On a recent flight home from Europe the movie selection was so limited I decided, reluctantly, to watch The Time Traveler’s Wife. My reluctance was not due to movie snobbery (I have lowbrow taste), but because when I am tired and 30,000 feet above the ocean, manipulative, sentimental romances make me cry; not just sniffles, but full tears occasionally accompanied by sobbing. Watching action and adventure films is no antidote, since tears and heaving shoulders are inevitable if the hero happens to find redemption, revenge or long-overdue respect. Left with no options, I began watching The Time Traveler’s Wife, expecting the worst, but I soon found myself too preoccupied by the premise to let loose with the sobs.
The protagonist, played by Eric Bana, has a genetic anomaly—Chrono-displacement Disorder, to be exact—that causes him to involuntarily travel through time (which is, it turns out, tough on a relationship). While I am a fan of fully suspended disbelief in the service of cheap entertainment, I found it bizarre that the creative minds behind the movie—and, I assume, the author of the book—felt that genetic science was the best way to explain time travel. It struck me as the equivalent of using cellular biology to describe gravity.
The more I thought about it, however, the more Bana’s chromosomal dilemma made perfect sense. It echoes the current place of genetics in our social consciousness. Genetics is all-powerful, it’s everywhere, and we can’t escape its reach. And so it’s only natural that Hollywood would embrace genetics as a mystical force powerful enough to tear Bana from the embrace of the lovely Rachel McAdams.
For decades we have been bombarded with headlines and magazine covers that extol the advances occurring in the area of genetics. We have been told that we are living through a “genetic revolution.” In 1994, Time magazine ran a cover story entitled “Genetics: the Future is Now.” A decade later, Time ran another genetics cover, telling us this time that “gene science has changed our lives.” And, if you believe the headlines, scientists have already located a gene for virtually every human condition you can think of. Even a short sampling of recent headlines bears this out: “Is ‘Laziness Gene’ to Blame for Couch Potatoes?”; “The God Gene: Does Our DNA Compel Us To Seek a Higher Power?”; “Always Lost?: It May be in Your Genes”; “Party Animal: It May Be in Your Genes”; “Marriage Problems? Husband’s Genes May be to Blame”; and, my personal favourite, “Genes May Effect Popularity, Researchers Say.”
But what is the truth? While I am fairly certain genes can’t transport us to another time or dimension, this extraordinary level of pop culture attention gives the impression that a revolution is afoot. If our genes can tell us whether we are destined to be lost, religious, lazy, unfaithful or unpopular, and if, as the magazine covers declare, the future of genetics is now, then shouldn’t we be able to put genetics to work for us?
My first trip to Mountain View, California was in 1997. I was at Stanford University as part of a research team looking at the social implications of the “Genetic Revolution.” Should kids get tested to find out genetic predispositions? Will insurance companies want to know your genetic background?
These all seemed like timely and important issues. We were still only a few years into the revolution. The massive Human Genome Project was not yet finished and, in 1997, it was easy to believe that society was only a few years away from enjoying myriad medical breakthroughs and concomitant social dilemmas. Few of us within the biomedical community doubted the potential of the field. I toiled away producing articles on how society should respond to the revolutionizing breakthroughs that were on the horizon.
Thirteen years later I was back in Mountain View to take advantage of one of the few tangible products of that revolution. The plan was to get a profile of my genes—or, at least, almost 600,000 genetic markers—by a company called 23andMe (so named because each one of us possesses twenty-three pairs of chromosomes). My journey to Mountain View to get tested by 23andMe actually began two years earlier, in an auditorium at the University of Toronto, in the fall of 2008. That event was a public lecture on direct-to-consumer genetic testing, and the auditorium was surprisingly full with what seemed like well over 500 people from all walks of life. I was sitting on the stage with Joanna Mountain, a Stanford assistant professor and the senior director of research for 23andMe. The focus of the event was whether the new era of commercial genetic testing offered any health benefits. Could genetic testing really provide the average person with information to improve their health?
Mountain told me, later, that that Toronto panel, which included a number of scientists and genetic clinicians from around the world, “was one of the most hostile panels I have ever been part of. I felt like it was me against six other people.”
I was one of the six.
When it was my turn to speak on that Toronto stage I told the audience that most of the information provided by genetic testing companies was useless, a complete waste of money. In response, in front of the audience, Mountain offered me the 23andMe service for free. It sounded like a dare.
I met Mountain’s strategic generosity with a firm and public “no thanks,” declining for three reasons. First, I believed the information would not tell me anything valuable about my current and future health status. Second, despite this skeptical view, I was worried that I was, in fact, just neurotic enough to over-interpret whatever results were provided, that I would become one of the “worried well.” Lastly, I didn’t want to come off as hypocritical and opportunistic (“Well, if you are offering it for free, sign me up!”). Although I had three reasons to say no to Mountain, I shared only the first with the audience.
But my curiosity grew. Perhaps I was interested in knowing what this test might say. I am, after all, as self-interested as the next person. How could more information about me not be worth knowing?
And so, more than a year after the public lecture, I emailed Joanna Mountain to take her up on her offer. She responded immediately and sent me the information necessary to order a 23andMe test kit from the company website. When I told my wife and four children of my plan, most were not thrilled. My wife was worried I’d discover health information that would cause her stress. My eldest daughter, who is eleven, wondered, not irrationally, why “anyone would want to know what will kill them.” My six-year-old son viewed the required spit collection process—23andMe sends you a tube to gather what seems like an entire mug of saliva—as a significant and insurmountable problem. “That is super gross, Dad,” he said. “Do it in the bathroom.”
With these lukewarm family endorsements secured, I put a large tube of my lukewarm saliva in an envelope and sent it across the US/Canada border.
Why get your genes tested? Trying to answer this complex question first requires a look at the scientific advances that have brought us to the point where a comparatively small company such as 23andMe can offer to test over half a million genetic markers for less than the cost of a cheap suit. Genes, as anyone with even a basic exposure to biology knows, are the units of heredity—a reality that was first illuminated in the 1860s by Gregor Mendel, an Austrian monk who diligently and meticulously studied the variation of pea plants in the courtyard of an abbey in what is now the Czech Republic. Mendel showed that traits, such as wrinkly pea skin, could be passed from generation to generation.
In the early 1900s, scientists built on and refined Mendel’s rules of inheritance, including their role in the development of disease. In 1908, for example, British physician Sir Archibald Garrod suggested that some diseases were due to “inborn errors of the metabolism.” It wasn’t until 1953 that the actual unit of inheritance, the gene, was famously described by James Watson and Francis Crick in a ridiculously short article in the journal Nature. The one page paper, one of the most famous in all of science, starts with the understated pronouncement that “we wish to suggest a structure” for DNA that has “novel features which are of considerable biological interest.” It then goes on to describe the double helix shape that has become the ubiquitous emblem of modern science.
In the 1970s and 1980s a variety of new technologies allowed scientists to read the chemical codes that make up our DNA. The complexity is staggering. Try to imagine your genetic material, your genome, as a string of letters…three billion letters. It would take ten years to read it out loud. New technology (sequencing) made it possible to start unraveling this big string to try and identify the place and function of genes. While still slow and expensive compared to today’s computer assisted and automated sequencing, the 1980s technology had progressed to the point where many in the scientific community thought it was time for a big step: the sequencing—or mapping—of the entire human genome. In April 1987 a group of leading scientists issued a report calling for the US government to “fund a major new initiative whose goal is to provide the methods and tools which will lead to an understanding of the human genome.”
This report was what initiated the Human Genome Project (HGP), the project that led to the genetic revolution, the era of genetic medicine, the biotech century, or whatever other hyperbole-laden label you wish to use. The report itself was enthusiastic about the potential for the project, understandably, since they were asking the US government for hundreds of millions of dollars, but they did add a caveat, tipping their hands to the unknowable meanderings of scientific inquiry: “We do not know what sequence information is the most valuable. It is likely that the most significant applications to medicine cannot be foreseen at the present time.”
The HGP was biology’s first foray into the realm of big science. Costing over $3 billion, it was a scientific effort on the scale of the trip to the moon and the Manhattan Project that, if measured against quantifiable technical goals, was a genuine success. In April of 2003, 99 per cent of the gene–containing part of the human sequence was finished to 99.99 per cent accuracy. The project was, in effect, complete.
Francis Collins was the head of the US arm of the HGP, and in the summer of 2009 Barack Obama appointed Collins as the director of the National Institutes of Health. Collins has consistently said that improving human health and reducing the burden of disease for all people was, and remains, the real goal of the HGP. Measured against this standard, the success of the HGP is less certain.
Since the completion of the HGP the technological advances have been breathtaking. Gene sequencing has improved to a velocity unimaginable even a few years ago. It is also vastly cheaper. A 2009 article in the journal Science outlined how a genome was sequenced for just $4,400. Many in the scientific community think that cheap genomes (as little as $500) are just around the corner. In only seven years (a true blink of the eye in the usual tempo of science), the cost of sequencing a genome has dropped from the billions to the thousands and soon to be hundreds. It’s like the Apollo moon project now costing the same as a flight from Edmonton to Toronto.
These are the technological advances —driven by computer automation—that have allowed companies like 23andMe to emerge. The cost, speed and efficiency of genetic research and analyzing the genetic markers (since 23andMe does not sequence entire genomes; rather, it looks at genetic markers along the genome that, through genetic research, are known to be associated with a disease or trait) has decreased to the point where it can be offered to the public at a reasonable rate.
But, more to the point, what does all this mean to me, for my health? Yes, it’s exciting, but can this technological genetic wizardry allow me to live a healthier life today? I had sent my saliva south. I was now waiting for answers, wondering if my 23andMe genetic profile would provide me with information I could use to make health decisions that mattered.
Two days before heading to Mountain View to meet with Joanna Mountain, I received an email from 23andMe telling me that my results were ready. The email said I could even look at the results now, on my computer. I was sitting in my home office when I got the email, enjoying a moment of guiltily surfing the net at precisely the hour I knew two kids were headed to bed and two others needed help with their homework. Perhaps not the best time to peek into one’s genetic destiny, but I was too nervous and excited to resist. I opened the web page. I found my profile. There it was. I could hear the normal family chaos rumbling outside my office, but I opened the results anyway. They were intriguing. Provocative. But then I read something…
“What the fuck?” I said, obviously louder than I’d meant to. I don’t often use profanity. Even from within my office, the outburst caused a brief and instantaneous moment of family silence.
I arrived at the 23andMe headquarters early in the morning. From the outside the company nerve centre looked like a typical business-park style office; the bland brick façade and modest corporate sign said more “insurance adjusters” than “paradigm-shifting hub of innovation.” I reminded myself that this company had garnered considerable international attention and created about the same level of controversy (in 2008, Time magazine declared its DNA testing kit, the one I used to collect my spit, to be the best invention of the year, but a number of jurisdictions, including California and New York, have locked horns with 23andMe, claiming, in brief, that it is providing an unregulated medical service).
I was early, though not that early, knowing Californians don’t work before 9 a.m. The building looked dead. The door was locked. I pressed a button, and soon a hip–looking, youngish employee opened the door without even asking who I was. Joanna Mountain arrived a few moments later. “Sorry I’m late,” she said apologetically. “Dropping the kids off.”
Mountain, whose look and speech is more professorial than corporate, walked me through an open-plan office. We sat in a brightly-coloured lunch room adjacent to an even more brightly-coloured workout room. “We have a Google mentality about fitness and lifestyle,” Mountain explained, referencing one of 23andMe’s biggest investors and Mountain View neighbour.
We logged onto my personal 23andMe web page and start chatting about the results, which are attractively arranged. Each “disease risk” is presented with a “confidence” rating (based on available research) and a listing of your risk (as a percentage) compared to the general population. The website offers results for dozens of disease risks. They are grouped together according to elevated risk, low risk and typical risk.
Here is what I found out: I do not have an increased risk for throat cancer (the disease that killed my mother); I do not have an increased risk for high blood pressure (despite the fact that regular blood pressure checks tell me my systolic pressure is consistently elevated); and I have an increased risk for celiac disease, prostate cancer and atrial fibrillation.
At first glance, it all appears somewhat ominous. Reading the phrase “increased risk for prostate cancer” is not a great way to start the day. But are these “risk” increases meaningful? Not really. Almost without exception, the increases are mild or moderate. And more importantly,they must be read within the context of daily life.
The 23andMe report provided me with five key elevated risks, those meant to be viewed as the most significant. The celiac risk was part of this group. My genetic markers indicated I have a 0.4 per cent chance of getting the disease. This is an increase over the population average of 0.1 per cent. I also have an increased risk of multiple sclerosis. My risk: 0.5 per cent. The population average: 0.3 per cent. When compared to the impact of obesity, not exercising, driving while talking on a cell phone, and, the big one, smoking, a 0.2 per cent increase in risk is essentially lost in the wash of the risks associated with life.
There was still the one piece of genetic information that had so unnerved me when sitting in my home office. I asked Mountain about that one piece of data. “Can that genetic result be right?”
“Probably,” she said.
My expression must have betrayed my disappointment about this particular result, because she added, quickly and with a patient smile, “Perhaps you have another genetic mutation that moderates its impact.”
In a 1999 New England Journal of Medicine article Francis Collins suggested that the main benefits of the HGP would be new drug therapies, gene therapy, pharmacogenomics (that is, drugs tailor-made for individual genetics) and preventive medicine (using genetic risk information to motivate behavior change). In the article, Collins used a hypothetical scenario to describe how, in 2010, the genetic revolution would impact our lives and the practice of medicine. The scenario represented a hopeful prediction made while the excitement surrounding the HGP, and the future of health care, was at its most intense.
Collins’ predictive scenario involved a visit by a typical male patient to a doctor, in which the doctor used an interactive computer program to take the patient’s family history and in which the patient took a battery of genetic tests for common diseases (again, using an interactive computer program to pick the tests). The hypothetical patient found he was at high risk for lung and coronary disease. And, as Collins put it in the article, “[c]onfronted with the reality of his own genetic data, he arrives at that crucial ‘teachable moment’ when a lifelong change in health-related behavior, focused on reducing specific risks, is possible.” The genetic risk information provided the patient with the “key motivation for him to join a support group of persons at genetically high risk for serious complications of smoking, and he successfully kicks the habit.”
Now, in the real 2010, the genetic revolution has not arrived quite as Collins had envisaged, (though to be fair to Collins, most predictions about the practical applications of genetics—such as gene therapy—have been wrong, or, at least, overly optimistic). Family physicians do not offer routine testing for genetic predispositions to common disease, and they do not have cool interactive computer programs to determine which genetic tests to order. And there seems to be no getting around the unalterable tendency of humans to persist in their bad habits, no matter how unhealthy.
A few days after returning from Mountain View I called Jonathan Kimmelman, who possesses a PhD in Molecular Biophysics and Biochemistry from Yale University and is now part of the McGill Biomedical Ethics Unit. Kimmelman has a strong understanding of both the science and social consequences of genetics, and it would be fair to say that the hype surrounding the potential clinical application of genetic technologies irritates him. Normally a man of mild manners and easy temperament, he becomes agitated when discussing the topic, although he does believe that some genetic technologies will have an important role in future health care systems. Kimmelman feels researchers are too confident about how basic research—conducted in labs using test tubes, computers and, when necessary, animals—will eventually play out on a human subject. “If we went back and looked at all the pre-clinical research that looked good and exciting,” Kimmelman told me, “we’d see that ninety-nine out of a hundred times we were wrong. I marvel at how people interpret these pre-clinical studies. You’d think the reality of the situation would change our perspective. The way people interpret pre-clinical evidence is often shockingly unsophisticated.”
Kimmelman also thinks that despite the glowing reports in the popular press and from people like Frances Collins there has, in fact, been a rapid deterioration in scientific support for the idea that genetic testing will provide vast amounts of useful clinical information. “In the mid nineties,” Kimmelman told me, “everyone was lined up behind the belief in the existence of highly predictive genes. Around 2002 or 2003that belief started to break up. People began to doubt its value. You still hear it discussed and presented as an exciting possibility, but no one really seems to believe it.”
Kimmelman may be something of an emerging star on social issues associated with biomedical innovation, but he is not doing direct genetic research. I wondered if a leading geneticist would agree with Kimmelman’s pessimistic vision? To find an answer to that question, I went to the top of the Canadian genetic research heap. Few people in Canada have had as direct an impact on genetic research, both scientifically and politically, as Tom Hudson, who is currently the president and scientific director of the Ontario Institute for Cancer Research. He has been the lead author on many renowned studies and was, for years, the director of McGill University’s Génome Québec Innovation Centre. He’s been both a participant in this research revolution (when the HGP money started to flow in 1991 he was at MIT, one of the major gene sequencing centres) and an energetic advocate of Canadian genetic research. In the late 1990s, Hudson was knocking on doors in Ottawa asking politicians for funding to establish Genome Canada, an entity that has since become the focal point for much of Canada’s leading genetic research.
When I met with Hudson, his time was, characteristically, short. “How much time do I have?” I asked him.
He glanced at his watch. “I can give you twenty-five minutes, maybe thirty.”
I have known Tom Hudson for over a decade, both professionally and personally; we have worked together on policy committees, shared bad coffee at too many conferences to count, exchanged ideas for our respective research projects, and swapped stories about our children. Yet despite my “in” Hudson has become so busy that I needed to make an appointment months in advance. For thirty minutes.
With time at a premium, I dove in. What, I asked him, is the value of genetic testing, right now, for my personal health?
“The genetic revolution will be more about the details of clinical care than the man on the street,” Hudson said, while leaning toward me across a table covered in science journals. “It will not help individuals make day-to-day decisions.”
He answered so quickly and with such confidence and intensity I was left with the impression it was a truism he rolled out frequently. I was a bit taken aback by his frankness, and so I asked him to expand on his answer.
He paused now, exhaled. “The science is moving so fast.” He settled back in his chair. “But you need to find things that allow for prevention, detection, diagnosis, something with clinical value. Those things take time. You just can’t find markers to predict disease. You need to acknowledge all the complicating factors, the environment, human behavior… everything. And if we find a genetic marker that predisposes someone to disease, we need to be able to modify the risks in a meaningful way.” He leaned towards me again. “For example, maybe your genetics put you at a higher risk for a certain cancer. We can get those people to get more screening. But we still need to do the clinical research to find out if this screening really makes a difference. Is it worth it?”
He was referring here to the fact that there are many examples of screening procedures that have not panned out as originally envisioned. I continued by asking Hudson what he thought was driving the broad public misperception of the immediate or near future clinical utility of genetic testing? Here, Hudson was in complete agreement with Jonathan Kimmelman. Too many basic researchers (and, as a result, many in the media) simply do not understand that good exciting science does not necessarily lead to good exciting clinical applications. “Just because it is valuable science,” Hudson said, “doesn’t mean it’s clinically valuable.”
There are many factors that add complexity to the transition between basic science and clinical application: the lab logistics of doing the research; gender and socio-economic factors (men typically don’t like to get screened); the lack of pharma-style funding for clinical trials. Robust clinical research, its significance and difficulty, is undervalued, under funded and misunderstood, Hudson noted. “There are many great basic scientists doing amazing things, but they are clueless about how to bring something to the clinic.”
As I was leaving Hudson’s office, it was becoming ever clearer that the relationship between genetic research and our physical health is considerably more complicated than we are often led to believe in the media. The so-called “genetic revolution” is more of an uncertain and iterative evolution. We have vast amounts of genetic information at our disposal, and incomprehensibly sophisticated technologies that allow for the speedy production of more and more of it, but we still appear to be nibbling indecisively around the edges of what to do with all the data.
As Hudson walked me to the elevator he continued to supply me with data about genetics, cancer, the speed of his sequencers and, most tellingly, his agency’s tobacco control work. “This tobacco project is having an impact, right now,” he said, holding a door open for me. “But it doesn’t have anything to do with genetics.”
It seemed a telling thing for a world-renowned geneticist to say.
Given the underwhelming performance of gene therapy and predictive testing, much of the current genetics rhetoric is focused on using genetic information to inform a healthy lifestyle. The watchword is prevention. The plan: procure our individual genetic information in order to help us make decisions about what to eat, what kind of exercise to do, and what kind of surveillance testing to get. If our genes can uncover a chronic disease we are at slightly increased risk of getting, might we be motivated to take evasive action? (“I am at increased risk for heart disease, I better start exercising and eating right!”) This is the prevention strategy Frances Collins alluded to in his 1999 New England Journal of Medicine article, wherein the hypothetical patient mustered the motivation to quit smoking when “confronted with the reality of his own genetic data.”
The past few years have seen a wide increase in the popular culture of stories and companies putting forward the notion of using genetic information to personalize lifestyles and become a proactive player in one’s own health. A company that goes by the name of My DNA Fragrance will, for instance, produce perfume from your DNA, because, as the website says, “Every person’s DNA blueprint is different. So no two fragrances will smell the same.” The health side of the equation is even broader. You can order (allegedly) genetically personalized sports drinks, nutritional supplements, and exercise programs. Genetics is being sold as a pathway to an individualized, healthy lifestyle, the message of almost all direct-to-consumer genetics testing companies and, for that matter, many researchers working in the field. The message of Navigenics, the biggest competitor to 23andMe, exemplifies this pervasive prevention ethos, int hat it claims to “use the latest science and technology to give you a view into your DNA, revealing your genetic predispositions for important health conditions and empowering you with knowledge to help you take control of your health future.”
There are, as I see it, two problems with the idea of using genetic information for the purposes of prevention and/or personalizing your lifestyle. The first we have already touched on—the research simply hasn’t uncovered genes that provide highly predictive information. (I’ll come to the second problem momentarily.)
The idea of personalizing your lifestyle with the help of genetic information looks to be almost as big a bust as gene therapy. In a 2008 article in the New York Times, David Goldstein, a geneticist from Duke University, was quoted as saying, “There is absolutely no question that for the whole hope of personalized medicine, the news has been just about as bleak as it could be.” He went on to add that, “[a]fter doing comprehensive studies for common diseases, we can explain only a few percent of the genetic component of most of these traits…It’s an astounding thing that we have cracked open the human genome and can look at the entire complement of common genetic variants, and what do we find? Almost nothing. That is absolutely beyond belief.”
Yes, it is beyond belief, especially when considering the ongoing push and profile of the idea of prevention. I set up an interview with David Goldstein, and in person he sounded only slightly more optimistic than he’d sounded in the 2008 Times article. In response to my question about where the field of genetics is heading he started with a cautionary note: “Predicting where science will take us in the near future is almost always a bad idea.”
New genome research techniques, such as those being used by Goldstein’s research team at Duke, will, he told me, lead to the identification of a “small number of individuals with high risk genes.” But Goldstein, much like Tom Hudson, is unsure what we will be able to do with that information. Goldstein told me that the public face of genetics—the idea that we can all access useful health information—has it backwards, in that it’s flipped the reality of what’s actually taking place.
“The idea of personalized genomics has run in the opposite direction of what the research actually says,” he said. In fact, gene chip technologies like those used by 23andMe, “can only provide information on low risk mutations with little meaning. Researchers will find a small number of high risk mutations, but we can’t do anything to help these people. Even if we can make those predictions, can we do anything to help those identified at high risk? We don’t have any particularly encouraging evidence.”
This leads directly to the second big problem with the notion of using genetic information for prevention or lifestyle personalization. Goldstein’s rhetorical question—“Can we do anything to help those identified at high risk?”—is just a different way of asking how successful we would ever be at getting people to adopt healthy habits. Will providing individuals with genetic risk information help change bad habits? Will knowing I’m at a slightly increased risk to get a particular disease be enough to get me on a treadmill or cram some broccoli down my throat?
Colleen McBride, chief and senior investigator for the Social and Behavior Research Branch at the National Human Genome Research Institute in Bethesda, Maryland, is one of a handful of scholars worldwide looking at how genetic information impacts health behaviours. Her team hopes to come up with data that will move the prevention debate beyond speculation, a point she made, in the simplest of terms, at the start of our conversation. “We need to bring evidence to these debates.”
Which begged the question of what we could learn from whatever evidence is currently available. What this evidence tells us is that genetic risk information isn’t very likely to change behaviour.
“Any risk communication expert would laugh at the suggestion,” McBride told me. “We have long known from other areas of research that the communication of risk is necessary but rarely sufficient. And even if people do change, they all relapse.”
In other words, you take the pounds off, you put them back on. Study after study has shown that it’s difficult, if not impossible, to get people to change their ways even when faced with powerful risk information. Humans are hard to motivate, and we are, by and large, slugs. Even armed with the knowledge that a behavior is unhealthy, dangerous or just plain stupid, we persist. Learning genetic risk information will do little, at least on its own, to change this reality. This has been understood for years, and a review paper published by McBride and her team in 2010 concluded that, “Genetic information based on single-gene variants with low-risk probabilities has little impact—either positive or negative—on emotions, cognitions, or behaviour.”
And it’s worth reiterating that most of the available genetic risk information, such as the information I received from 23andMe, is weak. Would a risk increase of 0.5 per cent really cause a person to stop eating potato chips? McBride’s bottom line: “Don’t go to these testing companies looking for risk information that will motivate you.”
There is a final nail to hammer into the coffin of the prevention idea (perhaps not the best metaphor when discussing risk information). If genetic risk information could supposedly change behavior in a positive direction, might it not also push people in the opposite direction? For every individual that is at an increased risk for a disease, there will be someone at a decreased risk (in fact, my 23andMe test seemed to show more “decreased risk” genes than genes that increased risk). A person might think, incorrectly, “It says here I have 0.5 per cent less chance of getting heart disease. Bring on the fries and gravy!” Even if we were to accept that genetic information could change behavior for the better, we would be no further ahead. Some people would change in a positive direction, some would order an extra poutine.
Despite the unsuccessful reality of the “genetic revolution”—few gene therapy successes; few highly predictive genetic tests for common diseases; a pressing need for decades of expensive clinical research to reveal what, if any, benefit will be derived from genetic testing; little evidence that genetic information motivates preventative health strategies—we are still constantly told that a genetic revolution is underway. Even as I was writing this article, Francis Collins published an editorial in Nature claiming that the genetic revolution has arrived, citing as evidence the existence of predictive tests, preventative strategies, and primary care physicians who practice genetic medicine.
Where is this revolution happening? Not in the world I live in. How, I wondered, can Collins’ view so dramatically conflict with the existing evidence? And how come we still see headlines that claim to have found the location of a gene for laziness, popularity and getting lost?
James Evans is a geneticist and clinical researcher at University of North Carolina who has keenly followed the socio-cultural portrayal of the genetic revolution. He chaired various United States federal policy committees on genetic issues and has conducted research at UNC on issues such as direct-to-consumer testing. To Evans, there are a number of factors that contribute to the hype.
To begin with, he says, “we always gloss over the stuttering, uneven pace of science which includes dead ends and wrong turns. This doesn’t negate the value of the research endeavor. On the contrary, we will be better off for doing this research. But science is an unpredictable, long, circuitous slog, and we always seem to forget this.” Evans has also noticed shifts in promised benefits. “There has been an erosion of claims in the face of reality. The claims have become less and less grandiose. It used to be gene therapy. Then it was highly predictive genetic tests. Now we have a focus on behavior change. But, trust me, behaviour modification is going to be a bust, too.”
The other principal factor that has over-hyped the revolution, according to Evans, has been technological advance. Things like the ability to sequence entire genomes have created an unattainable level of expectation. “The basic science,” he told me, “is moving much faster than we could have imagined. This sets up an expectation that we will reap benefits in patient care, but I’m skeptical that we’ll find robust genetic predictors of the kind that will make any difference for the individual.”
David Goldstein agrees with Evans. Scientists often blame the media for the hype around genetics, but, says Goldstein, “scientists have a lot of responsibility for the hyped portrayal of genetics. Scientists are under pressure to get research resources to come to them instead of the next guy. The genetics community wants to make it look like we are on course to help with common diseases, even if we aren’t. If we don’t create that impression, the money might go to another area, like stem cells.”
Geneticists, says Goldstein, should stop over-promising and start under-promising in order to avoid “an inevitable backlash.” The unpopularity of this position in the research community was made clear to Goldstein recently when a very prominent genetic researcher, whom he declined to identify, told him to “shut up or the money will go somewhere else.”
Bearing in mind that my personal journey through the world of the genetic revolution was less than convincing, I was conflicted about my own genetic testing experience. I knew that much—well, practically all—of the information provided by 23andMe was useless from the perspective of health care decisions. Still, I found it intriguing. I loved the fact that I had the longevity, good memory and slightly-above-average height genes (even though the research supporting the relevance of these genes is still thin). The ancestry aspect of the testing, which 23andMe also offers, was compelling. It turns out that I am, as Joanna Mountain put it, “Irish to the core.” I don’t have a single marker from any location on planet Earth save the Emerald Isle, though I am unclear how this informs anything other than my love for a good Guinness. Beyond this, visiting 23and Me provided me with no information that was I able to envision using to improve my health in any meaningful way.
But there was still that one genetic shocker, the one piece of genetic information that caused me so much anxiety and personal reflection, that made me swear out loud at home and stop my children in their tracks. Ironically, this bit of information had nothing to do with my health. Here I must caution that I am about to become somewhat immodest. I was about five years old when I realized I was fast, the fastest kid in every grade, which said a lot because we moved often when I was young. Sure, we never did live in Jamaica, but I still held various school and county records, and at the age of twelve I joined a track club and trained with Olympians, nakedly aspiring to be one. My passion continued throughout high school and university, but although I won or did well in some big races, it eventually became clear, crystal clear, that I wasn’t Olympic material.
It didn’t matter, because the sport gave me much: my first formal date; my first overnight trip away from my home; wild post-race parties that helped to establish close friendships; my wife. I met Joanne, a world class runner with all the right genes, at our track club. After university I shifted to sprinting with a bike on a velodrome, a sport I still pursue competitively and fairly successfully. I could continue, but you get the idea. Sprinting has been central to my personal history. I am a sprinter, through and through.
Or am I?
On that busy night when I first scanned the results from 23andMe, one thing jumped out. One 23andMe analysis is of the genes that code for “muscle type.” The test result said the following, in plain language: “unlikely sprinter.” My genes did not possess the code for quick twitch muscles. Zero, in fact. The narrative following the “unlikely sprinter” result also suggested I partake in endurance events.
Ouch. Damn Irish genes.
For days after reading that I sulked about, and frequently found myself looking at my legs, cursing their unsprinterly muscles. In its long history, Ireland has produced few world-class sprinters. It seemed I was now part of that unstoried tradition. But I wondered, Would the right quick-twitch genes have propelled me to Olympic glory?
Probably, or almost certainly, not. Some other physical failing would likely have limited my success. Short shins. Fat feet. Hairy, drag inducing legs. Of course, if I was born in this the era of the genetic revolution, my parents could get me tested for sporting propensities. Many companies now exist that will test your child—for as little as $150—to find out if he or she has the genes for speed or endurance. Atlas Sports Genetics, for example, will test children as young as one–year–old, allowing parents to make an informed decision about which sport to obsessively push, I mean “to encouragingly place,” their children in.
Had I taken such a test perhaps I’d have become a famous endurance cyclist. Or perhaps I’d have been just good enough to be distracted from university and would have flunked out. Maybe I would have detested the endurance sports I am apparently genetically suited to pursue, and would have done nothing but sit on my posterior. Most likely, due to the constellation of complications that make us human, I would not have been any better at climbing a mountain on a bike than dashing 100 metres down a track.
A few weeks after my visit to 23andMe, I ran into James Evans at a conference in Cambridge, England. With great sorrow, I told him of my non-sprinting-gene affliction and he offered me his sympathies.
“The fact that you don’t have a quick-twitch genetic predisposition but still enjoyed and excelled in sprinting just shows how complex things like sports are,” he said. “But it’s more profound than that. The greatest thing about having evolved is that we’re not slaves to our biological destiny. We can pursue activities regardless of various simplistic deterministic predispositions. We can violate the imperatives of biology.” Evans paused a moment before continuing, then smiled. “That’s how we find joy.”
I’ll raise a Guinness to that. EB