Lee Hartwell would be excused if he wanted to rest on his laurels at the age of 70 and enjoy the sort of retirement that you read about in personal finance magazines. Instead, he’s now setting out to do the most ambitious things of his career. He wants to change the way the world thinks about personalized medicine, help make the world a more sustainable place, and improve how children learn about science.
“I’m not a person who looks back,” Hartwell says. “I don’t tend to miss things. I look upon each stage as an experience and a learning opportunity. I came into this to learn about medicine, and it was an enormously powerful experience. Now it’s time to move on and use that knowledge.”
Hartwell made his name as a basic scientist; his fundamental discoveries about cell processes in yeast earned him the 2001 Nobel Prize. Then as the president and director of the Fred Hutchinson Cancer Research Center in Seattle, he oversaw 13 years of growth and integration between basic science, clinical practice, and public health. Now that Larry Corey has been tapped as his successor, Hartwell is preparing for his next major challenge: chief scientist of The Biodesign Institute at Arizona State University, starting Oct. 1. He told me about his vision for the next chapter of his career when I recently visited his office in Seattle.
His vision is to create a new wave of precise and predictive diagnostic tests, based on systematic analyses of all sorts of proteins in the blood that could be early warning signs of disease. These tests will enable physicians to answer basic problems, like determining when an emergency-room patient’s chest pain is just garden-variety or an early warning sign for a heart attack or stroke. Armed with that kind of individualized knowledge, physicians would be able to make more informed decisions about patient care, saving resources that are currently wasted.
Many people see this as essential to fixing healthcare in the future, but Hartwell is looking through an even wider societal lens. He talks about how this more efficient model of healthcare will help the world focus resources on global sustainability, like clean air, clean water, or as he puts it, “maintaining the planet in a way that will continue to support human life.” One part of that vision, for which he plans to devote half of his time, will be about improving K-8 science education. Done right, it could help foster a new generation of more scientifically literate citizens who will help support those initiatives.
One of Hartwell’s peers, Leroy Hood of the Institute for Systems Biology in Seattle, said he expects big things from Hartwell’s new mission. Hartwell, he says, “approaches the interrelated problems of personalized medicine and diagnostic biomarkers with creativity, originality and an amazing ability to catalyze significant strategic partnerships.”
Hartwell’s journey in personalized medicine, and rallying partners with complementary skills, started to take form about a decade ago, in his third or fourth year as president of the Hutch. As a basic scientist, he didn’t really know much about the practice of medicine. When he started digging into it, and figuring out how to connect the dots between science and medicine, he saw some huge gaps that need to be filled. By about 2015, U.S. healthcare spending is projected to reach $4 trillion a year, or about one-fifth of the nation’s gross domestic product. About 80 percent of that is spent on late-stage treatments of people who are severely ill, with only a tiny fraction devoted toward predictive or preventive medicine.
“One of the conclusions I came to about three years into the job, what was limiting in medicine was the evidence,” Hartwell says. “It’s the ability to know in detail what risks people have for disease, what disease they have, especially at an early stage, and how to respond. The ability to predict our actions in medicine is very, very poor. The system is all oriented toward late-stage intervention with therapeutics.”
The Human Genome Project, completed in 2003, was billed as a way of helping usher in the era of predictive, personalized medicine. It hasn’t yet materialized, and Hartwell says he’s not exactly a fan of most genomics companies. While the genomic code can be useful for how individual cancers differ, and should be treated differently, he’s more optimistic about scientists’ ability to glean information from a systematic review of the proteins in our blood, the complex 3-D molecules made from the information encoded in DNA. Many of the efforts to date have focused on finding a single protein “biomarker” that’s correlated with disease. That approach is “too narrow,” Hartwell says, and doesn’t fully account for the complex symphony of proteins that lead to disease. Scientists and clinicians will be better off investing years of effort on a systemic analysis of biomarkers that could lead to truly predictive early diagnostic tests, he says.
“What are the important questions they need to answer that would improve outcomes and reduce the cost of medicine? There’s enormous potential for controlling medical costs,” Hartwell says.
This effort is seeded with a $35 million contribution from the Virginia G. Piper Charitable Trust. That was one of the main elements that attracted Hartwell to move to Arizona State University in Tempe, AZ, he says. But it’s about more than just one big donation, he says. Arizona is also home to an important collaborator, the Translational Genomics Research Institute (TGen) in Phoenix. Arizona State also has strong departments in global sustainability, and science education, Hartwell says. He will continue to collaborate on his personalized medicine work with a number of key faculty at the Hutch in Seattle. And while Hartwell and his wife, Theresa Naujack, have found a new home in Arizona during the academic year, they still plan to spend their summers in Seattle, close to the faculty they will be working closely with at the Hutch, Hartwell says.
Much of Hartwell’s time is being spent traveling the world in a quest to garner support for this systematic research for personalized medicine. Shortly after our interview, Hartwell said he was getting on a plane to travel to Taiwan, where the government has expressed signs of support. He’s been spending time meeting with government officials in China, India, Singapore, Canada, and Luxembourg. The common thread is that they have interest in containing healthcare costs, and in potentially supporting research into diagnostics that catch health problems early, before the costs get impossibly steep.
The diagnostics industry isn’t really part of the equation just yet. The business model for diagnostics in the U.S., given the many years and the millions of dollars required for clinical trials, combined with the low prices charged for today’s tests, Hartwell says. Most companies today are forced to focus on a single, specific marker which might provide a faster and more realistic path to the marketplace, but doesn’t provide the full set of information doctors need, he says. So this is an effort that will have to spend many years in the nonprofit sector, backed by governments and philanthropists, before venture capitalists, entrepreneurs, and big diagnostic companies can get serious about implementing the new tools in a broad commercial strategy.
“We need to go a lot further in the nonprofit sector until we get a very well defined panel of markers that we know is providing us information around a very specific clinical question,” Hartwell says. “Once we get to that point, then it’s appropriate to hand it off to the commercial sector. I don’t know whether that handoff will be around the identity of the biomarker panel or whether it will be around the platform or device that makes the measurement. I see the commercial sector developing the devices and platforms.”
The research initiative isn’t really about creating a brand new institute, like the name Biodesign Institute suggests, but it will be a collaboration of faculty with different forms of expertise to contribute. In Arizona, Josh LaBaer, a proteomics expert formerly of Harvard Medical School, has been recruited along with Hartwell to the ASU personalized medicine initiative. Bioengineering professor Alan Nelson is bringing his expertise in spotting circulating tumor cells. John Chaput, a biochemist, adds his know-how of peptides, proteins, and nucleic acids can be engineered with certain attractive properties, like binding with specific targets on cells. Michael Birt, a health policy expert Hartwell has worked with for years in Seattle, will examine health policy implications.
At the Hutch in Seattle, health economist Scott Ramsey will add the economics dimension. A long list of faculty from a younger generation has also been enlisted. The group includes Mandy Paulovich on proteomics, Muneesh Tewari on microRNA, William Grady on colon cancer, Jason Chien on lung cancer. And Hartwell is also maintaining close ties to Sage Bionetworks, the nonprofit effort housed at the Hutch, that is seeking to spark an open source IT-style movement for greater collaboration in biology.
There are still some missing pieces of this personalized medicine puzzle that Hartwell is looking to fill. He is looking to add expertise in molecular imaging to provide another layer of information on top of what others are gathering at the level of genes and proteins, to help strengthen the connections between what’s going wrong at a basic biological level, and how it manifests itself in real-world medical settings. Getting more of that kind of information will help the scientists confirm earlier signals, and allay some fears that physicians might go overboard with treating people who have an early warning sign that might actually be a false alarm.
Finding the correlations in the vast pools of data that will come from gene sequences, protein analysis, and molecular images all depends on continuing advances in information technology, Hartwell says. But when I asked him about the potential of IT to move these fields of biology forward, Hartwell turned the question back to IT’s impact on education. This came up a couple times in our conversation, as if Hartwell wanted to make sure I didn’t forget how central science education is to his next career.
He insists it’s not something he’s doing on the side, but something he’s spending half his time on.
“There have been a lot of good experiments in science education at the K-12 level, but they are not sustainable, and not scalable. That’s what we need to do,” Hartwell says. “We need to figure out how to do good things in a classroom, and sustain them beyond a single individual and scale them to the world. I think IT is going to completely change education. I’m not sure that in 10 years or 20 years there will even be classrooms as we now know them. Our whole human life is being changed by IT in an incredibly dramatic way.”
Before I left Hartwell’s office, I had to ask the touchy question about his personal health at the age of 70, and whether he’ll be around to see some of his vision implemented. At least in conventional perceptions of aging, 70 sounds old to many people.
But Hartwell still has the lean build and graceful athletic gait of a far younger man. He could easily pass for 55. One of the ways he stays fit is by bicycle commuting. The day of our interview, his mountain bike was sitting there in the office, which he has regularly used to commute 5 miles each way from home to the Hutch. It takes him about a half hour, he says.
“It’s just right, an hour of riding every day is the right amount of exercise for me. I love it. I hate getting in a car,” Hartwell says. He adds: “I feel great, no health problems.”
How long can he imagine pursuing this new goal of advancing personalized medicine, global sustainability, and science education? Hartwell didn’t answer with a specific number. But he suggested it could be a long time.
“I think I’ll always be doing things I find interesting. It doesn’t seem like work to me,” Hartwell says. “I don’t play golf. I can’t imagine not having some interesting work to be doing. I’ll do it as long as I can.”