The Compatibility Gene by Daniel M Davis: "I am very rare but my wife is rather common"

The scientist Daniel M Davis has told the story of genetic compatibility - and the rejection that is its opposite - with great insight and decades of research. It's a field that may yield significant treasures in the decades to come.

The Compatibility Gene
Daniel M Davis
Allen Lane, 256pp, £20

“I am very rare but my wife is rather common.” This is not a sentence that would normally endear an author to you, let alone make you feel a little sorry for him. The thing is, it’s not great being exotic. Should Daniel M Davis get seriously ill, his chances of finding a transplant match are very bad. When he tells you that his wife is not one in a million but one in 100,000, you should feel good for her. Davis is one in four million, according to the genetic tests that the couple underwent. That’s very bad news, transplant-wise.

This all comes down to what Davis terms the “compatibility genes”. They are the set of genes that determine the make-up of your immune system and make you who you are.

We worry about where we came from. There is not a human civilisation on the planet that does not pay attention to its ancestors in some way. TV genealogy shows have probably amplified this trait, encouraging us to treasure our roots (or despair at them) in ever larger measure. So it’s no wonder we don’t cope well with the idea of organ transplantation: it messes with everything.

A study carried out in Sweden demonstrates the problem. In interviews with patients who had received someone else’s kidney, almost all of the subjects said that they felt it was best not to know too much about the donor. For some irrational, inexplicable reason, we are psychologically sideswiped by the idea that someone else’s meat has been installed inside our own. Some patients even worried about worrying about it, expressing a fear that too much “brooding” over the donor could lead their bodies to reject the foreign tissue.

We now know, thanks to a half-century of scientific sleuthing, that this isn’t true. Rejection of foreign bodies results from the activities of the compatibility genes. Davis’s enlightening book tells the extraordinary story of that discovery. As well as dealing with foreign tissue, the compatibility genes seem to influence our selection of biologically beneficial partners. It turns out that we look for complementary immune systems that enhance the chance of our offspring’s survival. Get it wrong at your peril: the compatibility genes are, it seems, frequently to blame in miscarriages. The contributions frommother and father have to be a good complementary pairing for a pregnancy to be successful. If Davis’s wife had chosen a more “common” man, she might have found herself with someone whose genes were too similar to her own, with adverse effects on the couple’s fertility. As Davis puts it, “Differences in our immune-system genes can influence who gets born.”

Sadly, science has not yet given us ways to cope with these differences. The best you can do is try to find a partner who somehow smells right. Evolution’s finest innovation might be the nose: we use it to check whether someone else’s immune system is complementary to our own.

Evolution is not perfect, however: given that as many as one in three pregnancies ends in miscarriage, cleary the smell is too subtle. Either that or we are all washing too thoroughly (or not doing enough investigative snogging).

It is almost ironic that the scientists who laid the foundations of this kind of research also had coupling issues. The Nobel laureate biologist Peter Medawar’s work elucidating what causes the rejection of transplants was so intense that he told his wife that she had claim on his love but not his time (and that he would be fine with an open marriage). The Danish biologist and sadomasochism fan Niels Jerne had a string of affairs before his wife (who had her share of lovers) committed suicide; it was only later, suppressing his grief with a gruelling work schedule, that Jerne uncovered the protective powers of antibodies. The Austrian Karl Landsteiner discovered the vital distinctions we know as blood groups. He also lived with his mother until she died. When he married shortly after that, the new Mrs Landsteiner faced the nightly distraction of her mother-in-law’s death mask on the bedroom wall. To her credit, the couple did manage to have a child.

Many more scientists are threaded through the pages of Davis’s thoughtful book and they all share one thing: the grinding heartbreak that is the slow progress of scientific discovery. It’s a heartbreak that Davis knows well; he is a leading figure in this subject. Though the science behind what causes our body to recognise itself and reject foreign material is more than 60 years old, he tells us, the conclusions we can draw from it are still fairly limited. Nonetheless, The Compatibility Gene is a fascinating, expertly told story of a field that may yield significant treasures in the decades to come.

Michael Brooks is the New Statesman’s science columnist 

The science behind our bodies' rejection of foreign material is 60 years old, Davis writes, but the conclusions we can draw are still limited. Photograph: Getty Images.

Michael Brooks holds a PhD in quantum physics. He writes a weekly science column for the New Statesman, and his most recent book is At the Edge of Uncertainty: 11 Discoveries Taking Science by Surprise.

This article first appeared in the 02 September 2013 issue of the New Statesman, Syria: The west humiliated

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Has this physicist found the key to reality?

Whenever we have ventured into new experimental territory, we’ve discovered that our previous “knowledge” was woefully incomplete. So what to make of Italian physicist Carlo Rovelli?

Albert Einstein knew the truth. “As far as the laws of mathematics refer to reality, they are not certain; and as far as they are certain, they do not refer to reality.” However good we are at maths – or theoretical physics – our efforts to apply it to the real world are always going to mislead. So perhaps we shouldn’t be surprised that reality is not what it seems – even when, like the Italian physicist Carlo Rovelli, you’ve done the maths.

It is a lesson we could certainly learn from the history of science. Whenever we have ventured into new experimental territory, we’ve discovered that our previous “knowledge” was woefully incomplete. With the invention of the telescope, for instance, we found new structures in space; Jupiter’s moons and sunspots were just the beginning. The microscope took us the other way and showed us the fine structure of the biological world – creatures that looked uninteresting to the naked eye turned out to be intricate and delicate, with scales and hooks and other minute features. We also once thought that the atom lacked structure; today’s technology, such as the particle colliders at the Cern research centre in Geneva and Fermilab in the United States, have allowed us to prove just how wrong that idea was. At every technological turn, we have redefined the nature of reality.

Unfortunately, we don’t yet have the technology to take the next step. The present challenge to physicists seeking to discover how things really are is to investigate our environment on a scale known as the “Planck length”. Rovelli tries to convey just how small this is. Imagine, he says, a walnut magnified until it is the size of the universe. If we were to magnify the Planck length by that much, we still couldn’t see it. “Even after having been enormously magnified thus, it would still be a million times smaller than the actual walnut shell was before magnification,” he tells us.

We simply cannot probe the universe at these scales using current methods, because it would require a particle accelerator the size of a small galaxy. So – for now, at least – our search for the nature of reality is in the hands of the mathematicians and theorists. And, as Einstein would tell us, that is far from ideal.

That is also doubly true when theoretical physicists are working with two highly successful, but entirely incompatible, theories of how the universe works. The first is general relativity, developed by Einstein over 100 years ago. This describes the universe on cosmic scales, and utterly undermines our intuition. Rovelli describes Einstein’s work as providing “a phantasmagorical succession of predictions that resemble the delirious ravings of a madman but which have all turned out to be true”.

In relativity, time is a mischievous sprite: there is no such thing as a universe-wide “now”, and movement through space makes once-reliable measures such as length and time intervals stretch and squeeze like putty in Einstein’s hands. Space and time are no longer the plain stage on which our lives play out: they are curved, with a geometry that depends on the mass and energy in any particular region. Worse, this curvature determines our movements. Falling because of gravity is in fact falling because of curves in space and time. Gravity is not so much a force as a geometric state of the universe.

The other troublesome theory is quantum mechanics, which describes the subatomic world. It, too, is a century old, and it has proved just as disorienting as relativity. As Rovelli puts it, quantum mechanics “reveals to us that, the more we look at the detail of the world, the less constant it is. The world is not made up of tiny pebbles, it is a world of vibrations, a continuous fluctuation, a microscopic swarming of fleeting micro-events.”

But here is the most disturbing point. Both of these theories are right, in the sense that their predictions have been borne out in countless experiments. And both must be wrong, too. We know that because they contradict one another, and because each fails to take the other into account when trying to explain how the universe works. “The two pillars of 20th-century physics – general relativity and quantum mechanics – could not be more different from each other,” Rovelli writes. “A university student attending lectures on general relativity in the morning, and others on quantum mechanics in the afternoon, might be forgiven for concluding that his professors are fools, or that they haven’t talked to each other for at least a century.”

Physicists are aware of the embarrassment here. Hence the effort to unite relativity and quantum mechanics in a theory of “quantum gravity” that describes reality at the Planck scale. It is a daunting task that was the undoing of both Einstein and his quantum counterpart Erwin Schrödinger. The two men spent the last years of their working lives trying to solve this problem, but failed to make any headway. Today’s physicists have some new ideas and mathematical intuitions, but they may also be heading towards a dead end. Not that we’ll find out for sure any time soon. If the history of science offers us a second lesson, it is that scientific progress is unbearably slow.

In the first third of his book, Rovelli presents a fascinating dissection of the history of our search for reality. The mathematical cosmology of Ptolemy, in which the Earth stood at the centre of the universe and the other heavenly bodies revolved around it, ruled for a thousand years. It was unfairly deposed: the calculations based on Copernicus’s sun-centred model “did not work much better than those of Ptolemy; in fact, in the end, they turned out to work less well”, the author observes.

It was the telescope that pushed us forward. Johannes Kepler’s painstaking obser­vations opened the door to the novel laws that accurately and succinctly described the planets’ orbits around the sun. “We are now in 1600,” Rovelli tells his readers, “and for the first time, humanity finds out how to do something better than what was done in Alexandria more than a thousand years earlier.”

Not that his version of history is perfect. “Experimental science begins with Galileo,” Rovelli declares – but there are any number of Renaissance and pre-Renaissance figures who would baulk at that claim. In the 12th century the Islamic scholar al-Khazini published a book full of experiments that he had used to test the theories of mechanics. The man who helped Galileo achieve his first academic position, Guidobaldo del Monte, also carried out many experiments, and possibly taught Galileo the craft.

It’s a small misjudgement. More ­irritating is Rovelli’s dismissal of any path towards quantum gravity but his own, a theory known as “loop quantum gravity”. He spends the last third of the book on explaining this idea, which he considers the “most promising” of all the assaults on the true ­nature of reality. He does not mention that he is in a minority here.

Most physicists pursuing quantum gravity give a different approach – string theory – greater chance of success, or at least of bearing useful fruit. String theory suggests that all the forces and particles in nature are the result of strings of energy vibrating in different ways. It is an unproven (and perhaps unprovable) hypothesis, but its mathematical innovations are nonetheless seeding interesting developments in many different areas of physics.

However, Rovelli is not impressed. He summarily dismisses the whole idea, characterising its objectives as “premature, given
current knowledge”. It’s a somewhat unbecoming attitude, especially when we have just spent so many pages celebrating millennia of ambitious attempts to make sense of the universe. He also strikes a jarring note when he seems to revel in the Large Hadron Collider at Cern having found no evidence for “supersymmetry”, an important scaffold for string theory.

As readers of his bestselling Seven Brief Lessons on Physics will know, Rovelli writes with elegance, clarity and charm. This new book, too, is a joy to read, as well as being an intellectual feast. For all its laudable ambition, however, you and I are unlikely ever to learn the truth about quantum gravity. Future generations of scientists and writers will have the privilege of writing the history of this particular subject. With theory ranging so far ahead of experimental support, neither strings nor loops, nor any of our other attempts to define quantum gravity, are likely to be correct. Reality is far more elusive than it seems.

Michael Brooks’s books include “At the Edge of Uncertainty: 11 Discoveries Taking Science by Surprise” (Profile)

Reality Is Not What It Seems: the Journey to Quantum Gravity by Carlo Rovelli. Translated by Simon Carnell and Erica Segre is published by Allen Lane (255pp, £16.99)

Michael Brooks holds a PhD in quantum physics. He writes a weekly science column for the New Statesman, and his most recent book is At the Edge of Uncertainty: 11 Discoveries Taking Science by Surprise.

This article first appeared in the 20 October 2016 issue of the New Statesman, Brothers in blood