That’s what’s going to be happening in cancer. If you didn’t know the HIV story, you would be depressed: you put all this work into the drug, and a year later the cancer has developed resistance. But if you understand that this is a game of probability, and there is only a finite number of cancer cells and each has only a certain chance of mutating, and if we can put together two or three independent attacks on the cancer cell, we win. If we invest vigorously in this and we attract the best young people into this field, we get it done in a generation. If we don’t, it takes two generations. That’s a very big difference.
JF: You mentioned schizophrenia alongside cancer. What is the genomic prospect for dealing with psychiatric diseases?
ESL: These diseases are the flip side of cancer. Cancer, you can study in a petri dish, because it’s about cells growing. You can also inject cancer cells into a mouse and study them. With psychiatric disease, you can’t do any of that. It is quintessentially a human condition.
That’s why genomics, in which Big Data meets DNA, has been so important for approaching psychiatric disease. By looking at tens of thousands of patients, we’ve gone from knowing about zero genes underlying schizophrenia, as recently as five years ago, to knowing roughly 100 genes today. And the genes are beginning to make sense. Some look like they’re telling us about particular kinds of calcium channels, others about particular ways that neurons grow.
I think the genetic clues as to what’s actually wrong in human disease, together with experimental tools of manipulating neurons in animal models, may allow us to produce animals that mimic the real molecular biology of human disease. I’m not Pollyanna. This is not around the corner. It’s not for next quarter; it’s not for next year. We play for the long game. I don’t want to overpromise in the short term, but it is incredibly exciting if you take the 25-year view.
JF: Any researcher can find ways to use extra money. But in genomics now, how significant is research funding as a limiting factor on progress toward therapies?
ESL: It is incredibly limiting right now. Young scientists who need to look at 100,000 cancer samples, or do functional tests inhibiting all the genes in the genome, or explore the use of chemicals in ways they never could before—they need an NIH [National Institutes of Health] that is able to place bets. With sequestration, and the NIH budget falling by about 25 percent in real terms over the past decade, the people reviewing grants naturally become more conservative. When there’s less money, reviewers don’t want to run the risk of wasting money on something that doesn’t work.
I’ve got to tell you, if you aren’t prepared to waste money on things that might not work, you can’t possibly do things that are transformative. Because for every successful transformative idea, there’s five times as many nonsuccessful transformative ideas. Nobody knows how to figure out in advance which ones they’re going to be.