The fear was based on the prevalent belief that knowledge of how genes worked was going to radically reconfigure medical practice. John Bell, Nuffield professor of clinical medicine at Oxford University, optimistically opined that same year in the British Medical Journal, that “within the next decade genetic medicine will be used widely for predictive testing in healthy people and for diagnosis and management of patients.” And knowing what the genes said was going to require doctors to daily make unprecedented and instant decisions about what should and shouldn’t be revealed about genetic information and genetic risks not just to patients, but to patients’ families, to insurance companies, to governments, and to employers.
Today it is highly unlikely any lawyer reading this article is feeling particularly knotted up by genetics-based lawsuits. This is because in 2012 the once exhilarating promise of clinical genetics (now frequently called clinical genomics) is being viewed by many people — including some in the legal profession – as a scientific hype existing somewhere between a fairyland and a fraud.
For example, last year Science magazine published an article entitled “Deflating the Genomic Bubble” where the authors, one of whom was Timothy Caulfield, Canada research chair in health law and policy at the University of Alberta, wrote: “If we fail to evaluate the considerable promise of genomics through a realistic lens, exaggerated expectations will undermine its legitimacy, threaten its sustainability, and result in misallocation of resources [and] . . . fuel unrealistic expectations for predictive genetic testing and uncritical translation of discoveries.”
The reason for what might be called a genetic counter-revolution is that genetics has proven to be complication incarnate. Cancers can have one kind of genetic makeup if situated in one place in the body, and quite another if they have metastasized to a different locale. Hundreds of genes have been associated with common diseases, each of which add or decrease by a few percentage points your risk of getting the disease, but are so common — some found in upwards of 50 per cent of people — that they must also be doing something very health positive in the body. The complications are so intrinsic and so knotted that in 2010, Harold Varmus, director of the U.S. National Cancer Institute, dismissively told the New York Times, “Genomics is a way to do science, not medicine.”
All true and all disappointing for those hoping for genetically revolutionized medicine, except — and that is the point of this article — if one is looking at the gene-based diagnosis and personalized treatment of certain rare kinds of heart conditions known as arrhythmias. In that arena not only has medicine experienced a tsunami of change, but as you will see the social/legal/ethical quandaries which doomsayers in the past believed would bedevil lawyers and regulators are beginning to surge into view.
And this potentially legal and ethically fraught rare heart genetics revolution is of particular import in Canada. In this country, for a number of reasons — close kin marriages in some areas, active genetics research, and world-class heart institutes — we have become among the planet’s leaders in both generating arrhythmia genetic advances and in generating the extremely knotted sociology a genetics’ revolution was supposed to bring forth.
I will lead you through this but to give context as to what has been occurring you need some medical background.
Arrhythmias are the electrical misfirings of the heart made famous by athletes trotting off playing fields, keeling over, and suddenly dying — often without any previous signs of illnesses. While physical heart changes are seen in some conditions, often an ECG or other imaging reveals nothing structurally wrong with the heart either before or after an attack. Effectively the heart battery just went dead.
While the condition can be very rare in the world population as a whole, striking one in 2,000 to one in 10,000 people, they can be very much more common in certain areas of this country. A Newfoundland variety of arrhythmogenic right ventricular cardiomyopathy (ARVC) has been diagnosed in about one in 500 people. Among the 5,400 Gitxsan aboriginals of northern British Columbia, the occurrence of people with the tribe’s special mutation of a long QT syndrome gene is one in 90.
Unlike diseases such as Huntington’s where a genetic test told carriers they would come down with a condition that medicine could do nothing to either forestall or cure, quite the reverse situation has occurred in many arrhythmias. For example, a heart attack is triggered in a genetically distinct version of long QT syndrome by exercise; in another the heart-stopping agent is a loud noise; in a third it is the restlessness of early morning sleeping patterns. Their specific genetic fingerprint says that person A should take beta blockers to ward off an attack and person B should have a defibrillator installed.
Preventative measures can be taken in some instances even before the condition manifests itself. Doctors in Newfoundland are so confident they can associate disease appearance with genetics that they now routinely recommend that the boys in their late teens and girls in their late 20s who carry the gene for a local variant of ARVC have heart-restarting defibrillators implanted in their bodies. Even — the rest of the sentence must be written in boldface — if they have no symptoms of the disease whatsoever.
With this as a background let’s look at what I believe is the only actual judgment in the area, a 2006 decision by the Supreme Court of Newfoundland in the case B.D. v. Eastern Regional Health Integrated Authority, a St. John’s Hospital complex.
It pitted a 30-year-old ARVC-gene-carrying man, who had had a defibrillator implanted in him, against his mother. The man wanted the defibrillator removed because, according to the judgment, “it adversely affects his life in other ways which makes its presence unacceptable to him.” His mother panicked at what she saw as her son’s reckless action and sought to have the removal blocked by the courts. She feared that without the defibrillator her son would die young and thus removal violated a primal dictum of medicine: First do no harm.
Here’s some additional background to justify her fears. Aided by family bibles, Newfoundland geneticists have determined that half the men who carried the gene were dead by the age of 40 and 80 per cent by 50. And, at the time that decision went to court, not a single man who had had a defibrillator implanted had died from subsequent heart attacks.
With this in mind, the Eastern Health heart surgeons themselves were completely uncertain how to respond to the man’s request, says Kathy Hodgkinson, an assistant professor of medicine at Memorial University whose doctoral thesis is on the Newfoundland ARVC gene. “If it was a drug he was taking, he could have quite happily made the decision to stop taking it any time he wanted. But in this case the doctors themselves had to act,” she says. “And there were no rules and precedents for them taking things out.”
Nonetheless, the case was decided on what were narrow grounds. While the mother’s feelings were noble — “She is doing what any loving mother might do if she is convinced her son is not thinking rationally and is putting his life at risk,” — Newfoundland and Labrador Supreme Court Justice James Adams noted the man was not a child and was competent to make his own decisions. With that in mind, the doctrine of informed consent was invoked, and the Canadian Health Care Practice manual was quoted: “a competent can refuse any medical treatment regardless of treatment and regardless of whether it was necessary to preserve life.” Ergo, the mother didn’t have standing to sue and the man had a right to ask doctors to take out the defibrillator.
Narrow and precedented, except a few months later the man’s body made a different judgment. He had the heart attack his genetics said was almost bound to happen. By good fortune, he was near a place where resuscitation equipment was available and he was saved. What did he do then? He decided that the defibrillator was worth it and had it reinstalled.
All of this leads to the knotty question of what will doctors do the next time a person who carries the fatal gene comes forward and asks to have the defibrillator removed? Will any of them refuse to do it because there is now overwhelming evidence of ICD’s effectiveness — death rates in men with defibrillators are today a tenth of those without — and so removal is patently harmful? Nobody is entirely sure because the correct genetic heart arrhythmias balance between the principles of “first do no harm” and “informed consent” is cloudy.
"Doctors could exercise the conscience clause, which says I can’t in conscience do that,” is how Bartha Knoppers, a McGill University law professor who is also director of the Centre of Genomics and Policy, suggests one scenario might play out. “I am increasingly interested in the clash between what we might call common sense and what the legal system tells doctors to do. I think there is an emphasis, some would say overemphasis, on individual autonomy,” says Trudo Lemmens, Dr. William M. Scholl chair in health law & policy at the University of Toronto. However, he also points out that doctors have to respect the fact that “people make many unwise choices.”
But what if the unwise removal resulted in a person having a heart attack while driving and killing others? Should you not be allowed to drive if you carry the gene and haven’t had a defibrillator implanted or had it removed? It is not an idle question but one that may be looming. But because of the prevalence of ARVC in Newfoundland and the sharp decline in the cost of genetic testing, there is a discussion of whether the province should test all babies for the disease at birth. And if they did shouldn’t that information be forwarded on to Newfoundland’s driver examination centres? Or conversely should there be a law in place that says if you carry the “Newfoundland curse” gene you can’t get a driver’s licence if you haven’t been tested and had a defibrillator installed?
Again clouds. Knoppers leans toward yes, pointing to existing laws related to denying licences to people with conditions like epilepsy. “If I am a third generation of epileptic and have decided not to get tested, yes, I think you shouldn’t be able to get a driver’s licence.” Erin Nelson, who teaches tort law and health care ethics and the law at the University of Alberta, is more skeptical. “I think it would be extraordinary if the province had access to health records. You would need rules to do that. I don’t think that there would be very many people in favour of that kind of legislation.”
But at the least should there be genetic tests for the condition before you can get a driving-related job? The Newfoundland cardiologists and geneticists have already had to deal with a case related not to driving but flying. A man without symptoms — again that must be emphasized — was first told he didn’t carry the ARVC gene and then, while studying to achieve his lifelong ambition of becoming a pilot, he was told he did have it. He was quite angry and didn’t want to change his life’s dreams based on what might be in the future or something not presently wrong with him. After much discussion, the doctors were able to convince him to drop out of flight school.
But what if reasoning hadn’t worked, and even more to the point, what if the connection between a gene defect and a subsequent heart attack was more diffuse? The Gitxsan’s version of long QT is much more predicatively problematic than Newfoundland’s ARVC. In 15 per cent of long QT carriers the first sign of the disease is a heart attack. In 35 per cent of people, carrying the disease has no apparent heart disease effect. In the rest, there are a variety of heart-related symptoms. Can Gitxsan long QT mutation carriers become truck drivers? Can they become pilots?
Lemmens points out what decides these issues today is a proportionality test. “You compare the magnitude of the risk and the likelihood of occurrence of risk happening — something can have a small likelihood of happening, but a big effect if it does. And because of that the court may say it is appropriate to impose restrictions.” But what isn’t clear, he admits, is exactly where that line is when it applies to arrhythmias’ variety of risks and consequences.
Then there is the question of a parents’ right to know about their child’s genetic predisposition. In Newfoundland, parents are beginning to demand that ARVC screening tests be conducted on infants or very young children. The problem is that there are no clinical manifestations of the disease before the age of 17 or 18 and as such no need to do anything either in terms of lifestyle changes or defibrillator implants. “The question is that if there is no manifestation of the disease, shouldn’t you wait until the child is old enough to decide for him or herself when and whether to be tested?” asks Christina Templeton, a paediatric cardiologist in St. John’s.
What is the doctor’s legal responsibility?
U of A’s Caulfield believes parents’ rights will win out. “You can’t withhold information about a child from a parent or a legal guardian because they are substitutes for those individuals in a legal sense.” Lemmens disagrees. “There is a tendency in the law to say that when there is no benefit to the child, they should have the right to make a decision for themselves at 18 or so,” he says.
Again the situation seems ripe for both a lawsuit and a subsequent Solomaic judgment.
However Newfoundland’s legal/moral quandaries are nothing in comparison to what has arisen at Partners HealthCare Center for Personalized Genetic Medicine at Harvard University in Boston, a facility designed both to test for heart-disease-causing genes and to translate genetic research results into medical practice.
Consider the sperm donor who at the time of donation was asymptomatic but later learned he both carried a gene for and had symptoms of another arrhythmia known as hypertrophic cardiomyopathy (HCM). Partners contacted all the families involved in the donation offering to test the children for the disease. One was a lesbian couple who had wanted their offspring to be half-biological siblings and so there was a risk both carried the gene. The couple came back and said they didn’t want their children to be tested. When asked why, they said there had been intense sibling rivalry between the two children and that if one tested negative and one positive that rivalry would likely be intensified.
What should the lab do, especially when signs of the disease were being seen in three of nine HCM-positive children born of the donor’s sperm, when symptoms don’t always precede an attack, and when defibrillators have been shown to prevent early deaths in many HCM carriers? More muddiness. “Somebody has to interpret whether this is a significant risk or is this the kind of decision-making we can leave up to parents,” says Lemmens. And because it is so fraught, he adds, “Maybe we will have to create a decision-making body to decide in these instances.”
And even more problematic — if possible — was the young boy with symptoms of heart disease who came to Partners for testing. He, too, tested positive for one of the HCM genes and then his mother was tested. She didn’t carry the gene. Mendel’s laws of dominant genetic inheritance tell us absolutely the father and his side of the family carried the gene. Samantha Baxter, a genetic counsellor at Partners, told the mother to tell the father and his brothers and sisters about the test results so they could test themselves and their children. However, “The mother was going through a rough divorce,” says Baxter, “and as she put it, ‘the dad’s side of the family no longer are her relatives, no longer are somebodies she needed to care about.’” As a consequence she said she wasn’t going to tell them and neither should the lab.
What would the law say was Partners’ “duty to warn” responsibility in the face of an explicit demand by the legal guardian of the child who was their formal patient to say nothing?
Knoppers points out that in France doctors can give letters with test results to patients and the patients in turn are supposed to send the letters to potentially affected family members. “If a person refuses the letter, the doctor sends information to the public health officer and the public health officer is mandated to then contact family members without revealing the identity of the patient,” she says. Such a system does not presently exist in this country.
So what did happen? In the instance of the lesbian mothers, Partners accepted that the women as legal guardians had the right not to test their children, but encouraged them to monitor the children regularly for any signs of heart disease. In the bitter divorce case, Baxter says the mother “somehow had told her sister the testing results and the sister said these results aren’t about us and she relayed them to everybody on the father’s side.”
So the nieces and nephews were tested, but when the mother learned, “I got this ugly phone call from her,” says Baxter, “where she threatened to sue me because how did they find out these variants when she told us not to tell them. And we said we never said anything, but she was still livid.”
And what does all the above portend for the future of rare heart diseases cases and the knots its application threatens to tie the law, lawyers, and regulators in? “This was the story that everyone thought was going to play out, and in this little universe it has,” the hyper-skeptical Caulfield tells me when I describe to him what has been happening with arrhythmias. “All of these old-school concerns are arising.”
Some of the research for this article was funded by a Canadian Institutes of Health Research Journalism grant.