This is a short essay I wrote for school. In a nutshell, insulin-like growth factor one is a protein that encourages muscle growth. The DNA code for the protein is inserted into the host cell by means of a transgenic virus, which causes the protein to be produced in the host cells. The technique has been shown to result in up to 30% gains in muscle mass and strength, which increases twofold when exercise is involved. Though no pathological side-effects have been observed in the test subjects, the technique is nowhere near ready to test on humans, and it probably causes cancer.
IGF-1: A Genetic Steroid?
In recent years, great advances have been made in the field of gene therapy. Of particular interest are the discoveries being made in muscular dystrophy research, because of their potential applications toward the enhancement of healthy humans. One such advance is the research being done at the University of Pennsylvania on a substance referred to as IGF-1: Insulin-like Growth Factor Number One.
A particular hotbed of research in this area has been the Pennsylvania Muscle Institute at the University of Pennsylvania, where a team of researchers led by associate director H. Lee Sweeney has been experimenting with muscular dystrophy treatments for over a decade.
In a 2001 article in Nature Genetics, Sweeney's team noted that the aging-related decline of the strongest, fastest muscle tissue in mammals could be combated by inducing myocyte hypertrophy with transgenically expressed IGF-1. This postnatal muscle-mass increase was not accompanied by any of the pathological side effects present in previous attempts (Musaro et. al). Though the study was performed on mice, the enormous implications were immediately apparent.
The next year, the same team published an article in Journal of Cell Biology describing the effects of the same method applied to mice exhibiting symptoms similar to a condition called Duchenne muscular dystrophy, which affects humans.
Duchenne muscular dystrophy is characterized by an absence of dystrophin, a compound that tethers the actin in a cell's cytoskeleton to the extracellular matrix, in essence holding muscle fibers together. This leads to tears and damage in the muscle fibers, in addition to an inability to repair themselves any faster than the damage occurs. A naturally occurring strain of mice, referred to as "mdx," exhibits identical symptoms.
When the IGF-1 gene was inserted into the muscle tissue of mdx mice, Sweeney's researchers noticed dramatic results: the mice's muscle mass increased 40% over the duration of the study, with proportional increases in strength. Additionally, the effects on the regenerative abilities of those tissues were not impaired by aging (Barton et. al.).
Similar results were obtained later in the same year by another team of researchers by blocking the expression of a gene called GDF8, which codes for a compound called myostatin. Believed to be a negative regulator in the growth of skeletal muscle, its absence alleviated similar dystrophic symptoms in both mice and cattle (Bogdonavitch et. al.).
These studies were brought to the attention of the public at large by Paul Recer in an Associated Press news report in mid-February of 2004. The article mentions that the healthy rats in the 2001 article mentioned above grew 15-30% in size and strength when the gene coding for IGF-1 was present, which more than doubled (and was maintained lifelong) when the mice were put through an exercise program.
Recer goes on the mention that, although the techniques developed by Sweeney's team were originally intended to someday combat muscular dystrophy in humans, the potential exists that they could be applied to healthy humans, which is particularly troubling in light of increasing concerns over athletic doping.
Sweeney's team's technique is intended to keep the gene in the targeted muscles, to avoid potentially damaging effects to other tissues were it to spread, which would also make its use undetectable except with a muscle biopsy and complicated genetic analysis. Recer quotes Richard Pound, of the World Anti-Doping Association, saying that "the sports community lost control of drugs for performance-enhancement in the 1960s to 1990s and has 'been playing catch-up ever since.'"
He does, however, stress that the techniques are years or more away from being ready for human testing, and the potential for cancer or other side-effects is not known. In addition, the procedure is complex and time consuming, and, as he quoted from Sweeney, "not something an athlete could do in his garage (Recer)."
A great deal of public concern over athletic doping has arisen in recent years. Only three days before Recer's article was released, an article appeared in the New York Times about a recent steroid-ring scandal involving the trainers of several high-profile professional athletes, including Barry Bonds, Kelli White, and Dwight Chambers (Curry).
Indeed, the subject was mentioned in the State of The Union Address:
Athletics play such an important role in our society, but, unfortunately, some in professional sports are not setting much of an example. The use of performance-enhancing drugs like steroids in baseball, football, and other sports is dangerous, and it sends the wrong message that there are shortcuts to accomplishment, and that performance is more important than character. So tonight I call on team owners, union representatives, coaches, and players to take the lead, to send the right signal, to get tough, and to get rid of steroids now (Bush).
Despite the techniques' hypothetical potential for abuse, their potential for the treatment of muscular dystrophy cannot be overlooked. Though much more research is necessary before a viable treatment for humans can be brought to market, the results achieved thus far speak almost for themselves: this type of technology has the potential to eliminate a debilitating disease, and, as Sweeney said in his interview with Recer, athletic abuse is at worst "a short term fear."
1. Barton, Elisabeth R., et. al. "Muscle-specific expression of insulin-like growth factor 1 counters muscle decline in mdx mice." Journal of Cell Biology 157.1 (2002): 137.
2. Bogdanovitch, Sasha, et. al. "Functional improvement of dystrophic muscle by myostatin blockade." Nature 420 (2002): 418.
3. Bush, George W. "The State of the Union Address." Washington, DC. 20 January 2004.
4. Curry, Jack. "4 Indicted in a Steroid Scheme That Involved Top Pro Athletes."New York Times. 13 February 2004: A1.
5. Musaro, Antonio, et. al. "Localized igf-1 transgene expression sustains hypertrophy and regeneration in skeletal muscle." Nature Genetics 27.2 (2001): 195.
6. Recer, Paul. "Gene therapy could build super athletes, scientist warns." USA Today. 16 February 2004.