"I want the country that eliminated polio and mapped the human genome to lead a new era of medicine — one that delivers the right treatment at the right time … . Tonight, I'm launching a new precision medicine initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier."
O-o-kay. Sounds, um, good.
But what the heck did those two vague sentences in President Obama's 2015 state of the union message really mean?
In a briefing a week later, the White House outlined more specifics. In his 2016 budget, the president has included an allocation of $130 million to fund the recruitment of a representative cohort of at least 1 million volunteers nationwide. Their detailed health histories and complete genomic makeup will be documented and pooled electronically.
Another $85 million will underwrite the refinement of this vast database to maintain privacy yet assure that health researchers can mine it to pinpoint the drivers of disease; pharmaceutical and biotech developers can use it to formulate new agents with unprecedented speed and efficacy; and local physicians can tap into curated data marts from their computers or smartphones to extract the specific treatment that will work for this individual patient.
Scaling the Heights
That's a pretty sci-fi prospect.
"It's a gigantic hill to climb," agrees Keith Yamamoto, vice chancellor for research at the University of California, San Francisco. As a key member of the National Academy of Sciences Committee that in 2011 coined the term in a seminal report titled Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease, he was among the principal architects of the new federal initiative.
But, to extend the mountain metaphor, the base camps are already solidly established. And "while the overall challenge is huge," acknowledges Yamamoto, "the good news is that it doesn't have to be realized completely to be effective. There are opportunities for some quick wins."
For example, he notes, next-generation or deep sequencing techniques have dramatically lowered the cost of reading out long swatches of DNA — even the 180,000 protein-encoding "exons" among 3 billion base pairs that comprise the unique genome of a single human being. As recently as 2007, that would have cost $1 million. Today it can be done for $1,000 — less, Yamamoto points out, than the price tag for a lot of tests hospitals and doctors run on patients (and insurers pop for) routinely.
Even now, deep sequencing is performed on every patient with metastatic lung cancer who checks into UCSF Medical Center. Despite the singular terminology, lung cancer is plural: "a family of diverse and complex diseases," Yamamoto explains. Ferreting out the exact DNA signature of the patient's tumor cells can point doctors to the appropriate therapy and enable them to track and adjust the treatment they've prescribed.
"In not very many years," Yamamoto predicts, "we'll be doing full genomic sequencing on everyone who comes through [a hospital] door. UCSF — uniquely, I believe, as an institution — has made the concept of precision medicine the overarching priority in all the ways we operate. We decided we'd essentially build a scale model of the national effort."
The Tip of the Iceberg
But UCSF is far from alone. The Mayo Clinic in Rochester, Minn., and Brigham and Women's Hospital in Boston, just two examples, rely on deep sequence testing of patients with cancer and conditions in which genes play a key role. Those include certain types of cardiovascular disease, pulmonary fibrosis, inflammatory bowel disease and even susceptibility to nosocomial infection by the pathogen Clostridium difficile.
Next-generation sequencing is now part of the initial diagnostic protocol for all cancer patients who come for treatment to BWH, according to Jeffrey Golden, M.D., chair of its department of pathology and head of its multispecialty Precision Medicine Committee. More than 6,000 patients have been beneficiaries of a test that examines 309 genetic indicators — "all actionable," he emphasizes — to focus drug therapy personally rather than generically.
At BWH, says Golden, the immediate thrust is to gather all clinically generated laboratory reports, radiology images, pulmonary function tests, EKGs and the like into a single repository, and then devise algorithms that will let doctors pull out expertly annotated information — integrated with genomic, metabolic, proteomic, microbiomic, exomic and all the rest of the "-omic" inputs derived from and relevant to the particular patient — that will make diagnosis, prognosis and therapeutic intervention more effective and efficient.
"We're defining precision medicine not the way most of the world is defining it," concedes Golden. "Most focus on the genome. The announcement by President Obama is a huge step forward. This is all music to my ears. But it's only the tip of the iceberg. Not everything is going to be solved by understanding the genome."
Pro and Con
That's an argument immediately leveled by critics of the president's announcement. Although his Precision Medicine Initiative appears to enjoy bipartisan political support, in a New York Times op-ed only a few days later, Michael Joyner, M.D. — ironically, an anesthesiologist and physiologist at the Mayo Clinic — derided it as "moonshot medicine."
"We would be better off," he complained, "directing more resources to understanding what it takes to solve messy problems about how humans behave as individuals and in groups. Ultimately, we almost certainly have more control over how much we exercise, eat, drink and smoke than we do over our genomes."
Fred Pelzman, M.D., a New York City internist, was far more enthusiastic.
"Personalized medicine," he noted in Medpage Today, "transforms the patient before us into something other than a member of ‘all patients over the age of 50' and into something more like ‘my patient who, because of his genetics, has some predilection to develop cancer. …[It] can potentially show us this: which patient will develop high blood pressure; which patients are salt-responsive; which patient will respond to which medicine; which patients' blood pressure, left uncontrolled, will lead to end-organ damage down the road."
Under the emerging paradigm, however, "physicians will be more dependent on technology and statistics in the diagnosis and treatment of disease than ever before," warned Philadelphia medical malpractice attorneys Dan Ferhat and Jason Poore. "A duty to review relevant databases may develop, which means that physicians and hospitals will need to ensure they have the most current and advanced technology. Physicians who fail to review the appropriate database before providing treatment could be considered negligent."
As precision medicine matures, they suggested in the Feb. 17 online issue of The Legal Intelligencer, "the more a physician will be tasked with relying on treatment recommendations provided by computer algorithms and less on his or her own professional experience and judgment. This may call for the retention of more information technology employees in medical facilities. Additionally, medical facilities may want to retain epidemiologists and statisticians in order to assess trends in the data, ensure study results are sound and accurate, and assist physicians with questions concerning data-driven outcomes. Retaining geneticists should also be considered in order to verify the results of complex genetic testing. Hospitals could also consider offering training programs on using available databases and related technologies."
Local health care providers, urges Ferhat, "have to try to get out front on this. Not necessarily defensively, but to get the best use of the data."
Coming to Terms
The Mayo Clinic houses its genomics research program in its Center for Individualized Medicine. Pelzman speaks of "personalized medicine." UCSF, BWH and the NIH have embraced "precision medicine." Do they all mean the same thing?
Not exactly, maintains Kristen Bole, assistant news director at UCSF.
"‘Individualized medicine' is the old term for future medicine that would be specifically produced for each individual patient," she specifies in an email clarification. "Some forms of that do exist, such as the ‘cancer vaccines' that use antigens from an individual patient's specific tumor and then train the patient's immune system to fight that tumor or cancer.
"‘Personalized medicine,'" she continues, "was the old standard term that covered both individualized medicine and genomic medicine — that is, identifying the genetic/molecular basis of a patient's specific form of a disease as well as the patient's own genetic background, to identify the best course of therapy for that patient … .
"‘Precision medicine,'" she explains, was adopted to describe "the future of modern medicine in response to the limited common definition of personalized medicine. [It includes] a broad analysis of genetic data from individuals worldwide, as well as clinical information from electronic health records, overlaid with environmental data that could give insights into the root cause of disease. That, in turn, would (a) help bench scientists more precisely identify the molecular (root) causes of disease; (b) help physicians understand why a patient was or was not responding to a certain therapy, or had negative side effects from it; (c) use each patient's response to disease or therapy to better inform other physicians and researchers … and (d) use all of that information to be able to determine up front precisely what form of disease a patient has and what medication would be suited for that patient.
"It also could help inform further drug development," she adds, including those that are "specific to so-called orphan diseases, such as rare forms of debilitating epilepsy, or else to understand why a given drug failed in clinical trials, but worked well for a small subset of patients. It also enables us to test drug compounds that are setting unused on shelves in pharmaceutical companies to see whether they would work for currently untreatable diseases. Clearly, this is a much broader term that encompasses everything from diabetes to cancer to brain trauma, and is the heart of the president's new initiative in precision medicine."
Still an Art
Golden prefers the label "anticipatory medicine."
In a recent issue of Brigham & Women's magazine, he amplified: "You can know who to treat and, more importantly, who not to treat. This will prevent patients from getting a drug, even something as simple as iron, which has definite side effects, because we know they're going to be okay in two months."
"Precision medicine, anticipatory health care, will evolve through academic medical centers," he added in a telephone interview, "but the goal is to develop algorithms that let us be agnostic to where the data [reside]. So the algorithms can be used anywhere. It won't matter whether the physician is in a small, a medium or a large health care system."
What's more, he declares, "I don't believe this will in any way change the art of medicine. It's going to give physicians more time to spend with the patients they need to spend time with. We are all biological organisms. We all have deviations. This will enable physicians to do a better job."
David Ollier Weber is a principal of the Kila Springs Group in Placerville, Calif., and a regular contributor to H&HN Daily.