For years after he nabbed two gold medals ill the 1964 Winter Olympic Games, Eero Mantyranta was dogged by rumors of deceit: The Finnish cross-country skier had something in his blood, something that gave him an edge over the competition.
Mantyranta never flunked a drug test--but the rumors nonetheless turned out to be true. Scientists discovered later that Mantyranta was born with a rare mutation (abnormality) in his DNA, the microscopic storehouse of hereditary information in every body's billions of cells. The quirk caused him to crank out unusually high levels of red blood cells, doughnut-shaped cells that fuel muscles with oxygen and help power athletes. Mantyranta's natural genetic advantage made him unbeatable.
Now scientists and sports officials fear the day when athletes born without such lucky genes, or individual units of heredity, could simply add them later--cheating not with drugs but with injections of DNA. It's called "gene doping," and the concept is simple: hijack state-of-the-art genetic technology to become a better, faster, stronger athlete. And that prospect has many sports officials worried; unlike other performance-enhancing drugs such as steroids (muscle-building hormones), gene doping could be nearly impossible to detect.
"Athletes are probably already ahead of us," says Theodore Friedmann, a genetics researcher at the University of California at San Diego.
ENTER MIGHTY MOUSE
For gene doping to work, athletes would first need performance-enhancing genes. Scientists experimenting with therapies for atherosclerosis, a life-threatening disease that clogs blood vessels, and cystic fibrosis, a genetic disorder marked by faulty digestion, have already pinpointed genes with the potential to become popular locker-room contraband.
How? Take research subject No. F66-52, aka "Mighty Mouse." Caged in the cluttered and slightly stinky laboratory of Se-Jin Lee, a molecular biologist at Johns Hopkins University in Baltimore, Md., F66-52 isn't your ordinary rodent. As Lee attempts to extract the furry brown lump from its cage, Mighty Mouse clings stubbornly to its metallic bars.
"He's just flexing to show off," jokes Lee.
But it's true: This rodent is ripped. Every time F66-52 squirms, thick knots of muscle ripple visibly beneath its shoulders and rump. An unaltered mouse cowering in the corner of a nearby cage looks wimpy by comparison. To create Mighty Mouse, Lee targeted a gene called myostatin, which he found plays a key role in muscle development (see diagram, p. 13). When the gene is blocked, muscles balloon. The strongest of the myostatin-depleted mice in Lee's lab boast four times the muscle mass of a typical rodent, he says.
To stop myostatin production, Lee and his team injected a protein called follistatin while the mouse was still a tiny fertilized egg. They still don't know exactly how it works, but the protein disables myostatin. As Mighty Mouse grew, so did its muscles. Lee hopes his research leads to new drugs for humans with diseases that cause muscles to wither, like AIDS. But he also knows that among athletes, "clearly there's the potential for abuse."
MUSCLES AT WORK
Genes that beef up muscles would be ideal for sprinters, weight lifters, football running backs--any athlete who craves quick power bursts. Marathoners, cross-country skiers, and others who prize endurance, meanwhile, might gain a boost from genes that increase blood flow.
That's because as muscles work for extended periods, they draw heavily on the oxygen contained in red blood cells to keep from tiring out. Marathoners, notes biologist Peter Schjerling of the Copenhagen Muscle Research Center in Denmark, typically boast four times more blood vessels feeding their muscles than sprinters. So for an athlete who needs to go the distance, "the more blood vessels you have, the better," he says. (Average adults have an estimated 100,000 miles of blood vessels snaking through their bodies.)
One candidate for gene doping is erythropoietin, or EPO, a chemical that regulates red-blood-cell production. Used routinely by doctors to treat anemia, a deficiency of red blood cells, EPO has become one of the most widely abused drugs in sports. Its allure is simple: By boosting the number of oxygen-rich red blood cells pumped throughout the body, muscles remain fresher longer. EPO is what cross-country skier Eero Mantyranta's body naturally overproduced.
GENE THERAPY: A DREAM?
But finding genes that enhance athletic performance is just the first step. A much tougher problem is inserting genes into human cells and controlling them, a procedure known as gene therapy. "Gene therapy is easy to imagine," says Friedmann. "But people tend to underestimate the problems."
After more than a decade of research, gene therapy has succeeded in treating only one or two rare disorders. And there have been serious setbacks: A University of Pennsylvania gene therapy volunteer died during an experiment in 1999.
To deliver a gene into a cell, researchers often enlist the help of one of nature's most efficient DNA delivery services: the virus. Little more than a microscopic capsule of DNA, a virus infects humans by inserting its genetic material into DNA found in our cells. With corrupted DNA, healthy cells then chum out billions of virus-infected cells that make the body sick. In gene therapy, scientists attempt to use this "insertion trick" to heal. First, they disarm the virus by removing most of its disease-causing DNA, and then replace it with the therapeutic genes they want delivered.
But a virus isn't always a reliable delivery system and may ferry its genetic cargo to the wrong location--say, heart-muscle cells instead of leg-muscle cells. And even if the engineered virus does hit the bull's eye, researchers still lack techniques to control the genes it delivers--to switch them on and off at will. (Genes naturally turn on and off over time to regulate chemical functions in the body.)
An always-on EPO gene could crank out so many red blood cells that blood would turn as thick as maple syrup, increasing the risk of artery-blocking clots that can cause heart attacks. Injected EPO has been blamed in the deaths of more than 20 cyclists since 1987.
If--or when--scientists do resolve all the challenges of gene therapy, it could mean big headaches for sports officials. Performance-enhancing genes would be indistinguishable from natural ones, making it very difficult to prove what genes an athlete was born with. "You can forget about a test," says Schjerling.
Still, even if gene-doping tests did emerge, some experts think cheaters would continue to risk re-engineering their DNA. After all, tests for steroids have been around for years. And as the recent news exposing rampant steroid abuse in professional baseball shows, these and other performance-enhancing drugs remain as popular as ever.
"There will always be those who cheat," says Gary Wadler, author of Drugs and the Athlete. "It gets back to the issue of money, fame, fortune."
Did You Know?
* Many genes build and maintain lean muscle mass. Dr. H. Lee Sweeney at the University of Pennsylvania researched one gene in particular that produces a potent muscle-building protein called IGF-1. The body produces less and less IGF-1 as it ages, which may explain why muscle mass typically begins to fade in people over 30. In one experiment, when Lee injected a mouse with IGF-1, it sprouted muscle mass 60 percent greater than that of a normal mouse. It's likely, says Sweeney, the same experiment will produce similar results in humans.
* The myostatin gene is "turned on" or expressed primarily inside the cells of skeletal muscles. For reasons still not understood, the gene produces chemicals that inhibit muscle growth. Both mice and cattle (Belgian Blue bulls) born with myostatin mutations develop adult physiques ripped with bulky muscles.
Language Arts: Write a science-fiction story in which genetic engineering--the scientific alteration of genes--is commonplace. For what reasons do people choose to change their genetic makeup? In what ways does the technology change society?
Critical Thinking: What would motivate an athlete to use illegal, dishonest, and physically harmful means to "excel" in a sport? What does good sportsmanship mean?
Directions: Read our story on gene therapy and athletes, then write a paragraph using the vocabulary words provided below.
1. Imagine you're a doctor at the 2012 Olympic Games. Your job: test athletes for illegal performance-enhancing substances. Write a paragraph on common cheating methods used by athletes to gain a competitive edge. (gene doping, gene, red blood cells, steroids)
2. Describe how gene therapy may help cure diseases that destroy muscles. (muscular dystrophy, mutations, virus)
Answers will vary but should include the following points.
1. One of the most common forms of cheating at the 2012 Olympic Games involves gene doping. We suspect one marathon runner has been injected with a gene that makes him produce more red blood cells. But unlike steroids, it's very difficult to test for the presence of illegal genes.
2. Genes that carry mutations can sometimes cause muscle-weakening diseases, tike muscular dystrophy. Gene therapy is a medical technique that replaces the faulty genes with healthy ones. A virus can be used to deliver healthy-genes into muscle cells.
IT'S YOUR CHOICE
Choose the correct answer(s) to these questions: 1 The myostatin gene (A) slows muscle growth. (C) produces follistatin. (B) makes muscles grow. (D) none of the above. 2 Which statements about DNA are true? (A) It's found only in humans. (C) It stores proteins. (B) It stores genes. (D) It weakens muscles. 3 Which of the following can be used to deliver a gene into a cell? (A) bacteria (C) myostatin (B) a virus (D) fungi
ANSWERS IN TEACHER'S EDITION
1. a, c 2. b 3. b
How to make a muscle mouse
An estimated 2,500 different genes (units of hereditary information) control muscle growth in both mice and humans. By blocking just one gene, scientists at Johns Hopkins University created a mouse flush with ripped, lean muscles. Here's how they did it.
1 FINDING A "MUSCLE GENE" ...
A) Myostatin is a gene found in mice and humans. To find out its effects on muscles, scientists deleted the gene from DNA found in 8-week-old (embryonic) mice cells. DNA is a helix of chemicals that stores genes.
B) Cells lacking myostatin were then injected into the cells of a normal mouse embryo.
C) The cells lacking myostatin mixed with the normal cells of the embryo.
D) Next, the embryo was allowed to grow in a pregnant mother.
E) Result: The genetically-engineered offspring (babies) had up to four times more muscle mass than average mice.
2 ... MAY ONE DAY HELP CURE DISEASE....
* Since deleting the myostatin gene in humans is impossible, scientists have identified a protein (cell-building chemical) called follistatin that blocks the gene. Follistatin produced muscle mice similar to those without the myostatin gene.
* Muscle-enhancing substances like follistatin could help treat diseases like muscular dystrophy (an inherited muscle-wasting disease) or AIDS-related muscle disorders.
The U.S. Food and Drug Administration's fact sheet on gene therapy: www.fda.gov/cber/infosheets/genezn.htm
Dr. Se-Jin Lee's research on muscle wasting at Johns Hopkins Medical Institutions: www.hopkinsmedicine.org/press/2002/MAY/020523.htm
"Unnatural Selection," by E.M. Swift and Don Yaeger, Sports Illustrated, May 14, 2001. pp. 86-93.