Advancing technologies, new genomic testing techniques, and championing for up-to-date health care policies are the focus of Dr. Yvonne Bombard and her lab. Dr. Bombard’s mission is shaping patient care with the fast-evolving health care tools of Medical Genomics.
Kevin Navarro Hernandez and James Sayre
A major aspect of the Canadian identity is its recognition and protection of historically marginalized groups. The protection of individuals based on gender, ethnicity, and physical ability have long been recognized in Canadian law – more recently joined by the protection of sexual orientation of individuals in 19961. These rights are at the heart of protecting individuals from direct discrimination on the bases of traits which are inherent to their personhood. From a biological perspective many of these protected traits– ethnicity, gender, physical ability, sexual orientation – are genetic at their root, but the protection against genetic discrimination was only ratified federally in 20172,3 thanks to the initiative of Dr. Bombard.
While observing patients being tested for Huntington’s disease during her PhD, Dr. Bombard witnessed genetic discrimination firsthand. A life-altering neurodegenerative disorder, Huntington’s disease is a rare genetic disorder that damages nerve cells, leading to reduced mobility, cognitive ability, and in some cases psychiatric disorders. One of the patients Dr. Bombard connected with shared how their employer upon learning of their diagnosis began to assign them fewer working hours, discriminately changed their job responsibilities and put the individual under surveillance at work. The disease had not advanced to warrant such changes. It was the employer’s knowledge of the diagnosis that prompted these actions making work much more difficult for the patient.
Dr. Bombard recalled: “I remember … phoning a legal scholar that I knew at the University of Toronto and asking for his advice; asking him, is this legal? Does this happen? Does Canada have any protections against this for their patients? And he said, no.”
Seeing there was no protection for those receiving rare disease genetic diagnoses, Dr. Bombard set about to describe a framework of protection for such patients. Her vision was to develop a system for those found to be at greater risk of being diagnosed with a genetic disorder; a system that allowed them to not only navigate their test results but to also learn what would be considered as discriminatory towards them because of their diagnosis. Dr. Bombard characterized this as a socio-medical relationship between patients and their employers, showing it to be fraught with difficult decisions, financial considerations, and emotional risks4,5,6.
Catalyzed and determined by her work with Huntington’s, Dr. Bombard pivoted her doctoral work towards the development of legal protection of individuals on a genetic composition basis, using what she had seen with Huntington’s disease as a model. Working with academic colleagues, legal scholars, and political allies, Dr. Bombard was instrumental in introducing Bill S201 to federal parliament. Bill S201 passed on May 4, 2017, in the federal legislature bringing the Genetic Non-discrimination Act into Canadian law2,3. This act protects individuals from being forced to undergo genetic testing, protects the results of previous tests from disclosure to employers and insurance providers, and bolsters Canadian’s right to medical privacy.
Dr. Bombard’s Lab Mission
Dr. Bombard’s work on behalf of patients receiving genetic testing did not end there. Dr. Bombard and her laboratory are in a constant race with the advances in genomics. The field of genomics grows daily as technology quickly develops, improving research methods and implementation of treatments for various genetic diseases.
Genomic medicine is expanding from a focus on research and diagnosis to prevention at the population level. As technology progresses and test costs fall, screening pre-symptomatic individuals through public health-based approaches could become feasible6,7. Recent studies found that restricting screening for patients who meet the family history-based criteria for breast cancer has missed more than 50% of individuals with pathogenic BRCA1 and BRCA2 (BRCA1/2) variants8. These findings are suggestive that population screening is the key towards preventative medicine. Being able to identify variants even in communities where there is no family history of rare diseases is bringing health care to everyone and a step towards making it universal.
Considerations for population genomics screening are whether to perform full gene sequencing or targeted variant testing. Other variables to consider are whether to test for novel variants or only known pathogenic ones, as well as performing deletion/duplication analysis in addition to sequence analysis. These kinds of decisions will have an impact on the test cost and cost-effectiveness effect on patients. Some of the most prevalent hereditary conditions that should be considered for population screening include familial hypercholesterolemia (FH), Lynch syndrome (LS), and hereditary breast and ovarian cancer syndrome (HBOC)8. These are some of the diseases that the Bombard lab is researching.
Issues with implementing population genomic screening include the optimal testing approach, penetrance of these conditions in the general population, clinical and cost-effectiveness, acceptability, health system capacity to implement such a program, ethical issues such as overdiagnosis, access challenges and equity6,7.
At the center of Dr. Bombard’s research, is a strong ethos of patient centric and collaborative care. As an extension of this ethos, part of her current work revolves around educating patients on the fundamentals of genetics. This opens the door to discussion about the implications of genetic testing, and describing how to best communicate results in a way that allows patients to make informed decisions about their care. This research has culminated in the development ofThe Genomics ADvISER (Genomics decision AiD about Incidental Sequencing Results), a platform designed to fill the gaps in contemporary care by offering education resources, exercises to help patients explore their values with regards to testing, and ultimately feel empowered in making their care decisions.
A common question is: What makes genetic testing different from other more common medical testing? Genetic testing can have unexpected and broader implications and responsibilities. It has the potential to open up avenues of far reaching medical consequences. Firstly, because genetic information is heritable, passed between parents and children, testing inherently provides information on related individuals. This can expand the implications of the testing beyond the individual for which it is intended. Furthermore, secondary findings – findings during genetic testing which are not related to the primary purpose of testing – are becoming far more common with increases in the use of Next Generation Sequencing techniques, and whole genome sequencing which return huge amounts of genomic information. “we’re now just inundated, bombarded, if you will,…with a lot of data that we have to sift through”. This is where the ADvISER platform helps bridge the gaps between this mass of information, physicians who are already stretched thin and patients who may be encountering the world of genomics for the first time, in potentially vulnerable states. Proponents for genomic medicine say that we should be sequencing everyone at birth, and while there is merit to this approach in terms of treatment, there is also subsequent fallout that is generated by secondary findings, implications for related individuals who are uninterested in genetic testing and the larger scale delivery of this information in a comprehensible form.
Dr. Bombard describes how “ ADvISER was actually also built, developed and then tested out of necessity because we were returning secondary findings…where we’re sequencing individuals and returning results”. Because of the untargeted nature of extensive genomic sequencing, like whole genome sequencing, secondary findings are an unavoidable product of genetic screening. Some sequence information can simply be overlooked, but what are physicians and patients supposed to do in cases where testing returns consequential and actionable secondary findings? This is where the ADvISER platform is intended to aid patients in the decision-making process to come to a conclusion which best aligns with their personal ethics around testing, treatment, and how to handle the potential uncertainties that comes with genetic testing9,10. Genetic testing has the potential of TMI (too much information). ADvISER helps doctor, patient and medical system disseminate the results of the genetic testing in order to plot a way forward for patient care.
Dr. Bombard’s field of research and job are challenging. In reply to what is the biggest challenge in policy research, Dr. Bombard said: “being mindful of the fact that there’s a fine line between being a scientist, a science advocate and a policy advocate”. The job comes with many responsibilities not only for her as an advocate, but also the responsibility of developing efficient policies that meet society’s needs. This is an ongoing process with no end in sight. During our interview with Dr. Bombard, she said: “the irony is that the technologies will constantly evolve and what we can bring into our system will have to evolve as well”. This means that even if the system is restructured and redesigned to serve the point in time we live in now, it will have to be reshaped to keep up with technological advances. The world of genomic policy is rapidly growing and changing. At the end of our interview, Dr. Bombard left us with this final quote about what her end goal as a pioneer of medical genomics in policy would look like: “I feel like mission complete is when we’ve structured our health care system for our patients via genomics and it is patient centered serving them in the way that they want and need”.
- Government of Canada. Canada.ca (2022). Available at: https://www.canada.ca/en/canadian-heritage/services/rights-lgbti-persons.html. (Accessed: 10th April 2023)
- Standing Senate Committee on Human Rights (41st Parliament … – Sencanada, sencanada.ca/en/Content/Sen/committee/412/ridr/11ev-51620-e.
- Branch, L. S. Consolidated federal laws of canada, Genetic Non-Discrimination Act. Genetic Non-Discrimination Act(2023). Available at: https://laws-lois.justice.gc.ca/eng/acts/G-2.5/page-1.html. (Accessed: 10th April 2023)
- Bombard, Y. et al. Managing genetic discrimination: Strategies used by individuals found to have the Huntington disease mutation. Clin. Genet. (2007).
- Bombard, Yvonne et al. “Perceptions of genetic discrimination among people at risk for Huntington’s disease: a cross sectional survey.” BMJ (Clinical research ed.) (2009). doi:10.1136/bmj.b2175
- “Why We Need a Law to Prevent Genetic Discrimination.” The Globe and mail, http://www.theglobeandmail.com/amp/opinion/why-we-need-a-law-to-prevent-genetic-discrimination/article31936476/.
- Mighton, Chloe, et al. “From the Patient to the Population: Use of Genomics for Population Screening.” Frontiers in Genetics. (2022) https://doi.org/10.3389/fgene.2022.893832.
- Manchanda, R., Loggenberg, K., Sanderson, S., Burnell,M.,Wardle, J., Gessler, S., et al. Population testing for cancer predisposing BRCA1/BRCA2 mutations in the ashkenazi-jewish community: A randomized controlled trial. J. Natl. Cancer Inst. (2015). https://doi:10.1093/jnci/dju379
- Bombard, Y. et al. Genomics ADvISER: development and usability testing of a decision aid for the selection of incidental sequencing results. Eur. J. Hum. Genet. (2018).
- Bombard, Yvonne et al. “Effectiveness of the Genomics ADvISER decision aid for the selection of secondary findings from genomic sequencing: a randomized clinical trial.” Genetics in medicine: official journal of the American College of Medical Genetics. (2020). doi:10.1038/s41436-019-0702-z
- Shickh, Salma et al. “Genetics Adviser: a protocol for a mixed-methods randomised controlled trial evaluating a digital platform for genetics service delivery.” BMJ (Clinical research ed.) (2022). doi:10.1136/bmjopen-2022-060899