Download Thesis - Michigan State University

The study of science as a whole has led to numerous amazing achievements, and
many of which have led to an increase in not only quality of life, but also an increase in
the duration of lifespan. As far as medicine is concerned, the science field as a whole has
been dedicated to preventing, curing, and treating various viruses and diseases. With the
invention of antibiotics (penicillin) in 1928 by Sir Alexander Fleming (Biologist London,
2000), many bacterial infections were able to be treated and cured much quicker than
ever before. However, as antibiotics became more mainstream, so did their misuse. Not
finishing the recommended dosage and a variety of other attributes have led to the
creation of the super-virus which is antibiotic resistant, and needs a much stronger more
potent antibiotic to cure it. Along the same lines, gene therapy was created to improve
muscular abilities in those suffering from muscular dystrophy and other various muscle
atrophy conditions. However, gene doping quickly emerged, and just as with any other
science, the use of muscle enhancement began to be used for a purpose other than for the
benefit of the greater good, and those suffering from disease. Gene doping is a prime of
example of when good science has been altered to bad science in order to serve those
seeking non-therapeutic and highly dangerous genetic enhancement. Gene doping has the
ability to greatly impair bodily function and its medical ramifications cause it to be far
too risky for pure athletic performance enhancement.
In 1998 a physiology professor, H. Lee Sweeney, at the University of
Pennsylvania in Philadelphia, researched a cure for muscular dystrophy and came out
with a study showing that gene therapy could actually enhance mouse muscle. The news
spread quickly with the help of the media coverage, and roughly half of all those
inquiring his results were healthy athletes looking for bigger and higher performing
muscles. Dr. H. Lee Sweeney was much surprised by this source of attention, and it was
this attention that led to a cascade of events further questioning the possibility of gene
doping. Gene doping is, according to the World Anti-Doping Agency, is the “nontherapeutic use of cells, genes, genetic elements, or of the modulation of gene expression,
having the capacity to improve athletic performance (www.wada-ama.org)." According
to Dr. Andrea Amalfitano, a molecular and microbiology geneticist at Michigan State
University, the theory of gene doping is feasible, however the actual method of which is
still in infancy, and is simply not probable at this day in age. However, theoretically
speaking, if it were to be practiced in the clinical setting, there would be horrible
repercussions as a result of its testing. For example, if muscle growth is stimulated up to
20-40% as Dr. Sweeney’s results show, a massive growth of cells through increased
divisions can cause cells to growth out of control therefore causing cancer, which is
essentially unchecked cell mutation and overgrowth. According to the American Cancer
Society, cancer is defined as,
Cells in a part of the body begin to grow out of control; all types of cancer start
because of out-of-control growth of abnormal cells. Because cancer cells continue
to grow and divide, they are different from normal cells. Instead of dying, they
outlive normal cells and continue to form new abnormal cells, . In cancer cells,
the damaged DNA is not repaired. (www.cancer.org).
Simply injecting a synthetic gene into a body can cause the out of control growth, thereby
causing cancer, such as leukemia. Three of the eleven French children, who were all born
with deficiencies, received gene therapy to thousands of genes at birth, and the three
eldest of the eleven children participants all have been diagnosed with leukemia, and one
of which has died as a result (Amalifitano, 2005). There exists a risk to benefit ratio, and
as it stands the risks of gene doping far outweigh the benefits of it.
A precursor to gene doping and a more common use of doping is through the use
of Erythropoietin, which is a glycoprotein hormone that helps to increase the number of
red blood cells in circulation, which will increase the amount of oxygen carried
throughout the blood in the body. Originally, erythropoietin injections were created for
those suffering from anemia, which is the deficiency of the oxygen carrying capacity of
blood. Erythropoietin is now used as a mechanism of oxygen transport and its delivery to
muscles and tissues in the periphery can greatly improve aerobic athletic performance.
The bettering of muscle oxygenation can be performed through the injection of
erythropoiesis, which is more appropriately called human erythropoietin (rHuEpo)
(Lippi, 2004) and has been used in numerous endurance athletes for more than a decade.
Yet, with more recent modes of detection of increased EPO through blood testing,
athletes are increasingly turning to other sources such as blood and gene doping for their
performance enhancement needs. EPO, although detectable, can still cause a respectable
amount of damage. Results of lab tests noted that animals' red blood cell counts almost
doubled within ten weeks, and produced incredibly thick blood. As a result, the animal
blood had to be thinned, and if not, would have caused heart failure amongst other
problems (Sweeney, 2004). Another fault of this mechanism of performance
enhancement is that the human body can sometimes sense the injected EPO as a foreign
invader, and then not only attack the injected EPO but also attack the body’s own EPO,
causing a horrific immune response against the viral vector delivery and eventual death.
Although EPO has been injected by athletes for years, now mechanisms for EPO gene
therapy are being created and will go to clinical trial as soon as these problems and others
are deciphered. (McCrory, p.192)
Along with studying EPO came the discovery of a new protein family named
hypoxia inducible factors (HIFs), which have brought about a greater understanding of
the detailed mechanisms of the response to hypoxia, which increases EPO in the body.
Genes controlled by HIF include coding proteins which induce EPO (red blood cell
production), and proteins that encode glycolytic enzymes which arouse additional energy
in climates of relative deficient oxygen, both which are vital in obtaining improved
aerobic athletic performance. However, with the discovery came horribly detrimental
consequences; along with beneficial effects on oxygenating blood, HIFs also encourage
genes which encode angiogenetic molecules and proteins apart of cell growth, survival,
division, and mortality, all of which may boost cancer growth and spread throughout the
body. (Lippi, 2004)
Many proponents of gene doping tend to skip of the details of its mechanism,
which are vital to its success. And it should be noted, however, that laboratory research
on transgenically modified mice does not always translate to success in the real world
with humans. Yet, in the lab, scientists have created “marathon mice” which can run
nearly two times as fast as normal mice. These mice were given an extra gene helping to
increase production of PPAR-delta protein, which increases the quantity of slow twitch
muscle fibers, and are pertinent in endurance events (Anonymous, p.3). PPAR-delta
(Peroxisome Proliferator Activated Receptor) is known to be a key role in the regulation
of metabolism and adiposity. PPAR-delta is also important in an adaptive metabolic
response of skeletal muscle to exercises testing endurance by limiting the quantity of
oxidative myofibers. Given the results that were obtained with animal testing, PPARdelta agonists may prove to have therapeutic usefulness by increasing fatty acid
consumption in both adipose tissue and skeletal muscle (Luquet, p.313). This stands to
pose many problems, and could lead to an eventual depletion of the fatty acids in the
body that are pertinent to many functions throughout the body and are extremely
preventative to many health issues, including heart attack, diabetes, atherosclerotic
plaque, heart disease, cholesterol, and high blood pressure (www.americanheart.org).
Considering its infancy, and the fact that it is not in clinical trials yet, gene doping
is not a current issue, but as more is learned about how its mechanism of success could
perform, it will become much more of an issue to be aware of. Much more information is
needed to know about how the mechanism of gene doping could actually work, and how
the injection of a new gene could potentially spread to the entire muscular system. Many
factors are needed simultaneously in order for success; including, the correct tissue, with
the correct dose, and at the correct time. Nonetheless, gene doping is highly risky and
should not be used for pure athletic performance. According to Dr. Amalfitano, a
molecular and microbiology geneticist at Michigan State University, the muscular system
comprises roughly forty percent of the body’s composition, and the biggest problem in
gene doping is having a method of spreading the effect of the doped gene from one of
about four to five-thousand cells per muscle to which it is injected, to spread not only
throughout the entire muscle, but also to the rest of the muscular system. Yet as more is
learned about the intricacy of the body and all of its pathways, the more accurate and
successful athletes will be able to use gene doping as a way of enhancing their muscles
for pure athletic performance. However, what side affects and risks are these athletes
willing to forego for the sake of winning an athletic competition? Long and short term
affects of gene doping should be made well aware of to all possible athletes. Besides
awareness of all the health risks, gene doping needs to be highly regulated in order to
derail black market sales, and having athletes dope in their garages, neglecting sterility
and other possible secondary effects of not practicing safe injection. Although the current
status of gene doping is still in its infancy, and not methodically possible at this point in
time, some athletes are eager to jump on the performance enhancement bandwagon, and
try anything which will give them the edge, which is pressuring scientists to develop
detection methods and regulatory means. Pressure of all angles is now on scientists,
athletes want to gene dope, anti-doping agencies and other various athletic committees
want detection methods immediately, and other government officials want regulation and
seek to run clinical tests to test its success in humans.
Reference List
Amalfitano, A.
American Cancer Society. www.cancer.org
American Heart Association. www.americanheart.org
Anonymous. In sport, are good genes just another cheat? New Scientist. London: August
28-September 3, 2004. Vol. 183, Issue 2462; pg. 3, 1 pgs.
Diggins, FW. The discovery of penicillin: so many get it wrong. Biologist.London. 2000
June: 47(3):115-9.
Lippi, G, and Guidi, G.C. Gene manipulation and improvement of athletic performances:
new strategies in blood doping. 2004. Italy.
Luquet S. et al. Roles of PPAR delta in lipid absorption and metabolism: a new target for
the treatment of type 2 diabetes. Biochem Biophys Acta. 2005 May
30;1740(2):313-7. France.
McCrory, P. Super athletes or gene cheats? British Journal of Sports Medicine. London:
June 2002. Vol. 37, Issue 3, pg. 192
Sweeney, H.L. Gene Doping. Scientific American. July 2004.
World Anti-Doping Agency. www.wada-ama.org