For James Watson, DNA was everything — not just his life's work, but the secret of life itself.
Over his long and storied career, Watson arguably did more than any other scientist to transform a once-obscure biological molecule, DNA, into the icon of science and society that it is today.
But when Watson died this week at the age of 97, his renown as the co-discoverer of the structure of DNA was tarnished by the fact that he had become a persona non grata in the two research fields that he pioneered: molecular biology and genomics.
Watson's penchant for making prejudiced and scientifically unfounded remarks about Black people, women, and others eventually forced even the institution that he had long directed, Cold Spring Harbor Laboratory, to cut all ties with him in 2019.
This fall from grace was remarkable given the heights he had achieved. In 1953, when he was not yet 25 years old, Watson worked with English researcher Francis Crick to piece together clues from various experiments — including work done by X-ray crystallographer Rosalind Franklin — in order to create the first accurate model of DNA's chemical structure.
"This structure has novel features which are of considerable biological interest," Watson and Crick wrote in the published report describing their model, in what has to be science's most famous understatement.
Knowing the structure of DNA made it suddenly obvious how a single molecule could both encode life's complexity and also reproduce itself, showing that this was the long-sought key to understanding the physical mechanisms of heredity.
"DNA was no mere discovery," says Howard Markel, a historian who wrote a book on how Watson, Crick, Franklin and others uncovered this molecule's structure. "It's a light switch moment."
In his opinion, the discovery is the equal of Charles Darwin's insights into how life evolves through natural selection.
Watson apparently shared that view. In an interview, when Markel asked him how he had felt as a young man after becoming certain that this structural model of DNA was correct, Watson replied, "I thought I was up there with Darwin."
"That's a striking comment," notes Markel. "I've been a citizen of academic scientific institutions and medical institutions for half-a-century, and everybody brags about their work. But in this case, the speaker was actually speaking the truth."
Quickly bored
It's telling that Watson once wrote a book entitled Avoid Boring People. This title encapsulates two of his basic approaches to life: be entertaining and stimulating, and associate with people who have interesting ideas.
Watson was born in Chicago in 1928, and by the age of 11 he was going on birdwatching walks with his businessman father, according to a speech he once gave.
Because of his interest in birds, "early on, I heard of Charles Darwin," Watson said. "I guess, you know, he was the big hero."
Watson entered the University of Chicago at the age of 15, intending to study zoology. "It was fun to get away from high school," he said. "I was no good in sports or anything like that."
At the university, Watson was "principally interested in birds and managed to avoid taking any chemistry or physics courses which looked of even medium difficulty," he later recalled.
He soon developed a serious interest in genetics, and in particular the nature of the gene, the most basic unit of heredity.
These days, genes are synonymous with DNA. Back then, however, no one knew what physical substance or mechanism was actually responsible for traits being passed from a parent on to offspring, despite the pioneering genetics work of Gregor Mendel and his pea plants in the 19th century.
Some researchers believed that genes must be complicated proteins. Others, however, were betting on DNA, a mysterious molecule that was first identified in the 1860s and found in basically every type of cell that scientists studied.
After getting a PhD in zoology at Indiana University, Watson did research jobs in Europe and eventually ended up at the Cavendish Laboratory in England. He was supposed to be researching myoglobin, a protein found in muscles.
But at the laboratory, he met Francis Crick, who also was studying proteins. "Perhaps even without Francis, I would have quickly bored of myoglobin," Watson said in his Nobel Prize lecture. "But with Francis to talk to, my fate was sealed. For we quickly discovered that we thought the same way about biology."
The Double Helix
The pair shared the belief that knowing the structure of DNA might solve the enigma of the gene. They also both assumed, rather conceitedly and optimistically, that they could figure out this structure in a matter of months, despite ostensibly working on other projects.
To do this, they tried to invent possible structures using chemical models made of cardboard and metal. They relied on hints and clues from other researchers' experiments to devise a physically plausible model that could account for all of the features of DNA that had been observed by other scientists.
They weren't the only ones racing to find DNA's structure, and they weren't working in isolation.
Perhaps most critically, they interacted with two researchers at King's College named Maurice Wilkins — who went on to share the Nobel Prize in physiology or medicine with Crick and Watson in 1962 — and Rosalind Franklin.
Franklin, a talented scientist, had to work in an atmosphere of constant sexism.
"There was a common room where the staff went to eat lunch, but because she was a woman, she wasn't allowed into it," says Elspeth Garman, a structural biologist at the University of Oxford who has written about Franklin's life. "The conditions for her at King's College were appalling."
And her relationship with Wilkins, who acted as though she should be his subordinate, was especially tense.
Nonetheless, Franklin persisted with her DNA research, producing new data such as the X-ray image known as "Photograph 51," which suggested a helical structure.
She had no way of knowing how much Watson and Crick relied on her observations to help them sort through possible configurations as they made their models.
Watson and Crick were friendly with Wilkins, who filled them in on the unpublished results coming out of Franklin's lab. They also saw an internal report with descriptions of her findings. This report was prepared for a review committee and shared with them by another scientist-pal, a breach of professional norms that later drew criticism.
In the end, when Watson showed Franklin their model of DNA's structure, soon to be known as the Watson-Crick model, she simply found it convincing. Later, they interacted as friends.
"I think she didn't bear him any grudges because I don't think she knew the extent of what he'd seen and when," says Garman. "I think she was very excited that they had got a model that agreed with all her experimental data, and the papers that she published that she submitted before she saw the model in March 1953 make it very clear how very near the solution she was herself."
Honest Jim
Franklin died from ovarian cancer in 1958, a few years before Watson, Crick, and Wilkins won the Nobel Prize, which is not awarded posthumously and can only be shared by three living scientists.
Because Franklin died so early, she never knew that Watson portrayed her in an unkind and sexist way in the influential book he wrote about the discovery, The Double Helix, which was published in 1968.
"Rosy," as Watson called her in the book (although she never used this nickname), got painted as an inexplicably hostile shrew, the lipstick-less comedic villain of the story who "did not emphasize her feminine qualities."
For a long time, this popular book shaped the public's entire understanding of how the structure of DNA was uncovered.
"Everybody knows about it, you know, and that's their view of Rosalind Franklin. And it's really unfair. I mean, she died in 1958 and ten years later, he publishes this stuff that she can't counter," says Garman. "It's unforgivable. I'm sorry but it is. It was so unnecessary. I mean, he had a Nobel Prize. Why did he need to do that to her?"
Though Watson's depiction of Franklin was particularly egregious, she wasn't the only one who got caricatured in the book. His certainly-not-boring tale mortified numerous colleagues, including Crick, who even tried to block the book's publication. Crick sent Watson a letter that said, "If you publish your book now, in the teeth of my opposition, history will condemn you."
The Double Helix, despite its flaws, caused a sensation. It gave the public its first gossipy glimpse into how high-stakes science actually worked, portraying scientists as real people with very human qualities and foibles, rather than being inscrutable demigods in white lab coats.
"It was meant to be a humorous book that would attract young people into science. And it did do that," says Nathaniel Comfort, a professor in the history of medicine at Johns Hopkins University who is writing a biography of Watson.
He notes that Watson originally had wanted to name his book Honest Jim, a nod to novels such as Joseph Conrad's Lord Jim and Kingsley Amis' Lucky Jim. Watson's book was more akin to pulp fiction than definitive history.
Nonetheless, the book has complicated historians' efforts to understand the truth of what really happened during this pivotal moment in the history of science.
"You know, it's very difficult for us to speak about this story without falling back on Watson's account of it," says Soraya de Chadarevian, a historian of science at UCLA. "But I think that's the job of the historian, to resist this."
In Watson's telling, for example, after he and Crick finally figured out DNA's structure, the pair popped into a nearby pub for lunch and Crick began "to tell everyone within hearing distance that we had found the secret of life."
Crick later denied that this ever happened. Markel says it was really Watson, the author of the story, who saw DNA as the secret of life.
"He was the apostle of DNA, if you will," says Markel. "He spread the gospel of DNA to his colleagues."
Watson was a canny creator of his own mythology, and had a reputation for doing and saying outrageous things, in part to be not boring and also apparently to amuse himself by getting a rise out of people — a habit that later got him into trouble.
For a long time, however, these habits worked for him, and his book helped make him a celebrity.
"It was a bestseller. Now, people are forgetting it," says de Chadarevian. "I think this is because Watson is shunned, and so also his book is shunned, and his treatment of Rosalind Franklin has become unbearable for students. Before, Watson's book was read in schools."
The Human Genome Project
While Crick eventually went on to engage in other pursuits, like trying to understand the nature of the conscious mind, Watson stuck with DNA.
After all, finding the structure of DNA was just the start. To truly understand genes and heredity, researchers had to learn to read the DNA code. They also had to develop tools that would let them manipulate DNA and do experiments.
Watson ran a lab at Harvard University and was a co-discoverer of messenger RNA, the molecule that carries DNA's instructions to cells' protein-making factories. His lab also made a key discovery about how genes get regulated.
"He had an amazing knack for recognizing the next problem to be done," says Comfort. "He had an enormous, absolutely enormous social network. He used that social network
to great advantage. He was a rockstar in science."
Watson wrote the first textbook of molecular biology, Molecular Biology of the Gene. In 1968, he became the director of Cold Spring Harbor Laboratory in New York.
There, he turned what had been a sleepy, financially-strapped research station into a world-class powerhouse for science. The place got decked out with the double helix, a motif he turned into a familiar and instantly recognizable symbol that he slapped on everything.
"He believed that this was the new science. He created tremendous enthusiasm for this new, molecular genetics," says Comfort. "He really went out of his way to become a popular figure representing DNA. And that is very much a part of our world today."
"It was his life story. And he always promoted — he was really the big booster for DNA, all along," agrees de Chadarevian. "And I think his influence grew, and also the importance of DNA grew."
By the 1980's, DNA science had advanced to the point where biologists were identifying genetic markers for conditions such as Huntington's disease. Federal officials decided to fund an ambitious megaproject to sequence all human genes. For biology, this was an unusual foray into large-scale, expensive science.
The then-controversial Human Genome Project needed a charismatic, persuasive director, and Watson got tapped for the job. He once said he got interested in this effort in part because his son had just been diagnosed with schizophrenia.
"Probably the reason I was enthusiastic was that I thought the Human Genome Project would eventually lead us to the genes behind mental illness," he said.
In 1988, at a press briefing to announce that Watson would lead the Human Genome Project, a reporter asked him about the legal and ethical implications of genetic testing. Watson, in an apparent spur-of-the-moment remark, announced that the project would devote 3 to 5 percent of its budget to the study of bioethics.
This was an unprecedented, transformative investment in studying the ethical questions posed by advances in biomedicine and genetics. Watson later said it was necessary to help insulate the Human Genome Project from any association with the discredited eugenics movement, which used sloppy "science" to justify social and racial prejudices in the early 20th century.
Unsubstantiated and reckless
Many of Watson's colleagues admired him, and he cared deeply about the researchers he mentored. He would even bring exceptional high school students into his home so that they could get real-world experience working in a lab at Cold Spring Harbor Laboratory.
"He'd give them a room in his house, and then he'd come down and have breakfast with them and so forth," says Comfort. "There's this other Jim that the public doesn't know about. One prominent scientist calls it 'Cornflakes Jim,' because he would come down and have his cornflakes and they would talk over the New York Times and stuff like that."
In public, though, Watson was larger-than-life. Markel describes him as owning a fabulous house, an incredible modern art collection, and going to black-tie galas where he rubbed shoulders with superstars.
"He was living every nerd's dream," says Markel.
The seeds of his professional downfall lay in the fact that Watson would sometimes say things that were extremely hurtful, including remarks that were sexist, racist, and anti-Semitic.
Plus, Watson's utter conviction in the importance of the gene led him to a belief in "genetic determinism," the idea that one's DNA essentially controls one's fate.
Towards the end of his life, Watson seemed as devoted to genetic determinism as the past eugenics movement had been.
"I think the genetic determinism really lay at the ultimate heart of a lot of the racist and sexist things that he said," says Comfort. "Especially the racist things."
In 2007, Watson made unfounded and disturbing statements about race and intelligence to a British newspaper during a book tour, saying he was "inherently gloomy about the prospect of Africa" because "all our social policies are based on the fact that their intelligence is the same as ours — whereas all the testing says not really."
Watson added that he wished everyone was equal but "people who have to deal with Black employees find this not true."
An uproar immediately ensued, with other biologists condemning his comments as both unscientific and ugly. Cold Spring Harbor Laboratory suspended him as chancellor, and the public apology that he made did not keep him from being shunned by the research community.
Despite these experiences, in a 2019 documentary produced by PBS, Watson said his views on race and intelligence had not changed, and that he viewed the average differences seen between Black and white populations on IQ tests as "genetic," rather than being the culturally constructed product of centuries of racial prejudice.
After that, Cold Spring Harbor Laboratory issued a statement saying that it unequivocally rejected "the unsubstantiated and reckless personal opinions" of Watson and had revoked his remaining honorary titles.
"It's some kind of a blindness, probably, that befell him at the end, that he thinks DNA is everything," says de Chadarevian.
But Watson was never one to give into critics and doubters, which may have made it hard for him to see when he was wrong. Holding on to his convictions, come what may, seemed to be part of his own DNA. It's a key aspect of his personality that went all the way back to the days when he was racing more-qualified researchers to puzzle out the molecule's structure or publishing a book that even his close friends condemned.
During a speech when he was in Stockholm to receive the Nobel Prize in 1962, Watson said that to succeed in science, researchers had to believe strongly in their ideas, even to the point where "they may seem tiresome and bothersome and even arrogant to our colleagues. I knew many people, at least when I was young, who thought I was quite unbearable."
In Comfort's view, Watson's life was a classic tragedy, in that the very things that brought him to fame and greatness ultimately proved to be his downfall.
"He built his entire career on DNA," says Comfort. "He rose and fell on DNA. DNA made him, and DNA unmade him."
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