On April 11th, the Gairdner Foundation announced the 2024 laureates of the Canada Gairdner International Award, the John Dirks Canada Gairdner Global Health Award, and the Canada Gairdner Momentum Award. These awards annually honor eight scientists for their outstanding contributions in understanding human disease and improving the health and well-being of people worldwide. Since 1957, the Gairdner Foundation has recognized 426 scientists, 98 of whom have subsequently won the Nobel Prize.

CAR T cells and next generation sequencing win 2024 Canada Gairdner International Award

Immunologists Zelig Eshhar at the Weizmann Institute of Science and Michel Sadelain at the Memorial Sloan Kettering Cancer Center are two of this year’s five recipients of the Canada Gairdner International Award for conceiving, developing, and applying CD19 chimeric antigen receptor (CAR) T cell therapy for cancer. CAR T cell development goes back to the 1980s when Sadelain started using recombinant retroviruses to introduce genes into mouse and human T cells. Working independently, Eshhar developed the first system to redirect T cell specificity to recognize certain antigens, primarily on cancer cells. Sadelain spent the 1990s improving this initial design, studying the signaling properties of primary T cells and how to engineer them so they could both recognize a desired antigen and expand appropriately to use as cell therapy. 

For at least 20 years, I kept hearing, ‘Why are you doing this? This will never work,’          
-Michel Sadelain, Memorial Sloan Kettering Cancer Center.

In a landmark research paper published in 2003, Sadelain and colleagues showed that it was possible to introduce a gene into human peripheral blood T cells using a recombinant retrovirus expressing a new T cell receptor that could recognize cancer cells (1). He named this new receptor chimeric antigen receptor, and it had specificity for the B cell molecule CD19. The resulting cells successfully treated several lymphomas and leukemias in mice. This work laid the groundwork for the FDA-approved CAR T cell therapies in use today, which employ gamma retroviral or lentiviral vectors effective for leukemias, lymphomas, and multiple myelomas. Despite the initial skepticism, this innovation led to a significant expansion of research and development in CAR T cells. 

“There's so much enthusiasm for this, and I can see a tremendous acceleration of this work,” said Sadelain. “It is now a field, not just a technique. It started with cancer, but there's a whole series of autoimmune disorders and other conditions [for which CAR T cells could be useful].”

The remaining three Canada Gairdner International Awards went to the University of Cambridge organic chemist Shankar Balasubramanian and physical chemist David Klenerman, as well as biophysicist Pascal Mayer at the University of Strasbourg. The awards acknowledged their role in the fundamental research behind sequencing DNA on a massive scale, which has had broad applications in the life sciences and medicine. 

Balasubramanian and Klenerman were using single molecule fluorescence to observe DNA polymerase copying DNA in real time when they realized that they could repurpose the same technique for fast DNA sequencing. “We thought this sounded exciting and thought about ways of getting the money to try our entire idea, not knowing if it would work,” said Klenerman. At the time the Human Genome Project was in full flight, which highlighted the need for a faster, cheaper way of sequencing DNA. Balasubramanian said that the award is a recognition of the technology’s wide impact. “It's a really nice example of curiosity-driven basic science that ultimately led to something quite useful,” he said. 

Balasubramanian and Klenerman cofounded the company Solexa, later acquired by Illumina, to make their sequencing technology widely available. Mayer led the initial development of DNA colony-based massively parallel sequencing by synthesis. This technology became a fundamental component of next generation sequencing that enabled the simultaneous mapping of millions of DNA fragments quickly and cost-effectively.

Looking ahead, Klenerman is leveraging similar single molecule fluorescence technologies to visualize protein aggregates that accumulate in neurodegenerative diseases, such as amyloid plaques and tau tangles in Alzheimer's disease. Recognizing that these large aggregates evolve from smaller ones, his team is developing techniques to identify and analyze these nanoscopic precursors, which could lead to more effective treatments and improvements in early disease diagnosis. 

Balasubramanian plans to continue following his curiosity about how DNA works. Since 1998, he has been working on G quadruplex secondary structures, formed in nucleic acids by guanine-rich sequences. These structures prevail in cancerous tissues compared to normal ones, and recent collaborations with clinicians have demonstrated their therapeutic potential for cancer treatment. “I'm hoping that it'll be another example of working on a fundamental problem that can be linked to biological function and disease,” he said. 

Improving the lives of children with enteric diseases for the 2024 John Dirks Canada Gairdner Global Health Award 

Gagandeep Kang, a physician-scientist at the Christian Medical College, leads the fight against enteric (intestinal) diseases in children in India and throughout the world. Her dedication was honored with the prestigious 2024 John Dirks Canada Gairdner Global Health Award, given for scientifically based research that has improved the health and well-being of those facing health inequities worldwide.

Kang investigates the complex interplay between enteric infections, gut health, and their long-term effects on child development, especially in settings with limited resources, such as India. Her extensive research program has made significant contributions, including her work developing a vaccine for rotavirus, a diarrhea causing virus (2). Through large-scale birth cohort studies, Kang's team uncovered crucial insights into how natural immunity patterns differed in India compared to developed countries.

“Diarrhea is not the most glamorous field of research. If anything, it's something that people would prefer to hide, and yet it's one of the biggest problems that we have,” said Kang. “Even though a lot of progress has been made in terms of vaccines and improving nutrition, I think the area is a marker of inequity in access to health.”

Kang’s research directly informed the development of more effective rotavirus vaccines specifically for the Indian population. Kang played a pivotal role in introducing two such vaccines into the national immunization program, resulting in a dramatic decline in rotavirus-related illnesses and deaths in children (3).

Kang also investigates other enteric pathogens such as cholera and typhoid, paving the way for potential new vaccines for those infections. She explores the long-term consequences of enteric infections on a child's development, highlighting the importance of early intervention. Kang also leads efforts to build scientific research capacity in India. In her previous role as the director of the Translational Health Science and Technology Institute (THSTI), she fostered local research capabilities and supported Indian vaccine development efforts.

“This is one of the biggest global health awards there is, so that was pretty amazing,” said Kang when asked about receiving the award. “I come from this really small town in southern India, and that's where the bulk of my work was done. And to be able to show people that you can do great work in small places, I think is what global health is all about.”

Kang's unwavering commitment to research continues to inspire, offering valuable insights for global efforts to combat enteric diseases.

“That's what my career path gives me. The opportunity to try,” she added. “I might fail again, but at least I know what the problems are. And I know the people who could potentially solve them, so perhaps bringing all of this together will allow us to really make a difference.”

From breast milk to disease resistance for the 2024 Gairdner Momentum Award

The 2024 Canada Gairdner Momentum Award recognizes scientific achievements from mid-career researchers whose work is shaping the future of health in distinct yet impactful ways. The two researchers honored with this year’s award are Meghan Azad, a pediatric health investigator at the University of Manitoba, and Christian Landry, a biologist at Université Laval.  

Azad is a leading figure in infant nutrition research. She focuses on understanding the influence of human breast milk on a child's health, not just in infancy but potentially throughout their entire life.

“On a bigger professional level, it's really exciting that lactation research is being recognized in this way,” Azad said when asked about how she felt about the award. By studying over 3,000 children, she has shed light on the connection between longer and more exclusive breastfeeding and healthier body composition, with a reduced risk of asthma (4).

“Awards like this put the topic on the radar,” she added. “I hope this can keep that momentum going.”

Her research delves deeper, exploring how the very method of feeding — breastfeeding directly or using pumped milk — can impact the infant microbiome (5). Her team found that bioactive components in breast milk can degrade during storage, potentially affecting the crucial exchange of bacteria between mothers and infants.

The influence of Azad's research extends far beyond academic circles. Her findings have the potential to inform public health policies and empower mothers to make informed choices about infant feeding. Additionally, her dedication to science communication fosters a deeper understanding of early life nutrition's lasting role in health.

“I think we can discover new things in [breast] milk. We can understand new ways of how it works and link that to child health, maternal health, and then use that information to do a bunch of things,” Azad added.

For his 2024 Gairdner Momentum Award winning work, Landry tackles the intricate world of cellular networks and mutations. His research group employs a unique approach, combining synthetic biology, experimental evolution, and systems biology to address one of biology's most fundamental questions: how mutations alter the function and performance of cells.

Landry's goal is to comprehend how individual variations, like mutations, influence complex traits and ultimately contribute to disease. By delving into the evolutionary context of cellular networks, Landry and his team have shown how organisms, including disease-causing pathogens, evolve (6). His research paves the way for the development of more resilient drugs, a critical aspect in the fight against emerging diseases and those with limited treatment options.

“We want to better understand how all resistance evolves but also maybe design better drugs in the future so we can overcome the resistance making mechanisms and the resistance mutations,” said Landry.

Understanding these principles is crucial not only for fighting anti-microbial resistance, but also for making advances in human genetics, evolutionary biology, and biotechnology. For instance, Landry and his team developed high-throughput tools that enabled the investigation of entire protein interaction networks (7). These tools offered insights into how mutations can rewire these networks and how their evolutionary history might influence the outcome of disease-causing mutations. 

“I’ve moved between fields during my training, and I’m always in between two or three fields,” Landry said. “I’m never sure where I belong. You never know if your ideas are just off the chart because they’re wrong, or they might just be creative and innovative. When you get an award like this, it confirms you’re at the right place and on the right spot.”

This year’s eight Gairdner Award winners represent the future of health research. Their dedication to uncovering the secrets of CAR T cell therapy, next generation sequencing, childhood enteric diseases, human breast milk, and cellular mutations holds immense potential to improve human health and well-being for generations to come. 

References

1. Brentjens, R. J. et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15.Nat Med  9, 279–286 (2003).
2. Kang, G. Success from the south: The rotavirus vaccine story and its lessons.The Lancet  403, 111–116 (2024).
3. Nair, N. P. et al. Rotavirus vaccine impact assessment surveillance in India: Protocol and methods. BMJ Open  9, e024840 (2019).
4. Klopp, A. et al. Modes of Infant Feeding and the Risk of Childhood Asthma: A Prospective Birth Cohort Study. J Pediatr  190, 192-199.e2 (2017). 
5. Moossavi, S., Miliku, K., Sepehri, S., Khafipour, E. & Azad, M. B. The Prebiotic and Probiotic Properties of Human Milk: Implications for Infant Immune Development and Pediatric Asthma. Front Pediatr  6, (2018).
6. Durand, R. et al. Cross-feeding affects the target of resistance evolution to an antifungal drug. PLoS Genet 19, e1011002 (2023).
7. Cisneros, A. F. et al. Mutational biases favor complexity increases in protein interaction networks after gene duplication. Mol Syst Biol  1-24 (2024).