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Don't listen to the naysayers

"You're a woman," a professor told Joan Steitz. "You'll get married and have kids. What good will a PhD have done you?"

By Richard Panek | Jul/Aug 2019

Richard Panek teaches writing at Goddard College. He is the author of several books on science, including, most recently, The Trouble with Gravity: Solving the Mystery beneath Our Feet.

Over the course of her career Joan Steitz has compiled a list. She calls it “Advice for Mentees,” and she included it near the end of the symposium in her honor at the Yale School of Medicine last March. Next year Steitz will have been a member of the Yale faculty for five decades; she holds a Sterling Professorship, the university’s highest honor among faculty; last year she received the national Lasker-Koshland Special Achievement Award in Medical Science, a recognition of a lifetime’s work, which in Steitz’s case includes making not one but two seminal contributions to her field. And all of those accomplishments were duly part of the celebration.

But so, at her insistence, was that list—not just the eleven items on her PowerPoint presentation but also a daylong dual emphasis on science and supportiveness. A coterie of Steitz’s mentees at various stages of professional development took turns reviewing how their own contributions to their field reflected Steitz’s, and how they had internalized the lessons of their common mentor. When the going gets tough, said one mentee, “I need to channel my inner Joan.”

The outer Joan, sitting in the front row of the Harkness Auditorium, laughed. But when her turn to speak came, she made sure to let the audience know that mentorship was serious business. Her tone was calm but authoritative, her posture straight, her manner deliberate. Serendipity was important, she said. Intelligence, too. Fortitude of a certain sort as well—though she didn’t mention that one, possibly because she didn’t need to. Within a month of her getting word that she would receive the Lasker Award, her husband of 52 years, fellow biologist Thomas A. Steitz, had been diagnosed with pancreatic cancer.

The timing of the symposium, barely four months after he had died, was awkward. “It’s just too close to Tom’s death,” she’d told me earlier. “I feel like I’d really like to get out of that and get away from that, and then we can start celebrating stuff about me.” But in the end she couldn’t resist either the cause (the symposium would be Yale’s second annual Perspectives of Women in Science Lectureship) or the opportunity to proselytize for mentorship. Without mentorship, she could not have gotten here—to the height of an extraordinarily dynamic field that barely existed when she was born—from there—a teenage girl learning about the double-helix structure of DNA and practically swooning, experiencing a sensation that decades later she can summon so emphatically that she might as well still be experiencing it, and maybe she is: “trembling with excitement.”

 

If making discoveries in science gives you joy, go for it.

That epiphany came while Joan Argetsinger was an undergraduate at Antioch College, in Ohio. Her father—a junior-high counselor and Antioch alum who encouraged her interest in science—had urged Joan to attend that college specifically because it offered the opportunity to work outside of the standard undergraduate environment. The college sent you places; Antioch sent Joan to a lab at MIT for two three-month stints. There, she found, all anybody was talking about was something called DNA.

The discovery of the double-helix structure of deoxyribonucleic acid was only seven or eight years old. The news was still so fresh that it hadn’t found its way into textbooks or curricula, at least at her college in Ohio. In the subject of genetics, the young Argetsinger recognized what scientists call a “black box.” Information goes in and information comes out—in this case, genetic information—but what happens inside the box is unknown. However, they were learning. Scientists did know that pairs of molecules, called base pairs, bonded together in long, varying sequences.

In 1957 one of the discoverers of the double helix, Francis Crick, articulated what he called molecular biology’s Central Dogma: the process by which the unique sequence of DNA molecules in the nucleus of a cell eventually builds the proteins mostly responsible for driving the one-of-a-kind assortment of tissues and organs that makes you you. Later biologists condensed Crick’s idea to a three-component, two-step process: DNA -> RNA -> protein. (Roughly speaking, information is transcribed from DNA into RNA, and then translated from RNA into a specific protein.)

“Wow,” Joan thought. “There’s a molecular basis for genetic phenomena.” She had, as she would later reflect on many occasions, “fallen in love with base pairs.”

The match, however, seemed unsuitable, and she and biology as star-crossed as Juliet and Romeo. She was a woman, and women didn’t run labs. For all she knew, women didn’t even teach science at the college level. And so when the time came for her to commit to a career, she threw over science for the sensible choice, applying to, and being accepted by, the Harvard Medical School. The summer of 1963 she embarked on what she assumed would be one final fling with the sciences, working in the lab of Joe Gall at the University of Minnesota. (He was later at Yale for many years.) But by the beginning of August she had realized she was about to make a terrible mistake. She contacted someone at Harvard whom she knew from his occasional visits to the MIT lab—someone who had once left a bouquet of daffodils on her desk—and asked if biology would take her back.

That connection was James Watson. When she’d first met him, she barely knew who he was—only that he and Crick were the ones who had discovered the double-helix structure she’d just learned about. Now the whole world knew who Watson and Crick were; together with Maurice Wilkins, they had won the Nobel Prize in Physiology or Medicine the previous fall. The whole world also now knew the significance of what they’d done. It was the kind of revelation that made the covers of magazines—for instance, an issue of Newsweek only three months earlier, featuring a photo of her former MIT lab director, Alex Rich, under the headline “Exploring the Secrets of Life.”

Thanks to Watson’s intercession, she entered a PhD program at Harvard just getting under way, Biochemistry and Molecular Biology. After her first year, she approached a prominent cell biologist and said she’d like to work in his lab. “But you’re a woman,” he said. “And you’ll get married and you’ll have kids, and then what good will a PhD have done you?”

At least, she later told herself, she had managed to leave his office before she started crying. Soon she visited her second choice as thesis adviser: Jim Watson. He welcomed her into his lab.

Joan Argetsinger had found her mentor.

 

Take on the most challenging questions.

Only later did she discover that she was the first woman to join Watson’s lab as a PhD student. Before long, he was accepting other women, and by the time Joan Steitz (she married Tom Steitz, a biochemist a year ahead of her, in 1966) left Harvard in 1967, the world was a different place for women.

Sort of. Even in a two-professional household, the common, unthinking assumption was still that a husband’s career took precedence. Tom accepted a postdoc position at Cambridge, so Joan needed to find a postdoc position there as well. Again she turned to Watson for guidance; again he interceded. He put in a word with his old pal Crick, who ran a lab with Sidney Brenner, the black-box opener who had helped discover mRNA, leaving the DNA -> RNA portions of the genetic black box in plain sight.

Steitz had a passion. She had a position. What she needed now was a problem to occupy her time at Cambridge, and she found it: the second ->.

Biologists knew that the second -> represented the work of the ribosome, the cellular “machinery” that takes genetic information from mRNA and synthesizes proteins. What they didn’t know was how mRNA connects with the ribosome. The problem was obvious to anyone in the field, but Steitz had an advantage—an ironic one: she was a woman. Or, to be more precise, she wasn’t a man.

Over the next two years the male postdocs would need to perform the kind of science that would either prove them worthy of a position at a prestigious US university, or not. Steitz carried no expectation of running a lab and every expectation of being a research associate in someone else’s lab. She had nothing to lose. A high-risk, high-reward project suited her just fine, and she made the most of it, using new technology just emerging from Fred Sanger’s lab to isolate and analyze the sequences bonding mRNA to ribosomes.

Her first publication, “Polypeptide Chain Initiation: Nucleotide Sequences of the Three Ribosomal Binding Sites in Bacteriophage R17,” appeared in 1969—in Nature, no less, a professional plateau that few researchers ever reach.

 

Stick to it—even if public opinion is against you.

The career path that Joan and Tom followed was still Tom’s—a position at the University of California–Berkeley—but the difference this time was that Joan was in demand, too.

Not that the Berkeley powers-that-be realized it. They told her that faculty wives made splendid lab assistants. Joan, however, was fielding offers for positions that themselves required lab assistants. She spent most of that semester traveling the country, giving talks about her research. After six months, she and Tom agreed they had to find a university where they could both hold positions commensurate with their growing expertise and reputations. In 1970, the two Steitzes joined the faculty at Yale’s fledgling department of Molecular Biophysics and Biochemistry. The classroom portion of her new responsibilities gave her pause (at least until Watson reassured her that he, too, had suffered nightmares of self-doubt when he became a professor at Harvard). The lab portion, however, provided her with precisely the opportunity she needed. In the work she’d published in Nature, she had shown how mRNA bonds to the ribosome. Now she designed an experiment that took the next, necessary step of demonstrating that this pairing actually causes the ribosome to do what biologists hoped it would do: initiate protein synthesis.

A decade had passed since Steitz had begun to fall in love with base pairs. The black box had few secrets left—or so the common wisdom held. She wasn’t so sure. All that anyone had studied was bacteria. What about the cells of higher organisms? What about mammals like us? In Watson’s lab, Steitz had heard her fellow researchers mocking the idea of studying mammalian cells, because a cell was a cell. But she’d heard something else in Watson’s lab, from Watson himself: “It’s not worth wasting your time on something if it isn’t going to give you an important answer.”

What particularly troubled Steitz was the amount of DNA in human cells. It’s seemingly more than nature needs. A bacteriophage (a virus that infects a bacterium) has a couple of hundred genes. A bacterium has tenfold more. “Higher” cells such as ours, however, have a thousandfold more. Just as curious, she thought, was that only about ten percent of the RNA in the nuclei of these higher cells become messengers on a mission to create protein; the rest remain in the nucleus and decay.

She spent part of her first sabbatical, in 1976, trying to generate experimental tools for figuring out what mechanism determines which nascent segments of RNA stay or go. Her approach was to try to create antibodies to attack a certain kind of protein in the nucleus that she suspected played a role in that determination. After six months of trying and failing to make antibodies, she gave up. The following year, the problem was still nagging at her. After an article appeared in Nature describing potential antibodies made by patients, she asked a new MD/PhD student in her lab, Michael R. Lerner, whether he knew where to find patients with the right kind of antibodies. He said he just might. Lerner popped across Cedar Street to Yale–New Haven Hospital, talked to a clinician, and returned with a few vials of blood from patients with systemic lupus erythematosus.

The result was one of those moments in science scientists live for. Steitz and Lerner got the answer to their question—yes, certain proteins determine which RNA in the nucleus stay or go—but they also got the answer to a question they hadn’t even thought to ask.

The answer was snRNPs—small nuclear ribonucleoproteins. The question: what mechanism determines which segments of RNA get to stay or go?

The world of RNA research had recently found that one reason RNA molecules are so puzzlingly abundant in the nucleus is that they actually consist of two kinds of code, those that are “junk” and get spliced out (introns) and those that are essential for creating mRNA (exons). Now they knew what did the splicing. It was Steitz and Lerner’s snRNPs (pronounced snurps).

In the decades to follow, Steitz’s lab has specialized in studying why that “junk” isn’t junk. By discovering and investigating varieties of snRNPs, her lab has been among the leading centers of research into not only what splicing does—regulate a basic biological process such as aging—but also what mutations in the splicing do: determine a basic biological disorder, such as accelerated aging. It’s work that has revolutionized the diagnosis and treatment of autoimmune diseases.

“Indisputably, Joan is the most famous contributor to the world of small RNA and RNP particles,” the UC–San Francisco geneticist Christine Guthrie once told ASCB, the journal of the American Society of Cell Biology, “and one of the greatest scientists of our generation.”

 

The list goes on.

When you start a new lab, keep the most important problems for yourself.

Your presence as someone actively engaging in research will set an example. Besides, you’re the expert.

 

Everyone (even undergrads) should have their own projects.

“That way,” Steitz said at the symposium, “they know for the first time that the answer to this question is what they’re seeing, and they’re the only person in the world that knows this, until they”—her voice dropped, almost to a whisper—“tell somebody else about it. It’s wonderful.”

 

Choose a supportive partner.

For more than 40 years Tom and Joan Steitz worked in the same department at Yale. In 1980, having fully established her career, Joan had a son, Jon; she credits Tom with sharing child-rearing duties. Before she was 45 she received the National Medal of Science and had been inducted into the National Academy of Sciences and the American Academy of Arts and Sciences. (Tom was no slouch, either. One night in the fall of 2008, Joan answered the phone, heard a Swedish accent, and handed the receiver to her husband. He’d won the Nobel Prize in Chemistry for his research on the ribosome.) Although their research didn’t exactly overlap, it didn’t exactly not, either. They kept each other up to date about developments in science and also about the sociology of science—in particular, their grievances about department politics, which they regularly aired at the dinner table, at least until the evening that their son Jon, at the age of 6 or 7, pleaded with them, “Please, no more ‘Ain’t it awful?’ tonight!” (Jon would later enter Yale College, where he joined the baseball team. After graduating, he played two seasons in the minor leagues before an injury ended his career. He is now a consultant at McKinsey.)

At some point in her talk at the symposium, though, one might wonder about that list—not so much the items on it as the drive to create it in the first place. Watson’s mentorship had always been an important factor in her career, and she herself had always kept in mind that she was setting an example for the women in her lab. Not until 2005, however, did Steitz begin to fully appreciate the role she could play in influencing others.

That year she served on a panel that would research and write a National Academies of Sciences report Beyond Bias and Barriers: Fulfilling the Potential of Women in Academic Science and Engineering. She’d always thought that her presence as a woman scientist serving on committees or presenting papers at conferences was a step in the direction toward gender equality—and it was. But through her work on the panel she saw that 20 percent or 40 percent representation wasn’t enough. The research she read argued that any disparity would have a muffling effect on the members of the traditional minority. Since then Steitz has emerged as a ubiquitous advocate for gender parity in the sciences, and in 2006 she became one of the founding members of the Rosalind Franklin Society, a nonprofit that, according to its website, “recognizes, fosters, and advances the important contributions of women in the life sciences and affiliated disciplines.”

The irony is inescapable. Rosalind Franklin has become the symbol of sexist victimization in the sciences—at the hands of none other than James Watson. In his groundbreaking 1968 bestseller The Double Helix—perhaps the first behind-the-scenes account of the scientific process that revealed, even reveled in, the every-“man”-for-himself psychology feeding the “gentlemanly” scientific process—Watson recounted how a colleague of Franklin’s, the future fellow Nobel laureate Wilkins, allowed Watson and Crick a sneak peek at her now-famous Photo 51 without asking her permission. From that photograph Watson and Crick deduced the double-helix structure.

While talking to Franklin in her office, Watson wrote in Double Helix, he “implied that she was incompetent in interpreting X-ray pictures.” In “Decoding Watson,” a PBS American Masters profile that first aired in January 2019, he was even more caustic. Hadn’t Franklin been in possession of the image for eight months without realizing what it indicated? “It’s stupid,” he said. “If she had a real friend who was intelligent they probably would have told her on a couple of occasions, ‘You’re an ass.’” (Data collection and data interpretation, as just about every other scientist will tell you, don’t always utilize the same skill set.)

Steitz remains protective of her mentor’s scientific reputation. She was interviewed for the documentary but refused to dish the dirt she felt the filmmakers wanted. As for Watson’s personal beliefs—including his assertions on multiple occasions that, in the aggregate, blacks are intellectually inferior to whites—she can only sigh.

“People are enigmas,” Steitz has said. “We all are. Some of us are just bigger enigmas in more-different directions than others.”

Take Joan Steitz. Ask her why she fell in love with base pairs, and her answer is itself enigmatic. “Different people like to view the world at different levels. It just so happens I don’t have to know where all the atoms are, but I certainly have to know where the molecules are.” Just so happens? Happens how? What’s inside the black box of falling in love?

“I have no idea,” she shrugs. And then she adds, not least because it’s in her genes to do so: “It’s biology.”

 

Teach: both by mentoring undergraduates and in the classroom.

Enough said.  

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