Our Time to Lead

Would you make your DNA and health data public if it may help cure disease?

Special to The Globe and Mail

Jill Davies, a genetic counsellor and program director with MedCan Clinics, is the first Canadian to volunteer her whole genome and personal information to be placed on a public website. (Fred Lum/The Globe and Mail)

Jill Davies is Canuck One.

The 39-year-old Toronto professional is the brave or, perhaps, foolhardy Canadian volunteer who will be first to go public this week in a project that will reveal the coded secrets hidden in her genome, the six billion chemical units of her DNA.

They may include not only her susceptibility to diseases such as cancer but the levels of her propensities to alcoholism, depression or obesity, or even personality traits such as risk-taking. She will also provide the personal context required to make sense of the biological data – her age, height, weight; medical records; details about how she lives, works and plays; and even her photo if she’s game.

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This information – everything but her name and address – will be placed on an online database that will be open and available to anyone in the world. Even in this digital age of perpetual show and tell, exposing oneself so completely amounts to a molecular full monty: Even without a name attached, any participant might be identifiable.

Ms. Davies is making a leap of faith that at least 100,000 of her fellow citizens are also being asked to take – even though Canadian law has no strict guidelines on how this confidential knowledge might be used or misused by any insurance company, employer, police force or identity thief.

Is she out of her mind? No – at least provided her country’s laws start catching up to her.

Ms. Davies is part of the Personal Genome Project – Canada, a vast new scientific and social experiment spearheaded by the University of Toronto’s McLaughlin Centre and the Hospital for Sick Children, in co-operation with a group at Harvard University.

It is a deliberate effort to jump-start what has proved to be the stalled genetic revolution.

Since the first human-genome map was unveiled in 2000, the field of genetics has taken sharp jabs for promising the moon and barely delivering a telescope. It was supposed to allow us to target not only a disease, but each individual’s unique version of it. It was a radical new way of seeing and even changing who we are, raising fears of a brave new world of genetic determinism.

Instead, so far there have been no big breakthroughs for common illnesses such as cancer, heart disease or diabetes. Some argue genetics’ power to predict illness is no better than reading a horoscope.

What has taken off at staggering speed is our ability to decode DNA. The cost of sequencing a human genome has fallen to about $4,000 from $3-billion in 2000. But the more genomes scientists read, the more they realize that humans are far more diverse than they thought. Data are needed on a much larger scale if researchers are ever going to be able to interpret the genomes of the whole array of humanity.

In China, the Beijing Genomics Institute is aiming to decode a million people. The Saudis are aiming for 100 Arab genomes, and an international consortium is tackling the 1,000 Genomes Project, sequencing anonymous donors from 14 countries.

The prime mover of the Personal Genome Project (PGP) in Canada is Stephen W. Scherer, a pioneering Canadian geneticist with a record of scientific breakthroughs. He co-founded and directs the Centre for Applied Genomics at the Hospital for Sick Children and is the director of the University of Toronto’s $100-million genomic-medicine institute the McLaughlin Centre.

He argues that it is not just genetic but personal information that is required. DNA is a living language that responds to how we live over time, with genes that can power up or down. Without that context, there is no way to tease apart the effects of genes from environment. Dr. Scherer is looking for tens of thousands of people like Ms. Davies who are willing to hang their laundry on the public line, so that scientists anywhere can study massive numbers of genomes alongside the related personal profiles.

The PGP also could help put Canada at the forefront of the medical field – a genomic economy that Forbes magazine has estimated will be worth $100-billion within the next 10 years.

Ms. Davies knew what she was getting into: She is the director of genetic counselling at MedCan, a private Toronto clinic, and had already “had every genetic test available” through private companies in the United States. She had found out, in particular, that she carries a gene variant that puts her at risk for Alzheimer’s, an unpleasant “surprise” that in the end allowed her to make lifestyle changes she hopes will delay the onset of the disease.

She thought she had no qualms, but just before her blood was drawn for the PGP, she says, “It hit me. … I’m about to make my information publicly available. Gee, do I want to do this?”

The PGP consent form acknowledges the risks of public exposure: Participants and their families might be stigmatized and lose the ability to obtain life insurance, a job or a loan. They could learn about health conditions they were unaware they had, discover they are not biologically related to their families, or even risk someone making a synthetic copy of their DNA and planting it at a crime scene.

And Canada is the only Group of Eight country without a specific law to protect the uses of genetic information.

“Science has outperformed legislation,” says Bev Heim-Myers, chair of the Canadian Coalition for Genetic Fairness, a Kitchener, Ont.-based group of 15 organizations devoted to patients with diseases that have genetic components.

As initiatives such as the PGP hasten ahead, society has barely begun to debate all the choices they might entail. It could produce a generation of the worried well, fearful of genetic risks that might never transpire, perhaps costing untold sums to the medical-care system. Open-source projects such as this could lead to genetic discrimination. A more complete picture of the genome could promote selective reproduction and the questions around abortion, eugenics and fairness that follow.

Dr. Scherer says the PGP is “definitely going to be a win for the research community if people participate.” But he acknowledges, “Whether it will be a win-win [for both research and the individual], we just don’t know.”

In fact, one October morning, as the PGP researchers met to iron out details, even the ethicist who has spent the past two years steering the project through approvals took the team aback by saying he wasn’t certain he would pony up his own genome for the cause.

“I’m 95 per cent there,” said Michael Szego, as his colleagues laughed in surprise. “I mean, I probably will, right? So I understand what people are going through.”

Later, Dr. Szego, of the Centre for Clinical Ethics at the University of Toronto, said his main concerns were around insurance, and the effects on his three young kids. “I have never had any genetic testing before.”

Many advocates argue that this is too momentous a set of issues for Canada to leave up to fate.

“It’s time,” Ms. Heim-Myers says, “that our federal and provincial legislators and decision-makers recognize that to move forward with this very promising research we must also protect Canadians.”

For most of his career, Dr. Scherer has been on the leading edge of surprising discoveries about human DNA, including some that demonstrate how much more complicated the genetic realm is than we used to imagine – and why it will require massive scale to assemble the whole picture.

He was part of the international team that overturned 150 years of science with proof that mom and dad do not always contribute equally to the creation of a child, with one copy of each gene. Some people can inherit several copies of a gene from one parent, or carry no copies at all, and still be healthy. These copy-number variants are part of what make individual genomes unique. But DNA varies in a multitude of other ways that researchers still do not understand.

I once went to see Dr. Scherer with my own questions about what “normal” looked like, genetically speaking. I had volunteered to be part of a hospital research project a few years previously, while I was pregnant with my first child, and doctors had snapped images of my chromosomes, a test known as karyotypying.

A genetic counsellor had called me to come into the hospital when the results came back. I panicked. Health-care professionals rarely suggest a visit to share good news.

A medical team was ready for me when I arrived: a genetic counsellor, a researcher, two doctors. (It was in the midst of the SARS outbreak, and it didn’t help that everyone sounded like Darth Vader from behind their face masks.) They had found a problem with one of my 46 chromosomes, they said – No. 11. It was inverted.

Inverted, I asked, as in upside down?

Inverted, they repeated – not the whole chromosome, but a good chunk of it.

Was it hanging like a bat in my cells, I wondered, or was it more like a Led Zeppelin track, playing backward and saying something sinister?

It was rare, they told me, to see such a thing – and troubling. Chromosome 11 is no genomic idler – it is tied to personality, with receptor genes linked to mood, pleasure and movement. So what did it mean that mine was belly-up?

“It may mean your entire genome is unstable,” they said. “These inversions are known to cause problems.”

They gave me a package of medical literature on chromosomal inversions and offered to scan my unborn child for the same anomaly – in case it led to doubts about continuing my pregnancy. It did, but I never did go for that scan.

Two years later, after the birth of a healthy child, I was still trying to make sense of my upside-down 11. Dr. Scherer invited me to a meeting of international scientists who were in town to discuss “structural variation in the human genome.”

A parade of researchers took to the podium, describing the quirks they were spotting in the genomes of perfectly healthy folks: swaths of deleted code, hundreds of thousands of extra bits, chromosome pairs that did not match, and inverted chromosomes of all sorts, inside out and backward.

“What the heck is normal?” one of the experts joked. Most agreed they could not know without a grand stockpile of genomes to reference. People were making critical medical decisions with only half the story.

Seven years later, that’s still true. Even in Dr. Scherer’s own lab, where he and his team are focused on solving the genetic mystery of autism, it can be tricky to tell when they have spotted a meaningful mutation – there are too few control genomes for comparison. Recently, he had no choice but to use his own DNA as a control.

“It’s a big problem for any genetic study,” he says – and worse for anyone studying patients from non-European ancestry, for whom control data are virtually non-existent. Genomes can vary dramatically between ethnic groups, but without a large bank of data drawn from different populations, researchers cannot tell what is common and what isn’t.

Elise Heon, ophthalmologist-in-chief at the Hospital for Sick Children, faced this challenge in 2009, when she was facing a tight deadline to place a Tamil patient in a promising gene-therapy trial. Dr. Heon had discovered a gene mutation in the girl, who had a retinal disorder that had left her legally blind, but she had no way of knowing if it was the cause of the girl’s disease or simply a variant common in Tamil people. Dr. Heon’s only hope was to find other Tamils, and collect samples from them quickly.

As it happened, Tamil protesters had gathered outside the U.S. consulate down the road from the hospital. Dr. Heon and a handful of other researchers packed spit kits and consent forms and headed to the protest to collect DNA samples that could be used as controls.

The mutation turned out to be the culprit, and the Tamil girl gained access to the trial, which improved her sight, and enabled her to walk without a cane.

Privacy is a relatively young concept, born with the rise of cities, George Church argues. For most of human history, everyone lived in villages, and extended families in homes without doors, and everyone knew everyone’s business.

Dr. Church is the lanky, 58-year-old Harvard University genetics professor and entrepreneur who created the U.S. version of the Personal Genome Project in 2005. He is on a mission to change global perceptions of genetic information.

He believes people are ready to share their DNA – more than 2,000 have already signed up for the project in the United States, and many more are clamouring to do it (including 250 Canadians who have contacted the project’s U.S. website).

Eventually, he hopes it will become a global movement. Britain is expected to join next year.

“There’s been a huge change in people’s perceptions of privacy,” Dr. Church says.

A few decades ago, people simply didn’t talk about their cancers, or their sexual orientations, or their psycho-social disorders. “But now people do talk about that. They talk about what pharmaceuticals they use to deal with it … because you can benefit by talking about it.”

And, says Dr. Church’s Canadian counterpart, Dr. Scherer, today’s fears are similarly overblown. “Genes are part of who you are, not all of who you are. Once enough people get their genomes out there, it won’t matter any more,” he says, noting that everyone carries risks for something. “It’s not a big deal, and it doesn’t need to be a big deal. We need to change the mindset.”

So far, the dozens of profiles that have been posted on the website for the U.S. project reveal an eclectic collection of human traits. One volunteer reports having flat feet, another major depression and gingivitis. There’s someone with an allergy to cats, and a middle-aged man who notes that he can sing on key. Dr. Church is the one with dyslexia, high cholesterol and narcolepsy.

Harvard’s ethics review board made the professor’s participation a condition of approval, believing that he should take the same journey as his volunteers.

The condition worried him a little. His father had died of senile dementia. Dr. Church, along with his wife and daughter, feared that he might learn he inherited the APOE-4 gene variant that would put him at a higher risk of Alzheimer’s. But even then, although there is no effective treatment for the condition, he felt a person could still take “make plans” if he knew.

“You could load up on long-term-care insurance, or decide where you want to be when you get Alzheimer’s,” he says. “You could enroll yourself in studies looking for treatments.”

Not everyone would be so sanguine about learning the dark secrets of their genetic codes – or publicizing them. So the Harvard ethics board established other conditions. Participants would have to pass an intensive exam – as they will in Canada – to ensure they understand exactly what they’re signing up for.

In the United States, the first phase of the project was limited to 10 volunteers, each of whom was required to have a Master’s degree in genetics or an equivalent discipline. The requirement led to charges of elitism. But Dr. Church says it was just another way to be assured that early volunteers were as informed as they could be before consenting, and that they “would have a positive experience.”

For the most part, he says, they have. Some have discovered welcome news – that they carry “super variants,” genetic traits that can protect against conditions such as heart disease.

In his own case, Dr. Church says the insight he has gained has been a “huge relief.” He learned that he does not carry even a single copy of the high-risk variants for Alzheimer’s.

As for any unexpected consequences of publicly exposing DNA, the only notable one was an e-mail from a doctor in Seattle asking when Dr. Church had last checked his cholesterol levels. The doctor suggested that as a vegan, Dr. Church’s levels should be lower. Was he taking the right drug to control them?

Dr. Church looked into it, and by switching drugs, has since cut his cholesterol by half.

Steven Pinker, the Canadian-born Harvard psychologist and author, joined the U.S. study and discovered that he carries a gene variant that puts him at high risk of sudden cardiac arrest. But he also learned he has a variant suggesting he has an 80 per cent chance of being bald – while at 58, Dr. Pinker famously sports a rock-star mane of hair.

Dr. Pinker’s hair is emblematic of what irks critics about genomics: It’s a fuzzy survey of susceptibilities, and sometimes just plain wrong.

Mack and Amanda Erno put off knowing for as long as they could. Their experience, while not part of the PGP, demonstrates the negative consequences participants might face.

The couple from Teepee Creek, Alta., population 20, always realized Amanda’s genome might harbour devastating news. Her mother had Huntington disease, a fatal neurodegenerative disorder that can strike in the prime of life. Mrs. Erno, a 31-year-old accountant, had a 50-50 chance of inheriting it.

Mr. Erno says his wife preferred not to know, even when an insurance company pushed her to have the test. Only after the couple were ready to start a family did they decide to find out.

The news was not good. But they were still determined to try for children. At first, they attempted in-vitro fertilization, hoping to implant an embryo without the Huntington gene. When that failed, they opted to have children naturally. Their daughter, Claire, was born in June 2011, and his wife is now pregnant with their second child.

Mr. Erno says Claire will likely grow up knowing, as his wife did, that she could develop the disease. Testing for it will be her decision to make in adulthood. “Maybe by then,” he says, “there will be something that can be done about it.”

Meanwhile, Mrs. Erno was denied life insurance, an act that the Canadian Coalition for Genetic Fairness calls genetic discrimination. The coalition is pushing for a law in Canada that would prevent insurers, employers, government agencies and other authorities from using genetic information in discriminatory ways.

The Ernos’ story isn’t unusual, says the coalition’s Ms. Heim-Myers, who is also chief executive officer of the Huntington Society of Canada. People can be denied life and disability insurance coverage, or face higher premiums, for risk variants that might never develop into an actual disease.

In the United States, legislators passed a hefty anti-genetic discrimination law in 2008 that applies to health insurers and employers.

But in Canada, anti-discrimination protection is only provided through the Human Rights Act, created in 1985, years before the first human-genome map even landed.

Some claim that we may not need further measures: Because we have a public-health system, they argue, no one will be denied treatment on the basis of their genes. Yet at the moment, there is no government official even in place to comment definitively on such matters.

Still, the Office of the Privacy Commission of Canada is so concerned about potential abuses in the area that it has pegged genetic privacy as one of its top four urgent priorities to investigate.

The Information and Privacy Office of Ontario offered input on the Personal Genome Project when Dr. Szego, the PGP ethicist, came around with the proposal. One staff member told him the project sounded reasonable; another thought it sounded “like a crazy idea.”

Ontario’s Privacy Commissioner, Ann Cavoukian, says she could see both sides: “I applaud these people who do it for the greater good of research, but really, it scares me,” she says. Not only are participants posting information without knowing how others will use it, they’re exposing code that also reveals traits about the rest of their family.

Participants might be affecting the lives of their future children, Dr. Cavoukian suggest – losing them a job, for example, with an employer “who doesn’t want to take any chances on someone they are going to spend a lot of time training and investing in.”

In the United States, employers and insurers are banned from even asking applicants if they have undergone genetic testing. But nothing in Canada prevents such questions.

Dr. Szego says any volunteer is free to quit at any time if things get uncomfortable. But he acknowledges that once the information is online, there is no telling who might download and post it somewhere else. “You can never say never with the Internet.”

Even so, just last month, Dr. Szego finally decided that he would join the project after all.

Ms. Davies – Canuck One – says she eventually put her anxieties aside. Many Canadians have already mailed away their DNA to direct-to-consumer private testing companies, she points out, without any assurances about the accuracy of the tests, the interpretation, or the confidentiality of their information.

Unlike those testing companies, the Canadian PGP will provide genetic counselling to volunteers after their DNA is sequenced. And researchers will check in regularly with participants to gauge the social implications of having genetic information posted online.

Rather than requiring a master’s degree of its initial volunteers, as the U.S. group did, the Canadians have opted to select people with high incomes, arguing that anyone who takes on the risks of participating should have the resources to hire a lawyer should an issue arise.

In the first year of the project, which is operating without a research grant, researchers are hoping for 35 volunteers who can afford to pay $4,000 for their DNA sequence and analysis – and can pick up the tab for decoding the genome of one other person.

Robert Eilers could be the perfect candidate. The 43-year-old property developer, based outside Milton, Ont., employs 650 people globally. He has no concerns about losing his job or his life insurance, has no children and, perhaps most important, harbours no fear of the unknown.

He was first won over to genetic testing after frustrating wait times in the public-health system sent him to the MedCan clinic.

He has recently had two scans of his genome, but the first one had him hooked. It revealed that he had been taking the wrong cholesterol-lowering drug for the past 20 years and that he has a propensity for high fat levels in the blood and for obesity, but a lower-than-average risk of developing coronary-artery disease.

Genetic testing gives a person a chance to prevent conditions instead of reacting to them, he says: “My genome says I have a predisposition to obesity. It doesn’t mean I have to be obese – it means I have to work out two or three times harder to stay fit,” he says. “If you drive a car, you don’t wait for the engine to start smoking before you do something about it.”

When Ms. Davies told him about the PGP, Mr. Eilers was keen from the get-go. “I would be very happy to do this for research,” he says. “This is the future of medicine.”

Yet for all the hypothetical risks covered in the project consent form, new possibilities continually pop up. On the morning the research team gathered in October, the following scenarios came to mind:

What if a police investigator happens to find a match, or even a close match, with a crime scene DNA sample and someone in the Personal Genome Project database? (If there was a court order, they would probably have to reveal a participant’s identity.)

What if there is a plane crash and the DNA could be useful for identification of victims? (Definitely, the team would help.)

What if someone desperately looking for a tissue or organ donor found a match in the Personal Genome databank? (Here, the group members weren’t so certain.)

Dr. Scherer says that if the risks of the project prove too great, moving the data out of the public sphere is always an option. “If it turns out there are so many bad stories that come out, we’ll just stop,” he says. “We’ll say, ‘Yeah, we better keep this data inside the medical system.’ ”

But he and Dr. Church believe that won’t happen. If enough people put their DNA data online, genetic information will be demystified, becoming less scary, less significant.

“There’s more revealing information on social networking sites,” Dr. Church says. Over time, he adds, “people would be less interested in the fact that I’m homozygous for APOE-3 than who I might have hooked up with last night.”

For more information about the Personal Genome Project, please visit Personal Genome Project Canada.

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