Schwartz: In Pursuit of the Gene

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James Schwartz, In Pursuit of the Gene : From Darwin to DNA. Cambridge, MA : Harvard University Press 2008. xiii + 370 pages, with notes and index; illustrated.

This book is a history of the idea of the gene. That characteristics could be inherited has been realized for centuries, as evidenced by successes in animal and plant breeding. Inheritance of human characteristics is assumed in the lore of royalty and societal classes, and manifestly evident in generations of royal portraits. However, details of how it worked, and through what agency, remained a mystery well into the twentieth century.

The idea of the gene did not come easily. Modern readers may be unaware that genes – indeed, any sort of mechanism for heredity -- were unknown at the time Darwin wrote his masterpiece on natural selection. Natural selection was a bold theory and it made several bold predictions, not least of which was that selection required variation in order to do its work, so there had to be some mechanism, subject to variation, that carried heritable characteristics.

Darwin developed a peculiar idea he called "pangenesis", at best a confused attempt to describe a mechanism for inheritance that barely avoided the Lamarckian heresy that acquired characteristics could be inherited. Pangenesis was effected by "gemmules", which provided the germ for the idea of the gene, but didn't come terribly close in detail. Francis Galton, cousin of Charles Darwin, performed the definitive experimental test that put to rest the theory of pangenisis and precipitated the search for a mechanism that could do what was needed.

What followed was a war of ideas as scientists groped their way towards an understanding of how inheritance behaved and tried to deduce the responsible agent in the body. As we know with hindsight, Gregor Mendel's work with peas lurked in the wings, ready to provide a part of the answer, but his work wasn't rediscovered until nearly 1900 when ideas about inheritance were starting to converge on a discrete mechanism (rather than continuous variation) as the core idea of inheritance.

"It has been Mendel, Mendel all the way, and I think the boom is beginning at last," Bateson wrote home after his presentations were over. [Presentations that greatly affected the young scientist Sutton.] The timely review of the basic facts of Mendelism is clearly evident in Sutton's next paper, which was submitted for publication on January 25, 1903.

Contrary to a widespread belief that the male passed on only the chromosomes he had inherited from his father, and likewise the female passed on only those she received from her mother, Sutton now maintained that the selection of the male or female homologue during the reducing division [of the cell to produce the egg or sperm cells] was an entirely random affair. From this it immediately followed that the segregation of the pairs of homologous chromosomes into sperm and egg cells followed exactly the same rules as the segregation of Mendel's factors. in particular, if a pair of contrasting characters (A/a) was located on one pair of homologous chromosomes, and another pair of contrasting characters (B/b) was located on a different homologous pair, then one would expect to see equal numbers of each of the four combinations of factors, the fact from which Mendel's law of independent segregation followed.

Sutton also realized that each chromosome must contain more than one factor, otherwise there could be only as many characters as chromosomes, which was clearly absurd. Furthermore, he suggested that traits that were located on the same chromosome must be inherited together, and thus he gave the basis for the linkage of genes, an idea that would be thoroughly explored in the decade ahead. With the publication of Sutton's remarkably lucid paper, the results of nearly three decades of intensive investigation of the nucleus and the chromosomes had finally come into accord with the facts of heredity that Mendel had elucidated in 1865. [p. 163]

Once heredity was clearly seen to be controlled at the cellular level, there was a protracted fight over whether the nucleus was the center of the action or whether the entire protoplasm of the cell somehow did the work. Discerning major elements of genetics through the study of generations of plants or fruit flies was a tour de force, especially without a molecular understanding.

Identifying the chromosomes as the agents of heredity was a dramatic development that nevertheless came with its own protracted controversies. Inferring much at all about the molecular operation of DNA well before its structure was determined by Watson and Crick seems astounding.

At one point the author writes this about one of the scientists:

...the real progression of his ideas was far less direct and considerably more interesting. [p. 79]

That could have served as a motto for the book! The trajectory from vague ideas about inheritance to the modern idea of the gene is far from direct but considerably more interesting for it. There is a certain excitement in watching the solution being discovered and intuited when we already know the answer; watching the dead ends struggle and lose adds to our understanding of science at work. It's a dramatic story and a fascinating case study in the history of ideas, this history of one profound idea: the "gene".

Science is fundamentally different from art, it is often claimed, because the sensibility of the scientist isn't involved. Had X not made the discovery, Y would eventually have gotten to the same place. made into a caricature, this is the view of scientists in white coats engaged in a selfless quest for truth. At the opposite extreme is the postmodernist idea that science is a social construct—that no independent, objective reality exists outside of one's perceptions. While both views are clearly absurd, I confess that I am more sympathetic with the former than the latter. The consequences of denying the existence of an objective scientific reality were dramatically illustrated in the Soviet Union in the period between 1933 and 1953 when the ideas about genetics that had been built up over the previous century were undermined and then outlawed, plunging Soviet agriculture into free fall.

While it may not matter in the long run how a scientific idea came into being, nonetheless learning about the thoughts, feelings, and interactions of the people who worked on it can illuminate the science in unexpected ways. This may be particularly true of the study of heredity, which is both the most mathematical and abstract of the life sciences and at the same time the most personal. Intimately connected with the origin of statistics, the early study of inheritance also touched on age-old philosophical questions about free will and determinism, the relationship of parent and child., and the extent to which human beings can be reduced to the sum of their parts. Fueled by their concern with these elemental themes, I believe, the early geneticists were a particularly passionate group. pathologically competitive in some instances and utterly selfless in others, prone to intense loyalties as well as overwhelming hatreds, singularly idealistic and ruthlessly pragmatic. [pp. ix—x]

Author Schwartz set out to tell it by focusing on the personalities involved, but he really was tracing the idea as it incubated and developed and evolved in the minds of the scientists who most shaped the idea. In modern parlance we might say the narrative watches the "gene meme" as it is born and, skipping from mind to mind, evolves into the recognizably modern idea of "gene" as embodied in a piece of DNA. And certainly personalities influence competition, peevish delays, and sudden advances, and that was all on display here. Clearly evident, too, is the scientific interplay of theorizing subject to experimental validation, which feeds back into new hypothesis. Schwartz shows us science not at its idealized best but as a realistic human enterprise.

Schwartz' writing does not draw attention to itself; it gives the impression of being journalistic and out to get the job done, but I found it effortless and pleasant to read, so I credit the author with a stylistic clarity that receded and let the story come through unimpeded.

We can applaud one decision of the author's:

In my view, discussing the history of genetics without describing actual experiments would be like analyzing the history of art without looking at any of the paintings. [p. xii]

This means that sometimes one reads a little slower to take in the description of the experiments and think about the meaning of the results, but it is essential and Schwartz describes the experiments with clarity and economy.

-- Notes by JNS

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