The League of Extraordinary Biologists
The Squealing Pig, on Smith Street in Mission Hill, is an Irish pub and sometime metal bar that shows kung fu ﬂicks. It is also, on certain nights, a place where medicine’s biggest problems are solved.
Three scientists from the Harvard Stem Cell Institute come to the Pig when they need to talk about their jobs. They are not your average scientists; they are freaks of overachievement, young and attractive and supremely ambitious. The goal of their research is nothing less than curing mankind’s last intractable diseases. That they are inching ever closer to that goal is only part of what makes them such a very big deal.
Amy Wagers, who works with the stem cells that form blood cells, learned to fly on trapeze bars while studying at Stanford. At the Pig, the petite blond 35-year-old could be mistaken for a teacher from the nearby Winsor School, and tends to talk with her hands, a demure smile breaking across her lips. Kevin Eggan, also 35, does stem cell research tied to ALS, lives in a Leather District bachelor pad, and rock-climbs in his spare time; his square jaw and chiseled build elicit stares from the women at the Pig. Konrad Hochedlinger, 33 and arguably even more handsome—high cheekbones, gray-blue eyes, and an olive complexion that belies his Austrian roots—skis the Alps when he’s home. His specialty is something called IPS cells, which might prove the biggest game-changer of them all, since they derive their healing powers not from nature, but from science.
On their own, Wagers, Eggan, and Hochedlinger have pulled off things in their labs that have never been done before, advances that have fueled the field’s headline-generating momentum. Collectively, the trio, along with their idiosyncratic bosses, have put Boston at the epicenter of a movement that proponents believe will be no less transformative than the Renaissance. But stem cell research is highly competitive, even when the scientists work for the same institution. As such, Florence in the 1500s may not be its best analogy; instead, think Houston in the early 1960s, when a generation of upstart scientists raced to be the first to the moon. Like John Glenn and company, Wagers, Eggan, and Hochedlinger all have a self-regard proportional to their talent. And like those young Mercury astronauts, the young stem cell researchers all want to put their stamp on history in a field that is advancing by the week.
The best way for them to do it—ironically, the only way—just happens to be in concert with one another, one drink at a time if necessary. Which means the biggest breakthrough may have already happened. Building this team was its own kind of miracle, requiring leaps of faith, back-channel overtures, massaging of considerable egos, and, in one case, the gumption necessary for a protégé to break with and then compete against a mentor who is more like a father to him.
The trick ever since has been keeping the trio together. The sessions at the Pig go a long way toward that. But it’s the thrill of the chase that provides the deeper bond.
To understand the hype around stem cells, it helps to first understand how they work. Crudely put, stem cells are like clay. Crudely, because clay cannot regenerate, cannot make more of itself, but also because the core of the analogy—the shared pliability—sells stem cells short. There are only so many things you can make out of clay, whereas stem cells can grow, or be grown by researchers, into brain cells, bone marrow cells, muscle cells, and so on. You can study how stem cells make more stem cells through cell division and gain insights into cancer, whose tumors are thought to form when cell division goes awry. You can manipulate stem cells to carry a disease, then test a potential therapy directly on them, supercharging the typical drug-discovery process and opening the door to entirely new medicines to fight the ravages of Alzheimer’s, Parkinson’s, and diabetes. All this is why stem cells are the source of such excitement, and of the kinds of hopes and pressures that rest on stem cell scientists like Wagers, Eggan, and Hochedlinger.
Modern stem cell research has its foundation in cell cloning, which scientists have been experimenting with for roughly 50 years. In the late 1990s one of the biggest names in cloning—and therefore the nascent stem cell field—was Rudolf Jaenisch, a curly-haired German who looks like a cross between Einstein and Mark Twain. Scottish researchers had just cloned Dolly the sheep, but Jaenisch, cofounder of MIT biomedical research collective the Whitehead Institute, soon advanced the miracle of Dolly through something called nuclear transfer. The process involved microscopically inserting the nucleus of an adult cell into a “denucleated” egg cell; this in turn allowed for the cloning of new cells. With the tools available at the time, nuclear transfer demanded more than mere brilliance. It required such manual dexterity that only a handful of people in the world could perform it, and none as well as Jaenisch. That gave him a virtual monopoly on cloning that lasted nearly a decade.
In 1998, Jaenisch came to the National Institutes of Health to give a lecture. Sitting in the audience was Kevin Eggan, then working at NIH. Jaenisch’s presentation blew him away. He reached out to Jaenisch afterward, and soon decided to give up his job to pursue a Ph.D. in biology at MIT.
Eggan grew up in Normal, Illinois. “I am, of the men in my family, the soft scientist, the weak intellectual link,” he says. “My dad’s a number theorist, and my brother works for the Aerospace Corporation now and can’t tell me what he does.” At the University of Illinois, Eggan got as far as abstract linear algebra before turning to biology and eventually microbiology. He had been headed to medical school when he had second thoughts, and deferred for the opportunity at NIH.
At MIT, Eggan quickly became known for the same thing at which Jaenisch excelled: nuclear transfer (or as Eggan describes it, “the hardest video game you’ve ever played”). His work required him to spend full days bent over a powerful microscope, using joysticks and foot pedals to zoom in and out on cells that—even under magnification—appeared no larger than the tip of a strand of hair. Eggan hunched over these cells so long and so intensely that he developed trucker’s sciatica. Worse, the smallest mistake would send him back to square one. “You have to ask yourself, are you the sort of person that when you got your Nintendo 64 and you started playing Mario Brothers, and you got to that really hard part, could you die a thousand times over and over and over again, and still be motivated to try again?” He was. Eggan mastered nuclear transfer at the age of 26.
In 1999 Jaenisch gave another lecture, at the Research Institute of Molecular Pathology in Vienna. This time 23-year-old Konrad Hochedlinger was in the crowd. As Jaenisch talked about what stem cell scientists were accomplishing, Hochedlinger sat enraptured. He was studying embryo development at the institute, where he’d received his master’s the year before, but wasn’t satisfied with the work. It didn’t feel big enough. A few days later he e-mailed Jaenisch, saying he would be visiting Boston soon, and asked whether Jaenisch would have half an hour to meet.
Neither of Hochedlinger’s parents had any interest in science. And neither did he, at first—he was into art and architecture. But when his older sister began to study biology, she encouraged him to follow in her footsteps.
Several weeks after his e-mail, Hochedlinger did indeed meet up with Jaenisch in Cambridge. Jaenisch was taken with the young man’s impatience for modest gains. He offered a spot in his lab to Hochedlinger, who gladly accepted. If in Eggan Jaenisch had found a protégé, in Hochedlinger he found something closer to a son.