Between 1997 and 2000, Richard Strohman published eight articles in Nature Biotechnology that are generally credited with giving a significant impetus to the development of today's "systems biology". The essay below is the first of them, and I am told was the most reprint requested and otherwise influential essay published in the journal then and since. (Otis)
15, 194 - 200 (1997)
The death, in 1996, of science historian and philosopher, Thomas Kuhn, and the publication of a new edition of The Structure of Scientific Revolutions (3 Edn., Univ. Chicago Press, 1996) have revived the question of whether Kuhnian revolutions have occurred in biology. Kuhn treated the subject of paradigm shift and revolutions -- the rise and fall of major models guiding scientific research -- only in the physical sciences. For those of us who have taken the opportunity to read or reread the new edition, there is the excitement of recognizing in contemporary biology many of the attributes of a Kuhnian revolution.
These attributes have been summarized recently by Adam Wilkins ("Are there Kuhnian revolutions in biology", BioEssays 18: 695-696) who, wile giving Kuhn credit for jogging the biological imagination and for awakening (temporarily) its mostly dormant theoretical aspect, delivers the opinion that, in biology, Kuhnian revolutions have never really happened. I think he may be right for the three cases he has examined: Mendel, Darwin, and Watson-Crick. But I think he misses the point that the Watson-Crick era, which began as a narrowly defined and proper theory and paradigm of the gene, has mistakenly evolved into a theory and a padigm of life: That is, into a revived and thoroughly molecular form of genetic determinism.
The paradigm of the gene stands as a model that has presided over the development of an extremely successful molecular biology that continues to reveal the enormous complexity of living things. As a paradigm of life -- genetic determinism -- it is an illegitimate offspring of the former, showing all the real signs of a Kuhnian revolution. In promising to penetrate and reveal the secrets of life, it has extended itself to a level of complexity where, as a paradigm, it has little power and must eventually fail. The failure is located in the mistaken idea that complex behavior may be traced solely to genetic agents and their surrogate proteins without recourse to the properties originating from the complex and nonlinear interactions of these agents.
A paradigm in trouble
There was a biological revolution with Watson and Crick, say Wilkins, but it gets a negative mark because it lacked the Kuhnian property of being derived from a decaying prior paradigm. Wilkins is quite correct, I think, in saying that, before Watson and Crick, there was no clear theory of the gene's inner workings: there was only a theoretical vacuum. The revolution that came from the double helix has largely been a technological one in which a huge research effort has developed to further our understanding of "...the nature of the genetic code, the mechanism of protein synthesis, and the manner of gene replication". (Wilkins, ibid.) But while this is a correct statement of what Watson and Crick were after, it is also an exceedingly narrow view of what was later adopted as a paradigm by those biologists who were so quickly recruited to the molecular cause. And it is certainly a narrow and distorted view of what has actually happened.
The findings of Watson and Crick brought a new energy to the existing paradigm of genetic determinism. Watson delivered himself of many public utterances to the effect that the code of life was written in DNA, and Crick's 1966 book (Of Molecules and Men, University of Washington Press, Seattle) was a nonstop defense of genetic determinism, pure and simple. And, of course, as we now recognize, the consensus around genetic determinism is extremely well developed and powerful. As a paradigm, it promises molecular diagnosis and therapt for everything from premature birth to death and, mostly because of such inflated claims, it commands the major share of our funded research in the life sciences.
The consensus around the gene as ultimate control agent has had the additional effect of diminishing the concept of the organism in experimental biology. In the mid-20th century, the life sciences in universities throughout the world still maintained strong programs in organismal biology, but today, in most universities, especially in the United States, if you are a biologist and are not cloning genes, you are mostly unfunded, unrecognized by incoming students attracted to the glitter of molecular biology, and poorly staffed by new faculty recruits. You are segregated into "historical" departments where, with a few notable exceptions, you will have no academic offspring, and the organism is left in the mainstream to be replaced by a collection of genes, selfish and otherwise.
Organisms, of course, and used in research, but only as devices that permit one to study the mechanisms of gene control. To the extent that interest in organismal complexity may be revived, the university would presently be hard put to produce a new generation of experts to serve that interest. Such is the nature of our unbalanced academic portfolio in the life sciences.
Thus, all the usual suspects of a Kuhnian paradigm in its different phases of rise and fall are present. (1) A consensus is created in which "normal science" provides further insights into the molecular-genetic mechanisms of life. Alternative paradigms such as systemic or epigenetic biology languish. (2) A profound shift occurs in our perception of the world (from organisms to gene machines) in which we learn more and more about mechanisms and less and less about life. (3) There is a rapid recruitment of scientists to the work laid out by the paradigm. (4) There is rapid development and deployment of a vast new (bio)technology. (5) The new technology dominates the training of the next generation of scientist. (6) Finally, through the inexorable process of science, paradigmatic anomalies are discovered with increasing frequency. Ultimately, the original scientific paradigm falls of its own scientific weight, with one Kuhnian caveat: There must be a pardigm ready to replace what has fallen.
If we are having a Kuhnian revolt against genetic determinism, it is one that lack this most salient Kuhnian attribute -- a new paradigm to replace the one in process of decay. If genes don't determine us then what does? The answers that "The environment determines...," or that "Genes together with environment determine...," complex behavior are really not help in biology because with either of these we are still left with the cell or organism as a neutral space in which random events somehow work out adaptive responses to changing conditions.
I shall try to show that our major trouble, and the reason why it is taking the Kuhnian revolution so long to complete itself, is that we have no theory of the cell or organism that explains how either of these manages to constrain or collapse an enormously complex realm of possibilty to a given adaptive reality. Until we do, if Kuhn was right, we will have to go on repairing a defective genetic paradigm that looks for answers in simplistic genetic programs of one sort or another. And that is precisely what the record is now showing. That a scientific revolution must experience a period of time suspended between a decaying and a new vision of the world is not surprising; it is to be expected. Watson-Crick and the renewed genetic determinism is not yet a half-century old.
The complete article may be read as a PDF file here.
Richard Strohman is emeritus professor of the University of California at Berkeley, Department of Molecular and Cell Biology. He is a former research director of the American Muscular Dystrophy Association. We reprinted the final essay in this NBT series earlier. It can be read, here. (Hank)
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