Bioengineering the perfect athlete (2008, Jul 16)


Bioengineering the perfect athleteLast Updated: Wednesday, July 16, 2008 | 8:04 AM ET By Matthew Herper Forbes Athletes can develop amazing strength and abilities without drugs, but world-class comptetitors are now operating near the limits of human physiology. (Ron Staton/AP)Will scientists ever create the perfect athlete?

Sure, someday. But creating drug-enhanced superhumans along the lines of Captain America or the Russian boxer who beat up Sylvester Stallone in Rocky IV is a lot harder than you'd think.

In fact, the most talked about super-steroid, a drug designed to treat muscular dystrophy, failed in a clinical trial earlier this year and has been discontinued by Wyeth, its maker.

Some drugs can dramatically improve the performance of weightlifters, sprinters and cyclists, and many current world records were probably achieved with the help of man-made chemicals. Steroids and Erythropoietin (EPO), a hormone manufactured to combat anemia in cancer and kidney dialysis patients, clearly increase strength and endurance, respectively. And because world-class athletes operate near the limits of human physiology, tiny differences add up. Tufts researcher Roger Tobin has estimated that a 10 per cent increase in a baseball player's muscle mass could double the number of home runs he hits.

But the number of really effective performance-enhancing drugs may stop there. Many athletes who dope could be loading their blood with placebos, or worse.

Human growth hormone (HGH) has been at the center of the doping scandal in baseball. But there is little evidence it actually works. When Stanford researchers pooled placebo-controlled clinical trials of HGH involving 300 patients, they found no benefit for muscle strength. Another placebo-controlled study conducted at the Garvan Institute of Medical Research in Sydney, Australia, found that athletes' performance improved whether or not they were taking real HGH because of the psychological impact of thinking they were taking strength-boosting meds.

Nine out of every 10 medicines that drug companies put into human testing fail, either because they're not safe, or because they aren't effective. Those studies may have involved too few patients to pick up an improvement in athletic performance from HGH, or athletes might need to take it for years at a time to get a meaningful improvement. In reality though, creating a new drug to do anything is tremendously difficult. Nine out of every 10 medicines that drug companies put into human testing fail, either because they're not safe, or because they aren't effective. In search of super-steroids Performance-enhancing drugs for athletes are no different. Steroids were invented 75 years ago. EPO sold by Amgen and Johnson & Johnson for its legitimate uses came around in the early 1980s, as did HGH, which is sold by Pfizer and Genentech. Scientists are trying to develop other drugs that athletes might choose to abuse, including gene therapies, a spate of experimental medicines that turn normal rodents into mighty mice, and new growth hormones. But no flood of super-steroids has yet emerged.

One of the most promising ways of increasing strength is by blocking a protein called myostatin that slows down muscle growth. Belgian blue cows, which lack the myostatin gene, are so covered with bulky, rippling muscles that they look like something out of a bovine superhero cartoon. Mice engineered to lack myostatin get far bulkier than if they are given steroids. In one documented case where a human baby lacked the gene to make myostatin, he was unusually strong. At age four he could hold a 7-pound barbell in each outstretched hand, according to the New England Journal of Medicine.

Given all that biological evidence, a drug that blocks myostatin would seem like a slam dunk as a treatment for muscular dystrophy — and as a drug ripe for abuse by athletes. Wyeth, one of the world's largest pharmaceutical companies, created a myostatin-blocking drug and put it into clinical trials for Duchenne muscular dystrophy, a muscle-wasting disease that kills hundreds of men each year before they reach their mid-thirties. Over-the-counter supplements that claimed to block myostatin took off with weightlifters.

But earlier this year, Wyeth published disappointing results about its myostatin blocker, MYO-029. And then, deep in a filing with the U.S. Securities and Exchange Commission, Wyeth quietly announced that it had canceled all testing of the experimental drug.

Se-Jin Lee, the molecular biologist at Johns Hopkins University who discovered myostatin in mice in 1992, says it's "disappointing" that MYO-029 is dead, but he still believes blocking myostatin holds promise. Acceleron, a Cambridge, Mass.-based biotech firm, is still pursuing the approach. As for those dietary supplements, "They must be bogus."

But what really disappoints Lee is that discussion of a promising treatment for a devastating disease becomes entangled in discussions of doping. The benefits go far beyond the Duchenne muscular dystrophy, a disease that is diagnosed in only 600 American boys a year, to diseases like cancer and AIDS. Such drugs could even have a big effect on the muscle weakening that comes with aging.

"Everybody gets old; everybody is going to lose muscle mass," Lee says. "If you look at the benefit of buying people five more years of independent living, it seems a little out of whack to be worrying about sports records."

And despite all the difficulties inherent in drug development, medicines that could enhance athlete performance are still moving forward. Acceleron and some other companies are working on several different drugs that hit myostatin. And Affymax, a Palo Alto biotech firm, is working on what may be a cheaper, easier to use version of EPO.

These are baby steps, but also reminders that someday, performance-enhancing drugs will be able to really push the limits of what the human body can do — like it or not.