The previous post on this blog took issue with the view (expressed by a UK government advisory committee) that we are witnessing a “genomic revolution”. Paul Martin and I suggested instead that what we are witnessing is in fact a gradual process of incremental and additive change entirely consistent with the general trend in diagnostics innovation in the twentieth century.
In this post I want to elaborate on that view by way of commenting on a couple of things – a new report on personalised medicine from United Healthcare and an interview with Matt Posard, Illumina’s senior VP for Translational and Consumer Genomics.
The viral marketing of personalised medicine?
The United Healthcare report is a very useful piece of research because it puts hard figures on the hype surrounding personalised medicine. The most interesting part of the document is the data on trends in testing, the volumes of tests used, the costs associated with that volume, all broken down by test type. The report uses three categories: infectious diseases, cancer and inherited conditions/other. For me, the major take-home from these figures is the confirmation that in terms of test volume (defined in the report as number of test procedures per 1,000 UnitedHealthcare members) the big growth area for the molecular diagnostics industry has not been the applications which have been attracting the greatest headlines (and the largest amount of ELSI research) i.e. companion diagnostics, susceptibility testing and rare disease genetics. Infectious disease testing far outstrips these applications.
In other words, the molecular diagnostics industry enjoys its status as the fastest growing sector of the diagnostics industry because it has found a quicker, cheaper and more accurate way of diagnosing infectious disease than traditional pathology techniques – thus far the viral (or microbial) genome has outpaced the human genome in the space of clinical practice. Since the report cites 1% growth rates for cancer testing but 9% growth rates for infectious disease testing and for inherited conditions/other testing, this is a gap which is likely to grow rather than diminish. The smart money (and when I say money, I mean public and private investment) should be on that continuing to be the case for some time to come, not least because of the huge growth potential for DNA-based infectious disease testing in some of the rising powers such as Brazil and India.
What, you might ask, has this got to do with personalised medicine? Are patients suffering from infectious diseases now being stratified according to the genetic profile of their infection? The answer for the most part is no. There are exceptions, such as Hepatitis C where treatment selection is guided in part by viral genotype (but for the limitations of this approach see section 4.7 of a recent UK guideline) and HPV testing, which discriminates between low and high-risk strains of HPV (but, as noted in a previous post, in cervical cancer screening cytology remains the primary diagnostic modality not DNA testing). So for the most part the only strain is the mental effort required to try and fit DNA-based infectious disease testing into our common understanding of what personalised medicine might mean. We need to be very careful not to bundle infectious disease testing together with other categories of testing to put a global figure on the growth in personalised medicine. This is a move which would grossly exaggerate how significant the field is now and how quickly it is likely to grow. Personalised medicine, understood as the use of genomic (or proteomic/metabolomic) data to stratify the care of patients, remains a niche market and is likely to remain so for some time to come.
So has DNA-based infectious disease testing got anything to do with personalised medicine? This type of application has provided molecular diagnostics companies with a large and (relatively) risk-free market allowing them to develop platform technologies which generate revenue streams which in turn can help to support investment in higher-risk applications like pharmacogenetics. Infectious disease testing is also an application which is likely to drive investment in point-of-care molecular diagnostics, which, again might pave the way for innovation in areas like companion diagnostics where turnaround time is cited as one issue deterring clinical uptake. So there are important interconnections, but those do not mean that DNA-based infectious disease testing is personalised medicine and we should not collapse the two when putting together statistics about the growth of personalised medicine.
Illumina – redefining the consumer in consumer genomics
The other type of hype which I want to address in this (lengthy) post are two linked ideas: the proposition that consumers are going to drive growth in personalised medicine by demanding access to their personal genomes; and the idea that in the future we will all have our genomes sequenced. I have argued elsewhere that the direct-to-consumer genetics business model is unproven and that many companies have moved away from it because it is unlikely to prove profitable, and my last post (with Paul Martin) questioned the vision of a future where we all have our genome sequences lodged in the healthcare system ready for accessing every time a doctor needs to treat us. These issues are illuminated (no pun intended) by the GenomeWeb publication Clinical Sequencing News which this week carries an interview with Matt Posard of Illumina, the industry leader in genome sequencing technologies.
Like Affymetrix (the microarray company it has begun to overshadow) Illumina has moved into clinical applications. Some years ago Affy set up a CLIA-certified lab but they subsequently sold it to Navigenics; it remains to be seen whether Illumina manage the transition from research tools manufacturer to clinical service provider with greater success.
The Posard interview is interesting because it reveals the caution and conservatism with which Illumina is approaching this space. In key respects this is a case of business as usual, not a revolution in healthcare. For instance for Illumina, the consumer is not a member of the public but a doctor or pathologist:
“The mission really is to enable genomics-based healthcare. The way we intend to do that is not just look at what we sell as an instrument and a set of consumables, but [also] the report that a physician is going to look at. So our primary customer, if you will, is going to be clinical geneticists as well as pathologists because it’s those groups that will ultimately sign off on the report.”
Posard does envisage some kind of consumer market for the general public, but its limits are revealing: “If it’s someone that’s struggling with an undiagnosed disease, it’s always going to go through a physician, without question.” That is a statement which sits uneasily with the heady rhetoric which demands unmediated access to the genome as a fundamental right. It moves the terrain of discussion onto the ground where I would suggest most stakeholders, including most of the industry, sit: some things can be sold DTC, other things should be ordered through a physician. Deciding where to draw the line provokes disagreement, but the need for a line has broad support, not least because the unfettered market would be one in which industry bore significant risks, as Posard makes clear:
“The risk or the responsibility that’s on Illumina and the other providers is [that], when somebody is exploring their own genome, they will find markers that have risk predisposition for different diseases. Making sure those results are provided responsibly and, in some cases, with professional counseling or support to help that individual through that information is the responsibility of the provider of those products.”
My colleague Michael Hopkins wrote a few years ago about the issue of commercial risk management in the genomics industry and his paper remains highly salient. Michael was also lead author on a highly influential paper called “The Myth of the Biotech Revolution” which countered biotech hype with a sober assessment of the scale and pace of change in the biopharmaceutical industry. The Posard interview is similarly revealing for his caution about how quickly genome sequencing will become a routine part of patient care. He begins with the classic figure of five years down the line, a timespan frequently invoked by those who promote expectations around genomic technologies. But Posard ascribes that optimistic vision to other commentators; he is rather more pessimistic in the timeline he envisages: “I think for my children and their generation, particularly, for them and for their kids, clinical sequencing and whole-genome [sequencing] are going to become standard of care.”
Given that Illumina are fighting off a takeover bid by Roche, the politics of expectations management are probably even more complicated than usual in this case. Nevertheless, it is a strikingly pessimistic assessment of the pace of change. Posard makes a series of comments, about the need to demonstrate clinical utility, and to have technologies which work within the clinical laboratory setting, which demonstrate a keen awareness that the rapid pace of technological progress in sequencing technology is moving on a timeline quite different to those which govern the clinical adoption of new diagnostics.
This acceptance that gene-sequencing must come to an accommodation with the challenges of the existing diagnostics innovation system, is reflected in Posard’s view of the FDA. He suggests that NGS products will transform the regulatory paradigm but he also explains that regulatory approval by FDA is central to Illumina’s move into clinical applications: “Our diagnostic business unit is in routine discussions with the FDA to ensure that we get the proper labels for the various products that we’ve been talking about,” Posard says, and he suggests that, in large part, products like the MiSeq platform can be accommodated within the current regulatory system.
What we see then, is the same tension which Paul Martin and I highlighted in the report from the Human Genomics Strategy Group: a transformative vision of a future in which we will all have our genomes sequenced is at odds with a more pragmatic acceptance of the need to demonstrate clinical utility and the need to work within existing paradigms, whether it be FDA approval or physician-led (rather than consumer-driven) healthcare. How are these to be reconciled? For many proponents of the genomic revolution, the mechanism which now appears to be favoured is a collapse of the distinction between research and clinical practice. Only when we have turned the entire population into genomic research subjects, it is argued, will we have sufficient data to reveal the latent utility of clinical sequencing. This is a solution which raises as many questions as it might hope to answer, pushing the question of clinical utility downstream whilst bringing to the fore equally intractable issues of public trust in the management of data privacy and the handling of unexpected findings of unknown clinical significance. But that is a discussion for another post.
 Hopkins, M.M. & Nightingale, P., 2006. Strategic risk management using complementary assets: Organizational capabilities and the commercialization of human genetic testing in the UK. Research Policy, 35(3), 355-374
 Hopkins, M.M. et al. (2007) The myth of the biotech revolution: An assessment of technological, clinical and organisational change. Research Policy, 36(4), 566-589