Mechanical Doping

Interesting article on the latest "buzz" involving cycling and doping...

http://www.nytimes.com/2010/06/05/sports/cycling/05cycle.html

Gene Doping: From The Inside Out

Defined by the World Anti-Doping Agency as “the non-therapeutic use of cells, genes, genetic elements, or of the modulation (adjusting) of gene expression, having the capacity to improve athletic performance", this relatively new form of performance enhancement is possibly going to turn doping on it’s head, while pushing ethics and morality in sport and the sport industry to the fore.

First of all, what is a Gene?
Inside human cells, genes provide a sort of “blueprint” or instruction for protein production. Genes are made up of chains or arrangements of DNA. This determines how the cell will function and also its physical attributes.

Gene doping developed out of the concept of gene therapy; treatment developed to cure or ease genetic diseases and disorders such as muscular dystrophy or sickle-cell anaemia. Damaged or flawed genes are replaced with modified, functional ones. These same techniques that can help ordinary people stay healthier could be used to create “superathletes”; weightlifters who “naturally” have larger thigh muscles, cyclists who have more aerobic/type 1 muscle fibers or higher aerobic enzymes produced in those muscles.

Changes in the expression of genes is not a new concept in the science of the human body. Many ordinary medicines can have this effect, as well as daily activities. Training and exercise at least partly modify the expression of one’s genes. But it’s this possibly permanent baseline transformation of the building blocks of the athlete’s body using technology that could be the next big illegal thing. (And possibly is already...). Universities of Washington and Florida were able to give trichromatic vision to squirrel monkeys (naturally dichromatic, using only two primary colours) using gene therapy, possibly leading to a treatment for colour blindness in humans in the future. Higher endurance and increase in musculature in “marathon mice” arose when a group of scientists studied three proteins controlled by a gene that influence how the body manages fats and sugars. This type of research eventually turned towards athletic performance.

How does gene doping work?
Usually a performance-enhancing gene is injected into an athlete carried in a harmless/damaged virus or bacteria (a vector; vehicle to transfer foreign genetic material into another cell). These synthetic genes now in the cells result in altered production of proteins/chemicals and cell function, continuing long-term in most cases.

One of the first gene therapy products associated with genetic doping appeared on the eve of the Turin 2006 Olympic Winter Games, where Repoxygen emerged as a possible substance in use at the Games. This medication was initially considered as a way to fight anaemia.

Detection can prove very difficult. The synthetic genes used most likely appear identical to the natural genes. Identifying the vector or particles of it is possible, but only through muscle biopsies (procedure in which a piece of muscle tissue is removed and examined microscopically). This is not ideal for athlete as some damage, swelling and weakness for a short time results. Genetic “bar codes” or markers can be produced by manufacturers/scientists for their therapeutic products, but this would require input from all relevant parties and administrators. Patterns of protein production and protein levels can also sometimes be analysed. The World Anti-Doping Authority is currently working on a test to check the expression of all 25,000 of the human body's genes, which will look for abnormal patterns.

There are many dangers and possible side effects of gene doping. Often a single gene will have more than one effect in the body and over time illicit other unwanted responses from the body. As with most substances, people’s bodies respond differently and their immune systems especially so. What looked like a successful bid to cure a severe immuno-deficiency disorder, the so-called bubble-baby syndrome, was stopped when some of the children in a French study developed leukaemia, which proved unexplainable. Increased risk of cancer is often a result of the change in DNA within cells. Some hereditary genes might become altered which will then affect children born to athletes. (Interesting thought: If those children grow up to be athletes, would they then also be identified and banned from competition...?)

The ethical issues raised are ever increasing. Cheating is taken to a whole new level. Are we getting closer and closer to playing God? With regards to the uncertainty of long-term effects, who’s to blame when things go wrong? Not only the athlete, but the sports community and society as a whole, will be harmed. Overall, the uniqueness and variety of sport would be removed.

BELGIAN BLUE BULL demonstrates the effect of blocking the antigrowth factor myostatin. A natural genetic mutation in this breed produces a truncated, ineffective form of myostatin, which allows muscle growth to go unchecked. The absence of myostatin also interferes with fat deposition, making these “double-muscled” cattle exceptionally lean.

Here's a really interesting case of when things go wrong:
http://en.wikipedia.org/wiki/Jesse_Gelsinger

Jed

EPO: The Blood Booster

Doping with EPO (Erythropoietin) seems to have begun in the 1980’s with competitive endurance athletes and The World Anti-Doping Agency (WADA) placed it on its list of banned substances in 1990. A reliable and valid detection test developed by French scientists was adopted and implemented in time for the 2000 Olympic Games. This performance enhancing substance has been linked to sudden deaths of athletes and many doping scandals over the years.

Erythropoietin is a naturally occurring hormone, which is produced by the kidneys. It stimulates the bone marrow to produce more red blood cells (RBC’s). This therefore increases the heamatocrit (non-liquid element of blood) and heamoglobin (oxygen carrying chemical) levels of blood. It was first developed as a drug to treat anemia, kidney failure and post-surgery blood loss. It can also be used to assist recovery from chemotherapy and deal with complications of HIV/Aids.

By raising the amount of red blood cells in the blood, the potential to transport oxygen around the body is increased. This improves energy production, especially through the aerobic/endurance energy system, which decreases the use of the anaerobic/short-term energy system, levels of lactate and fatigue. The marker for physical fitness / aerobic capacity, VO2 max, is then increased. Studies have shown time to fatigue/exhaustion (exercise tolerance) can be extended by up to 17% while taking EPO!

But it’s not all good. The increased heamatocrit/RBC levels causes hyperviscosity of the blood (excess density). Some side effects can include raised blood pressure, dehydration, nausea, lethargy, fever and seizures. This thicker blood can increase chance of heart attacks and stroke, as the cardiovascular system is overloaded. Often, once the drug is abused, the amount of RBC production that will actually take place becomes hard to predict, adding to the risks involved. In recent years, in addition to more extensive and accurate testing, some sporting codes have set up safety cut off levels of heamatocrit (50%), although this has been seen as unsuitable, as ‘normal’ levels of heamatocrit vary greatly from person to person.

The most well-known incident of EPO use in sport occurred around the 1998 Tour de France, when the Festina cycle team was found with large quantities of EPO and other banned substances during the 17th stage. Other high profile cases of EPO doping include two cross-country skiers at the 2002 Winter Olympics, an female Ironman World Champs silver medallist and a double cross-country world champion. Along with the laboratory manufactured versions of EPO, newer advanced bone marrow stimulating chemicals/drugs are being developed, such as CERA (Continuous Erythropoiesis Receptor Activator). This modern option for doping has a unique action on bone marrow that differs slightly to EPO and it’s effects can last longer inside the body. A test for CERA was a surprise addition to the 2008 Tour de France and later two-time stage winner Stefan Schumacher was found guilty of doping. In 2009 the International Olympic Committee (IOC) declared that it was to re-test blood and urine samples from the Beijing Summer Olympics for CERA and in November of last year, the Olympic 1500m champion Rashid Ramzi was stripped of his gold medal after testing positive.

Here’s a few links that you might find interesting:
WADA – http://www.wada-ama.org/en/
Doping Cases - http://en.wikipedia.org/wiki/List_of_doping_cases_in_sport

Jed