Dna: The Secret of Life

by Watson, James

  Altogether more sinister was the growth of negative eugenics – preventing the wrong kind of people from having children. In this development, a watershed event occurred in 1899 when a young man called Clawson approached a prison doctor in Indiana called Harry Sharp (appropriately named in light of his enthusiasm for the surgeon's knife). Clawson's problem – or so it was diagnosed by the medical establishment of the day – was compulsive masturbation. He reported that he had been hard at it ever since the age of twelve. Masturbation was seen as part of the general syndrome of degeneracy, and Sharp accepted the conventional wisdom (however bizarre it may seem to us today) that Clawson's mental shortcomings – he had made no progress in school – were caused by his compulsion. The solution? Sharp performed a vasectomy, then a recently invented procedure, and subsequently claimed that he had "cured" Clawson. As a result, Sharp developed his own compulsion: to perform vasectomies.

  Sharp promoted his success in treating Clawson (for which, incidentally, we have only Sharp's own report as confirmation) as evidence of the procedure's efficacy for treating all those identified as being of Clawson's kind – all "degenerates." Sterilization had two things going for it. First, it might prevent degenerate behavior, as Sharp claimed it had in Clawson. This, if nothing else, would save society a lot of money because those who had required incarceration, whether in prisons or insane asylums, would be rendered "safe" for release. Second, it would prevent the likes of Clawson from passing their inferior (degenerate) genes on to subsequent generations. Sterilization, Sharp believed, offered the perfect solution to the eugenic crisis.

  Sharp was an effective lobbyist, and in 1907 Indiana passed the first compulsory sterilization law, authorizing the sterilization of confirmed "criminals, idiots, rapists, and imbeciles." Indiana's was the first of many: eventually thirty American states had enacted similar statutes, and by 1941 some sixty thousand individuals in the United States had duly been sterilized, half of them in California alone. The laws, which effectively resulted in state governments deciding who could and who could not have children, were challenged in court, but in 1927 the Supreme Court upheld the Virginia statute in the landmark case of Carrie Buck. Oliver Wendell Holmes wrote the decision:

  It is better for all the world if, instead of waiting to execute degenerate offspring for crime, or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind . . . Three generations of imbeciles is enough.

  Sterilization caught on outside the United States as well – and not only in Nazi Germany. Switzerland and the Scandinavian countries enacted similar legislation.

  Racism is not implicit to eugenics – good genes, the ones eugenics seeks to promote, can in principle belong to people of any race. Starting with Galton, however, whose account of his African expedition had confirmed prejudices about "inferior races," the prominent practitioners of eugenics tended to be racists who used eugenics to provide a "scientific" justification for racist views. Henry Goddard, of Kallikak family fame, conducted IQ tests on immigrants at Ellis Island in 1913 and found as many as 80 percent of potential new Americans to be certifiably feebleminded. The IQ tests he carried out during World War I for the U.S. Army reached a similar conclusion: 45 percent of foreign-born draftees had a mental age of less than eight (only 21 percent of native-born draftees fell into this category). That the tests were biased – they were, after all, carried out in English – was not taken to be relevant: racists had the ammunition they required, and eugenics would be pressed into the service of the cause.

  Although the term "white supremacist" had yet to be coined, America had plenty of them early in the twentieth century. White Anglo-Saxon Protestants, Theodore Roosevelt prominent among them, were concerned that immigration was corrupting the WASP paradise that America, in their view, was supposed to be. In 1916 Madison Grant, a wealthy New Yorker and friend of both Davenport and Roosevelt, published The Passing of the Great Race, in which he argued that the Nordic peoples are superior to all others, including other Europeans. To preserve the United States' fine Nordic genetic heritage, Grant campaigned for immigration restrictions on all non-Nordics. He championed racist eugenic policies, too:

  Under existing conditions the most practical and hopeful method of race improvement is through the elimination of the least desirable elements in the nation by depriving them of the power to contribute to future generations. It is well known to stock breeders that the color of a herd of cattle can be modified by continuous destruction of worthless shades and of course this is true of other characters. Black sheep, for instance, have been practically obliterated by cutting out generation after generation all animals that show this color phase.

  Despite appearances, Grant's book was hardly a minor publication by a marginalized crackpot; it was an influential best-seller. Later translated into German, it appealed – not surprisingly – to the Nazis. Grant gleefully recalled having received a personal letter from Hitler, who wrote to say that the book was his Bible.

  Although not as prominent as Grant, arguably the most influential of the era's exponents of "scientific" racism was Davenport's right-hand man, Harry Laughlin (see Plate 6). Son of an Iowa preacher, Laughlin's expertise was in racehorse pedigrees and chicken breeding. He oversaw the operations of the Eugenics Record Office, but was at his most effective as a lobbyist. In the name of eugenics, he fanatically promoted forced sterilization measures and restrictions on the influx of genetically dubious foreigners (i.e., non-northern Europeans). Particularly important historically was his role as an expert witness at congressional hearings on immigration: Laughlin gave full rein to his prejudices, all of them of course dressed up as "science." When the data were problematic, he fudged them. When he unexpectedly found, for instance, that immigrant Jewish children did better than the native-born in public schools, Laughlin changed the categories he presented, lumping Jews in with whatever nation they had come from, thereby diluting away their superior performance. The passage in 1924 of the Johnson-Reed Immigration Act, which severely restricted immigration from southern Europe and elsewhere, was greeted as a triumph by the likes of Madison Grant; it was Harry Laughlin's finest hour. As vice president some years earlier, Calvin Coolidge had chosen to overlook both Native Americans and the nation's immigration history when he declared that "America must remain American." Now, as president, he signed his wish into law.

  Like Grant, Laughlin had his fans among the Nazis, who modeled some of their own legislation on the American laws he had developed. In 1936 he enthusiastically accepted an honorary degree from Heidelberg University, which chose to honor him as "the farseeing representative of racial policy in America." In time, however, a form of late-onset epilepsy ensured that Laughlin's later years were especially pathetic. All his professional life he had campaigned for the sterilization of epileptics on the grounds that they were genetically degenerate.

  Hitler'S Mein Kampf is saturated with pseudoscientific racist ranting derived from long-standing German claims of racial superiority and from some of the uglier aspects of the American eugenics movement. Hitler wrote that the state "must declare unfit for propagation all who are in any way visibly sick or who have inherited a disease and can therefore pass it on, and put this into actual practice," and elsewhere, "Those who are physically and mentally unhealthy and unworthy must not perpetuate their suffering in the body of their children." Shortly after coming to power in 1933, the Nazis had passed a comprehensive sterilization law – the law "for the prevention of progeny with hereditary defects" – that was explicitly based on the American model. (Laughlin proudly published a translation of the law.) Within three years, 225,000 people had been sterilized.

  Positive eugenics, encouraging the "right" people to have children, also thrived in Nazi Germany, where "right" meant properly Aryan. Heinrich Himmler, head of the SS (the Nazi elite corps), saw his mission in eugenic terms: SS officers should ensure Germany's genetic future by having as many children as possible. In 1936
, he established special maternity homes for SS wives to guarantee that they got the best possible care during pregnancy. The proclamations at the 1935 Nuremberg Rally included a law "for the protection of German blood and German honor," which prohibited marriage between Germans and Jews and even "extra-marital sexual intercourse between Jews and citizens of German or related blood." The Nazis were unfailingly thorough in closing up any reproductive loopholes.

  Neither, tragically, were there any loopholes in the U.S. Johnson-Reed Immigration Act that Harry Laughlin had worked so hard to engineer. For many Jews fleeing Nazi persecution, the United States was the logical first choice of destination, but the country's restrictive – and racist – immigration policies resulted in many being turned away. Not only had Laughlin's sterilization law provided Hitler with the model for his ghastly program, but his impact on immigration legislation meant that the United States would in effect abandon German Jewry to its fate at the hands of the Nazis.

  In 1939, with the war under way, the Nazis introduced euthanasia. Sterilization proved too much trouble. And why waste the food? The inmates of asylums were categorized as "useless eaters." Questionnaires were distributed among the mental hospitals where panels of experts were instructed to mark them with a cross in the cases of patients whose lives they deemed "not worth living." Seventy-five thousand came back so marked, and the technology of mass murder – the gas chamber – was duly developed. Subsequently, the Nazis expanded the definition of "not worth living" to include whole ethnic groups, among them the Gypsies and, in particular, the Jews. What came to be called the Holocaust was the culmination of Nazi eugenics.

  Eugenics ultimately proved a tragedy for humankind. It also proved a disaster for the emerging science of genetics, which could not escape the taint. In fact, despite the prominence of eugenicists like Davenport, many scientists had criticized the movement and dissociated themselves from it. Alfred Russel Wallace, the co-discoverer with Darwin of natural selection, condemned eugenics in 1912 as "simply the meddlesome interference of an arrogant, scientific priestcraft." Thomas Hunt Morgan, of fruit fly fame, resigned on "scientific grounds" from the board of scientific directors of the Eugenics Record Office. Raymond Pearl, at Johns Hopkins, wrote in 1928 that "orthodox eugenicists are going contrary to the best established facts of genetical science."

  Eugenics had lost its credibility in the scientific community long before the Nazis appropriated it for their own horrific purposes. The science underpinning it was bogus, and the social programs constructed upon it utterly reprehensible. Nevertheless, by midcentury the valid science of genetics, human genetics in particular, had a major public relations problem on its hands. When in 1948 I first came to Cold Spring Harbor, former home of the by-then-defunct Eugenics Record Office, nobody would even mention the "E word"; nobody was willing to talk about our science's past even though past issues of the German Journal of Racial Hygiene still lingered on the shelves of the library.

  Realizing that such goals were not scientifically feasible, geneticists had long since forsaken the grand search for patterns of inheritance of human behavioral characteristics – whether Davenport's feeblemindedness or Galton's genius – and were now focusing instead on the gene and how it functioned in the cell. With the development during the 1930s and 1940s of new and more effective technologies for studying biological molecules in ever greater detail, the time had finally arrived for an assault on the greatest biological mystery of all: what is the chemical nature of the gene?

  CHAPTER TWO

  THE DOUBLE HELIX:

  THIS IS LIFE

  I got hooked on the gene during my third year at the University of Chicago. Until then, I had planned to be a naturalist and looked forward to a career far removed from the urban bustle of Chicago's South Side, where I grew up. My change of heart was inspired not by an unforgettable teacher but a little book that appeared in 1944, What Is Life?, by the Austrian-born father of wave mechanics, Erwin Schrödinger (see Plate 7). It grew out of several lectures he had given the year before at the Institute for Advanced Study in Dublin. That a great physicist had taken the time to write about biology caught my fancy. In those days, like most people, I considered chemistry and physics to be the "real" sciences, and theoretical physicists were science's top dogs.

  Schrödinger argued that life could be thought of in terms of storing and passing on biological information. Chromosomes were thus simply information bearers. Because so much information had to be packed into every cell, it must be compressed into what Schrödinger called a "hereditary code-script" embedded in the molecular fabric of chromosomes. To understand life, then, we would have to identify these molecules, and crack their code. He even speculated that understanding life – which would involve finding the gene – might take us beyond the laws of physics as we then understood them. Schrödinger's book was tremendously influential. Many of those who would become major players in Act 1 of molecular biology's great drama, including Francis Crick (a former physicist himself), had, like me, read What Is Life? and been impressed (see Plate 8).

  In my own case, Schrödinger struck a chord because I too was intrigued by the essence of life. A small minority of scientists still thought life depended upon a vital force emanating from an all-powerful god. But like most of my teachers, I disdained the very idea of vitalism. If such a "vital" force were calling the shots in nature's game, there was little hope life would ever be understood through the methods of science. On the other hand, the notion that life might be perpetuated by means of an instruction book inscribed in a secret code appealed to me. What sort of molecular code could be so elaborate as to convey all the multitudinous wonder of the living world? And what sort of molecular trick could ensure that the code is exactly copied every time a chromosome duplicates?

  At the time of Schrödinger's Dublin lectures, most biologists supposed that proteins would eventually be identified as the primary bearers of genetic instruction. Proteins are molecular chains built up from twenty different building blocks, the amino acids. Because permutations in the order of amino acids along the chain are virtually infinite, proteins could, in principle, readily encode the information underpinning life's extraordinary diversity. DNA then was not considered a serious candidate for the bearer of code-scripts, even though it was exclusively located on chromosomes and had been known about for some seventy-five years. In 1869, Friedrich Miescher, a Swiss biochemist working in Germany, had isolated from pus-soaked bandages supplied by a local hospital a substance he called "nuclein." Because pus consists largely of white blood cells, which, unlike red blood cells, have nuclei and therefore DNA-containing chromosomes, Miescher had stumbled on a good source of DNA (see Plate 9). When he later discovered that "nuclein" was to be found in chromosomes alone, Miescher understood that his discovery was indeed a big one. In 1893, he wrote: "Inheritance insures a continuity in form from generation to generation that lies even deeper than the chemical molecule. It lies in the structuring atomic groups. In this sense, I am a supporter of the chemical heredity theory."

  Nevertheless, for decades afterward, chemistry would remain unequal to the task of analyzing the immense size and complexity of the DNA molecule. Only in the 1930s was DNA shown to be a long molecule containing four different chemical bases: adenine (A), guanine (G), thymine (T), and cytosine (C). But at the time of Schrödinger's lectures, it was still unclear just how the subunits (called deoxynucleotides) of the molecule were chemically linked. Nor was it known whether DNA molecules might vary in their sequences of the four different bases. If DNA were indeed Schrödinger's code-script, then the molecule would have to be capable of existing in an immense number of different forms. But back then it was still considered a possibility that one simple sequence like AGTC might be repeated over and over along the entire length of DNA chains.

  DNA did not move into the genetic limelight until 1944, when Oswald Avery's lab at the Rockefeller Institute in New York City reported that the composition of the surface coats of pneumonia bact
eria could be changed. This was not the result he and his junior colleagues, Colin MacLeod and Maclyn McCarty, expected.

  For more than a decade Avery's group had been following up on another most unexpected observation made in 1928 by Fred Griffith, a scientist in the British Ministry of Health. Griffith was interested in pneumonia and studied its bacterial agent, Pneumococcus. It was known that there were two strains, designated "smooth" (S) and "rough" (R) according to their appearance under the microscope. These strains differed not only visually but also in their virulence. Inject S bacteria into a mouse, and within a few days the mouse dies; inject R bacteria and the mouse remains healthy. It turns out that S bacterial cells have a coating that prevents the mouse's immune system from recognizing the invader. The R cells have no such coating and are therefore readily attacked by the mouse's immune defenses.

  Through his involvement with public health, Griffith knew that multiple strains had sometimes been isolated from a single patient, and so he was curious about how different strains might interact in his unfortunate mice. With one combination, he made a remarkable discovery: when he injected heat-killed S bacteria (harmless) and normal R bacteria (also harmless), the mouse died. How could two harmless forms of bacteria conspire to become lethal? The clue came when he isolated the Pneumococcus bacteria retrieved from the dead mice and discovered living S bacteria. It appeared the living innocuous R bacteria had acquired something from the dead S variant; whatever it was, that something had allowed the R in the presence of the heat-killed S bacteria to transform itself into a living killer S strain. Griffith confirmed that this change was for real by culturing the S bacteria from the dead mouse over several generations: the bacteria bred true for the S type, just as any regular S strain would. A genetic change had indeed occurred to the R bacteria injected into the mouse.