"These marvelous artistic objects"

How a work of art kept a future Harvard chemistry professor from dropping out of college

Stuart Schreiber¹, a Harvard professor for nearly forty years, has made major discoveries about how cells use proximity to transmit crucial messages and to regulate which of our genes are turned on and off at any given time. He discovered a non-genetic change in cell state that leads to a previously unknown mechanism of cancer drug resistance. His vision for “diversity-oriented synthesis” led to the building of countless chemical compounds that better mimic the bioactive ones found in nature like taxol, penicillin, and the precursor to statins. He founded or co-founded 14 biotech companies that have put 16 life-changing drugs on the market, and he has now launched two major biomedical research institutes. But he very nearly wasn’t a scientist at all.

For his Oakton High School degree in Fairfield, Virginia, Schreiber selected the “Work Study Program” that credited a certain number of hours per week of employment towards a three-year high school degree. These three years entailed classes from 7:30-10:30 AM with one extra class during the final summer. He swapped science classes, including chemistry, for others better suited for the path he was pursuing, like Automotive Maintenance and Repair, I, II, and III. Each fall, he was provided textbooks and a locker. At the end of each spring, he asked for the locker combination again to retrieve the unused books. He was intent on getting out of his house but he never expected to leave his hometown.

He took the mandatory SAT exams one morning around 1973 after a long night out with his friends. The stunning results didn’t change how his parents saw him: in his mother’s eyes he could do no wrong and in his father’s no right. (The latter fact dogged him for his entire life until a commercial DNA kit explained everything at age 61.) But thanks to a nudge from his sister, he enrolled in her alma mater, the University of Virginia, where she had paved the way by excelling as one of the first women to attend the university.

Schreiber was put off by the idea of sitting in a classroom—something he’d done very little of for the past three years—so when pressed to choose a major, he chose forestry. He had no interest in “sitting in an office wearing a nice shirt,” he said. He wanted to work outside and saw forestry as a link to carpentry, whose symmetry and craftsmanship had already captured his attention. But there was a catch. His dorm advisor explained that Schreiber would have to take chemistry to major in forestry. “Sign me up,” he replied. The advisor explained that the required “weed-out” chemistry course would be out of his reach since he’d never taken chemistry in high school, and steered him toward the humanities.

Soon after, Schreiber found himself sitting in a classroom full of students discussing Jean-Paul Sartre’s No Exit far too seriously for his taste. “I thought they must be joking,” he said. Sartre once called genius “the brilliant invention of someone who is looking for a way out.” Schreiber just wanted out of that classroom. Seeing no other option, he decided to drop out of school, reasoning that he hadn’t any interest in academics to begin with. He didn’t feel comfortable in Charlottesville in general or at university in particular.

His sister was there when Schreiber called home to inform their mother that he was dropping out, so she grabbed the phone and did what she calls “the big sister thing.” She told him it was ridiculous to listen to what anyone else said about his own abilities. It was his life, and he should make his own decisions, not based on what some dorm advisor told him. Just give the chemistry class a shot.

She had no illusions that her brother would listen to her, and Schreiber doesn’t exactly recall relenting to his sister’s advice. But he clearly remembers the chair he occupied in the 450-seat lecture hall the first time he attended that chemistry class in the way other people remember where they were when they learned that John F. Kennedy had been shot.

He’d already missed several weeks of the class. Looking around at the other students, he wondered how they knew to take notes or to have notebooks with them at all. He was just there to give it one last shot, and he might have walked away as quickly as he had from Sartre. Then came the moment when everything changed. His professor, Russell Grimes, drew 3D shapes on the chalkboard in colored chalk. To Schreiber, they were “marvelous artistic objects”. He stared at them, mesmerized, needing to know what they were. It marked an awakening for him, later describing it as the moment that his perception of science as the rote memorization of dull facts switched “to thinking that it was about beauty and art and life”.

A less marvelous interpretation. The original included white chalk for some of the lobes. But this gives you a general sense of what they would have looked like.

Devouring his textbook later, Schreiber would come to understand that these objects, called d-orbitals, that to most people probably look like botched balloon animals, are models of the atom. They represented the probability of finding an electron in a certain 3-dimensional space. They were very different from the Walt Disney version of chemistry he’d seen in high school, and indeed different from the iconic image of the atom that still persists in popular culture today. Electrons don’t zoom around the nucleus of an atom on some predetermined orbit. The atom is not a miniature solar system, with the nucleus as its sun and electrons its orbiting planets.

The scale suggested by the solar system model of the atom is also way off. If the entire atom were the size of the 450-person lecture hall where Schreiber sat, mouth agape, suspended in time, then the atom’s nucleus—everything except for the electrons—would be a miniscule piece of lint in his pocket. Atoms have so much empty space that if you removed that space from matter, you could fit the entire human race into that same pants pocket. As for the misleading orbiting electrons, the Heisenberg Uncertainty Principle states that the exact position and momentum of an electron cannot be known at the same time. This makes them elusive, slippery little beasts. But as elusive as they may be, they inhabit a real form that, while invisible, has real observable consequences, like a secret.

From that moment on, the effortlessness with which he consumed the material was less like learning and more like lights blinking on in unknown corners of his brain, rousing dormant knowledge, the way Tokyo must look from space as dusk falls. How else to explain that not only did he earn straight As, he didn’t get a single problem wrong from then on. Buzzing with ambition, he went to the chair of the chemistry department, Professor Richard Sundberg. Sundberg’s lab was building complex molecules called indole alkaloids like vincristine and vinblastine which are still the frontline treatment for leukemia.

He informed Professor Sundberg that he intended to become a synthetic organic chemist at a major East Coast university, to which Sundberg gently laughed. He offered Schreiber an easy project that would give him a nice laboratory experience. Undeterred and seeing that project for what it was, Schreiber asked to work on the giant anti-cancer drugs they were building. Sundberg agreed to give him one of the most challenging pieces of the build—9 carbon atoms connected in a ring. It was the molecular equivalent of wrangling an angry toddler into a car seat while blindfolded, and he did it.

He would perform similar feats as a graduate student at Harvard, then, after only three years of graduate school, as a professor at Yale. He would move back to Harvard to use chemistry to study biology, risking his fame in organic synthesis to follow his curiosity. After accidentally backing into chemistry through forestry, he would go on to become a pioneer in the field of chemical biology and one of the most well-known figures in biotech. And it all started with a drawing (although equal credit must be given to the big sister).

1. In full disclosure, Stuart Schreiber is my boss. He fully supports the story’s appearance here, but did not ask for it. Like all of the posts, views expressed are my own and do not represent or reflect the institute where we work.