by Lone Frank
ONE OF THOSE who jumped at the chance to be a part of the revolution is blogger Jen McCabe, whom I meet by chance in cyberspace. I’ve collapsed into a chair in front of the computer and am surfing around lazily, trying to get sleepy enough to go to bed, but McCabe wakes me up with the intense pitch of her posts. McCabe has not only reported for duty at 23andMe but has decided to open her gene profile for the first time while the world wide web looks over her shoulder. At home in her apartment, she has rigged up a slightly shaky web cam and, with her face right in the lens, describes how “… cool it is to be able to give something back to the community.” This is the enthusiasm of youth in full glory.
Her seven-minute-long video has been seen a few thousand times, so she may already be on her way toward recruiting the next wave of research revolutionaries.
It starts somewhat jumpy. “Oh, God, wow,” exclaims the well-scrubbed woman several times. She seems overwhelmed. “I’m surprisingly nervous, actually,” she confesses. She has waited two days since the notification that her results were ready arrived in her in-box. “I didn’t think I would be nervous about sharing this information, but yesterday I made a list of the pros and cons.”
She holds a handwritten placard up to the camera. Under “pros” you can glimpse words such as “transparency” and “patient-driven research.” Under “cons” she has very naturally written “privacy,” but I cannot understand why “dad” is also there.
“Well, but now I’m doing it, I’m going to look at my results for the first time so you can see how I react.” Very considerate of her.
“Wow, oh my gosh,” she says again. “Look at this. I have a gene variant that increases the probability that I can’t tolerate gluten because of a deficiency in the enzyme alfa1-trypsin. Wow. This is absolutely news to me.” She sounds a little shaken, too, though the implications of this finding are manageable enough.
“But I carry no variants for cystic fibrosis, and I don’t have the alcohol flush reaction – yes! But wait, they say I can likely tolerate lactose, and that’s not true, I always drink soy.”
She points eagerly at the screen, but the camera is too far away to focus on anything.
“I’m not resistant to malaria or to HIV infection. But look here: I’m a sprinter!”
It appears that McCabe has a variant of the ACTN3 gene, which gives her quick muscle fibers, which makes her more suited to explosive sports than endurance sports. “So, that’s why it was never any use pushing myself to run cross country in school,” she says, smiling uncertainly.
“This is probably really exciting for those of you watching, but I must admit I was really nervous about this,” she says. “But the good news is that I don’t have variants for what I might be worried about – sickle cell anemia and hemochromatosis. And I wanted to share all this with you; it’s because I think it’s important to advocate in favor of patient-driven research.”
McCabe looks into the camera with wide eyes.
“Search for more information on the Net, because this is incredible.I have never been so interested in checking data since I got my first credit card records.”
Here in the weak glow of my screen, I ask whether I should follow this bouncy young American and leap into the great research revolution. It costs less than a hundred dollars to get a gene profile – a tenth of what I’ve already coughed up for deCODEme – and I’m already a convert. It’s easy, too. I just need to navigate to that gorgeous and user-friendly website and click a few times, and they’ll send a test kit.
In a way, this is donating our bodies to science. In this case, it simply happens before we die and we get the option of watching the researchers scrutinize our bits and parts for greater meaning. Like a little dose of immortality.
It’s late, and I’m content just to dip my toe into the water this first time. I set up a free 23andMe account with Research Revolution voting rights. The list is something of a mixed bag: migraines, psoriasis, severe food allergies, arthritis, celiac disease, lymphoma/leukemia, multiple sclerosis, ALS, epilepsy, and testicular cancer. These are all diseases that deserve every possible resource, but I end up casting my vote for the only one with which I have a personal relationship: migraine. Not that I myself have had any terrifying attacks, but an uncle and a cousin have seriously suffered. I know it’s a nasty condition. And it helps my resolution that migraine is already number one in the race with 216 reported patients. Number two, psoriasis, has only 99.
Strange that it feels good to check it off. It really does feel like taking a small role in a growing movement, or perhaps like taking part in the future. But does it work to ask people to provide data themselves? Will they keep accurate records? Will they understand the scientists’ questions? And will they answer these questions honestly – especially when it comes to such tricky topics as diet, drinking habits, or following doctors’ instructions? Self-reported data can make researchers grind their teeth. Can 23andMe find something interesting in its non-random volunteers that traditional research groups, with their randomized studies, real subjects, and recognized universities, cannot?
“I’m a believer,” writes Daniel MacArthur on his blog, Genetic Future. He puts weight on the effective viral marketing by which people who are already part of the project bring in friends and acquaintances. “As patient cohorts get ever larger and 23andMe’s analysis becomes more sophisticated, there’s every reason to expect that this approach will eventually yield the power required to generate novel associations.”
And if Google, which has married into the enterprise, continues its generous support of its finances for another few years, MacArthur sees great possibilities.
“I wouldn’t be shocked to see this research model eventually gather larger cohorts than even the largest academic consortiums, particularly for less common diseases with particularly strong grass-roots activists.”
THE FIRST RESULTS of the research on the volunteer users are made public not long after MacArthur’s comment. In Hawaii, where the American Association of Human Genetics is holding its annual conference, 23andMe’s principal scientist, Nick Eriksson, unveils the findings.
As Eriksson talks, people in the hall hold their breath. It comes to light that the research team, along with partners at Stanford and Columbia University, has identified new genetic traces for three human characteristics. What have they found? Have they finally tracked down definitive data on the genes involved in Parkinson’s or something that indicates a cause for testicular cancer? Not exactly. They have found two SNPs that are strongly associated with curly hair, a single SNP that is linked to the sneeze reflex that some people experience when they are exposed to strong light, and a SNP that seems to increase the risk of aspargus anosmi, the condition that makes you unable to detect the unpleasant smell of the sulfurous compound methanethiol, which is formed in urine after digesting asparagus.
“Much of human genetic variation remains entirely unexplained,” states Eriksson’s team. To remedy this, the researchers have focused on twenty-two “ordinary traits,” as these are called in the presentation, the genetics of which no one else has really shown any interest in. Using questionnaires, Eriksson and his colleagues have determined if volunteers are right-or left-handed, if they have a dominant eye, if they have ever had braces on their teeth, if they have had their wisdom teeth removed, if they get carsick on drives in the country, if they have an optimistic temperament, and if they prefer to exercise in the morning or in the evening. Somewhere in the vicinity of ten thousand volunteers replied to the questions. Then, the researchers only needed to go to the computer and compare their answers with the information they already had about the users’ genes – a gene profile covering half a million SNPs. To answer the skeptics at the Hawaii meeting, Eriksson asserted that the method itself seems to work: the researchers identified a series of familiar genetic associations in their data – that is, clear links between SNPs and physical characteristics such as hair color, eye color, and freckles.
Erikks
on had proved that you can, apparently, conduct accurate research on self-reported, user-generated data. But should you? Isn’t it an appalling waste of time, money, and scientific creativity if you spend these efforts on what makes hair curly or what makes someone bothered by the smell of long-digested asparagus? Weren’t there more pressing questions that could have been posed to the nearly ten thousand volunteers? Isn’t this exactly what critics of consumer genetics disparagingly call “recreational genetics?”
It could be argued that the whole point of genetic democratization – that anyone may someday be able to afford to buy an insight into their genes – is that the patients, that is, the people themselves will influence how the information is used, in research and in life. Who says that serious diseases are the only things you’re allowed to be interested in, and that disease genes are the only things serious enough to merit attention? Why shouldn’t everything be fair game? Ultimately, consumer genetics is about exploring and discovering yourself at a molecular level – and whatever the consumer demands, the market supplies.
“AREYOU HERE, too?”
George Church, a professor at Harvard University, seems mildly surprised to see me at yet another conference in Boston. A short time ago, at the Consumer Genetics Show, I exchanged some polite words with him, and here we are again with nametags and cups of coffee. This time, the setting is Microsoft’s elegant building in Cambridge, and it’s much more exclusive. In fact, it costs one thousand dollars – twice as much as the market price for the cheapest SNP profile – to get in, unless you have a free press pass. The focal point is Church’s own special version of consumer genetics – the Personal Genome Project.
PGP, as it is called among friends, is not only highly personal, it is also wildly ambitious. Its vision is to enrol one hundred thousand volunteers who will, free of charge, have their total genome sequenced in exchange for putting it and a broad range of their health information on the Internet. An enormous data reservoir that will make it possible to look for links between genes, environmental factors, and human traits. Data that includes the name and a picture of the participant and is freely accessible to anyone who might want to look.
“I’m inspired by the Wikipedia model,” says Church, shoving a quarter of a bagel into his mouth. For him, the project is an attempt to create a biological parallel to the computer world’s “open source” movement, where software is free and any volunteer can make improvements and increase overall knowledge. The particularly innovative thing about the Personal Genome Project is that pure amateurs will have access to the data, too.
“These are extremely valuable data, and it would be crazy to restrict them to businesses or academics. The thing is that we can’t know who the future innovators are. The technology is inexpensive enough that everyone can be a part, and the next Bill Gates or Steve Jobs could easily prove to be a fifteen-year-old kid who gets some ingenious idea by rummaging around our database at home in her room.”
Church himself was one of those people who started his career by building computers in the playroom. Now, many years and a number of inventions later, he has been named by Newsweek magazine as one of the world’s “10 hottest nerds.” The American journalist Carl Zimmer calls him “arguably the smartest, most influential biologist you never heard of.” Right now, chomping away, with his wavy hair and a big beard, Church reminds me more of a jolly lumberjack. I remark ingratiatingly that his project makes 23andMe and their Research Revolution look like a May Day rally in the rain.
“Yes, well, we are different from any other project,” he says. It is not just the large number of participants that sets his vision apart, but how thoroughly they are measured and analyzed. The Personal Genome Project incorporates health data from volunteers – their health issues, what medications they take, their diet – and then conducts follow-up studies. For example, the research team sends volunteers for brain scans to better understand the structure and functionality of that organ. It also looks closely at each person’s immune system, and how the person reacts to various infections. Finally, they take a skin biopsy, which is transformed into immortal stem cells and preserved in a biobank, from where anyone with a strong research proposal can order a batch. As Church points out, “You can get a little piece of Steven Pinker.” To investigate how the mind works, I wonder?
You can get a piece of George Church himself, for that matter. Both he and the celebrity psychologist, Pinker, are among the first ten named participants – the pioneers – who also include the Internet guru Esther Dyson. On the project’s website, you can learn, for example, that Church is adopted and dyslexic, while Pinker is of Polish-Jewish extraction on both sides, suffers from esophageal spasms, and takes cholesterol-lowering drugs and folic acid as a dietary supplement. The fifty-eight-year-old Dyson lets it be known that she “… has pretty much never been sick and never missed work.” The only thing she permits herself is regular use of sleeping pills and a daily intake of the hormone estradiol for her menopause symptoms.
At first glance, the project seems taboo-breaking. A sort of genetic exhibitionism. How can they do it? And how do they think they can recruit hundreds of thousands of others to perform the same information striptease?
“At the moment, there are fifteen thousand people in line,” says Church, a revelation which shakes me a bit. “First, they have to take an entrance exam that shows that they understand enough about genetics to know what they’re getting into.”
We are talking about ordinary Americans who, according to Church, fall into three categories: people who believe they are unusually healthy and want to help medical research by making themselves available; people who believe they are terribly sick and, therefore, have nothing to lose but everything to gain; and, finally, people who are genealogy fanatics. They have been tested by the Genographic Project and by 23andMe, and they just can’t get enough.
“These guys are experts; they know more about genetics than I do,” he says as he crushes an empty paper cup. I ask – half in jest – whether he has room for one more, but am rejected because of my nationality. The project only has official authorization to use American citizens. But there are major international plans to collaborate with centers in other countries, which will then start their own genome projects, following the same pattern. In fact, South Korea is already in the offing, as the second personal genomics project to open its doors.
“TODAY, THERE ARE thirteen complete, named, and publicly accessible genomes,” says Church, pointing toward the auditorium, where two hundred participants are gathering. “But this is the first and last conference at which we can gather everyone with a complete genome sequence in one room.”
Some of the thirteen pioneers have decided to stay at home. Steven Pinker, for instance, is not here, but James Watson, the pioneer of all pioneers, has flown in from Cold Spring Harbor. The old man seems to be in fine form, wearing a well-fitting tweed jacket, and with a young assistant to look after him. As the first on the stage, he directly addresses Church, stating that he needs to get on with things and sequence some more genomes at the Harvard lab.
“No more talk, just get it done!” he grunts.
Giggles and hushed whispers spread among the spectators, and the day’s interviewer, the radio host Robert Krulwich, hurries to the next point on the agenda. The experienced science journalist does not hide that he is skeptical about all this publicly accessible genetic information, but he starts gently.
He turns to Henry Louis “Skip” Gates Jr., the Harvard professor of African American Studies. He and his ninety-seven-year-old father have both been sequenced: “the first African Americans and the first father-son pair,” as Gates notes. He adds that if anyone in the room has not seen the television series that came out of the project, we should buy his DVD. He then continues in a less business-minded voice. “First and foremost, I wanted to immortalize my father,” he says.
From my seat at the back of the auditorium, I can’t help but think that this jovial man is proba
bly best known for his scrape with a white policeman, who thought the professor was breaking into his own home in upmarket Cambridge. “Racist” was shouted by one side, “arrogant academic” by the other. The matter had to be resolved by President Obama, who invited the parties to a media-transmitted conciliatory beer in the White House garden.
“It was deeply moving,” Gates says, referring to a scene in the television series in which father and son look at their respective genomes for the first time.
“The most fantastic thing was that we could separate my father’s sequence from my own and thereby get that part of my DNA that came from my mother. It was like having my mother brought back. Dad cried, and I was on the verge of it myself. It was powerful.”
“Why is that?” Krulwich wanted to know. “A DNA sequence is just a printout with graphs in different colors.”
“What is a photograph?” Gates asks calmly. “It’s ‘just’ a graphic representation of a real person on paper. The genome is a metaphor for a person in the same way, and just as people once had to learn to look at photographs, we now have to learn to see the person in these graphs and bases. It’s all a part of our identity.”
Then, the dark-skinned Gates tells us that, by the way, he’s really white. His mitochondrial DNA and his Y chromosome point directly to origins in Europe.
“For thirty-five percent of black American men, their Y chromosome comes from some slave owner, and that’s a shock for many people. But as far as I’m concerned, genetics has to do with breaking down the myths of racial purity. It’s good for us to realize that we are all a human version of bouillabaisse – a wonderful mixture.”
Unfortunately, after this feel-good beginning to the day, Gates has to leave for a budget meeting with his dean. Now we hear from a couple of businessmen: Jay Flatley, the CEO of Illumina, and Greg Lucier, who runs Life Technologies. Both companies dabble in genome sequencing, and both directors exude an air of purposeful no-nonsense. Flatley and Lucier have had their genomes sequenced and made public, and Krulwich wants to know whether they are nervous that shareholders and board members will dig into the data and find things they don’t care for.