JF: What are the comparable next steps in genomics?

ESL: Before we could understand the genetic basis of inherited diseases and cancer, we first had to get a sequence of the human genome. The first 15 years of work [on the Human Genome Project], and about $3 billion of cost, was devoted to getting one sequence of one human being, to use as a starting reference point.

The next job was to go figure out how people with a disease, whether it’s diabetes, schizophrenia, or a lung tumor, differ from that reference. That would require looking at the genomes of thousands and thousands of people to spot the changes. Remember that it took 15 years and $3 billion just to get the first person’s sequence. The idea of doing that thousands of times over would have seemed crazy—except that an amazing transformation over the past 12 years brought down the cost of sequencing genomes by about a million-fold. That has allowed us to look at thousands of people and see the differences among them, to discover critical genes that cause cancer, autism, heart disease, or schizophrenia.

For the first time, after 25 years of genomics, we can finally pop the hood on the car and see what’s wrong. The rate of progress is just stunning. As costs continue to come down, we are entering a period where we are going to be able to get the complete catalogue of disease genes. I think in another five or six years, we should have a complete catalogue. That is not a cure for disease. The next level will be seeing how these individual genetic components fit together, into circuits. You could say that right now we are discovering all the parts of a Boeing 747 and meticulously laying them out on the floor of a hangar. That’s actually pretty impressive, to get all the parts! Still, the plane doesn’t fly yet. This next generation of young scientists is figuring out the functional circuits into which all these parts fit.

JF: I feel lowbrow asking this, but on what timeline will patients see the results? Are these therapies decades away, or a few years?

ESL: It’s important to define your goals. Therapeutic development has already been transformed by genomics. There are 800 different anticancer drugs in clinical development today. Cancer drugs used to be just cellular poisons, but almost all of these new ones are targeted at particular gene products that have been discovered.

But it’s just a start. Some of the new cancer drugs can miraculously make tumors disappear. The problem is that, a year later, the cancer in many cases comes roaring back, because some of the cells have developed mutations that make them resistant. So genome scientists are now finding and targeting these mutations as well. Remember in the 1980s, when HIV was a fatal disease? What made it become a chronic, treatable disease? It was a combination of three drugs. Any one of those drugs alone, the virus could mutate its way around. But with the combination of all three, the chance that a virus could find its way around all of them was vanishingly small.