Dr. Jan Friedman discusses where we are and where we go from here
If you had asked Dr. Jan Friedman, Professor of Medical Genetics at UBC, when he was a promising young med student in New Orleans, if he imagined a day when we could know which patients were likely to respond well to a particular treatment and which patients would develop serious side effects, he’d say “not likely”. In a recent conversation with Genome BC, Dr. Friedman told us that he, “couldn’t imagine anyone asking a question like that back then. The idea would have been preposterous.”
But this idea is central to what we understand as “precision health” today. And the preposterous has become possible thanks to leading edge research of principal investigators like Jan Friedman, one of many world class researchers in the life sciences who call British Columbia home. We sat down with Jan to discuss the evolution of medical genetics and to learn more about what the future may hold for precision health.
Genome BC (GBC): How far has the use of genomics come in improving the diagnosis and treatment of patients?
Jan Friedman (JF): I have been doing research into the genetic causes of intellectual disability for more than 45 years. When I first started, the only genetic test we had was a chromosomal analysis, which could identify a genetic cause in people with Down syndrome and a few similar conditions – no more than 5% of all of those with intellectual disability. Incremental improvements in the technology increased this diagnostic rate to about 10% over the next 30 years, but we were stuck there until genomics became available. This first led to chromosomal microarray analysis, which doubled our ability to find genetic causes, and then to exome sequencing, which doubled it again.
Today, we are using whole genome sequencing in our research studies to replace all of these earlier tests. With it we can find a genetic cause in about half of all people with moderate or severe intellectual disability. This makes it possible for us to provide better care and genetic counselling for many, many more affected families.
GBC: How are genomic tools changing diagnostic and treatment success today?
JF: Genomic testing for intellectual disability and other birth defects is one of the most successful and widely used clinical applications of genomics today. Non-invasive Prenatal Testing (NIPT), testing fetal DNA extracted from the mother’s blood to identify certain serious fetal abnormalities, is now available as an insured service to any pregnant woman in BC whose pregnancy has been found to be at high risk through conventional screening tests. NIPT enables many women to get reassurance that their fetus does not actually have one of these conditions without having to undergo the risks and stress of amniocentesis.
Cancer therapeutics is seeing the use of genomics in the analysis of tumors, leading to greater success in treatment through precision drug therapies that target specific conditions. Better diagnosis and treatment for conditions like familial cancers, cardiac arrhythmias, and immunodeficiencies are also on the horizon as we move from conventional testing to testing for many possible genetic variants all at once. And testing for genes that predispose people to serious side effects of medications or that alter the way some people’s bodies interact with drugs can be used to make treatments for many other conditions safer and more effective.
GBC: What are some of challenges to overcome in order to see broader application of clinical genomics?
JF: Our healthcare system is government-supported, so when we want to introduce a new application clinically, we must prove its validity and cost-effectiveness. When we confirm a diagnosis through genetic testing, the news isn’t good, but diagnosis can lead to a dramatic improvement in therapy. For example, we may be able prescribe medications that would not normally be considered for a disorder, but for one particular patient, works much better than the medications that are typically prescribed.
In other cases, just being able to explain what has gone wrong and why is of incredible value to families. We see many families who spend many years and thousands of dollars of their own money, in addition to large amounts of health system resources, trying to find an explanation for their child’s birth defects. When we can help end their “diagnostic odyssey” through genomic testing, they often tell us they feel like they’ve won the lottery.
Genomic technology is new, and genomic medicine is not something that most doctors or health professionals were exposed to in residency, so it is important to provide ongoing education opportunities to enhance uptake and understanding. We also need to train and hire more genetic counselors and physicians who can make genomic medicine available in a safe and responsible fashion to everyone in BC who can benefit from it.
GBC: If we are able to achieve broader use of genomics in clinical diagnosis, what are some of the societal impacts we would need to address?
JF: Genomics is a powerful technology. It can be misused, so there needs to be a commitment to careful and responsible use. The importance we place on confidentiality and privacy of patient information does not change with genomics.
Genomics is the science of variation—our genome records the combination of differences that makes each of us unique—differences that we inherit from our parents and grandparents and their parents and grandparents, differences that may be shared with many other people or with only a few others in the entire world. In order to understand these normal differences among people—and each of us has millions of them at a genomic level—and to distinguish them from the one or two disease-causing differences that we might find in someone with a serious genetic disorder, we need to share genomic information with physicians and scientists all over the world.
And when we share this information, we need to do it while protecting privacy and while respecting each individual’s right to control what is done with her or his own genomic information. But it is something we need to do if we want patients in BC to benefit as much as they can from genomic medicine.
Genomic variation runs in families. My genome may provide information about others in my family who are not being tested. There are implications beyond the individual.
Another consideration is that when we do genome-wide testing for one particular disease in a person we’re looking at all of the genes at once. This can result in finding something incidental and that the person who was being tested might not want to know.
I’m reminded of a little girl we tested for intellectual disability. We did not find the cause of that problem, but we did find a genetic change that greatly increases the chance that she will develop cancer 30 or 40 years later. Do we tell her parents? What if she inherited this from one of her parents, who is already at the age where special cancer screening would be recommended? What are the implications of having this information in the medical record if they want to purchase life insurance for their child or for themselves? These situations require genetic counselling for the family, both before the testing so that they can decide if they want to hear about findings unrelated to the reason the test is being done and after so that they can change their mind in the changed circumstances.
The professional guidelines on this are different between Canada and the USA. In the US there is a list of 58 genes that a lab is obligated to tell you about, regardless of why the test was done, unless you specifically say you don’t want to know. Here in Canada, no such list exists. If we happen to find a disease-causing genetic change in a child, the parent must be told if the condition can be prevented or improved by treatment in childhood. If it is not treatable in childhood, the parents are not told. If we test an adult, we ask them if they would like to know about genes that we happen to find that can cause diseases unrelated to the reason for testing, and we only tell them if they ask us to do so.
*(It’s important to note that in the US, there are protections under the Genetic Information Nondiscrimination Act. Similar legislation is in development in Canada, but has yet to become law.)
GBC: From your perspective, where does genomics go from here?
JF: Genomic technologies have transformed biological and medical research, but our understanding of how the genome actually works is still rudimentary. This is an immensely exciting time for students in genetic and genomic science. Clinical applications of genomics are just the beginning, but they will affect every area of medicine over the next 10-20 years. Genomics, like any very powerful technology, must be used responsibly. It can be misused, and we must avoid that. Finally, personalized medicine is all about the person—each person, each patient.
About Jan M. Friedman, MD, PhD, FAAP, FABMG, FCCMG, FRCPC
Dr. Friedman’s research bridges clinical genetics and basic science. His lab’s work is focused in three major areas: First, the application of advanced genomic technology to identifying the causes of intellectual disability; Second, using genetic epidemiology to elucidate the pathogenesis of neurofibromatosis 1 and 2; and third, the development of a knowledge base on human teratogenic risks resulting from maternal treatment with various medications during pregnancy.
Jan is also interested in the societal implications of genetics and is collaborating in several projects studying various social, economic, and ethical aspects of clinical application of new genomic technologies