Profs zero in on immunity

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      Things seem to be going pretty well in Brett Finlay’s life these days. The wiry UBC microbiologist returned from Ottawa on February 11 after attending a ceremony appointing him an officer of the Order of Canada. In addition, the federal government recently licensed a cattle vaccine that he developed for a deadly strain of E. coli, which should sharply reduce the likelihood of another Walkerton-style outbreak of contaminated water in Canada.

      If that’s not enough, he’s also heading a team of scientists, funded by software billionaire Bill Gates, that is tackling the world’s most vexing medical problems. They’re trying to come up with innovative treatments for the deadliest bacterial and parasitic diseases, including tuberculosis, malaria, dysentery, and childhood diarrheas of unknown origins. The Bill and Melinda Gates Foundation invested US$8.7 million in the project after Finlay responded to its call for proposals to solve one of several “grand challenges” facing humanity.

      “As you know, antibiotic resist ­ance is a big issue,” Finlay told the Georgia Straight at his UBC office, “and our grand challenge was how do you come up with alternative therapeutics for bacterial infections that would otherwise lead to drug resistance.”

      For Finlay, the key could turn out to be refining “innate immunity”. Tradi ­tionally, scientists have focused on developing vaccines to prevent diseases, or creating anti ­biotics to conquer them. Finlay pointed out that all multicellular organisms have an innate immunity that can fight off most infections.

      “Historically, immunology has worked a lot on what we call ”˜T'  and  'B’ cells, but these only kick in a week after infection,” he said. “So the question is, ”˜How the heck did you survive that first week?’”¦There is this innate immune system, pre-existing defences, that is very effective at fighting most things off.”

      Fortunately, Finlay and fellow UBC microbiologist Bob Hancock had already discovered that peptides, which are chains of naturally occurring amino acids, have dual capabilities. Scientists knew for years that these compounds could kill bacteria. But several years ago they found that peptides could also modulate the body’s immune system. In effect, these peptides could switch on the body’s innate immunity to fight bacteria, viruses, and parasitic invaders.

      “Antibiotics are a compound that kill bacteria,” Finlay said. “So bacteria goes to great lengths to figure out how to survive it. But these compounds [peptides] don’t kill the bacteria. So what they do is tweak the host’s defences to be that much stronger.”

      Hancock, speaking to the Straight by phone, said there are two aspects to innate immunity: surveillance and amplification, which removes pathogens. “It works a little bit indiscriminately, however,” he said. “The surveillance works well, and the removal of bacteria”¦when they’re at low levels works really well. But if you start to get sustained or more substantial threats ­say you have a larger dose of this foreign pathogen or virus—then the innate immune system starts to become amplified. Unfortunately, you can consider it more or less like a tactical nuclear strike. It’s in there to try to destroy the microorganism, but it’s not really specific. Therefore, it has the potential to cause harm to your own cells.”

      Hancock said that peptides appear to stimulate “good parts of innate immunity” without causing harmful inflammation, which can lead to septic shock. “Sepsis kills somewhere between 140,000 and 200,000 people in our society, North American society, every year,” he said.

      This has created a new avenue of exploration in fighting illness. And it’s why the Gates foundation, the U.S. National Institutes of Health, Genome Canada, and the Canadian Institute of Health Research have all opened up their coffers and provided massive amounts of research funding.

      Hancock and Finlay also cofounded a company called Inimex Pharmaceuticals Inc., which is producing molecules that stimulate an immune response to treat infections in mice. A computer program helps reveal how the body responds to infection. “And knowing that, we go and tweak that pathway,” Finlay said.

      Finlay said he expects that Inimex will begin conducting clinical trials on humans within two years. In addition, he said, Inimex has turned over a compound to the Gates-funded project. Melinda Gates is the “driving force” behind the foundation, Finlay said. He also noted that Bill Gates asked very intelligent questions at the sessions he attended. And the foundation has exacting standards, requiring research teams to achieve annual targets in order to qualify for the next year’s funding.

      “Managing that is quite intense,” Finlay said. “But I think the biggest benefit is just working with this dream team of scientists. I know them all well and chose them carefully for that reason.”

      He acknowledged that even though the Gates foundation has funded 43 challenges, it’s likely that most will miss the mark. “But even if two or three of these things work, it will change the world,” he said. “These are big, bold initiatives, so there are going to be big failure rates.”

      So far, he said, scientists have not observed bacteria developing resistance to naturally occurring compounds that stimulate the body’s innate immunity. However, he added that the “jury is still out” on whether or not this will always be the case.

      Finlay said that because peptides regulate the immune system’s response, it’s possible that they could one day have an impact on autoimmune diseases, such as arthritis and multiple sclerosis. For those diseases, symptoms arise when the immune system turns on itself for no apparent reason, but peptides could have an immune-dampening effect, he suggested.

      “The company is certainly thinking about it,” Finlay said.

      The media have a tendency to get overly enthusiastic about the prospects of medical research, which can create false hope among those suffering from debilitating medical conditions. And Finlay is not one to oversell the potential of his work, despite all the attention it’s generating from funding agencies. But with a chuckle, he said he has already exceeded the expectations of one important person in his life, who thought he was making a mistake by becoming a scientist.

      “My mother-in-law said I would never have a job and never have any friends,” he quipped.

      This comment was made the day after Finlay’s visit in Ottawa with the governor general.