A Vision for Personalized Medicine

Leroy Hood has been at the center of a number of paradigm shifts in biology. He helped to invent the first automated DNA sequencing machine in the 1980s, along with several other technologies that have changed the face of molecular biology. And in 2000, he founded the Institute for Systems Biology, a multidisciplinary institute in Seattle dedicated to examining the interactions between biological information at many different levels, and to moving forward a new perspective for studying biology. The next revolution he plans to help shape is in medicine, using new technologies and new knowledge in biology and informatics to make its practice more predictive, preventative and personal.

Hood says that with each of the major transitions he’s been a part of, he has faced skepticism. The human genome project, for example, had many naysayers. But he says the best way to overcome doubts is with results. To that end, Hood has founded a startup called Integrated Diagnostics, which is developing cheap diagnostics that could be used to detect diseases at earlier, more treatable stages. He has also developed a partnership between the Institute for Systems Biology and Ohio State Medical School, where he hopes to show how combining existing medical and genomics technologies can affect the practice of health care today.

Hood contends that digitizing medical records–the health-care industry’s major push at the moment–is just one small part of the informatics overhaul the field needs to undergo. And pharmacogenomics–the practice of using an individual’s genetic makeup to choose drugs –provides only a limited example of the potential power of personalized medicine.

TR: How do you see the future of personalized medicine?

LH: I think personalized medicine is too narrow a view of what’s coming. I think we’ll see a shift from reactive medicine to proactive medicine. I define it as “P4” medicine–powerfully predictive, personalized, preventative–meaning we’ll shift the focus to wellness–and participatory. That means persuading the various constituencies that this medicine is real and it’s here. Physicians will have to learn a medicine they didn’t learn in medical school.

TR: What new technologies will drive the revolution in medicine?

LH: Individual genomes will become a standard of medical records in 10 years or so, and we will have the power to make inferences [about an individual’s health] when combined with phenotypic information. Then we can begin to plan strategies for individual health care in ways we have never done before.

Nanotechnology approaches to protein measurement–such as measuring 2,500 proteins from a drop of blood–will also be important. We want to develop tests to asses 50 organ-specific proteins from 50 organs as way of interrogating health rather than disease.

The third technology that is going to be transformational is the ability to get detailed analysis from a single cell. We can analyze transcriptomes and RNAomes, proteomes and metabolomes [the collection of transcribed genes or messenger RNA, total RNA, proteins and metabolites, respectively, in the cell]. That information will reveal quanti cellular states that will say lots about normal mechanisms and disease mechanisms. For example, we are doing an experiment now where we take 1,000 cells from glioblastomas [a type of brain tumor] and select transcripts from each of those cells. We’re discovering interesting new things about what constitutes a tumor.

The final driver is going to be what I generally call computational and mathematical tools, the ability to deal with data dimensionality that is utterly staggering. If we have patients in 10 years with billions of data points, being able to compare that with individual genotype-phenotype correlations will give us deep and fundamental new insights into predictive medicine. But the challenge is, where will we get the cycles to make those computations and where will we get storage for all this data?

LH: Medicine is going to become an information science. The whole health-care system requires a level of IT that goes beyond mere digitization of medical records, which is what most people are talking about now. In 10 years or so, we may have billions of data points on each individual, and the real challenge will be to develop information technology that can reduce that to real hypotheses about that individual.

TR: Will there be consequences beyond medicine?

LH: I think the P4 medicine revolution has two enormous societal consequences. It will absolutely transform the business plans of every sector of health care. Which will adapt and which will become dinosaurs? That’s an interesting question, but it will mean enormous opportunities for companies.

I also think it will lead to digitization of medicine, the ability to get relevant data on a patient from a single molecule, a single cell. I think this digitization in the long run will have exactly the same consequences it has had for the digitization of information technology. In time, the costs of health care will drop to the point where we can export it to the developing world. That concept, which was utterly inconceivable a few years ago, is an exciting one.

TR: What will be the challenges in implementing this vision of medicine?

LH: I think the biggest challenges will be societal acceptance of the revolution. We are putting together something we call the P4 Medical Institute. The idea is to bring in industrial partners as part of this consortium to help us transfer P4 medicine to the patient population at Ohio State University, which is both the payer and provider for its employees. We plan to announce further details of this project in two or three months.