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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.

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

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A Lab of One’s Own: the forgotten female scientists who shed stereotypes about women’s abilities

Every woman in this book deserves a biography of her own.

You might assume that there’s not much left to be written about the suffragette movement. But what has been ignored is that in the quiet corridors of university science departments, important battles were fought by women whose names were quickly forgotten. They weren’t always high-profile campaigners, but by forcing open the gates to the male-dominated worlds of science and engineering they helped shed stereotypes about women’s abilities.

In A Lab of One’s Own, the Cambridge historian Patricia Fara documents these scientists’ stories, painting a picture of a world that clearly wanted to remain male. It was the First World War that gave women unprecedented access to careers for which they had until then been deemed unsuitable. From all walks of life, they began working in munitions factories, developing chemical weapons (at one point, 90 per cent of industrial chemists were women) and building war machinery, while male scientists were on the battlefield.

These weren’t safe jobs; 200 women producing TNT died from poisoning or accidental explosions. Their achievements were so immense that even the prime minister Herbert Asquith, who opposed female suffrage, was forced to admit that there was hardly a service “in which women have not been at least as active and efficient as men”.

There is understandable anger in Fara’s voice. Despite their skill and dedicated service – often working for less pay than their male counterparts, or none at all – female scientists faced appalling resistance. Women were shunted into the worst roles, mocked for what they wore (trousers or skirts, they could never seem to get it right), and their ideas were ignored. Trade unions fought to protect men, meaning most women went unrepresented, promptly losing their jobs once the war was over.

Again and again, they had to carve out spaces for themselves then battle for the right to keep them. Britain’s scientific societies pulled elaborate tricks to block female members in the first half of the 20th century. One graduate, Emily Lloyd, managed to gain admission to the Royal Institute of Chemistry only by cleverly using the gender-neutral “E Lloyd” to sit the qualifying exam.

But getting through the door was only half the challenge. At Cambridge, men stamped their feet while women walked to their reserved seats at the front of the lecture theatres (imagine how they must have felt when Philippa Fawcett, daughter of the suffragette Millicent Fawcett, beat them all to come top in the Cambridge Mathematical Tripos exams in 1890). Women-only labs were given inferior facilities. Even scientists who worked alongside their husbands sometimes weren’t given credit when their joint work was published.

Every woman in this book deserves a biography of her own. Martha Whiteley, for example, who did pioneering work on mustard gas and wounded her arm when she tested it on herself. And the chemist Dorothea Hoffert, who researched varnish and food before having to give up work when she got married. The personal tales of these remarkable figures could benefit from more spacious storytelling, but as a scholarly account, Fara’s book offers a window into this fascinating chapter of history.

What’s also intriguing is the unease that men felt on seeing women doing “their” jobs. Soldiers worried about “the masculinisation of women” back home. There were fears that uniforms and protective overalls would drain femininity, and that by choosing to study and work rather than reproduce, clever women were depriving the nation of clever babies.

Unsurprisingly then, after the war, things went back swiftly to how they were before. Even in medical schools, where women had made huge strides, “the traditional masculine culture reasserted itself”. Women did win the battle in the end, although the war continues. As Fara makes clear, this was not only through the force of their intellects but also by taking the example of male clubs and forming their own networks. Women’s colleges became hotbeds for campaigning, particularly Newnham in Cambridge. The Women’s Engineering Society, the British Federation of University Women, and others were set up partly to help women fight entrenched efforts to hold them back.

“It is with much interest that we learned a few weeks ago that women chemists in London had formed a Club,” a snobbish editorial in the journal Chemistry and Industry began in 1952. “Most men are clubbable one way or another, but we did not know this was true of women. We wonder if this formation of a Club for women chemists is another sign of female emancipation.”

It was. By banding together and defending their rights, women found a strength that many before the war assumed they would never have. These pioneers not only helped win women the vote, they changed what it meant to be a woman. l

Angela Saini is the author of “Inferior: How Science Got Women Wrong – and the New Research That’s Rewriting the Story” (4th Estate). Patricia Fara will appear at Cambridge Literary Festival, in association with the New Statesman, on Friday 12 April.​

A Lab of One’s Own: Science and Suffrage in the First World War
Patricia Fara
Oxford University Press, 352pp, £18.99

This article first appeared in the 15 February 2018 issue of the New Statesman, The polite extremist