The Beautiful Cure: The lethal complexity of our immune systems

How immunology – the study of the immune system – went from a marginal area of clinical medicine to a health revolution.

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When I was a medical student 40 years ago, immunology – the study of how our bodies fight infection – was a rather marginal area of clinical medicine. Frank MacFarlane Burnet and Peter Medawar had shared the Nobel prize in 1960 for their work on immunological tolerance, which laid the foundations of our understanding of why transplanted organs were rejected. The discovery of immunosuppressive drugs (in particular cyclosporin in the 1970s) made transplant surgery possible, and autoimmune diseases (such as rheumatoid arthritis and Crohn’s) – illnesses where our immune systems attack our own bodies rather than just alien infections or transplants – had first been described in the 1960s. Nevertheless, relatively little was understood about the immune system and clinical immunology was not considered to be an important or prestigious area of medical practice. Nor was it thought that the immune system could “see” cancer cells, and the idea that it might be enhanced and harnessed to treat the condition was seen as little short of quackery.

How things change! Daniel M Davis’s wonderful book The Beautiful Cure recounts how research into the immune system in recent decades has resulted in what amounts to a health revolution. Immunotherapy drugs are now worth billions of dollars, and cancers and autoimmune diseases that were once considered untreatable can now be fought and, in a few cases, even cured. There is little doubt that there will be further progress in the years to come.

Davis recounts in exceptionally clear and sympathetic prose how all this came about. The immune system (in all creatures, not just humans) is an immensely complex population of white blood cells (as opposed to the red cells that carry oxygen from the lungs) and associated proteins that eliminate germs that invade our bodies from the outside world. It is a system that needs to be ramped up rapidly when an infection develops, but which – like any military force – must be kept under tight control as it wields destructive, lethal power.

It must differentiate between harmful and non-harmful alien substances (such as some kind of new food molecule) and also recognise as “self” all the cells and proteins of the body it is defending. B lymphocytes, for instance, can produce up to ten billion different antibodies, meaning they are equipped to attack a whole variety of substances that they have not yet even met. Davis describes how the many-layered immune system of accelerators and brakes was slowly uncovered by years of dogged scientific research, with many Nobel prizes being won on the way. He also explains how there is still much that we do not understand.

At the beginning of this book, Davis recounts a conversation between the brilliant and witty physicist Richard Feynman and an artist. The artist extols the beauty of a rose and says that science makes the flower dull. Feynman retorts that science “only adds to the excitement and mystery and awe of a flower”. Davis’s book illustrates this wonderfully well – the immune system is a thing of great beauty and awe-inspiring complexity. So much so, I might add, that it is hard to conceive of a divine intelligence smart enough to design it. It is the product, instead, of many millions of years of trial and error.

Readers of this book will learn about the legions of dendritic cells, regulatory T cells, and natural killer cells, armed with tumour necrosis factors, cytokines and co-stimulatory proteins that with their precise and elegant choreography keep us – most of the time – alive and well. They will learn how these cells can be enhanced to treat cancer and autoimmune diseases.

But they will also read one of the best accounts I have yet come across of the nature of biological science and discovery. It is a story of a few brilliant and stubborn individuals, such as Charles Janeway, who predicted “innate immunity” before it was found, and Ralph M Steinman, who discovered dendritic cells and became an experimental subject for immunotherapy after he was diagnosed with pancreatic cancer. He survived for four years – much longer than average for the disease. The phone call saying that he had won the Nobel prize arrived a few hours after his death, making him the only posthumous recipient of the award (its rules specify that it can only be given to the living). And then there is Steven Rosenberg, whose experimental cancer therapy using the cytokine IL-2 failed for the first 66 patients but cured the 67th.

There were many other such individuals, but The Beautiful Cure is also a story of teamwork and international co-operation (to an extent that surely is starting to make the Nobel prizes a little invidious). It shows science to be an intensely emotional endeavour – new ideas that eventually prove to be correct are often met initially at meetings with sniggering and abuse. There is professional jealousy and furious competition to get results out first. Billions of dollars are now at stake, and there has been much litigation. Some scientists become millionaires from patents and royalties. It is all very human, and not at all dull, whatever Feynman’s artist friend might have thought. But it is driven above all, Davis tells us, by scientists’ curiosity – “following their nose” – and their deep faith that nature is coherent. “Triumph,” Davis writes, “came from imagination and hard work, but also from a web of coincidences, chance events and serendipities”.

The book ends on a suitably cautious note. The new “miracle” cures and treatments only work for a minority of patients – the media tends to pass over the many failures and the fact that side effects can even be fatal. Treatment is immensely expensive and this can only serve to exacerbate further the great inequalities in health between rich and poor, and young and old, both within and between countries.

There is a much greater need for new antibiotics as bacterial resistance accelerates, and for dealing with the diseases of poverty, than there is for new cancer drugs. Cancer is a thousand different conditions and overwhelmingly a disease of old age, even though the advertisements for cancer charities always show pictures of sick children and young adults.

Even if further understanding and manipulation of our immune systems eventually cures all cancers – at immense expense – what happens next? How then shall we die? Just as with global warming, science’s triumphant progress is stirring up some very difficult problems. 

The Beautiful Cure: Harnessing Your Body’s Natural Defences
Daniel M Davis
Bodley Head, 272pp, £20

This article first appeared in the 08 February 2018 issue of the New Statesman, The new age of rivalry