Using genetic data to identify people at risk of developing common diseases and recommend tailored, preventive measures has the potential to save hundreds of billions of dollars in healthcare costs, according to researchers writing in the Lancet. Personalized and precision medicine has delivered targeted therapies for cancers and rare genetic diseases, but the authors argue that realizing their full potential will require changes to the US health system to incentivize preventive measures.
Dr. Maynard Olson, Professor Emeritus of Medicine and Genome Sciences, University of Washington (webpage):
Expertise: New methods of genome analysis and the application of these methods to the study of the human and other genomes. Dr. Olson was a member of the committee for the 2011 National Research Council report, ‘Toward Precision Medicine’.
“The opinion paper by Dzau et al. poses a mix of conservative and radical ideas. Neither will be easy to implement, but the authors are certainly right that economic incentives within the health-care industry are poorly aligned with the enormous opportunities posed by advances in genetic analysis. The long-term dream of using complete knowledge of an individual’s unique genetic program to guide health care decisions has become a practical goal due to dramatic technical innovations in DNA analysis and the ability, via the internet, to manage the staggering amounts of data on which precision medicine would depend.
“The conservative part of the argument is that there is low-hanging fruit in personalized medicine that could be harvested now. Particularly in common, chronic diseases such as heart disease and type 2 diabetes, enough is already known about genetic predispositions—supplemented with more conventional clinical indicators—to improve our ability to recognize patients at high risk of future health problems and to intervene effectively. The main concern of these authors is that incentives within the health-care system, particularly in the United States, are poorly structured to exploit this opportunity.
“The more radical subtext of Dzau et al. is that incentives are even less well aligned with capturing the largest potential benefits of precision medicine, which will depend on acquiring new knowledge by mining genome sequences, electronic medical records, and other data about individuals. Simply stated, no one has the incentive to pay for the long-term infrastructure required to mine the rich veins of new knowledge that would be certain to be found if the infrastructure were built. The benefits of developing this enormous new resource for biomedical research would be even larger, but also still longer term, than those on which Dzau et al. focus.
“Dzau et al. correctly focus on policy issues since the obstacles to moving forward are neither technical nor scientific. In the United States, the opportunity costs of inaction are potentially devastating. The foremost of these, is that our population may lag substantially in enjoying health benefits from a scientific and technological revolution that we, to a substantial extent, created.”
Dr. Robert Nussbaum, Chief of UCSF Division of Medical Genetics & Holly Smith Distinguished Professor in Science and Medicine, University of California, San Francisco (webpage):
Expertise: If and how genetic and genomic information can be used to improve health care by improving outcomes, reducing adverse reactions, lowering costs and promoting health through risk education.
“The commentary is right on target in terms of the full promise of personalized and precision medicine. Most people still think of precision medicine in terms of creating targeted drugs for very sick patients, but the real hope is that we’ll be able to identify risk long before people get sick.
“Until now, identifying individuals at greatly increased risk for breast, colon, and a variety of other cancers has relied on focusing on those individuals with suggestive family histories.
“At UCSF, by combining germ line and tumor testing, we are looking to identify those individuals and their relatives in the population who are at increased risk for cancer, but who ordinarily would not have been offered hereditary cancer testing because of small families, missing family medical history data, or a failure to recognize a hereditary cancer pattern in the family. This approach will lead to improved surveillance and prevention, which will not only improve the quality of life for these individuals, but also save significant health care costs.
“One example we are particularly excited about is our new Hereditary Cancer Prevention clinic that will focus on patients who have no diagnosis of cancer but have significantly increased risk due to genetic predisposition.
“In cancer, prevention strategies, as well as early detection and cure, are the goal, and finding everyone who is at increased risk because of their genetic makeup is a key element of precision medicine.”
Dr. Daniel Lowenstein, Executive Vice Chancellor and Professor in the UCSF Department of Neurology, University of California, San Francisco (webpage):
Expertise: Approaches designed to advance our understanding of the complex genetics that are thought to underlie a substantial portion of the idiopathic epilepsies.
(N.B. Dr. Lowenstein gives an example of the potential for precision medicine to re-purpose existing drugs for treating common diseases.)
“In 2007, the NIH started a project spanning 40 research institutions to collect the genetic and clinical data from thousands of epilepsy patients, to try to make progress in treating this debilitating disorder. This research has led to the identification of a number of disease-causing gene mutations that give rise to certain forms of the so-called “epileptic encephalopathies”, a particularly severe epilepsy syndrome that arises in infancy and early childhood.
“One of the mutations was found in the KCNT1 gene. This discovery led members of the team to study the gene mutation further, where they determined that quinidine, a drug used for certain cardiac diseases arising from abnormalities of the same ion channel in the heart, partially rescued the effect of the mutation.
“Since quinidine was clinically available, clinicians at the Children’s Hospital of Philadelphia received approval to try the drug in one of the children with the KCNT1 mutation. Remarkably, the child’s seizures went from nine per day to none. Further experience in the use of quinidine in other children with KCNT1 mutations suggest that the effect is variable, ranging from complete cessation of seizures to little or no effect. Nonetheless, these studies constitute a proof-of-principle demonstration of the identification of a genetic basis of epilepsy, discovering a potential therapy for the specific mutation in vitro, and then introducing the treatment into a patient to ameliorate the disease. This is the dawn of precision medicine in epilepsy.”
‘Aligning incentives to fulfil the promise of personalised medicine‘ by Dzau et al, published in the Lancet on Thursday, May 7, 2015.
Declared interests (see GENeS register of interests policy):
Dr. Maynard Olson: I was a member of the Scientific Advisory Board at Illumina for several years, ending in fall 2014.
No other interests delcared.