June 8, 2013
A strand of DNA. Photograph: Alamy
In the almost year-long lead-up to having my whole genome sequenced, I have no fears about it. Or at least just a couple of tiny wobbles that I easily dismiss. I've gone through a rigorous, informed-consent process that has explained some of the conditions I may have, the predispositions to certain diseases that I may uncover. And I've signed the forms with a breezy it's-always-better-to-know attitude, tick, tick, tick.
Then, on the morning I'm due to get my results, at a genetics symposium in San Diego, I wake early, flick open my computer and read the news: banner headlines on every front page revealing Angelina Jolie 's BRCA1 gene and her decision to have a double mastectomy. It's hard not to be a bit unnerved. I've always thought it better to have information than not have it, and that, anyway, you largely know from your family history what nasty diseases are floating around your gene pool.
"Not necessarily!" a geneticist called Bob Best cheerfully tells me at breakfast. The BRCA1 gene doesn't always show itself if it comes down your father's line. "And then there's de novo mutations which just appear out of nowhere." The thing is, he says, that "we know so much less than we used to know. Ten years ago, James Watson testified to Congress that once we had the genome sequenced, we would have the language of life. But it turns out that it's a language we don't understand."
I tell him about Jolie and he almost falls off his chair. "You're kidding me! That's a total game-changer." By the time the first speaker, Eric Topol, the director of the Scripps Translational Science Institute, takes to the stage with a presentation called "Digitising Human Beings", Angelina is the talk of the symposium. "This is the moment that will propel genomic medicine forward," says Topol flashing her image on to the screen behind him. "It's incredibly important symbolically."
Analysing a DNA sequence transparency. Photograph: Alamy
It's hard to overstate how new genomic science is, how quickly it's changing, how revolutionary it's likely to be. Jolie's tough choice was still a choice, a choice made possible through the leaps and bounds that have been made in genetic testing. But whole genome sequencing is going to take this to a new level. It's the complete code of everything in our bodies and it's right on the threshold of going mainstream. The first human genome was fully sequenced less than a decade ago. It took 13 years and cost $2.7bn. The first individual's (the previous ones had been composites) genome – Craig Venter's – was sequenced just six years ago, in 2007.
"And tomorrow," Matt Posard, senior VP at Illumina, the technology company that's organised the symposium and makes the sequencing machines, "everyone in this room will be able to hold their genome in their hand, like I am." And he holds up an iPad on to which Illumina is going to download our results. "You will be able to surf your genome and find out everything about yourself."
It does have more than a slight air of science fiction about it. Sequencing the human genome was such a major breakthrough, such huge news when the announcement of the first draft of the human genome was made back in 2001 and it feels as if that was about two minutes ago. I can't actually quite believe I'm here.
But then, the room is full of geneticists who also can't quite believe they're here. Scientists who have spent their whole career in the field, and they're mostly as giddy as schoolchildren about having their own genomes sequenced – all of it, not the "snip" tests that some companies have started to do, or the exome, the protein-coding region of it, but all of it. It's the holy grail: whole genome sequencing.
At the welcome drinks reception, I chat to Colin Smith, a professor in functional genomics from the University of Surrey. Did you ever imagine you would have your own genome sequenced? I ask him. "Never!" he says. When did you think it might ever become a possibility? "When I got the email from Illumina inviting me here."
It's only possible because of the astonishing drop in the price of sequencing. There's a widely published graph that shows it dropping at four times the rate of Moore's law (the law that states that computer processing power doubles every two years), though Euan Ashley, a Scottish assistant professor at the Stanford School of Medicine, illustrates it even more graphically.
"Every day, I drive past this Ferrari dealership in Palo Alto," he says, "and I see the 458 Ferrari Spider which retails at $398,000. I've worked out that if that was the cost of sequencing at the time of the Human Genome Project , and the price had dropped at the same rate, the car would now cost 40 cents."
The cost of sequencing a single human genome today is a tiny fraction of what it was – it has gone from $2.7bn in 2003 to the $5,000 that everybody in the room has paid – and that includes the iPad that has your results. Nobody thought the price would drop so far so fast. When I first looked into doing this article, it cost $48,000, "though we could do you a press rate of $35,000," the PR of another company, Knome, told me. Hmm, I said, I may have to take a raincheck. That was less than three years ago.
Model of a DNA strand. Photograph: Alamy
Interpreting the results and returning the data to individuals, though, is still in its infancy. It's still a time-consuming, painstaking process. Illumina held the first "Understand Your Genome" event last autumn, and this is the second. It is the first time a large cohort of individuals has had its genomes sequenced and been given the results, the idea being to let genetics professionals experience the process and understand what's involved before it comes down to the rest of us. Jay Flatley, the CEO of Illumina, estimates that to date fewer than 500 individuals have had their whole genome sequenced. More have been done, anonymously, for research, but only 500 individuals have ever had their results returned to them. "And you're one of them."
I feel overwhelmed, privileged. And just a little bit worried. The life sciences are, in some ways, the final frontier. During one of the panel sessions, somebody asks Bonnie LeRoy, a professor in genetic counselling, where we are, chronologically, now with genomics and she says: "It's the moon landings, right? It feels like we've just landed on the moon. Except I'm old enough to remember the moon landings and everybody was engaged, everybody in the world knew about them. It's like we're on the spaceship but nobody knows about it."
She's right. Every day, there's another story about another gene being found in the newspapers, and yet the great personal health breakthroughs haven't quite happened But they will. When sequencing is applied to a mass population, we will have mass data, data that will reveal who knows what. In the opening session, Illumina's Jay Flatley talks confidently about how in a few years, all newborns will have their genome sequenced, and in five to 10 years, cancer will be downgraded to a chronic disease. It sounds like an outrageous piece of boosterism but in fact, everybody I speak to, in the US, in the UK, agrees that the genomic breakthroughs in cancer treatment are already underway and it really is transforming treatment of the disease.
"Chemotherapy is just medieval," says Eric Topol. "It's such a blunt instrument. We're going to look back on it like we do the dark ages." Tumours can now be sequenced and drugs tailored to the individual. It's the dawn of personalised medicine and it's already happening in the NHS, but with it being the NHS, it's piecemeal and few doctors have ever been trained in genomics, let alone GPs.
Last autumn, I blithely skipped along to my surgery and asked my GP to countersign my consent form. A locum took it away and said they'd be in touch. Then my doctor, without ever meeting me (in fact, she's never met me), sent me an email that contained phrases like "can of worms", "I would urge you to think very carefully about getting this done" and, ultimately, "we do not feel as a practice that we can take this on".
Howard Jacob, director of the Human and Molecular Genetics Center in Wisconsin shows Carole Cadwalladr how to use the MyGenome app on her iPad. Photograph: Brent Altomare
At the time, I fumed about that. The information is out there and very shortly it's not going to cost $5,000, it'll be more like $500 and then $50. People are going to start getting their genomes sequenced and the NHS is going to have to deal with it. I'm cheered by Eric Topol's talk, even if some of the things he sees coming seem, to me, as likely as personalised rocket ships. ("In the future, people like Angelina might not have to have a double mastectomy. You might have a sensor in your blood which at the first sign of plasma would send a cancer ringtone to your phone, and that is eminently do-able.")
But he thinks it's "crazy" that a doctor who knows nothing about genomics should stand between us and our personal information. "The situation today of this asymmetry where the doctor has all the information and the patient has just a little bit and typically they have to beg for that – that is going to change."
The NHS has been go-ahead in other areas, though. Earlier this year, David Cameron committed £100m for the sequencing of 100,000 patients . It's the most ambitious programme of any country, and people who have been lobbying the NHS for years to wake up to genomic science, such as Ron Zimmern, of the PHG genetics think-tank, are excited as a kitten. "It's a potential treasure trove!" he tells me. "We're in a unique position in this country; because of the NHS and the records system, we can link it back to real people's health."
The closer I come to getting my results, though, the more I start to understand where my GP is coming from. There are 6.4 billion base pairs in every genome. The results alone take up half a terabyte of data, data that is now held in the Amazon cloud and that can, like all digital data, be potentially hacked and leaked. When Illumina first held this symposium last October, it had clinically interpreted 354 known disease-causing genes. This time around, it had done 1,600. Tina Hambuch, associate director of clinical services at Illumina, explained that in the 47 genomes of the people at the symposium, they'd found that those 1,600 genes were implicated in 1,221 conditions. They then evaluated 23,144 variants for possible roles in those conditions and concluded that 65 were likely to be pathological variants" that may play a role in causing disease. It had taken a small army of people to work this out, who'd read and reread the papers, two double-blind groups who looked at all our mutations. The cost of getting the data may have fallen through the floor, but working out what to do with it is an expensive, tricky business that computing has yet to solve.
At the drinks party, people are excitedly sharing their results. Colin Smith, the geneticist from Surrey, tells me how he's got mutation on a particular gene. "And both copies of that gene are mutated and that gene makes an enzyme that doesn't work at all. It means that if I have a particular class of drugs, it would kill me. Or at least there's a good chance it could kill me. And these are quite widely used immunosuppressants used in anti-cancer treatment or transplantation."
Somebody else, he tells me, has found a mutation that means that he – and potentially his children – could die if ever put under anaesthetic. "What did they find on yours?" he asks me. I don't know yet, I say. He raises his eyebrows but then he has pretty good reason. His father had Huntington's, one of the nastiest genetic diseases around, a fatal, neurodegenerative disorder that typically hits in middle age, and which, as the child of an afflicted parent, Smith stands a 50% chance of developing himself.
He was tested seven years ago. "And I tell you after going through the test for that, this was a breeze." He's someone who knows, first hand, how genes are the luck of the draw. "I was going to give up my job and move to Sicily if it was positive," he says. And then he wishes me luck.
I am, it has to be said, a little bit nervous by the time I get my results. It's simple, common-or-garden curiosity and excitement about the science that has brought me here. A few years ago, I wrote a novel that hinged on genetics, but there's no terrible disease in my family that I wanted to know more about. In San Diego, though, I start to think a bit harder about what everyone in my family has died from… and I realise that I don't even know. The Welsh Cadwalladr side of my family, my dad's, have had a tendency to drop dead at a relatively young age, but largely due to diseases that I'd assumed were related to being poor, working-class, Welsh. My grandfather smoked and died of emphysema. My dad smoked and died of lung cancer.