2012 September 10 Monday
War Against Athletic Doping Has Failed

In a Wired piece Ian Steadman argues How Sports Would Be Better With Doping and how the war against doping has already failed.

Dwain Chambers, the UK’s fastest sprinter in the 100 meters, was banned from competing in the Olympic Games after testing positive for the anabolic steroid tetrahydrogestrinone. He claimed in his autobiography that at least half of the U.S. racing team at the 2008 Summer Games used illegal substances. The battle to control drug use never, ever seems to end. Why don’t we accept doping will always happen and legalize it?

The article quotes professors who argue that most doping is not detected. Very likely many world records are now held by athletes who did it with the help of performance-enhancing drugs. Steadman' article hits many of the points about the advantages of athletic enhancement I've been making for years. Why suffer the limitations that nature gave us in our genes? We can do better. Use of drugs to boost performance basically turns athletes into guinea pigs for treatments that will some day help the rest of us. We'll get faster progress in biomedical science if athletes are allowed to do doping.

In the 2020s I expect gene therapies to finally mature to the point where they move into widespread use for many purposes. Fewer humans will be fully genetically natural even before offspring genetic engineering begins. Parents will choose to give their kids gene therapies to do many types of enhancement to boost their quality of life and potential for success in many endeavors. We should not create regulatory regimes that discourage this development.

We are hurtling toward a future where most humans from birth will not be genetic wild type. We'll genetically engineer offspring to reduce the genetic load of lots of slightly harmful mutations that we all carry. Will those offspring be allowed to compete in the Olympics? They'll have advantages far larger than those that can be gained from drugs used for athletic doping and will be much healthier with longer life expectancies.

By Randall Parker    2012 September 10 11:29 PM   Entry Permalink | Comments (8)
2012 August 26 Sunday
Easy To Cheat At Athletic Drug Doping

Brian Alexander says use of many small doses and other techniques makes it easy for athletes to cheat and use performance-enhancing drugs.

However, declaring somebody a doper based on the test requires a judgment call, so labs tend to err on the side of caution. Some estimate that for every EPO user discovered, 10 others get away. On the other hand, there have also been cases of false positives.

So many false negatives combined with the false positives underscore the weaknesses of current doping detection methods. Alexander reports that anti-doping agencies are

How many world records are held by athletes who used drugs to reach their performance peaks. Some claim steroid usage is widespread. Another article on this topic reports that the athletes have been able to adjust their doping techniques in response to new doping detection methods. Sure, some athletes get caught when new testing methods first get introduced. But the advantages of doping outweigh the risks of getting caught.

In the longer run I expect a greater understanding of DNA sequences to enable more reliable detection of doping. The reason is fundamental: If a person's athletic performance exceeds the performance limits imposed on them by their genes then they must be cheating in order to reach top ranks. Doping detection will turn into a game where the anti-dopers sequence an athlete's DNA and create a profile that project's the athlete's natural limits. If the athlete performs in excess of those limits then the athlete must be cheating.

Of course, once genetic testing results and other biological testing results can be fed into a computer that can accurately predict each athlete's peak performance then what becomes of games as a way to measure relative performance? How to retain athletic competitions as settings where humans compete? The answer is obvious: make athletic games into contests between rival scientific teams. The winning athlete should be like a winning car racer who competes with the help of engineers who design better race cars. Rival bioengineering teams should compete to develop humans who can win in each sport. If bioengineering crews for athletes were legitimized then the rate of advance of bioengineering would accelerate.

By Randall Parker    2012 August 26 09:36 PM   Entry Permalink | Comments (6)
2012 August 21 Tuesday
Human Max Speeds Compared To Fast Animals

The recent Olympics reminds us of the outer limits of human physical performance. But how do we compare to other animals? An assortment of animals can move faster than humans.

Humans can run at a maximum speed of 23.4 miles per hour (37.6 kilometres/hour) or 10.4 metres per second, which gives them the edge over the Dromedary camel.

But only just, as these animals can run at a top speed of 22 mph (35.3 kph) or 9.8 metres/second.

While reading these numbers a thought occurred to me: genetic engineering will enable such huge increases in human performance that natural athletes will become uninteresting. What is interesting about 23.5 miles per hour once genetically engineered humans can do 30 mph? Anti-doping regimes maintain their support mainly because doping is seen more as an easier way to reach the top than as a way to break records. But if cheating with doping is really as widespread among elite athletes as some think then we already are getting excited and cheering on the pharmaceutically enhanced. If current anti-doping testing regimes can only catch the most egregious violators we are getting our expectations raised to expect levels of performance that natural humans can't achieve. We will want records to be broken. Once enhanced humans break those records in very dramatic fashion I think natural human athletes are going to come to be seen as boring and very much a fashion of a quaint past.

Will genetically reengineered humans some day reach cheetah speed?

A cheetah is around twice as fast as the world's top sprinters at 64 mph (104 kph) or 29 metres/second. But the pronghorn antelope also puts in a very respectable 55 mph (89 kph) or 24.6 metres/second.

And let's not forget the North African ostrich, which at 40 mph (64kph) or 18 metres/second, is the world's fastest running bird. Or sailfish, which reach a swimming speed of 67 mph (108 kph) or 30 metres/second.

What I wonder about fast race horses: How do they compare to other types of horses for long distance speed? If you want to travel more miles per day what kind of horse can sustain the highest speed for hours?

Then, of course, there are thoroughbred racehorses, the fastest of which has managed 55mph (88kph), and greyhounds at 43 mph (69kph).

Birds are probably the fastest animals for distance travel. What bird can travel the most miles in a day? Geese? Ducks? Other?

And birds would win a few gold medals too. Peregrine falcons can reach speeds of 161 mph (259 kph), while ducks and geese rival cheetahs, with speeds of 64 mph (103 kph) in level flight.

Do not be surprised some day if human distance runners use pure oxygen canisters feeding oxygen directly into their blood streams so they can sustain fast speeds longer. If the Olympics forbids them from competing then I expect sports contests for bioengineered will be organized and those contests will become more popular and interesting than natural wild type competitions between natural humans.

By Randall Parker    2012 August 21 11:19 PM   Entry Permalink | Comments (15)
2012 August 07 Tuesday
Worries On Genetic Doping For Athletic Enhancement

What's wrong with gene therapy to boost athletic performance? Yet another worry article about what could be a very positive development.

Officially, UK Anti-Doping, the body which oversees the control of performance enhancing drugs in Britain, says genetic manipulation as a form of performance enhancement "is currently a theoretical rather than a proven issue".

But Andy Parkinson, UKAD's chief executive said: "I wouldn't be surprised if someone out there is trying to do it, and I think that's very worrying."

My worry is that gene therapy is such a hard problem (e.g. cancer risks, difficulties in delivering genes to enough cells, difficulties in delivering genes to only the desired types of cells, etc) that gene therapy won't make much difference to athletic performance any time soon. But as I've recently argued a gene therapy arms race to enable genetically less well endowed athletes to compete with the genetically fittest athletes would generate many medically useful spin-offs. If organizers of athletic events allowed biotechnological enhancements for athletic performance the rest of us would benefit from a faster rate of progress in the development of medical treatments for many diseases of old age.

So why the opposition to all manner of athletic doping, including gene therapy? I think some of the opposition stems from a desire to believe that athletes win by a more determined and sustained exercise of willpower. We want to see people succeed by doing large amounts of hard work aimed at a lofty goal. But I think this desire is based on wishful thinking. The outcome of Olympic sporting competitions hinge greatly on relative athlete genetic fitness. Those lucky few who have a low burden of harmful mutations have big advantages. Those who have still other genetic variants that make them fast distance runners (or other genetic variants that make them fast sprinters) will win the races.

None of this is meant to say that individual effort does not matter. Of course the drive and effort of the athlete plays a role. But individual effort in elite sporting events only matters among those genetically most well endowed. If athletes could use gene therapies to boost their athletic performance then the effect might be to close the gap between the genetically most and least well endowed. Then with genetic differences lessened we'd get mores sporting contests whose outcome would be decided individual efforts and judgments of peers.

By Randall Parker    2012 August 07 10:21 PM   Entry Permalink | Comments (5)
2010 May 04 Tuesday
Growth Hormone Boosts Sprinting Speed

Growth hormone if you have the need for speed.

Injections of human growth hormone can improve sprint capacity enough to turn the last-place finisher in the Olympic 100-meter dash into a gold-medal winner, according to a study released Monday.

So says the LA Times. But no. The study participants were not fit enough to equal the last place finish in the Olympics.

The eight-week study, one of the most rigorous examinations of growth hormone and athletic performance to date, involved 96 healthy, recreationally trained athletes with an average age of 27.

The incorrect assumption of the reporter is that growth hormone will boost the performance of everyone equally. But the biological differences that separate top Olympic performers from each other might be very different in character than the biological differences that separate them from everyone else.

A study that measured performance boost from growth hormone in subjects with a wider starting range of abilities would tell us more about whether growth hormone level is a performance-limiting factor over the full range of human ability. Maybe it is. Maybe its not. If the last place and first place Olympics 100-meter dash runners took growth hormone would the gap between them narrow or widen or stay the same? It would be interesting to know.

What I'm really curious to know: Do genetic differences determine a substantial amount of the relative rankings of top athletics in major competitions like the Olympics? If so, then in the future surreptitious acquisition of genetic samples of top Olympic athletes could provide a big advantage in betting on competitions. Also, an athlete that wins with less than the best genetic profile will raise red flags with athletic competition officials to look for signs of doping.

By Randall Parker    2010 May 04 12:20 AM   Entry Permalink | Comments (1)
2009 July 01 Wednesday
Mechano Growth Factor Hormone For Stronger Muscles

Bored of the same old hormones for boosting your muscle mass? Wnat to try a new trendy buffing hormone? Mechano Growth Factor (MGF) could become the next rage for athletic dopers.

Scientists in the UK and Denmark have shown that if elderly men were given growth hormone and exercised their legs showed an appreciable muscle mass increase. Dr. Geoff Goldspink (Royal Free and University College Medical School, UK) says: "This raises the question: Can age-related loss of muscle strength and increased fragility be ameliorated by the therapeutic application of mechano growth factor (MGF)?". There is hope that MGF can also help sufferers of diseases such as muscular dystrophy, ALS, renal disease or cancer, for whom intensive exercise is not an option. It may even prove useful to ameliorate muscle loss resulting from long periods in zero-gravity conditions during space travel. Dr. Mark Lewis (University College London, UK) will present their latest results on how MGF exerts its effects during his talk at the Society of Experimental Biology Annual Meeting in Glasgow on Wednesday 1st July 2009.

When muscles are stretched during exercise, they produce a specific substance known as mechano growth factor (MGF) that activates stem cells already present in the tissue. Once activated, these progenitor cells begin to divide, creating additional muscle fibres and increasing the size and strength of the muscle. In addition to intensive exercise, muscles need to be stimulated by growth hormone (GH) in order to release MGF. Since there is a natural decrease in the levels of this hormone as we age, this may combine with the lack of intensive physical activity to cause muscle wasting in elderly people. "The downside", warns Dr. Goldspink, "is that MGF has great potential for doping in sports. A synthetic version is already available over the internet, and although it is still very expensive, it is expected that new technologies will bring down the price to make it comparable to that of human insulin".

The downside? I hear negativity coming from Dr. Goldspink when optimism seems more the order of the day. New ways for athletes to boost their performance? Don't we want them to improve? Don't we want continuous improvement leading to the perfection of human bodies? Aren't we hearing the march of transhumanist progress? Isn't progress good? Don't we need the prospect of stronger bodies to boost our spirits as Peak Oil approaches?

My bottom line on drug doping by athletes: Why should we care? Why should we only want to see natural wild type bodies compete? That would be tantamount to saying that car races should only be done with standard mass produced factory cars. But we expect more from our race cars, much more. Why not expect more from humans?

The way I see it: Some people get the luck of the genetic draw and have incredible athletic bodies. If lucky genetic naturals want to compete only with each other, fine. Have contests for genetic naturals. But why not other contests between those boosted athletes who can strut with the latest that biomedical science and technology have to offer?

By Randall Parker    2009 July 01 10:46 PM   Entry Permalink | Comments (14)
2009 March 13 Friday
Genetic Variants Mean Personalized Athletic Drug Testing Needed

Only genetic tests can tell us what we need to know to determine whose hormone ratios are natural.

Current steroid (testosterone) doping tests should be scrapped for international sport, because they ignore vital ethnic differences in hormone activity, suggests research published ahead of print in the British Journal of Sports Medicine.

Testosterone, and other hormones that boost testosterone levels, such as growth hormone, are among the most widely abused performance enhancers used in sport, according to the World Anti-Doping Agency.

Evidence of abuse is determined by the testosterone: epitestosterone ratio, or T:E ratio for short, in the urine. The threshold is set at above four for everyone, and confirmed by chemical analysis (gas chromatography).

To highlight the inadequacy of the current test, the researchers tested the steroid profiles of football players of different ethnicities, after they had deliberately added steroid to their urine samples.

The scientists think that a variations of the UGT2B17 gene account for some differences in the testosterone: epitestosterone (T:E) hormone ratio.

They used gas chromatography, and took account of a variation (polymorphism) in the UGT2B17 gene.

Previous research has indicated that variations in this gene account for some of the differences in the urinary T:E ratio between men of white and Asian ethnic backgrounds. The gene affects metabolism, and therefore the rate at which testosterone is passed out of the body into the urine.

They included 57 men of Black African origin; 32 of Asian origin; 32 of Hispanic origin; and 50 of white (Caucasian) origin in their research. All the men were aged between 18 and 36.

The frequency of these genetic variations differs between races.

The results revealed the genetic variation in almost one in four (22%) of the African footballers; in eight out 10 (81%) of the Asian players; one in 10 of the white men, and in 7% of the Hispanic players.

Based on these findings, the Swiss researchers "recalibrated" the thresholds for each ethnic group.

They should measure a larger sampling of people of different races to get more accurate estimates of the frequencies of UGT2B17 gene variations in each race. Perhaps that work has been done already? Anyone know? International HapMap database anyone?

These scientists calculate that different T:E ratios should be seen as the natural typical ratios to expect for each race. But these ratios do not work for individuals for the same reason the races differ on average: People within a race will differ in which genetic variation they have in UGT2B17.

The new T:E ratios were: 5.6 for men of African origin; 5.7 for white men, and 5.8 for men of Hispanic origin. For men of Asian origin, the ratio was 3.8.

While the press release is vague on this point the press release might be hinting at the need to do genetic testing on athletics to discover what their hormone ratios should be.

A single indiscriminate threshold to pick up steroid abuse in international sport is "not fit for purpose," the authors conclude. Instead, the reference ranges should be tailored to an athlete's individual endocrinological (hormonal) passport, they suggest.

"[Such a] passport may detect modifications induced by abuse of testosterone and its precursors, but also alterations in the steroid profile caused by indirect androgen doping products," they conclude.

A complete genetic profile will eventually be needed for each athlete to determine the expected natural range for a wide variety of hormones and other chemicals and structures within the body. Athletes will use their genetic natural ranges in order to know how much cheating they can get away with. They'll use drugs and other therapies to push their physiology to the limits achievable through extreme exercise.

Genetic profiling of athletic potential will lead to acceleration of human evolution. Parents will give their offspring ideal genetic variants for athletic performance. Then genetic testing will show future athletics as more capable of extreme (at least by today's standards) levels of achievement. Then athletic associations be faced with the decision of whether to test parents in order to determine whether Lance or Mary Lou has natural genetic variations.

In the long run I expect anti-doping testing regimes for athletes to collapse due to impracticality. Few humans will be wild type. When rules against genetically engineered competitors require the banning of most humans from Olympic and other amateur and professional athletic competition then people will reject the rules.

By Randall Parker    2009 March 13 11:13 PM   Entry Permalink | Comments (9)
2008 August 13 Wednesday
More Doping Tests For 2008 Olympic Games

Emily Singer in Technology Review reports on more extensive uses of tests to detect banned treatments for athletic enhancement.

In an attempt to catch those athletes out, the Olympic antidoping lab has dramatically stepped up testing compared with previous games, conducting 1,000 more tests than in Athens in 2004 and double the number at the Sydney games in 2000. That increase comes largely from greater numbers of tests per sample, rather than from an increase in the number of samples collected.

Note the greater number of tests per sample. That probably reflects the use of gene chips and other miniaturization of biological testing devices. That miniaturization results in a level of automation, precision, and cost reduction that enables such a large number of tests on a single sample. So this is not so much a report on increased vigilance as increased ability to be vigilant.

The sports organizations are trying to stay ahead of the development of performance enhancement drugs.

The IOC and the World Anti-Doping Agency (WADA) are also developing new testing techniques, although they won't give details about any new tests that they plan to run at this year's Olympics. "We need the elements of secrecy to try to be ahead of the game," says Catlin. This secrecy won WADA a dramatic victory at the Tour de France last month. Its drug-testing lab caught several cyclists using a longer-lasting form of EPO called CERA. Soon after the athletes were caught, it was revealed that the agency had been working with Swiss drugmaker Roche to develop a test to detect CERA while the drug was still being tested by the U.S. pharmaceutical company Amgen.

I expect some future performance enhancement treatments will be harder to detect. As we learn how exercise causes the body to grow bigger muscles, more vasculature, and other changes that enhance performance we will also learn many more ways to intervene. Some of these ways will so closely mimic what exercise normally does to the body that it will be hard to tell them apart from exercise. Already recent advances have identified two compounds that mimic the effects of exercise. Many more will be found.

Attempts to regulate enhancement of athletes will run up against even tougher obstacles in the future. First off, genetic engineering to enhance offspring will put the earliest intervention point for athletic enhancement to before birth. Will some people be banned from athletic competition because they were genetically engineered? Some of them will be hard to detect unless their genetic sequences are compared against that of both parents.

Genetic enhancement after birth will become common as well. Parents will seek to remedy health and other deficiencies in their children by getting them gene therapies and stem cell therapies as advances make more forms of enhancement possible. Genetic "Wild type" humans will some day be the exception.

The identification of all the genetic variants that enhance athletic performance will show that Olympic athletes are, for the most part, lucky winners in a sort of genetic lottery. While their training helped them get to the Olympics their fortunate genetic endowments will show that most people do not have the genetic profiles needed to compete at the Olympic level. Some will find this unfair and will argue that everyone should be allowed to get the same genetic advances added to their bodies after birth so that they too can compete at the highest level. How will this debate turn? I expect the proponents of enhancement will eventually win the debate and sports competitions between enhanced humans will become more common than competitions between wild type humans.

By Randall Parker    2008 August 13 09:37 PM   Entry Permalink | Comments (2)
2007 September 19 Wednesday
Steroid Use Boosts Home Runs With Small Muscle Mass Increases

Enough balls reach near the outer edge of the playing field that a few percent increase in ball speed coming off the bat is enough to increase home runs by 50% to 100%.

MEDFORD/SOMERVILLE, Mass. -- Steroid use by a Major League Baseball slugger may produce only modest increases in muscle mass and bat and ball speed but still boost home run production by 50 percent or more, according to a new study by Tufts University physicist Roger Tobin.

Tobin, a specialist in condensed matter physics with a long-time interest in the physics of baseball, will publish his paper "On the potential of a chemical Bonds: Possible effects of steroids on home run production in baseball" in an upcoming issue of the American Journal of Physics.

As Tobin's paper notes, Babe Ruth's record of 60 home runs in a single season stood for 34 years until Roger Maris hit 61 homers in 1961. For the next 35 years, no player hit more than 52 home runs in one season. But between 1998 and 2006, players hit more than 60 home runs in a season six times. Barry Bonds hit 73 home runs in 2001—topping Maris' mark by an astonishing 20 percent.

According to Tobin, the explosion in home runs coincides with the dawn of the "steroid era" in sports in the mid-1990s, and that surge quickly dropped to historic levels in 2003, when Major League Baseball instituted steroid testing.

What happens once parents start genetically engineering their kids at the stage of embryos to contain genes that make them super athletes? One solution: create baseball leagues where everyone genes genetically tested and people with closely equivalent genetic potentials play each other. But will the audience want to watch any league aside from the top league?

A 10% increase in muscle mass produces a 4% increase in ball speed as the ball leaves the bat.

Tobin reviewed previous studies of the effect of steroid use and concluded that muscle mass, the force exerted by those muscles and the kinetic energy of the bat could each be increased by about 10 percent through the use of steroids. According to his calculations, the speed of the bat as it strikes the pitched ball will be about 5 percent higher than without the use of steroids and the speed of the ball as it leaves the bat will be about 4 percent higher.

To determine the ultimate impact on home run production, Tobin then analyzed a variety of models for trajectory of the baseball, accounting for gravity, air resistance and lift force due to the ball's spin. While there was considerable variation among the models, "the salient point," he says, "is that a 4 percent increase in ball speed, which can reasonably be expected from steroid use, can increase home run production by anywhere from 50 percent to 100 percent."

The article also provides an estimate of speed increases of balls thrown by juiced up pitchers.

One way to cut down on home runs on juiced up or genetically enhanced teams is to just make the playing field bigger. But a higher rate of home runs might be a good idea for a sport that has a fairly slow speed of play as compared to many other sports. So the genetically engineered players of the future might increase audience satisfaction.

When people start genetically engineering highly athletic offspring this is going to create some pretty big disagreements between nations over international sports. Will the Olympics try to remain genetically natural? They'll have to get genetic samples from parents to prove whether an athletic as a particular combination of athletics enhancing genetic alleles naturally or not. But even such a test won't work entirely. Two prospective parents could choose the ideal combination of their chromosomes to have a child who has the most ideal combination of genes from the two parents.

Genetic testing of parents also won't be possible for offspring whose mothers used sperm donors. Johnny doesn't know who his Dad is. Should that fact rule him ineligible for going to the Winter Olympics as a skier? Of course some moms will choose sperm donors based on great genetic profiles for athletics. So the use of sperm donors will allow natural babies will be born with athletic abilities at a higher rate than is currently the case.

We are living in the end of the era of "wild type" humans. The people around you all carry genes that they got as a result of natural mutations. We are approaching the era where wild type gradually (or not so gradually) gets replaced with the engineered and chosen. This conversion will happen in a very uneven fashion across the world due to differing levels of affluence, regulations, and beliefs.

Not everyone will use offspring genetic engineering. Of those who use it not all will use it as extensively and different people will use it to achieve different goals. Even athletic goals will differ. People who want tall basketball players will chose different genetic alleles than those who want ballet dancers or tennis players or swimmers or golf players. Will more people choose the muscle type ideal for sprints or the muscle type ideal for long distance runners? Will more go for basketball height or defensive lineman solidness? What will be the most popular athletic forms for genetically engineering parents?

By Randall Parker    2007 September 19 09:56 PM   Entry Permalink | Comments (3)
2004 August 24 Tuesday
Mouse Engineered For Marathon Running, Resistance To Obesity

Some researchers at the Salk Institute have developed a transgenic mouse with more slow twitching muscle fibers and a resistance to obesity when fed a high fat diet. (same article here)

LA JOLLA, CA — A molecular switch known to regulate fat metabolism appears to prevent obesity and turns laboratory mice into marathon runners, a Salk Institute study has found.

The discovery of the switch could lead to treatments for obesity and disorders associated with it, such as heart disease and type 2 diabetes. The study, led by professor Ronald Evans and his postdoctoral fellow Yong-Xu Wang, appears in the September issue of the Public Library of Science Biology journal (PLoS Biology). Evans is also an Investigator of the Howard Hughes Medical Institute.

Evans, Wang and team discovered that activation of the switch, a receptor called PPAR-delta, increases the rate at which the body burns fat. This makes PPAR-delta an exciting potential target for drugs that treat diabetes and lipid disorders. The team produced a genetically engineered mouse endowed with the activated form of PPAR-delta in its skeletal muscles. The result was a dramatic increase in "non-fatiguing" or "slow twitch" muscle cells and a mouse capable of running up to twice the distance of a normal littermate without training.

By expressing genes for an activated form of the receptor PPAR-delta, we created a mouse that could, compared to normal mice, run marathons, said Evans. The activated form of PPAR-delta produced muscle fibers that enhanced endurance exercise." By turning on PPAR-delta, the team had produced highly efficient muscle fibers that burned fat more rapidly. As a result, the mice were almost unable to gain weight even in the absence of exercise.

"These muscles also provided resistance to obesity, despite the level of exercise," said Evans. "By manipulating this receptor, it is possible to design treatments that change our muscle makeup and help resist obesity and associated metabolic disorders.

To test the concept, Evans and his team treated normal mice with an experimental drug called GW501516 that activates PPAR-delta. These mice also expressed genes for slow-twitch muscles and gained less weight when given a high-fat diet. This drug is now in the earliest stages of being tested on people for its effects on obesity and other disorders of fat metabolism such as high blood cholesterol.

This experiment underscores the importance of metabolism in fighting obesity and improving fitness, said Evans. Activating the PPAR switch may prevent physical fatigue and enhance the quality of exercise, which may lead to a new class of drugs to promote weight loss and treat diseases arising from an overweight population.

If GW501516 turns out to be safe to use then consider the benefits. The drug may increase your muscle mass, reduce your body fat, lower your cholsterol, and reduce your risk of insulin resistance all at the same time.

A substantial portion of the population of Western nations (and probably other nations as well) will embrace the use of drugs and gene therapy that alters muscle metabolism for health reasons alone. The prospect of competing in athletic competitions will not be the main allure of body engineering for most people. The ability to keep off excess fat, prevent the loss of muscle mass with age, lower cholesterol, and avoid type II insulin-resistant diabetes will together attract more people than the drive to perform better in competitive sports.

The research paper for this report was published in PLoS Biology which offers on-line access at no cost The full research paper drives home the point that upregulation of PPARδ (also spelled above as PPARdelta) made the transgenic mice resistant to obesity.

A number of previous studies have shown that obese individuals have fewer oxidative fibers, implying that the presence of oxidative fibers alone may play a part in obesity resistance. To test this possibility, we fed the transgenic mice and their wild-type littermates with a high-fat diet for 97 d. Although the initial body weights of the two groups were very similar, the transgenic mice had gained less than 50% at day 47, and only one-third at day 97, of the weight gained by the wild-type animals (Figure 4A). The transgenic mice displayed significantly higher oxygen consumption on the high-fat diet than the control littermates (unpublished data). By the end of this experiment, the control littermates became obese, whereas the transgenic mice still maintained a normal body weight and fat mass composition (Figure 4A). A histological analysis of inguinal fat pad revealed a much smaller cell size in the transgenic mice (Figure 4B), due to the increased muscle oxidative capacity. While there was no significant difference in intramuscular glycogen content, the triglyceride content was much less in the transgenic mice (Figure 4C and 4D), which may explain their improved glucose tolerance (Figure 4E). We also placed wild-type C57BJ6 mice on the high-fat diet and treated them with either vehicle or the PPARδ agonist GW501516 for 2 mo. GW501516 produced a sustained induction of genes for type I muscle fibers; this, at least in part, resulted in an only 30% gain in body weight, a dramatically reduced fat mass accumulation, and improved glucose tolerance, compared to the vehicle-treated group (Figure 5). Thus, muscle fiber conversion by stimulation with the PPARδ agonist or the activated transgene has a protective role against obesity.

A synopsis that accompanies the research paper makes the point that most people lack the ideal genetic coding to be a sprinter or to be a marathon runner or both.

Have you ever noticed that long-distance runners and sprinters seem specially engineered for their sports? One's built for distance, the other speed. The ability to generate quick bursts of power or sustain long periods of exertion depends primarily on your muscle fiber type ratio (muscle cells are called fibers), which depends on your genes. To this extent, elite athletes are born, not made. No matter how hard you train or how many performance-enhancing drugs you take, if you're not blessed with the muscle composition of a sprinter, you're not going to break the 100-meter world record in your lifetime. (In case you'd like to try, that's 9.78 seconds for a man and 10.49 seconds for a woman.)

Of course that doesn't prevent those at the highest levels from using the latest performance enhancer to get that extra 1% edge. But wait until trainers hear about the Marathon Mouse. A new study by Ronald Evans and colleagues provides evidence that endurance and running performance can be dramatically enhanced through genetic manipulation.

Skeletal muscles come in two basic types: type I, or slow twitch, and type II, or fast twitch. Slow-twitch fibers rely on oxidative (aerobic) metabolism and have abundant mitochondria that generate the stable, long-lasting supplies of adenosine triphosphate, or ATP, needed for long distance. (For more on muscle fiber metabolism, see synopsis titled “A Skeletal Muscle Protein That Regulates Endurance”) Fast-twitch fibers, which produce ATP through anaerobic glycolysis, generate rapid, powerful contractions but fatigue easily. Top-flight sprinters have up to 80% type II fibers while long-distance runners have up to 90% type I fibers. Coach potatoes have about the same percentage of both.

In the future we are going to be able to use drugs and gene therapy to tune our metabolisms to operate more like the metabolisms athletes who perform best in specific types of sports. But note that we will have to choose how we want to optimize our bodies. An ideal optimization for sprinting will reduce performance in distance running and vice versa.

The drug GW501516 which the Salk team used to upregulate PPARδ may not be causing its main anti-obesity effect by increasing the amount of slow twitch muscle. A different research team at the University of Queensland reports that GW501516 causes changes in lipid metabolism and in energy uncoupling.

Activation of PPARß/δ by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, ß-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARß/δ agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPAR{gamma} induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage

The reference to energy uncoupling suggests that GW501516 and PPARδ might be causing more of the energy that is produced by breaking down sugars to be given off as heat.

By Randall Parker    2004 August 24 02:58 PM   Entry Permalink | Comments (3)
2004 August 23 Monday
Genetically Enhanced Athletes In 2008 Olympics?

Some athletes may already be experimenting with gene therapy to enhance their performance.

"I wouldn't be surprised if somebody (in sports) is trying it as we speak," University of Western Ontario genetics expert Dr. Shiva Singh said. "If you can do it for a diseased muscle, why can't you do it for a normal muscle?"

Many of the therapies developed for muscular dystrophy, muscle injuries, aged muscles, and other muscle disorders will be easily adapted to enhance performance well beyond the natural level of performance. So banning the development of genetic enhancement therapies is not feasible.

Anne McIlroy of the Globe and Mail has an excellent overview of the developments that are leading toward the genetic enhancement of athletic performance. She reports that genetically enhanced athlets may show up at the 2008 Summer Olympics to compete.

Many experts believe that the first genetically modified athletes could be competing at next Summer Olympics.

"I would think the Beijing Olympics may be the time to pick it up on a widespread basis," says Geoffrey Goldspink, an expert in muscle regeneration at the University College Medical School in London. He is already working on a test to detect genetic cheaters for the U.S. anti-doping agency.

...

In 1964, Finnish cross-country skier Eero Mantyranta was suspected of blood doping after winning two gold medals because he had so many red blood cells in his system. Three decades later, he was cleared when researchers found that he and many of his family members have a genetic mutation that increases their red-blood-cell count by 20 per cent.

Eventually the World Anti-Doping Agency will have to face what to do about children genetically engineered to be faster, stronger, and more coordinated from birth. Take the mutation carried by someone like Eero Mantyranta (or the myostatin gene mutation that has produced a super-muscular baby in Germany) and imagine couples who decide to have children and choose to incorporate a mutation like Mantyranta's mutation in their offspring. The kids will never have been given the chance to turn down their performance enhancing genotypes. They may even have only naturally occurring enhancements - just not ones their own parents possess. Lots of performance-enhancing genetic variations are naturally occurring. We let people who by chance naturally get great genetic variations from their parents to compete at the Olympic level. Should people be banned from Olympic sports because their parents gave their kids the same exact variations using genetic manipulations of sperm or eggs or freshly fertilized embryos? If so, why?

Andy Miah argues that genetic enhancement ought to be allowed but genetically enhanced athletes ought to compete in separate categories.

Gene therapies hold so much promise for helping humanity, Dr. Miah says, that he has urged the WADA not to treat them simply as a new form of illegal doping. For example, gene therapy potentially could be used to repair the injured muscles of athletes. Would that use also be illegal? "It's that kind of boundary that's unclear from the present rulings," he says. By making genetic modification illegal, athletes may seek out "rogue scientists," he says. "If we do prohibit it, we push it underground, and we don't know what athletes are doing. They don't know what they're doing." If we regulate instead, "we can try to make sure they're doing it in a safe manner," he says.

Miah points to paralympics competitions where people with different kinds of disabilities compete in different classes. But there is an more striking way in which athletes have been put into different classes based on innate abilities: the division of athletes by sexes. Men have an innate advantage in musculature and even in the strength of some connective parts (e.g. the weaker Anterior Cruciate Ligament in women makes the frequency of ACL injuries much higher in women than in men). Most people (aside from some feminists) accept it as normal that men and women compete in separate groups in most sports. Why shouldn't we take the same approach with genetically modified athletes?

Shannon Klie has an excellent Better Humans article that reviews a number of the recent discoveries of genetic variations which enhance musculature and performance. Klie quotes the argument of USCD cancer research and WADA board member Theodore Friedmann, MD that sports is threatened by a loss in the belief of spectators that the contests are a measure of innate abilities and developed skills.

But while Friedmann thinks that it's inevitable that genetic therapies will be incorporated into international sports, he worries about their effect on the nature of sport. He says that instead of a feat of athleticism being the result of skill, training and dedication, in the future people will wonder if it's a simple product of bioengineering. "It's a threat to sport as we know it," he says.

But I think Friedmann is overlooking two obvious points:

  • As we learn more about existing genetic variations that show just how much individuals differ in their genetic potential the public will come to realize just how much of superior athleticism is due to factors that the athletes have no control over: their own genetic endowment. We will be seen as innately very unequal from each other in physical abilities for genetic reasons that do not reflect on our drive or personal conscious choices. Once DNA sequencing becomes cheap sports announcers will compare competitors in terms of their genetic advantages and disadvantages.
  • Tens or hundreds of millions of people already enjoy watching sports that have a very large element of engineering team competition as part of the total competition. The engineering competitions range across sports and encompass designs of shoes, bicycles, race cars, race boats, sail boats, and countless other items used in a variety of sports.

Once it becomes safe and easy to do genetic enhancement a large fraction of the population will choose to genetically engineer their bodies to improve their looks, strength, resistance to infections, and a great many other qualities. To keep genetic engineering out of professional sports will then require some small fraction of the human population to keep itself in "wild type" state so that "natural" sports can continue to be practiced. My guess is that most potential athletes will decide that is a sacrifice that is too large to be worth it. If existing sports organizations keep their bans on genetic enhancement in effect then new sporting organizations will be formed to hold competitions between the genetically enhanced and the crowds will shift their interests toward the competitions between genetically enhanced athlets. WADA is a reactionary organization in an ultimately futile fight for a type of sports that will eventually be seen as anachronistic.

What is the psychological basis of the opposition to genetic enhancement of athletic performance? Is genetic enhancement seen as a threat to athletics as a sort of folk religion aimed at the worship of what humans can accomplish if they will their selves to power with strong free wills? Or is genetic enhancement more threatening because it is perceived as reducing the role for chance in determining outcomes? Or is it born more from a desire to see human bodies and not machines as the height of human accomplishment? What do you see as threatened by genetic enhancement?

By Randall Parker    2004 August 23 12:00 AM   Entry Permalink | Comments (7)
2004 August 13 Friday
Quick Testosterone Muscle Boosting Makes Use Hard To Detect

The New Scientist reports on a surprising result where it was found that testosterone works so rapidl to boost muscle mass that athletes may be able to escape detection from blood tests by using testosterone for short periods.

The received wisdom is that testosterone must be injected weekly for at least 10 weeks. Yet sports scientist Robert Weatherby of Southern Cross University in Lismore, New South Wales, Australia, who conducted the study, found the biggest increase in performance came after just three weeks.

Taking testosterone for short periods only, taking smaller doses, or doing both, would reduce the chances of athletes getting caught by drugs testers. "Athletes have probably already figured this out, and we are just confirming that scientifically,"

More methods that increase athletic performance while leaving smaller chemical footprints will be found. It will becoe steadily more difficult to detect illegal drug use.

One factor that may shift the advantage back toward the anti-doping agencies is the identification of all the DNA sequence variations that have some effect on athletic performance. Once DNA sequences can be tested for each athlete it will become possible to state that for some athlete his performance exceeds his genetic potential and that therefore he must be cheating. But such DNA testing is still several years away and in the meantime banned performance boosting techniques will become harder to detect. So expect more successful cheating.

By Randall Parker    2004 August 13 03:27 AM   Entry Permalink | Comments (9)
2002 December 06 Friday
Banned Athletic Doping Drug List Needs Revision

Athletes are not allowed to drink coffee or other caffeinated beverages? That seems excessive. Also, cannabis is far more likely to impair than it enhance performance ("Oh, wow, like I totally spaced and forgot I was supposed to be competing in the finals today"). At least the list is going to be fixed.

Insulin is one of a number of drugs that should be removed from the list of banned substances as part of a more scientific approach to the anti-doping battle, a member of the IOC's medical commission said Thursday.

Dr Harm Kuipers told a conference in Madrid that only substances that could be shown both to enhance performance and to produce adverse effects in athletes' health should be prohibited.

He said that caffeine, narcotics such as heroin and morphine, glucocorticoids, pseudo ephedrine and cannabis were all likely to be removed when the World Anti-Doping Agency produces a revised list of banned substances next year.

By Randall Parker    2002 December 06 01:18 PM   Entry Permalink | Comments (1)
2002 November 28 Thursday
Athletic Anti-Doping Testing Seen As Insincere

An article by Selena Roberts in The New York Times examines the International Olympic Committee's half-hearted attempts to police athletic doping by the World Anti-Doping Agency which now has a lab which is supposed to develop new tests to detect hormonal and genetic enhancement of athletic performance. Their efforts are seen by various experts as a cynical attempt to be seen as doing something to control doping. The IOC has such a large interest in the high viewing ratings that come with seeing world records broken that it is argued that they just want to appear to be sincere about controlling doping:

To experts, $18 million is hardly enough in the lab-room chase to develop drug tests that will stand up in a court of law. Athletes remain ahead of the science to nab them, with a head start from the I.O.C.

"I think a lot of the I.O.C. is driven by money," Yesalis said. "A lot of them are greedy. What has evolved is they've done a controlled retreat. At first, they didn't do drug tests at all. Then people started talking about doping, and it was bad for publicity. So it's like, `Well, we'll put in place a drug-testing system that we all know won't catch anyone, but the public won't know.'

There is just no way that the WADA and the USADA (United States Anti-Doping Agency) are going to manage to prevent wider doping by athletes. First of all, they are just not going to apply the resources needed to tackle the problem. But even if they did try harder the problem of detection will become steadily more difficult as gene therapy techniques for optimizing tissues buried deep in the body become possible. See my previous posts on the subject.

By Randall Parker    2002 November 28 01:34 PM   Entry Permalink | Comments (0)
2002 October 28 Monday
Anti-Doping Agencies Versus Athletes And Biotech

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

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

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

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

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

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

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

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

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

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

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

By Randall Parker    2002 October 28 12:04 AM   Entry Permalink | Comments (0)
2002 October 02 Wednesday
Athletic Genetic Manipulation To Be Banned

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

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

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

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

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

This article predicts genetically engineered athletes within 10 years:

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

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

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

Gene Therapy Will Still Become Widely Used For Athletic Purposes

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

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

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

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

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

By Randall Parker    2002 October 02 04:14 PM   Entry Permalink | Comments (12)
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