If the scientist’s job is to ponder the stars, the banker’s is to funnel his vision into stellar panels. For while scientific theory can be enthralling, it’s in danger of racking up lost gigabytes and circuitry dust. But when a smart businessman and a top scientist get together, not only can the partnership lead to pragmatic accomplishments, it can actually change the course of scientific inquiry.
Such has been the case at Harvard. The study of evolution is always moving, but nowhere has it been livelier than in Brattle Square, where, ten years ago, a financier named Jeffrey Epstein set up the Program for Evolutionary Dynamics with a $30 million gift to the university, $6.5 million of which was a current-use gift to the PED. His mission was not to coddle neo-Darwinian theorists (because, honestly, couldn’t $30 million be used to vaccinate the entire country of Zaïre?) but to embolden a pragmatic use for the study of natural selection.
It was in August 2003, with the cooperation of Lawrence Summers, then president of Harvard, that the Program for Evolutionary Dynamics set up for business, and, under the direction of Martin Nowak, a professor of mathematics and biology, it revolutionized the way in which evolution is studied and utilized. PED became one of the first programs to give a high priority to the use of mathematics in studying the evolution of microbiology. It also became one of the first departments to develop a mathematical model of how human cancer cells evolve, as well as infectious bacteria and viruses such as HIV. The program’s models have led to key discoveries toward combatting diseases of all kinds and have encouraged researchers around the world to make new discoveries of their own.
It all started in early 2000 when Epstein, a New York hedge-fund manager with a passion for cutting-edge science, invited Nowak to organize a conference on the evolution of language. Nowak was then head of the Program in Theoretical Biology at the Institute for Advanced Study at Princeton and had already published a substantial amount of work on the mathematics of the HIV virus, infectious bacteria, and cancer cells. Before going to Princeton, Nowak had been the head of the mathematical-biology group at Oxford University. His work was not just theoretical but keenly practical.
By 2003, Epstein already had a substantial track record in science philanthropy. He had supported the research of many prominent scientists, including Stephen Hawking, Marvin Minsky, Eric Lander, George Church, and Nobel laureate physicists Gerard ’t Hooft, David Gross, and Frank Wilczek. He was also a member of the New York Academy of Science, a member of Rockefeller University’s board, and actively involved in the Santa Fe Institute, the Quantum Gravity Program at the University of Pennsylvania, and the Mind, Brain & Behavior Advisory Committee at Harvard. Epstein himself was not a scientist per se. He had studied physics at Cooper Union in New York and mathematics at the Courant Institute in New York, leaving both without a degree, and moved on to teaching calculus and physics at the Dalton School in Manhattan. He was then scooped up into options trading on Wall Street and applied his acumen and mathematical wit to the markets.
But Epstein’s heart remained in the pure sciences. He was fascinated by fundamental questions on the one hand and, on the other, eager to apply scientific theory to the real world. It was this combination that drew him to Nowak. For not only was Epstein eager to probe a brilliant mind about the origins of life, but, with his connections at Harvard, he was able to provide Nowak a powerful platform to put groundbreaking medical research into immediate practice.
One of the major diseases that the program studies is human cancer. In 2012, Nowak and two postdoctoral students, Benjamin Allen and Ivana Bozic, developed the first mathematical model of how human colon-cancer cells evolve and specifically how they become immune to inhibitor-drug therapy. Their research was conducted at the request of the Pathology and Oncology Department at Johns Hopkins University. The department was trying to understand how the KRAS gene in colon-cancer cells becomes activated after inhibitor-drug therapy, making the cells resistant to treatment.
By developing a mathematical model of the growth of colon-cancer cells, Nowak and his team showed that the KRAS gene is not actually activated or “switched on” by inhibitor therapy; rather, a small percentage of colon-cancer cells with an already activated KRAS gene are immune from the start and come to predominate as the other cancer cells are destroyed by the inhibitor drug. The discovery was critical in changing the approach to inhibitor-drug therapy. Instead of applying drugs in sequence to fight secondary and tertiary resistance, the researchers at Johns Hopkins are now exploring the effects of using a cocktail of inhibitor drugs to capture all colon-cancer cell types: those with the activated KRAS gene and those without. The same tailored approach is underway for other cancers.
#page#In 2010, Ivana Bozic and Martin Nowak co-authored a pivotal mathematical study that showed that most solid tumors contain 40 to 100 genetic mutations, but that on average only 5 to 15 of those actually drive tumor growth. The findings were essential to the researchers at Johns Hopkins and elsewhere because they demonstrated the importance of isolating a key minority of mutated tumor cells for effective inhibitor treatment.
“Mathematics in medical research reveals patterns that are otherwise hidden,” remarked Epstein, who maintains a frequent presence at PED. “It’s exhilarating when a mathematician can determine molecular and cellular behavior with the precision of an engineer and share those findings with physicians.”
Also in 2010, PED presented to Bert Vogelstein, professor and director of the Ludwig Center for Cancer Genetics and Therapeutics at the Johns Hopkins Kimmel Cancer Center and the Howard Hughes Medical Institute, a mathematical model showing the genetic evolution of pancreatic-cancer cells from the time of initial mutation to non-primary malignant cells. What Nowak’s team had found was surprising: that pancreatic cancer, one of the most lethal forms of cancer, is not fast and furious as had been thought, but rather slow growing. In fact, given the amount and type of genetic disparity between the cellular stages, it appears that it takes about ten years for an initiating mutation to develop to a parental, non-metastatic founder cell and another six years for cells to become malignant.
The significance of these findings is that they highlighted the importance of isolating pancreatic mutations prior to metastasis. Johns Hopkins scientists are now focusing on developing a screening method for pancreatic cancer similar to the protocol used for breast and colon cancers. Though early stages of pancreatic cancer cause no known symptoms, the Johns Hopkins team is looking into pancreatic-screening endoscopies for patients of a certain age.
Over the past two years, Nowak and his team have also collaborated with Johns Hopkins to develop a database to map and predict the effect of drugs on the HIV virus. Like cancer cells, HIV often develops resistance to drug cocktails. This is a major problem for patients, and the trial and error of clinical trials can be hugely debilitating. Using data collected from thousands of blood tests on more than 20 anti-HIV drugs, the model calculates each drug’s ability to suppress viral replication and avoid resistant HIV strains. The model also factors in different drug combinations and dosages, and information about the patient such as blood type, age, and sex, to arrive at the most precisely engineered predictor of results for future patients.
At least on the surface, Epstein’s motivation for applied science differs from Nowak’s. While Nowak is a practicing Roman Catholic and a declared humanist with a desire to serve society, Epstein is first and foremost a problem solver, interested in strategy and intellectual puzzles. He is equally devoted to physics, artificial intelligence, and the human brain. According to Nowak, Epstein was fascinated with his game theory of win–stay, lose–shift and eager to see how it could be applied to the markets. That is not to say that Epstein has no interest in purely humanistic endeavors. He has given thoughtfully to countless organizations that help educate underprivileged children, notably in the U.S. Virgin Islands, where his foundation is based. But his essence is in uncovering unsolved problems, a perhaps insatiable desire.
Much has been written about the Program for Evolutionary Dynamics and Martin Nowak’s work. Nowak is the recipient of numerous awards and the author of several books. And while Jeffrey Epstein remains an obscure figure, tarnished now by a series of scandals involving underage women, one of which led to an 18-month jail sentence, he is nonetheless the talented catalyst, the accelerator of all this medical discovery. Whatever his ignominy, Epstein’s continued bond with Nowak and PED emphasizes that nature is not fastidious nor judgmental, nor is its dynamic always gradual. Discovery can be sparked into being by an unlikely source, and its value does not depend on the makeup of its originator.