in which they were (i.e. a small box) by inducing a light electric shock on their paws.

This paradigm engaged the hippocampus to process information about the context that can be used to predict shock. The hippocampal contributions to this paradigm are thought to engage similar processes as declarative memories in humans. "According to the cellular theory of memory, new memories require new protein synthesis to be stored," explains Dr Nader.

"The hippocampus also has a second level of consolidation called systems consolidation theory. This posits that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. This is why amnesiacs such as H.M. (the patient of neuropsychologist Brenda Milner) who have damage to their hippocampus can remember events that happened a few years ago but can't remember recent events."

Before testing cellular reconsolidation in the hippocampus, professors Nader and Ledoux showed that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependant contextual fear memory, but only if the memory was reactivated prior to infusion. "This demonstrated that memories stored in the hippocampus can undergo cellular reconsolidation or restorage," said Dr. Nader. "Surprisingly, the effect occurred even if reactivation was delayed for 45 days after training, a time when declarative memory is independent of the hippocampus. In fact, we found that if you lesion the hippocampus 45 days after conditioning, there is no effect. Therefore the memory of the context has to be independent of the hippocampus. However, if the memory is now reactivated immediately prior to lesions, there is a large effect. Thus, mature old memories stored in our cortex return to being dependent on the hippocampus after they are reactivated, an instance of systems reconsolidation."

Consider the implications if this can be made to work for humans. Traumatic memories could be erased. Is that good or bad? It seems a scary prospect. But also memories of crime could be erased and a perpetrator could claim in all honesty to have no memory of having committed a particular act. Even more nefarious uses of such a technique could be imagined. A criminal or a government could force someone to recall a memory that they don't want a person to have and then erase it.

By Randall Parker 2003 January 04 02:08 PM  Brain Memory
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2003 January 03 Friday
The Coming Demystification Of Embryonic Stem Cells

Another piece of the puzzle of what defines embryonic stem cells falls into place.

Scientists have identified a gene that is required during early mammalian embryogenesis to maintain cellular pluripotency – the ability of an embryonic cell to develop into virtually any cell type of the adult animal. This discovery by Dr. Robin Lovell-Badge and colleagues at the MRC National Institute for Medical Research (London, UK) that the Sox2 gene is necessary to sustain the developmental plasticity of embryonic cells sheds new light on the molecular cues that direct early embryogenesis, as well as the genetic requirements for embryonic stem cell maintenance. The report is published in the January 1 issue of Genes & Development.

"Stem cells must have specific genes that give them their characteristic properties. Our work describes one such gene, Sox2, that appears essential for multipotent stem cell types in the early embryo," explains Dr. Lovell-Badge.

Early in mammalian development, a pre-implantation stage embryo called a blastocyst forms. The cells of the blastocyst are at a developmental fork in the road: The cells on the surface of the blastocyst become trophoblast cells, while the cells on the inside of the blastocyst become the inner cell mass (ICM). The ICM is further specified into epiblast and hypoblast cells, which, together with trophoblast cells, give rise to the entire embryo and its associated tissues: epiblast cells differentiate into all the cell types of the embryo, hypoblast cells differentiate into the yolk sac, and trophoblast cells differentiate into the chorion and much of the placenta, including a range of specialized cell types.

Dr. Lovell-Badge and colleagues have identified Sox2 as one of the only two known transcription factors (master gene regulators) to be involved in the specification of these three embryonic cell lineages.

I'm reporting this because it is an example that illustrates the on-going demystification of embryonic stem cells (ESCs hereafter) and cell differentiation (differentiation is the process by which cells change to become cells dedicated to specific end purposes such as organ cells). There are many more pieces of the puzzle yet to come. Most of what makes ESCs have their unique quality of pluripotency (the ability to become any other cell type) is still unknown. These unknowns help fuel the ethics debate about ESC use. The debate over the use of embryonic stem cells is, for the most part, a debate about whether there is something ethically unique about embryonic stem cells.

As science progresses a large number of advances such as the one excerpted above will show at a molecular level what exactly makes embryonic stem cells different from other cell types including other stem cell types. All or almost all of the differences will turn out to be different regulatory states for genes (slightly complicated by the fact that some of the regulatory states will be caused by concentrations of some regulatory molecules floating around). There will be a unique combination (or a unique set of combinations) of genes that must be activated and inactivated to make an embryonic stem cell.

When all those details of genetic regulation of stem cell state get worked out and published in scientific journals the effect this will have on some (though not all) observers will be to rob embryonic stem cells of a spiritual dimension. Embryonic stem cells (ESCs) will be defined by a list of genes that are on or off. The genes will have obscure names such as Sox2 and perhaps FoxM1B. It will become possible to send chemicals or perhaps gene therapy plasmids into a differentiated cell and order it to become an ESC. Therefore it will no longer be necessary to use fertilization or cloning to create an ESC. Note that this ability to instruct any cell type to become any other cell type will effectively make other cell types pluripotent (albeit with the requirement of advanced biotech tools to manage the transition into other cell types). At the same time, it will become possible to directly and quickly turn an ESC into any other cell type.

Even as ESCs become demystified the necessity of their use will decline as well. The genetic regulatory state that uniquely defines each and every cell type will become known. With that knowledge and with knowledge about how cells change genetic regulatory states will come knowledge of how to manipulate the regulatory mechanisms of the genome to instruct a cell to change its cell type. Techniques for turning any cell type into any other cell type will become available. Therefore there will be far less need for ESCs as a starting point for the creation of cell therapies and replacement organs.

When it becomes possible to use non-ESC cells to accomplish anything that can be done with ESCs many conservative commentators may breathe a sigh of relief and argue that the medical use of ESC can now be banned without any harm. They will think that there will be no need to challenge conception as the starting point of a rights-possessing legally protected being. However, this sort of view misses the real ethical challenge that biotechnology poses for humanity: a bright line definition of human life as starting at the moment of conception using traditional mating to combine sperm and egg is not a defensible position from which to define a human life. One can't simply ban any technology that makes that bright line inadequate. Such technologies are, by their very possibility, an intellectual challenge to traditional definitions of humanity. But their ethical challenge is not just an abstract one. Technologies will be used even if their use is criminalized (as is demonstrated by the massive illegal industries that run illegal factories for making illicit narcotics).

If some human teenagers step forward 25 years from now out of a secret cult in the Amazon and claim their bodies were grown separately from their head using specially engineered cells that never were embryonic stem cells and which were never even cloned using an egg we are still going to be faced with the question of whether to treat those people as fully human and accorded of all the rights of a human. It is inevitable that when faced with these beings we will resort to asking questions about what they are like as fully developed beings regardless of how they came to be created.

As biotechnology advances many new methods for creating humans will be developed that are different than the ways new humans have been made naturally. Using these technologies it will become possible to create humans who feel and think in ways that are well within the range of how existing humans think now. These technologies will make it possible to create humans that will not be able to be visibly distinguished from humans made from normal sexual reproduction. But it will also become possible to create sentient beings that differ from humans in an assortment of ways with such things as chimeric bodies, enhancements of muscles, coordination, eyesight, and other abilities and even to create disembodied fully sentient minds that live in a vat. Even if the creation of such beings are outlawed by every nation on the planet (which I think unlikely) and even if the people who do such things are caught and punished after they have created such beings we will still have to judge whether the sentient beings that they create have rights as humans.

The practical and ethical challenge that biotechnology poses is the question of what are the attributes of a rights-possessing being. Sexual reproduction between the egg and sperm of two existing humans is an inadequate definition of how a rights-possessing human being comes into existence. So many kinds of sentient beings will be able to be created via other pathways that we will need to come up with workable practical criteria for what sorts of beings will be allowed to live, which of those will be allowed to roam free in our societies, which will be allowed to enter into contracts, and which will be accorded full rights as members of a society. It is quite possible that there will come to be creatures that are sentient yet bioengineered to be such a threat to society that they will be shot on sight. At the same time it may become possible to create sentient beings that, while not dangerous, may be missing some essential quality that make them able to, say, serve on a jury or to fulfill some other obligation of society. Therefore there may be categories of beings whose rights will be restricted in a variety of ways. Even if one holds that such beings are an abomination whose creation should be outlawed we will still need to decide what should be done about them should a group or individual manage to create them.

Pandora's Box is opening. There is no appeal to supernatural authority or to tradition that will let us close it back up again. We can not deal with the ethical challenges that biotechnology poses simply by outlawing any manipulation of cells that challenges long-standing definitions of humanity that are based on how reproduction happens naturally. We have to face the question of what are the essential qualities of a rights possessing being and even whether there are types of beings that possess lesser sets of rights.

By Randall Parker 2003 January 03 12:50 PM  Biotech Society
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2003 January 02 Thursday
Christine Stolba Fears Reproductive Choice With Biotech

Christine Stolba (see short bio) fears that feminist rhetoric in favor of reproductive choice will lead to a consumer-driven eugenic society.

We are not all mothers yet, but if we continue along the path our feminist ethical guides have laid down, we run the risk of ending up in a consumer-driven eugenic society. With ever more sophisticated ivf techniques, genetic screening, and artificial wombs, the physiological process of pregnancy and childbirth could become just another commodified “life experience.” Like climbing Mt. Everest or meditating on an ashram, seekers of the exotic could experience the “adventure” of childbirth the old-fashioned way, while some women would make use of artificial wombs to avoid the hassles of pregnancy.

Its not clear from her essay whether she blames this likely outcome solely or mainly on feminism. Nor it is clear what about that outcome causes her to object to it. In her mind is it bad to use biotech to give embryos genetic variations that, for instance, boost intelligence or make personality be different? Is her problem with the possibility that feminists will use biotechnology to create genetically engineered feminist-minded children (yes, I expect that will become possible to make every male have the moral sensibilities of Alan Alda). Or is her deeper objection to the idea that feminists, by encouraging reproductive choice, will help lead the way into a sort of free-for-all reproductive chaos where individuals, whether feminist or not, will make all sorts of unwise decisions about what genetic characteristics their children will have?

Conservatives are fearful of changes. They tend (often quite wisely) to defend established institutions, traditions and practices. They are right to sense that biotechnology will allow people to separate previously related acts and to produce reproductive practices and outcomes that are radically different than what has been the case for humanity's existence up until now. For instance, already artificial insemination makes it is possible for a woman to have a child without having to have sex with a man or even to meet the man who will become the biological father. This already allows most male involvement in procreation to be dispensed with and yet most women are still having babies with men they know. It is important to recognize the benefits that most women feel they gain by having a child with a man (emotional, financial, and other practical considerations). These benefits have prevented what might have predicted would happen as a consequence of the creation of sperm banks.

As Stolba points out, eventually it will even become possible to bring a fetus to term in an artificial womb and to choose which genetic characteristics the baby will have. It is not foolish to feel some degree of apprehension when pondering these monumental changes in human society. But in Stolba's essay she spends more time attacking feminists, feminist ideology, and feminist ideas about reproduction than she does articulating exactly what harm she expects to result from allowing individuals complete freedom to make decisions to use forthcoming reproductive technologies. Just because some radical academic feminists make an argument that doesn't mean that people will do what they suggest. Also, even if people do what they suggest that still doesn't mean that the people did it because the feminists suggested that they should do it.

To be fair to Stolba, some feminists have certainly advocated a number of changes in society which have had some deleterious consequences and no doubt some of the feminists she quotes are peddling some ideas which would be harmful if put into widespread practice. Given the limits to our understanding of human nature if we start changing some aspects of human institutions (or with genetic engineering even changing human nature) we can too easily make some change to society which will cause some unexpected horrible social pathologies which won't become obvious for many years after the change is made. There's a defendable humility at the foundation of a conservative argument that defends the traditional ways to make and raise children.

However, the technological advances that will make artificial wombs and genetic engineering possible are coming. These advances do create real specific potential dangers to our society. It would be helpful if conservatives tried to focus more on the specific dangers and the specific motivations that will cause people make choices that the conservatives find potentially harmful. One fear is that men will be cut out of the reproductive picture. But artificial insemination has been available for decades and in spite of radical feminist arguments against the male patriarchy there is not big rush of women choosing artificial insemination in order to allow them to avoid male involvement in a child's upbringing. Plus, it is also already possible for a woman to raise a child on her own pretty easily in a more conventional fashion without recourse to any biotech. There are women (I know one who did this) determined to have a child on their own who meet a guy in a big city, have a one-night stand when they are fertile, get pregnant, and then never tell the guy and lose contact with him. Women choosing that route to reproduction are also still the exception. So fears about the use of biotech have to be placed in perspective. Absent a motive to use a technology people will not use it.

Is there an unsatisfied demand among women to cut males out of the reproductive picture? I don't see it. Nor do I expect the radical feminist theorists to make much headway trying to convince women to do so. However, I do see a capability that biotechnology may provide that could provide women with a far more powerful incentive for having children by use of an anonymous male donor's sperm: once personal DNA sequencing becomes possible it will be more obvious what genetic flaws or advantages each potential mate has. The perceived and real difference in genetic quality between a sperm bank sperm donor and a mate's DNA will create a greater incentive to use sperm bank sperm. This illustrates how if one looks at the details of biotechnology one can spot where the real forces for change in society will come from as a result of what biotech makes possible. An examination of those details could result in a more effective conservative critique of the dangers that biotech poses for human institutions and human nature.

By Randall Parker 2003 January 02 11:31 PM  Bioethics Reproduction
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2003 January 01 Wednesday
Electrospinning Used To Create Small Blood Vessels

Tissue engineering is a hot field. Electrospinning is a promising technique for making a three dimensional scaffold for growing replacement tissue.

RICHMOND, Va. – Traditional heart bypass surgeries require using veins from the leg to replace damaged blood vessels. Using a nanotechnology developed by Virginia Commonwealth University researchers, doctors soon could be using artificial blood vessels grown in a laboratory to help save half a million lives every year.

The new technology produces a natural human blood vessel grown around a scaffold, or tube, made of collagen. Using a process called electrospinning, VCU scientists are making tubes as small as one millimeter in diameter. That’s more than four times smaller than the width of a drinking straw and six times smaller than the smallest commercially available vascular graft.

VCU Biomedical Engineer Gary L. Bowlin, Ph.D., said patients don’t always have enough spare veins for a heart bypass, and even when they do, complications and failures often result because they are not compatible. “So what’s really needed is a blood vessel you can pull off the shelf,” said Bowlin.

After the scaffold is spun, smooth muscle cells are “seeded” or placed on its surface in a laboratory. The cells grow and within three-to-six weeks the tissue-engineered blood vessel is ready to implant.

Unlike current synthetic plastic blood vessels, collagen is a natural component of the body, allowing cells to grow on its surface and avoid rejection. “The cells are in a happy environment and they’re just going to stay and think ‘I’m a blood vessel, I’m going to act like a blood vessel,’” said Bowlin.

The collagen scaffold is biodegradable and eventually is replaced by the body. Pre-made blood vessels could be made available to emergency rooms where every second counts. Other applications include pediatric surgery where implanted blood vessels must grow with the patient and diabetic patients who often lose blood vessels to vascular disease.

The same collagen electrospinning technology can also be used to regenerate or replace skin, bone, nerves, muscles and even repair spinal cord injuries, according to co-inventor Gary E. Wnek, Ph.D., a VCU chemical engineer. “Anything you want to repair can start from a scaffold. We’re very excited about the potential,” said Wnek.

Practical applications of the new technology could be commercially available within three years.

The VCU researchers are pursuing commerical development of their technology.

Through VCU, the researchers formed a company called NanoMatrix to produce and test their products. Within two to three years, NanoMatrix expects to have products on the market, Bowlin said.

His co-inventors are Gary E. Wnek, a chemical engineer interested in nerve repair, and David Simpson, an associate professor of anatomy and neurobiology, who is looking at hearts and skeletal muscles.

``We're trying to make corneas, cartilage, skin, bones, tendons,'' Bowlin said. ``The Holy Grail is to make a whole liver, a whole heart, but we have to take baby steps.''

NanoMatrix and VCU are pursuing US government funding thru the National Institute of Standards and Techology Advanced Technology Program. The NanoMatrix grant application summary provides an idea of their direction of development.

More than 1.4 million surgical procedures that require arterial prostheses are performed each year in the United States, approximately 500,000 of these are coronary artery bypass operations. Because there are no acceptable synthetic prostheses for small-diameter blood vessels, surgeons must harvest the patient's own blood vessels for the transplant. This procedure is time-consuming, prone to complications, and greatly increases the recovery time for the patient. It also limits the number of patients who are good candidates for the surgery, because there are only a few vessels in the body potentially available for transplantation. Attempts have been made for years to develop a viable synthetic or tissue-engineered prostheses for small blood vessels, but all have had high failure rates for one reason or another. To answer this need, NanoMatrix proposes a three-year project to design and fabricate three-dimensional (3D) "scaffolds" out of collagen, the body's natural structural material, that can be seeded with various types of cells to mimic natural, small-diameter blood vessels. Studies suggest that muscle cells, once implanted in the scaffold, will develop the function, shape, morphology, and cellular architecture of the "normal" vessel. In practice, natural blood vessels are difficult to mimic -- they are composed of three distinct layers of different types of cells and attempts to artificially create the blood-vessel tube have been frustrating. NanoMatrix's innovation is a novel "electrospinning" technology to produce nanofibers from collagen and other biological proteins, together with a special bioreactor to culture the implanted cells on this scaffold of collagen. Electrospinning has been used in the past to produce very fine fibers of polymers -- and even collagen -- but lacking precise, controlled orientation of the fibers. NanoMatrix will design and build an electrospinning device that incorporates computerized, multi-axis controls to build collagen scaffolds with the proper layering and orientation to mimic blood vessels. A novel cell culture bioreactor will maintain the constructs and prevent necrosis as the cells grow. Human endothelial cells, smooth muscle cells, and fibroblasts will be used in the inner, middle, and outer layers, respectively, of the vascular constructs. A key challenge will be to achieve the proper alignment, architecture, abundance of cell types, and behavior in each cell layer. The company will optimize the structure, mechanical properties, and biological efficacy of the vascular grafts and then conduct implantation studies. Virginia Commonwealth University (Richmond, Va.) will be subcontracted to conduct the tests. ATP support is necessary because the long history of previous failures to develop small artificial blood vessels discourages venture capital. If successfully developed and approved for clinical use, the new technology could replace all other vascular grafts, reduce coronary bypass surgical costs by 10 percent and other hospital costs as well, and improve productivity and quality of life for people who undergo vascular graft procedures. The technology platform also would be applicable to the engineering of skin, cartilage, bone, muscle, heart muscle, neural tissue, and other tissues.

This page has a good set of diagrams that explain the electrospinning process.

In 1934, a process was patented by Formhals [1-3], wherein an experimental setup was outlined for the production of polymer filaments using electrostatic force. When used to spin fibers this way, the process is termed as electrospinning.

In the electrospinning process a high voltage is used to create an electrically charged jet of polymer solution or melt, which dries or solidifies to leave a polymer fiber [4, 5]. One electrode is placed into the spinning solution/melt and the other attached to a collector. Electric field is subjected to the end of a capillary tube that contains the polymer fluid held by its surface tension. This induces a charge on the surface of the liquid. Mutual charge repulsion causes a force directly opposite to the surface tension [6]. As the intensity of the electric field is increased, the hemispherical surface of the fluid at the tip of the capillary tube elongates to form a conical shape known as the Taylor cone [7]. With increasing field, a critical value is attained when the repulsive electrostatic force overcomes the surface tension and a charged jet of fluid is ejected from the tip of the Taylor cone. The discharged polymer solution jet undergoes a whipping process [8] wherein the solvent evaporates, leaving behind a charged polymer fiber, which lays itself randomly on a grounded collecting metal screen. In the case of the melt the discharged jet solidifies when it travels in the air and is collected on the grounded metal screen.

The collage scaffolding is biodegradable. Now, you might be asking "Sounds great, but where will we get the natural immunocompatible human collagen from?" Silk worms! Japanese researchers have genetically engineered silk worms to make human collagen.

The team, from Hiroshima University and other institutions, constructed a DNA sequence that encodes for the production of human Type III procollagen, a mini-chain that is a kind of precursor to the full collagen molecule, which is a long-chained polymer. This DNA was combined with other genetic material and then injected into silkworm embryos.

The resulting silkworms secreted procollagen along with silk proteins in forming their cocoons. The researchers reported in Nature Biotechnology that they had found it relatively simple to separate the procollagen from the silk.

A type of human collagen has also recently been made in mouse cells.

Los Angeles, Dec. 23 –– Researchers at the Keck School of Medicine of the University of Southern California, along with colleagues from across the country, have for the first time genetically engineered mouse cells to produce a type of human collagen--type VII--that is missing in a family of inherited skin diseases called dystrophic epidermolysis bullosa. They also prompted the mouse cells to create the structural fibers that normally arise from type VII collagen. Their work was published in the December issue of Nature Genetics.

"This is the first demonstration of in vivo gene therapy where the genes have made a large extracellular molecular structure that you can actually see with a microscope," says David Woodley, M.D., professor and chief of dermatology at the Keck School and the principal investigator on this study. Scientists from Shriners Hospital for Children in Portland, Oregon, Northwestern University in Chicago, and Xgene Corporation in San Carlos, California, also participated in the study.

Woodley was helped by his previous efforts in the field: In 1992, he and some of his colleagues became the first team to clone the human gene for type VII collagen, which is one of the key components of the skin's extracellular matrix. Collagen makes up the tendrils and fibrils that provide a cushion for the skin's cells to rest upon; type VII collagen, in particular, is critical to the creation of the skin's so-called anchoring fibrils.

The goal of the USC researchers is to treat some human inherited skin diseases. They are studying the human type VII collagen gene in the mouse in preparation for the development of a gene therapy to treat the sufferers of these diseases. The mouse may not turn out to be a useful organism for the production of human collagen. Still, its an important result.

By Randall Parker 2003 January 01 04:03 PM  Biotech Organ Replacement
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Home Steak Incubator To Make Self-Cannibalism Possible

Vladimir Mironov, head of the Medical University of South Carolina’s (MUSC) Shared Tissue Engineering Laboratory, has proposed the development of a method to grow steak from cell culture for space missions. NASA turned down his grant. The reason given for rejecting the grant application is that astronauts can do fine on protein pills. How unimaginative. Space exploration should be conducted in ways that maximize the fun and innovation. Mironov could still turn to the big fast food companies for funding. Imagine Burger King, McDonalds, or Wendy's patties grown to the exact needed shape.

One problem that meat cell growth faces is the need to exercise the growing muscle cells to develop the ideal texture.

He suggests using a bioreactor with a branching network of hundreds of tiny edible tubes that act like artificial capillaries to convey nutrients to the growing meat. But to satisfy those who crave the texture and mouthfeel of a good steak, you need to develop something that mimics the texture of real meat.

That means generating a complex structure of muscle and connective tissue, and to do that, the muscle myoblasts need to stretch and contract regularly. In other words, not only must you feed your steak well, you have to give it plenty of exercise too.

The article mentions a vegan student who wanted to take a biopsy of her own tissue and then culture it to make self-steaks that would allow her to eat meat without feeling that she killed an animal. Of course, if one took a biopsy from a cow and grew a steak its not like one would have to kill the cow in order to get meat either. Still, perhaps you taste good. Since it will probably be no harder to grow human muscle tissue than to grow cow muscle tissue this could become quite a popular thing to do for anyone who doesn't find the idea of eating their own tissue to be nauseating (makes me queasy just thinking about it).

Mironov's main interests appear to be the growth of cardiovascular replacement tissues

Perfusion Bioreactor with Circumferential and Longitudinal Strain of a Tubular Construct for Accelerated Tissue Engineered Vascular Wall Histogenesis
Vladimir Mironov
Vladimir Kasyanov
Roger Markwald
Department of Cell Biology and Anatomy
Medical University of South Carolina, Charleston
e-mail: mironovv@musc.edu

A bioreactor is a key element of cardiovascular tissue engineering technologies. Increased use of stem cells as a cell source in cardiovascular tissue engineering is transforming this field into an in vitro approach that seeks to accelerate recapitulation of in vivo embryonic vascular development. The purpose and goal of existing bioreactors are to provide the pulsatile flow through an engineered construct and thus to generate periodic radial distension (circumferential strain) of the vessel wall. The important mechanical element of embryonic vascular development is longitudinal strain associated with arterial longitudinal growth. Thus, in order to "biomimic" the embryonic mechanical vascular environment (EMVE), perfusion bioreactor must also include the functional capacity for longitudinal strain. To accomplish this, we have developed a novel perfusion bioreactor. This bioreactor was designed and fabricated to provide the simulation of the EMVE including capacities for both circumferential and longitudinal strain of cardiovascular engineered tubular constructs. Results indicate this new bioreactor can provide the new critical component of biomechanical conditioning which is essential to mimic EMVE and accelerate vascular wall histogenesis.

Mironov points out that the discovery of stem cells (and by this he means non-embryonic stem cells that are found in adult organisms) has greatly increased the prospects for tissue engineering.

“Anatomy is no longer a static science,” Mironov said. “The discovery of stem cells has reinvented a classical microscopical anatomy—a tissue biology science, which is now again a vibrant, booming discipline. It no longer considers tissue a static, solid structure, but rather as elastoviscous, constantly renewing its dynamic community of cells and extracellular matrix.”

In the labs and on the near horizon are perfusion and bioengineering techniques to keep transplant organs alive and fresh longer, procedures to shrink a malignant tumor by blocking its blood supply, and plans to grow human organs with the careful manipulation of stem cells.

The growth of muscle tissue for human consumption is relatively easy as compared to its growth for medical applications. Quite a few scientists working on that harder problem. Here's a discussion by UCLA graduate student Carrie Caulkins on the problems that need to be solved to grow muscle tissue to replace damaged, diseased, or aged muscle.

One of the main focuses of the Tissue Engineering Department at UCLA is the design and fabrication of highly porous tissue engineering scaffolds with novel material formulations to control cell-substrate, cell-cell, and cell-signal interactions.

Future challenges in polymer scaffold processing include the development of fabrication techniques that will allow manufacturing of high-strength scaffolds for hard tissue replacement at load-bearing sites, and the ability to incorporate and deliver growth factors into scaffold construction, without loss of growth factor activity. This challenge likewise affects the cellular and signaling aspects of tissue engineering, and prompts the need for more research on cell-cell interactions and the chemical and protein signaling involved.

Once the harder case of muscle or organ growth outside of a living organism has been solved for medical purposes the ability to do it for food production will be trivial by comparison. Therefore it seems reasonable to expect the easier problem of growing cells for meat consumption will be solved as well. When that technology becomes really mature we'll be able to buy home meat growing devices just as we can today buy home bread makers.

Herman Vandenburgh of Brown University is working on modelling the effects of gravity on muscle development.

For Vandenburgh, the primary goal of his space research is developing pharmaceutical countermeasures to prevent the muscle wasting that occurs in space, "helping man explore a new environment, and a very hostile environment at that." His research group has developed a tissue culture system for preliminary tests of these countermeasures. "It's really the classical way of doing these types of experiments," he said, "You first test out new drugs in tissue culture, on cells outside the body, and then the next set of experiments are in animals. You hope you see a similar type of effect as you saw in cell culture. Then you go from animal to human. At each stage you have to hope that what happens early on is going to follow through. It's much more difficult to predict what's going to happen if you go right into doing animal studies."

While Vandenburgh is interested in solving this problem for astronauts this work might also be useful for growing meat in a cell culture. Recall that the first article above mentioned the problem of exercising the growing muscle tissue. Exercise and gravity both affect how muscle cells grow and organize themselves. so any attempt to solve those problems for human health will provide useful information for how to grow more realistic steaks.

Robert G. Dennis, Ph.D., University of Michigan Biomedical Engineering Assistant Professor, and member of the U Mich and MIT Biomechatronics (cool word, no?) Groups, lays out his tissue engineering Vision for the Future

Imagine the technology to seamlessly integrate hybrid prosthetic devices with their human users. Instead of bulky and ineffective synthetic mechanisms, prosthetic devices could have tissues integrated directly into them. One of our primary objectives is to integrate living muscle actuators into prosthetic devices. As the art and science of tissue engineering evolves, so too will the hybrid prosthetic devices, incorporating a greater percentage of more sophisticated engineered tissues, until the device eventually becomes fully biologic. We are working on the technology to grow the engineered tissues from small samples of the native tissue of the user, so that when complete the engineered prosthetic device will be fully compatible with the user, employing no foreign biological elements.

Imagine engineered tissues that can fully replace injured tissue, or be used for the surgical correction of congenital deformity.

Imagine the end of animal testing. New drugs and surgical procedures will be tested directly on engineered tissues. Tissues will be grown from small samples of cells without requiring animals to be killed. New drugs and procedures can be tested on human tissues that are engineered in culture, eliminating the cost and clinical uncertainty of animal testing.

Imagine engineered meat as a food source, eliminating the need for raising and slaughtering livestock.

Imagine a world with living computers, robots, and other devices, that operate silently and efficiently, are fault tolerant and can heal themselves, can adapt to their environment, are energy efficient, produce no harmful byproducts, and are 100% biodegradable. Humans will be able to interact with their creations in ways never dreamed possible.

Imagine the day when clattering, inefficient, synthetic electro-mechanical contrivances seem quaint and frivolous. From the first time that a proto-human grasped the first stone tool and used it to shape the environment, the use of living tissues as tools has been set in our destiny.

This is a future that most of us will live long to see. Tissue engineering will allow the reversal of aging of many parts of our bodies by replacement with newer and even better and longer lasting parts.

Robert G. Dennis say there are only three groups in the world working on engineering functional skeletal muscle.

The State of the Art in Functional Skeletal Muscle Tissue Engineering can be easily summarized by first defining the function of skeletal muscle. Though muscle tissue performs many functions for the body, some arising from the emergent properties of muscle cells organized into whole muscle organs, such as heat generation and protein synthesis, the most basic definition of muscle tissue function is the generation of controlled force, work, and power. It is necessary to quantify the contractility of the muscle tissue, to organize the tissue in such a way as to promote the generation of directed force, and exert control over the contractions for research in this area to be considered engineering, rather than cell biology. After all, spontaneous contractions in cultured skeletal muscle cells were first reported in 1915 (Lewis), and this was not construed as 'engineering'. Defining Functional Skeletal Muscle Tissue Engineering in this way, it is possible to assert that at this time there are only three research groups in the world engineering functional skeletal muscle in vitro: Herman Vandenburgh and Paul Kosnik in Providence, RI; myself and Hugh Herr at MIT, and the Muscle Mechanics Laboratory at the University of Michigan.

Update: Some Chinese eat aborted and stillborn babies. I'd excerpt from it but its too disgusting.

Update II: More on cannibalism in China. Not for the faint of heart.

By Randall Parker 2003 January 01 02:02 PM  Biotech Organ Replacement
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