Do you really want to know what you might die of? New research answers the questions you may be afraid to ask . A pioneering 'personal genome service' has just been launched internationally, with a brilliant young Dublin geneticist on the team. Davin O'Dwyerreports
Brian Naughton's mother likes grapefruit, but Naughton and his three brothers have never been partial to it. A matter of personal preference, one might think, except that Naughton has a pretty good idea why his mother might like grapefruit more than her sons - she has the gene for bitter-taste receptors, but they do not. He knows this because he is involved in a pioneering company that promises to revolutionise our understanding of our DNA and change the way we think about our health, our families and our futures forever. The world of consumer genetics is nearly upon us, and Naughton is trying to make sure it happens sooner rather than later.
If your understanding of DNA is largely informed by CSI: Crime Scene Investigation or vaguely remembered Leaving Cert biology classes, prepare to become considerably better acquainted with it. Until very recently, it was impossible to read our own genome, the hereditary information stored in DNA that determines everything about us from our hair colour to our height to our risk of getting a range of diseases - there was just way too much data, about six billion points of genetic code. But since the Human Genome Project succeeded in mapping the human genome in 2003, the science has been developing at breakneck speed, to the point where you can now pay $999 (€690) to get an overview of your genome and gain an insight into why you are the way you are. The company that offers this pioneering service is 23andMe, a California-based start-up that Naughton helped create.
It has been a fascinating journey for the 28-year-old Blackrock native.
Naughton studied human genetics in Trinity, where I was good friends with some of the other students in his class, and I gradually got to know him during our time there. They were a close-knit group of very smart, motivated people, but they all had an evident respect for Naughton - he was not only top of the class, but, almost more importantly, he had a wickedly droll sense of humour behind the quiet exterior. Upon graduation, much of the class went their different directions to embark on PhDs. Naughton went to Stanford University in Palo Alto, California, to study biomedical informatics (BMI, or the application of computers and data analysis methods to biological and medical data, to the curious layman).
"For the last year or more of my PhD, there was only me and a guy called Serge Saxonov in the lab," he says, his accent now as much Bay Area California as south Co Dublin. "We spent maybe more time than we should have playing around with web applications like javascript and HTML. We both decided we were not destined for academia, and of course, being in Silicon Valley, there was a lot of talk about start-ups and new Web 2.0 companies [second generation of web-based communities]. We were interested in the concept of Web 2.0, but we were still interested in biology, and there seemed to be a good opportunity to combine both."
That opportunity was the flood of post-Human Genome Project research on SNPs (pronounced "snips"), essentially variants in the human genome that scientists were correlating to phenotypes, which is the observable, physical characteristics of a particular gene. So if you have a certain SNP at a particular point of your genome, it will result in the brown-hair phenotype, say, or the bitter-taste receptor phenotype.
"These studies were becoming more common while Serge and I were finishing up," he says. "The results were frequently being published, but there was no way of getting that information and applying it to people."
Luckily, a professor that Saxonov was working with introduced the two grad students to Anne Wojcicki and Linda Avey, who were in the process of founding 23andMe (a reference to the 23 pairs of chromosomes that contain our DNA), a company that would allow people to "Google their genome". The Google metaphor was apt, because Wojcicki's then boyfriend, and now husband, was Sergey Brin, co-founder of Google.
"We met in a famous Venezuelan cafe called Coupa in Palo Alto, five minutes from Stanford. It's where all the start-ups meet. Every table has young tech nerds huddled around. If you arrive for a meeting early, you do try and overhear what other people are talking about, just in case," says Naughton. "The four of us hit it off. Serge and I were on the same page as Anne and Linda, but coming at it from a different angle, the science angle. We wanted to build the 'thing', Anne and Linda wanted to build the company.
"Serge and I were the first two employees - I started at the end of summer 2006, the day after I handed in my PhD. I was pretty excited to get started."
The third employee was a friend of Saxonov's from Harvard called Alex Wong.
"The company got a little apartment where we did all our coding for the first few months, while Anne and Linda did everything else. Alex focused on the coding of the website and getting everything working, while Serge and I did the biological coding. It was just the three of us for a couple of months, but now we're at nearly 40 staff."
Brin and then Google were early investors, and the 23andMe headquarters are just down the road from Google's.
"The Google connection helps," says Naughton, "because people have very positive feelings towards Google, and there are a lot of benefits to being associated with them. But we're not a subsidiary; we're independent." The company unveiled its "personal genome service" last November in a barrage of high-profile media coverage - including a front-page New York Times piece and a Wired magazine cover story proclaiming the "Age of the Genome". It was launched internationally at the World Economic Forum in January.
As the highest-profile purveyor of "consumer genetics", 23andMe is blazing some particularly sensitive trails. It goes to great lengths to educate customers and explain the concepts involved, all too aware of how unacquainted most people are with the science. The sci-fi dystopian vision of a Gattaca-style future, where we are designed at a genetic level to be perfect, has an all-too-powerful hold on the imagination.
There are no designer babies at 23andMe, however. Upon paying their $999, customers receive a slickly packaged green box, more Apple computer than Pfizer pharmaceutical. The box contains a test tube for a saliva sample (the company requires a sizeable amount of saliva to extract the genetic information) and an envelope in which to return the sample. Instead of sequencing the entire genome, which is still exorbitantly expensive, 23andMe looks for 600,000 specific SNPs that offer a thorough overview of the genome. Once the analysis is complete, customers can log on to 23andme.com and see what their DNA reveals about them, about their bodies, their ancestry, whether they have greater athletic endurance or a higher risk of glaucoma, and more.
"There are three areas on the site," explains Naughton. "Gene Journal is the main part, the part that people find easiest to understand. If they want to know their risk of diabetes, say, it makes it easy to grasp. The journal tells you about a bunch of phenotypes, such as Type 2 diabetes, bitter-taste receptors, lactose intolerance, a bunch of stuff like that. The number of Gene Journal articles is growing, because we're learning more and more about the genome, so the 600,000 SNPs can tell you a lot about phenotypes that are not yet on our site. We expect it to grow to hundreds of phenotypes, eventually.
"The second part is the Ancestry section. We do the mitochondria test, which indicates the maternal line. Every mitochondria can be classified by groups called haplogroups, which are indicative of your ancestry, so if you have an African haplogroup, it means your mother, or your mother's mother, or your mother's mother's mother, etc, was African. We'll soon be testing the Y chromosome, which is the paternal line equivalent.
"The third part is a social feature. If you link your account to a friend's or family member's account, then they will show up on your features, allowing for a lot of comparison functions. Say you and your sibling are both on our database and you're linked up - on average you share 50 per cent of your DNA, but it's pretty random which 50 per cent. It depends on which pair of grandparents you got each chunk from. But with Genome Labs, you can compare siblings.
"I've got my family in the database, so I can see with my brothers the pattern of inheritance, which part of our genomes are the same, which are different. You can, by chance, share a lot more with one sibling than another. You can then compare phenotypes, so we can see which brother has the same gene for eye colour. Or, for instance, one of my brothers is a perfect tissue-transplant match, and we know which pair of grandparents are responsible for that. It's amazing not just to know that, but to be able to see exactly where it comes from."
This is all bleeding-edge technology, and 23andMe must face ethical considerations that have never been dealt with before. The widespread lack of understanding about the science means there is a lot of room for misunderstanding, and the perception that consumer genetics services are somehow playing God, or that calculating the risk of disease is merely a type of fortune-telling, are serious obstacles.
"The ethical implications are a huge deal," says Naughton, "and there's a lot of energy expended about the best way to present the information and to do it responsibly. At the same time, we believe that people can handle their genetic information, and we also believe that you can't give people just the eye-colour information, say, and hide the rest of it from them. We don't want to take a paternalistic attitude; that's the basic philosophy.
"You can't deny people access to their family history, you can't say it's not right for people to know that their uncle or father had a heart attack, but that's very predictive as to whether they're at increased risk of heart disease. No one would argue that you shouldn't have the right to know that, and that's how we feel about your genetic data. Being pale is a predictive for getting skin cancer, but there are other SNPs that also mean you're at a higher risk of getting cancer that you can't see. Just because you can't see it doesn't mean it's not equally as out there as your family history, or phenotypes that you can see."
Essentially, 23andMe is making previously invisible phenotypes visible, and while that may sound daunting, Naughton feels the consequences will be wholly positive.
"For example, currently, your doctor has your medical records, but very few people know what's in their medical records or even what could be in their medical records, but with 23andMe and the consumer genetics world that's coming, everyone will have access to their own data. You'll see all this information organised about your genetics, info that you couldn't get before. You have the idea that it's your responsibility to know a lot more about your body than you now do.
"We obviously want to make sure there's as little misunderstanding as possible about what the information is telling you. It's definitely difficult for people to just understand everything immediately, so there's a lot of education to be done. We have some cartoonish intros to genetics on YouTube that are really good, that get across what we're doing."
In an effort to prevent discrimination based on one's genetic make-up, the US Congress is in the process of passing a bill, the Genetic Information Non-discrimination Act (Gina), that would make it illegal to deny a job or health insurance on the basis of a person's genetic make-up. Drafting effective legislation as the technology develops is notoriously difficult, however, and there will more than likely be some difficult test cases in the years ahead as we grapple with the reality of our now readable genome.
In Silicon Valley, though, future obstacles are to be hurdled rather than avoided. How has Naughton found studying and working in the original Googleland? Are there any lessons we can take to enhance our entrepreneurial and technological prospects?
"There is this attitude here that you can start a company, and if it fails, it doesn't really matter . . . if you're good you can always get another job. It's different in Ireland, because we weren't always so prosperous, so there was an impetus to get a stable job, because then you won't be unemployed, right?
"The other really important thing is the critical mass of programmers and money and talent in one small area. That part is actually really difficult to replicate in Ireland, or even in Britain. I mean, there's a lot of money in London, but there's not the high concentration of programmers and technically minded people. It becomes self-fulfilling, because if you want to be in that environment, you move to Silicon Valley, and then there's one less person in Dublin or London who's interested in coding. So it's partially the attitude, partially the confluence of money and technical ability. It's also important that Stanford is right there, because the Stanford computer science department has got to be the best place in the world to come out of to start a tech company. These are all things that are really hard to get up to critical mass."
Naughton is in that rare position of working in a pioneering field with potentially far-reaching consequences.
"Everyone, when they hear what we're doing, wants to talk about it. Even people who are concerned about the amount of information that will be released, because they feel it's disruptive, want to get engaged. That feeds everyone at the company, because we all want to be disruptive; we want to change how people think about their genetics and how they think about taking care of their health and owning that to a greater extent. We think it's going to be a huge change, the idea of personalised medicine. Knowing a lot more about yourself is a really empowering thing. You often hear people say something like 'My son is dyslexic.' But that's a new phrase; it didn't exist until maybe 20, 25 years ago. I think similarly, in the not too distant future, people will be saying how their son has a variant of a certain gene. I think everyone will take on the language of genetics, adopt the terminology the same way people adopted the language of the internet."
Just as the internet was a radicalising force that was quickly absorbed into our quotidian lives, so will consumer genetics, Naughton believes. Ultimately, though, 23andMe is leading the way in a field that could be just as revolutionary, and which could irrevocably change our sense of ourselves.
See www.23andme.com