Translational medicine

The past couple of decades have seen a major emphasis on “translational medicine”, the idea that promising treatments need help to transition more quickly from the lab bench to the bedside. The biggest beneficiaries have been two big ideas: “personalised medicine” – using a person’s genome to offer tailor-made treatments – and “regenerative medicine” – using stem cells to repair their organs.

But are these lofty ideas delivering on their promise? In an opinion piece published in the Journal of the American Medical Association in October 2016, three prominent researchers argue they may not be. Epidemiologists John Ioannides from Stanford University and Michael Paneth from Michigan State University, with physiologist Michael Joyner from the Mayo Clinic, say these big ideas are soaking up resources at the expense of others that may have a bigger impact on health, such as finding new methods to curtail smoking. They call for “a wholesale re-evaluation of the way forward in biomedical research”.

Personalised medicine was the promise of the Human Genome Project, completed in 2003. The idea is that reading your genome, plus access to electronic medical records to keep tabs on a person’s health, will deliver tailor-made prevention strategies. For instance, if you carry a high-risk breast cancer gene, the recommendation would be to have a mastectomy. Personalised medicine will also deliver tailor-made therapies, usually drugs, as well as “gene therapy” to correct the faulty gene.

Regenerative medicine, born in 1998 when researchers mastered the art of growing human embryonic stem cells, promised a new era of “spare parts” for ailing bodies.

According to the critics, about 60% of research funding in the US is now funnelled into these fields, with a huge upswing in the number of papers published.

But does having your genome read really help? Common conditions such as type 2 diabetes, depression and heart disease involve hundreds of different genes. Pinning down a faulty gene that can be targeted with a drug has proved elusive.

Cancer has been another area of great promise with limited returns. The idea is that reading the DNA of a person’s tumour should reveal its Achilles heel. There have been some stunning successes where rogue genes that drive a tumour’s growth or help it evade the immune system have been matched with drugs that can disable those genes. But so far, we’ve not seen benefits on a large scale.

Gene therapy has also been disappointing. Even simple disorders, such as sickle cell anaemia that results from a single wonky version of the haemoglobin gene, have not benefited from attempts to replace the faulty gene.

There is also another downside to personalised medicine, say the authors of the JAMA article: “The inevitable overdiagnosis and overtreatment that follows from more intensive monitoring”. The authors also cast doubt on the likely impact of stem cell therapy and regenerative medicine. Even some of the most promising trials in heart disease, they say, may be flawed.

“So what?” you may ask.

We know it takes decades to turn discoveries into treatments. We know failure is par for the course. The critics don’t deny that. But with so much competition for research grants, these big ideas may be strangling other great ideas.

The solution, say the critics, is two-pronged. On one hand, the funding formula needs to be reset, with a higher proportion going to high-risk “blue sky” ideas. On the other, the mechanisms to evaluate the performance of big ideas need to be reviewed. Relying on the number of studies published is self-serving, they say, because publications tend to follow fads.

“After several decades of substantial investment, the fundamental question is whether these big ideas have improved quality of life and life expectancy, by how much, for how many, and for whom,” write Ioannides, Paneth and Joyner. “These are public dollars that should benefit the many, not the few.”

It is not an argument to stop funding research in the areas of personalised and regenerative medicine. These big ideas may yet deliver. But perhaps it is time for other ideas to be given a place in the sun. The debate is worth having.