Friday, 31 March 2017

Seven scientists win the 2017 Gairdner Awards

Seven researchers have each been awarded a 2017 Gairdner Award for seminal work in areas including child nutrition and treatment for cardiovascular disease. Brian Owens reports.
Cesar Victora, an epidemiologist at the Federal University of Pelotas in Brazil, has won the 2017 John Dirks Canada Gairdner Global Health Award for his work on maternal and child health in developing countries.
When Victora graduated from medical school in 1976, he went to work in community health in a slum in Porto Allegre, Brazil. He saw a lot of malnutrition, diarrhoea, and other infectious diseases, and the same children kept coming back. “I was treating disease episodes, but these kids remained vulnerable, and many ended up dying”, he tells The Lancet.
That is what drove him into preventive medicine and epidemiology. He was particularly interested in child nutrition, because he had noticed that very few women in Brazil breastfed their children at that time. “It was seen as old fashioned and primitive”, he says.
Victora looked at the scientific literature around breastfeeding and found that what existed was largely from the turn of the 20th century, using outdated methods that would not pass muster in a modern scientific publication. Victora's research, using the latest study designs and data, led to a major publication in The Lancet in 1987 that showed that breastfeeding was protective against infant deaths from infectious diseases and led WHO and UNICEF to recommend exclusive breastfeeding for the first 6 months of life.
His research has also shown how important infant nutrition is for the rest of a person's life. In 1982, he and his colleague Fernando Barros started the Pelotas Birth Cohort Study, which has been following 6000 babies born in Pelotas ever since. Results from this study have shown the importance of nutrition in the “first 1000 days”—from conception to age 2 years. “The whole pattern of adult health, chronic diseases, and what we call human capital—intelligence, productivity, physical strength—is largely defined by nutritional effects in the first 1000 days of life”, says Victoria.
The Gairdner award is a great honour, says Victora, who is the first Brazilian scientist to win the accolade. “It motivates me to continue my work in this important area”, he says.

Other award winners

The awards are given out by Canada's Gairdner Foundation for important discoveries in biomedical science. In addition to Victora's award for global health, the foundation is recognising five other individuals from around the world with its Canada Gairdner International Awards, for contributions to a variety of scientific fields, and one final award is reserved for a Canadian. Each comes with a US$100 000 prize.
Huda Zoghbi, a neurologist at Baylor College of Medicine in Houston, USA, is being recognised for her work to uncover the genetic basis of Rett syndrome and its implications for autism spectrum disorders. She says her work was inspired during her clinical training, when she was struck by how Rett syndrome, a condition that affects mainly girls, was distinct from all other neurological disorders. It is neither a developmental disorder that is present from birth, nor a degenerative disease that begins immediately after birth and progresses steadily. Instead, babies are born healthy but starting around age 1 year or 2 years, they begin to gradually miss developmental milestones.
“It intrigued me, the fact that they all went through the same course, I knew it had to be genetic”, she says, and she resolved to find the gene responsible. That would not be easy, since the condition was known to arise sporadically rather than run in families, and, in 1983 when she started the work, the human genome had yet to be sequenced. But Zoghbi rose to the challenge. “Sometimes the good thing about being young is [that] you are naive”, she says.
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Cesar Victora
Gairdner Foundation
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Huda Zoghbi
Daniela Xu
It took 16 years of grinding genetic sleuthing, but Zoghbi eventually identified the single gene, MECP2, responsible for Rett. Being caused by a single gene theoretically makes diseases a good candidate for treatment, but Rett and the other neurological conditions linked to MECP2 have proven frustratingly difficult to deal with, as the level of expression needs to be tightly controlled to ensure normal function. “I thought finding the gene was the hardest thing, but I was quickly humbled”, Zoghbi says. “Finding a treatment is much harder.”
David Julius, a molecular biologist at the University of California, San Francisco, USA, is being honoured for his work on the molecular basis of somatosensation—how we sense heat, cold, and pain. “I work at the nexus of pharmacology and folk medicine”, says Julius. “Exploiting knowledge gathered over hundreds of thousands of years to study pathways in the brain.”
Julius uses natural compounds such as capsaicin from chili peppers and menthol from wintergreen plants that mimic the physical sensations of heat and cold by activating the same biochemical pathways. “These chemicals activate receptors on nerve cells whose normal job is to sense changes in temperature”, he says.
These chemicals helped him to identify the receptors responsible for these sensations, ion channels called TRPV1 that sense heat and TRPM8 that sense cold. Targeting these receptors could help treat conditions such the hypersensitivity to cold that often arise with chemotherapy treatment for cancer. The TRP family of receptors are also the target of several inflammatory agents, suggesting they could be targets for treatments for a variety of chronic pain conditions.
Rino Rappuoli, chief scientist at GSK Vaccines in Siena, Italy, won the award for pioneering the technique of reverse vaccinology, which led to the creation of a vaccine against meningococcus B, a rare but deadly disease that kills otherwise healthy children and adolescents.
In the early 1990s, meningococcus B was proving to be an elusive vaccine target, because the B antigen is identical to a molecule found in human beings, meaning it was impossible to develop an antibody for it. But when Craig Venter published the influenza genome in 1995, Rappuoli sensed an opportunity. Rather than starting with the whole, live pathogen, if he had the bacteria's full genome, he could pick out proteins that could be useful in generating antibodies—hence, reverse vaccinology. He asked Venter to sequence meningococcus B, and used the sequence to identify 91 cell surface proteins—dozens more than had ever been found before. “At that point I knew we were going to make a vaccine”, says Rappuoli. “We were sitting on a gold mine.”
Rappuoli and his colleagues were eventually able to narrow down the search to three surface proteins that could generate useful antibodies, which went into the vaccine. The vaccine was approved in Europe in 2013, and in the USA in 2015. “It's already saving lives”, he says.
Lewis Kay, a molecular biologist at the University of Toronto, Canada, won his award for a more fundamental discovery—developing nuclear magnetic resonance (NMR) spectroscopy to study the structure and dynamics of proteins and molecular machines. “In structural biology we tend to think about static molecules, but actually the majority of them are changing shape to interact within the cell, and that changes their function”, he says.
The NMR techniques Kay developed allowed him to see the “invisible states” of proteins—those transient shapes that the proteins might exist in for only a short time. This development has helped researchers to discover how abnormal conformations are involved in conditions such as neurodegeneration. “The ability to see the invisible has allowed us to see the starting points of neurodegeneration”, he says.
It also opens up potential new targets for drugs by discovering binding sites far removed from the active site that nevertheless change a protein's function by changing its shape.
Akira Endo, president of Biopharm Research Laboratories in Tokyo, Japan, won the award for his discovery of statins, the inhibitors of cholesterol biosysnthesis that have become a common treatment for cardiovascular disease.
Endo discovered the first statin, compactin, in 1973 after 2 years of searching for useful molecules in various varieties of mold and fungi. But it almost didn't make it out of the laboratory, because it was ineffective at reducing cholesterol in rats. The British pharmaceutical company Beecham (now part of GSK) had discovered compactin around the same time, but abandoned it because of its failure in rats. Endo, however, persevered, studying the molecule's mechanism of action to determine why it wasn't working in the model organism.
“Our results suggested that it would be effective in animals with higher blood cholesterol, like humans”, he says. The statin class of anticholesterol drugs have gone on to become the largest-selling class of drugs in the world today—taken by more than 40 million people.
Finally, Antoine Hakim, a neurologist at the University of Ottawa, Canada, won the 2017 Canada Gairdner Wrightman Award, which is given to a Canadian researcher, for his research on treating and preventing stroke.
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David Julius
Steve Babuljak
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Rino Rappuoli
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Lewis Kay
Brooke Wedlock
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Akira Endo
Tokyo University of Agriculture and Technology
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Antoine Hakim
University of Ottawa