Born to run? Genetic tests claim to measure athletic prowess.

In preparation for the Olympics, London is building up excitement with an event organized by Progress Educational Trust (PET) and the Royal Society of Medicine, and exploring the genetic underpinnings of athletic prowess. Supported also by the Wellcome Trust, the event has been given a very catchy title indeed: Genetic Medalling, and will take place tomorrow, June 7th, at 630 pm at the Royal Society of Medicine (1 Wimpole Street, W1G 0AE). What are the genes that confer a competitive edge to people? Are there favorite genetic bakgrounds? Are there individuals simply “born to run”?

Photograph by Sarah Norcross


These issues have implications over the enhancement debate in relation to fairness in sports. When does a genetic or biological advantage become unfair, if ever? Is there a threshold that we should put on individuals being genetically or biologically exceptional?
Similar arguments underpin the new IAAF rules regulating the eligibility of women with hyperandrogenism to compete with other female athletes. The rationale -being disputed in “When gender isn’t a given“- is that women who are too exceptional in terms of hormones have a competitive edge which is unfair over the rest of the female athletes. This was also one of the rationales for Caster Semenya’s gold medal in the 800 meters being taken away at the Berlin World Athletic Championship in 2009.

The implications of this debate on fairness and the construction of categories in sports have not escaped the organizers of the event, who write that “If we do find performance-related genes, how might this affect our attitude to sporting ability, fairness, equity and justice? To take an extreme scenario, would it be fair to segregate some sporting events based on ‘race’ if it turns out that certain ‘races’ have a genetic advantage?” The all concept of race is extremely dubious, as over thirty years of research have shown uncontroversially that within the Homo Sapiens there is no biological basis for our common social understanding of race (Lewontin 1972; Barbujani, Magagni et al. 1997; Serre and Paabo 2004).

Some companies in the US are already making a profit from selling genetic tests which supposedly measure the athletic potentials of kids, for example a company called ‘American International Biotechnology Services‘ and another aptly called Atlas Sports Genetics and claiming to be able to “map” the genetic underpinnings of athletic prowess.
Parents would therefore be encouraged to “invest” on their children and steer their education in one way or the other, for example signing them up with a basketball team or a swimming one. And as higher education is tremendously expensive in the US, the companies selling the tests advertise them as possible decision making tools as to which scholarship parents should aim at.

One of these even planned selling the test at big drugchain stores such as Walgreens (Walgreens is more or less the American equivalent of the British Boots). On May 11, 2011, the FDA stepped in and stopped one of the companies and sent Bill Miller, chief executive of American International Biotechnology Services, a letter demanding justification for marketing his Sports X Factor test without the agency’s authorization.
If you do not believe that you are required to obtain FDA clearance or approval for the Sports X Factor Test Kit, please provide us with the basis for that determination“.
A hearing is expected to take place soon.

As I was reading the article by Rob Stein on the Washington Post (note, thanks to Katrina Karkazis for pointing that out to me), I found a particularly spot-on on some lateral implications of this new quest for the holy genetic grail (or medal!) on the meaning of sports itself. So here’s the comment, and thanks to Bob who kindly reminds us: “What ever happened to playing sports just because it’s FUN?”…

Those interested could also read:

Barbujani G, Magagni A, et al. (1997). An apportionment of human DNA diversity. Proceedings of the National Academy of Sciences U S A 94(9): 4516-9.

Camporesi S, Karkazis K (2011) Opinion: When gender isn’t a given. Special for the Mercury News, May 22, 2011.

Karama C. Neal. (2008) Use and Misuse of “Race” in Biomedical Research. Online Journal of Health Ethics, Vol 5, No 1

Lewontin, R (1972). The apportionment of human diversity. Evolutionary Biology 6: 381-398.

Serre D, Paabo S. 2004. Evidence for gradients of human genetic diversity within and among continents. Genome Research 14(9): 1679-85.

Stein R, (2011) Genetic testing for sports genes courts controversy
Washington Post, May 18.

The platypus in cancer drug development, and benefits from participating in Phase 0 trials.

It is a matter of fact that the drug development process is anachronistic. It was developed in the ’60s and is not suitable for new, molecularly targeted agents that are now being developed in the molecular biology laboratories. In the past forty years, the advances in terms of unraveling the molecular pathways deregulated in tumours have been astonishing, but have not resulted in the equal great expected advancements at the bedside. That is what is called the ‘gap of translational research‘. This gap is especially acute in the field of oncology, where the percentage of New Molecular Entities (NME) that make it from experiments of animals to entry to the market is only 5 %, and it is estimated that it currently takes 12 to 15 years from drug discovery until marketing, compared with an average of 8 years in the 1960s. Quoting David Steensma (Dana Farber Harvard Cancer Centre) on the anachronisms of the drug development process: “Like the duckbill platypus, the contemporary clinical trial development process is an organism that no rational person would have designed a priori. Its awkward present form evolved because of decades of tinkering with administrative structures at NCI and the National Institutes of Health, reactions to specific events or perceived risks, and changing needs of various governmental and nongovernmental stakeholders”.
This problem was recognized in 2004 by regulatory agencies FDA & EMA and prompted the issuing of new guidelines, which take the name of Phase 0 trials. Phase 0 trials are investigational new trials, which administer sub-pharmacological doses to the participants. They have no intention to treat and, at least as intended by regulatory agencies, aim at eliminating therapeutic failures early in the cancer drug development for agents without biological effectiveness, thus reducing costs and time of drug development.
Phase 0 trials are different in design from traditionally Phase 1 cancer trial, where a starting dose is selected, designed to be safe based on animal toxicology studies, and then doses are escalated to a maximum tolerated dose (MTD), defined by toxicity. The Phase 1 trial design results in a high proportion of the patients being treated at doses so low that there is no therapeutic effect at all, while an abundant bioethics literature demonstrated the existence of a widespread “therapeutic mis-estimation” (i.e. a wrong belief about the probability of receiving therapeutic benefits derived from participation) among participants of Phase 1 cancer trials. From this perspective, Phase 1 cancer studies with low doses of agent are no different in practice from Phase 0 studies, since both have no therapeutic effect, though the latter do not seem to pose the same problems of therapeutic mis-estimation, as by definition do not intend to treat. As put by Dr Shivaani Kummar , principal investigator for the first Phase 0 trial performed at NCI-NIH “A patient’s decision to participate and to provide biopsy samples for research purposes as part of a phase 0 trial is not clouded by any perception of direct medical benefit”.
Could it still be argued that Phase 0 trials offer a benefit to the participant? Adopting the framework developed by Nancy King (Center for Genomics & Society, UNC Chapel Hill), the answer is yes. King does not equate benefit derived from participation in clinical research with therapeutic benefit, and actually distinguishes three possible kinds of benefits deriving from participation in clinical research: a) direct benefit to subjects, defined as “benefit arising from receiving the intervention being studied”; b) collateral benefit to subjects (or “indirect” benefit), defined as “benefit arising from being a subject, even if one does not receive the experimental intervention” (for example, a free physical exam and testing, free medical care and other extra care/check ups, or the personal gratification of altruism); c) aspirational benefit, defined as “benefit to society and to future patients, which arises from the results of the study”. Within the classification outlined by King, benefits derived from Phase 0 trials could belong both to subclass b) and c).
In addition, it could be argued that subjects have an interest in participating in research, because they can derive benefits (understood in King’s framework) from it, and such benefits would advance their well-being. But the relationships between the concept of interest, well-being and benefit are too complex to be dealt with in a single post. Till later!

Further reading

Agrawal M, Emanuel EJ. Ethics of phase 1 oncology studies: reexamining the arguments and data. JAMA 2003. 290, (8): 1075-1082.

Butler D, Translational research: Crossing the valley of death. Nature 2008; 453:840-842.

King NM. Defining and describing benefit appropriately in clinical trials. The Journal of Law, Medicine & Ethics 2000;28(4): 332-343.

Kummar S, Kinders R, Gutierrez ME, Rubinstein L, et al. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clinical Oncology 2009; 27(16): 2705-2711.

Miller M. Phase I cancer trials. A collusion of misunderstanding. The Hastings Center Report. 2000; 30(4): 34-43.

Steensma DP. The ordinary miracle of cancer clinical trials. J Clin Oncol. 2009 Apr 10;27(11):1737-9.

President Obama calls for a review of human subjects’ protection following the unraveling of the Guatemala STD study.

On October 5, 2010, I reported on this same blog on the recently discovered Tuskegee-like scandal, which took place in Guatemala in the ’40s and saw the purposeful infection of prisoners and other vulnerable populations with the syphilis bacterium (https://humanitiesandhealth.wordpress.com/2010/10/05/clinton-delivers-formal-apology-for-a-newly-discovered-tuskegee-like-study/). The study was only recently brought to light thanks to the studies of Wellesley College history professor Susan Reverby, which resulted in a formal apology delibered by Secretary of State Hillary Clinton on October 1, 2010, much on the footsteps of the apology given by former President Bill Clinton in 1997 to the Tuskegee victims.

More than two months have passed since Hillary Clinton’s public apology, and now President Obama has officially asked the Presidential Commission for the Study of Bioethical Issues to undertake an exhaustive review of human subjects’ protection guidelines. As we can read in the Presidential Memorandum, says Obama:

In light of this revelation [The Guatemalan study], I want to be assured that current rules for research participants protect people from harm or unethical treatment, domestically as well as internationally. I ask you, as the Chair of the Presidential Commission for the Study of Bioethical Issues, to convene a panel to conduct, beginning in January 2011, a thorough review of human subjects protection to determine if Federal regulations and international standards adequately guard the health and well-being of participants in scientific studies supported by the Federal Government. I also request that the Commission oversee a thorough fact-finding investigation into the specifics of the U.S. Public Health Service Sexually Transmitted Diseases Inoculation Study”.

The Presidential Commission for the Study of Bioethical Issues was appointed by Barack Obama one year ago to substitute the dismantled “President’s Council of Bioethics” and is chaired by political theorist Amy Gutmann, who symbolizes the greater emphasis put by the President on the policy implications of ethical positions taken by the Commission.

The past few years have witnessed an increasing number of clinical trials being moved offshore, i.e. to low and middle income countries, and as reported by Nellie Briston on the Lancet this week: “A thorough review of the safeguards in place to protect modern human trial participants is appropriate and timely” .

Also on a related topic, the Commission will need to explore the relationship between the FDA and Helsinki Declaration regulating internationally clinical research on human subjects. The Helsinki Declaration was controversially shelved by the FDA in October 2008, which favoured instead the adoption of Good Clinical Practice (GPC) Guidelines, which represent a weaker ethical standard as, for example, they are silent on the use of placebos in clinical trials when there exists an active treatment as an alternative.

The Presidential Commission will start its work on the issue in January and has 9 months to deliver the reports.

Further readings

Bristol, N. US reviews human trial participant protection, The Lancet 2010; 376(9757):1975-6, doi:10.1016/S0140-6736(10)62247-7; http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962247-7/fulltext?rss=yes

Camporesi, S. The FDA decision to shelve the Helsinki Declaration: Ethical considerations, ecancermedicalscience, June 10, 2008; doi=10.3332/eCMS.2008.LTR76, http://www.ecancermedicalscience.com/comment-letters-to-the-editor.asp?doi=10.3332/eCMS.2008.LTR76#letter

McNeil, D. U.S. Apologizes for Syphilis Tests in Guatemala, The NewYorkTimes, October 1, 2010, http://www.nytimes.com/2010/10/02/health/research/02infect.html

Presidential Memorandum-Review of Human Subject Protection, November 24, 2010, http://www.whitehouse.gov/the-press-office/2010/11/24/presidential-memorandum-review-human-subjects-protection