Two Generations of Geneticists, Two “Precision Medicine” Wish Lists

Xconomy Seattle — 

In late 2012, President Obama awarded Leroy “Lee” Hood the National Medal of Science for a lifetime of achievements, including the invention of machines that made the historic Human Genome Project possible.

So when Obama announced yesterday a “precision medicine initiative”—something that would surely require ever-deeper knowledge about the personal genetic differences that influence health and disease—I asked Hood for his thoughts.

He didn’t mince words. “It’s so vague and fuzzy, I don’t know what it means,” Hood said this morning from Southern California.

More details should follow, but not at this early date. (The National Institutes of Health referred all questions to the White House, which didn’t return inquiries.)

Hood would like to see an actual entity emerge, something akin to the original publicly funded Human Genome Project, which was run by Francis Collins, now the NIH’s director. “The Human Genome Project provided crystal-clear focus on which technologies to develop,” said Hood. “With this, there are a lot of decisions to make whether it’s to be focused and coherent, or if it provides a little something for everybody.”

That’s a good point. Precision medicine means many things to many people (Hood prefers the term “personalized”). An initiative under that rubric could extend widely to all corners of modern medical research. “Precision medicine is just saying ‘we’ll take measurements’—and you can measure everything,” said Hood, who is president of the Institute for Systems Biology in Seattle.

As I noted earlier today, the NIH has put precision medicine front and center for some time now and provided this definition in its latest budget proposal: “Precision medicine refers to the tailoring of treatments to the individual characteristics of each patient… NIH undertakes the challenges of precision medicine through myriad strategies.”

If a focused initiative emerges, Hood would like to see better computational tools to determine when disease begins. He’d also like to see the smart phone, or some offspring of it, become the main diagnostic tool. Tissue-on-a-chip technology, which the NIH highlighted in its most recent budget as part of its focus on precision medicine, is also “extremely promising,” he said.

Much of Hood’s wish list dovetails with his current mission of kickstarting a decades-long “longitudinal” comprehensive survey of the state of health of up to 100,000 people. (I interviewed his co-lead investigator, Nathan Price, about the project last summer; they’re just now analyzing data from the first 100 volunteers.)

For ideas about which nitty-gritty bioinformatics tools could use more funding to push faster toward better treatments for complex diseases like diabetes and cancer, I asked David Mittelman. He’s a geneticist, entrepreneur, and chief scientific officer of Tute Genomics in Provo, UT. He mentioned three areas:

—Improvements in the identification of complex mutations such as copy-number variations and splice variants.

—More experimental data on the consequences of genetic changes. Mittelman referred to a project funded by the NIH and highlighted on Collins’s blog last year. The lead researcher is Jay Shendure of the University of Washington in Seattle.

—Better standards, performance testing, and calibration of the variety of sequencing methods and processes available. “Stuff like [this] generally requires government funding,” said Mittelman, whose previous startup, Arpeggi, built a free community-based test site for next-generation sequencing. “We can’t have personalized medicine if every instrument or clinical group gets a different answer.”

If Obama’s initiative turns out to be not a Human Genome Project 2.0, or something with similar focus, but a repackaged call for more NIH funding—“a little something for everybody,” as Hood says—that would be welcome, too, by Hood and countless other researchers.

Except for the brief spike from the post-crash stimulus package, NIH funding has been flat for years, which factoring for inflation, actually means NIH funding has decreased for more than a decade.

The presidential push could also benefit a bipartisan Congressional initiative called 21st Century Cures, cosponsored by Reps. Fred Upton (R-MI) and Diana DeGette (D-CO). Upton is chair of the House Energy and Commerce committee and wants to introduce legislation early this year. Upton and DeGette have convened hearings, discussions, and roundtables in Washington and around the country, but there’s still little indication what the legislation will entail.