Range, page 28
When I spoke with Smithies in 2016, he was ninety years old and in his lab. He was thinking about how the kidney separates large and small molecules. “At the moment, it’s a Saturday morning theoretical experiment,” he said.
What struck me as Smithies spoke was his joy in experimentation. Not just in his lab, but in his life. He embodied a number of tenets I set out to explore in this book. From the outside, he looked like the consummate hyperspecialist. He was a molecular biochemist, after all. Except, molecular biochemist wasn’t really a thing when Smithies was in training. First he studied medicine, until he attended a talk by a professor who was combining chemistry and biology. “He lectured about this new subject which hadn’t yet been invented, in a sense,” Smithies told me. “It was marvelous, and I thought, ‘I’d like to do that. I’d better learn some chemistry.’” He turned on a dime and switched to studying chemistry. He never even thought to feel behind. On the contrary, “that was really very valuable, because at the end I had a good background in biology and wasn’t frightened of biology, and then I wasn’t frightened of chemistry. That gave me a great deal of power in the early days of molecular biology.” What sounds like hyperspecialization today was actually a bold hybrid at the time.
Smithies was a professor at the University of North Carolina when we spoke. He passed away nine months later, at ninety-one. To the end of his life, he encouraged students to think laterally, broaden their experience, and forge their own path in search of match quality. “I try to teach people, ‘Don’t end up a clone of your thesis adviser,’” he told me. “Take your skills to a place that’s not doing the same sort of thing. Take your skills and apply them to a new problem, or take your problem and try completely new skills.”
Smithies lived the advice he gave. In his fifties, he took a sabbatical in order to venture a mere two floors away in the same building to learn how to work with DNA. He never did find a precursor to insulin, and by the time he was awarded the Nobel Prize in 2007, it was as a geneticist, for figuring out how to modify disease-causing genes so that they could be studied in animals. In that regard, he was a late specializer. I told Smithies that I had recently talked with the provost of a large research university who was using data analytics to assess contributions and make hires and promotions. The provost told me that chemists reliably fall off a cliff twenty years after they get their PhDs. Smithies laughed. “Yeah, well, my most important paper was published when I was about sixty,” he said. A 2016 analysis of ten thousand researchers’ careers determined that there is no standard relationship between experience and contribution; an individual’s most impactful paper was as likely to be their first as their second, their tenth, or their last. (Researchers did tend to publish more frequently at younger ages, though.)
When I mentioned to Smithies that his starched-shirts memory was an example of lateral thinking with withered technology, he added that in 1990 he shared the Gairdner Award (a sort of pre-Nobel) with Edwin Southern, who also wielded a childhood memory that, on its face, seemed totally unrelated. “His was a memory of cyclostyling,” Smithies said, referring to an old document-copying device that used glazed paper and a stencil system. With that in mind, Southern created the “Southern blot,” a ubiquitous method for detecting specific DNA molecules. Gunpei Yokoi would have been delighted. And yet those were nothing compared to the withered technology employed by Tu Youyou, who in 2015 became the first (and so far only) Chinese national to win the Nobel Prize in Physiology or Medicine, and the first Chinese woman in any category.
Tu is known as the “professor of the three no’s”: no membership in the Chinese Academy of Sciences, no research experience outside of China, and no postgraduate degree. Before Tu, other scientists had reportedly tested 240,000 compounds searching for a malaria cure. Tu was interested in both modern medicine and history, and was inspired by a clue in a recipe for medication made from sweet wormwood, written by a fourth-century Chinese alchemist. Technology doesn’t get much more withered than that. It led her to experiment (at first on herself) with a sweet wormwood extract known as artemisinin. Artemisinin is now regarded as one of the most profound drug discoveries in medicine. A study on the decline of malaria in Africa attributed 146 million averted cases to artemisinin-based therapies between 2000 and 2015. Tu had a lot of disadvantages, but she had an outsider advantage as well that made it easier for her to look in places others would not dare. The kind of advantage Smithies sought on Saturday mornings.
Over his career, Smithies filled and kept 150 notebooks. “That was also Saturday,” he repeated, as he walked me through important pages. When I pointed it out, he replied, “Well, I’ve had people say, ‘Why did you come to work any other day!’”
* * *
• • •
The breakthroughs, of course, were exceptions. One Saturday morning experiment accidentally dissolved an important piece of equipment. In another, Smithies contaminated his shoes with a putrid chemical. He thought he had aired them out sufficiently, until he heard one elderly woman ask another if she smelled a dead body. Smithies could not resist “picking up anything” to experiment with, he said, a habit his colleagues noticed. Rather than throw out damaged equipment, they would leave it for him, with the label NBGBOKFO: “no bloody good, but OK for Oliver.”
An enthusiastic, even childish, playful streak is a recurring theme in research on creative thinkers. University of Manchester physicist Andre Geim employs (with no relation to Smithies) “Friday night experiments” (FNEs). It was a Friday night when he began the work that led to his 2000 Ig Nobel Prize. The Ig Nobel is given for work that at first blush seems ridiculous or trivial. The mascot is an image of Rodin’s The Thinker sculpture, except “The Stinker” has fallen off his pedestal and is lying on his back on the ground. Recipients are asked beforehand if they are willing to accept the award, so they can weigh reputational concerns. Geim won for levitating a frog with strong magnets. (Frogs, and the water they contain, are diamagnetic, or repelled by magnetic fields.)
Needless to say, FNEs are not funded, and most amount to nothing. After the frog, though, another FNE produced “gecko tape,” an adhesive inspired by a gecko’s feet. And then there was the one that started with using Scotch tape to rip thin layers of graphite, the material that comprises pencil lead. That low-tech affair culminated in the 2010 Nobel Prize in Physics, for Geim and his colleague Konstantin Novoselov’s production of graphene, a material one-hundred thousand times thinner than a human hair and two hundred times stronger than steel. It is flexible, more transparent than glass, and an excellent electrical conductor. Spiders fed graphene have spun silk many times tougher than the Kevlar in bulletproof vests. Graphene consists of carbon strips one atom thick, an arrangement previously considered purely theoretical. When Geim and Novoselov submitted their initial work to one of the world’s most prestigious journals, one reviewer said it was impossible, and another deemed it not “a sufficient scientific advance.”
Art historian Sarah Lewis studies creative achievement, and described Geim’s mindset as representative of the “deliberate amateur.” The word “amateur,” she pointed out, did not originate as an insult, but comes from the Latin word for a person who adores a particular endeavor. “A paradox of innovation and mastery is that breakthroughs often occur when you start down a road, but wander off for a ways and pretend as if you have just begun,” Lewis wrote. When Geim was asked (two years before the Nobel) to describe his research style for a science newsletter, he offered this: “It is rather unusual, I have to say. I do not dig deep—I graze shallow. So ever since I was a postdoc, I would go into a different subject every five years or so. . . . I don’t want to carry on studying the same thing from cradle to grave. Sometimes I joke that I am not interested in doing re-search, only search.” Deviating from what Geim calls the “straight railway line” of life is “not secure . . . psychologically,” but comes with advantages, for motivation and for “questioning things people who work in that area never bother to ask.” His Friday evenings are like Smithies’s Saturday mornings; they balance the rest of the week’s standard practice with wide-roaming exploration. They embrace what Max Delbrück, a Nobel laureate who studied the intersection of physics and biology, called “the principle of limited sloppiness.” Be careful not to be too careful, Delbrück warned, or you will unconsciously limit your exploration.
Novoselov was Geim’s PhD student, taken on board after Geim’s colleague told him that Novoselov “seems to be wasting his life” in another lab. When Novoselov arrived, he found equipment that was similar to that in his previous lab, but “this flexibility and the opportunity to try yourself in different areas which was interesting.” A Science profile of him bore the section titles “Going for Breadth” and “Spread Thin,” which would sound really bad and like he was falling behind if the article wasn’t also about how at thirty-six he was the youngest physics Nobel laureate in forty years.
Like Van Gogh or Frances Hesselbein or hordes of young athletes, Novoselov probably looked from the outside like he was behind, until all of a sudden he very much wasn’t. He was lucky. He arrived in a workspace that treated mental meandering as a competitive advantage, not a pest to be exterminated in the name of efficiency.
That kind of protection from the cult of the head start is increasingly rare. At some point or other, we all specialize to one degree or another, so the rush to get there can seem logical. Fortunately, there are pioneers who are working to balance the cult of the head start. They want to have it all—the mental meandering along with the wisdom of deep experience; the broad conceptual skills that make use of Flynn’s scientific spectacles even within training programs for specialists; and the creative power of interdisciplinary cross-fertilization. They want to reverse the Tiger trend, not just for themselves, but for everyone, and even in domains synonymous with hyperspecialization. The future of discovery, they argue, depends on it.
* * *
• • •
It only takes a few minutes of conversation to gather that Arturo Casadevall is a beaker-half-full kind of guy. One of the greatest days of his life was when gravitational waves were detected, and that’s not his field. “Two black holes collide in space a billion years ago, and for a billion years those gravity waves travel through space-time,” he narrated, eyes widening. “When the original signal began, life on Earth was unicellular, and in that time humanity manages to build two interferometers and measure it. I mean, what an accomplishment that is.” He is also an MD-PhD and a star in his own domains, microbiology and immunology. He has studied AIDS and anthrax, and has illuminated important aspects of how fungal diseases work. His “h-index,” a measure of a scientist’s productivity and how often they are cited, recently surpassed Albert Einstein’s.* So his peers took it seriously when he arrived at the Johns Hopkins Bloomberg School of Public Health in 2015, as chair of molecular microbiology and immunology, and warned that scientific research is in crisis.
In a lecture to his new colleagues, Casadevall declared that the pace of progress had slowed, while the rate of retractions in scientific literature had accelerated, proportionally outpacing the publication of new studies. “If this continues unabated,” he said, “the entire literature will be retracted in a few years.” It was science gallows humor, but grounded in data. Part of the problem, he argued, is that young scientists are rushed to specialize before they learn how to think; they end up unable to produce good work themselves and unequipped to spot bad (or fraudulent) work by their colleagues.
The reason Casadevall came to Hopkins, from a comfy post at New York City’s Albert Einstein College of Medicine, is that the new gig offered him the chance to create a prototype of what he thinks graduate science education, and eventually all education, should be.
Counter to the prevailing trend, Casadevall—with Gundula Bosch, a professor of both biology and education—is despecializing training, even for students who plan to become the most specialized of specialists. The program, known as the R3 Initiative (Rigor, Responsibility, Reproducibility), starts with interdisciplinary classes that include philosophy, history, logic, ethics, statistics, communication, and leadership. A course titled “How Do We Know What Is True?” examines types of evidence through history and across disciplines. In “Anatomy of Scientific Error,” students are detectives, hunting for signs of misconduct or poor methods in real research, while also learning how errors and serendipity have led to momentous discoveries.
When Casadevall described his vision of broad education on a professional panel in 2016, a copanelist and editor of the New England Journal of Medicine (an extremely prestigious and retraction-prone journal) countered that it would be absurd to add more training time to the already jam-packed curricula for doctors and scientists. “I would say keep the same time, and deemphasize all the other didactic material,” Casadevall said. “Do we really need to go through courses with very specialized knowledge that often provides a huge amount of stuff that is very detailed, very specialized, very arcane, and will be totally forgotten in a couple of weeks? Especially now, when all the information is on your phone. You have people walking around with all the knowledge of humanity on their phone, but they have no idea how to integrate it. We don’t train people in thinking or reasoning.”
Doctors and scientists frequently are not even trained in the basic underlying logic of their own tools. In 2013, a group of doctors and scientists gave physicians and medical students affiliated with Harvard and Boston University a type of problem that appears constantly in medicine:
If a test to detect a disease whose prevalence is 1/1000 has a false positive rate of 5%, what is the chance that a person found to have a positive result actually has the disease, assuming you know nothing about the person’s symptoms or signs?
The correct answer is that there is about a 2 percent chance (1.96 to be exact) that the patient actually has the disease. Only a quarter of the physicians and physicians-in-training got it right. The most common answer was 95 percent. It should be a very simple problem for professionals who rely on diagnostic tests for a living: in a sample of 10,000 people, 10 have the disease and get a true positive result; 5 percent, or 500, will get a false positive; out of 510 people who test positive, only 10, or 1.96 percent, are actually sick. The problem is not intuitive, but nor is it difficult. Every medical student and physician has the numerical ability to solve it. So, as James Flynn observed when he tested bright college students in basic reasoning, they must not be primed to use the broader reasoning tools of their trade, even though they are capable.
“I would argue, at least in medicine and basic science where we fill people up with facts from courses, that what is needed is just some background, and then the tools for thinking,” Casadevall told me. Currently, “everything is configuring in the wrong way.”
He compared the current system to medieval guilds. “The guild system in Europe arose in the Middle Ages as artisans and merchants sought to maintain and protect specialized skills and trades,” he wrote with a colleague. “Although such guilds often produced highly trained and specialized individuals who perfected their trade through prolonged apprenticeships, they also encouraged conservatism and stifled innovation.” Both training and professional incentives are aligning to accelerate specialization, creating intellectual archipelagos.
There is a growth industry of conferences that invite only scientists who work on a single specific microorganism. Meanwhile, a complete understanding of the body’s response to a paper cut was hampered because hyperspecialists in hematology and immunology focus on pieces of the puzzle in isolation, even though the immune response is an integrated system.
“You can do your entire career on one cell type and it’s more likely you keep your job by getting grants,” Casadevall told me. “There is not even pressure to integrate. In fact, if you write a grant proposal about how the B cell is integrating with the macrophage [a basic interaction of the immune system],* there may be no one to review it. If it goes to the macrophage people, they say, ‘Well, I don’t know anything about it. Why B cells?’ The system maintains you in a trench. You basically have all these parallel trenches, and it’s very rare that anybody stands up and actually looks at the next trench to see what they are doing, and often it’s related.”*
Substitute a few specific terms, and the system of parallel trenches he described could fit many industries. While I was researching this book, an official with the U.S. Securities and Exchange Commission learned I was writing about specialization and contacted me to make sure I knew that specialization had played a critical role in the 2008 global financial crisis. “Insurance regulators regulated insurance, bank regulators regulated banks, securities regulators regulated securities, and consumer regulators regulated consumers,” the official told me. “But the provision of credit goes across all those markets. So we specialized products, we specialized regulation, and the question is, ‘Who looks across those markets?’ The specialized approach to regulation missed systemic issues.”
In 2015, Casadevall showed that biomedical research funding rose exponentially over a recent thirty-five-year period, while discovery slowed down. Life expectancy in countries at the biomedical cutting edge, like the United Kingdom and the United States, recently declined after decades of improvement. The flu annually kills hundreds of thousands of people worldwide while humanity fights it with a cumbersomely produced vaccine from the 1940s. Casadevall’s mother is ninety-three, and on five medications that were available when he was a medical resident in the 1980s. “Two of them are older than I am,” he said, and two others are barely younger. “I cannot believe we can’t do better.” He paused for a moment, tilted his head, and leaned forward. “If you write an interdisciplinary grant proposal, it goes to people who are really, really specialized in A or B, and maybe if you’re lucky they have the capacity to see the connections at the interface of A and B,” he told me. “Everyone acknowledges that great progress is made at the interface, but who is there to defend the interface?”
