Research Profile - In praise of the pout

Dr. Peter L. Davies
Dr. Peter L. Davies
 

A slimy eel-like fish that lurks in maritime depths holds a secret that could solve the problem of keeping organs cold until they can be transplanted.

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The ocean pout is an ugly fish, eel-like and slimy-skinned. Long ignored as it lurked in the waters off the east coast of Canada and Maine, the unattractive creature might have quietly carried on its life of nibbling on mollusks had scientists not become fascinated with its one remarkable trait: it doesn't freeze even when the sea above it does.

The unpleasant pout, it turns out, is a miracle of evolution. Over the past few tens of millions of years, the pout began to produce antifreeze proteins in its blood that bind to the surface of ice crystals and stop them from growing. This allows the pout to make its home in waters too frigid for prettier fish, leaving it a clear path to the buffet on the maritime floor.

At a Glance

Who – Dr. Peter L. Davies, Canada Research Chair in Protein Engineering, Queen's University.

Issue – Transplantation is currently a high-speed operation in which the live organ must be kept cold – but not frozen – and delivered quickly to the recipient's surgical team.

Approach – Dr. Davies is leading a five-year, CIHR-funded study of ice-binding proteins found in some fish, insects, grasses and fungi that prevent them from freezing or being damaged by the cold.

Impact – The study could lead to new techniques to treat and store organs so that they can be kept very cold for longer periods of time.

The Next Step – Having discovered that some antifreeze proteins are 10 times better at lowering freezing points than others, Dr. Davies is investigating how they might be improved even further with enhancer proteins.

What excites health researchers such as Dr. Peter Davies of Queen's University about the pout is the potential its antifreeze proteins hold for keeping donated organs cold – but not letting them freeze – as they wait to be transplanted.

"If you can keep an organ cold it will last longer and the colder you can keep it, the better," says Dr. Davies, who leads a five-year Canadian Institutes of Health Research project to investigate the structure, function and evolution of ice-binding proteins. "Once you start to get a bit below zero degrees, then you're running the risk of ice crystals forming and damaging the organ."

Ocean pouts aren't the only living things that have found a way to flourish despite deep cold. Some insects, plants and fungi also have the ability to cope with freezing and carry on.

"Many of these organisms actually allow themselves to freeze," explains Dr. Davies. "With grasses, for example, the antifreeze proteins stop the ice crystals from getting bigger, and damaging the structure of the plant so the plant can survive a number of freeze-thaw cycles."

Ice cream manufacturers have already adapted this approach. Unilever, the Anglo-Dutch conglomerate, found a way to reproduce the pout's ice-binding protein by altering the genetic structure of yeast. This allows the company to make smoother, creamier-tasting low-fat frozen treats that stand up better to the temperature changes involved in long-distance shipping and storage.

Dr. Davies can foresee similar applications for organ transplants in the not-too-distant future that would allow physicians more time to find better donor-recipient matches.

"You want to keep the ice crystals small and not have them grow and damage the organ beyond repair. The objective is to be able to perfuse (supply) the organ with biological solutions that have no damaging effect, but will keep it as cold as possible. Theoretically, with antifreeze proteins we should be able to go down to about -5 and -6 degrees (Celsius) without ice causing problems."

It could also be possible to store organs in even colder conditions and still have them available for transplantation. Again, nature holds the key, according to Dr. Davies.

"How do insect larvae survive down to -30 without freezing? What's their secret? Part of it is antifreeze protein, but there must be something else. We're actively researching what those other components are, and how their properties give added value to the antifreeze protein."

Dr. Davies stresses that his protein research is basic investigative biochemistry with the key goal of expanding knowledge. But he is excited about its strong potential for medical application – especially for the future of organ transplantation and tissue preservation.

"In the future we should be able to prevent freezing in an organ at even lower temperatures. And if we were able to get it down to -20, the potential for long-term storage is huge."

"You can imagine that if a fish develops an antifreeze protein they then can get access to a biological niche where there's a richness of food and fewer predators. So the selective advantage of being able to go into these icy waters is considerable. They adapted through evolution to occupy these niches."