Is Tim Dowling married to the right woman? A new book suggests that we unconsciously select the perfect partner by sniffing out their 'compatibility genes'. He talks to the author about MHC genetics and alleles – then nervously asks his wife to take a DNA test
At first, I'm not even sure how best to frame the question in order to secure my wife's participation.
"Would you mind taking a quick DNA test," I say, "to determine our genetic compatibility?"
"Am I going to be told I have a fatal disease?" she asks.
"No," I say. "It's just to find out whether or not we were meant to be together."
"Oh," she says. "Fine. Whatever."
On the day we each spit into separate test tubes, I don't yet understand how a DNA test can offer evidence of compatibility, because I am only on page eight of Daniel M Davis's book The Compatibility Gene. But here's the gist of the idea: there are a small number of human genes – a tiny section of the short arm of chromosome six – that may play a role in determining how attractive you are to a potential mate. Suitable partners can literally sniff each other out, finding an optimal genetic other half using their noses.
The basis for this notion is the so-called smelly T-shirt experiment, first performed by a Swiss zoologist called Claus Wedekind in 1994. He analysed a particular bit of the DNA of a group of students, looking specifically at the major histocompatibility genes (MHC). The students were then split into 49 females and 44 males. The men were asked to wear plain cotton T-shirts for two nights while avoiding anything – alcohol, cologne etc – that might alter their natural odour. After two days the shirts were placed in cardboard boxes with holes in them, and the women were asked to rank the boxes by smell using three criteria: intensity, pleasantness and sexiness.
Wedekind's results appeared to show that the women preferred the T-shirts worn by men with different compatibility genes from themselves, raising the possibility that we unconsciously select mates who would put our offspring at some genetic advantage. The experiment was controversial, but it did alter scientific thinking about compatibility genes. And while the mechanism behind this phenomenon is poorly understood, that hasn't stopped dating agencies from employing MHC typing as a matchmaking tool. One lab offering such testing to online agencies (you can't smell potential partners over the internet; not yet), a Swiss company called GenePartner, claims: "With genetically compatible people we feel that rare sensation of perfect chemistry."
As I walk to the postbox with my two test tubes of spit in an envelope, the idea of testing my genetic affinity with my wife suddenly strikes me as foolhardy. Twenty years of marriage should be the very definition of compatibility, but what if the results tell a different story? I don't want to discover that on a cold winter's night two decades ago, my wife took one sniff of me and fell in love with my deodorant. I don't think they even make that kind any more.
Davis also tested his marital compatibility for the book and, while he may be a director of the University of Manchester's Collaborative Centre of Inflammation Research, he admits to similar, not wholly rational, misgivings.
"It was definitely more weird than I thought," he told me, adding that his wife was "unexpectedly nervous about what they might find." He needn't have worried – they were pronounced perfectly compatible.
They aren't called your compatibility genes because they help you find a compatible partner; they're called that because they govern the acceptance and rejection of transplanted organs. And that's not their intended role, either. As Professor Steven Marsh – deputy director of research at the Anthony Nolan Histocompatibility Laboratories, where I sent my spit – puts it: "The molecules that give you your tissue type, they're not there just to make transplantation difficult. Their job is to fight infection." They are, in short, your immune system.
Davis's book tells the story of the search for these compatibility genes, from the early days of blood transfusion to the cutting-edge science that has yet to appear in the textbooks. "I kind of wanted to step back and take in the big picture," he says. "You can quite easily have a successful career in science without knowing how you got where you are." As a journalist and a layman I am normally happy to summarise decades of tireless research with the words, "It's complicated", but some further explanation is warranted.
Your immune cells don't know a virus from a transplanted kidney; they work by distinguishing between "self" and "non-self". The "self" is expressed at the molecular level, by your MHC genes; they provide the signature that gives your tissue its identity. Actually, your body also produces immune cells that would attack your own tissue, but they are killed off by your thymus in a process known as "thymic education". The T in T-cell denotes an immune cell that has survived this screening.
Your MHC genes also encode the instructions to produce HLA molecules – human leukocyte antigens – that display proteins from inside your cell on its surface. "If you have a virus," says Marsh, "these are the molecules that are taking little bits of the virus [protein segments called peptides], showing it to other cells in the body, and saying: 'What is this? Is this me, or is it foreign?'" HLA molecules possess a groove into which peptides fit, but there are lots of different types of HLA molecules, and some are a better fit for certain peptides than others. The range of HLA types you possess – effectively your genetic "self" – comprises your ability to fight off certain diseases, and your susceptibility to others. They are distributed among us in a way that protects the population as a whole – so an epidemic can't kill us all – but at the personal level a healthy diversity of HLA types is an obvious benefit. When someone smells attractive to you, so the notion goes, you're smelling HLA types you don't have.
It is not completely understood how all this works at the molecular level, but it is at this forefront that Davis toils. "My research is in developing microscopes that look with better resolution at immune cells and how they interact with other cells," he says. This interaction is "reminiscent of the way neurons communicate" in the brain, raising the possibility that your compatibility genes are responsible for more than just fighting infection, and could even influence how your brain functions. I confess to Davis that I don't really understand this part. "None of us do," he says. "I just happened to write a book about it."
But how does the smelling thing work – if it works? It has been shown that mice can, and do, detect compatibility genes by smell, and that stickleback fish also choose mates by their odour, but in humans, Davis admits, the jury is out. "How it works on the olfactory level is basically not understood at all," he says.
Marsh points out that your HLA genes share a neighbourhood on the genome with certain olfactory receptors, and that these are inherited together. "The fact that these genes are right next door to your HLA genes suggest they may have some role in mate selection," he says. "But this might be a bit of pre-history. It may have been important when you were a mouse."
Two weeks after posting our samples, following a car journey that does little to enhance our compatibility, my wife and I finally locate the histocompatibility laboratories. As we are ushered into a boardroom, I prepare myself for revelations I may not like, or even comprehend.
The labs do not analyse HLA types in order to facilitate dating. They do rather more important work, matching tissue types for bone marrow transplants and saving lives. Sharing HLA types with a donor reduces the risk that a stem cell graft will be seen as non-self, and rejected. There are 500,000 potential donors on Anthony Nolan's register, and they have access to a further 750,000 from other UK registers, plus a worldwide database with 22 million names on it. They also spend a lot of time educating the public about stem-cell donation, which is not the invasive surgical procedure it once was.
"It's actually very straightforward," says Ellen Marshall, Anthony Nolan's communications manager. "Ninety per cent of people donate by a method called peripheral blood stem cell collection, which is similar in nature to giving blood." Basically, they take blood out of one arm, harvest stem cells from it, and return it to the other arm. You only donate in the event that you're matched with a recipient, and to join the register all you have to do is send them your spit, as I did.
I can't make much sense of the test results without first getting a bit of education from Marsh. We are primarily concerned, he tells me, with the five major histocompatibility genes: HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ. You inherit these in a block and you end up with two sets, one from each parent. Each set is known as a haplotype; each specific version of a gene is called an allele. Without further testing it is not possible to know for sure which alleles came from which parent, but because certain ones are commonly found together, they can make a statistical best guess about your haplotypes.
"We'll do you first," says Marsh, handing me a sheet of paper with some numbers on it. "That's your tissue type." I nod, because it seems like the right thing to do.
My HLA-A allele on one haplotype, he explains, goes by the name HLA-A*32:01:01. Lots of people have it, apparently. The HLA-B*53:01:01 on the other haplotype, however, is rare among Caucasians, but commonly found in west Africa. He produces two maps showing the geographical spread of my sort of haplotypes. One is most frequently found in Ireland; the other in Russia.
This makes sense. Although I was born in America, I am about as genetically Irish as it is possible to be, the only potential exception being my father's mother, who was adopted. My father once told me she was a Chechen, but he actually has no idea, and tends to change his story depending on which interesting nationalities happen to be in the news. According to my DNA, however, he may have been right.
Statistically speaking, I possess the 39th most common haplotype among European caucasians, alongside the 125th.
"So they're not quite the commonest ones," says Marsh.
"Let's face it," says my wife. "They're pretty common."
"It's a different sort of common," I say. "This is science."
Marsh produces my wife's report. I immediately spot that we share one allele – the aforementioned HLA-A*32:01:01. But this bit of matching type does not mean we aren't one another's type.
"That's the only one you share," says Marsh. "You're quite different, so if the whole sniffing-your-mate-out is to be believed, then you've managed to sniff out a good mate."
It's not a terribly romantic revelation, but it's a relief. As he explains to my wife that her haplotypes are rarer than mine – "much, much rarer," she says – Marsh can barely conceal his excitement. You don't need to be a scientist to see that he is withholding some information that pleases him.
"Interestingly, there's also a B*27 knocking around there," he says. I know from reading Davis's book that having a B*27 gene increases your risk of contracting ankylosing spondylitis, but I'm pretty sure my wife hasn't got ankylosing spondylitis.
"Occasionally we come across people with types we've never seen before," says Marsh. Oh God, I think. Not her.
"You have a new B*27 allele that we've never seen before in the world," he says. "We'll be sequencing you properly, your sequence will go in the database, and we'll give it a new number." My wife beams.
"I feel like I've won a rosette!" she says. She instantly forgets why we've come – to test our compatibility. She is no longer interested in that little piece of good news. On the car ride home she is insufferable.
"I can't wait to tell everyone I've got an unknown – what have I got?"
"An allele," I say.
"A brand new allele," she says. "Yours are all common, whereas mine is unique, like me."
"That's great," I say. "Good luck finding a match for your next bone marrow transplant."
Later I feel bad about saying this, because she's my wife, and she is unique. I smelled her out of thousands.
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