Somatic gene therapy

.Sports doping with gene transfer:
a virtual or a concrete possibility?

(Gendoping: virtuell oder konkret?)
(Dopage génétique: une réalité virtuelle ou concrète?)

Last update: March 04, 2005

This page will be regularly updated with facts, comments & reactions on this topic.
You are welcome to send your feedback by email to
Sandro Rusconi

 

'Gene-based doping: now, tomorrow, never?

The current western world's perception of sports is based on the romanthic concept of 'mens sana in corpore sano'. This highly positive and very appreciable attitude, which implies that sports should be an intrinsically 'healthy' activity, is a principle that we should strongly defend. However, this is challenged by the individual ambition and the strong commercialisation in the elite sports, in which what finally counts is not the health of the athletes, but money and fame.

Therapy of various diseases through gene transfer is a long-term vision of scientists and clinicians. Amongst the many difficulties, the strategy of using genes as drugs begins to show its very first promising results. However, the current technology is still much to immature to guarantee the necessary safety to justify treatment of non-lethal diseases.

In spite of the immaturity-status of gene transfer, the sports-doping scene has manifested interest in gene transfer as a doping vehicle. People seem to believe that with gene-transfer everything will be easier and less detectable. The recent results with the enhancement of muscle performance with the growth factor IGF-1 have suscitated the wildest dreams in the mind of reckless sports managers or athletes. But people forget that gene therapy is currently intrinsically dangerous and that even doping with gene transfer is relatively easily detectable.

This page must be interpreted as a strong warning attempt about the risks of engaging in these extremely hazarduous experimentations.
Ergo: Athletes and coaches, stay away from gene transfer!
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Media Box

press releases

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  • New York Times ( The Lab animal, Jan 18, 2004)
  • Assoc Press (Gene Therapy Could Lead to Super Athletes, Feb 15 2004)
  • Assoc press (Muscle building gene therapy ... Feb 16,04)
  • BetterHum web (Muscle-bound Rats Prompt Sporting Debate, Feb 16, 04)
  • New York times (Gene doping is 'new frontier' for sports cheats, feb 16 2004)
  • New scientist (Study raises fears of genetically modified athletes, feb 16 04)
  • Iowa State DN (Gene therapy on rats could possibly lead to 'superathletes', March 03 2004)
  • Stuff.co (Genetic engineering is next doping threat, March 16 04)
  • radio netherlands (Muscles, maladies and mischief, march 22, 2004)
  • daily champion (Genetic Research Boosts Athlete Cheats, march 26, 04)
  • Assoc press (Experts believe athletes and coaches will soon turn to gene doping..17.04.04)
  • Molecular Therapy (genetic doping is detectable, sept 2004) !
  • Indiana Express (Feb2005, on poor detectability)
  • OLDER DOCs
  • Science daily (Mighty Mice Are Less Susceptible ... Nov 26, 2002)
  • science daily ("Mighty Mice" Gene Is Mutated In Beefy Bovines, Nov 13 1997)


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The Lab Animal

New York Time, January 18, 2004

By MICHAEL SOKOLOVE

On a brisk day last month, I was led through a warren of red brick buildings on the campus of the University of Pennsylvania in West Philadelphia and then up to a fifth-floor molecular physiology laboratory. I had come to visit some mice -- and to get a peek at the future of sport.

I had heard about these mice, heard them called ''mighty mice,'' but I was still shocked at the sight of them. There they were in several small cages, grouped with normal mice, all of them nibbling on mouse chow pellets. The mighty mice looked like a different animal. They were built like cattle, with thick necks and big haunches. They belonged in some kind of mouse rodeo.

The Penn researchers have used gene therapy on these mice to produce increased levels of IGF-1, or insulinlike growth factor-1, a protein that promotes muscle growth and repair. They have done this with mice before birth and with mice at four weeks of age. A result has been a sort of rodent fountain of youth. The mice show greater than normal muscle size and strength and do not lose it as they age. Rats altered in the same fashion and then put into physical training -- they climb little ladders with weights strapped to their backs -- have experienced a 35 percent strength gain in the targeted muscles and have not lost any of it ''detraining,'' as a human being will when he quits going to the gym.

To the scientists, H. Lee Sweeney, chairman of Penn's department of physiology, and Elisabeth Barton, an assistant professor, the bizarre musculature of their lab specimens is exciting. This research could eventually be of immense benefit to the elderly and those with various ''muscle wasting'' diseases. ''Our impetus, going back to 1988, was to develop a therapy to stop people from getting weak when they get old,'' Sweeney, 50, explained. ''They fall and injure themselves. We wanted to do something about that.''

Barton, 39, has the broad shoulders and athletic build of the competitve cyclist and triathlete she once was. ''You see children with muscular dystrophy, and their parents are just so broken up because it's so sad,'' she said. ''You see grandparents who can't get out of bed. These are the people this is for.'' But the Penn team has become acutely aware of a population impatient to see its research put into practice -- the already strong, seeking to get stronger still. Sweeney gets their e-mail messages. One came from a high-school football coach in western Pennsylvania not long after Sweeney first presented his findings at a meeting of the American Society for Cell Biology. ''This coach wanted me to treat his whole team,'' he said. ''I told him it was not available for humans, and it may not be safe, and if I helped him we would all go to jail. I can only assume he didn't understand how investigational this is. Or maybe he wasn't winning, and his job was on the line.''

Other calls and e-mail messages have come from weight lifters and bodybuilders. This kind of thing happens often after researchers publish in even the most arcane medical and scientific journals. A whole subculture of athletes and the coaches and chemists who are in the business of improving their performances is eager for the latest medical advances. Sweeney knows that what he is doing works. The remaining question, the one that will require years of further research to answer, is how safe his methods are. But many athletes don't care about that. They want an edge now. They want money and acclaim. They want a payoff for their years of sweat and sacrifice, at whatever the cost. ''This was serious science, not sports science,'' Dr. Gary Wadler, a United States representative to the World Anti-Doping Agency, said when I spoke to him about the Penn experiments. ''As soon as it gets into any legitimate publication, bango, these people get ahold of it and want to know how they can abuse it.'' Sweeney's research will probably be appropriated before it is ever put to its intended medical purpose. Someone will use it to build a better sprinter or shot-putter. There is a murky, ''Casablanca''-like quality to sport at the moment. We are in a time of flux. No one is entirely clean. No one is entirely dirty. The rules are ambiguous. Everyone, and everything, is a little suspect.

Months before the great slugger Barry Bonds was summoned before a grand jury in December to answer questions about his association with the Bay Area Laboratory Co-Operative, known as Balco, which has been at the center of a spreading drug scandal after the discovery of a new ''designer steroid,'' tetrahydrogestrinone (THG), a veteran American sprinter named Kelli White ran the track meet of her dreams at the World Championships in Paris. She captured the gold medal in the 100-meter and 200-meter races, the first American woman ever to win those sprints in tandem at an outdoor world championship. In both events, the 5-foot-4, 135-pound White, a tightly coiled ball of power and speed, exploded to career-best times.

On a celebratory shopping trip on the Champs-Elysees, White, 26, glimpsed her name in a newspaper headline and asked a Parisian to translate. She learned that she had flunked a postrace drug test and that her medals and $120,000 in prize money were in jeopardy. Later, she acknowledged that she had taken the stimulant modafinil, claiming that she needed it to treat narcolepsy but had failed to list it on a disclosure form. What she added after that was revealing, perhaps more so than she intended. ''After a competition,'' she told reporters in Europe, ''it's kind of hard to remember everything that you take during the day.''

The THG scandal and the attention focused on Balco, which has advised dozens of top athletes (including Kelli White) on the use of dietary supplements, has opened the curtain on a seamy side of sport and on the fascinating cat-and-mouse game played between rogue chemists and the laboratory sleuths who try to police them.

But White's statement exposed another, deeper truth: elite athletes in many different sports routinely consume cocktails of vitamins, extracts and supplements, dozens of pills a day -- the only people who routinely ingest more pills are AIDS patients -- in the hope that their mixes of accepted drugs will replicate the effects of the banned substances taken by the cheaters. The cheaters and the noncheaters alike are science projects. They are the sum total of their innate athletic abilities and their dedication -- and all the compounds and powders they ingest and inject.

A narrow tunnel leads to success at the very top levels of sport. This is especially so in Olympic nonteam events. An athlete who has devoted his life to sprinting, for example, must qualify for one of a handful of slots on his Olympic team. And to become widely known and make real money, he probably has to win one of the gold medals that is available every four years.

The temptation to cheat is human. In the realm of elite international sport, it can be irresistible.

After Kelli White failed her drug test, the United States Olympic Committee revealed that five other American athletes in track and field had tested positive this summer for modafinil. Did they all suffer from narcolepsy? That would be hard to believe. More likely, word of modafinil and its supposed performance-enhancing qualities (perhaps along with the erroneous information that it was not detectable) went out on the circuit. It became the substance du jour.

For athletes, performance-enhancing drugs and techniques raise issues of health, fair play and, in some cases, legality. For sports audiences, the fans, the issues are largely philosophical and aesthetic. On the most basic level, what are we watching, and why? If we equate achievement with determination and character, and that, after all, has always been part of our attachment to sport -- to celebrate the physical expression of the human spirit -- how do we recalibrate our thinking about sport when laboratories are partners in athletic success?

Major League Baseball, which came late to drug testing and then instituted a lenient program, seems to have decided that the power generated by bulked-up players is good for the game in the entertainment marketplace. The record-breaking sluggers Mark McGwire and Sammy Sosa have been virtual folk heroes and huge draws at the gate. Their runs at the record books became the dominant narratives of individual seasons. (Barry Bonds has been less popular only because of a sour public persona.) But the sport is much changed. Muscle Baseball is the near opposite of what I and many other fans over 30 were raised on, a game that involved strategy, bunting, stolen bases, the hit-and-run play -- what is called Little Ball.

Professional basketball is not generally suspected of being drenched in steroids and other performance enhancers. But anyone who has seen even a few minutes of old games on the ESPN Classic network from, say, 20 years ago, is immediately struck by the evolution of players' physiques. Regardless of how it happened, today's N.B.A. players are heavier and markedly more muscled, and the game is tailored to their strengths. It is played according to a steroid aesthetic. What was once a sport of grace and geometry -- athletes moving to open spaces on the floor, thinking in terms of passing angles -- is now one primarily of power and aggression: players gravitate to the same space and try to go over or through one another.

But it is sports that have fixed standards and cherished records that present fans with the greatest conundrum. If what's exciting is to see someone pole vault to a new, unimaginable height -- or become the ''world's fastest human'' or the first big-leaguer since Ted Williams to hit .400 -- how do we respond when our historical frame of reference is knocked askew by the suspicion, or known fact, that an athlete is powered by a banned substance?

In elite sport, the associations of competitors who have never been sanctioned for drug use or known to fail a drug test can still raise questions. Marion Jones, the breathtaking sprinter and featured American performer of the 2000 Sydney Olympics, was married to the shot-putter C.J. Hunter -- who was banned from those games after testing positive for the steroid nandralone. Jones later divorced Hunter, but then trained (briefly) with Charlie Francis, the disgraced ex-coach of Ben Johnson, the disgraced Canadian sprinter who was stripped of an Olympic gold medal. Carl Lewis, the greatest U.S. Olympian in history and a longtime crusader against performance-enhancing drugs -- it was Lewis who was outsprinted by the steroid-fueled Ben Johnson at the 1988 Games in Seoul -- has been accused of flunking a drug test of his own before the 1988 U.S. Olympic Trials. Lance Armstrong, brave cancer survivor, fierce and inspiring competitor, has kept up a long association with an Italian doctor in the thick of a sprawling drug scandal in Europe, although Armstrong himself has never come up positive on a drug test.

Even the substances themselves are murky. Because the $18-billion-a-year dietary-supplement industry is (at best) loosely regulated, some of the potions in the vitamin store at your local mall could well be tainted by steroids or growth hormones. The Food and Drug Administration just got around to banning the sale of ephedra last month, long after the herbal stimulant was blamed for numerous serious health problems, along with the sudden death last year of Steve Bechler, a Baltimore Orioles pitcher.

The whole situation cries out for a dose of clarity, but the closer you look, the fuzzier the picture. Start with the line between what's legal and illegal when it comes to enhancing performance. The line, already blurry, is likely over time to disappear entirely.

I visited a U.S. swimmer last September as technicians sealed up his bedroom, after which they installed equipment that reduced the amount of oxygen in his room and turned it into a high-altitude chamber. This is a common and legal training method that Ed Moses, America's best male breaststroker, said he hoped would increase his count of oxygen-carrying red blood cells. A whole team of long-distance runners sponsored by Nike lives in a much more elaborate simulated high-altitude dwelling in Portland, Ore. The desired effect of the so-called ''live high, train low'' method -- sleep at altitude, train at sea level -- is the same as you would get from taking erythropoietin, or EPO, which increases red-blood-cell production and is banned in sports.

Two other U.S. swimmers, in the lead-up to the Olympic Games in Sydney, were on a regimen of 25 pills a day, including minerals, proteins, amino acids and the nutritional supplement creatine, an effective but not necessarily safe builder of muscle mass. Much of the mix may well have been useless, but athletes tend to take what's put in front of them for fear of passing up the one magic pill.

''I like to think we're on the cutting edge of what can be done nutritionally and with supplements,'' the swimmers' coach, Richard Quick, said then as his athletes prepared for the 2000 games. ''If you work hard consistently, with a high level of commitment, you can do steroidlike performances.'' One of his swimmers, Dara Torres, who increased her bench press from 105 pounds to 205 pounds and swam career-best times at the age of 33, said at the time that her goal was to ''keep up with the people who are cheating without cheating.'' And who are the cheaters? Everyone else. One primary motivation to cheat is the conviction that everyone else is cheating.

To draw the often arbitrary lines between performance enhancing and performance neutral, between health endangering and dicey but take it at your own risk -- to ensure that sport remains ''pure'' -- a vast worldwide bureaucracy has been enlisted.

At the lowest level are those who knock on the doors of athletes in their homes and apartments in the United States and Europe and in the mountain villages of Kenya and at the training sites in China and demand ''out of competition'' urine samples. Higher up on the pyramid are the laboratories around the world chosen to scan the urine (and blood) of elite athletes for the molecular signatures of any of hundreds of banned substances. At the top of the drug-fighting pyramid are the titans of international sport -- the same people who cannot see to it that a figure skating competition is fairly judged.

The titans created the World Anti-Doping Agency, which works with governments and designated national organizations, including the United States Anti-Doping Agency. In combination with the urine-sample collectors, the various couriers in the chain of custody and the laboratories, W.A.D.A. is charged with making sure that the world's premier athletes are clean -- and additionally that they have not concealed drug use through the use of various ''masking agents.'' (The latest U.S.A.D.A. list specifically prohibits the following brand names: Defend, Test Free, Test Clean, UrinAid and Jamaica Me Clean.)

It is all an immensely complicated endeavor, one that requires W.A.D.A. to keep up with the onrushing science, to disseminate information to thousands of athletes, to navigate in different legal systems so that accused competitors get due process and, lastly, to manage the worldwide trafficking of urine samples. And it is all, in the end, quite possibly pointless.

Despite the hundreds of people and tens of millions of dollars devoted to the effort, international and national sports organizations may just lack the will to catch and sanction cheaters. The United States, specifically, has been singled out as negligent in its oversight. ''The real issue is that USA Track and Field has become a complete and utter scofflaw,'' the W.A.D.A. president, Richard Pound, a Canadian, told me. ''They have gone to extraordinary lengths to hide identities and data and to exonerate athletes who have tested positive.''

Can you really have a serious antidoping effort without the full cooperation of the world's most powerful nation -- and most powerful sports nation? It's hard to see how.

The tougher question is whether it will be scientifically possible to stay ahead of the cheaters. The rogue scientists and coach-gurus have been winning for years, and they have ever more tools available to them. THG, which set off the Balco inquiry, is only a slightly more clever version of an old thing: an anabolic steroid -- the kind of blunt builder of muscle mass and strength prevalent in sports since the 1950's. But its discovery required an insider tip, and THG is child's play compared with what's coming in the near future (if, in fact, it is not here already): genetic manipulation in order to improve athletic performance.

Ultimately, the debate over athletic doping extends beyond sport. ''The current doping agony,'' says John Hoberman, a University of Texas at Austin professor who has written extensively on performance drugs, ''is a kind of very confused referendum on the future of human enhancement.''

Pete Rose was the prototypical ''self-made'' athlete, which is code for a sort of seeming nonathlete who makes the most of his meager abilities. But fans overlooked important genetic traits that made him baseball's all-time hits leader -- chiefly, uncommon durability that allowed him to play 24 seasons virtually injury free. And what did Rose do to attain that? Nothing, really. As the son of a semipro athlete who played sandlot baseball and football into his early 40's, he came by that blocky, unbreakable body by way of genetic inheritance. In the off-season, Rose maintained himself by playing casual basketball a couple of times a week and eating greasy food and heaping bowls of potato chips.

When it comes to elite sport, there is no such thing as self-made. No amount of dedication can turn someone of average ability into a world-class sprinter, an N.B.A. player or a champion marathoner. You can't be an Olympic pistol shooter without some innate steadiness of hand or a Tour de France cyclist without a far-above-average efficiency at moving oxygen to muscles. Even a humdrum, physically unimpressive player on a major-league baseball team has something -- usually extraordinary hand-eye coordination -- that is not apparent to those who regard athletic gifts only in terms of great size, speed, endurance or power.

The former Olympic track coach Brooks Johnson once told me that sport at its highest level should be viewed as a competition waged among ''genetic freaks.'' He mentioned Carl Lewis and Michael Jordan. But anyone who reaches the top echelon of Olympic competition or draws a paycheck for playing sports professionally should be considered in the same category. You cannot will yourself into an elite athlete, or get there through punishing workouts, without starting out way ahead of the rest of the human race.

You may, through pure dedication, be able to jump one level -- from a middle-of-the-pack Olympic sprinter to the final heat, from a marginal N.F.L. prospect to a midround draft pick. Chemical enhancement can produce more significant improvements, but the principle is the same. You've got to start out as a member of the athletic elite.

At the 1996 Summer Olympics in Atlanta, a middling Irish swimmer named Michelle Smith de Bruin raised suspicions when she won three gold medals. She later flunked drug tests. But before the presumed cheating, she was already a competitor on the international swim scene, not a lap swimmer at the Dublin Y.

The use and abuse of performance-enhancing drugs in elite sport, or doping, as it has been called since around 1900, is a mutant form of an exclusive competition. It is an effort by individuals who are already part of a thin slice of humanity -- the genetic freaks -- to gain an edge against one another, to exceed their physiological limits in a way that they could not through pure training. (The word itself is believed to derive from the Dutch word dop, an alcoholic beverage consumed by Zulu warriors before battle.)

While systematic doping -- with the collaboration of chemists, doctors, coaches and trainers -- is a modern phenomenon, scientific interest in athletes is not new. The medical establishment once viewed athletes with curiosity and occasionally with alarm. The act of training and pushing yourself to physical limits was considered dangerous or even a form of sickness. Sports science was observational, an opportunity to study the body in motion by looking at individuals at the extremes of human capacity.

The British physiologist A.V. Hill, a Nobel laureate in 1922, went to Cornell to study sprinters because, as he wrote, ''matters of very great scientific interest can be found in the performances of that extraordinary machine, the human athlete.'' John Hoberman, the historian of sports doping, has written that scientists and doctors viewed the high-performance athlete as ''a wonder of nature -- a marvelous phenomenon that did not require improvement.''

Certainly, athletes have long sought their own chemical and nutritional means to enhance performance. The ancient Greeks ran and wrestled in the nude because nothing, not even fabric, was supposed to interfere with the purity of sport, yet they ate mushrooms, sesame seeds, dried figs and herbs that were believed to give a precompetition energy boost. Marathoners and cyclists as recently as a century ago competed under the influence of strychnine, which is both a stimulant and a poison. Cyclists also used caffeine, cocaine, alcohol and even heroin.

What changed everything -- what transformed performance-enhancing efforts from the realm of superstition into a true science -- was the isolation of the male hormone testosterone in 1935. That led to the development by the late 30's of synthesized testosterone variants, or anabolic steroids. The difference between steroids and all previous performance enhancers was that steroids demonstrably worked -- and they worked really well.

Nearly every drug used by athletes to boost performance started out as a therapeutic miracle.

Steroids are still prescribed for men with serious testosterone deficiencies. AIDS patients and others with muscle-wasting conditions are dosed with steroids.Until the mid-80's, people suffering from severe anemia, as a result of chronic renal failure or other causes, had to undergo frequent blood transfusions. The development of recombinant human erythropoietin was a godsend. Instead of transfusions, anemics could get injections to boost their red-blood-cell count.But what would the effect of EPO be on a person with a normal or better than normal red blood count? What could it do for an already genetically gifted, highly trained endurance athlete? Just what you would expect: make a superendurance athlete.

EPO swept the professional cycling circuit in Europe like a plague, nearly wrecking the sport. There were police raids, huge stockpiles of EPO confiscated from cyclists' hotel rooms, arrests, trials, wholesale suspensions of competitors. ''Each racer had his little suitcase with dopes and syringes,'' a former doctor for European professional cycling teams told a British newspaper. ''They did their own injections.''EPO migrated to other endurance sports, including cross-country skiing, marathoning and orienteering. Inevitably, it showed its fatal flip side. ''In simplest terms, EPO turns on the bone marrow to make more red blood cells,'' says Gary Wadler, the American delegate to W.A.D.A. ''But there's a very delicate balance. You can have too much EPO. The body is a finely tuned instrument. It has feedback mechanisms to keep it in balance. What these athletes are often trying to do is get around the feedback, to trick their own bodies.''

Between 1989 and 1992, seven Swedish competitors in orienteering -- a mix of running and hiking that is sometimes called ''cross country with brains'' -- died, apparently from heart attacks. Nearly all were in their 20's. As many as 18 Dutch and Belgian cyclists died under similarly mysterious circumstances between 1987 and 1990.''At first they said it was some kind of virus, a respiratory virus,'' Wadler says. ''But what kind of virus only knocks off the most fit individuals in their country? The autopsies were private. All the deaths were not definitively linked. But it was EPO. That was obvious to a lot of people.''

For weight lifters and competitors in the ''throwing'' sports of shot-put, javelin, discus and hammer, the performance enhancer of choice has long been steroids. Anabolic steroids (anabolic means tissue building) increase muscle mass and enhance the explosiveness needed for a wide range of other athletic endeavors: sprinting, jumping, swimming, serving a tennis ball, swinging a baseball bat, delivering a hit on the football field. They afford an additional benefit in a violent sport like football because one of their side effects is aggressiveness or, in extreme cases, so-called roid rage.

Their use is starkly high risk, high reward. Other side effects include liver tumors, impotence, breast enlargement and shrunken testicles in men and male sexual characteristics in women. (Some of the side effects for women include enlargement of the clitoris, deepening of the voice, facial hair and male-pattern baldness.) If you want a peek at the future of performance-enhanced sport -- at what drug-laced athletes can accomplish -- look back to the mid-80's, the apex of East Germany's shameful and ruthlessly effective doping program. The East Germans were not the only practitioners of extreme pharmacological sport, only the most flagrant and well organized. (East Germany is the only nation known to have systematically doped athletes, often minors, without their knowledge.)

''Things really got out of hand in the 1970's, 80's and 90's,'' Richard Pound of the W.A.D.A. says. Even as the science of detection improved, the International Olympic Committee and other global sports bodies were constrained, he says, by a ''hesitancy to offend'' either side while the world was still divided between East and West. ''We looked away, and it snowballed.''

Steroid usage works particularly well for women athletes, because they naturally make only a fraction of the testosterone that men produce. John Hoberman says: ''In the 80's, what we saw was this new breed of monster athletes, particularly on the female side.'' Certain records from this heyday of unpoliced steroid abuse -- particularly in sports in which raw strength is a primary requirement -- suggest that performances were achieved then that are unlikely to be matched by a clean competitor. The top 14 men's hammer throws in history occurred between 1984 and 1988. In the women's shot-put, you must go all the way down to the 35th farthest throw in history to find one that occurred after 1988.

Until last April, the top 10 men's shot-put throws in history occurred between 1975 and 1990. Then, at a competition in Kansas, the American shot-putter Kevin Toth finally broke into that elite group. His distance, 22.67 meters, was the farthest that anyone had put the shot in 13 years. Six months later, Toth's name was among the first to surface in the Balco scandal. Published reports said he had tested positive for THG, the new designer steroid.

In women's sprinting in the 80's, the star -- and still the world-record holder in the 100- and 200-meter dashes -- was Florence Griffith Joyner, FloJo. Americans loved her style, her body-hugging track suits, her long and fabulously decorated nails, her ebullience. Elsewhere in the world, and even in the United States among those with a knowledge of track and field, FloJo's exploits were viewed with more skepticism.

After Joyner died in 1998, at 38 (the cause was related to a seizure), a strange hybrid of a column appeared in the New York Times sports section. Written by Pat Connolly, who had coached Evelyn Ashford, the woman whose 100-meter record Joyner smashed, it was partly a tribute and partly a posthumous indictment. ''Then, almost overnight, Florence's face changed -- hardened along with her muscles that now bulged as if she had been born with a barbell in her crib,'' Connolly wrote. ''It was difficult not to wonder if she had found herself an East German coach and was taking some kind of performance-enhancing drugs.''

FloJo had been a very good, but never a champion, world-class sprinter. Her 1988 performance in Seoul was -- in the damning parlance of international sport -- anomalous. We don't normally think of baseball in the context of hammer throwing, shot-putting or women's sprinting. But in terms of anomalous performance, baseball is East Germany in the 1980's: a frontier.

Just as in the steroid-drenched days of Olympic sport, a deep suspicion has attached itself to some of the latest records in baseball. This accompanies the grotesqueness of the appearance of some of the players. Curt Schilling, the All-Star pitcher, memorably told Sports Illustrated in 2002, ''Guys out there look like Mr. Potato Head, with a head and arms and six or seven body parts that just don't look right.''

I'm not sure whom, exactly, Schilling had in mind, but for me, his comment recalls a particular photograph taken in the 2002 season. The subjects are the home-run kings Barry Bonds and Sammy Sosa, sitting together, both of them with thick necks and bloated-looking faces. They look, well, freakish -- as well as starkly different from their appearance as young players. Bonds entered baseball lean and wiry strong, much like his late father, the All-Star outfielder Bobby Bonds. Sosa, early in his career, was not particularly big and showed little power at the plate.

The question of how many home runs it is possible to hit in one season is more open-ended than, say, the fastest possible time a person can achieve in the 100-meter dash. Factors like the size of the ballpark, liveliness of the ball and skill of opposing pitchers affect the outcome. Nevertheless, a century's worth of experience amounted to a pretty persuasive case that around 60 home runs, for whatever combination of reasons, was about the limit.

In 1927, Babe Ruth slugged 60, which remained the record until 1961, when Roger Maris (in a slightly longer season) hit 61. But in 1998 Mark McGwire of the St. Louis Cardinals obliterated Maris's record by hitting 70 home runs. Late in that season, a reporter snooping around McGwire's locker spotted a bottle of androstenedione, or andro, a substance usually described as a steroid ''precursor'' that provides a steroidlike effect (and that is still unregulated in the major leagues). McGwire was forced to acknowledge that his strength was neither entirely ''God given'' nor acquired solely in the weight room. But at least McGwire entered baseball already big and as a prodigious home-run hitter; he hit 49 in his first big-league season, a record for rookies. Contrast that with the career arcs of Bonds and Sosa, which are unlike any in the game's long history.

Bonds had never hit more than 46 home runs until the 2000 season, and in most years his total was in the 30's. But at age 35, when players normally are on the downside of their production, he hit 49 home runs. The following season he turned into superman, breaking McGwire's record by hitting 73. Bonds's totals in the next two seasons, 46 and 45, were artificially low because pitchers walked him a staggering 346 times. His new capabilities had thrown the balance between pitcher and hitter completely out of whack: the new Barry Bonds was too good for the game. He needed a league all his own.

Sosa's progression was even more unusual. In his first eight major-league seasons he averaged 22 home runs, although his totals did steadily increase and he hit 40 in 1996, then a career high. He was selected an All-Star exactly once. Unlike Bonds, he was not considered among baseball's elite players. Then in 1998, McGwire's record-breaking year, Sammy Sosa hit 66 home runs -- 6 more than the great Babe Ruth had hit in his best season. Sosa wasn't done. The following year he hit 63, followed by seasons of 50, 64 and 49 -- the best five-year total in baseball history.

That there is rampant steroid use in baseball, at all levels, is undeniable. Ken Caminiti, the 1996 National League M.V.P., admitted his own use in a Sports Illustrated article in 2002 and estimated that at least half the players in the big leagues built strength with steroids. The former slugger Jose Canseco has acknowledged steroid use. In a 2002 USA Today survey of 556 big-league players, 44 percent said they felt pressure to take steroids.

Last year, The Washington Post published a sad series of stories revealing that teenage prospects in the baseball-rich Dominican Republic, the source of nearly one-fourth of all players signed to U.S. pro contracts, are taking veterinary steroids to try to get strong enough to attract the interest of scouts.

Whether Sosa and Bonds have built home-run power chemically cannot be known definitively. Nobody has presented evidence that they have, and both vehemently deny it. Sosa's name has not surfaced in the Balco case, and he has not testified before the grand jury.

Bonds did testify in December. The home of his personal trainer and boyhood friend, Greg Anderson, has been searched by federal agents. Bonds has acknowledged patronizing Balco, which under Victor Conte, its founder, has specialized in testing athletes' blood to determine the levels of elements like copper, chromium and magnesium and then recommending supplements. Experts I talked to say they consider Conte's theories medical mumbo jumbo, but he consulted with dozens of top athletes, including Marion Jones; Amy Van Dyken, an Olympic champion swimmer; and Bill Romanowski, a linebacker in the N.F.L. Jason Giambi of the Yankees was also a client and also testified before the grand jury.

In an article that appeared last June, Bonds told Muscle and Fitness magazine: ''I visit Balco every three to six months. They check my blood to make sure my levels are where they should be. Maybe I need to eat more broccoli than I normally do. Maybe my zinc and magnesium intakes need to increase.'' Bob Ryan, a veteran Boston Globe sports columnist, is among the baseball devotees who want to believe all Bonds is taking is broccoli and vitamins. But with both Bonds and Sosa, the presumption of innocence he would like to grant them clashes with the accumulation of circumstantial evidence and his own common sense. ''I knew every baseball benchmark from the time I was 10 or 11 years old,'' Ryan says. ''I knew 60, and I knew 61. I knew 714 (the former career home-run mark held by Babe Ruth). Stats frame who a player is. They're part of the romance of the game, the enjoyment.''

Bonds, with 658 career home runs, could surpass Hank Aaron's all-time total of 755 in just two or three more seasons. If he does, what will it mean? Will it carry the romance of other cherished baseball records? ''Bonds was a leadoff man who could run early in his career, and now he is this hulking slugger,'' Ryan says. ''Sammy, same thing. You want to believe it's all due to weight training and nutrition, but you have these guys hitting 40 home runs, maximum, and then well into their careers, they're in the 60's and 70's. It doesn't happen.'' But Ryan is not seeking much new information on this subject. ''I'm afraid of what you're going to tell me next,'' he says at one point in our conversation. ''I'm living in some sort of denial. I'm afraid to look under the rock.''

The world Anti-Doping Agency, imperfect as it may be, is generally considered an improvement over the patchwork approach to drug enforcement that preceded it. Created in 1999 at the World Conference on Doping in Sport in Lausanne, Switzerland, the agency was intended to bring coherence to antidoping regulations and ''harmonization'' among all the different nations and sports bodies expected to enforce them. In theory, it is the ultimate authority on matters of drugs and sport -- looming over national Olympic committees and the national and international federations of all the individual sports and making it more difficult for those parochial interests to protect athletes caught doping.

W.A.D.A.'s medical committee devoted several years to compiling an impressively voluminous list of banned substances. But the role of W.A.D.A. and its president, Richard Pound, is mainly bureaucratic and political. W.A.D.A. can't slow science down -- or influence a culture that hungrily pursues human enhancements of all kinds. ''All of these issues are going to be moot in 20 or 30 years,'' says Paul Root Wolpe, a professor of psychiatry at Penn and the chief of bioethics at NASA. ''We already are seeing a blurring of the line between foods and drugs, so-called nutraceuticals. In the future, it will be more common, accepted. We'll eat certain engineered foods to be sharp for a business meeting, to increase confidence, to enhance endurance before a race or competition.''

Currently, in determining whether to put something on its banned list, W.A.D.A. considers whether a substance is performance enhancing, contrary to the spirit of sport or potentially dangerous to health. ''If it meets two of the three criteria, we are likely to put it on the list,'' Pound says. But the first two criteria are ambiguous. Steroids and EPO are clearly performance enhancing. But so might Gatorade be, if you believe its advertising and all the data on the ''science of hydration'' disseminated by the Gatorade Sports Science Institute. And plenty of sports drinks claim to do more than Gatorade. ''You identify a line and draw it somewhere,'' Pound says. ''Why is it the 100-meter dash and not the 97-meter dash? It just is.''

Between Gatorade and anabolic steroids lie all those powders and pills and injectibles that elite athletes put into their bodies, in quantities and combinations that may enhance performance or may prove innocuous. In most cases, no one is quite sure. Less open to interpretation is ''potentially dangerous to health.'' Any medical or pseudo-medical activity that takes place underground or in the black market is, by definition, dangerous. Nearly everyone, regardless of how they feel about abortion, will agree that it's more dangerous when it occurs in a back alley. Steroid use, dicey in most situations, is certainly more so when it takes place in the dark.

So issues of health are the strongest rationale for W.A.D.A. and the whole antidoping effort: to protect athletes from their own worst instincts. (Though the sports world is selective about its concerns for athletes' health. Offensive lineman in the N.F.L. just keep on getting fatter. The typical career of a major-league pitcher usually involves the gradual deterioration of shoulder and elbow.) But safety is going to become less of an issue.

''Right now we have a crude way of enhancing muscle mass,'' Wolpe says. ''Years from now we'll look back on it, and it will seem low tech. When it's all on the dining-room table, there will not be the same kind of health issues we are seeing now with the unregulated and illicit supplements and drugs.'' What I learned during my visit to Lee Sweeney's lab at the University of Pennsylvania is that lifting his research for purposes of athletic enhancement is not from some sci-fi future. It's possible -- now.

Sweeney and his team know for sure they can build muscle mass and strength. Their next step as they try to determine if their methods are safe for humans will be to experiment on larger animals, most likely dogs with muscular dystrophy. I asked Elisabeth Barton what would happen if some rogue nation or outlaw conglomerate of athletes asked her to disregard scientific prudence and create a human version of the mighty mice. Could she do it? ''Could I?'' she answered. ''Oh, yeah, it's easy. It's doable. It's a routine method that's published. Anyone who can clone a gene and work with cells could do it. It's not a mystery.'' Behind her, Sweeney nodded his head in agreement. ''It's not like growing a third arm or something,'' he said. ''You could get there if you worked at it.''

Sweeney said that once someone decided to use gene therapy to enhance performance, ''you would not be limited to what I'm doing. You could change the endurance of the muscle or modulate the speed -- all the performance characteristics. All the biology is there. If someone said, 'Here's $10 million -- I want you to do everything you can think of in terms of sports,' you could get pretty imaginative.''

To strengthen leg muscles for a sprinter, Sweeney said, he would ''put the whole leg on bypass. I would isolate the leg and put in the virus through the blood. It would be more efficient than injections, which you would need a lot of because you're dealing with large muscles. But this is nothing a vascular surgeon couldn't do.'' Could one already be doing it? ''I don't know that it's not happening.'' IGF-1 is already available on the Internet in ingestible form. It is advertised as a component of various powders and pills, and in this form it falls somewhere in that vast, murky area of legal, quasi-legal, black-market and plainly illegal substances for sale in the semiregulated supplement industry. But Sweeney says that any nongenetic transfer of the protein would be ineffective -- it would not circulate in the blood in levels high enough to build muscle -- and unsafe, because to the extent that it does circulate, it would target nonskeletal muscle, including the heart. (The mighty mice have shown no signs of enlarged hearts or other organs and no sign at all that the IGF-1 is circulating in their bloodstreams.)

For the elite athlete, that would be one of the benefits of genetic IGF-1. It wouldn't circulate in the blood. It would be detectable only through a muscle biopsy. It took a long time for the world's athletes to agree to submit to blood tests; it's difficult to imagine them consenting to having investigatory needles stuck in their muscles. W.A.D.A. invited geneticists and others involved in the latest medical research to a conference in 2002 on Long Island. The antidoping officials were (and still are) focused on the IGF-1 research at Penn, so Lee Sweeney was there. He listened as Richard Pound tried a very tough sell.

The W.A.D.A. president told the scientists that he certainly appreciated the work they were doing, knew that they approached it with single-minded dedication and understood full well that nothing was more important than seeking cures for dread diseases. He then talked about another ''humanistic activity'' that he said was already threatened by science of a certain kind -- the current science of performance enhancement -- and could be ruined by the misuse of their research. As they moved forward, Pound asked, could they somewhere keep in mind the interests of sport?

As Pound recalls, the initial responses he got were somewhat dismissive: ''They said we work at the gene level. You can't really tell what was altered from what was there naturally.'' Pound, a lawyer, then asked rhetorically: ''What if I could assure the Nobel Prize in Medicine would be awarded to the person in this room who figured out how to make a test to determine if a competitor had been genetically enhanced? You could do it, right?'' Pound got an acknowledgment that detection might be possible with enough resources devoted to it. Lee Sweeney generously consults with W.A.D.A. and other antidoping officials. He's sympathetic to their cause. He just says it's hopeless. ''There will come a day when they just have to give up,'' he says. ''It's maybe 20 years away, but it's coming.''

There is a parallel from the past for the entire issue of performance-enhancing drugs, one tied to what was once another unwelcome substance in sports: money. Some casual followers of the Olympic movement may still not fully realize that nearly all of the participants are now paid professionals. There never was any big announcement that the cherished concept of amateurism -- athletes competing for the pure love of sport -- had been discarded. But over time, the changed reality has been accepted. Top athletes profiting from under-the-table payments? The public didn't care, and the ideal of amateurism expired, outdated and unenforceable.

One of the last things Pound said to me indicated that he knows, too, that W.A.D.A.'s mission has an expiration date pending. Maybe genetic enhancements really won't work for athletes, he speculated. ''If you strengthen the muscle to three times its normal strength, what happens when you break out of the starting blocks? Do you rip the muscle right off the bone?'' Pound seemed to like the thought of this gruesome image. He paused, then extended the thought. ''That would be nice if that happened,'' he said. ''It would be self-regulating.''

Michael Sokolove, a contributing writer for the magazine, is the author of ''The Ticket Out: Darryl Strawberry and the Boys of Crenshaw,'' to be published in April.


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Gene Therapy Could Lead to Super Athletes

Source&date, Feb 15, 2004

<http://story.news.yahoo.com/news?tmpl=story&cid=624&ncid=753&e=10&u=/ap/20040216/ap_on_sc/super_athletes>

Associated Press, By PAUL RECER, AP Science Writer

SEATTLE - A gene therapy that has been shown in rats to double muscle strength and power could illegally be used to build super athletes, a researcher said Monday. Sports officials are looking for ways to detect the genetic manipulation.

Lee Sweeney of the University of Pennsylvania said that laboratory studies show that injecting a virus carrying the gene for insulin-like growth factor 1 into lab rats caused their target muscles to grow in size and strength by 15 to 30 percent. When the technique was used on rats that were also put through an exercise program, the animals doubled their muscle strength.

"The things we are developing with diseases in mind could one day be used for genetic enhancement of athletic performance," Sweeney said at the national meeting of the American Association for the Advancement of Science (news - web sites). Richard Pound of McGill University and the World Anti-Doping Agency, an organization that polices performance-enhancing drugs in international athletics, said his agency already has passed regulations forbidding genetic manipulation in athletes. But he is concerned that the new muscle-building therapy may not be easily detected. "We would like to be there early (in the research) and to help regulate it," said Pound. "We'll find a way."

There are blood and urine tests to detect most performance-enhancing drugs, but the gene therapy detection would be much more difficult. Sweeney said that the presence of added genes in muscle could be detected now only through a muscle biopsy, a severely invasive procedure.

The gene therapy is being developed to increase the strength of muscles for the elderly and for treatment of muscular dystrophy, a muscle wasting disorder. Sweeney said that as people age, muscles weaken and his lab is trying to determine if gene therapy would slow or reverse this decline. "The same approaches could be used in a normal person's muscles to make a them stronger and better able to repair themselves," said Sweeney. It would also keep the muscle at its peak performance for a longer period of time, he said.

The treatment has not been tried on humans because of safety concerns and Sweeney said it may be years before it is ready for human clinical trials. But word of the research has reached the sports community and Sweeney said that half of the e-mails he receives now come from athletes or trainers wanting to get information about the muscle-building therapy.


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Muscle building gene therapy might build super athletes, scientist warns

PST SEATTLE (AP) Feb 16 2004

http://www.sfgate.com/cgi-bin/article.cgi?f=/news/archive/2004/02/16/sports1620EST0295.DTL

PAUL RECER, AP Science Writer (02-16) 13:20 PST SEATTLE (AP) --

Gene injections in rats can double muscle strength and speed, researchers have found, raising concerns that the virtually undetectable technology could be used illegally to build super athletes.

A University of Pennsylvania researcher seeking ways to treat illness said studies in rats show muscle mass, strength and endurance can be increased by injections of a gene-manipulated virus that goes to muscle tissue and causes a rapid growth of cells."The things we are developing with diseases in mind could one day be used for genetic enhancement of athletic performance," Lee Sweeney said Monday at the national meeting of the American Association for the Advancement of Science.

Sports officials said the gene therapy has the potential of betraying the very essence of sport -- athletes using their natural talents and training to compete.Tom Murray of the Hastings Center, a research organization, said it would be like allowing an athlete to compete in the Boston Marathon wearing roller blades."Performance enhancing drugs have been a concern in sports and gene therapy has the potential to kick it up a notch," said Murray, who has studied the issue of doping in sports. "It makes the challenges greater (of controlling performance-enhancing measures)."

Murray said he "has no doubt athletes will be in touch with Sweeney" when they learn of his research. Sweeney said that already half the e-mails he receives are from athletes or sports trainers. Richard Pound of McGill University and the World Anti-Doping Agency, said the sports community lost control of drugs for performance-enhancement in the 1960s to 1990s and "we've been playing catch-up ever since." Now gene therapy looms as an even more serious threat, he said.

"Sport is and should be an effort to see how far you can go with your natural talents honed by exercise and skill perfection," he said, and not by manipulating genes to build muscle. He said international sports already has regulations forbidding gene therapy for performance improvement and his agency hopes to be active in efforts to control use of the technique as the science develops.

Sweeney said that his laboratory studies show that injecting into muscles a manipulated virus that carries a gene for insulin-like growth factor 1 (IGF1) causes target muscles in rats to grow in size and strength by 15 to 30 percent. The inserted gene causes formation of extra IGF1 which, in turn, prompts the growth of muscle cells.

When the technique was used on rats that were also put through an exercise program, the animals doubled their muscle strength, he said. "If a normal person would inject this, their muscles would get stronger without them doing anything," Sweeney said. "If they are athletes in training, the rat study indicates that their training would be much more effective, injury would be overcome more easily and the effect of the training would last a much longer time."

The effect appeared to last throughout the life of the rats.

He said the technique was designed so that the IGF1 gene stays in the target muscle and does not move into the blood stream where it could cause damage to other organs. Sweeney said the gene therapy was being developed to treat muscular dystrophy and the natural decline in muscle strength associated with aging.

Unlike performance-enhancing drugs, Sweeney said the gene therapy could not be detected by blood or urine tests. He said it would require a biopsy of specific muscles followed by a sophisticated DNA laboratory study to detect the use of gene therapy in an athlete. Sweeney said because of the potential of cancer and other side effects, it may be years before the muscle-strengthening gene therapy is ready for human trials.

"There are issues of safety," he said. "It is not going to be as trivial as taking a drug." Sweeney said the gene therapy technique is highly complex and requires expert laboratory preparation. "This is not something an athlete could do in his garage," he said. "The athlete couldn't do this without a lot of help." He said that some countries, in a drive for athlete glory, could allow the gene therapy, just as earlier in history Olympic programs in some countries tolerated the use of performance-enhancing drugs. "That is the short-term fear," Sweeney said.


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Muscle-bound Rats Prompt Sporting Debate

Betterhumans web site 16.02.2004

http://www.betterhumans.com/News/news.aspx?articleID=2004-02-16-2

By Dwayne Hunter, Betterhumans Staff, 2/16/2004

Engineered to have larger leg muscles, animals spark discussion of genetic doping Rats engineered to grow bigger leg muscles following weight training have prompted discussion of genetic enhancement in sports. Lee Sweeney of the University of Pennsylvania in Philadelphia and colleagues have used gene therapy to make rats that build and retain muscle better after exercise. Such genetic enhancement of skeletal muscles could help athletes, patients rehabilitating from injury-induced muscle wasting and elderly people with muscular weakness, the researchers say.

Growth factor

To conduct their study, the researchers used a virus carrying a gene for IGF-I. IGF-I is a growth factor that promotes gains in muscle strength and mass. The virus was injected into the hind-leg muscles of rats that were then put through ladder-climbing exercises. The rats bulked up more than rats given only exercise and rats given only the gene therapy. They also retained more muscle mass after they stopped working out.

Strength satellites

The researchers think that muscle-precursor stem cells called "satellite cells" were responsible for the increased muscle mass and strength. Their findings support the theory that exercise "primes" satellite cells: Exercised satellite cells expressed IGF-I receptors that made them more responsive to the increased levels of IGF-I. While the application of the gene therapy approach to humans is still hypothetical, the experiment has prompted discussion of such genetic engineering in sports. It was presented in Seattle, Washington at the annual meeting of the American Association for the Advancement of Science, where Richard Pound from the World Anti-Doping Agency compared the situation with new doping techniques such as genetic doping to the period 30 to 40 years ago when drug detection techniques and regulatory mechanisms were not in place for sports competition.

The rat research will be published in the March 2004 issue of the Journal of Applied Physiology


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Gene doping is 'new frontier' for sports cheats

NY times, February 16, 2004

http://www.timesonline.co.uk/article/0,,1-1004273,00.html

rom Mark Henderson, Science Correspondent, in Seattle

A "gene doping" technique that makes the muscles of mice grow up to 30 per cent stronger will be the next frontier of cheating in professional sport, scientists gave warning today. The new form of gene therapy, which is being developed to treat patients with muscular dystrophy and other wasting diseases, will inevitably be abused by athletes seeking the ultimate illegal edge, according to the researchers behind it and anti-doping experts.

Experiments at the University of Pennsylvania have revealed that when normal mice are injected with a modified virus that adds a vital growth gene to their cells, they develop into heavily muscled, super-strong animals that the scientists have nicknamed "mighty mice". The effects are almost doubled when the gene therapy is coupled with a weight-training regime. Such genetic enhancements would deliver vast improvements in speed, power and strength if given to an athlete, said Lee Sweeney, who led the Pennsylvania research.

Gene doping has the potential to boost an unscrupulous sportsman's performance more steeply even than existing drugs such as anabolic steroids and erythropoeitin (EPO). It would also be extremely difficult to detect, as it mimics the quirks of inheritance that give some athletes a natural genetic advantage. Dr Sweeney told the American Association for the Advancement of Science conference in Seattle that while the technology was designed for bona fide medical purposes, it was "inevitable" that it would eventually be abused "off label" in sport.

He has already been approached by coaches and athletes, mainly bodybuilders, seeking to try gene therapy, even though the technique is barely ready for patient trials. "This is but one example of a number of potential gene therapies that are being developed with disease treatment as the goal, but if given to a healthy individual would provide genetic enhancement of some trait," Dr Sweeney said. "As these developments go forward, they inevitably will find their way into the healthy population. "The prospects are especially high that muscle-directed gene transfer will be used by the athletic community for performance enhancement, just as many drugs are used and abused today. "It is unclear what the risks are that are associated with such use. In many cases, policing such abuse in the sports community will be much more difficult that in the case of drugs, since detection will be difficult."

In the experiments, Dr Sweeney's team genetically engineered a harmless virus to carry a gene known as insulin-like growth factor I (IGF-I), which is critical to muscle growth and repair. The gene is often missing or faulty in patients with wasting diseases such as muscular dystrophy, and the goal of the work is to design a means of fixing this genetic mistake and curing these conditions.

When the virus was injected into normal, healthy mice, their muscles grew in size and strength by between 15 and 30 per cent. The genetically-enhanced muscles were more durable, and repaired themselves much more quickly when damaged. The added IGF-I gene also stopped the ageing process in its tracks: when middle-aged mice were injected with it, and then grew old, they suffered none of the muscle wastage typical of old age.

The benefits of gene doping were greater still when combined with a training regime. The team injected IGF-I into the muscle of one leg of a rat, which was then kept in a cage in which it had to climb ladders regularly to reach food. At the end of this training, the gene-doped leg was nearly twice as powerful as the untreated one, and retained its strength for longer when training was stopped. The findings, which will be published next month in the Journal of Applied Physiology, indicate that gene doping in human athletes would provide benefits even greater than those of anabolic steroids.

The therapy would enhance lean muscle mass, allow athletes to train for longer and to recover more quickly from injury, and would prolong their careers by slowing down the muscle wastage that takes place with age. Dick Pound, chairman of the World Anti-Doping Agency, said he was concerned that gene doping would become a major problem for sport. "I'm certainly worried about the potential," he said. "I don't think we're going to see it in Athens [at the 2004 Olympics], and I rather doubt Beijing [in 2008], but 2012 is certainly realistic. "The thought that we might be able to cure muscular dystrophy is wonderful, but what's not so good is the idea you'd have an 8ft shot-putter who could throw the shot 100 metres into the crowd."

Many existing performance-enhancing drugs used in sport were originally developed for medical use. Synthetic EPO, for instance, is used for treating anaemia, and human growth hormone for treating growth deficiencies and wasting diseases. Thomas Murphy, president of the Hastings Centre, a US bioethics group, said athletes were certain to start using gene enhancement, even before it is available for therapeutic use. "Knowing what I know about athletes, long before it's perfected people will be peddling gene enhancement technologies," he said. "I'm sure somebody out there is formulating a business plan about how they're going to do this." He said gene therapy would pose great challenges for testing regimes, as it would be extremely difficult to detect. One possibility would be to test athletes for an immune response to the viral vector involved. "I'm not completely pessimistic about the prospects of detection, but neither am I optimistic," he said. Dr Pound said another answer would be to insist on the development of a test to show whether gene therapy has been used before potential techniques are allowed to begin clinical trials. Any test would have to be sensitive enough to discriminate between artificial and natural performance-enhancing genetic oddities. "If God did it to you, your competitors have to live with it," Dr Pound said. "If your genetic consultant did it, that's different."


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Study raises fears of genetically modified athletes

11:00 17 February 04 NewScientist.com news service

http://www.newscientist.com/news/news.jsp?id=ns99994688

A study showing that gene therapy can make muscles respond much better to exercise has raised the prospect of genetically modified athletes.

"Half of the emails I get are from patients," says Lee Sweeney, at the University of Pennsylvania, and leader of the research. "And the other half are from athletes." The researchers injected rats with a modified virus that transported a gene to their hind leg muscles. The gene triggered increased production of a growth hormone called IGF-I. Combined with an intensive exercise regime of ladder climbing, this caused the rats' muscles become 15 to 30 percent stronger than would be expected with exercise alone. Even without exercise, the genetically modified rats' muscles grew by 15 to 20 per cent, Sweeney says. The research is aimed at developing treatments for diseases such as muscular dystrophy. Such therapies are not yet ready for use in humans and such genetic enhancement is likely to remain beyond the reach of athletes for some time. But the prospect of genetically modified athletes is already alarming drug testers.

Muscle biopsy

"It's a matter of some concern," says Dick Pound, chairman of the World Anti-Doping Agency. "What's most disturbing is that some of the first inquiries have come from trainers." Genetic enhancements are already banned under international sporting rules. But, unlike many of the drugs used to enhance performance, genetic modifications would leave no trace in the blood or urine. A muscle biopsy would be the only means of detection.

Sweeney says genetic researchers may therefore need to design their treatments to be susceptible to discovery. "Given current testing, athletes would be able to get away with it," he says. "They would have to change the testing mechanism." There is also concern that athletes will put their health at risk by using untested genetic technologies. Gene therapies used to correct illnesses have had only limited success and two patients treated with gene therapy for "bubble boy syndrome" in France developed leukaemia as a result. It is also possible that genetic modifications targeting IGF-I could make muscles so strong that they could damage the recipient's bones, Sweeney says.

The research was presented at the annual meeting of the American Association for the Advancement of Science in Seattle, Washington. Journal reference: Journal of Applied Physiology (vol 96 p 1)


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Mighty Mice Are Less Susceptible To Muscular Dystrophy Gene's Effects

Science Daily, 26 Nov 2002

http://www.sciencedaily.com/releases/2002/11/021126072241.htm

The Johns Hopkins scientists who first discovered that knocking out a particular muscle gene results in "mighty mice" now report that it also softens the effects of a genetic mutation that causes muscular dystrophy. The findings, scheduled for the December issue of the Annals of Neurology and currently online, build support for the idea that blocking the activity of that gene, known as myostatin, may one day help treat humans with degenerative muscle diseases.

Working with mice carrying the genetic mutation that causes Duchenne muscular dystrophy in humans, the scientists discovered that mice without the gene for myostatin had less physical damage to their muscles and were stronger than other mice with the Duchenne mutation. "'Knocking out' the myostatin gene isn't possible for treating patients, but blocking the myostatin protein might be," says senior investigator Se-Jin Lee, M.D., Ph.D., professor of molecular biology and genetics at Johns Hopkins School of Medicine. "However, myostatin still needs to be studied in people to see if it has the same role in our muscles as it has in mice."

The researchers caution that, even if myostatin does limit muscle growth in people, blocking it would not cure muscular dystrophy or any other degenerative muscle condition because the underlying cause of disease would be unchanged. "However, increasing muscle mass and strength by blocking myostatin could conceivably delay progression or improve quality of life," notes first author Kathryn Wagner, M.D., Ph.D., assistant professor of neurology at Hopkins.

The Hopkins team bred mice without the myostatin gene with mice carrying the genetic mutation that causes Duchenne muscular dystrophy in humans. Muscular dystrophy mice completely lacking myostatin were more muscular and stronger than those with myostatin at 3, 6 and 9 months of age, the researchers report. Perhaps most importantly, their muscle tissue appeared to be healthier.

Duchenne muscular dystrophy is the most common muscular dystrophy and the most common inherited lethal disease of childhood, affecting 1 in 3,500 live male births. (The genetic mutation that causes it is found on the X chromosome, and so is "covered up" in girls, who have two X chromosomes.) There's no good treatment at this time, and few patients survive into adulthood.

Early in the disease in humans, the regenerative capacity of stem cells in muscle, known as satellite cells, keep up with the damage, but eventually the damaging factors win. The result is not just loss of muscle, but also its replacement with non-muscle tissues, essentially scar tissue and fat. This scarring process, called fibrosis, is also seen in mice with the muscular dystrophy-causing mutation. The Hopkins team reports that loss of myostatin function significantly reduced the amount of fibrosis, suggesting that the muscle regenerative process was improved.

The Hopkins scientists hope to unravel the mechanism of muscle regeneration in mice with and without myostatin, possibly revealing even better targets for improving the process. They also plan to use special genetic manipulations to turn off the myostatin gene in adult mice, rather than at conception, to see if losing myostatin later in the course of muscular dystrophy is also beneficial.

Authors on the study are Wagner, Lee, Alexandra McPherron and Nicole Winik, all of The Johns Hopkins University School of Medicine. Funding was provided by the National Institutes of Health, the Duchenne Parent Project, and the Muscular Dystrophy Association.

Myostatin was licensed by The Johns Hopkins University to MetaMorphix, Inc., and sublicensed to Wyeth Pharmaceuticals, Inc. Lee and McPherron are entitled to a share of sales royalty received by the University from sales of this factor. Lee, McPherron and the University own MetaMorphix stock, which is subject to certain restrictions under University policy. Lee is a paid consultant to MetaMorphix. The terms of these arrangements are being managed by the University in accordance with its conflict of interest policies.

Related Web site:

http://www3.interscience.wiley.com/cgi-bin/abstract/99519627/START

 


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"Mighty Mice" Gene Is Mutated In Beefy Bovines

Science Daily , Date: 1997-11-13

http://www.sciencedaily.com/releases/1997/11/971113074953.htm

Courtesy of the University of Whatever

Gene's ability to slow muscle growth extends beyond mice

The same genetic "secret formula" that gave unusually large muscles to the "mighty mice" engineered by Johns Hopkins is also at work naturally in specially bred cattle that have extra muscle, according to a new report from the researchers. "Mutations in the myostatin gene in two different species produced the same result," says Se-Jin Lee, M.D., Ph.D., an assistant professor of molecular biology and genetics. "This strongly suggests that the normal human form of the gene, which we've already identified, helps suppress muscle growth. If we can find a drug that blocks myostatin activity, patients with muscular dystrophy or muscle wasting due to AIDS or cancer may really benefit."

Results of the study, which was supported by grants from the Edward Mallinckrodt, Jr. Foundation and MetaMorphix, Inc. are published in the Nov. 11 issue of the Proceedings of the National Academy of Science. Cattle breeders knew nothing of myostatin when they succeeded in developing more muscular cattle breeds like the Belgian Blue and the Piedmontese. Hopkins researchers went searching for mutant forms of myostatin in these cattle after discovering what eliminating it could do to mice.

"We wondered right away if interfering with the gene in livestock could give us animals with more meat and relatively less fat," says Alexandra McPherron, Ph.D., a Hopkins postdoctoral fellow. "We first became aware that there might be some breeds of livestock that already have mutated myostatin when someone described a large-muscled breed of sheep to us." Through literature and Internet searches, researchers learned of the Belgian Blue breed of cattle. From genetic information available online, they could see that the cattle's altered gene appeared to be in the same spot on the genetic code as human and mouse myostatin.

To confirm their suspicions, Lee and McPherron then analyzed DNA from cattle blood samples supplied by a ranch in Missouri. They also detailed the DNA blueprint of the myostatin gene from 12 non-double-muscled breeds of cattle and found that their copies of myostatin were all normal.

Scientists also sequenced the myostatin gene in humans, chickens, pigs, turkeys, sheep, baboons, zebrafish and rats, and found that there were relatively few differences among the species. Rights to myostatin are owned by The Johns Hopkins University and exclusively licensed to MetaMorphix Inc. MetaMorphix was established in 1995 to capitalize on work by Hopkins and Genetics Institute, a private pharmaceutical company, in the field of growth and differentiation factors. Lee is a shareholder in and scientific founder of the company.

Under an agreement between MetaMorphix and The Johns Hopkins University, McPherron and Lee are entitled to shares of royalty received by the University from MetaMorphix. The University, McPherron and Lee also own MetaMorphix stock, which is subject to certain restrictions under University policy. Lee is also a consultant to MetaMorphix. The terms of this arrangement are being managed by the University in accordance with its conflict-of-interest policies.


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Gene therapy on rats could possibly lead to 'superathletes'

Iowa State Daily News March 03, 2004

http://www.iowastatedaily.com/vnews/display.v/ART/2004/03/03/404554e5652c0

By Jennifer Nacin, Daily Correspondent

A muscle-growing drug designed to fight muscle-wasting illness may have implications for athletic departments across the country if it is made available in the medicinal market.

There is concern among American sports officials that the new drug, a gene for insulin-like growth factor-1 (IGF-1) -- originally designed to help people with muscle-wasting illnesses such as AIDS or muscular dystrophy -- could be used illegally to build "superathletes." The drug is virtually undetectable and could make users' muscles larger and stronger without much effort.

The drug is being tested at the University of Pennsylvania, where trials showed a 15 to 30 percent increase in the mass, strength and endurance of the muscles of lab rats after they were injected with a gene-manipulated virus. Officials in the ISU athletic department said they had not heard about this study and were surprised to hear what it could do. They said they were concerned that, if the drug does work on humans the way it is supposed to, it could have damaging physical side effects on anybody who takes it for performance-enhancing purposes.

"Everyone in athletics, period, would be concerned," said Mark Coberley, head football athletic trainer. "To level playing fields, you would like people to perform with their own natural abilities. That's why they have drug testing." The NCAA has strict regulations against the usage of performance-enhancing drugs and gene therapy. "It's very closely monitored anymore, with drug testing by the NCAA and our own drug tests," said Terry Allen, associate head football coach. "[The NCAA] can come in at any time, at least three times a year." Allen said members of Iowa State and the Big 12 Conference conduct additional random drug tests on student-athletes throughout the year. Coberley said if the gene therapy is released for human usage, it will not go unnoticed. "I'm sure that the appropriate governing bodies will take whatever action is necessary, if needed," Coberley said.

Marc Shulman, team physician at the Thielen Student Health Center, said there may not be cause to worry because results in lab rats may differ from results in humans. "It takes a lot of research to see if it works the same in humans as it does in lab animals," Shulman said. Douglas King, professor of health and human performance, agrees. "In terms of some aspects of physiology, there are some differences in rats and humans," King said. "The bodies may not deal with it in the same way."

Although there is concern physical damages could occur from using this muscle-building gene therapy, good results are possible for those who need to take it. "There are a lot of good things that come from gene therapy," Shulman said. "It has to be in the right patients at the right time for the right reasons." He said a good example of the appropriate use for this type of gene therapy would be in patients with muscular dystrophy, who experience significant loss of muscle mass.

A bad use of such therapy would be for the purposes of enhancing physical performance. "I don't think athletes here would take the risk of losing their scholarships and the [possibility of experiencing the] unknown medical risk of these things," Shulman said. Coberley said he wasn't aware of any abuse by ISU athletes.

Shulman said for now, he expects more concern for non-athletes who aren't sanctioned by any organizations and would take gene therapy drugs to enhance their appearance. He said they could be at greater risk of physical harm due to side effects including liver damage, testicle and ovary changes and mental disorders.


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Genetic engineering is next doping threat

16 March 2004

http://www.stuff.co.nz/stuff/0,2106,2847465a1823,00.html

LONDON: Back in the depths of time athletes used ginseng, opium and steroids from sheep testicles to enhance their performance. Anabolic steroids made their debut in sport in the 1940s and 50s and chemical agents followed.

Now the big fear is that advances in biotechnology and gene therapy could result in genetically modified athletes with the bodies of Greek gods and the prowess of Superman overwhelming ordinary mortals at future Olympics. Gene therapy, to treat or prevent disease, has not developed with the speed scientists had initially hoped but it is moving forward and it could be just a matter of time before it infiltrates sport.

"If the science develops and the regulatory and ethical frameworks are not properly established, I think there is a danger. We've seen it with the use of drugs that were developed for therapeutic purposes," said Dick Pound, president of the Montreal-based World Anti-Doping Agency (WADA). "The science could probably be misapplied."

Genetic doping is unlikely to be an issue at the Athens Olympics in August or the Turin Winter Games in 2006, but it could be a problem come Beijing in 2008. "It's a realistic problem which we may have to face, but not today," said Dr Bengt Saltin, director of the Centre for Muscle Research at Copenhagen University and a member of the International Olympic Committee (IOC) science committee. "The Beijing Olympics would be the earliest possible occasion."

Researchers have identified the gene for erythropoietin, or EPO, which stimulates the production of red blood cells - important for endurance sports such as the marathon and cycling. Synthetic EPO, which is used to treat anaemia and is banned by the IOC, was at the centre of a doping scandal that rocked the Tour de France cycling classic in 1998.

Scientists have already injected bits of the EPO gene, using a weakened virus, into the leg muscles of monkeys in research that may one day help kidney patients awaiting an organ transplant to maintain a steady supply of red blood cells. "There were quite positive results but they can't control it enough," Saltin said, referring to the research. "When they find the control of the gene then they will definitely use it on kidney patients and I don't think the road to the sporting world is very far."

One of the chief doping problems for sport is anabolic steroids. Androstenedione, nandrolone and stanozolol bulk up muscle mass and increase strength. "In so many sports the muscle mass and the strength is the critical factor," said Saltin. Steroids are non-specific and as researchers learn more about local growth factors, improving individual muscles with injections or genetic modification could become a possibility. "There is very good research in the field because there are muscular dystrophy patients with selective loss of muscles. If you could find how to counteract that with these local factors it will help many patients around the world," Saltin said.

Dr Lee Sweeney of the University of Pennsylvania and his team have already coaxed muscles in mice to grow up to 30 per cent stronger. They injected mice with a growth gene known as insulin-like growth factor I (IGF-I). "The prospects are high that muscle-directed gene transfer will be used for performance enhancement," Sweeney told a science conference where he presented the research. At the moment, scientists believe genetic engineering is too dangerous and too little is known about the technology and its impact to pose an immediate problem. However, they believe it could be just a matter of time before it reaches sport.

In the meantime, WADA plans to keep up with advances in the technology and the with people likely to bend or break the rules. "In the case of drugs, I think the genie was allowed to get out of the bottle early on, before people realised what the full implications would be and before the science got developed to the point where you could detect these sort of things," said Pound. "In genetics, our objective is to try and be there as the policy framework is developed, to be part of that process."

Saltin believes doping controls have never been as good and this trend will continue. "We have seen through the years that there are always people willing to use their knowledge, experience and technology to improve the athlete's performance. If those people were not around the problem would be so much easier to handle," he said.


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Muscles, maladies and mischief

radio netherlands 2, 22 March 2004

http://www.rnw.nl/science/html/040322rf.html

by Laura Durnford of our Science Unit, 22 March 2004

A gene therapy approach intended to help the ill and the elderly could aid athletes aiming to augment their natural abilities. Research published in this month's edition of the Journal of Applied Physiology shows that gene enhancement increases the strength of leg muscles in 'weight-trained' rats. But there are growing concerns that the technique could be abused to give a secret boost to competitive athletic performances.

This report was featured in Research File. Listen to the programme in full. (29:30)

By taking advantage of rats' innate liking for climbing ladders, scientists from the University of Pennsylvania Medical School in the USA were able to implement an 'exercise programme' in which the rodents repeatedly climbed small ladders in order to receive a food reward. Over time, extra weight was added to a small 'backpack' that each of the creatures wore, so mimicking the effects of weight-training. Some of these animals received 'gene therapy', others did not. A third group was genetically enhanced but did no extra exercise.

Professor Lee Sweeney, who's Chairman of the Department of Physiology, says gene therapy alone produced muscles that were "about 15 percent bigger and stronger", which was equivalent to the gains from weight-training alone. "But if we did both, train them and give them genetic enhancement, they got twice as strong, they got 30% stronger and much healthier looking muscle." The gene enhanced animals also gained the extra strength faster and maintained the effects for longer after weight-training ended, as compared with their non-enhanced counterparts.

In this form of gene therapy the scientists use a 'Trojan horse' approach. A virus known to specialise in entering skeletal muscles is adapted so that it carries a synthetic gene into the muscle cells. There the gene produces a protein &endash; in this case a growth factor called 'IGF-1' which promotes muscle growth and repair. "In fact the weight training was severe enough that there had actually been some scarring in the muscle of the non-genetically enhanced animals," adds Professor Sweeney, "whereas the genetically enhanced ones had repaired so rapidly, there was no scar tissue and the muscles looked much healthier."

Athletic Advantage

Professor Sweeney and his team conducted the study because they had already "had so many enquiries as to whether it really would be an enhancement" if athletes were to use gene therapy techniques in order to boost their muscle power and performance. He [80b_rat] says the study findings "showed that it would actually provide an athlete with marked enhancement."

While some members of the athletics community have already begun to ask how they may be able to make use of these methods, yet others are becoming increasingly concerned about this potential new 'doping' threat. They believe gene enhancement could become an issue as early as the 2008 Olympic Games in Beijing. And there is currently no regulatory mechanism or detection technique in place to keep a check on potential abuse.

Detection difficulty

Professor Sweeney says one problem in devising ways to detect this sort of gene enhancement is that only urine and blood can be taken from an athlete for testing, meaning that some indirect sign of the gene's presence would have to be identified: "you'd only find the gene if you could get a biopsy of the muscle, so you'd have to look for something that might show up in either the blood or the urine. In some cases that would be easy to do and in other cases it might be nearly impossible."

Medical muscle

While the prospect of genetically enhanced athletes is a valid concern, it's perhaps as well not to lose sight of the fact that a large number of other people could benefit from these techniques. Professor Sweeney's primary aim is to alleviate the kind of metabolic and stability problems that occur as a result of muscle loss in old age or in diseases such as muscular dystrophy. "We've shown that producing, or over-producing in this case, [Rat muscle] IGF-1 in muscles can prevent almost all of ageing-related changes," he says, although safety concerns about gene enhancement will mean that therapeutic use in the elderly is not likely in the immediate future. However, he envisages applications for muscular dystrophy, where "you might not be able to genetically correct the problem itself, but by allowing the muscle to repair more rapidly and by trying to make the muscle bigger, it would actually improve the condition in these patients, hopefully slowing down the progression of the disease. That's probably where we'll take this first."


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Genetic Research Boosts Athlete Cheats

Daily Champion March 26, 2004

http://allafrica.com/stories/200403260218.html

Ayodeji Fashikun, With Agency Reports, Lagos

The world of sports seems to be in trouble. This is informed more by the quanta of drug related sports based cheats either testing positive to one banned substance or the other. The population of those in the centre have increased especially in the last five years to date.

Tennis with its stained hands was diplomatic enough in clearing one of its biggest stars, Greg Rusedski. Athletics, swimming, weightlifting, football, the martial arts etc have had a fair share of the drug hangover. Or how else do we describe the situation where a new revelation that athletes will soon try to enhance their bodies with gene technology is raised by the results of a new study to boost muscles in rats?

The scientist behind the research says his intention was to find new ways of treating muscle-wasting diseases. (Whatever that means.) Lee Sweeney, from the University of Pennsylvania, says trainers are already making inquiries about his technology. "I would say half the e-mails I get now are from athletes," he told an American science conference in Washington State. The other half is from patients with muscular dystrophy." Sweeney and colleagues injected their rats with a virus which carried a gene into muscle cells to produce a growth hormone called IGF-I.

The rodents given the therapy and put on an exercise programme developed bigger and stronger muscles. The scientists also found the rats with genetically elevated levels of IGF-I retained more of their muscle mass after they stopped exercising. All this could be of considerable help to patients with muscular disorders and muscle loss associated with either disuse or ageing. But the benefits are also those that athletics cheats have sought in the past from standard drug technologies.

Hijacking research

While the leap from laboratory animals to human beings is still hypothetical, Lee Sweeney and other speakers here at the annual meeting of the American Association for the Advancement of Science said it was inevitable that athletes and their trainers would attempt to hijack the rat research. "The world anti-doping code at the moment includes gene transfer technology as a banned practice," said Dick Pound, the chairman of the World Anti-Doping Agency (WADA).

This is where the fears of the world of sports is planted when Pound said, "We're not sure of course we can detect it. Today, in fact, it would be quite difficult." The speakers suggested that any clinical trials of new gene technologies to treat disease might include a requirement on the part of scientists to develop a test that could also be used on sports people to check there is no abuse of the research. "The only way to detect this would be through a muscle biopsy," said Sweeney, an associate professor of physiology at Penn.

Thomas Murray, a bioethicist and president of The Hastings Center in New York, has looked closely at the issue of drugs in sport. He said sports administrators would have to raise their game yet again. "Performance enhancing drugs in sport have posed a challenge to what we care about in sport - what gives it meaning," he told the meeting. "Gene transfer technologies have the potential to kick it up a notch and make the challenge even greater."

Gene therapy has had a chequered history. It has long promised to revolutionise medicine by correcting or replacing faulty genes in patients - to cure diseases for which current drugs will only treat symptoms. But the process of getting corrected genes into patients' cells can be haphazard, and clinical trials have resulted in at least one death. Two boys in France treated for X-Scid, popularly known as "bubble boy disease", developed leukaemia.

Pound said it was essential that sports governing bodies worked with science to make sure the fruits of the genomic age went solely to diseased patients and not to gold medal frauds. "In terms of these genetic applications, we're at the beginning of the cycle," he said.

"In the 60s, 70s, 80s and even the 90s, sport rather lost control of drug use. We've been playing catch-up ever since - with some success. What we'd like to do with this new branch of science is be there early to help in the formation of the regulation of it." The rat research will appear in the March 2004 issue of the Journal of Applied Physiology.


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Experts believe athletes and coaches will soon turn to gene doping in an attempt to gain a performance edge.

http://sfgate.com/cgi-bin/article.cgi?f=/news/archive/2004/04/17/sports1444EDT0356.DTL

(04-17) 11:44 PDT UTRECHT, Netherlands (AP) --

Authorities told at a workshop on gene doping Saturday that recent discoveries have made it inevitable that athletes and coaches will try to abuse gene therapy to gain an edge in speed, strength or endurance -- despite huge health risks.

"I'm very pessimistic -- I think it won't take very long," said Hidde Haisma, a professor of gene therapy at the University of Groningen. The needed tools "are available at labs around the world," he said. Though the idea of manipulating genes to enhance performance has been around for more than a decade, it gained attention this year after a University of Pennsylvania study showed that muscle mass, strength and endurance in rats can be increased by altering their genes.

Scientists have treated roughly 3,000 humans suffering from life-threatening illnesses with gene therapy, but few cases have been successful and some have been fatal. In one non-human study where monkeys' genes were manipulated to produce an extra protein called erythropoietin, some of the monkeys developed the disease anemia. Given the risks involved, the first gene doping in the sports world may be in an animal sport like dog racing, Haisma said.

But Olivier Rabin, science director at the World Anti-Doping Agency, said human athletes won't wait long. He pointed to instances when athletes began using new steroids "straight from the test tube, before they were even tested on animals." Current blood and urine tests cannot detect gene doping, and Haisma said the most promising technique of detection involved analyzing the proteins in blood samples, looking for a suspicious spike. "There is no doubt in the minds of people working in the sports community that gene doping is coming," he said.


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Sport's latest threat: Form-fitting Genes

Indiana Express

http://www.indianexpress.com/full_story.php?content_id=63231

KEVIN VAN VALKENBURG Posted online: Sunday, January 23, 2005 at 0000 hours IST

Sometime in the near future, an athlete might walk into a lab and ask for an injection that will bring a world of possibility. Take this and hit home runs like Barry Bonds, the athlete would be told. Take it and fly around the track like Marion Jones. This might sound like another story about steroids, but it's not. The topic is genetic doping. Because it uses DNA to stimulate or block natural chemicals, it won't show up in a blood or urine test. With billions of dollars at stake every year in sports and the lure of fame stronger than ever, gene doping is expected to be the next big issue for sport.

Experts in the field of genetic research predict it could happen in five or 10 years. Or sooner. ''I don't think it would surprise any of us if tomorrow we picked up a newspaper and saw that (an athlete) had died of a stroke after getting involved with gene therapy'', said Dr. Theodore Friedmann, director of the gene therapy program at the University of California at San Diego and considered to be the world's top authority in the field.

Genetic doping has the potential to make a mockery of what is currently considered fair athletic competition. The World Anti-Doping Agency has formed a panel &emdash; led by Friedmann, it will meet next month &emdash; to study the issue and come up with methods for detection. ''There's no firm evidence right now that people are using genetic manipulation to enhance performance'', he said, ''but there have been a number of studies done with mice and rats that suggest such a thing can be done.''

Gene therapy isn't a new concept by any means. Over the past 30 years, scientists have been making numerous breakthroughs. Techniques have been developed in rats in which a synthetic version of the gene that produces insulin-like growth factor 1, or IGF-1, can be used to spur muscle growth or repair at the cellular level.

IGF-1 normally occurs naturally in cells, and when it's injected directly into the muscles it has little effect. But scientists at the University of Pennsylvania, led by Dr. Lee Sweeney, have developed a technique in which the gene can be carried into cells using a harmless virus. There the gene fuses with the cell's DNA and causes the body to produce more IGF-1, a protein that helps rebuild muscles when they deteriorate.

In other studies, scientists have used similar techniques to block a protein, myostatin, that limits muscle-building in the body. With myostatin blocked, lab mice in studies developed twice the normal muscle mass. Such results have given hope to people with diseases like muscular dystrophy, in which muscles can't repair as fast as they deteriorate.

So far, IGF-1 hasn't been studied in any human clinical trials, but Wyeth Pharmaceuticals recently conducted the first human clinical trial with a myostatin inhibitor. What worries both scientists and anti-doping officials is the scope for abuse in the name of athletics, Friedmann said.

Dr. Steven Ungerleider, a prominent sports psychologist and the author of Faust Gold: Inside the East German Doping Machine, said that as long as the science is out there, athletes will be willing to abuse it. And while Ungerleider says he believes it's unlikely there will be another situation like what happened in the 1970s and 1980s in East Germany &emdash; where the government was behind a doping scandal and cover-up that involved nearly 10,000 athletes &emdash; there are plenty of scientists working independently, with little or no oversight, on the next phase of performance enhancement.

Part of what will probably make genetic doping appealing to athletes is the difficulty of detection. In the case of IGF-1, because the synthetic gene activates natural chemicals that repair and build muscles, evidence of doping would be difficult to find. Detection might involve a magnetic resonance imaging scan or muscle biopsies, which would require inserting a large needle into the muscle.

''You would need muscle biopsies done relatively close to competition'', said Dr. Steven Roth, a professor of kinesiology at the University of Maryland. '''How many athletes are going to agree to that? It's not feasible.''

The issue of testing becomes even more complex because it crosses borders and requires cooperation from numerous authorities to be viable and credible. John Hoberman, the author of several books on athletic doping, including the forthcoming Testosterone Dreams, said that doping-control officers who travel around the globe to test athletes are often greeted by violence. ''I know stories of one doping officer who was attacked by a mob in the street,'' said Hoberman. ''It's a global problem that's going to require a global solution.''

Hoberman also said that, eventually, society must come to terms with what exactly is performance enhancement and what level is acceptable. ''Athletic doping right now is taking place in a society where an entire range of performance-enhancing drugs have become ordinary,'' Hoberman said. ''The president and the attorney general aren't out there saying that Botox is an outrage and Viagra is an outrage, and so there is a huge disconnect between how athletes are required to be drug-free and ordinary citizens are not.''

Friedmann said genetic doping might force society to address the larger question of what sports should really be about. ''A lot of us grew up with the very romantic view of sports,'' he said. ''Athletics is such an important part of society because it's about accomplishment against physical odds. Doping in general poses the questions of, 'What is sport? What do we want sport to be? Do we want it to be about athletic achievement or about pharmacology?' We can all sit here and glorify a few more home runs, and it's terrific, but it's not sport any longer.''

 

(LA Times-Washington Post

 


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Genetic Doping with erythropoietin cDNA in primate muscle is detectable

MOLECULAR THERAPY Vol. 10, No. 3, September 2004

Françoise Lasne,1,* Laurent Martin,1 Jacques de Ceaurriz,1 Thibaut Larcher,2

Philippe Moullier,2,3,* and Pierre Chenuaud2

1National Anti-Doping Laboratory, 92290 Chatenay-Malabry, France

2INSERM U 649, CHU Hotel-Dieu, and

3EFS Pays de Loire, 44035 Nantes, France

 

Forthcoming 'genetic doping' is predicted to be undetectable. In the case of recombinant human
erythropoietin (rhEPO), a hormone used in endurance sports, it is being predicted that exogenous drug
injections will be replaced by the transfer of the corresponding gene into some of the athlete's own cells.

The hormone thus produced inside the organism is assumed to be completely identical to the physiological
one. Our results show that this is not the case and open up optimistic prospects for antidoping control involving gene transfer....

...please, read the rest in the original article...

here the central figure : isoelectric focussing analysis of Urine and serum Epo (Western blotted):
- lane 1, signals recombinant Epo (CHO cells)
- lane 2, signals recombinant Epo (BCK cells)
- lanes 3, 4 , 5; Epo signals normal urine (4) and normal macaque serum (4 and 5)
- lanes 6,7; Epo signals from serum of gene treated macaques

conclusion:

when expressed after muscle gene transfer, Epo is improperly processed and can be distinguished from naturally expressed Epo.


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