A decade ago, we laid out the parts of the 747. Now we’re laying out the wiring diagram — setting out how the parts work together. Once we have that, we’re 80 percent of the way to solving the plane’s problems.
Eric Lander is not actually talking about jumbo jets. A mathematician and biologist who is one of the founding fathers of the Human Genome Project, he is, rather, talking about us — our bodies, their diseases, and the revolution that the Human Genome Project is bringing in the treatment of those diseases.
The “parts list” — the sequencing of the human genome — was completed a decade ago, in 2003. In the next decade or two, Lander anticipates, the wiring diagram will be completed. The progress so far is already having a drastically beneficial effect on the treatment of diseases, but the revolution will kick in with full force by the mid-century, he says.
We’ll be able to thwart all disease and live forever? Far from it, Lander counters firmly. But more people will die from what he pleasingly calls “healthy old age.”
The founding director of the Broad Institute of Harvard and MIT devoted to utilizing human genome research in medicine, Lander, 56, was in Israel this week for the “First Annual Broad-Israel Cell Circuits Symposium” — a gathering of researchers and students, from the Broad Institute, Harvard, and Israel’s universities, on the cutting edge of human genome research and its applications for medicine.
The Israeli scientific community is “off the scale” when it comes to combining crucial biology and info-technology skills, with “an outrageous number of people working on the interface of biology and mathematics in the study of cell circuitry.” The Broad-Israel partnership is aiming to galvanize funding and bring Israeli and American trailblazers together on an increasing number of joint projects, all designed to speed our progress toward thwarting cancers, Alzheimer’s, diabetes and other diseases.
Squeezing an interview into a packed schedule, Lander, a stellar researcher who co-chairs President Barack Obama’s Council of Advisors on Science and Technology, is gracious and patient in conveying the fundamentals of his lifesaving work to an absolute ignoramus. We sit down in the restaurant of the conference center at Jerusalem’s Mishkenot Sha’ananim, and Lander does his courteous best to condense his life-changing work — changing all of our lives, that is — into a short overview for an interviewer with as much scientific wisdom as “The Big Bang Theory’s” endearingly vacant Penny.
Looking first to the recent past, he summarizes that “In most of the 20th century we didn’t know much about the real causes of cancer, or of diabetes, Alzheimer’s, schizophrenia. We diagnosed the symptoms, not the causes. And most therapy dealt with symptoms, not causes… Looking back, they’ll laugh and say ‘Medicine was barbaric in the 20th century, with occasional successes.'”
And now? “Now we’re laying the groundwork for a systematic strategy.”
The goal of the Human Genome Project was to get that parts list — “to find the 20,000 human genes, and the controls of those genes,” says Lander. With that in place, “we could ask which parts were altered in which diseases — which were inherited mutations, which changed in the course of a life span,” and so on.
The project began in 1990. “It was not clear we could deliver, but it has worked stunningly well,” he says. “Ten years ago, in April 2003, we completed sequencing the first human genome” — at a cost of $3 billion. In the decade since, experience and constantly evolving technology has meant that the cost of sequencing each human’s genome has come down from $3 billion per person to $3,000 — “though I can give you the sequence of just your genes for only $600,” says Lander. A quip doubtless readily comprehensible to anyone with a modicum of scientific knowledge, this soars a considerable distance above my head.
Possibly registering my rather blank response, Lander returns to basics. He tells me that, like everyone, I have approximately 60 mutations that are unique to me, plus lots of rare mutations, plus lots of common mutations. “Great,” he says. “So now let’s say we’ve mapped you. So what? The challenge is to interpret that map.” This is where we move from the parts of the 747 to the wiring.
“Looking at one person who is suffering from schizophrenia, or has had a heart attack, is no great help, but if I can look at 1,000 or more, I start to see the same mutations. And if I look at thousands or tens of thousands…”
As recently as 2009, he elaborates, “we knew zero of the genes that underlie schizophrenia. Today we know 93.”
Similarly, researchers are able to systematically catalog the fundamental causes of cancer, the mutations that cause lung cancer, those that cause breast cancer, the set of genes that underlie most cancers and those that are particular to certain cancers. “Genome studies have identified 225 genes that are involved in cancer,” he says, and while “that is not the complete list, we can begin to see the end of the complete list. In five years, we’ll have it.”
And once you’ve identified all the relevant genes, and understand how those genes work together in biological circuits, that’s the hard part?” I ask. “Treatment and prevention are the easy part?”
Is he saying that by mid-century we’ll have cured cancer? Again, essentially, Lander’s answer seems to be a yes. “Cancer is very complicated, but finitely, not infinitely,” he says. “It’s a numbers game.”
Essentially yes, Lander responds, and stresses that progress so far is already affecting therapies for cancer and other diseases. “The circuitry is the hard part.” Once that’s done, “being able to make and test drugs that affect the processes may take a decade. But, it’s not the hard part. Once you really know the process, you can usually treat the disease. If you know the pathway of the disease, then 80 percent of the problem is solved.”
This approach, he says, “is now clearly the predominant paradigm in medicine. You can see it is working. Over the long run, it will mean huge progress” in countering disease.
Is he saying that by mid-century we’ll have cured cancer? Again, essentially, Lander’s answer seems to be a yes. “Cancer is very complicated, but finitely, not infinitely,” he says. “It’s a numbers game.” Map its progress, understand how it develops, develop drugs, figure out how to use them in the right combinations and you can knock it out.
What will this revolution do to life expectancy, I wonder? Is he ushering in an era of Methuselahs? Lander says he’s seen a study suggesting that if all cancer is halted, then life expectancy goes up three years on average in the United States.
Not immortality, then? A firm no. “This does not lead to immortality. The goal is that people should die healthy of old age! My interest is not immortality; my interest is to stop people from dying of cancer, Alzheimer’s. And, to help 18-year-olds suffering from inflammatory bowel disease. Immortality is not why we do this, and I’ve not seen any evidence of it being feasible.”
Given the self-evident economic benefit of accelerating this research — notably including the radical reduction in health-care costs — I ask Lander about funding, wanting to assume that the field has all the money it needs. In fact, he says, “we’re nowhere near the limits of how fast we could go. Genetic analysis has gotten a million fold cheaper, making it finally possible to take on large-scale biomedical projects. It has attracted the best generation ever of molecular biologists. And yet the US is cutting funding for molecular research. There’s been a 25% fall in funding for biomedical research in the last decade,” he reports. “That’s crazy. Biomedical research is underfunded by a factor of two or three.”
Whether the revolution is achieved 25 years sooner, or 25 years later, he emphasizes, “it will eventually get done. But there’s so much opportunity right now. Given that opportunity, given the economic benefits of research, and given the potential reduction in health-care costs down the road,” Lander says, the lack of funds is plain foolish. “If Alzheimer’s, for instance, is going to cost a trillion dollars a year in the US, then we should be investing more heavily in steps to avert it,” he urges.
And with that, Lander is up and away, returning to the company of the young scientists who are taking the revolution forward — the pioneers whose work, if we’re lucky, will enable us to die of healthy old age.
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