IEEE PULSE presents

Leroy Hood’s Systematic Approach

Feature March/April 2014

This is the first in a series of features on EMBC 2014, the 36th Annual International Conference of IEEE’s Engineering in Medicine and Biology Society, taking place in Chicago, IL, USA in August.
In the 1970s, as a young faculty member at Caltech in Pasadena, California, Leroy Hood spent much of his time working on developing technologies for analyzing the molecular structure of DNA. In the next 25 years, Hood and his colleagues would go on to develop five key instruments for deciphering DNA codes, including the first automated DNA sequencing machine. Hood would also become the leader of two of the 16 teams working in parallel on decoding different parts of the genome in the Human Genome Project. Early on in all this, one thing became abundantly clear to Hood, who holds both an M.D. and a Ph.D in biochemistry: all too frequently, scientists segregate themselves into separate academic silos, such as molecular biology, chemistry, engineering, and computer science. However, if the most important scientific riddles are to be solved, a more integrated, holistic approach is needed, as happened in the 1980s, when a team with varied specialties was the key to making that first sequencing machine possible.
And so, Hood, in 2000, established the Seattle-based Institute for Systems Biology (ISB), wholly dedicated to an integrated approach focusing on the ever-widening intersection of the fields of biology, medicine, and technology. Hood, who is the founder and head of the Institute and a 2013 recipient of the IEEE Healthcare Medal, will deliver the opening keynote address at the 36th Annual International Conference of IEEE’s Engineering in Medicine and Biology Society, EMBC 2014, in Chicago in August.
Hood recalls being an early advocate for the Human Genome Project, at a time when the vast majority of biologists opposed the project, as either unfeasible or unwise. But the project not only succeeded in its aims, it launched a dizzying progression of ever faster and more inexpensive technology for duplicating that feat.
The most remarkable thing about the hugely ambitious project, says Hood now, is that “it demonstrated explicitly how the needs of biology can lead to transformational new technologies that can, in turn, revolutionize biology.” Seizing upon those tools and others now emerging, he is hoping to catalyze a transformation that could be the most significant yet.
The ISB is dedicated, he says, to exploring a systems approach to understanding and treating disease – and, just as importantly, to understanding and promoting wellness. “We take a global, holistic approach to understanding both health and disease,” he says.
ISB is now plunging into one of its most audacious research projects, one that, if it succeeds, could help usher in an utter transformation in the way health care is delivered, with the potential to provide better care, faster, and potentially at lower cost. The project could lay the foundation for what Hood sees as the next logical paradigm shift in medical care, which he refers to as “P4 Medicine.”
The four Ps, all of which are existing trends in medical care that are at various stages of development and implementation, are these: predictive, personalized, preventive and participatory medicine.
Predictive medicine could rely both on the tools of genetic mapping to build detailed pictures of disease susceptibility or resistance, or variations in response to drugs or treatments, and also on increasing capabilities for monitoring and analyzing physical indicators. That, in turn, can lead to a highly personalized approach both to the treatment of disease, and to preventive measures aimed at maintaining wellness, rather than just responding to disease. And finally, feedback can be provided using today’s portable media to give immediate information about the vital signs they can monitor, and their implications and suggested courses of action, making the whole process highly participatory.
As Hood puts it, this approach “differs from classical evidence-based medicine by being predictive rather than reactive, focused on the individual rather than on averages, focused on wellness much more than disease, and creating virtual data clouds for each patient, and integrating this data.”
Hood said recently, in accepting one of his many awards, that his vision for P4 medicine is that these virtual clouds of data points “will surround each patient and that we will have computational tools to reduce that enormous data dimensionality to simple hypotheses about health and disease, and to sculpt these phenomena, with exquisite specificity, for each individual.” And that, he says, would unleash a transformation in healthcare.
Among other things, he says, this will provide enormous new opportunities for the development of products and services that could launch significant new companies, and transform some older ones. It will also enable individuals, armed with voluminous data on their own history and prognosis, and with access to networks of people in similar situations through social networking and other media, to have an unprecedented degree of informed control over their own treatments. And it provides some real hope for turning around the rapid escalation of healthcare costs—and opening up its benefits to populations that are presently only marginally served by the advances of modern medical technology.
Hood, who has racked up over 36 patents, 100 awards, and 750 published papers, is not just making speeches about this radical rethinking of health and wellness. He is putting the resources of his Institute—and hoping to attract much more—toward launching a pilot project for what could become one of the most comprehensive studies of human health and disease ever attempted. If the project achieves even part of its ultimate planned goal, it could provide an unprecedented vein of rich ore for data miners to sift through for many years to come.
The project was launched March 2014, in a nine-month pilot for what ultimately could be a decades-long longitudinal study, comparable in scope to the Nurses’ Health Studies, which encompassed over a hundred thousand subjects over a span of decades. But the amount of data to be collected in this new version, thanks to the possibilities unleashed by technological advances, will go far beyond anything those studies could have imagined.
This first phase is called the Hundred Person Wellness Project. It began by producing a complete genome map for each of its hundred volunteers—some of whom are individuals, and some entire families participating together. Sequencing technology has already advanced so far—in part thanks to the automated sequencing technology that Hood pioneered decades ago—that such individualized analysis is now feasible. What’s more, these devices have been advancing at the kind of Moore’s Law rates familiar in the electronics world, and as the study grows, Hood believes, the prices for such individual genomes will become ever-more affordable.
After that initial sequencing, and a battery of basic tests of blood, urine, saliva, and stool to set baseline profiles for each patient, they will then wear unobtrusive devices to monitor some parameters, such as pulse, respiration, and activity levels, over long periods of time. Other parameters will be measured once every three months, including unusually comprehensive blood tests monitoring over 100 parameters.
Nothing about this experiment will be blind: Patients and their health care providers will have access to any and all information, any time they want. And patients will be welcome—in fact, encouraged—to make changes to their diet, exercise, and other lifestyle factors in response to that information. Some other researchers have criticized this flouting of the traditional approach of research with control groups and random assignments, but Hood feels this is an essential part of the new approach that he espouses.
After the initial pilot study of 100 people, Hood hopes that phase two will be a one-year study with 1,000 subjects, followed by 10,000, and ultimately a 100,000 person study for 25 years. The hope is that, by monitoring people who are healthy today over a long enough period during which many of them will end up developing a variety of disease conditions, the continuous monitoring of so many parameters will begin to reveal patterns of precursor signals that could be used to predict disease conditions—potentially far earlier than is now possible.
“Understanding those early indications, enabling early diagnostics, could change the trajectory of diseases very early on. That alone could potentially save hundreds of billions of dollars in healthcare costs,” Hood says.
But the essence of Hood’s drive to get this project into full operation lies in the potential transformation in the ways patients and physicians participate in the delivery of healthcare, and a revolution in the degree to which individualized information can improve health outcomes for all. Having already lived through and nurtured several revolutionary advances in biomedical technology, he is eager to help launch what he hopes could be the most transformational changes yet.

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