A decade ago, sequencing the over 3 billion bases of the human genome, which gave birth to the field of modern “Genomics”, was a disruptive force in science and technology that changed the way we think about disease forever. The development of this technology has led to the sequencing of 100+ eukaryotic and prokaryotic species including not only homo sapien and close relatives such as the Neanderthal but also e.coli, HIV, mouse, chimp, and a host of other organisms. Today, we are so efficient at generating these data that sequencing a human genome in a couple of days is the norm and digital interpretations of these genomes have been performed tens of thousands of times over. While generating human genomic sequences, and to a lesser extent analyzing the digital readout of these genomes, has become commonplace, the impact of this information on society on the whole is just starting to be felt. The impact on society and specifically the field of healthcare is a building wave that will soon take shape as a disruptive force in clinical education, day-to-day practice, and the financial infrastructure behind our healthcare system.

Individual sequencing

For an individual to have his or her genome sequenced today the cost is ~$1000 USD with the cost per “base” falling every day as this technology becomes more and more ubiquitous. This technology has the potential to benefit millions, if not billions, of people worldwide but as the cost drops individuals will undoubtedly come to the clinic at a higher and higher rate having their genome sequenced prior to the recommendation of any healthcare worker which will change the current paradigm of “have disease/syndrome get sequenced” to “already sequenced, what can this tell me about my disease risk?” The question is, ‘how will this disrupt the current way medicine is practiced and markets are branded?’

The academic conundrum

Currently, the average amount of hours that a typical medical school student spends training in genomics is limited, excluding those specializing as clinical geneticists. However, the field of genomics is so rapidly expanding that it is almost impossible for curricula to keep up despite the impact that this information will have on day-to-day jobs in medicine. The need for an uptick in education of clinical partners in healthcare has become ever important. These would include clinically certified geneticists, genetic counselors, medical geneticists, and bioinformaticians. The latter is an extremely under filled position that would benefit any and all healthcare institution in the years and decades to come as genomic information available in the clinic becomes more common place. However, are the decision-makers, both public and private, willing to make an investment in the short-term to prepare for the wave of genomic information that will inevitably hit the clinic? Also, do we as a community have the motivation to retroactively train individuals who are already in practice?

The wider impact of genomics

In chronic disease treatment there is an established model of the ‘case manager’. Initially a nurse reaches out to help a patient that has chronic disease. Next, the patient is assisted through the process of checkups, screenings, and treatment until the disease is not present or no longer manageable. The case manager leads this process. As genomics becomes more and more disruptive would our healthcare system benefit from a genetic information manager? How will individuals process this information outside of contact with a genetic counselor (someone who is dedicated to this) who is typically called upon by referral? Should this information be processed in a family-wise fashion? One’s genomic information affects everyone in their family tree and these dynamics can be complicated and outside the training of today’s genetic and genomic specialists. Further, who pays for this “pre-disease” counseling which could be both emotional and biological?

Dropping costs

As costs drop and individuals seek out this information on their own marketing, branding, and drug-genome interaction awareness becomes important. We already know that pharma-genomic information is profoundly important. For example Azathiaprine, given to an individuals with a specific genetic variant, is associated with a lethal side effect. In fact it is considered malpractice to not check the status of enzyme function by genetic testing of TMPT. The HIV drug Abacavir works well except for the fact that it will kill some individuals carrying a specific genetic variant. In unselected patients, 5-8% develop a potentially deadly hypersensitivity reaction within the first 6 weeks of antiretroviral therapy. Prospectively screening individuals for the risk variants (HL-B*5701 status) prior to starting therapy costs ~$17/person and avoids the far more expensive and deadly hypersensitivity reactions in more than 500 people for every 10,000 treated. Clinical practice and insurance coverage rapidly included this step. This has been hailed as model for adoption of a pharmacogenomics test.

Beneficial effects

These types of interactions will encourage pharma companies to develop a genetic test at the same time as the drug where the standard of care may be to test for the genetic variant along with prescription. Further genetic and genomics studies can actually help companies directly market to consumers as the individual becomes more intimate with their genome. This will cut down marketing to target by genotype, could potentially, avoid life threatening side effects and liability

Financials of Genomics

This leads us to the financial aspect of genomics that will certainly be a disruptive force in healthcare. Even though the costs of generating genomic information are at an all-time low, because of the relatively few diseases that can be specifically diagnosed from a genomic test insurance companies have not bought into the idea of covering the sequence of each individual genome as a good practice in preventive medicine. Thus, the out of pocket cost for the patient remains high. So, this leaves us with another question, ‘What is the cost/benefit of having healthy people receive their genomic information given the lack of understanding of the diseases that cause the most healthcare burden worldwide (ie vascular disease, cancer, Alzheimer’s, diabetes)?

The ethical issues

As with any technological innovation, the genomic revolution and implementation of genomics in clinical care has raised a slew of ethical issues related to genetic privacy (who can and cannot have access to genomic data – patients, families, spouses, employers), ownership (who controls what can and cannot be done with my genetic information – research, commercialization, public health), impact on family members (does the fact that my genetic information has relevance to my relatives give them any rights to know or not to know), and perhaps most acutely, the right not to know or to change my mind about knowing. On a very small scale, the story of the discovery of the gene implicated in Huntington disease has relevance. Prior to the genetic variant being known, ¾ of at risk individuals claimed a desire to know their genetic status, but once the test became available fewer than ¼ have chosen to get testing. The ability to decide whether to know or not may be more important to many than the actual knowing.

The legal / patent issue

Genomics provides ample opportunity for branding which we already see. Companies, hospitals, and clinics position themselves at the vanguard claiming cutting edge practice and innovation. A quick perusal of the New York Times Magazine demonstrates multiple healthcare systems are touting their use of genomics to target cancer treatment, tailor therapy, and identify risk. On the other hand, broadly available genome-wide data has substantial implications for companies that patented genomic information (e.g. Myriad Genomics for BRCA1), a controversial practice. Both the United States Supreme Court in 2013 and the Australian High Court in 2015 ruled that naturally occurring DNA sequences are ineligible for patents. In the European Union, some genomic sequences can still be patented, but with specific criteria. Nearly all Latin American countries have banned patents on genetic sequences. The situation in Asia is less clear. Broad availability of whole genome data will undoubtedly challenge the tenability of at least diagnostic genomic patents on a practical level.

The future prospects…

What are the avenues that excite us? The science driving this disruptive force continues to evolve and change. We have gone from individual genetic tests, the genome-wide association studies, to exome sequencing (cheaper but incomplete way to get genetic information), whole genome sequencing, and now a raft of other -omics (epigenomics, proteomics, metabolomics, and metagenomics) will be added to the mix and interact with genetic information creating an exponential growth of information. Under the current standard for clinical investigation, physicians and other practitioners tend to take a stepwise process going from more focused and targeted testing to broader methods. Broad scale availability of whole genome sequencing at an attainable price, will upend this process and may in fact eliminate other intermediary technologies.

Bradford B. Worrall, MD, MSc
Harrison Distinguished Teaching Professor and
Vice-Chair for Clinical Research of Neurology
and Professor of Public Health Sciences
University of Virginia

Stephen R. Williams, PhD
Assistant Research Professor
Department of Neurology
University of Virginia​

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