"There was bound to be a stage when we could identify people at risk and not be able to do anything about it. We are there now. We're stuck."
-Geneticist Dr. Marie Claire King, who identified the chromosome carrying the BRCA1 gene.
Until recently, bio-ethical debates about genetics were tuck behind the doors of academic conferences and confined to the pages of obscure scientific journals. For over 20 years, scientists have been aware of dozens of genes which have the potential to trigger cancer. However, it wasn't until the medical and commercial wrangling over a mutated gene associated with an increased risk of breast cancer erupted five years ago that the debate came out of the scientific closet.
During those same last few years, genes linked to cystic fibrosis, epilepsy, Parkinson's disease, Alzheimer's and even tendencies toward heroin addiction and obsessive-compulsive disorder have also been mapped out. Every other week, it seems, the location of another 'defective gene' is announced by scientists associated with the $3 billion Human Genome Project, private bio-tech companies or university researchers, raising the hope that genetic therapy will soon be able to cure conditions and diseases.
Predictive genetic testing -- that is, identifying genes which may escalate a person's lifetime risk -- is just the tip of an iceberg made up of ethical, medical social, legal and commercial questions. Should predictive genetic testing be offered to individuals if there is no medical treatment to reduce their chances of acquiring a disease? Should a bio-tech company, a researcher or a university be allowed to lay claim to a piece of human life, in the same way a company takes out a patent on a soft drink formula? Are there conditions under which genetic screening should be offered or prohibited? Who pays, and most importantly, who decides?
The case of Fiona Webster, followed in the Globe and Mail last summer, framed predictive genetic testing as a 'right to know' issue, and characterized her strong family history of breast cancer as 'a curse.' The London woman went public with her bid to push the Ontario Health Insurance Plan (OHIP) to pay more than $3,000 to a private US company for the procedure, which would mean having her genes compared to those of other family members.
Webster didn't want to wait to have testing completed in Ontario, and OHIP refused to pay for expedited testing in a private US clinic. In Canada, genetic testing for BRCA1 and BRCA2 is available on a limited experimental basis to women in BC and Ontario who have a significant first generation family history of the disease. Because of licensing complications and a legal battle over the patents in the US, testing done on Canadian women is done on an experimental basis only; it can take up to two years to have DNA analyzed. The issue is indirectly complicated by the fact that Canada has so far refused to recognize patents on human genes, or on any higher forms of life.
The Utah company that Webster sought out is owned by Dr. Mark Skolnick, the geneticist who in September 1994 first isolated the BRCA1 gene. He quickly filed two patents in the US related to the gene -- one on the 'composition of matter' and the second on a 'method of use' which would give his bio-tech company, Myriad Genetics, exclusive rights to license a test to be developed later. Not surprisingly, when the public got word of the discovery of a gene for breast cancer, the fact that women who have a mutated BRCA1 gene can't do anything about the gene somehow got lost in the hype.
Skolnick then horrified women's health advocates -- the feminist contingent -- when he began proselytizing that women who tested positive for the mutant gene might want to consider having their ovaries or their breasts removed, "to reduce their risk of dying as much as possible."
So great is women's fear of contracting breast cancer that doing anything may seem better than waiting, especially for women whose mothers or sisters have had the disease. Fiona Webster was thinking about having a double mastectomy when someone donated the money to have the testing done in the US. Luckily, she didn't have the mutated gene sequences that Myriad tests for.
Because predictive genetic testing is still in its infancy, many people believe it is akin to a test for breast cancer. This is one of the reasons why counselling is at least as important as the testing itself. According to Nora Gambioli, Executive Director of the Canadian Breast Cancer Network, there is a shortage of genetic counsellors in Canada to help women make an informed decision about predictive genetic testing. That counselling includes dealing with emotional trauma, possible family rifts (since family members are asked to provide blood samples) and "decision-making that could involve having mutilating surgery in the hope of preventing disease onset". Dr. Susan Love summarizes the quandary in To Dance With the Devil: The New War on Breast Cancer: "The way you present it (test results) is crucial. You say, 'Have your breasts cut off if you have the gene,' and women are going to have their breasts cut off." Karen Stabiner, author of To Dance With the Devil added, "Any recommendation was going to come off sounding like a rule -- not because the doctor meant it that way, but because women were so eager for a definitive answer."
We all have a BRCA1 and BRCA2 gene. If they are normal, our lifetime risk of breast cancer -- that is if we live to be about 90 -- is about 10 percent. The presence of a mutated or altered gene, which is prevalent among those with a strong family history of breast cancer, increases that risk to between 46-85 percent. It's about odds, in other words, not diagnosis.
The Canadian Breast Cancer Network's position statement on predictive genetic for breast cancer testing sums up a best case scenario: "A positive test may promote needless stress, while a negative test may confer a false sense of security."
Love was somewhat less diplomatic. She saw the patenting of BRCA1 as little more than a money grab. And according to Dr. Marie Claire King, who worked for 17 years to locate this breast cancer gene, medical science wouldn't be doing a woman a favour by telling her she had the gene when there was nothing she could do but worry. King strongly believed, however, that genetics could help researchers understand breast cancer and that it might lead to treatments tailored to those who have breast cancer and test positive for a specific genetic mutations.
King also believed in scientific collaboration, which is why she announced to the research community that the gene was somewhere on chromosome 17. In fact, she was working cooperatively with scientists in Britain and Canada to isolate the gene when she was scooped by Skolnick. A year later, another gene, BRCA2 was discovered and Myriad Genetics and another company, OncorMed, became involved in a legal dispute over patent rights.
Patent rights are of little interest to women who want to find out they have a breast cancer gene mutation. They want to take action, but what are the options? Having a double mastectomy will reduce the odds of developing breast cancer as much as 90 percent, however conducting major surgery on healthy people is highly questionable. Somewhere between 15-44 percent of women with a mutated gene won't develop breast cancer, and if they do, the odds of surviving are about 75 percent. And even after a double mastectomy, there is still a small chance that breast cancer can still develop.
Encouraging women to have more frequent mammograms may seem like good advice, however mammograms are not generally useful diagnosing breast cancer in premenopausal women and miss an estimated 15 percent of tumours. Dr. Jane Gibson, a lab director in Orlando, Florida, reported that women with another breast cancer gene, called ATM, "may not be the best candidates for frequent mammograms, since radiation causes this type of cancer to grow."
Sharon Batt, breast cancer survivor and director of research at Breast Cancer Action Montreal, says women with a genetic predisposition to breast cancer would be inclined to look to drug therapy. In particular, to last year's National Cancer Institute study on tamoxifen. The six-year NCI study was halted a year early because the oncologists involved in the study were convinced that tamoxifen had proven itself as a treatment for women with a higher than normal risk for breast cancer.
However, Batt, author of the groundbreaking book Patient No More (Gynergy Press) says that the risks of taking tamoxifen outweigh any potential short term benefits the drug may have among healthy women. In the NCI study, which included Canadian women, those in the tamoxifen group had a 45 percent lower incidence of breast cancer (85 cases) compared to those in the control group (154 cases) for the duration of the study. While this was good news for Zeneca Pharmaceuticals, makers of tamoxifen, the prognosis for women was iffy, since tamoxifen did nothing to reduce overall death rates. There were 5 breast cancer deaths in the control group and 5 deaths in the tamoxifen group-3 breast cancer and 2 from pulmonary embolisms, a known risk of tamoxifen. Additionally, women taking tamoxifen had more than twice the number of uterine cancers as women in the control group, and three times the rate of pulmonary embolism (blood clots in the lungs). Batt and other breast cancer activists were furious that a drug that put healthy women at risk and offered at best 'disease substitution' was heralded as a 'breakthrough.'
Within six months of the NCI study, the US Food and Drug Administration gave tamoxifen the green light as a 'short term preventive treatment,' a previously unheard category of drug therapy. The FDA could not say that tamoxifen prevents cancer, since it appears to at best defer onset for a few years as well as increase the risk for pulmonary embolisms and uterine cancer. The North American results haven't been published in a peer-reviewed journal. Meanwhile, published results of British and Italian trials show no preventive benefit for tamoxifen.
Adriane Fugh-Berman of the National Women's Health Network told the US FDA that it is not acceptable to put healthy women at risk when there are no proven long term benefits of prescribing the drug. "Acceptable risks for the sick are not acceptable risks for the well," she said.
She was referring to the fact that when used as a post-surgical treatment to prevent recurrence among postmenopausal women with estrogen-positive tumours, tamoxifen reduces recurrence of breast cancer by 50 percent for about 5 years. Then its effects wear off. Batt points out that women with BRCA genes seem to be more likely to have estrogen-negative tumours -- that is, tumours that are unreceptive to tamoxifen's estrogen-blocking properties. Nonetheless, the FDA stamp of approval means US doctors can prescribe it for women vaguely categorized as 'high risk' and there are worries that Health Canada will follow suit.
Dr. Neil Sharpe, author of In Control Making the Most of the Genetic Test for Breast Cancer shares at least one of the Canadian Breast Cancer Network's fears: genetic discrimination. Sharpe, a Canadian geneticist, advises in his book: "Generally speaking, if two or more members of a family have had breast, ovarian, colon, or prostate cancer and if any of these were diagnosed before the age of 50 you should have your doctor refer you to a genetics clinic." He also warns that insurance companies could use genetic testing to eliminate people from receiving benefits. Insurance applicants must provide detailed health and medical information to determine their eligibility and premiums; they also sign a waiver that entitles the company to seek any medical records, which may be used to determine insurance rates or deny coverage.
The Canadian Breast Cancer Network, whose board members are cancer survivors, is recommending legislation to prohibit genetic discrimination, a move also underway in the US, where genetic privacy bills are being debated at the state level. The fear is not imagined. In 1990, the Supreme Court of Canada ruled that an insurance company did not have to pay the insurance of a Quebec man genes is a red herring anyway -- since it "focusses on the one piece of the puzzle we can do absolutely nothing about."
Echoing her sentiment, Gambioli, notes, "It's important to remember that only about 5 percent of breast cancer cases involve a mutation in these genes." Epidemiologically speaking, that means 95 percent of breast cancers are triggered by something other than defective genes. This is a sore spot with breast cancer activists, who are trying to shift public health policy and cancer research away from drug treatments and mammograms (early detection and self-exams are still important) to actually preventing the disease.
Leading the way in this paradigm shift are North American breast cancer advocates and researchers, like those who gathered at the First World Conference on Breast Cancer in Kingston in 1996 and will come together again in Ottawa this July. Near the top of their revolutionary breast cancer agenda is an end to cancer-causing pollutants in the environment. The Canadian Breast Cancer Network wants organochlorines, a class of hormone-mimicking toxins with a strong link to breast cancer, prostate cancer and non-Hodgkins lymphoma to be phased out completely. Three quarters of the rise in cancers are attributable to environmental factors, according to Samuel Epstein, a professor of environmental medicine at the University of Illinois.
The term 'patient no more' is a signal that women are positioning themselves differently, refusing to be grateful for breast cancer treatments haven't changed outcomes in a significant way in the last 50 years, while incidence has increased. Breast cancer research is predominantly funded by mammogram and pharmaceutical drug companies, whose profit motivations are at odds with the increasingly political breast survivors' movement.
At the same time, public awareness about cancer hasn't changed much since 'the war against cancer' was declared by US president Richard Nixon at the end of the Vietnam War. A belief in the race for a cure ensures that the cancer agenda will remain focussed on chemical and radioactive weapons to fight 'the war.' The breast cancer survivors' movement has not only questioned the battle plan, but has challenged the authority of the generals and even questioned who the 'enemy' is.
Drug companies, now called biotechnology firms, have also undergone major changes in the past 30 years. They now call themselves bio-tech companies, a reflection of the fact that their products are as likely to include genetically engineered components for vaccines, genetically altered foods and crops, in addition to conventional pharmaceutical drugs, pesticides, plastics, and industrial chemicals. The industry has also come under heavy criticism in North America and Europe for wielding too much influence within public health protection agencies, and also at the international trade table, where biotech companies are pushing international agencies like the World Trade Organization to ensure globalized access to markets for gene altered crops and foods, potentially overriding individual countries' health and patent restrictions.
To say that women's health advocates ruffle feathers when they criticize the medical establishment as well as the practices of some drug companies, is an understatement. They want to know why, if preventing breast cancer is important to the medical community, drugs known to increase incidence of breast cancer are prescribed at an alarming rate. Premarin, for instance, is at the top of the prescription bestseller list in Canada, yet the latest research on hormone replacement therapy's top two selling points that it reduces the risk of heart disease and osteoporosis -- suggests the drug's benefits have been oversold. And according to a 1996 British study by Dr. Ellen Grant, women taking hormone replacement therapy for more than 10 years had a 43 percent higher death rate from breast cancer than breast cancer patients not on HRT.
Since Skolnick first isolated the BRCA1 gene, blood samples have revealed more genetic mutations or alterations associated with inherited risks of breast cancer, leading many, including Skolnick to admit that the notion of a single gene responsible for inherited breast cancer is unlikely. At the same time, genetic research has helped in the development of a new breast cancer drug that shows encouraging signs in a small percentage of women who have breast cancer. HER-2/neu is a gene test done after cancer is already diagnosed; the presence of a defective or 'altered' HER-2/neu gene characterizes a particularly aggressive form of cancer, which is likely to recur. The new drug, Herceptin helps regulate the overproduction of a protein on the outside of this gene, temporarily reducing tumour growth for 40 percent of patients, when combined with another cancer drug, taxol. Interestingly, the drug maker age of women who have breast cancer. HER-2/neu is a gene test done after cancer is already diagnosed; the presence of a defective or 'altered' HER-2/neu gene characterizes a particularly aggressive form of cancer, which is likely to recur. The new drug, Herceptin helps regulate the overproduction of a protein on the outside of this gene, temporarily reducing tumour growth for 40 percent of patients, when combined with another cancer drug, taxol. Interestingly, the drug maker shared its science with Fran Visco, president of the National Breast Cancer Coalition in the US in order to enlist her group's support and help oversee its drug trials.
It's important to remember that genes are not foreign substances like bacteria or viruses, which can simply be rooted out. They perform beneficial functions, the complexity of which is not yet understood. For example, when scientists deleted a breast cancer gene called WINT1 from mice, they knocked out their cerebellum. A New York Times article reported that a gene that developed in the 14th century from survivors of the bubonic plague appears to provide natural immunity to HIV. A gene that causes sickle cell anemia when it is present in two copies protects against malaria in people who inherit just one copy, while the cystic fibrosis gene protects against typhoid fever.
Remember your biology class? Each of our cells contains 23 pairs of chromosomes, one set from each of your parents. The chromosomes are made of deoxyribonucleic acid (DNA), the ladder-like structure which is made up of genes -- about 100,000 of them, maybe more. The whole notion of patenting human gene sequences and claiming ownership rights on plant and animal life forms is something that many feminists, scientists, farmers, consumers groups, environmentalists and medical researchers are also fighting on a global scale.
Indigenous people in the southern hemisphere are fighting what they see as a global usurpation of farmers' traditional agricultural rights to breed their own crops, keep seeds and a desire to prohibit foreign multinationals from dominating their food supply. Recently, India refused to acknowledge a US company's patent claim on South-Asian bred Basmati Rice. Indian physicist Dr. Vandana Shiva, author of Bio Piracy doesn't hesitate to call agricultural patenting a new breed of colonialism. Many scientists have expressed repugnance at the prospect of reducing the genetic diversity in the world's food crops, a trend which is predicted to exacerbate crop blights, encourage more resistant bacteria and bugs to evolve and weaken the stability of world food crops.
The World Medical Association, which represents doctors in 77 countries, believes that no doctor should take part in patenting life forms because it puts them in a conflict of interest. Many countries have banned such patents, while the US is considered the most lax.
Canadian patent policies and practices are uneven. Patent law doesn't currently recognize patents on higher life forms (an entire mammal for example), but it doesn't appear to prohibit them either. There are currently no venues to appeal patents, let alone refuse them on moral grounds. Meanwhile, the 'knowledge economy' is an official element of the federal government's industrial strategy, with subsidies to bio-tech companies expected to double to more than $600 million in 2 years, rivalling direct subsidies to the oil and gas industry.
In its benign state, the ability to decipher the code of a gene is merely information. In the context of globalization and an increasingly borderless marketplace, 'intellectual property rights' are an industrial euphemism for patent rights on living matter discovered in the lab or 'invented' by crossspecies genetic combining or cloning.
Bio-tech firms operating in Canada are already producing genetically altered crops, including genetically engineered soy, potatoes, grains and canola oil. Contracts make it illegal for Canadian farmers to keep seeds. Canada's food directorate requires no labelling on genetically altered food, even though no long term testing has been done to determine whether consumption is safe.
Human genetic material is also used in 'pharming,' a new wave of drugs manufactured by genetically altered animals. The Scottish bio-tech company whose researchers cloned Dolly were in search of a cheap way to reproduce sheep into whom a human breast milk gene had been inserted. The sheep manufacture milk containing a component from human breast milk that could become a treatment for cystic fibrosis. Since the genetic make up of the invention is 'new' it is arguably patentable.
If you can splice a fish gene into a tomato to give it a longer shelf life or slip a potato-beetle killing bacteria into the cell structure of a potato, should you be able to patent animal or human genes because your technology could be profitable? A 1992 report by the Privacy Commissioner of Canada compared the potential impact of unlocking the gene to that of unlocking the atom 50 years ago; both discoveries have the potential to alter life as we know it.
Like the unravelling of a strand of DNA, commercialized genetics has unleashed an ethical flurry of scientific, medical, social and legal progeny that we are only beginning to conceive.…