Viewing entries in
Gene Doping

CNN on gene doping

CNN on gene doping

Last week, I featured in a CNN article on the future of doping. It was great to chat with the author about all of the things that can be brought to bear on this subject, but there's so much more to be said than is covered in the final edit. Take a look and then return to here, if you'd like more.

For me, at the core of this subject are questions about evolution, transhumanism, and how we make sense of our place in the world. Modern sports have always been pursuits that test the limits of our human capacity physically, through a combination of mental, physical, and technological synthesis. Gene doping remains emblematic of a brave new era in which I believe our currently held views on doping will come under question and make little sense to uphold. That doesn't mean there is an easy solution to the problem of cheating in sport. Whether it is doping or other means, these tendencies to break rules in order to gain an unfair advantage will occur, regardless of what those rules are.

The argument on behalf of supervised doping has been espoused by a number of my peers, since I published first on this around 10 years ago. Over this time, I have become less convinced that it will be an effective way of securing either a level playing field - of any kind - or that it would significantly reduce the potential harm that the collective athletic population will be exposed to, when compared with the present system.

The details of this argument are within a manuscript I am currently writing, which updates my perspective on the subject, but the key message I would like to get across is that we are moving rapidly into an era of gene editing whereby the means by which we determine what counts as human or even achievement in sport will need substantial revision.

Moreover, we will find there to be strong moral arguments in favour of doping like practices in society more widely, which will then urge anti-doping to re-position its value system. These conditions are why we need a fresh look at the problem, not just to solve the next few Olympics, but to ensure that it is fit for purpose for the next century.

 

Sport 2.0 #sportfuture

Sport 2.0 #sportfuture

This week, I am in Lausanne for the Sport Future Rendezvous 2016 conference, organized by good friend Professor Jean-Loup Chappelet at the University of Lausanne. I took the chance to talk about the biodigital interface, the growth of e-sport, biotechnological change, ingestible sensors, and virtual realities. But the big controversy, as always, was my views around doping, which did hijack the futures debate a little. In any case, here's my presentation.

 

 Thanks to Michel Filliau for the photograph.

Bioethics and the Future of Sport

Bioethics and the Future of Sport

Jacketfinal1.jpg

What: Scientific congress on genetics and sportWhen: July, 2012 Where:  Federal University of Sao Paulo Who: mainly genetic scientists

Here's a film from a talk I gave in Sao Paulo earlier in the year - translated into Portuguese. I also did a book signing while there for the Brazilian version of 'Genetically Modified Athletes.

Here's the presentation to accompany it

BBC2 Newsnight

BBC2 Newsnight

AndyNewsnight.png

I finally got around to watching myself on BBC Newsnight, which went live a few days ago. We talked about gene doping, human enhancement and the future of sport. Another fun experience on a great show.

Ethics @ Work: Let the 'Mutant Games' begin (2008, Apr 14)

Ethics @ Work: Let the 'Mutant Games' begin Aug. 14, 2008 Asher Meir , THE JERUSALEM POST We are fortunate that the sporting news from Beijing has come mainly from the playing field, and not from the laboratory. Cycling coverage is always a close race between the results from the course and the results of the drug policing, but following the disqualification of a number of Russian women athletes, doping has been pretty much out of the news at the Olympics. However, the reality of doping is always looming in the background, and the spectators are left wondering, does s/he or doesn't s/he? The assumption that doping is more or less pervasive, and that the vagaries of defining and detecting it will always make enforcement arbitrary, has led a number of observers to draw a fascinating parallel between today's prohibition on doping and the previous prohibition on professionalism. Nowadays the Olympics are all about money. The papers are filled with estimates of how much a gold medal costs in terms of the infrastructure needed to create champions (it's about $30 million) and much how one is worth in terms of endorsements (often seven figures for tennis players or track athletes, more like five or six for fencers or synchronized swimmers). It's hard to believe that as recently as the 1980s strict rules against professionalism were in place. Anyone who earned money from sport (this once applied even to teachers of sport), or anyone who competed against others who earned money from sport, was disqualified. The legendary American athlete Jim Thorpe, who won two Olympic gold medals in the 1912 Stockholm Olympics, had his medals stripped after it was revealed that he had played minor league baseball years before. Strict enforcement of the amateurism rules would have meant that only independently wealthy individuals would be able to compete. What happened instead was a cynical and arbitrary application of the rules. The Soviet bloc had athletes who were professionals in every sense, though their profession was usually listed as soldier or student, while the West had an elaborate system of under-the-table payments, "expense" payments, trust funds and so on. The system was a nightmare, since all athletes received money but only some were disqualified. Finally in the 1990s the system fell apart. The de facto professionalism of Soviet bloc athletes, which gave them an immense advantage in international competition, was a critical factor. The parallel to doping is expressed as follows: Just as it was practically impossible to compete on an international level in the 20th century without accepting money, so it is practically impossible to compete on an international level in the 21st century without using performance-enhancing substances. (This of course has not been proven.) The exact definition of doping is subject to dispute, just as the exact definition of professionalism is. Both can take place in secret, making enforcement necessarily arbitrary. The conclusion: Rules against doping should fall by the wayside just as rules against professionalism did. The counterargument is as follows: In the case of professionalism, almost all the athletes wanted to get money, and most of the spectators didn't mind if they did. In the case of doping, almost all of the athletes prefer not to take performance-enhancing substances, and almost all of the spectators also prefer that they don't. The athletes prefer no doping because doping regimens require a huge amount of effort and expense, and because many of the drugs are dangerous. For example, the endurance-enhancing drug EPO thickens the blood, and is the prime suspect in the sudden early deaths of a number of cyclists. Insiders tell of cyclists getting up in the middle of the night to exercise in order to get the blood moving to prevent their doped blood from killing them; obviously they would prefer getting a good night's sleep. The spectators prefer no doping because they don't care about outcomes, they only care about the competition - a level playing field. Women's tennis is nearly as popular as men's, even though the top women are no match for mediocre male players, because it is a fair and exciting game. The playing field is most level without doping. But what if it's not true? The same "arms race" hypothesis was advanced for professionalism in sport, and was proven false. Maybe the athletes want to push the envelope of the ultimate capabilities of the technology-aided human body, while the spectators want to see the tallest, fastest and strongest athletes science can provide! John Tierney of The New York Times has an interesting suggestion to test this idea: Set up an alternative "no-holds-barred" competition with no doping tests allowed. (He even gives some suggestions for names, including the "Mutant Games.") One must assume that the regular leagues will ban anyone who takes part in these competitions, even if they submit to the testing regimen, just as the amateur rules forbade not only professionals but also amateurs who competed against them. If the athletes are chafing at the testing regimen and the spectators want to see drug-aided competitors, then the new league will draw competitors and spectators; if not, then the "arms-race" hypothesis of doping will have been proven true. There is a slight problem with this test, due to the great prestige of the official events. Attempts to establish professional athletic competitions in the 20th century were unsuccessful, because athletes discovered they could make much more money in the more prestigious amateur leagues. Yet when the prestige events themselves allowed professionals, everyone was happy. I personally am strongly inclined to believe the received wisdom; that doping is a destructive arms race, and that everyone besides the undertakers would be happy to get rid of it. But Tierney's suggestion is an interesting way to see if the received wisdom is correct. ethics-at-work@besr.org Asher Meir is research director at the Business Ethics Center of Jerusalem (www.besr.org), an independent institute in the Jerusalem College of Technology.

Gene doping in sport: fact or fiction? (2008, Dec 6)

Gene doping in sport: fact or fiction? Experts believe it is only a matter of time before athletes manipulate their genetic material to gain an unfair advantage despite the current lack of proven cases. A science journalist, who has published a novel on the theme, and a scientist working in the field of genetics talked to swissinfo about the likelihood and dangers of gene doping in sport.

Since the times of ancient Greece, a minority of athletes have employed a variety of potions to artificially boost their performance. More recently, amphetamines, anabolic steroids and hormones have been the drugs of choice.

The World Anti-Doping Agency (WADA) has recently turned its attention to the threat of gene doping and officially banned the practice in 2003. There have already been suspicions of some athletes using the gene therapy Repoxygen to increase their red blood cell count and thereby allow the body to absorb more oxygen.

Professor Max Gassmann of Zurich University's Institute of Veterinary Physiology has manipulated the erythropoietin (EPO) gene of mice to produce more oxygen carrying red blood cells – a process that could eventually be transferred to humans.

Gassmann does not think gene doping has infiltrated sport at the moment but believes some people may already be testing its potential, just as beneficial gene therapy is currently undergoing clinical trials.

"I can hardly imagine that we had a gene doping cheat winning at the Beijing Olympics," he told swissinfo. "But there has been doping throughout history and if gene doping becomes viable then you cannot stop it, because people want to win." Fictional leap Author Beat Glogger has taken the theory a stage further by writing a thriller – "Run For My Life" – about genetically modified athletes. Glogger, also a science journalist, and Gassmann contributed to a Swiss sports ministry document warning about the risks of gene doping.

Scientists have already identified more than 150 genes that potentially influence performance in sports. These include genes that control muscle growth, muscle speed and the production of red blood cells.

"I take the next step into fiction by saying it is possible to manipulate the genes that control speed, power, endurance and even mental strength. These are the four key factors for athletic performance," Glogger told swissinfo.

There are many cases of people with naturally malfunctioning genes. Most of the time this results in health problems, such as muscular dystrophy, but the rare occurrence of a mutation can also bring benefits.

Finnish cross-country skiing legend Eero Mäntyranta won race after race in the 1960s because of a natural genetic mutation that helped his blood absorb large amounts of oxygen. It would be very hard in future to determine if such a case was caused by nature or gene manipulation, according to Glogger.

"If, after the introduction of the relevant genes, the body produces more EPO or testosterone by itself then you cannot detect it - it looks like you are a natural," he said. To die for However, athletes run a high risk of developing serious diseases such as cancer or even dying if they submit to gene manipulation that is still in the early days of scientific development.

Gassmann's genetically modified mice live only half as long as other mice. Scientists know how to modify genes and introduce them into the body, but not how to control the behaviour of such genes once they have been implanted.

"Whatever you put into the body is hard to control. If you realise it is no good then it is almost impossible to stop, and that is what could happen with gene cheating athletes," Gassmann said. "It is easy to switch on a light but much more complicated to dim it."

One method of controlling modified genes is to develop drugs that act like on and off switches, but this process is still in its infancy.

"Gene doping could be undetectable and it could improve performance but you could also die," Glogger warned. Just like the characters in his book.

swissinfo, Matthew Allen in Zurich

Couch-Potato Drugs Are WADA’s First Banned for Gene-Doping Ties (2009, Jan 14)

Couch-Potato Drugs Are WADA’s First Banned for Gene-Doping Ties By Mason Levinson Jan. 14 (Bloomberg) -- Two drugs that activate genetic switches, fooling the body into believing it has exercised, are the first to be added to the Olympic sports prohibited list for their ties to gene doping. The drugs, whose effects were first disclosed in a report published online by the journal Cell on July 31, were added to the nine-page list issued by the World Anti-Doping Agency under the “Gene Doping” classification as of Jan. 1. It’s a category that is likely to grow over the next five to 10 years, said Dr.Gary Wadler , who heads WADA’s Prohibited List Committee, as gene therapy becomes “part of the matrix of what physicians have to treat patients.” “There’s gene-therapy stuff going on in research labs everywhere in the world,” Wadler said in an interview at his Manhasset, New York, office. “I think they’re going to cause breakthroughs, and those breakthroughs, if they have any application to enhance athletic performance, then you’ll ultimately see it banned.” One of the drugs is a synthetic protein called Aicar that, when given to mice, improved endurance by 44 percent after four weeks, even without exercise. The other is an experimental medicine made by GlaxoSmithKline Plc , GW1516, which remodeled the mice’s skeletal muscle and raised their endurance levels by 75 percent when the animals also ran on a treadmill. WADA ’s 2009 prohibited list includes nearly 70 anabolic steroids; about 60 stimulants; hormones; diuretics and other masking agents; blood-doping methods; and several narcotics. The Montreal-based agency oversees anti-drug programs for Olympic- level sports. 2002 Prediction Wadler said he “predicted the future” when in 2002 he wrote a chapter on emerging science and technologies for the textbook “Performance Enhancing Substances in Sport and Exercise.” In it, he discussed the implications of the U.S. Human Genome Project, which was launched in 1990, and examined gene transfer therapy. “The dissection of the human genetic code not only opened a Pandora’s box of diagnostic tools and methods; it has significantly paved the way for an array of therapeutic interventions never conceived before and has spawned the field of pharmacogenetics,” he wrote at the time. WADA held a gene-doping workshop for scientists, ethicists, athletes and representatives from the Olympic movement in March 2002 and again in December 2005 and June 2008. It formed its expert panel on gene doping in 2004. ‘Couch Potato’ Last July, a news release , titled “Exercise in a Pill,” announced the results of the study by the Salk Institute for Biological Studies in San Diego that detailed the effects of Aicar, which it called the “ultimate couch-potato experiment,” as well as the effects of GW1516. The findings may lead to the development of obesity and muscle-wasting-disease treatments, and has implications for the treatment of diabetes and lipid disorders. By activating different genetic switches with the two drugs, the scientists were able to increase fat burning and the mice showed major transformation of skeletal muscle fibers. In giving the mice GW1516 and a regular exercise regimen, for example, they saw a 38 percent increase in “slow twitch” muscle fibers, which relate to a muscle’s endurance. “They have the capacity of changing the patterns of gene expression in cells and tissues, so our view is that that’s a form of gene manipulation,” Theodore Friedmann , chairman of WADA’s Gene Doping Panel, said in a telephone interview. “I don’t think that list is going to shrink. It’s probably going to increase markedly over the years.” Test Procedures Ronald Evans , who is a professor in the Salk Institute’s Gene Expression Laboratory and led the research into the use of Aicar and GW1516 to manipulate signaling pathways, also developed a test to readily detect the drugs in blood and urine, and is working with WADA to enact its implementation. While these drugs can be easily detected, other gene- therapy methods are much more problematic for WADA, and in turn sports associations and leagues. These involve the use of genetic techniques to bring doping substances to muscle tissue and other targets without passing through blood and urine, thereby confounding testing efforts. “It’s better for patients, but it also makes it more challenging because of doping,” Wadler said. Friedmann, who runs a gene-therapy laboratory at the University of California, San Diego, said WADA has mounted a major research program to develop ways to find evidence of gene manipulation. Drug’s Effect “WADA is very forward-looking into designing new forms of doping detection based on the new principle that you don’t look for the drug itself, you look for the effect of the drug,” said Friedmann. In February, the committee will begin reviewing the 2009 list, assessing research and what they’ve learned about doping through everything from medical journals to police investigations. They’ll then tweak the list and turn it over to WADA’s Executive Committee for final approval Oct. 1, giving sports organizations three months to adopt new regulations and understand the changes. To contact the reporter on this story: Mason Levinson in New York atmlevinson@bloomberg.net .

The World’s First GM Human Embryo Could Dramatically Alter the Future (2009, March 20)

The World’s First GM Human Embryo Could Dramatically Alter the Future “The advance of genetic engineering makes it quite conceivable that we will begin to design our own evolutionary progress.” ~Isaac Asimov, famous thinker and sci-fi writer Cornell University researchers in New York revealed that they had produced what is believed to be the world’s first genetically altered human embryo—an ironic twist considering all the criticism the US has heaped on South Korea over the past several years for going “too far” with its genetic research programs. The Cornell team, led by Nikica Zaninovic, used a virus to add a green fluorescent protein gene, to a human embryo left over from an in vitro fertilization procedure. The research was presented at a meeting of the American Society of Reproductive Medicine last year, but details have emerged only after new controversy has emerged over the ethics and science of genetically modifying humans. Zaninovic has pointed out that in order to be sure that the new gene had been inserted and the embryo had been genetically modified, scientists would ideally want to keep growing the embryo and carry out further tests. However, the Cornell team did not get permission to keep the embryo alive. The GM embryos created could theoretically have become the world’s first genetically altered man or woman, but it was destroyed after five days. British regulators form the Human Fertilization and Embryology Authority (HFEA), have warned that such controversial experiments cause “large ethical and public interest issues”. Much of the debate stems from the fact that the effects of genetically altering an embryo would be generational and permanent. In other words, if we create a mutant baby and it grows up to have children of it’s own—they’ll all be mutant gene carriers too. Genes injected into embryos and reproductive cells, such as sperm, affect every cells in the body and would be passed on to future generations. Critics say current humans don’t have the right to tamper with the gene pool of future generations. On the other hand, proponents of such technology say that this science could potentially erase diseases such as cystic fibrosis, hemophilia and even cancer. In theory, any “good” gene could be added to embryos to offset any “bad” genes they are currently carrying. That could potentially mean the difference between life and death for many children. John Harris, the Sir David Alliance Professor of Bioethics at Manchester University, takes it a step further. He believes that as parents, citizens, and scientists, we are morally obliged to do whatever we can genetically to make life better and longer for our children and ourselves. Society currently devotes so much energy and resources towards saving lives, which, in reality, is simply postponing death, he notes. If it is right to save life, Harris reasons, then it should also be right to postpone death by stemming the flow of diseases that carry us to the grave. For Harris, having the ability to improve our species lot in life but refusing to do so, makes little sense. He has a difficult time understanding why some people are so insistent that we shouldn’t try to improve upon human evolution. “Can you imagine our ape ancestors getting together and saying, ‘this is pretty good, guys. Let’s stop it right here!’. That’s the equivalent of what people say today.” Ethicists, however, warn that genetically modifying embryos will lead to designer babies preloaded with socially desirable traits involving height, intelligence and coloring. Dr David King, director of Human Genetics Alert, warns, “This is the first step on the road that will lead to the nightmare of designer babies and a new eugenics.” Harris, however, doesn’t support that argument. He says it’s not about “beauty” it’s about health, and what parent wouldn’t want a healthy child, he asks. “Certainly, sometimes we want competitive advantage [for our children], but for the enhancements I talk about, the competitive advantage is not the prime motive. I didn’t give my son a good diet in the hope that others eat a bad diet and die prematurely. I’m happy if everyone has a good diet. The moral imperative should be that enhancements are generally available because they are good for everyone.” The only other route to equality, he says, is to level down so that everyone is as uneducated, unhealthy and unenhanced as the lowest in society – which would be much more unethical in his opinion. Even though we can’t offer a liver transplant to all who need them, he says, we still carry them out for the lucky few. “Much better to try to raise the baseline, even if some are left behind.” The Human Fertilization and Embryology Bill in currently under consideration in Britain will likely make it legal to create GM embryos in that country, but only for research—implantation in the womb will still be banned—at least for now. However, ethicists believe that the legislation could easily be relaxed even further in the future. People who believe that genetically modified humans is something way into the future might want to consider that many experts are worried that some forms of it are already happening in the sports world. Faster, bigger, better, stronger—in theory, the single most effective way to radically alter your physical capacities is to manipulate your genes. Athletes are beginning to take notice. Now that we’ve mapped out the human genome and identified exactly which genes make you buff, tough and rough—experts are concerned about the future of genetic doping. Gene doping could spawn athletes capable of out-running, out-jumping and out-cycling even the world’s greatest champions. However, researchers at the University of Florida are attempting to prevent that from happening by detecting the first cases of gene doping in professional athletes before the practice becomes mainstream. Montreal-based World Anti-Doping Agency (WADA), responsible for monitoring the conduct of athletes, is working with investigators around the globe to develop testing to identify competitors who have injected themselves with genetic material that is capable of enhancing muscle mass or heightening endurance. “If an athlete injects himself in the muscle with DNA, would we be able to detect that?” asked one of France’s leading gene therapy researchers, Philippe Moullier, M.D., Ph.D., director of the Gene Therapy Laboratory at the Universite de Nantes in France. Right now, he says the answer is clearly “no”. But that may soon change. The UF scientists are among several groups collaborating with national and global anti-doping organizations to develop a test that can detect evidence of “doped” DNA. “WADA has had a research program in place for some years now, to try to develop tests for gene-based doping,” said Theodore Friedmann, M.D., head of the agency’s panel on genetic doping and director of the gene therapy program at the University of California, San Diego. Nearly every day now we are inundated with new genetic discoveries. Scientists can now pinpoint many specific genes including being lean, living a long life, improved self-healing, thrill seeking behavior, and having an improved memory among many other incredible traits. Many believe that these genes can be manipulated in ordinary humans, in effect creating Super-Mutants. Theoretically, options are nearly limitless. Even a gene that exists in another species could be brought over to a human cell. Imagine some of the incredible traits of the animal kingdom that some humans don’t possess such as night vision, amazing agility, or the ability to breath underwater. The precedence for these types of radical changes is already in place. Experimental mice, for example, were successfully given the human ability to see in color. If animals can be engineered to have human traits, then humans can certainly be mutated to have desirable animal traits. It is even thought possible to so drastically alter human genomes that a type of superhuman species could emerge. The fear with germline engineering is that since it is inheritable, offspring and all succeeding generations would carry the modified traits. This is one reason why this type of engineering is currently banned- it could lead to irreversible alteration of the entire human species. Ethics, not scientific limitations, is the real brick wall. Most scientists believe manipulating genes in order to make an individual healthy is a noble and worthwhile pursuit. Some are against even that notion, arguing that historically amazing individuals have sometimes been plagued by genetic mental and physical disorders, which inadvertently shaped the greatness of their lives. Should we rob the human race of character shaping frailty? Very few scientists would dare to publicly endorse the idea of using genetic engineering to make a normal, healthy individuals somehow superior to the rest of the human race. “The push to redesign human beings, animals and plants to meet the commercial goals of a limited number of individuals is fundamentally at odds with the principle of respect for nature,” said Brent Blackwelder, President of Friends of the Earth in his testimony before the Senate Appropriations Committee. However, would it be so bad if the human race were slightly improved? What if a relatively simple procedure could make an individual and his or her offspring resistant to cancer? After all, Nature isn’t always right. Nature has naturally selected many people to carry the burden of uncomfortable and often lethal genetic disorders. If nature knows best, then shouldn’t we quit trying to “improve” upon nature by “curing” people of genetic conditions we consider inferior? Many say we shouldn’t change human genetics, UNLESS it’s the RIGHT thing to do. Who gets to decide where the line is between righteous endeavor and the corruption of nature? These are the questions facing our generation. Posted by Rebecca Sato Related Galaxy posts: Can Humans Live to 1,000? Some Experts Claim We Can — Others Want to Prevent That The "Mickey Mouse" Experiment -Mice with Human Eyes Enhancing Evolution: Do Humans have a Moral and Ethical Duty to Improve the Human Race? Are We Close to Creating Super-Mutant Humans? The Story of a Biologist & the Extension of the Human Life Span Scientists Bio-engineer a Virus that Destroys Cancer Cells "Mind Children": Transhumanism & the Search For Genetic Perfection Sources & Related Stories: http://www.sciam.com/article.cfm?id=000E7ACE-5686-10CF-94EB83414B7F0000 http://www.timesonline.co.uk/tol/news/uk/science/article3908516.ece http://www.andhranews.net/Health/2008/May/11-Scientists-create-first-44379.asp http://press.princeton.edu/titles/8480.html

WADA eyes research on gene doping (2009, Jan 16)

WADA eyes research on gene dopingDANIA BOGLE, Observer staff reporter bogled@jamaicaobserver.com Friday, January 16, 2009

THE World Anti-Doping Agency (WADA) is investing lots of money and resources into conducting research into how to detect gene doping as it continues its fight against cheating in sport.

WADA programmes development manager, Tom May, made the revelation at the panel discussion on Drug Free Sport during the Jamaica Anti-Doping Agency's two-day Symposium which wrapped up yesterday at the Knutsford Court Hotel in Kingston.

May spoke to advances in science which have already developed the ability to clone animals and possible future advances which might help dishonest athletes cheat.

Gene therapy already allows for the alteration of DNA to help the body fight certain diseases.

May explained that through gene doping an athlete could manipulate the body to grow bigger muscles or help them develop at a faster rate.

"We don't think it's quite in place but we don't think we can wait for it to occur," he said.

The WADA has already pumped close to US$8 million into the gene doping research.

Meanwhile, International Association of Athletics Federation (IAAF) Medical and Doping Commission member, Dr Herb Elliott, also noted that the International Olympic Committee (IOC) and IAAF were also collaborating on a number of projects on the subject, including one at the Royal Caroline Institute in Sweden.

He discouraged the use of doping in sport, saying, "Doping Kills", adding that the dangers or using anabolic steroids included developing liver, heart, and kidney disease as well as epilepsy.

"It's one way of killing yourself by degrees," Elliott said. He added that in men, impotence and low sperm count were among the dangers, and mentioned the case of a female Bulgarian athlete who became pregnant while doping. The child, he said, was now a virtual 'vegetable' needing to visit the hospital at least once per week.

"Young ladies, don't take any foolishness it you wish to become a mother someday," Elliott implored.

The JADCO Symposium was part funded by GraceKennedy and UNESCO and involved athletes and officials from all national sporting associations.

Genetic Engineering Limits—A Planet Responds (2008, Dec 22)

Genetic Engineering Limits—A Planet RespondsRichard Hayes December 22nd 2008 Cutting Edge Genetics Analyst Over the past half century, the world has been transformed through rapid developments in communications, transportation, weaponry, and trade. A vast infrastructure of intergovernmental institutions has been established to help ensure that these and related developments generate more benefit than they do harm. These include global institutions such as the United Nations and the World Bank, regional groups such as the European Union and the African Union, and those with issue-specific agendas such as the Intergovernmental Panel on Climate Change and the World Health Organization. Although the record of these institutions is far from perfect, a world without them would be fraught with even more risk than it is today. The rapid development of powerful new human biotechnologies raises precisely the sort of questions that such intergovernmental institutions are positioned to address. If developed wisely, these technologies could help prevent and cure diseases that have afflicted humanity for millennia; if misapplied, they could pose new and profoundly consequential risks. Detailed knowledge of the human genome might lead to improved medical diagnostics, but could also lead to a Gattaca-like world in which affluent couples genetically modify their embryos in an attempt to create “designer babies.” The creation of clonal human embryos gives researchers tools to help investigate the developmental origin of congenital diseases, but brings us closer to the day when rogue scientists might attempt to create live-born human clones. Genetic interventions intended to help those suffering from degenerative muscular diseases could be used by athletes to illicitly enhance their strength and endurance. Many countries are adopting comprehensive national policies that establish guidelines, regulations, and laws stipulating which applications of the new human biotechnologies are permitted and which are not. But the greater majority of the world’s countries have not adopted policies regarding these technologies. Intergovernmental institutions are in a position to play major leadership roles in ensuring the proper use of the new human biotechnologies. They can promote greater understanding of both the benefits and the risks that these technologies pose; develop statements of principles to guide national policies; prepare model national legislation; and take the lead in negotiating binding multilateral treaties and conventions.

It will not be an easy task to come to formal agreement on even a minimal set of international principles and policies. These technologies are new and the issues involved are complex. But the encouraging news is that many key intergovernmental institutions have already begun taking steps to address the new human biotechnologies, and broad areas of at least implicit agreement are evident. The United Nations In 2001 France and Germany proposed a binding UN treaty calling for a prohibition on human reproductive cloning. An early procedural vote suggested unanimous support for this measure. A significant number of countries subsequently expressed opposition to banning reproductive cloning without simultaneously banning the use of cloning for research purposes. This led to extended controversy, and the debate became, essentially, a debate over the acceptability of research cloning. By 2003 it became clear that a consensus concerning research cloning could not be achieved. In 2005 a non-binding declaration opposing both research cloning and reproductive cloning was introduced and received a plurality of votes (46 percent), which under UN rules makes it the official UN position. However, the lack of a clear consensus rendered moot any proposals to promote this position further. In the absence of a formal global treaty, individual countries have proceeded to adopt their own policies addressing human cloning. By 2007 human reproductive cloning had been banned by 59 countries—including the great majority of those with robust biomedical research sectors—and approved by none. In 2007 scholars associated with the United Nations University noted that the prohibition of reproductive cloning might be considered to have attained the status of customary international law. This was not the case for cloning for research purposes, however, as policies adopted by individual countries varied widely. UNESCO The United Nations Educational, Social and Cultural Organization (UNESCO) is a specialized agency of the United Nations working to promote international collaboration through education, science, and culture. In 1993 UNESCO established a Bioethics Programme within its Division of the Ethics of Science and Technology. The Programme is led by the International Bioethics Committee (IBC), consisting of 36 outside experts, and the Intergovernmental Bioethics Committee (IGBC), consisting of representatives from 36 member states. The Bioethics Programme has sponsored three major nonbinding international agreements. The Universal Declaration on the Human Genome and Human Rights was adopted unanimously by the UNESCO General Conference in 1997 and ratified by the UN General Assembly in 1998. The declaration calls for member states to undertake specific actions, including the prohibition of "practices which are contrary to human dignity, such as reproductive cloning of human beings." It also calls on the IBC to study "practices that could be contrary to human dignity, such as germline interventions." The International Declaration on Human Genetic Data was adopted in 2003. The declaration is intended "to ensure the respect of human dignity and protection of human rights and fundamental freedoms in the collection, processing, use and storage of human genetic and proteomic data, and of the biological samples from which they are derived, in keeping with the requirements of equality, justice and solidarity, while giving due consideration to freedom of thought and expression, including freedom of research." The Universal Declaration on Bioethics and Human Rights was adopted in 2005. The declaration used a human rights framework to establish normative principles in fifteen areas, including human dignity and human rights; equality, justice, and equity; and protecting future generations. These principles cover a wider range of issues than did the previous two bioethics declarations. UNESCO took the lead in negotiating the International Convention Against Doping in Sports in collaboration with the World Anti-Doping Agency (WADA), which had been established earlier by the International Olympic Committee. The Convention includes language banning the use of genetic technology to enhance athletic performance in official athletic events, referred to as "gene-doping." It entered into force on February 1, 2007, and has been ratified by 86 countries. The earlier Copenhagen Declaration on Anti-Doping in Sport has been signed by 192 countries. Council of Europe The Council of Europe is an international organization of 47 member countries working to foster democracy and human rights. It maintains a Bioethics Division, guided by a Steering Committee on Bioethics. The Council's Convention on Biomedicine and Human Rights was opened for signatures in 1997 and went into force in 1998. As of March 2008 it had been signed or ratified by 34 countries. It explicitly prohibits inheritable genetic modification, somatic genetic modification for enhancement purposes, social sex selection, and the creation of human embryos solely for research purposes. The Convention is perhaps the single most well-developed intergovernmental agreement extant addressing the new human biotechnologies, banning human reproductive cloning through an Additional Protocol on the Prohibition of Cloning Human Beings, which went into force in 1998. European Union With 27 member states, the European Union and its constituent bodies play a major and growing role in European policy integration. Article 3 of the EU's Charter of Fundamental Rights, entitled "Rights to the Integrity of the Person," prohibits human reproductive cloning, "eugenic practices, in particular those aiming at the selection of persons," and "making the human body and its parts as such a source of financial gain." Importantly, the EU disburses some $5 to 6 billion U.S. every seven years for biomedical and health-related research, and sets policies on the use of these funds. Under the current programme, which runs from 2007 to 2013, these funds cannot be used for research that involves human reproductive cloning, inheritable genetic modification, the creation of human embryos solely for research purposes, or the destruction of human embryos.

African Union The African Union (AU) is an intergovernmental organization consisting of most African nations. At its 1996 Assembly of Heads of State, the AU (then called the Organization of African Unity) approved a Resolution on Bioethics that affirmed "the inviolability of the human body and the genetic heritage of the human species" and called for "supervision of research facilities to obviate selective eugenic by-products, particularly those relating to sex considerations." World Health Organization The World Health Organization (WHO) and its governing body, the World Health Assembly, are specialized agencies of the United Nations that address issues of international public health. In 1997 the WHO called for a global ban on human reproductive cloning. In 1999 a Consultation on Ethical Issues in Genetics, Cloning and Biotechnology was held to help assess future directions for the WHO. The draft guidelines prepared as part of this consultation, Medical Genetics and Biotechnology: Implications for Public Health, called for a global ban on inheritable genetic modification. In 2000 WHO Director-General Dr, Gro Harlem Brundtland reiterated opposition to human reproductive cloning. In September 2001 the WHO convened a meeting to review and assess "recent technical developments in medically assisted procreation and their ethical and social implications." The review covered, among other items, preimplantation genetic diagnosis, intracytoplasmic sperm injection, and cryopreservation of gametes and embryos. In February 2002 the WHO repeated its opposition to human reproductive cloning and cautioned against banning cloning techniques for medical research. In October 2002 the WHO established a Department of Ethics, Equity, Trade, and Human Rights to coordinate activities addressing bioethical issues. Group of Eight The Group of Eight (G-8) is an international forum for the governments of Canada, France, Germany, Italy, Japan, Russia, the United Kingdom and the United States. It convenes annual summits to consider issues of common concern, typically of an economic or military nature. At its June 1997 summit in Denver, Colorado, the G-8 called for a worldwide ban on human reproductive cloning. According to the Final Communique of the Denver Summit of the Eight, the leaders of the G-8 nations agreed "on the need for appropriate domestic measures and close international cooperation to prohibit the use of somatic cell nuclear transfer to create a child." The Consensus There appears to be broad support for applications intended to prevent or cure disease, but strong opposition to applications that involve selecting or modifying the genes of future generations for non-medical purposes. There is wide opposition as well as to human reproductive cloning and to non-medical genetic modification, including athletic “gene doping.” The one practice for which a consensus does not appear to be in the cards is medical research involving human embryos. Some intergovernmental institutions explicitly support this and others oppose it. Real opportunities exist for one or more respected intergovernmental institutions to mount a global initiative to clarify, codify and promote—indeed, to universalize—those human biotech policies about which broad agreement exists, while agreeing to disagree on the fewer number about which disagreements persist. Such an initiative would go a long way towards ensuring that these powerful new technologies are used in the best interests of all humanity. Cutting Edge Genetic Analyst Richard Hayes is executive director of the Center for Genetics and Society and can be found at www.geneticsandsociety.org. This article draws on an appendix of an article published by Science Progress, and on data compiled on CGS's BioPolicyWiki.

For a full account of the state of policies among individual countries see The Quest for Global Consensus on Human Biotechnology in The Cutting Edge News Nov 24, 2008.

Gene doping in sport: fact or fiction? (2008, Dec 6)

Gene doping in sport: fact or fiction?Experts believe it is only a matter of time before athletes manipulate their genetic material to gain an unfair advantage despite the current lack of proven cases. A science journalist, who has published a novel on the theme, and a scientist working in the field of genetics talked to swissinfo about the likelihood and dangers of gene doping in sport. Since the times of ancient Greece, a minority of athletes have employed a variety of potions to artificially boost their performance. More recently, amphetamines, anabolic steroids and hormones have been the drugs of choice. The World Anti-Doping Agency (WADA) has recently turned its attention to the threat of gene doping and officially banned the practice in 2003. There have already been suspicions of some athletes using the gene therapy Repoxygen to increase their red blood cell count and thereby allow the body to absorb more oxygen. Professor Max Gassmann of Zurich University's Institute of Veterinary Physiology has manipulated the erythropoietin (EPO) gene of mice to produce more oxygen carrying red blood cells – a process that could eventually be transferred to humans. Gassmann does not think gene doping has infiltrated sport at the moment but believes some people may already be testing its potential, just as beneficial gene therapy is currently undergoing clinical trials. "I can hardly imagine that we had a gene doping cheat winning at the Beijing Olympics," he told swissinfo. "But there has been doping throughout history and if gene doping becomes viable then you cannot stop it, because people want to win." Fictional leap Author Beat Glogger has taken the theory a stage further by writing a thriller – "Run For My Life" – about genetically modified athletes. Glogger, also a science journalist, and Gassmann contributed to a Swiss sports ministry document warning about the risks of gene doping. Scientists have already identified more than 150 genes that potentially influence performance in sports. These include genes that control muscle growth, muscle speed and the production of red blood cells. "I take the next step into fiction by saying it is possible to manipulate the genes that control speed, power, endurance and even mental strength. These are the four key factors for athletic performance," Glogger told swissinfo. There are many cases of people with naturally malfunctioning genes. Most of the time this results in health problems, such as muscular dystrophy, but the rare occurrence of a mutation can also bring benefits. Finnish cross-country skiing legend Eero Mäntyranta won race after race in the 1960s because of a natural genetic mutation that helped his blood absorb large amounts of oxygen. It would be very hard in future to determine if such a case was caused by nature or gene manipulation, according to Glogger. "If, after the introduction of the relevant genes, the body produces more EPO or testosterone by itself then you cannot detect it - it looks like you are a natural," he said. To die for However, athletes run a high risk of developing serious diseases such as cancer or even dying if they submit to gene manipulation that is still in the early days of scientific development. Gassmann's genetically modified mice live only half as long as other mice. Scientists know how to modify genes and introduce them into the body, but not how to control the behaviour of such genes once they have been implanted. "Whatever you put into the body is hard to control. If you realise it is no good then it is almost impossible to stop, and that is what could happen with gene cheating athletes," Gassmann said. "It is easy to switch on a light but much more complicated to dim it." One method of controlling modified genes is to develop drugs that act like on and off switches, but this process is still in its infancy. "Gene doping could be undetectable and it could improve performance but you could also die," Glogger warned. Just like the characters in his book. swissinfo, Matthew Allen in Zurich

Gene doping - the battleground (2008, Nov 15)

I interviewed for Simon, got him to Florence for the gene doping meet, gave him a copy of my book and he didnt even bother to quote me. Bad form Simon! Gene doping - the battleground Telegraph Sport take a look at the front-line of drug-enhanced sport.

By Simon Hart Last Updated: 5:47PM GMT 15 Nov 2008 Myostatin What is it? A protein that inhibits muscle growth in animals and humans. How can it benefit athletes? If the gene responsible for myostatin is switched off, muscles will increase in size. Does gene modification work? Successful in trials on mice and dogs and set to go into commercial use as a veterinary treatment next year. Untested on humans but known to produce an immune reaction, so risky. Can it be detected? No, but researchers hope to find ways of testing for the virus used to deliver the gene. IGF-1 What is it? Insulin-like growth factor 1, a natural protein that promotes muscle- growth and repair but declines with age. How can it benefit athletes? Over-production of IGF-1 will cause an increase in muscle mass and strength. Does gene modification work? Successful in animal trials but human application still being tested. Has to be injected locally into muscle because high levels in the bloodstream cause problems with other tissues. Can it be detected? Not without a muscle biopsy. EPO What is it? A naturally occurring protein that produces red blood cells. How can it benefit athletes? A richer supply of oxygen-carrying blood cells reduces fatigue in muscles, which makes EPO so beloved of endurance athletes such as road cyclists and cross-country skiers. Does gene modification work? Offers prospect of permanent source of extra EPO rather than short-term burst. Trials on monkeys have had mixed results, with some producing dangerously high amounts of EPO and others developing immune responses. Very risky for humans at present. Can it be detected? Preliminary research suggests it will be detectable to drug-testers. What if... ...genetically modified animals were allowed into sport? By Andrew Baker · Lewis Hamilton dedicates second world motor racing title to the artificially enhanced hamsters who turn the wheels of his McLaren. “I’d have been nowhere without Nibbles, Whiflet, Coco and Mr Muscles,” the driver acknowledges. · Ranks of matadors decimated by giant, four-horned bulls. · Scientifically improved chimpanzee wins Tour de France. “The team pay me peanuts,” the muscular ape tells reporters on the Champs Elysees.’’What could be better?” · Air-breathing octopus with eight rackets wins Wimbledon singles title.Defeated finalist Andy Murray vows to clone himself and enter next year’s men’s doubles. · Greyhound Derby won by Tiny, a powerful Chihuahua who runs between his opponents’ legs. · Dee Caffari towed to victory in Vendee Globe round-the-world yacht race by killer whale fitted with genetic SatNav. “To be honest, I read my book most of the way”, the skipper confesses.

Drug cheats may benefit from animal test Lee Sweeney, professor of physiology at the University of Pennsylvania, is a popular man in the world of sport.

By Simon Hart Last Updated: 5:48PM GMT 15 Nov 2008 He gets between five and 10 emails a week from athletes, some from Britain, and so many phone calls that his secretary has stopped putting them through. And that is in a quiet week. If he publishes an academic paper or does a media interview, a flurry of 50 or more calls and emails usually follows, as it did 10 years ago when he first revealed his 'mighty mice' to the world at a meeting of the American Society for Cell Biology – laboratory mice with enormous muscles that retained their strength and regenerative ability even when the animals reached old age. Sweeney's super-strong rodents were the product of his pioneering research into gene transfer technology and the implications were clearly not lost on the athletes and coaches who got in touch, one of whom offered $100,000 for what the mice were getting. Shockingly, Sweeney also received a request from a high school American football coach for his entire team to be genetically modified. Sweeney told him what he is still telling everyone a decade later, that bulking up on gene therapy is not yet safe enough for humans and would require heavy-duty immune suppression. He always gets the same response. "Even if I explain to them that to make it work might require all sorts of heroic measures, they basically say, 'Fine. I'll do it'. And if it's a matter of money, they'll get the money." Sweeney has never been contacted by a name he recognises – "I don't get Barry Bonds calling me up" – and says most of the would-be guinea pigs appear to be young athletes trying to make the big time. "Some of them are from Europe," he says. "I get quite a few from the UK and Germany." He says he would feel uneasy about passing on their names to the anti-doping authorities but is sufficiently concerned to have accepted a seat on the gene-doping panel of the World Anti-Doping Agency (Wada), who are funding eight research projects on gene-doping detection in a desperate attempt to stay ahead of the cheats. Sweeney is bracing himself for another surge of calls and emails next year when his work moves from the laboratory to the commercial world with a muscle-building gene therapy for dogs. It will be available not only for dogs with muscular diseases but dogs that are just old and immobile who, after an injection in their liver, could soon be running around like puppies again. "We are now in the final stages of getting all the approvals to offer this through the veterinary hospital as a treatment to try to improve strength in pet dogs," he says. "As the dogs get weak their owners get upset that they can't walk around any more. So we're hoping that within the next year we will begin the era of genetic enhancement in dogs." Sweeney hopes his new canine anti-aging treatment will be just the start. Humans have the same gene that Sweeney is manipulating in dogs and the next step will be to treat people with serious genetic diseases such as muscular dystrophy. Ultimately, he hopes to give the elderly, like the pampered pooches of Pennsylvania, greater muscle strength and mobility in their final years. But any breakthrough will inevitably be seized upon by dope cheats in the same way that clinical drugs such as steroids, human growth hormone and the red blood cell-boosting EPO soon found their way into kit bags. With the prospect of as yet undetectable, lifelong enhancement, how could any drug cheat resist? As gene transfer technology enters the medical mainstream as a treatment for numerous diseases from blindness to cancer, scientists are agreed it is only a matter of time before it crosses over into sport. Some predict that London 2012 could be the first genetically modified Olympic Games. Others say the Beijing Games may already have that dubious honour. "We do not have any proof that gene doping has been practised yet but we have had signs that people are interested and they are looking at it," says Arne Ljungqvist, chairman of the International Olympic Committee's medical commission. Evidence that sport is closing in on the science came two years ago when German police discovered an email sent by Thomas Springstein, the disgraced former coach of sprinter Katrin Krabbe, complaining about how difficult it was to get hold of Repoxygen, a sophisticated agent for delivering EPO by means of gene transfer. Springstein was later convicted of giving doping substances to children. Cyclists are also beating at the door. A French gene expert, Professor Philippe Moullier, had his eyes opened when a couple of former Tour de France cyclists paid a visit to his laboratory in Nantes, where he is experimenting on EPO genes in monkeys as a treatment for anaemia. The pair were working for an anti-doping organisation – or at least that is what they told Moullier – and said they wanted to learn about his research. "The thing that really surprised me was that when I told them it was just the start of the technology, they told me that the riders would not care," says Moullier. "They would go for it if they had a chance to be undetectable. "They said there were kids in the Tour de France who would do anything just to have the most advanced technology. It's a concern because there are still severe adverse side-effects. We are taking such care before it comes to patients so we are scared to see guys who are ready to use it. It's terrible." If the risks are no deterrent, cheats still have to overcome the complexity of gene modification, though if the BALCO conspirators were able to find a biochemist capable of altering a molecule and synthesising a new designer steroid, engaging the services of gene expert should not be beyond the wit and wealth of an athlete determined enough to cheat. "I think the real threat is from scientists and clinicians who decide they want to make money off the athletes to make this available," says Sweeney. "There are people in India and China who will do stem cell transplantation in anyone who'll pay them. There is no evidence anything they are doing has any effect on the patients but they'll do it for money. At some point someone will say, 'I'll do immune suppression if you want me to and I'll put in any gene you want'." Sweeney admits that day could not be far away. "The bottom line is that we're going to be able to do genetic enhancement for serious diseases," he says. "It's not beyond the realm of possibility that over the next few years, if someone has sufficient help and sufficient motivation, it could be done outside that arena."

Elderly dogs to be offered genetic enhancement to make them young again Frail elderly dogs could be injected with genes which allow them to run around like puppies, with technology which could be approved by next year.

Simon Hart and Laura Donnelly Last Updated: 12:09AM GMT 16 Nov 2008 An American professor is preparing to market a form of canine gene therapy, which would see dogs injected with substances which switch off the genes that regulate their muscle growth. Prof Lee Sweeney, from the University of Pennsylvania, has pioneered research into gene transfer technology, a field in which poorly functioning and abnormal genes are manipulated, switched off or replaced. Ten years ago he created "mighty mice" in the lab with enormous muscles and strength in old age. Now he says experiments on dogs have been so successful that he is preparing to market the treatments to owners of ageing pets across the United States. He said: "We are now in the final stages of getting all the approvals to offer this through the veterinary hospital as a treatment to try to improve strength in pet dogs. "As the dogs get weak their owners get upset that they can't walk around any more. So we're hoping that within the next year we will begin the era of genetic enhancement in dogs." Under the therapy, dogs would be given an injection into the liver of an inhibitor which switches off the gene which produces myostatin, a protein which inhibits muscle growth in animals and humans. The treatment has passed laboratory trials, but regulatory authorities are now discussing whether the dogs would have to be held in quarantine after treatment, because of possible risks if humans came into contact with their waste after the procedure, Prof Sweeney said. Scientists hope the same technology could be used in humans, to treat serious genetic diseases such as muscular dystrophy. Human trials of gene therapy have faced difficulties due to the risks of introducing new genes into cells or unintentionally interfering with genes other than those being targeted, which can include inducing cancers. In some cases the immune system may also have to be suppressed, which can also have increase the risk of infection and other diseases. Despite the dangers attached to the use of genetic transfer in humans, the professor of physiology is regularly contacted by athletes desperate to use the technology to enhance their performance. Gene doping is one of the greatest fears of sports regulators, because injections of genes directly into muscle would be almost impossible to detect. Prof Sweeney says every week he refuses approaches from athletes who will do anything to get their hands on genetic material, including one from a high-school football coach who wanted his entire team to be genetically modified. He tells them that bulking up on gene therapy is not yet safe enough for humans, and would require heavy-duty immune suppression, even if it were legal. Prof Sweeney said he always gets the same response: "Even if I explain to them that to make it work might require all sorts of heroic measures, they basically say 'Fine, I'll do it'.

Enhanced Olympians

How "Gene Doping" Could Create Enhanced OlympiansRick Lovett for National Geographic News August 14, 2008 Although China has aggressively tested athletes at the Beijing Olympics for performance-enhancing drugs, no case of so-called gene doping has yet been detected.

But experts say Oympic athletes may soon be able to genetically enhance their muscles to be faster, stronger, and better able to recover after workouts—if they aren't already.

Gene doping uses techniques similar to gene therapies developed to treat muscle-wasting diseases, such as muscular dystrophy.

Injected into an athlete, a harmless virus could carry a performance-enhancing gene and splice it into a muscle cell, said Theodore Friedmann, a gene therapy researcher at the University of California, San Diego (quick genetics overview ).

A synthetic virus called Repoxygen, for example, has been used this way in animal tests to insert a gene for erythropoietin (EPO), a hormone that tells the body to make more red blood cells, which carry oxygen to muscles.

EPO is important in the treatment of anemia, and it's also a favorite doping agent for cyclists, runners, and cross-country skiers.

Athletes are well aware of Repoxygen's potential: A German coach was accused of trying to obtain it before the 2006 Winter Olympics.

Gene-doping may also work by modifying genes that are already in an athlete's cells but whose functioning he or she might want to control.

It's not a new concept. Many ordinary drugs can have this effect, as can daily activities.

"Training and athletic workouts probably do their work at least partly by modifying the expression of genes," Friedmann said.

Cheating Delayed?

A few years ago it was believed that wholesale gene doping was just around the corner. But clinical trials of legitimate gene-therapy methods have run into hitches.

"There have been deaths," Friedmann said.

And an otherwise successful attempt to cure severe combined immunodeficiency disorder—the so-called bubble-baby syndrome—was halted when some of the children developed leukemia.

Also the gene-therapy viruses that might lend themselves to cheating don't work as easily as had been hoped.

The problem is that the human immune system tries to fight them off, said H. Lee Sweeney, a physiology professor at the University of Pennsylvania.

"That's caused most of the trials to stop," Sweeney said.

In future tests patients may have to be hospitalized during treatment, with their immune systems suppressed.

"I'm not sure an athlete is going to be willing to be put in the hospital for six weeks right in the middle of their training," Sweeney said.

"Naked" DNA

Less ambitious forms of gene doping may be right around the corner, though.

Dispensing with the troublesome virus-based delivery system, this type of doping would inject "naked" DNA directly into a muscle.

Nearby cells would take up some of the DNA, and if that DNA controls an important hormone, like EPO or human growth hormone (HGH), it might be enough to do the job.

It's not so different from injecting EPO or HGH directly, but it would save money, because it would only have to be done once.

"You could probably get a molecular-biology major to make it for you for a couple hundred dollars," Sweeney said.

Testing for this type of doping would be easy, though, since the athlete's body would still carry too much of the hormone.

Testing for full-blown gene doping will be more difficult. Just be safe, the International Olympic Committee is hanging on to Olympians' genetic samples for eight years, in case testing methods catch up with currently indetectable doping methods.

For its part, the World Anti-Doping Authority is working on a test to determine the expression of all 25,000 of the human body's genes, looking for abnormal patterns, said the University of California's Friedmann, who chairs the agency's genetics panel.

But sports authorities may eventually have to accept gene doping as a fact of life, scientists say.

The same techniques that could create superathletes will likely also help ordinary people stay fitter and healthier.

"I think [gene therapy] will change the way we all live and how health care treats the average person," the University of Pennsylvania's Sweeney said.

"You can't legislate it out of sport, because you'd be depriving people of a standard of care."

Finding the golden genes (2008, Aug 13)

Finding the golden genesBy Patrick Barry Web edition : Wednesday, August 13th, 2008

Advances in gene therapy could tempt some athletes to enhance their genetic makeup, leading some researchers to work on detection methods just in case. Click here to see an animation of how one gene therapy can enhance endurance. This month — 8/8/08, to be precise — the curtain rose on what many experts believe could prove to be the first genetically modified Olympics. For the unscrupulous or overdriven Olympic athlete, the banned practice of “doping” by taking hormones or other drugs to enhance athletic prowess may seem so last century. The next thing in doping is more profound and more dangerous. It’s called gene doping: permanently inserting strength- or endurance-boosting genes into DNA. “Once you put that gene in, it’s there for the rest of that person’s life,” says Larry Bowers, a clinical chemist at the U.S. Anti-Doping Agency in Colorado Springs, Colo. “You can’t go back and fish it out.” Scientists developed the technology behind gene doping as a promising way to treat genetic diseases such as sickle-cell anemia and the “bubble boy” immune deficiency syndrome. This experimental medical technology — called gene therapy — has begun to emerge from the pall of early failures and fatalities in clinical trials. As gene therapy begins to enjoy some preliminary successes, scientists at the World Anti-Doping Agency, which oversees drug testing for the Olympics, have started to worry that dopers might now see abuse of gene therapy in sport as a viable option, though the practice was banned by WADA in 2003. “Gene therapy has now broken out from what seemed to be too little progress and has now shown real therapies for a couple diseases, and more coming,” says Theodore Friedmann, a gene therapy expert at the University of California, San Diego and chairman of WADA’s panel on gene doping. While gene therapy research has begun making great strides, the science of detecting illicit use of gene therapy in sport is only now finding its legs. To confront the perceived inevitability of gene doping, Friedmann and other scientists have started in recent years to explore the problem of detecting whether an athlete has inserted a foreign gene — an extra copy that may be indistinguishable from the natural genes — into his or her DNA. It’s proving to be a formidable challenge. Genetic makeup varies from person to person, and world-class athletes are bound to have some natural genetic endowments that other people lack. Somehow, gene-doping tests must distinguish between natural genetic variation among individuals and genes inserted artificially — and the distinction must stand up in court. Scientists are fighting genetics with genetics, so to speak, enlisting the latest technologies for gene sequencing or for profiling the activity of proteins to find the telltale signs of gene doping. Some techniques attempt the daunting search for the foreign gene itself, like looking for a strand of hay in an enormous haystack. But new research could also lead to an easier and more foolproof approach: detecting the characteristic ways that an inserted gene affects an athlete’s body as a whole. Resurgence of gene therapy In 1999, 18-year-old Jesse Gelsinger died during a gene therapy trial for a rare liver disease. Investigators later attributed his death to a violent immune reaction to the delivery virus rather than to the therapeutic gene. His death was a major setback for the field. It also may have scared away early would-be gene dopers. In recent years, safety and efficacy of gene therapy have shown signs of progress in numerous clinical trials for conditions ranging from early-onset vision loss to erectile dysfunction. As scientists develop ways to use safer, weaker viruses for delivery, and as gene therapies wind their way through clinical trials, athletes and coaches might start to see gene doping as even more viable than they already do. In the courtroom during the 2006 trial of Thomas Springstein, a German track coach accused of giving performance-enhancing drugs to high-school–age female runners, prosecutors read aloud an e-mail Springstein had written that would shock the sports world. “The new Repoxygen is hard to get,” the e-mail read, according to press reports. “Please give me new instructions soon so that I can order the product before Christmas.” Repoxygen isn’t merely another doping drug such as a hormone or the latest designer steroid — it’s an experimental virus designed to deliver a therapeutic gene and insert it into a person’s DNA. British pharmaceutical company Oxford BioMedica developed Repoxygen in 2002 as a treatment for severe anemia. The therapy “infects” patients with a harmless virus carrying a modified gene that encodes erythropoietin, a protein that boosts red blood cell production. This protein, often called EPO, is itself a favorite among dopers seeking to increase their oxygen capacity, and hence their endurance. Viruses have the natural ability to inject genetic material into their host’s DNA. The host’s cells can translate that gene into active proteins as if the foreign gene were the cells’ own. So by delivering the gene for EPO within a virus, Repoxygen could potentially increase the amounts of EPO protein — and the change would be permanent. Athletes might also be tempted by perhaps the most tantalizing gene therapy experiment of all: the “mighty mouse.” In 1998, H. Lee Sweeney and his colleagues at the University of Pennsylvania School of Medicine injected mice with a virus carrying a gene that boosted production of insulin-like growth factor 1, or IGF-1, a protein that regulates muscle growth. As a result, the mice had 15 percent more muscle mass and were 14 percent stronger than untreated mice — without ever having exercised. The treatment also prevented the decline of muscle mass as the mice grew older. Other genetic paths to increase muscle strength and volume could include the gene for human growth hormone or segments of DNA that block a protein called myostatin, which normally limits muscle growth. Endurance might also be boosted by the gene encoding a protein called peroxisome proliferator-activated receptor delta, or PPAR-delta. Mice engineered to have extra copies of this gene hopped onto a treadmill and, without ever having trained, ran about twice as far as unaltered mice. The extra PPAR-delta improved the ability of the mice’s muscles to use fat molecules for energy, and it shifted the animals’ ratio of muscle fiber types from fast-twitch toward slow-twitch fibers — a change that would improve muscle endurance in people as well. Ronald Evans and his colleagues at the Salk Institute for Biological Studies in La Jolla, Calif., published the research in 2004. Since then, Evans says, he has been routinely approached by curious coaches and athletes. “I’ve had athletes come to my lectures and go to the microphone and say, ‘If I took this drug, would it work with EPO and growth hormone?’ I mean, they would ask this publicly,” Evans says. “Based on athletes I’ve talked with, I’d say that it’s a reasonable possibility that gene doping will be used in this Olympics, and I think there’s a very high probability that it will be used in the next Olympics,” he says. Elusive signs Around the time that Evans was announcing his “marathon mouse” results, WADA kicked off a funding program to focus scientific research on strategies for detecting gene doping. “A key part of our project is to try to define what we call signatures of doping,” says Olivier Rabin, a biomedical engineer and director of science for WADA. “We are looking at the impact of those kinds of genetic manipulations at different levels.” The first and most obvious approach is simply to look for the inserted gene among the roughly 6 billion “letters” of genetic code in both sets of a person’s chromosomes. For clinical gene therapy trials, finding the inserted gene is fairly easy. Scientists know the exact sequence of the gene they inserted, and often they know where on the person’s chromosomes the gene should have ended up. Standard DNA sequencing techniques can reveal the genetic code for that region on the chromosomes, and the unique sequence of the inserted gene will be in plain view. With gene doping, the situation is much trickier. “In sport, you don’t know where that gene will be put, what virus was used or even what particular variety of gene was used,” Friedmann says. “You don’t have the advantage of knowing where to look and for what, so the argument is to look everywhere.” Another difficulty is that copies of the foreign gene wouldn’t be in all of a person’s cells. The gene-carrying viruses selectively target certain tissues such as muscle or liver (the liver helps to regulate muscle metabolism). Some blood cells might also take in the viruses’ genetic payloads, but it’s questionable whether a standard blood sample from an athlete would contain the gene. Instead, anti-doping officials would have to sample muscle tissue directly using punch biopsies, a procedure that is mildly painful. “No one’s expecting that an athlete will agree to a muscle biopsy,” Friedmann says. “That’s a nonstarter.” Still, direct detection of inserted genes could work in some cases. Evans points out that an artificially inserted gene for PPAR-delta would be much smaller than the natural gene. That’s because the natural gene is far too big to hitch a ride on the carrier virus. Fitting the gene onto a virus means only a trimmed down version of the gene can be used. This distinctive genetic pattern would only exist in a person who had undergone gene doping. In other cases, genes would end up in tissues where they’re not normally active, making detection more straightforward. For example, the liver and kidneys normally produce the protein EPO, which makes red blood cells, but gene doping could deliver the EPO-coding gene directly to muscle tissues. The trick, then, is to find a noninvasive way to detect where EPO production is occurring inside the body. One solution is to use medical imaging techniques such as PET scans. In research funded by WADA, Jordi Segura and his colleagues at the Municipal Institute for Medical Research in Barcelona, Spain, attached slightly radioactive “flags” to molecules made during EPO production. A standard PET scan can spot this radioactivity, revealing where EPO was being made in the bodies of mice injected with gene-doping viruses, the team reported in the October 2007 Therapeutic Drug Monitoring. The researchers showed that production of EPO in muscle tissue was a telltale sign of gene doping. With radioactivity that is relatively mild, the labels are routinely used in medical imaging to diagnose diseases and don’t pose a significant hazard. But Friedmann notes that asking athletes to undergo such a procedure could be controversial. Detection by proxy Another approach is to look for signs of the viral “infection,” rather than for the gene itself. Even a weakened virus could trigger a mild, and specific, immune reaction that might show up in a blood test. Perhaps the greatest challenge facing this method is that viruses aren’t the only way to deliver a gene into a doper’s body. “The reality is that you can just inject naked DNA directly into tissues” with a syringe, Evans says. “Direct injection could be more local and harder to detect.” This relatively crude way to insert a gene won’t spread the gene as widely through a person’s body as viruses injected into the bloodstream would. But many cells near the site of injection could take in the gene, perhaps enough to improve athletic performance. Microscopic, synthetic spheres of fat molecules called liposomes can also shuttle doping genes into the body. To prevent dopers from evading detection by simply changing delivery vehicles, scientists are also exploring a third approach to developing tests: proteomics, the detailed study of all the proteins in the human body. Regardless of the vehicle used, adding a new gene to the body’s tightly woven web of interacting genes and proteins will cause ripples of change to spread throughout that web. “There will be a body-wide response no matter what gene you use or where in the body you put it,” Friedmann says, “and those changes can be used as a signature of doping.” Painful biopsies wouldn’t be required. Because the cascade of changes in protein activity would be widespread, anti-doping officials could test using blood, urine, hair or even sweat. Tools developed for the burgeoning fields of genomics and proteomics allow scientists to see the activity levels of thousands of genes or proteins simultaneously. In preliminary unpublished experiments, Friedmann and his colleagues injected a type of muscle cell with the gene for IGF-1. Activity of hundreds of genes changed as a result, including a boost in the activity of genes that control production of cholesterol, steroids and fatty acids. All of these changes might be detectable with simple blood tests. WADA is funding half a dozen or so ongoing studies on this proteome-based detection strategy, but research in this area is still at an early stage. “There’s good reason to think that’s likely to work, and a number of labs are having some nice results,” Friedmann says. As for whether any tests for gene doping will be ready in time for the Beijing Olympics, anti-doping authorities aren’t giving away many hints that might help dopers evade detection. “We never say when our tests are going to be in place,” WADA’s Rabin says. Even if detection methods do lag behind the games, dopers may want to think twice before assuming they’re in the clear, Friedmann notes. “With stored [blood and urine] samples, one always has the option of going back some months or years later and checking again with the newest tests.” Just in case the dangers of tampering with a person’s genetic makeup weren’t enough of a disincentive.

new age of biotechnology

A new age of biotechnology promises bigger, faster, better bodies—and no existing tests will catch it.by Michael Behar; additional reporting by Jocelyn Rice Image courtesy of MashDnArt under a Creative Commons license

The chime on H. Lee Sweeney’s laptop dings again: another e-mail. He doesn’t rush to open it. He knows what it’s about. He knows what they are all about. The molecular geneticist gets a handful every week—often many more, depending on what is in the news—all begging for the same thing, a miracle. Ding. A woman with carpal tunnel syndrome wants a cure. Ding. A man offers $100,000, his house, and all his possessions to save his wife from dying of a degenerative muscle disease. Ding, ding, ding. Jocks, lots of jocks, plead for quick cures for strained muscles or torn tendons. Weight lifters press for larger deltoids. Sprinters seek a split second against the clock. People volunteer to be guinea pigs.

Sweeney has the same reply for each ding. “I tell them it’s illegal and maybe not safe, but they write back and say they don’t care. A high school coach contacted me and wanted to know if we could make enough serum to inject his whole football team. He wanted them to be bigger and stronger and come back from injuries faster, and he thought those were good things.”

The coach was wrong. Gene therapy is risky. In one experiment a patient died. In another the therapy worked, but 4 of the 10 human subjects—young children—got leukemia. To some, such setbacks are minor hiccups, nothing to worry about if you want to cure the incurable or win big. In the last several years, Sweeney, a professor of physiology and medicine at the University of Pennsylvania, and a small cadre of other researchers have learned how to manipulate genes that repair weak, deteriorating, or damaged muscles, bones, tendons, and cartilage in a relatively short time. They can also significantly increase the strength and size of undamaged muscles with little more than an injection. At first the researchers worked with only small laboratory rodents, mice and rats. More recently their efforts have shown promise with dogs. Human testing is years away, but gene therapy has already become a controversy in professional and amateur sports, where steroids, human growth hormone, and other performance-enhancing drugs have been a problem for years. With the Olympics opening in Beijing on August 8, the subject is only going to get hotter. “It’s the natural evolution of medicine, and it’s inevitable that people will use it for athletics,” Sweeney says. “It’s not clear that we will be able to stop it.”

Sweeney became interested in gene therapy in 1988, shortly after scientists pinpointed the gene responsible for Duchenne muscular dystrophy . He wanted to find out if there was a way to counteract the disease genetically. Children with muscular dystrophy lack the gene required to regulate dystrophin, a protein for muscle growth and stability. Without enough dystrophin, muscle cells atrophy, wither, and die. Sweeney’s plan was to introduce the dystrophin gene by hitching it to the DNA of a virus that can transport genes into cells. As it turned out, viruses were too small to carry that gene, so Sweeney began searching for a smaller gene that would at least mimic dystrophin. He settled on a gene that produces insulin-like growth factor 1 (IGF-1), a powerful hormone that drives muscle growth and repair. The IGF-1 gene fit nicely inside a virus and was more appealing because it could potentially treat several kinds of dystrophy. In a series of experiments beginning in 1998, Sweeney and his team at the University of Pennsylvania injected IGF-1 genes into the muscles of mice and rats and watched in wonder as damaged tissue repaired itself.

It’s inevitable that people will use gene therapy for athletics. It’s not clear that we will be able to stop it. For years afterward, Sweeney spent much of his time scrutinizing the rats and mice he had injected with IGF-1 genes. He put them through a rigorous exercise program, strapping weights to their hind legs and repeatedly prodding them up a three-foot-high ladder. After two months, the rodents could lift 30 percent more weight, and their muscle mass had swollen by a third—double what his control group of mice (those without IGF-1) achieved with weight training alone. In another experiment Sweeney gave IGF-1 to mice but curbed their exercise. They too bulked up, jumping 15 percent in muscle volume and strength.

Next up for testing were dogs, which come closer than rodents to approximating human biology. The results were similarly striking. Sweeney has now begun developing and testing another type of gene therapy in dogs and comparing its effects to those of IGF-1. The new therapy is based on a protein called myostatin, which normally regulates muscle growth. By dosing dogs with the gene for a myostatin precursor, Sweeney has found he can throw a wrench into the molecular machinery of myostatin signaling, removing a critical check on muscle growth and allowing deteriorating muscles to regain their strength.

On a visit to the University of Pennsylvania, I ask Sweeney to show me his IGF-1 mice. He leads me to a cramped lab where a bubbling tank of liquid nitrogen spews a cold fog across the floor. Rows of transparent plastic containers, each about the size of a shoe box, are stacked on a chrome pushcart, a pungent, musky odor emanating from them. Inside each box are several chocolate-colored mice. Sweeney points out two groups in neighboring containers and asks, “Which set do you think we’ve given IGF-1?” I lean in for a closer look. The mice in the left box look as if they have been watching Buns of Steel videos . Each mouse boasts a rock-hard rump and shockingly large, perfectly chiseled gastrocnemius and soleus muscles (which, in humans, make up the calf). In the adjacent cage, two control mice appear scrawny by comparison. The results are impressive, and I wonder out loud just how easy it would be for someone to reproduce Sweeney’s results in a human. “I wouldn’t be surprised if someone was actively setting up to do it right now,” he says. “It’s not that expensive, especially if you are just going to do it to a small population of athletes.”

+++ That is exactly what worries officials at the World Anti-Doping Agency and the U.S. Anti-Doping Agency. In anticipation of the 2004 summer Olympics, in Athens, the world agency put gene doping on the International Olympic Committee’s prohibited list, which includes everything from cough syrup to cocaine. The prohibition defines gene doping as “the nontherapeutic use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance.” But no one thinks for a minute that gene doping isn’t already starting to happen. “Sport is supposed to be fun,” says former Olympic swimmer Richard Pound , ex-president of the world agency and a vocal champion of the antidoping cause. “But it is surrounded by people who are conspiring to destroy the athlete and the game.”

Gene doping is different from chemical performance-enhancing techniques. Human growth hormone, for example, occurs naturally in the body and will accelerate cell division in many types of tissue. Taken in high doses, it can provide a head-to-toe muscle boost and can even add a few extra inches of height. Anabolic steroids are chemical relatives of testosterone. They are believed to be in wide use in professional sports—although most athletes deny it—and their illegal use recently ignited explosive, high-profile controversy in Major League Baseball and Olympic track-and-field events. Last year track star Marion Jones admitted that she had used steroids while training for the 2000 Olympics and was stripped of all five of her medals. Steroids are also popular with weight lifters because they foster new muscle growth in the upper body. Synthetic erythropoietin, or EPO, a chemical naturally produced by the kidneys, is a favorite of triathletes, marathon runners, Tour de France cyclists, and others who engage in long periods of aerobic activity. EPO flushes fatigued muscles with oxygen to stave off exhaustion.

These and other substances can be detected in blood and urine tests because they drift through the circulatory system for hours, days, or months. Gene doping is not so easy to spot. Genetic modifications become an indistinguishable element of the DNA in targeted muscles. The only way to prove that someone has used gene doping is to biopsy a suspicious muscle and look for signs of DNA tampering. It is not hard to imagine that most athletes will object to having bits of flesh sliced from the very muscles they’ve spent years honing. “Athletes aren’t going to say, ‘Hey, take a muscle biopsy before my 100-meter run,’” comments Johnny Huard , who developed his own set of muscle-building genes as professor of molecular genetics, biochemistry, and bioengineering at the University of Pittsburgh School of Medicine.

Lack of easy detection makes gene doping extremely attractive to athletes. But the incredible muscle-building power of doping is the big draw. Sweeney believes gene-doped athletes would readily surpass their personal bests and could even smash world records. Sprinters and weight lifters would see the most benefit, their peak speeds and maximum strength amplified. “Athletes would be able to push their muscles harder than ever before because their muscles would repair themselves so much faster,” he says. “And they wouldn’t have to retire when they were 32.”

Antidoping agency officials are convinced that athletes will try gene doping, despite its dangers. “In the current climate there is even more pressure than when I was competing,” says Norway’s 1994 Olympic speed skating gold medalist, Johann Koss , a physician and former member of the World Anti-Doping Agency’s executive board. “People will take shortcuts. Being the best in the world offers huge financial gains.”

In a poll, American athletes said they would take any drug that would help them win, even if they knew the drug would eventually kill them. Pound cites a poll of American athletes who said they would take any drug that would help them win, even if they knew the drug would eventually kill them. “Nobody ever said athletes are ?the smartest people in the world,” he comments. “This is why there has to be paternalism. This is why I don’t let my kids drive the car at age 13, even though they tell me they can do it safely.”

Pound has good reason to worry. The newest gene therapies work on mice, rats, and dogs with no apparent adverse effects. Until clinical trials are completed, however, it is impossible to know exactly what the effects will be on humans. Sweeney acknowledges, for instance, that IGF-1 could make precancerous cells grow faster and stronger.

“We have absolutely no clue” about side effects, Huard says, but he and other researchers are worried about immunologic reactions to the virus that serves as the gene carrier. That reaction is apparently what killed 18-year-old Jesse Gelsinger , according to researchers at the University of Pennsylvania. Gelsinger had a rare liver disease and was participating in gene therapy research at the university when he died. The Food and Drug Administration immediately terminated all gene therapy trials there, and the incident prompted federal regulators to establish new rules for human gene therapy research.

More and more, Sweeney says, the immune system is proving to be the most difficult hurdle in developing gene therapy for humans. Treatments that appear perfectly safe in rodents and dogs can provoke a devastating immune response when adapted for humans and other primates. The problem, Sweeney says, is that the viruses researchers use for delivering therapeutic genes infect primates but not other mammals. So while a dog’s immune system will simply overlook the intruder, a human’s will recognize it and launch a massive attack. Researchers are now working to develop ways to suppress the immune system long enough for the virus to safely deliver its genetic cargo.

+++ Another concern is that the vector virus might run amok. Scientists believe that is what happened during a 1999 French gene therapy trial on a group of 10 young children with X-SCID, an immune deficiency disorder known as boy-in-the-bubble syndrome . Researchers engineered a virus to carry a replacement gene to repair the immune systems of the sick children. The technique cured nine of them, and scientists initially deemed the trial an overwhelming success. Nearly three years later, however, doctors diagnosed two boys in the study with T-cell leukemia. Two more leukemia cases have since come to light; one patient has died. Somehow the virus carrier—not the replacement gene—had managed to touch off the blood disease, an international medical team reported in 2003. A parallel study in England initially looked more promising, but recently leukemia struck one of its participants as well.

Those incidents sparked widespread condemnation that stifled nascent research initiatives. The climate for gene therapy research has since begun a slow rebound. A variety of human trials are now under way with tighter safeguards, but most experiments are confined to animals.

Beyond the medical and regulatory setbacks, the largest roadblock to commercializing the technology is money. For years Sweeney’s efforts to launch dog studies were thwarted by a lack of funding. Human trials are even costlier, so for now, Sweeney says, IGF-1 and myostatin gene therapies remain on the distant horizon. He nonetheless keeps a list of telephone numbers from desperate parents who have contacted him.

Meanwhile, amateur athletics is trying to come to grips with gene doping. Every few years the World Anti-Doping Agency hosts a symposium where scientists, regulatory officials, and athletes gather to discuss gene doping. Theodore Friedmann, who directs the program in human gene therapy at the University of California at San Diego, spearheaded the first of these workshops six years ago. “People intent on subverting gene therapy will do so,” says Friedmann, who has advised the National Institutes of Health and congressional leaders on gene-related issues. “The technology is too easy. It’s just graduate student science.”

That bothers Arne Ljungqvist , the World Anti-Doping Agency’s health, medical, and research committee chairman, who doles out several million dollars in grant money every year to research groups looking at gene doping and its detection. Additionally, Friedmann, who chairs the agency’s antidoping panel, is working to establish testing protocols. “So far the results are sitting in the form of research advances,” he says, “but not in the form of real detection methods.” One concept is to hunt for what Friedmann calls physiological fingerprints. Introducing foreign genes into muscles, he says, “is going to produce changes in the way muscles secrete things into the blood and, therefore, into the urine.” In the same way breast and colon cancer alter the pattern of proteins in the bloodstream, genes linked to IGF-1 or EPO will, in theory, leave traces. Surveillance organizations like the U.S. and world antidoping agencies “will look for those signatures and patterns that can be tied, with confidence, to the existence of a foreign gene,” Friedmann says. Although it may be years in development, Fried­mann envisions a noninvasive imaging device akin to an X-ray that detects bits and pieces of leftover viruses used to introduce performance-enhancing genes.

Ironically, the misuse of gene doping in sports is more clearly defined than its proper use. When physicians begin curing athletic injuries with gene therapy, the boundaries of healing and enhancement will blur. “There will be a fuzzy line between what is a medically justifiable treatment of injuries and what is performance enhancement,” Friedmann says. “There is nothing terribly noble about an athlete destroying a career with an injury if one can medically prevent or correct it. I would be hard-pressed to say that athletes are not eligible for this or that manipulation. It has always been obvious that there are therapeutic-use exceptions. There is no reason to think that therapeutic-use exceptions would be dis­allowed for genetic tools.”

That, of course, opens the door for abuse. In some instances, athletes would require only minuscule improvements to nudge them into the winner’s circle. “Olympic athletes don’t need to see a drastic change,” Huard says. “Sometimes the gold medalist is only a fraction of a second over the silver.” It would be very easy for a team physician to surreptitiously let therapeutic genes continue working for a few hours, days, or weeks after an officially sanctioned treatment ends.

With no viable testing mechanism on the horizon, it is possible that at least one of the 10,000-plus Olympic competitors in Beijing this summer will have experimented with gene doping. “Nothing would surprise me,” Friedmann says. For the time being, though, gene doping is not only illegal but also unsafe and probably ineffective. “If it’s done now,” he says, “it will certainly be done badly.”Additional reporting by

+++ The Muscle Maker Gene therapy offers a shortcut to bulking up: At the University of Pennsylvania, H. Lee Sweeney is developing a way to turn the liver into a factory that churns out a muscle growth promoter called myostatin propeptide . He injects a virus carrying the growth promoter gene into an animal’s veins, where it courses through the bloodstream and into the liver. There, it infects liver cells and delivers its genetic package. A signal from the virus tells the liver cells to manufacture the growth promoter, which is then secreted back into the bloodstream and ferried off to muscles throughout the body. Normally, myostatin puts the brakes on excessive muscle growth. But when there is too much myostatin propeptide around—delivered by the virus and pumped out by the liver—myostatin cannot do its job and muscles keep growing.

Click here to see the rest of DISCOVERmagazine.com's special Olympics coverage.

Gene Doping May Be Next Big Thing for Athletes Seeking Edge (2008, Aug 12)

Gene Doping May Be Next Big Thing for Athletes Seeking EdgePosted by Sarah Rubenstein The science of genetics has opened up a world of potential new treatments for tough diseases. But those of you who’ve been watching the Olympics may be interested to know genes could become the next “steroids.”

Right out of the “don’t try this at home” play book, the Baltimore Sun over the weekend ran an article detailing the many ways Olympic athletes can still manage to skirt anti-doping rules. Though the degree to which it’s happening is unclear, one interesting idea is what’s being dubbed “gene doping.”

Here’s how the newspaper explains it: Inject the body with a gene that triggers growth in specific tissues such as muscle. That could increase the muscle but be tough to detect in a test, because the enhancement was produced by the body’s own instructions.

Se-Jin Lee, a Johns Hopkins molecular biologist , found recently that with two injections over two weeks, he could increase muscle mass in mice by 60% — no training required, according to the Sun. He’s only testing in animals, but it wouldn’t be hard to try the technique in humans, he acknowledged.

China: No evidence for gene doping at Games but worry remains (2008, Aug 10)

No evidence for gene doping at Games but worry remains

www.chinaview.cn 2008-08-10 17:22:21

BEIJING, Aug. 10 (Xinhua) -- Gene doping may not be present at the ongoing Beijing Olympic Games but anti-doping experts remain worried that illegal use of gene therapy.

David Howman, director general of the World Anti-Doping Agency (WADA), voiced his concerns over illegal practices in this area on Sunday.

"We worry about unfair practices. My concern is somebody is trying to do it without having it properly, medically verified and ethically confirmed. It is like manufacturing drugs without under proper scrutiny," he said. He was here to oversee the anti-doping program at the Games which opened on Friday.

WADA plays the role of independent observer for the program and carry out about 1,000 of the 4,500 tests during the Games. It also set up an anti-doping outreach program for athletes in the Olympic Village.

"We are doing a lot of work in gene therapy because we want it to be in place for the good public health reasons. What we worry about is being abused by those want to cheat. It should not be abused by athletes," said Howman.

At this point, WADA doesn't believe gene doping is present.

"No evidence, nothing is coming forward to suggest that gene doping is going on," said WADA president John Fahey. "No gene doping is occurring a this point of time."

WADA has held three gene doping symposiums with experts, scientists, ethicists, athletes, and representatives from the Olympic Movement and governments studying the issue. The third symposium was held in Saint Petersburg in June this year.

Fahey said all participants of the symposiums agreed that more research should be done.

"There is a recognition that there must be sufficient research to find the detection process in advance because it is a concern it may become something in the lexicon of doping in the days ahead," said the Australian.

WADA has been conducting 22 projects on developing a system for detecting gene doping. Howman said combined efforts were needed to combat the problem.

"We do a lot of research and we would like to do more but we haven't got a lot of money, so we rely on other countries and research bodies to help us with it," he said.

Beijing Olympics warned of 'gene doping' threat (2008, Aug 5)

Beijing Olympics warned of 'gene doping' threatA new generation of 'genetically modified' athletes could mar the Beijing Olympics as sportsmen and women go to new lengths to realise their goals.

By Telegraph staff Last Updated: 2:36PM BST 05 Aug 2008

 Keeping clean: A doping control area at the National Aquatics Centre prior to the Beijing Olympics Photo: Reuters Leading British scientist Dr Andy Miah, who is currently in Beijing conducting research during the Games, claims that "gene doping" will become the latest headache for the sport.

Athletes will be able to improve their performance by inserting or inhaling foreign DNA. The process sees genes either injected into muscle of bone cells and their proteins fed into the tissue or red blood cells.

"In 2004, people were starting to talk about its use at the Athens Olympics," Dr Miah says in the Evening Standard. "This year the case is even stronger that this will be the first genetically-modified Games. Many scientists will say it's still not possible, but I'm not taking this for granted.

"We need to assume that it's happening. It's already feasible."

While the threat at this year's Games is thought to be minimal, Dr Miah fears London 2012 could feel the full force of the latest and most damaging threat to the sport.

He said: "London 2012 should be watching Beijing very carefully to see what's possible. There has never been a 'clean' Olympics.

"The main problem for sports is that there are so many technologies that are under the radar of antidoping that its policies do little more than to point us to successes of antidoping testing."

The 'genetically modified' process was added to the World Anti-Doping Agency list of banned substances in 2003, but today's claims are sure to put WADA on full alert.

A representative of WADA, Frederic Donze, said: "We have been preparing for gene doping since 2002.

"We have to believe that athletes will try anything to get an edge and this might occur at the Olympics and we work on that basis."

Beijing: the first genetically modified Olympics? (2008, Aug 4)

Beijing: the first genetically modified Olympics?"The curtain will rise on what many experts believe could prove to be the first genetically modified Olympics.

For the unscrupulous or overdriven Olympic athlete, the banned practice of doping by taking hormones or other drugs to enhance athletic prowess may seem so last century. The next thing in doping is more profound and more dangerous. It called gene doping: permanently inserting strength- or endurance-boosting genes into DNA.

Once you put that gene in, it's there for the rest of that person's life, says Larry Bowers, a clinical chemist at the U.S. Anti-Doping Agency in Colorado Springs, Colo. You can't go back and fish it out.

Scientists developed the technology behind gene doping as a promising way to treat genetic diseases such as sickle-cell anemia and the bubble boy immune deficiency syndrome. This experimental medical technology called gene therapy has begun to emerge from the pall of early failures and fatalities in clinical trials. As gene therapy begins to enjoy some preliminary successes, scientists at the World Anti-Doping Agency, which oversees drug testing for the Olympics, have started to worry that dopers might now see abuse of gene therapy in sport as a viable option, though the practice was banned by WADA in 2003.

Gene therapy has now broken out from what seemed to be too little progress and has now shown real therapies for a couple diseases, and more coming, says Theodore Friedmann, a gene therapy expert at the University of California, San Diego and chairman of WADA's panel on gene doping.

While gene therapy research has begun making great strides, the science of detecting illicit use of gene therapy in sport is only now finding its legs. To confront the perceived inevitability of gene doping, Friedmann and other scientists have started in recent years to explore the problem of detecting whether an athlete has inserted a foreign gene an extra copy that may be indistinguishable from the natural genes into his or her DNA.

It's proving to be a formidable challenge. Genetic makeup varies from person to person, and world-class athletes are bound to have some natural genetic endowments that other people lack. Somehow, gene-doping tests must distinguish between natural genetic variation among individuals and genes inserted artificially and the distinction must stand up in court.

Scientists are fighting genetics with genetics, so to speak, enlisting the latest technologies for gene sequencing or for profiling the activity of proteins to find the telltale signs of gene doping. Some techniques attempt the daunting search for the foreign gene itself, like looking for a strand of hay in an enormous haystack."

This is what living in a culture of greed, competition, and winning above all instead of fairness and loving what you do is doing to people. Even to the point of inserting this foreign DNA and not knowing for sure what it will do to your body. So we eat genetically modified food (without our knowledge) and now can genetically modify our own bodies all to profit those who don't care about the affects this is having on us... and athletes that are women who do this and get pregnant afterwards ... what risks would their children now face? Is winning and $$$ and endorsements REALLY all that important? So what will the new trend be: Bodies by Monsanto?