Wednesday, October 5, 2016

Matt Ridley: Mental illness is the greatest research challenge

Mark Zuckerberg, chief executive of Facebook, and his wife Priscilla Chan, a paediatrician, have announced their intention to spend $3 billion over ten years on medical research. Having met them last year, I thought I would take the liberty of making a suggestion as to how they spend their money.

Dear Priscilla and Mark,

Your plan to fund medical research and challenge humanity to “cure, prevent or manage all diseases by the end of the century” has certainly caught the world’s attention. As Bill Gates has done with malaria, mainly through the use of bed-nets, and Jimmy Carter with guinea worm, mainly through water filters, a famous philanthropist financing fresh approaches can make a big difference, even with limited funds.

But it will be important to get the most bang for your buck. So I want to suggest a sort of triage: avoid the problems that are too hard and too easy; tackle the ones that are tough but soluble. That means focusing on the brain. Naming the distinguished neuroscientist Cori Bargmann as president of science at the Chan-Zuckerberg initiative is the right move.

You’ve rightly stated that there are four main categories of disease: heart disease, cancer, neurological and infectious diseases. By 2100, with the right policies, heart disease and infectious disease will be easily beatable without your money, or much new research; while most cancer will be undefeated by the end of the century, however well you and others spend research money. It’s neurological disease where you should focus.

Infectious diseases are already in headlong retreat. Deaths from them are now rare in the western world and falling rapidly in the developing world. Malaria mortality worldwide fell by 60 per cent in the first 15 years of this century. HIV mortality is down by 25 per cent in six years. All the tools exist to make the same happen to every other virus, bacterium, fungus, worm and protozoan that used to kill us by the million. Vaccines and drugs are getting better every year.

The ebola epidemic showed how quickly we can get a lethal virus under control even in very poor countries, despite some early mistakes. Influenza will cause scares from time to time, but with modern genomics we can sequence it and design countermeasures faster and faster. Tuberculosis will fight a defiant rearguard action, but we know what to do. Drug resistance will be a recurring problem, but not an insuperable one. Emergent infections such as zika and dengue will need fresh approaches, but they are beatable with the right policies. We’ll crack the common cold eventually.

We will need research to understand another category of disease that is getting worse still: allergies and auto-immune diseases. They are mostly a consequence of our success against infectious disease. The immune system used to “expect” to be down-regulated by parasites and without them it over-reacts.

Heart disease is the leading cause of death in the world, causing about one-third of all deaths, but the mortality rate is falling fast in most countries, and we know how to make it fall faster: less smoking, healthier living and prompt treatment. Much the same is true of stroke. With enough funding and political will, these diseases can be defeated.

By contrast, although we’ve pretty well cracked the causes of cancer, we have failed to work out how to cure it since declaring “war” on cancer half a century ago. Genetic mutations in dividing cells (caused by cigarette smoke or other factors, including bad luck) result in uncontrolled cell division. And then Darwin gets involved: within each tumour there is a ferment of genetic experimentation, as cell lines compete for ways to grab resources, grow and divide, despite the signals from the body telling them not to. Eventually, the competition is for ways to survive and counter the chemotherapy drugs, too, which is why initial cure is so often followed by relapse.

The core of the problem is that cancer risk is a byproduct of ageing. A fascinating paper published by a team from Harvard Medical School last month comes to the remarkable conclusion that the risk of cancer doubles every eight years — for all kinds of cancer — and that this is also the rate at which all other risks of ageing double.

Short of genetically engineering people so they have extra copies of the tumour-suppressor gene p53 (as elephants do), there’s probably nothing we can do about this. We can cure childhood and young-adult cancers and expect to see people live for a long time (childhood leukaemia death rates are down by 90 per cent), but we’re never going to get rid of the increasing risk of cancer in old age.

Neurological disorders are different. Many strike young, and we are still fumbling in the dark with most of them, treating the symptoms and not the causes. We still struggle to explain what triggers the onset of Alzheimer’s or Parkinson’s diseases. Plaques form, yes, but that’s like saying spots form on measles patients. Deeper down, something prevents the proper folding of proteins, or their solubility, or both: but what? My money’s on the study of telomeres (the caps at the end of each strand of DNA that protect our chromosomes), for what it’s worth.

In the case of multiple sclerosis, I’m increasingly confident that we will soon agree that the cause is “endogenous retroviruses” — that is, ancient DNA copies of past infectious agents’ genes, copied into our genomes and reawakened by something, but by what, and how? In the case of schizophrenia, autism and other mental illnesses, we’re even further from a full understanding. Yet there is every reason to think that once we can understand them we can cure them.

Treatments for neurological diseases are still in the dark ages. Talking cures work a bit, sometimes. Some drugs work well, others not so much. But there is every reason to think these problems are soluble. If something goes wrong in a brain it should be fixable, once you can identify the cell and the molecule where the problem is happening. By 2100, I predict, neurology and psychology should be unrecognisably better than today.

So if you want value for money focus on the diseases of the brain: that’s where we need research breakthroughs. At the moment Britain spends about four times as much on cancer research as mental health research. That’s probably the wrong way round.

Good luck and best wishes,
Matt.


Matt Ridley, a member of the British House of Lords, is an acclaimed author who blogs at www.rationaloptimist.com

1 comment:

paul scott said...

A masterly inspection of neurological disease, and at the same time a well placed dig at the grandiose stupidity of Mark Zuckerberg.