February 17 2011
Practical genomics medicine is here now, not years away, if only you will open your eyes and look
The pursuit of the perfect end-state can drive a belief that there are limitless opportunities for improvement. Although perfection can never be fully realized, its pursuit can propel achievement of value and excellence; that is the rationale behind the Baldrige and other quality awards. The pursuit of perfection can be distinguished from ‘perfectionism'. Perfectionism is retrospective—hind-sighted and judgmental in its point of view. It devalues what has already been done because it is not perfect. By contrast, the pursuit of perfection is prospective and nonjudgmental. It asks the question, What choices and investments should we make today to move closer to the perfect end-state?
It was with these thoughts in mind that I read with dismay the post by Katherine Hobson in the Wall Street Journal health blog last week. In it, she says that real benefits of genomics and personalized medicine are still many years away, citing just-published papers in the prestigious British journal Nature. This is a nasty rumor; a cliche; a bad meme that keeps coming back like a bad penny.
In one of the Nature articles, Eric Green and Mark Guyer of the U.S. National Human Genome Research Institute write that, to improve the effectiveness of health care, knowledge has to progress from understanding the structure of genomes, to understanding their biology, to understanding the biology of disease and then advancing the science of medicine. They make it sound as if none of those has happened yet, and as if all of them have to be 100% complete and perfect before any profound improvements in health can happen.
That simply isn't true. Partial understandings, so long as they are validated and reproducible in multiple independent studies, can yield—and have already yielded—valuable practical everyday results and improvements. Green and Guyer assert that five things are “required” or imperative if genomic medicine is to be able to make major improvements in health:
- Making genomics-based diagnostics "routine", much like a blood panel is now.
- Defining the genetic components of "diseases of all types" through study of “upwards of a million patients.”
- Comprehensively characterizing cancer genomes to understand what molecular pathways are altered in different subtypes of cancer.
- Creating practical ways to keep physicians and patients up to date on the latest knowledge about genetic variants and their association with disease or treatment response.
- Investigating the role of the human microbiome to see what role the bacteria in our gut and elsewhere play in our health and disease.
Number (1) is not true. There are several thousand laboratory tests that are broadly available and that are not part of CBC and chemistry blood 'panels', and yet no one would say that all of those other tests produce no public health value, nor would anyone say that the only tests that produce public health improvements are the few general screening panels like CBC and Chem21. Genomics tests, including direct-to-consumer SNP microarray tests, are readily available now and have numerous important practical uses.
Number (2) is not true; you do not need to study all disease-types in order to begin to deliver major benefits to the health of large percentages of the population, nor is it necessary to study a million or more patients. Statistically significant and reliable and actionable effects can be discovered in relatively small cohorts of people if the gene variations' statistical effect-sizes is large, as it is in quite a lot of instances (have a look at Ginsburg's and Willard's books, links below).
Number (3) is not true; cancer is not the only high-value category of chronic health conditions and, besides, it is not essential to comprehensively understand “all” of the signaling pathways before major safety and effectiveness benefits are achievable. Green and Guyer are arbitrarily elevating a 'nice-to-have' into a 'must-have'.
Number (4) is not any more or less salient for applied genomics and personalized medicine than it is for any other medical practice. If some doctors choose to remain ignorant and refuse to avail themselves of the journal articles and other materials from which they can learn about practical genomics testing and applications, consumers who are able to do so will vote with their feet and seek care from other doctors who are expert and up-to-date. The free market does work, eventually—even in health care, even in health care with genomics-based choices and second-opinions.
Number (5) is another 'nice-to-have', true in its own way but hardly a pre-requisite to genomics's delivering major improvements in health.
Adam Fein and other WSJ commenters object to Hobson's blog post's and the Nature articles' belittling the scope and value that genomics already is delivering today. As evidence of practical value that is real and already reasonably pervasive, they reference the FDA's list of more than 60 drugs and the genomic biomarkers that already are fundamental to safe and effective pharmacogenomics-based prescribing every day. As a contributor to new discovery datamining-based research in applied pharmacogenomics, I can tell you that the number of drugs for which there are today important, practical, pharmacogenomics-based means to personally tailor the dose or selection of drug is much, much larger than FDA's list—more than 300 medications. The fact that FDA's list only has 60 or so medications on it is a reflection of how behind-the-curve current FDA leadership is. Green's and Guyer's asserting that improvements have only so far materialized "in a few circumstances" is simply incorrect.
Katherine Hobson responded to Fein's comment by saying that her remarks were meant to address only Green's and Guyer's “profound improvements in the effectiveness of healthcare” statement, essentially asserting that she meant only to speak about improvements in treatments' effectiveness and not about improvements in safety. She implies that the only improvements worth caring about are ones that concern treatments' effectiveness. However, not many consumers and clinicians and pharmacists and health plan and public health leaders would agree with such a narrow definition of value. Not many Wall Street analysts would accept Hobson's narrow definition of value either.
But the practical applied genomics material exemplified here in the Cerner blog stands as its own sort of rebuttal to Hobson's and Green's and Guyer's claims. These things do not require space-program-sized budgets or massive organizations or national data repositories that are so far only in formative stages. They just require small-scale intense collaboration between research groups and companies who are working on the same topics--the same conditions and treatments and populations and genes.
In another of the Nature journal articles that prompted Hobson's blog post, Eric Lander at MIT's Broad Institute opined that journalists chiding genome scientists "for not yet having cured most diseases" is a spurious feature of contemporary journalism where expert pundits pander to a market that craves sensationalism and lacks any incentive to value incremental progress and small milestones. That may be true. The media companies publish what sells.
A perfectionistic stance that only recognizes or acknowledges value or bestows approval when some ultimate end-state has been reached is politically in league with the status quo, and, as Lander says, it manufactures its own sensation. It is like a pundit chiding ongoing efforts to reduce hunger or poverty and denying that those have any value until not a single person is any longer in need--a goal that has a very slim odds and a very long time-horizon. Pundits like Ms. Hobson want to persuade readers that the genomics community's promise of 10+ years ago has been broken, that those who have been involved in touting the promises and potential of genomics have been disingenuous, that the gold mine is a "bust", the pay-off nowhere in sight, and the matter merits no further interest on your part.
Democratic theory holds that journalism should be a rigorous watchdog critiquing those in power and who want to be in power; should discern truth from lies; and should present a wide range of informed positions (McChesney, p. 25). Ms. Hobson's WSJ blog post does none of those.
Is this Hobson's and Green's and Gueyer's Gladwell-esque expectation of a fulcrum or 'tipping point', expecting applied genomics's going 'viral'? Maybe so. Given the current economy and insurance coverage and regulatory climate plus the time it will take for busy doctors to get knowledgeable and tool-up, it's quite unlikely to play out like that.
But the quiet transformation is already underway, and much of it is being driven by consumers, not doctors. Patients and family members are powerfully motivated to find out what the latest tests and information are that are pertinent to the diseases that affect them, even if their [present] doctors are not so motivated. If necessary, consumers pay for the tests out-of-pocket and move their portable electronic health records and switch to doctors who can and will respond to their needs and their information.
Guyer and Green do note that “electronic health records systems capable of handling family history and genomic data are required to fully utilize genomic information for patient care.” They then assert that all existing clinical informatics architectures are largely incapable of storing genomics data in a way that allows the information to be searched and annotated and shared. But Cerner Millennium Helix and related systems do this today.
"Genomics will only achieve its potential to improve health when the advances it engenders become accessible to all," they say. What idealistic planet do Green and Guyer live on? Theirs is a noble wish, surely. But can they name a single health technology or service that is accessible to all? Even one? No, they cannot. Arguing that genomics and personalized medicine will not have delivered important value or "achieved their potential" until all diseases are cured and universal free care is plentiful everywhere is distinctly unhelpful.
The era of grossly asymmetric power in the doctor-patient relationship is ending. The dawn of the era of consumer-driven health more or less coincides with the dawn of applied genomic medicine. It is not surprising that stalwart "experts" of the status quo don't yet realize that the tide has already turned. The fact is, not every improvement has to be associated with block-buster products, multi-billion-dollar brick-and-mortar corporations, and a market that is abnormally consolidated through centralized federal regulation. Some improvements involve long-tail services, rendered by many tens of thousands of licensed health consultants serving myriad market segments and niches of patients and families who have similar conditions and genetic markers and who are connected by health-centric online social networks and integrated genomics-enabled EHR systems, plus affordable intellectual property for genomics decision-support that can be delivered on virtual network-based media anywhere in the world.
In short, applied genomics medicine isn't a Gladwell-esque fad. And it is not a mythical “El Dorado” for us, arrival deferred to some uncertain year in the distant future. For many consumers and for a large number of important common health conditions, it is present reality. Status quo-loving pundits and perfectionistic experts who are unable to see this, don't let the door hit you on your way out.
Douglas McNair, MD PhD, Senior VP, is one of three Cerner Engineering Fellows and is responsible for innovations in decision support and very-large-scale datamining. McNair joined Cerner in 1986, first as VP of Cerner's Knowledge Systems engineering department; then as VP of Regulatory Affairs; then as General Manager for Cerner's Detroit and Kansas City branches. Subsequently, he was Chief Research Officer, responsible for Cerner's clinical research operations. In 1987, McNair was co-inventor and co-developer of Discern Expert®, a decision-support engine that today is used in more than 2,000 health care facilities around the world. Between 1977 and 1986, McNair was a faculty member of Baylor College of Medicine in the Departments of Medicine and Pathology. He is a diplomate of the American Board of Pathology and the American Board of Internal Medicine.
Anderson C. The Long Tail: Why the Future of Business is Selling Less of More. Hyperion, 2008.
Anon (editors). Best is yet to come. Nature 2011;470:140.
Borden S. Journalism as Practice. Ashgate, 2007.
Christians C, et al. Normative Theories of the Media: Journalism in Democratic Societies. Univ Illinois, 2009.
Ginsburg G, Willard H, eds. Essentials of Genomic and Personalized Medicine. Academic, 2009.
Ginsburg G, Willard H, eds. Genomic and Personalized Medicine. Academic, 2008. (2 volume set)
Hamilton J. All the News That's Fit to Sell: How the Market Transforms Information into News. Ashgate, 2006.
Hernandez L, ed. Diffusion and Use of Genomic Innovations in Health and Medicine. IOM NAP, 2008.
Hobson K. Genomics won't lead to big health-care improvements for many years. WSJ Health Blog, 09-FEB-2011.
McChesney R. The Political Economy of Media: Enduring Issues, Emerging Dilemmas. Monthly Review, 2008.
Riley W, et al. Defining quality improvement in public health. J Public Health Mgt & Practice FEB-2010.
Suttles G, Jacobs M. Front Page Economics. Univ Chicago, 2010.