Joseph D. Terwilliger, Ph.D.
Professor of Neurobiology (in Psychiatry, in the Gertrude H. Sergievsky Center, and in Genetics and Development) – Columbia University
Research Scientist V – New York State Psychiatric Institute
Early in my career, my focus was on development and analysis of statistical methods and computer software for disease gene mapping and population genetics. However, over time I got frustrated because more and more potential collaborators shared the same basic problem – convenience samples of data, collected by convenience in their clinical settings, in their typically urban setting with small families from heterogeneous populations.
Out of frustration with this reality, I began trying to think more about how to identify and pursue research in natural experimental settings, where there was something available in a given population/dataset that closely resembled something experimental geneticists might do in a more malleable species (human genetics being necessarily observational and not experimental for obvious ethical reasons).
To this end, I began travelling the world, in search of useful natural experiments, building collaborations in many parts of the world where people are quite isolated, typically for a variety of geographical, historical, political and cultural reasons. I organized lecture courses on “Logical Reasoning in Human Genetics” with my long-time collaborator Ken Weiss, which we have taught in some form in many countries across all the inhabited continents, in an effort to dissuade scientists from wasting time on Genome Wide Association Studies of samples from their hospital or clinic, and rather focusing on working with special populations and large pedigrees wherever possible.
I built my career by standing up to folks like Francis Collins and Eric Lander before it was cool, pointing out that all the genome sequencing in the world was not going to solve the fundamental problem that most late-onset common human diseases are influenced by hundreds or thousands of genes, each with hundreds or thousands of functional variants, none of which act independently of one-another. In 1996 when i started down that path, it was highly unpopular – people might come to me in the bathroom at a conference and say, “you’re probably right, but shut up because we are now getting funded,” but although I had science on my side, big science took off anyway, and the NIH and others spent hundreds of millions trying to make these diseases meaningfully genetic, with virtually no real success. Today they collect bigger and bigger sample sizes and add more and more layers of -omics, but without hypothesis-driven research, it largely returns much of the same – uninterpretable sets of statistically significant but etiologically trivial signals. Basically a whole lot of nothing that looks like a lot of red lights on machines that go ‘ping.’
Today, I continue my work, focused primarily on natural experiments in unusual populations around the world from Venezuela to Finland, from Qazaqstan to Korea and many other places. My work has taken me to most of the countries America has a problem with, including North Korea, Xinjiang (China), Venezuela, Iran, Libya and more. That experience introduced me to the concept of science diplomacy, where science is used to build relationships between academics in countries that have bad official relations as a way of building trust and relationships where politicians are unable to go themselves. I’ve been active in those efforts for the last 25 years, working with other scientists around the world to build collaborations in the most difficult places – this even led me to have the opportunity to live in North Korea, and teach at the university there, and I even had an exchange program funded between Kim Il Sung University and Columbia University which only ended in 2017 when the use of US passports for travel to the DPRK was banned by the Department of State. Once again politicians, rather then doing their job as diplomats, interfered with private citizens who did their job better than they did.
Research Interests and Activities
Complete List of Scientific Publications
Course Organizer – Logical Reasoning in Human Genetics
Online version of Logical Reasoning in Human Genetics – Tunisia Edition
co-Principal Investigator – Maracaibo Aging Study
