Precision medicine, hope or hype?

Cristina Roure

Fifteen years after the human genome has been deciphered, after 3 billion dollars and after 13 years of intense network research, the cost of sequencing the entire genome has been reduced a thousand times and more than 20 million people already get concrete results. In a few weeks, from a simple saliva sample, these people will receive comprehensive information about their genetic material for less than $100 thanks to companies such as 23andMe or Ancestry. In the United States, through an alliance between Genomind and the Albertsons pharmacy office chain, patients treated with psychoactive drugs can receive advice from their pharmacist so that their doctor prescribes a pharmaceutical-genetic test and perform it in the same pharmacy office. It’s spectacular that a series of emerging diagnostic technologies target healthy people to predict or detect diseases early: immune footprint to predict various types of cancer and infectious diseases, biomarkers for Alzheimer's disease, or exhaled breath tests for early detection of lung cancer.

In general, the extraordinary benefits of precision medicine are supposed to be evident, they are already here and they will significantly exceed their costs because moving from a "reactive medicine based on averages" to a "proactive based on individual data” will be cheaper and prevent suffering and unnecessary treatments.

The scientific evidence is undoubtedly more complex and controversial than what is publicized in the general and academic media, but the truth is that there is an exaggeratedly optimistic utopian vision of pharmaceutical genomics and precision medicine in general. This exaggerated and sensationalist view of the anticipated benefits of science is not new; In English, it's known as science-hype and has accompanied the development of genomics since its inception(1). Besides, it grows in an ecosystem paid by multiple actors with diverse interests and who press hard for early implementation:

• The scientific community. The most relevant scientific journals want to publish the most avant-garde research to increase their prestige. Institutions also contribute to the creation of expectations through press releases that help them position themselves and obtain more funds to investigate. The competitive nature of the academic environment and the pressure to publish induce the exaggeration in the titles, the conclusions and the value of the results, which transcend the public even before they are published.
• The media, the citizenship and patient communities. Precision medicine is presented in the media in a sensational and exaggeratedly positive way so that it confuses and seduces with a simplified vision while reducing uncertainties and amplifying the benefits. Only one in three news items in the press include some worrying or negative aspects(2). How science is presented to the public creates expectations, stimulates debates and reinforces the pressure exerted for the implementation of emerging technologies, which in many cases are not prepared to be applied in clinical practice.
• The governments. Economic growth and the creation of new jobs have become the new justification for the promotion and financing of biomedical research by governments, beyond the interest in curing diseases or creating knowledge. This is because it’s about improving the productivity and competitiveness of the country's economy, which results in greater pressure for the research commercialization and the generation of disproportionate expectations regarding its prompt clinical application.
• The market and the industry. Precision medicine generates great enthusiasm among investors, so the big pharmaceutical companies are creating alliances with technological start-ups of genetic diagnosis for the development of new and sophisticated targeted therapies. This summer, 23andMe signed an agreement, with economic content, to share its genetic, biographical and health database with Glaxo. Roche bought Foundation Medicine and offers its clients the determination of the complete genetic profile of the patient's tumour, linked to the purchase of their immunotherapy products for cancer.

All these factors press for the implantation of personalized medicine in clinical practice to offer its spectacular results to patients. However, the reality is different and the expectations that some genetic polymorphisms explain most diseases have vanished. Hundreds of genetic variants are involved in each disease and the function of each of them is difficult to decipher.

The accuracy of scientific measurements without clinical application is useless. There are dozens of pharmaco-genomic tests in mental health for more than a decade, but there are no practice guidelines to apply them, rigorous evaluations of their clinical validity, or comparative analyzes between them. The early detection of Alzheimer's disease will be of little use to patients if effective treatment is not available. According to Vinay Prasad, precision oncology is inspiring, but it’s still a hypothesis that has not worked so far and may never work (3). I encourage you to read an interview in the interesting MIT Technology review dedicated to precision medicine last November, in which Prasad reviews the risks of exaggeration and premature adoption of personalized medicine improperly evaluated (4).

The prediction that precision medicine will reduce healthcare costs seems unlikely, just think about the application of targeted therapies with an exorbitant cost and that they are aimed at a small number of people. The new diagnostic tools represent spectacular technological advances, but they don’t provide immediate improvements in the health or well-being of people and, nevertheless, make them potential patients with the associated anxiety, overdiagnosis and overtreatment. We need new diagnostic tests to detect real problems, not to generate them.

We also run the risk that hype rhetoric associated with this precision medicine overshadows other low tech interventions as dated and old, but with much more real impact on mortality, morbidity or life expectancy (fight against antimicrobial resistance, promotion of healthy habits, etc.). Even worse, hype rhetoric will eclipse the importance of complex aspects of the person, such as culture, values and preferences, which are not part of the great prevailing biomedical bubble.

Ray Moynihan says that the challenge of medicine lies in providing hope without exaggeration, "hope without hype." You have to deflate the bubble and reduce the exaggeratedly optimistic rhetoric and probably interested in precision medicine. A more rigorous and realistic alternative vision of the potential benefits of individualization is essential if we aim to prevent premature and widespread implantation threatening people's health and the sustainability of the system.

Bibliography

1. Caulfield T, Condit C. Science and the sources of hype. Public Health Genomics2012; 15:209–217 

2. Marcon AR, Bieber M, Caulfield T. Representing a “revolution”: how the popular press has portrayed personalized medicine. Genet Med. 2018; 20:950–956.

3. Prasad V. The Precision Oncology Illusion. Nature 2016; 537: S63.

4. Precision Medicine. MIT Technology Review. 2018; 121 (6)52-55.