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There's no great demand for most potential human enhancements. Only a few daredevils, for example, would risk surgery to upgrade their vision from normal to extraordinary. But when it comes to sports—higher, faster, stronger—no such restraint exists. Athletes, enticed by fat contracts, Olympic medals, and fan adulation, will accept almost any health risk to steal an advantage. And eventually, some of their cheats will cross over to a mass audience. Steroids and nutritional supplements—certified by home-run records and 350-pound offensive linemen—have already found their way to every major high-school sports program in the United States.
But current sports enhancements don't appeal broadly, for two reasons. First, they take too much work: Anyone who injects steroids can get very strong, but only if he lifts weights regularly. And second, they're dangerous. Steroids raise cancer risk, promote impotence, and cause mood changes. EPO (erythropoietin)—a red blood cell booster often used by endurance athletes (especially cyclists and cross country skiers)—can thicken the blood, increasing the possibility of blood clots, heart attacks, and strokes.
For 9-to-5 supermen and superwomen who want the free lunch—stronger without effort, faster without danger—here's what the future may offer.
Bicep brought to you by IGF?Bicep brought to you by IGF?
1) Bodybuilding for Couch Potatoes
The Background
Muscle weakness is a great unacknowledged enemy of our aging society. As you get older, you lose muscle mass. (The medical term for this is sarcopenia.) Shrinking muscle mass leads to more falls, more broken bones, more disability, and a declining quality of life. Low muscle mass also makes it harder for old people to survive trauma since muscles are reservoirs of proteins and metabolites needed in an emergency. In recent years, doctors have been virtually dragging seniors to the weight room to get them buffed up.
But maybe your grandmother won't have to pump iron, and neither will you. There's a treatment that could boost muscle mass without (much) work: a gene for something called Insulin-like Growth Factor.
The Project
The IGF gene is a multitasker. It makes different proteins, depending on the circumstances. When a muscle is exercised by a long-distance runner, the gene manufactures something called IGF-1. But when a muscle is intensely stretched or contracted, as by a weight lifter, the gene produces Mechano Growth Factor. MGF, which was discovered by University of London professor of anatomy Geoffrey Goldspink, instigates muscle growth by activating the "satellite cells" in the muscle, causing them to divide and fuse, creating the nuclei for new muscle cells.
Both MGF and IGF-1 encourage muscles to grow. (IGF-1 seems to activate protein synthesis necessary for new muscle cells.) Scientists have created mighty mice using both compounds. When Goldspink injected a gene for MGF into mouse muscles, he recorded a 20 percent increase in muscle mass in two weeks and a 25 percent increase in muscle strength—without the mouse hitting the weight room and without apparent side effects. Similar tests have been done on mice using IGF-1. They, too, became supermice, though it took longer.
Goldspink hopes MGF could be a therapy for the sick and frail: Muscular dystrophy and age-related muscle loss are the obvious targets. But he has no doubt "there will be misuse of MGF" by athletes and bodybuilders. (In fact, the International Olympic Committee has already commissioned him to develop a test for MGF, IGF-I, and human-growth hormone abuse.) But it won't just be hard-core muscleheads who experiment with MGF; if it turns out that MGF is safe and effective in 65-year-olds with sarcopenia, 50-year-olds will start asking for it, then all the rest of us. If you could get 25 percent bigger pecs without a visit to the gym, wouldn't you consider it?
The Obstacles
No clinical trials of MGF have started yet. The technique for inserting the gene into muscles is not complicated, but gene therapy is never easy. Although Goldspink's experiment resulted in Schwarzenegger mice, that doesn't mean that MGF will successfully pump up normal humans. Goldspink saw no side effects in his mice tests but wonders if prolonged application of the gene would cause damage. (Goldspink expects a single dose of the gene would last about a year.) And as for IGF-1, it may have health risks that MGF does not. For example, it could damage the heart if it is injected directly into the bloodstream.
The Timeline
Goldspink hopes MGF will be used therapeutically within five years. Athletes are already experimenting with IGF-1, which is widely sold on the Internet (mostly by companies that seem less than concerned about its safety). So far, MGF hasn't found its way to the gym black market because Goldspink has tightly limited its distribution and because MGF is tricky to make, but it's just a matter of time before MGF slips out to athletes.
If MGF doesn't work or isn't safe, here are two more treatments that might become quicker-bulker-uppers.
A back to better bear agingA back to better bear aging
2) Running Forever
The Background
The other goal for muscular enhancement is increasing endurance. Endurance depends on oxygen uptake and delivery. If you don't get enough oxygen to muscles, lactic acid production spikes, and you weaken and tire. Great long-distance athletes like Lance Armstrong are able to keep collecting oxygen and feeding it to muscle cells long after you and I would fade. Oxygen is carried by hemoglobin, the chief component of red blood cells. So, generally, more red blood cells means better wind. (Endurance, incidentally, is not the same as speed. Speed depends on muscle strength, which is why sprinters so frequently abuse steroids.)
In the early '60s, endurance athletes took blood transfusions from others to increase their red blood cell count. This wasn't very safe—transfused blood can carry disease or provoke immune reaction—so a few years later they started banking their own blood months before competition. This way, the body would have time to regenerate the lost red cells, and then, at competition time, the athlete would take the transfusion of his own blood, giving himself an extra measure of hemoglobin-rich blood.
Eventually, scientists and trainers cottoned on to EPO, a natural compound whose function is stimulating the bone marrow to produce more red blood cells. Amgen began producing synthetic EPO, and many endurance athletes started injecting it several times a week. (The most recent long-acting variation, darbepoetin, is even more effective and can be injected every couple of weeks.)
But artificial EPO is dangerous: Too much EPO supercharges red cell production, which, as noted above, can thicken the blood and cause heart attacks. Frequent needle injections are inconvenient and unpleasant. And tests can detect synthetic EPO—a problem for competitive athletes.
The Project
There are two potential strategies for those who desire convenient, safe, and undetectable methods for boosting oxygen capacity and extending endurance.
The EPO Gene
The first is to engineer a gene for EPO that enables the body to increase its own EPO supply. Dr. Gary Wadler of NYU Medical School, author of Drugs and the Athlete and the White House adviser on doping, described how this will be done in a recent article, "Future and Designer Drugs: Emerging Science and Technologies." The EPO gene can be attached to a small bit of DNA called a plasmid, which would be injected into the muscle. Many muscle cells would absorb the new gene and start pumping out extra EPO. To prevent the EPO from running wild—from stimulating so many red cells that the blood thickened—the gene would have an on-off switch that would be activated only when the patient took a particular drug. This EPO gene therapy, Wadler told me, "is likely to be first to market" of the new sports enhancement technologies.
The Obstacles
Both the gene therapy and the on-off switch are new. There's no long-term data about how safe and effective they are.
The Timeline
Now, or very soon.
Fake Blood
A second potential endurance enhancement is fake blood. Doctors and hospitals have long hunted for a safe blood substitute. Donated blood is dangerous (HIV, hepatitis, etc.), and it's difficult to collect. A product that could safely tote oxygen like hemoglobin would make surgery and emergency medicine much easier. It could also supply athletes with a safe, covert way to hike endurance.
There are two promising leads. Drug companies are spending millions to make artificial or modified hemoglobin. These manufactured substances haven't been perfected yet—the molecules tend to degrade quickly, and they may have their own health risks—but they soon will be.
A more radical idea is exploiting compounds called perfluorochemicals, which are related to Teflon. PFCs can absorb enormous amounts of oxygen—50 times as much as normal blood, in some cases. Several companies are testing PFC-emulsion blood substitutes. Rumors circulated about PFC use at the 1998 Nagano Olympics, according to Wadler. Long-distance cyclists have also been accused of doping themselves with PFCs.
The Obstacles
Artificial hemoglobins have been cranky in tests but remain promising. There is worry about the side effects of PFCs, which can cause platelet dysfunction and flulike symptoms, according to Wadler.
The Timeline: Both manufactured hemoglobin and PFCs are likely to be used widely in a few years, assuming clinical trials go well.
There's no great demand for most potential human enhancements. Only a few daredevils, for example, would risk surgery to upgrade their vision from normal to extraordinary. But when it comes to sports—higher, faster, stronger—no such restraint exists. Athletes, enticed by fat contracts, Olympic medals, and fan adulation, will accept almost any health risk to steal an advantage. And eventually, some of their cheats will cross over to a mass audience. Steroids and nutritional supplements—certified by home-run records and 350-pound offensive linemen—have already found their way to every major high-school sports program in the United States.
But current sports enhancements don't appeal broadly, for two reasons. First, they take too much work: Anyone who injects steroids can get very strong, but only if he lifts weights regularly. And second, they're dangerous. Steroids raise cancer risk, promote impotence, and cause mood changes. EPO (erythropoietin)—a red blood cell booster often used by endurance athletes (especially cyclists and cross country skiers)—can thicken the blood, increasing the possibility of blood clots, heart attacks, and strokes.
For 9-to-5 supermen and superwomen who want the free lunch—stronger without effort, faster without danger—here's what the future may offer.
Bicep brought to you by IGF?Bicep brought to you by IGF?
1) Bodybuilding for Couch Potatoes
The Background
Muscle weakness is a great unacknowledged enemy of our aging society. As you get older, you lose muscle mass. (The medical term for this is sarcopenia.) Shrinking muscle mass leads to more falls, more broken bones, more disability, and a declining quality of life. Low muscle mass also makes it harder for old people to survive trauma since muscles are reservoirs of proteins and metabolites needed in an emergency. In recent years, doctors have been virtually dragging seniors to the weight room to get them buffed up.
But maybe your grandmother won't have to pump iron, and neither will you. There's a treatment that could boost muscle mass without (much) work: a gene for something called Insulin-like Growth Factor.
The Project
The IGF gene is a multitasker. It makes different proteins, depending on the circumstances. When a muscle is exercised by a long-distance runner, the gene manufactures something called IGF-1. But when a muscle is intensely stretched or contracted, as by a weight lifter, the gene produces Mechano Growth Factor. MGF, which was discovered by University of London professor of anatomy Geoffrey Goldspink, instigates muscle growth by activating the "satellite cells" in the muscle, causing them to divide and fuse, creating the nuclei for new muscle cells.
Both MGF and IGF-1 encourage muscles to grow. (IGF-1 seems to activate protein synthesis necessary for new muscle cells.) Scientists have created mighty mice using both compounds. When Goldspink injected a gene for MGF into mouse muscles, he recorded a 20 percent increase in muscle mass in two weeks and a 25 percent increase in muscle strength—without the mouse hitting the weight room and without apparent side effects. Similar tests have been done on mice using IGF-1. They, too, became supermice, though it took longer.
Goldspink hopes MGF could be a therapy for the sick and frail: Muscular dystrophy and age-related muscle loss are the obvious targets. But he has no doubt "there will be misuse of MGF" by athletes and bodybuilders. (In fact, the International Olympic Committee has already commissioned him to develop a test for MGF, IGF-I, and human-growth hormone abuse.) But it won't just be hard-core muscleheads who experiment with MGF; if it turns out that MGF is safe and effective in 65-year-olds with sarcopenia, 50-year-olds will start asking for it, then all the rest of us. If you could get 25 percent bigger pecs without a visit to the gym, wouldn't you consider it?
The Obstacles
No clinical trials of MGF have started yet. The technique for inserting the gene into muscles is not complicated, but gene therapy is never easy. Although Goldspink's experiment resulted in Schwarzenegger mice, that doesn't mean that MGF will successfully pump up normal humans. Goldspink saw no side effects in his mice tests but wonders if prolonged application of the gene would cause damage. (Goldspink expects a single dose of the gene would last about a year.) And as for IGF-1, it may have health risks that MGF does not. For example, it could damage the heart if it is injected directly into the bloodstream.
The Timeline
Goldspink hopes MGF will be used therapeutically within five years. Athletes are already experimenting with IGF-1, which is widely sold on the Internet (mostly by companies that seem less than concerned about its safety). So far, MGF hasn't found its way to the gym black market because Goldspink has tightly limited its distribution and because MGF is tricky to make, but it's just a matter of time before MGF slips out to athletes.
If MGF doesn't work or isn't safe, here are two more treatments that might become quicker-bulker-uppers.
A back to better bear agingA back to better bear aging
2) Running Forever
The Background
The other goal for muscular enhancement is increasing endurance. Endurance depends on oxygen uptake and delivery. If you don't get enough oxygen to muscles, lactic acid production spikes, and you weaken and tire. Great long-distance athletes like Lance Armstrong are able to keep collecting oxygen and feeding it to muscle cells long after you and I would fade. Oxygen is carried by hemoglobin, the chief component of red blood cells. So, generally, more red blood cells means better wind. (Endurance, incidentally, is not the same as speed. Speed depends on muscle strength, which is why sprinters so frequently abuse steroids.)
In the early '60s, endurance athletes took blood transfusions from others to increase their red blood cell count. This wasn't very safe—transfused blood can carry disease or provoke immune reaction—so a few years later they started banking their own blood months before competition. This way, the body would have time to regenerate the lost red cells, and then, at competition time, the athlete would take the transfusion of his own blood, giving himself an extra measure of hemoglobin-rich blood.
Eventually, scientists and trainers cottoned on to EPO, a natural compound whose function is stimulating the bone marrow to produce more red blood cells. Amgen began producing synthetic EPO, and many endurance athletes started injecting it several times a week. (The most recent long-acting variation, darbepoetin, is even more effective and can be injected every couple of weeks.)
But artificial EPO is dangerous: Too much EPO supercharges red cell production, which, as noted above, can thicken the blood and cause heart attacks. Frequent needle injections are inconvenient and unpleasant. And tests can detect synthetic EPO—a problem for competitive athletes.
The Project
There are two potential strategies for those who desire convenient, safe, and undetectable methods for boosting oxygen capacity and extending endurance.
The EPO Gene
The first is to engineer a gene for EPO that enables the body to increase its own EPO supply. Dr. Gary Wadler of NYU Medical School, author of Drugs and the Athlete and the White House adviser on doping, described how this will be done in a recent article, "Future and Designer Drugs: Emerging Science and Technologies." The EPO gene can be attached to a small bit of DNA called a plasmid, which would be injected into the muscle. Many muscle cells would absorb the new gene and start pumping out extra EPO. To prevent the EPO from running wild—from stimulating so many red cells that the blood thickened—the gene would have an on-off switch that would be activated only when the patient took a particular drug. This EPO gene therapy, Wadler told me, "is likely to be first to market" of the new sports enhancement technologies.
The Obstacles
Both the gene therapy and the on-off switch are new. There's no long-term data about how safe and effective they are.
The Timeline
Now, or very soon.
Fake Blood
A second potential endurance enhancement is fake blood. Doctors and hospitals have long hunted for a safe blood substitute. Donated blood is dangerous (HIV, hepatitis, etc.), and it's difficult to collect. A product that could safely tote oxygen like hemoglobin would make surgery and emergency medicine much easier. It could also supply athletes with a safe, covert way to hike endurance.
There are two promising leads. Drug companies are spending millions to make artificial or modified hemoglobin. These manufactured substances haven't been perfected yet—the molecules tend to degrade quickly, and they may have their own health risks—but they soon will be.
A more radical idea is exploiting compounds called perfluorochemicals, which are related to Teflon. PFCs can absorb enormous amounts of oxygen—50 times as much as normal blood, in some cases. Several companies are testing PFC-emulsion blood substitutes. Rumors circulated about PFC use at the 1998 Nagano Olympics, according to Wadler. Long-distance cyclists have also been accused of doping themselves with PFCs.
The Obstacles
Artificial hemoglobins have been cranky in tests but remain promising. There is worry about the side effects of PFCs, which can cause platelet dysfunction and flulike symptoms, according to Wadler.
The Timeline: Both manufactured hemoglobin and PFCs are likely to be used widely in a few years, assuming clinical trials go well.
