The long and winding road

Simultaneously abstract and personal, the early study of heredity touched on age-old philosophical questions about free will and determinism, the relationship between 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, the geneticists of the 19th and early 20th centuries were a particularly passionate group, pathologically competitive in some instances and utterly selfless in others. They were prone to intense loyalties as well as overwhelming hatreds, singularly idealistic and ruthlessly pragmatic.

For these reasons I chose to take a novelistic approach to the history of genetics, which was possible because many of the players who made the key discoveries were skilled, prolific letter writers. From these letters and other primary source material, it was possible to trace the idea of the gene as it left one consciousness and entered another. Sometimes ideas were passed down from one scientist to another just as the originator intended. Other times, terrible confusion in one person's mind resulted in a brilliant illumination in the next. Still other times, researchers found the correct path by accident after setting off on the wrong one or, conversely, began with a brilliant flash of insight and proceeded to wander deep into the wilderness. In the end, I found that the history of the evolving concept of the gene coalesced into a coherent narrative, a complex scientific and human drama unfolding over more than a hundred years.

The story of the gene begins with Charles Darwin's arcane and deeply flawed "provisional hypothesis of Pangenesis," which reflected his conversion to another highly problematic theory, that of Lamarckian inheritance. Despite its many problems, Darwin's Pangenesis theory posited the existence of microscopic hereditary particles, a construct that would play a crucial role in the development of modern ideas about the gene. No sooner had Darwin proposed his model than his cousin, Francis Galton, commandeered it to support a theory of inherited intelligence that was itself based on a host of erroneous assumptions and ad hoc arguments. Nonetheless, Galton's hereditary theory was much closer to the truth than that of his far more emotionally balanced, reasonable, and steadfast cousin. Meanwhile, unbeknownst to Darwin and Galton, Gregor Mendel had managed to divine the essence of modern genetics in 1865, working alone in a monastery in Austrian Silesia.

The Dutch botanist Hugo de Vries also tried to enlist Darwin's theory of Pangenesis in the service of his own Mutation Theory, hoping to displace Darwin as the central figure in modern biology. In the course of his work, De Vries stumbled on Mendelism but failed to recognize the importance of Mendel's work and instead spent the remainder of his life devaluing Mendel's achievement and promoting his own erroneous theory in its place.

The cause of Mendelism was then taken up by English zoologist, William Bateson, who was driven to a feverish pitch in its defense by his desire to expose the folly of his once best friend Frank Weldon, who stubbornly refused to acknowledge that inheritance might be governed by concrete structural elements that were passed from parent to offspring. Bateson, who felt Weldon had betrayed the pursuit of truth, later himself refused to accept the idea that the genes were arranged on chromosomes.

The post-1900 development of classical genetics took place largely in Thomas Hunt Morgan's Columbia University laboratory, where between 1912 and 1915 his three graduate students - Alfred Sturtevant, Calvin Bridges, and Hermann Muller - integrated Mendelism and the chromosome theory to form the basis for modern genetics. Ironically, Morgan stood opposed to all three of the major developments in contemporary biology - Darwinism, the chromosome theory, and Mendelism - when he began to study the common fruit fly in 1909. The following year, despite his doubts about both Mendel's factors and the importance of the chromosomes, Morgan discovered the first definitive proof that a Mendelian factor was associated with a particular chromosome - the sex-linked X chromosome.

But Morgan's continued equivocation about Darwinism and the implications of the chromosome theory led to a falling out with Muller, who had already begun to see his way toward a new synthesis of Mendel and Darwin. Despite a well-known account written by Sturtevant late in his life depicting Morgan's laboratory as a kind of scientific utopia, the atmosphere was fraught with rivalries. While Morgan and Sturtevant partially succeeded in tainting Muller's reputation, Muller went on to develop the modern theory of the gene, which served as the foundation for modern molecular biology. In fact, without any structural knowledge of DNA, Muller laid out the conceptual basis for the current effort to identify the genes involved in complex human traits.

The path leading to the development of the modern gene concept was a circuitous one, at least in part because of the prejudices and idiosyncrasies of the scientists who undertook the journey. Danger lurked in the very passions that made scientific progress possible. This is truer than ever today, as scientists attempt to dissect the genetic basis of human disease and even complex psychological traits. Nevertheless, in the case of the gene, clarity was eventually achieved. One thing that helps is the system itself - no matter what prejudices a scientist brings to his work, each new idea, in order to survive, must be tested in controlled experiments and must hold up under the scrutiny of other scientists. At the same time, this system and the scientific freedoms it rests on cannot be taken for granted. At a time when we are increasingly in control of our destiny, genetic and otherwise, it is worth reflecting on the nature of scientific inquiry and the requirements for its long-term health.

James Schwartz is the author of In pursuit of the gene: From Darwin to DNA. He is an independent scholar and science writer who lives in Brookline, Massachusetts with his wife and two sons.

James Schwartz
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