An AI-powered algorithm that can deduce the structure of proteins is among the breakthroughs recognized by the 2023 Gairdner Awards, Canada’s most prestigious accolade for research related to human health conducted anywhere in the world.
The international awards, which come with $100,000 per winner, were announced on Thursday by the Toronto-based Gairdner Foundation. Five are for discoveries in biomedical research, with a sixth prize set aside for achievements in global health. This year the foundation also introduced a pair of $50,000 “momentum” awards for mid-career scientists who are making exceptional contributions to health research in Canada.
Established in 1957, the Gairdners have earned a reputation for anticipating future Nobel Prize winners. Over the past decade, researchers behind immunotherapy for cancer and CRISPR gene-editing are among those who got the Nobel nod after first taking home a Gairdner.
Here is a guide to the latest winners, who will receive their awards at a celebration in Toronto later this year.
Illustrations by Murat Yükselir
Demis Hassabis and John Jumper
Canada Gairdner International Award
The unique way that a protein folds is one of the most complex but fundamental operations in nature. It is how the information encoded in our DNA is transformed into the multitude of three-dimensional shapes that enable life and that are often key to the treatment of disease.
In 2016, Demis Hassabis felt ready to take on the puzzle of predicting the structure of a protein using its genetic sequence – a monumental challenge akin to guessing what kind of object a giant box of Lego blocks will make without a picture of the end result.
Such a task is beyond the capacity of the human brain, but Dr. Hassabis, founder and chief executive of the AI research company DeepMind, was looking for a different way to get at the problem. Purchased by Google the year before, Britain-based DeepMind had just scored a major coup with AlphaGo, the computer program that bested South Korea’s Lee Sedol, who was then the world’s top-ranked player of the subtle and highly intuitive board game known as Go.
To Dr. Hassabis, the computational details of protein folding appeared to have many things in common with Go. The question was whether the machine-learning approach he and his team had employed to overcome Mr. Lee could tackle one of the most important unsolved challenges in molecular biology.
“We pretty much started the project almost the day we got back from Seoul,” Dr. Hassabis said.
What he envisioned was AlphaFold, a machine-learning algorithm that was inspired by an MIT-created video game released several years earlier to crowdsource the job of digitally folding proteins step by step to citizen scientists. That effort had been surprisingly successful, leading Dr. Hassabis to wonder if artificial intelligence could mimic and then exceed the intuition of human players in the same way that AlphaGo had done.
To spearhead the project Dr. Hassabis hired John Jumper, an Arkansas native with a diverse scientific background that had taken him from condensed matter physics to finance to a PhD in machine learning as applied to proteins.
“It really was a pivotal moment in my career,” Dr. Jumper said. “I could see the line all the way from what I thought I was good at to what I really wanted to do, which is to help people.”
By 2018, the first iteration of AlphaFold was ready for its debut. The arena in which it had to compete was CASP, a competition established in 1994 to test the ability of computer software to deduce protein structure. Results that contestants come up with are compared with actual protein structures that have been determined the hard way using traditional and time-consuming laboratory methods but kept secret.
AlphaFold outperformed its competition at CASP by a mile, but the victory was bittersweet. The algorithm was nowhere near reaching the accuracy needed to produce useful science. The DeepMind team had hit a brick wall, and after a few more months of frustration, Dr. Hassabis decided to start from scratch.
“It was quite a scary time,” he said. “You’re trying to build back with a more general system that maybe has a higher ceiling, but it’s harder to get to that point.”
For months the new version, AlphaFold2, performed more poorly than the original, but the algorithm improved by leaning more heavily on the molecular understanding of proteins. Another key development was an approach that led to much faster solutions, even though they were often wrong.
“That lets you test your ideas at an incredible rate,” Dr. Jumper said. “You go from taking days to evaluate each idea to seeing instantly how wrong they are and then starting to find the good ones.”
In November, 2020, AlphaFold2 conquered CASP, becoming the first algorithm to achieve a score above 90 per cent at predicting the structures of proteins. The algorithm has since been used to predict more than 200 million structures that make up human cells and those of 47 other organisms, all available in a growing database open to researchers everywhere.
“I hope that AlphaFold heralds a new dawn for digital biology,” Dr. Hassabis said. “Where you can do a lot of the searching for therapeutics” using algorithms. – Ivan Semeniuk
Bonnie Bassler, E. Peter Greenberg and Michael Silverman
Canada Gairdner International Award
Growing up on the high plains of Nebraska with a veterinarian father, Michael Silverman dreamed of being a cattle rancher. The problem, he said, was that the job called for a lot of cattle and a lot of land, “and I didn’t have either.”
Instead, he went to work in the 1960s studying plant disease at an experimental farm run by the U.S. Department of Agriculture and the University of Nebraska. The role involved culturing a lot of bacteria, and it was then that Dr. Silverman, who later earned his PhD in 1972 at the University of California at San Diego, discovered his true calling.
“I found that working with bacteria was kind of like being a rancher,” he said. “I had huge herds and I could breed them and nurture them and change their genes and their characteristics.”
In San Diego, Dr. Silverman became interested in a type of marine bacteria called Vibrio fischeri, which produce a luminescent glow. The bacteria can live symbiotically with squid that use the chemically generated light to disguise their silhouettes from predators that are stalking them from below. But such a strategy requires bacteria to work together as a group. How did each bacterium know when there was enough of a community around to light up?
The answer, first suggested by Harvard biologist J. Woodland Hastings in the 1970s, was that bacteria emit a signalling chemical that helps determine who else is in the neighbourhood. But it was Dr. Silverman, using the tools of genetics available in the 1980s, who worked out exactly how the bacteria did it.
Meanwhile, E. Peter Greenberg, who had studied under Dr. Hastings, became interested in the same process. While an assistant professor at Cornell University he made discoveries related to the signalling system in Vibrio fischeri independently of Dr. Silverman. But the real breakthrough came after Dr. Greenberg had moved to the University of Iowa and learned that a type of bacteria that colonizes the lungs of people with cystic fibrosis used a genetically similar signalling system to decide when to become virulent.
Dr. Greenberg, whose daughter was born with cystic fibrosis, decided to change his research direction to look deeper at the signalling phenomenon. When it came time to describe it in a 1994 research paper, it was the brother-in-law of a colleague who coined the term for what the bacteria were doing.
“He said, ‘Oh, It’s like they need a quorum,’” Dr. Greenberg said. The idea of quorum-sensing bacteria was born.
The final winner in the group, Bonnie Bassler, would go on to show that quorum sensing is widespread in the bacterial world. She was first introduced to the idea in the late 1980s when she was an uninspired graduate student and heard Dr. Silverman speak about his work.
“I was sort of thinking maybe I don’t even like science,” Dr. Bassler said. “And then this man gets up and he tells the most amazing experiment that I had ever heard in my life.”
By the time the talk was over, she was convinced she would be working with Dr. Silverman and became a postdoctoral researcher in his lab. She would later continue the work after setting up her own lab at Princeton University, where she and her team have opened up the field, discovering new quorum-sensing molecules and showing how viruses can use them to spy on what bacteria are doing.
The work has provided new insights into infection and, more broadly, into the hidden conversations that are taking place in the microbial world. – Ivan Semeniuk
John Dirks Canada Gairdner Global Health Award
While working as a scientist at the Institute of Nutrition of Central America and Panama in Guatemala City, Jose Belizan was intrigued to learn that Mayan women, who often live in abject poverty, had extremely low rates of pregnancy-related hypertension disorders such as pre-eclampsia.
His research would reveal that their corn-based diet was high in calcium. Corn itself isn’t rich in calcium, but, in Mayan culture, it is soaked in lime water (a solution of calcium oxide) before being ground to make tortillas.
That finding would have a dramatic impact on the health of pregnant women and their babies worldwide. About 45,000 women and 500,000 newborns die each year owing to hypertensive disorders in pregnancy.
Dr. Belizan’s research showed that calcium supplementation could cut the number of women suffering hypertensive disorders by half, and sharply reduce mortality in pregnant women and their babies, especially in low-income settings.
For this groundbreaking work, and other innovative and influential contributions to maternal health, the Gairdner Foundation has named Dr. Belizan this year’s winner of its Global Health Award.
The citation says the Argentine, who is a medical doctor with a PhD in reproductive health sciences, is being honoured for the “development of innovative, evidence-based and low-cost global interventions in maternal and child health during the perinatal period that improve well-being and care during pregnancy, reduce morbidity and mortality, and promote equity in vulnerable populations.”
The awards committee also noted that he is a rare scientist whose work spans the spectrum from basic research through to clinical practice and on to implementation of community interventions.
“Through his work within these communities, he educates and empowers pregnant people, and witnesses real-life health problems, which informs his outstanding scientific contributions,” the citation notes.
Dr. Belizan said that he was “extremely happy” to be recognized by the prestigious Gairdner Awards not only personally but because it underscores the importance of public health in Latin America and around the world.
“There is a lot of inequity in the world,” he said in an interview. “We have to find ways to make a difference, to close the gaps.”
He said his greatest frustration is that three billion people worldwide still have inadequate calcium intake, a problem that is easily fixable.
In addition to his decades-long work trying to reduce hypertensive disorders in pregnant women, Dr. Belizan has greatly influenced the rates of cesarean sections and episiotomies.
His research showed that c-sections were being used far too often and that routine episiotomy was largely unnecessary, which influenced obstetric practice around the world.
“I’m very proud that this work resulted in a dramatic drop in these procedures because they were often harmful for women,” Dr. Belizan said. – André Picard
Canada Gairdner Momentum Award
Christopher Mushquash is driven by a desire to understand the mechanisms by which culture and traditional cultural practices can help people when they have difficulties with mental health and addictions.
Culture gives people a sense of identity and purpose, he explained.
“It makes us hopeful and helps us belong, and provides meaning, and when we have those things in place, we’re more likely to be pulled along a pathway toward wellness,” said Dr. Mushquash, a Canada Research Chair in Indigenous Mental Health and Addiction and professor in the department of psychology at Lakehead University.
His work, studying how to bring together the best of psychological interventions with traditional cultural practices, has led to improving care in mental health and addictions for Indigenous peoples in Canada.
Dr. Mushquash, who is Ojibwa and a member of Pays Plat First Nation, was born in Sioux Lookout and grew up in northwestern Ontario. While he wanted to help his community, his career path has not been a direct one. He initially studied biochemistry. But as he began learning about psychology, and with the guidance and support of mentors, his focus turned to mental health and addictions – and to the capacity and knowledge held within First Nations cultures and traditional practices to help address those issues.
These cultures and traditional practices are diverse, and unique to the people to whom they belong. In his own culture, for example, a smudging ceremony is an important spiritual practice that helps ground people in who they are and where they belong within the natural world, allowing their minds and emotions to be in a good place. The psychological construct of emotional regulation is well understood culturally, he said; in fact, a smudge ceremony is a powerful intervention for those who practise it.
“There’s an ability for traditional practices, but also psychological evidence-based practices, in a sense, to speak with each other, as long as the mechanisms of action that underlie each are the same,” he said.
Given the range of cultural practices among various communities, Dr. Mushquash said, it’s not his place to say which of them to use and how, but rather, to help health systems understand them and how they may be applied. He takes a community-led participatory approach to research, with the goal of supporting communities to answer the questions that are most important to them and ensuring they have the resources to sustain the programs that work for them.
“For me, the real success is that this area of work in Indigenous mental health and addiction is highlighted on a much broader scale,” he said. – Wency Leung
Canada Gairdner Momentum Award
When most people think about brain tumours, they think about glioblastoma, one of the deadliest adult cancers. But the most common form of brain tumour, meningioma, is paradoxically among the least studied.
Gelareh Zadeh, the Dan Family Chair and professor of neurosurgery at the University of Toronto, is working to remedy that. Even though meningioma is thought to be benign, many of these tumours are aggressive and difficult to manage, and besides surgery, very little is effective in controlling them, she explained.
Dr. Zadeh is focused on understanding the biology of these and other lesser-researched tumours to help predict patient outcomes, make decisions about potential targets for therapeutics and seek new treatments. The approach looks at brain tumours in a new way, based on molecular profiling that involves genomic and epigenomic information, proteomics and plasma-based biomarkers.
She and her collaborator, Daniel De Carvalho, have shown that a plasma-based biomarker can be used to distinguish different tumour types and potentially be used to determine when a tumour has become malignant, without the need for a biopsy.
Ultimately, this would allow neurosurgeons to predict a patient’s prognosis with a simple blood test.
If it reveals an aggressive prognosis, doctors can intervene sooner by operating on the tumour early, or possibly providing radiation therapy, said Dr. Zadeh, who is also a senior scientist at the Princess Margaret Cancer Centre, University Health Network and medical director of the Krembil Brain Institute.
In another key area, she and her team have found pathways that lead a benign tumour to become malignant in peripheral nerve tumours. What’s exciting about this, she said, is that some of these pathways are ones for which there are already drugs available, used for other types of cancer.
To share data and conduct large-scale analyses, Dr. Zadeh has helped create an International Consortium on Meningiomas, bringing investigators together to identify gaps in care for patients, shape further research and share their findings.
For Dr. Zadeh, the most gratifying part of her work is that the discoveries she makes in the lab are brought to clinical practice in a way that guides and affects the management and care of patients.
“To me, that is the most rewarding element of what I do.” – Wency Leung