Monday, April 30, 2012

"...genetic determinism of disease is a reductionistic fallacy that is now collapsing."

I received an interesting email today as part of a loose group of geneticists, statisticians, epidemiologists, and molecular biologists that my mentor participates in regularly. It was a forwarded rant, pasted in its entirety below, from Jonathan Latham, Executive Director at the Bioscience Resource Project.

Dear Friends and Colleagues

In the eighteen months since we published (to some scepticism) The Great DNA Data Deficit: Are Genes for Disease a Mirage? there have been important developments in human genetics that are relevant to the food and environmental movements worldwide, and that deserve to be very widely known.

In particular, two scientific publications, the first from Jan 2012:
The mystery of missing heritability: Genetic interactions create phantom heritability by O. Zuk, E. Hechter, S. Sunyaev and E. Lander in the Proceedings of the US National Academy of Sciences.

and even more recently, from April 2012:
The Predictive Capacity of Personal Genome Sequencing by NJ Roberts, JT Vogelstein, G. Parmigiani, KW Kinzler, B. Vogelstein and VE Velculescu in Science Translational Medicine.

These papers have powerfully vindicated the scientific conclusions of our article. We draw your attention to three noteworthy aspects:

1) the lead authors of each (B. Vogelstein and E. Lander) are among the most highly cited biomedical researchers in the world
2) that their analyses, though new, are based on data that has been available since the human genome was sequenced. It is a rethink, not new data.
3) these papers demonstrate that leading medical geneticists no longer have realistic expectations that most human disease occurrence can be explained by inherited genetic predispositions.

In other words, genetic determinism of disease is a reductionistic fallacy that is now collapsing. Geneticists now face a long retreat from Moscow and the interesting question of who will rewrite the textbooks and tell the public.

We would also like to point out some others who have stuck their necks far out and predicted these events long before we did.
Joseph D Terwilliger and Kenneth M Weiss Linkage disequilibrium mapping of complex disease: fantasy or reality? Current Opinion in Biotechnology 9: 578-594 (1998)
Jay Joseph (The Gene Illusion, 2004)

One last point is perhaps worth making. It is important to appreciate that, with a few exceptions, research geneticists have not merely been wrong in this matter, but that they have actively and grossly misled society as a whole. They could have and should have known that genetic predispositions might after all explain very little in the way of disease, but they routinely failed to make clear that possibility and went far beyond the actual evidence in order to obtain public funds and prestige. Caveat emptor.

yours sincerely

Jonathan Latham and Allison Wilson

What I find interesting, both in this casual email and in some of the linked articles, is the accusation of deception. I'll grant that in a research landscape that promotes harsh competition and limited rewards only for those at the very top, the "significance" section of many grant proposals may be often overblown in order to try to secure funds. However, this exaggeration is done with the completely transparent knowledge that the reviewing committee is not stupid. We are scientists communicating with our peers (other scientists) and it is not likely that this exaggeration is fooling anyone. 

There is also the fact that many geneticists, rife with excitement, have communicated regularly with popsci and lay press regarding the possibilities that lie ahead in genetics. Here, though, is where I raise the question of intent. Latham's email says "research geneticists have not merely been wrong in this matter, but that they have actively and grossly misled society as a whole." I find this statement to be grossly misleading, itself. When the Human Genome Project was completed, yes, you couldn't take ten steps in any direction without tripping over an article about how genetics was going to solve all of our medical problems. But in more recent years, I've been hard-pressed to find statements by respected geneticists that still make such claims. Heck, I even wrote about this myself over two years ago (cliff's notes: we don't have enough knowledge or genetic information to actually give someone a definite measure of their likelihood for developing diseases.) What you're more likely to find, in my opinion, are statements like mine from geneticists that are optimistic but that are representative of the theme that there is still so much we don't know, and THAT'S why continued research is important. It's absolutely not because we think we are trying to convince anyone that we already have the answer, and just want more money ... just because.

The linked January 2012 paper from Zuk and Hechter presents the idea, as if it's a novel one, that interactions and pathways between genes, as well as interactions between genes and the environment, are more likely to explain complex disease pathology than genetic heritability alone. Allow me to remove my 'serious hat' for a second when I say: Well, duh! Labs have been exploring GxG (gene-gene) and GxE (gene-environment) interactions for years, but the problem? It's hard. At present, the mathematical and statistical models available to us cannot adequately address these interactions, but tons of labs are working on it

I have long been frustrated by the way that science research as a whole is portrayed and reported on in the popular media. I think that these misrepresentations of more responsible research are at fault for any misconceptions that society at large has regarding genetic research or biomedical science in general. I do not believe that the blame lies at the feet of geneticists, who are constantly adapting their work and techniques to incorporate and address the newest ideas and knowledge in the field.

Now, my whole response here is an OPINION piece, so, as with anything op-ed, citations needed.

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