A radical critic of genetic reductionism and genetic determinism

Richard Strohman, professor emeritus of molecular and cell biology at the University of California, Berkeley, died last month. Strohman was a leading critic of genetic reductionism, the idea that a single gene corresponds with a single trait or disease. He advanced the idea of epigenetic control, meaning that the genes are directed by something beyond the genes. As he put it, “another kind of information management system must be present rather than genetic determinism.” Clearly this is true. For example, the well known fact that the chimpanzee genome is 98.5 percent identical with the human genome indicates that genes alone are not determining the phenotype, but rather some program beyond the genes that makes the same genes manifest in different ways in different species.

This is from an obituary of Strohman:

He lectured frequently and wrote numerous papers dealing with the limits of genetic reductionism in biology and medicine, centering much of his criticism on the highly touted project to sequence the human genome, which was completed in 2003. Today, non-genetic, or epigenetic, factors are widely believed to play a major role in development and in human disease, according to long-time colleague Richard Veech, M. D., chief of the Laboratory of Metabolic Control in the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health. “I think he was very far ahead of his time and ran against the grain in explaining the importance of epigenetic control,” Veech said. “We had the genome and everything was going to be changed by that, but that clearly was not so.” Friend and colleague Harry Rubin, UC Berkeley professor emeritus of molecular and cell biology, said that “Dick would take a contrarian view about things in general, but I think he was correct in criticizing the idea that a few genes could explain the most important human diseases, such as cancer and heart disease, and could lead to treatments. Human disease is much more complicated than we suspected, and Dick saw that and drew peoples’ attention to that in what he wrote.”

He was a member of the Faculty Peace Committee which opposed the Vietnam war, and a member of the group Faculty for Social Responsibility, which, in the 1980s, promoted nuclear disarmament and opposed a U. S. military build-up and interventionist policies in Central America. He was a member of the American Society of Cell Biology and the Society for Developmental Biology and a fellow of the American Association for the Advancement of Science

Here is the opening section of an article Strohman wrote in 2001. What he’s saying here is astonishingly radical, but in conformity with what the doubters of the Darwinian-deterministic-reductionist orthodoxy have been saying all along. Among other things, Strohman posits a feedback loop by which the environment affects the DNA, an absolute impossibility according to orthodox thinking. This would throw out the Darwinian paradigm of evolution by accidential genetic mutations naturally selected, and open the way to a new Lamarkianism, in which new biological information appears in species not as a result of random changes, but as a result of purposive responses to the environment.

Toward a new paradigm for life:
Beyond genetic determinism

When the highly anticipated sequencing of the human genome was completed in February, a headline in the San Francisco Chronicle announced: “Genome Discovery Shocks Scientists.” The discovery was that many fewer genes were found (30,000) for the human genome than had been expected (100,000), and discussion focused on the wonder of it all: that a fertile human egg could create such a different organism than a mouse egg, where the human egg had only 300 unique genes not found in the mouse.

News articles also made much of the fact that many genes interacting with one another seemed to be as important in determining human diseases as a few “major” genes. Another bit of news was that there are more proteins and genes and this was a surprise because of the accepted idea that each gene encodes a single protein.

But on all of these matters, except for the 300 unique human genes, the “discoveries” were not new, nor were they shocking. We have seen suggestions of 30,000 to 40,000 genes for at least a year; we have known for some time that different species have highly similar genomes—humans and chimps for example; and genetic interaction has been part of freshman genetics for at least 30 years. Finally, we have known for years that DNA sequences within one gene may be used in coding many proteins.

In short, many biologists, world wide, have known for decades that genetics alone is not sufficient to explain life’s complex outcomes, and that another kind of information management system must be present (see below). For them, none of this news was a surprise and we must ask why our HGP scientists appeared to be so shocked.

Perhaps it has to do with something more than just “surprising and challenging new data.” To me, it suggests nothing less than than the failure of genetic determinism: the biological theory that complex characteristics of human beings are caused by specific genes.

But after almost a century of life sciences dominated by this theory, and after ten years of the HGP dedicated to finding the genes for human diseases, their diagnosis and cure, and with the human genome finally sequenced, and biotechnologists and drug companies standing by around the world to implement these diagnoses and cures-after all that, to announce that the entire project was based on an incomplete and flawed theory would have been much more than “shocking.” It would have been a scandal….

If Gould and Venter are correct in saying that genes alone cannot tell us who we are, then what will tell us? If the program for life is not in our genes, then where is it, and what is it? Many of us have been saying for years that there is no program in the sense of an inherited, pre-existing script ready to be read. Rather, inside each cell there are regulatory networks of proteins that function to sense or measure changes in the cellular environment and interpret those signals so that the cell makes an appropriate response. ________

Figure 1.The genetic determinist view of life.

Phenotype (function) = Genes x Environment

DNA———>>Proteins——>> Function

________

The causal pathway is linear: proteins are encoded by DNA and therefore DNA may be said to encode function. Environment acts as a trigger to activate pre-set programs in DNA. Ever since Watson-Crick and the double helix of DNA (1953) we have been working with the genetic model in Fig.1. Now we realize there is another information processing system in cells. This second informational system is co extensive with the cell itself, consists of many interconnected signaling pathways and is described here under the heading of “dynamics”; the part of dynamics having to do with control of gene expression is, for historical reasons, called epigenetic regulation. __________

Figure 2. The epigenetic regulatory view

Phenotype = Genetics x Dynamics x Environment

DNA——->> Proteins——->> Function

Protein Control Networks
(Open to Environment)

___________

Protein networks feedback information from the outside world to DNA, and change patterns of gene expression in a context dependent manner. “Dynamics” refers to regulatory networks of proteins that function partly to connect signals from the environment to DNA where patterns of DNA expression change. The control pathway of gene expression is not closed, one way and linear as in Fig. 1: it is dynamic and circular (non-linear). What, then, is the role of genes?

Genes specify information necessary to make proteins and the genome provides a collective informational source. However, by itself a genome is passive: DNA, for example cannot make itself, and cannot construct a protein never mind an actual cellular function. DNA has been called the book of life by HGP scientists but for many other biologists DNA is not a book but simply a collection of words from which a meaningful story of life may be assembled. [Emphasis added.]

In order to assemble a meaningful activity or story, a living cell uses a second informational system. Let me give an example. We know that at least 100 genes are related to a heart disease . These genes code for at least 100 proteins, some of which are enzymes. So you have a dynamic/ epigenetic network of 100 proteins, many biochemical reactions, and many reaction products. [LA writes: I don’t understand how 100 genes coding for 100 proteins results in a dynamic/epigenetic network; it sounds like the conventional, non-dynamic view.] It is dynamic because it regulates changes in products over time, and it is epigenetic because it is above genetics in level of organization. The output from these networks change in response to signals from the body and from the environment. And some of these changes feed back to DNA to regulate gene expression. The key concept here is that dynamic/epigenetic networks have a life of their own—they have network rules—not specified by DNA: and we do not understand these rules.

In short, genetics alone does not tell us who we are, or who we can or will be. The new findings of epigenetic or dynamic regulatory systems in cells describe an information management system that we have known about for quite a while but are only now beginning to understand. While, as Gould says, the genetic reductionist theory has collapsed, the epigenetic, or dynamic, point of view retains genetics as part of a new theory or paradigm for life, one that has striking implications for the future of the life sciences. [cont.]

Posted by Lawrence Auster at August 16, 2009 07:26 PM | Send