A meatheads dream, a reality? Gene doping.

Long ago, in the late 19th century, meatheads around the world were aroused by whispers of a new form of performance enhancement. “No longer shall we worry of the burdens of rotating injection sites and peripheral collapse or scarring, for scientists will soon have the ability to edit our very being!” Meatheads they may be, but this is certainly a prophecy not likely to be left unfulfilled for long…

In 1998, the Sweeney group first published a paper in which they described the insertion of small segments of DNA into the genome of mice. These pieces of DNA encoded for insulin-like growth factor 1, a cell surface protein required for the reception of growth factor, leading to increased muscle growth and regeneration. This resulted in “Schwarzenegger mice”, mice with increased strength. This finding alone purportedly earned Sweeney a phone call from a desperate high school football coach who wanted his whole junior squad doped! Sweeney declined, of course.

10 years on, in 2008, the generation of the PEPCK Cmus supermouse blew people’s minds. PEPCK-C is an enzyme which removes oxaloacetic acid which builds up during strenuous respiration, hindering the Citric Acid Cycle (the reaction series responsible for the generation of ATP (energy) from glucose). The gene for this enzyme was introduced into mice at the germ-line stage, and resulting in hyperactive mice that could run for 5 kilometres at 20metres/min, compared to the average 0.2km at the same speed achieved by their wild-type brethren. Theoretically this could be applied to humans, but only at the germ-line. Maybe of interest to crazy sports-parents who want elite sporting children? These supermice, however, were overly aggressive and sexually-active. Advantages and disadvantages I suppose…

EPO, erythropoietin, is a hormone which plays a key role in red blood cell production. EPO injected intravenously is used as a treatment for anaemia, but has also been used for doping purposes due to the effect of increased red blood cell production and capacity for oxygen, increasing sporting proficiency. EPO is therefore seen as a likely candidate for gene doping. By viral transfection, macaque monkeys were administered the gene for EPO, and it worked. However, it worked just a tad too well. The monkey’s blood became so thick with red blood cells that doctors had to constantly bleed them to avoid myocardial infarction. What’s more, the immune system then kicked in, drastically depleting the red blood cell count, rendering the monkeys severely anaemic. Doctors eventually euthanized.

Gene therapy however is such a promising area and is still the focus of intense research. Sweeney is still going at it, and recently published an article in August 2013 in which a system for tissue-specific expression of genes delivered via adenoviral particles can be achieved. This hails good times for patients which could possibly benefit from this kind of treatment. However, elite athletes are also keeping a close eye on these developments, ever-hunting that next big performance-enhancing scientific breakthrough.

Till next time,

James

Barton ER, Morris L, Musaro A, Rosenthal N, & Sweeney HL (2002). Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. The Journal of cell biology, 157 (1), 137-48 PMID: 11927606

Hanson RW, & Hakimi P (2008). Born to run; the story of the PEPCK-Cmus mouse. Biochimie, 90 (6), 838-42 PMID: 18394430

Rivera VM, Gao GP, Grant RL, Schnell MA, Zoltick PW, Rozamus LW, Clackson T, & Wilson JM (2005). Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood, 105 (4), 1424-30 PMID: 15507527

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