Richard P. Lifton

he has spent a career finding connections between diseases and the mutated genes that cause them. After nearly 25 years at Yale, Richard P. Lifton moved to Rockefeller to become president last fall. We asked him to share his outlook on the present state of bioscience, and his visions for the future.

What’s the promise of bioscience at this point in history? We’ve learned a tremendous amount about health and disease over the past century, yet it seems we continue to fight many of the same battles.

We are in an extraordinary time of scientific opportunity. With the sequence of the human genome in hand, we have, for the first time, a bounded problem. We have the ability to understand what each gene is doing in the context of a living human being, what happens when it is mutated, what happens when it is turned on or off.

This is a galvanizing realization. Linking mutations in each gene to human traits—singly and in combination with environmental factors and other genetic variants—will set the stage for us to understand biochemical and physiologic mechanisms that link genes to specific traits and disease susceptibilities. The knowledge that emerges from this work will define our opportunities to develop preventative and therapeutic strategies for disease for the next 50 years.

This is in many ways a reflection of the availability of new technologies. How important is the development of tools to the practice of biology?

It’s not just the development of technology, it’s the convergence of multiple technologies, and it’s the ongoing evolution of those technologies, which is continuing at an extraordinary pace. We now have large data sets—in many fields, not just genomics—that are richly informative for understanding everything from biological structures and their interactions with small molecules to complex network interactions, at scales ranging from single-cell metabolism to population dynamics. It’s increasingly clear that advanced computation is playing a critical role in the development of life science.

Even a decade ago there were many branches of life science in which one could get through an entire career without ever relying on serious computation. Today, trainees in many labs spend as much time analyzing large data sets as working at the bench, a rapid and surprising transformation.

How does Rockefeller best contribute to this type of scientific exploration?

Historically, Rockefeller has been remarkable for bringing together truly brilliant scientists from diverse disciplines in a relatively sparsely populated environment, which has long promoted interactions across disciplines. Technological advances have now eliminated many of the former boundaries between disciplines in science, and most scientists have to be comfortable working in many historically distinct areas. As a result, the rest of the world is coming to some of the collaborative models that we at Rockefeller have done very well for some time.

How can academic institutions like Rockefeller help ensure that science will generate new therapies and other useful innovations?

One of the reasons our country has invested heavily in the life sciences is the recognition that goes all the way back to Rockefeller’s founding in 1901: that understanding the fundamental causes of human maladies provides the best opportunity for devising effective approaches to prevent or treat disease.

So coming from that premise, fundamental discovery, which includes much of what we do at Rockefeller, need not have immediate clinical application. Understanding critical principles of biology lays the foundation from which normal and disease biology are subsequently understood. Nonetheless, our collective responsibility as scientists doesn’t stop with discovery in basic science. We currently rely largely on a system in which academic institutions do basic science, and translation most commonly occurs in industry. Unfortunately, the assumption that industry fully understands the implications of work in academic labs is not always well-placed. Many outstanding ideas will lack a champion in industry, and their potential will remain unfulfilled. This motivates increased efforts within academia to actively promote potential translational avenues, either alone or preferably in collaboration with industry collaborators.

“With the sequence of the human genome in hand, we have, for the first time, a bounded problem. We have the ability to understand what each gene is doing in the context of a living human being.”

There are different ways that clinical translation can happen, and one can argue about where to draw the line as to how far an academic institution such as ours ought to go down the path toward commercialization. Establishing the clinical potential of a target—for example by showing the impact of a small molecule that modulates activity of a gene product or pathway—may often be sufficient to promote a target’s in-depth exploration in industry. Programs like those now in place at Rockefeller are well-positioned to move interesting ideas into projects that will become tomorrow’s new therapies.

What drew you to science?

I grew up in the space age, and science and technology were important forces in shaping my early thinking about the world. Also, like many young people at that time, I heard John Kennedy’s appeal to altruism. He promoted thinking about using science to advance humanity.

But the farther I got into my medical training, the more I became interested in the intersection of medicine, science, and technology. Science is the surest way to illuminate the mysteries of health, well-being, and illness. Making fundamental discoveries about how life works remains a profoundly moving experience, and the clinical impact of some of these discoveries only deepens the experience. In a complex world with often-conflicting motivations, science’s commitment to uncovering enduring truths provides a refreshing clarity of purpose. I can’t imagine a greater privilege than exploring—and occasionally solving—these mysteries, and having this new knowledge benefit humanity.