Precision Medicine: A White House Initiative and a Conversation with David Goldstein

Federal Government’s New Focus on Precision Medicine Dovetails with P&S Strategic Plan

Two Columbia faculty members participated in President Obama’s presentation of details of the precision medicine initiative he announced during this year’s State of the Union address. Columbia University’s precision medicine initiative was announced by CU President Lee Bollinger in early 2014, and the P&S strategic plan has identified precision medicine as a priority.

Tom Maniatis

Dr. Maniatis and Wendy Chung, MD, PhD, associate professor of pediatrics in medicine, were invited to the White House to participate in the announcement. Dr. Chung directs the clinical genetics program at Columbia and conducts research on a wide range of human genetic disorders.Both are members of the Columbia precision medicine task force. Columbia’s precision medicine initiative has gained steam with the arrival in January of David B. Goldstein, PhD, as founding director of Columbia’s Institute for Genomic Medicine, a university-wide program to integrate genetics and genomics into research, patient care, and education at Columbia University Medical Center and NewYork-Presbyterian Hospital.

“My hope in coming to Columbia is that we will be able to ensure that all patients who could benefit from genome sequencing will have their genomes not only sequenced, but carefully interpreted,” says Dr. Goldstein.

Dr. Goldstein, author of more than 200 papers on the clinical applications of genomic analysis in AIDS, hepatitis C, schizophrenia, and epilepsy, was recruited from Duke University, where he was director of the Center for Human Genome Variation and the Richard and Pat Johnson Distinguished University Professor with appointments in molecular genetics & microbiology and biology. Here are answers to questions posed to him about the promise of precision medicine and his vision for the Institute for Genomic Medicine.

Much of your research has been in the field of pharmacogenetics, looking for clues in a patient’s genetic traits or disease profile to predict responsiveness to a particular drug protocol. How is that going?

There has been a lot of enthusiasm and even hype for this work, and the reality is that we still have very few real-world examples. And while I would not want to add to the hype, I do personally expect that to change before too long. There’s every reason to believe that understanding the exact underlying molecular cause of a condition will guide how we treat it, and we in fact already see very clear examples of this in some of the work we and others are doing in epilepsy.

Why the move to Columbia?

The work that needs to be done in precision medicine goes beyond the boundaries of a single investigator’s lab, no matter how big that laboratory is. The vision Columbia has outlined is the most integrative and comprehensive I’ve seen, bringing in the Morningside campus, CUMC, and NewYork-Presbyterian with a charge to pursue clinically applied investigations. As soon as I heard President Bollinger articulate his vision, I knew I wanted to be involved.

What is your own vision for the institute?

We’re going to pick a few key clinical areas where we think we can make a really big difference. One major focus will be on epilepsy and using comprehensive genomic approaches to figure out what’s wrong with kids who have serious genetic diseases. A more general focus will be to carefully interpret the genomes of all patients with unresolved or undiagnosed genetic diseases.

How might the institute’s work help someone with epilepsy?

If we sequence a patient with epilepsy and find there’s a mutation in a particular potassium channel gene, we can put the protein that gene encodes into a well-established laboratory protocol and test an FDA-approved drug that targets that protein. My colleagues in Melbourne, as part of the Epi4K and Epilepsy Phenome/Genome Project research teams, are already pursuing exactly this kind of work. You can prove that the effects of a mutation that causes epilepsy can be interrupted in the lab with a particular drug. Then you know to try that drug in patients with that kind of epilepsy.

This is where having an integrated program is so important. If we just get the mutation, we can’t do much with that. We have to understand what that mutation does, biologically, and how it relates to the mutations in other patients, so we can group patients based on the different underlying processes that have gone awry and not just their symptoms. One of my highest priorities at Columbia is to create a mechanism for handing over the mutations to really good biology labs that can investigate how those mutations create the effects that they do.

What do you tell patients about the current realities of precision medicine?

When I talk to families about participating in the kind of research we do, I always tell them that there is a pretty decent chance that we will find out what is wrong genetically, but I also tell them that there isn’t a very high chance that we will be able to do something clinically that will make a big difference. Sometimes we really do learn how to essentially save a kid, just by looking at the genome, and that is the most wonderful thing that can happen. But it is a minority of cases and we have to make that clear.

So why do families still choose to participate?

Most families and patients want to know why. Even if we can’t make a big difference clinically, simply putting a name to a condition, and providing a genetic explanation, is of real value. It provides peace of mind. It provides an explanation. It allows families to reach out to other families that they know have similar conditions, to create support groups, to create advocacy groups. Explaining the basis of disease is a part of practicing good medicine, and genomics is a critical part of that effort.

Where do you draw inspiration in your quest for clinically relevant genomics?

In terms of personalized and precision medicine, cancer treatment is no longer aspirational—it’s demonstrated. Everyone agrees that the future of cancer therapeutics is to target treatment to exactly what has gone awry in tumors. All sorts of great work in that field is already going on at Columbia. My personal ambition is to add a few more disease areas to that roster. I want to make epilepsy next. And I want to make sure we do everything for kids with undiagnosed disease, for complicated pregnancies. Cancer is an example of where we want to be.