Issue 07

SPARK

Dr. Michael Smith: The Legacy

Twenty five years ago Dr. Michael Smith became British Columbia’s first Nobel Laureate.

Smith’s Nobel Prize was awarded for his work on site-directed mutagenesis, a revolutionary technique that allows scientists to make a genetic mutation precisely at any spot in a DNA molecule, helping us better understand how genes work, and what happens when they go wrong.

Michael Smith stamp image © Canada Post Corporation (2004).
Michael Smith stamp © Canada Post Corporation (2004).

This technique underpins much of our current understanding of genetic diseases from cancer to HIV/AIDS, and helped propel BC to international prominence as a world leader in genomics research.

But Smith’s impact stretched far beyond genomics. He was a tireless advocate for emerging scientific talent, women in STEM (Science, Technology, Engineering, and Mathematics) and interdisciplinary collaboration in order to apply science for the good of humanity.

https://www.youtube.com/embed/AznzHqwIa7U
Celebrating the 25th anniversary of Dr. Michael Smith's Nobel Prize|6:06

Named in his honour, the Michael Smith Foundation for Health Research is proud to continue Smith’s legacy with every funding award we issue. Read on to explore how MSFHR-funded researchers are continuing the tradition of scientific excellence and collaboration, making significant discoveries, and bringing the benefits to British Columbians.

Chapter 01

Building the foundations

Cancer starts as a genetic change in one cell.

At the Michael Smith Genome Sciences Centre (GSC) at BC Cancer, researchers are using tools and techniques underpinned by Dr. Michael Smith’s work to understand these changes, learn why and how cancers form and spread, and figure out how to ‘turn off’ the genes that drive cancer growth, and ‘turn on’ our body's cancer defenses.

The GSC, founded and initially led by Smith and his colleague Dr. Victor Ling, opened its doors a year before Smith’s death in 2000, and quickly put BC on the map as an international leader in genomics research.

Ling, who was vice president of research at BC Cancer at the time, had recruited Smith out of retirement to develop the centre. It was a master strategic move given Smith had recently won his Nobel Prize, and was Canada’s most famous scientist, popular with the research community, government and the public at large.

Dr. Marco Marra, director of the GSC, who had completed his PhD at Simon Fraser University but was pursuing post-doctoral studies at Washington University in St. Louis, remembers his first interactions with Smith. “I remember our conversations vividly because Michael was working with Victor to establish a genomic centre at BC Cancer and at the time I was skeptical that Canada, much less Vancouver, could be competitive in this area. Of course I was wrong. With Michael’s passion and energy behind the centre it was a great opportunity to come back to Canada and work in my field.”

Not only did Smith develop the GSC, but to this day the vast majority of the work conducted in the centre’s labs relies on chemistry that Smith was instrumental in developing, both for site-directed mutagenesis and later DNA sequencing. These techniques have resulted in new made-in-BC treatments and practices that have led to BC having some of the best cancer treatment outcomes in the world.

Michael’s chemistry — from site-directed mutagenesis to the DNA sequencing approach he helped Fred Sanger develop — underpins many of our major advances in cancer understanding and treatment for the last two decades, from personalized medicine and drug development, to advanced diagnostics.

“Site-directed mutagenesis was a ground-breaking technology, the CRISPR of its day, that allowed an explosion of activity in genomics and genomics research. Michael is known for that Nobel Prize-winning work, but his legacy stretches far more broadly across the fields of DNA sequencing and manipulation, and capacity building in BC,” explains Dr. Steve Jones, head of bioinformatics and co-director of the GSC, and another of Smith’s early recruits who was drawn back to BC from the UK’s Sanger Institute to head up the centre’s bioinformatics function. “Michael’s chemistry — from site-directed mutagenesis to the DNA sequencing approach he helped Fred Sanger develop — underpins many of our major advances in cancer understanding and treatment over the last two decades, from personalized medicine and drug development, to advanced diagnostics.”

Smith reading DNA sequences, BC Cancer

Smith left behind not only the chemistry that formed the foundations of modern genomics research, and infrastructure that would allow BC to thrive as an international leader in the field, but also the vision that we could use the tools of genome science — which largely didn't exist at the time — to make a positive impact in the lives of people living with cancer.

“Michael had the ability to see the potential in people, and in research,” reflects Marra. “He had real vision. Some days we can all be a little shy of vision, but we must look for that potential and pursue it with rigour.”

Having been repatriated to BC by Smith, Marco Marra and Steve Jones (pictured in header image with Smith at the Genome Sciences Centre, February 2000) became two of MSFHR’s first Scholars (2001 and 2003 respectively), both receiving second Scholar awards five years later. MSFHR has funded over 160 researchers at BC Cancer since 2001, supporting world-class cancer and genomics research for the benefit of British Columbians.

Chapter 02

Competition to collaboration

If genomics allows you to study DNA and genes — the recipes for life — proteomics helps us understand the results of those recipes — the proteins in our cells and tissues, where they are, what they do, and what that means for the function of an organism.

Proteomics touches every form of life sciences research — from helping us understand disease development in conditions such as cystic fibrosis and muscular dystrophy to informing new diagnostic tools, drugs and the emerging field of personalized medicine.

It’s still a relatively young field of research, having developed out of our advances in genomics research over the past quarter of a century. Where Dr. Michael Smith’s site-directed mutagenesis allows you to manipulate DNA, proteomics lets you look at the result of those changes, and what they mean for how the body functions.

But just a decade ago, the proteomics community in BC was fragmented, with individual researchers and laboratories working separately, and in competition with one another, burdened by the prohibitive cost of maintaining high-tech proteomics equipment.

To address this, colleagues from the University of British Columbia (UBC), University of Victoria (UVic), and BC Cancer, applied for MSFHR funding in 2007 to create the BC Proteomics Network (BCPN). The goal was to encourage collaboration, training, and resource sharing between researchers who had previously been competitors.

An engineer services a mass spectrometer in UBC’s Michael Smith Laboratories.

“A mass spectrometer, the fundamental piece of equipment in proteomics research, can cost up to $1.4M to purchase, and across the province we could spend $500,000 to $700,000 per year maintaining all the instruments. For many labs, the maintenance costs can kill a research project before it’s even started,” explains Dr. Leonard Foster, BCPN’s former scientific director and a professor in the department of biochemistry and molecular biology at UBC. “Through the network we were able to hire an engineer to maintain critical equipment, saving over $400,000 a year in operating costs.”

By pooling resources through the network, labs were able to unleash the potential of proteomics research and make this ground-breaking technology available for researchers and clinicians across the province, helping them understand more about the proteins at the root of countless diseases.

For Dr. Leigh Anne Swayne, an associate professor at UVic, her work on the proteins involved in brain healing after injury or stroke, and in diseases such as schizophrenia, would not have been possible without the UVic Genome BC Proteomics Centre, one of the facilities that makes use of BCPN maintenance support.

Learn more about Dr. Swayne’s work on brain healing

“Within the province, the BC Proteomics Network has given us a huge advantage for our protein-related discovery work, and solidified BC’s position as a world leader in the development, use and application of genomics and proteomics technologies,” explains Dr. Thibault Mayor, BCPN scientific director and a professor in the department of biochemistry and molecular biology at UBC. “We are very proud to support cutting-edge proteomics through infrastructure, training and education, which will have a lasting impact for the next generation of researchers and clinicians in BC and across Canada.”

The BC Proteomics Network was funded by an 11-year Technology/Methodology Platform award from MSFHR. This award provided funding of $4.3M over three phases, and helped 13 BC research teams attract over $5.2M in additional grant funding. Subsequently, the team behind the BCPN secured a $11.1M Genome Canada grant to expand nationally. Leonard Foster, Thibault Mayor and Leigh Anne Swayne are all MSFHR Scholar award recipients (2005, 2012 and 2014 respectively).

Chapter 03

From lab to life

Studying DNA, genes and proteins might seem impersonal, but for clinical geneticist Dr. Suzanne Lewis, genetics research holds the power to understand and manage the symptoms of autism spectrum disorder on an individual basis.

Autism spectrum disorder (ASD) is a developmental condition that affects brain growth with impacts that vary dramatically from person to person. Typically diagnosed in childhood, some people with ASD exhibit repetitive behaviours and experience communication and social interaction challenges that have only a mild impact on their day-to-day life. Others have more severe symptoms and associated medical conditions that can prevent them from speaking or living independently.

Dr. Suzanne Lewis

“People talk about autism like they did about cancer 30 years ago, a single label for a single entity. Now we know there are many different sub-types of cancer, and we can’t treat them with a one-size-fits-all approach. Through genetics, we’re learning it’s the same with autism,” explains Lewis, an investigator and clinical professor at BC Children’s Hospital, and chief medical officer & vice president of research at the Pacific Autism Family Network.

In reality what we call ‘autism’ is likely a group of symptoms associated with many different underlying genetic and environmental causes. But for Lewis, her job as a clinical geneticist is more than just understanding the cause of the disease, it’s about reading the signs in a person’s genetic makeup and using that to help the child and their family understand potential challenges and strengths. This genetic information can equip the family with information that can help predict, and in some cases even prevent, future complications such as epilepsy.

Lewis explains, “We’re working towards identifying different subtypes of autism using a whole body perspective. Not just a person’s genetics but also their observable traits, the microorganisms living in their body, their proteins and environmental impacts to understand autism in a more holistic way.”

Lewis’ research into the underlying genetic mutations and their impacts relies on tools and techniques built on Dr. Michael Smith’s discovery of site-directed mutagenesis. “Michael was a brilliant biochemist, and even though he was largely laboratory based, his vision was very much focused on the benefits his work could provide in clinical medicine, and merging those two spheres so lab scientists and clinical scientists could work side-by-side to improve patient care.”

Currently, the cause of autism is elusive in as many as 80% of cases, but by collecting data on genotype/phenotype correlation, Lewis is helping to change that. “The goal is to understand the genetic causes and consequences of autism and be able to diagnose it earlier, because the earlier the diagnosis, the earlier interventions can begin and the better the outcomes for people with ASD and their families.”

Dr. Suzanne Lewis is a 2005 MSFHR Scholar and the co-lead on a 2017 Reach award. Reach awards support health researchers and research users to collaboratively plan and implement dissemination activities. Dr. Lewis’ team is using their award to design a web platform to help families of children with autism spectrum disorder access and use research evidence.

Chapter 04

The legacy lives on

Dr. Michael Smith’s Nobel Prize, and his dedication to using his position to advance BC research as a whole, was a game changer for the province.

It catapulted the expertise of local scientists onto the world stage and put BC on the map as a place for world-class research.

By nurturing future scientific talent and creating many of BC’s leading research institutions, from Genome British Columbia and the Michael Smith Laboratories at UBC, to the Michael Smith Genome Sciences Centre at BC Cancer, Smith built much of the infrastructure that allows BC research to continue to thrive.

Following his death in 2000, the BC government created MSFHR, BC’s health research funding agency, to continue Smith’s work to nurture research talent and grow research capacity in the province. MSFHR is proud to continue this work and honour his legacy with every funding award we issue.

  • In research you really have to love and be committed to your work because things have more of a chance of going wrong than right. But when things go right, there is nothing more exciting.

    Dr. Michael Smith
    1993 Nobel Laureate, 1932-2000

  • Michael helped create significant infrastructure that has helped BC thrive as a research hub. I think he would be pleased to see the organizations he lent his name to continue to be at the leading edge of not only science, but at the leading edge of how science can impact health and society more broadly.

    Dr. Marco Marra
    Director and distinguished scientist, Canada's Michael Smith Genome Sciences Centre, BC Cancer, and professor and head, Department of Medical Genetics, UBC
    2001 and 2006 Scholar, former MSFHR Board member

  • It was Michael’s work that first attracted me to Vancouver. His lab was full of really diverse projects using completely different techniques, run by some of the best scientists at the time — it was really mind broadening. He was a builder, not just building labs but also building capacity to advance science here in BC.

    Dr. Chris Overall
    BC Proteomics Network co-lead and a professor in both UBC’s Centre for Blood Research and Faculty of Dentistry. He spent five years as a post-doc in Smith’s lab

  • Working in science in BC, you realize how many amazing things are associated with Mike. His fingerprints are everywhere. He really put Canada on the map in terms of scientific research but from working with him as a young faculty member I remember him as very humble, and very honest. He was a true scientist — he just loved science.

    Dr. B. Brett Finlay
    Professor of microbiology, Michael Smith Laboratories, UBC

  • One of the coolest things Mike Smith did with his Nobel Prize money was donate part of it to the Society for Canadian Women in Science and Technology. By investing in SCWIST he supported an entire faction of the scientific population and helped raise the voices of women in STEM. It was a really tremendous commitment from somebody who was a true visionary in this field.

    Dr. Jennifer Gardy
    Senior scientist, BC Centre for Disease Control and assistant professor, School of Population and Public Health, UBC
    2016 Scholar, 2004 & 2006 Research Trainee

As we work to continue Smith’s legacy, MSFHR is thinking deeply about what it takes to be a responsive and responsible research funder, now and in the future. To learn more, read our Forward Thinking blog series.

With thanks to BC Cancer, Genome BC, the Michael Smith Laboratories at UBC, and members of BC’s health research community who have provided photos and shared their memories of Michael Smith to celebrate his science and his legacy.