With Tim Geary, Director of the McGill Institute of Parasitology

By Jim Hynes

Tim Geary has been working on parasites, and drugs for treating humans infected with them, for more than 30 years. The Grand Rapids, Mich., native came to McGill in 2005 after a long career in the pharmaceutical industry. He talked to The Reporter about parasites, the Institute of Parasitology and the sizeable grant he and research partner Dr. Eliane Ubalijoro received earlier this week (http://publications.mcgill.ca/reporter/2011/01/geary-gets-grant-to-combat-parasitic-diseases/).

Tell us a about the Institute.

We’re often confused with the Institute of Parapsychology [Laughs]. In the old days there were a number of departments of parasitology, because parasites in people were still common. Now this remains the only named institute of parasitology in Canada, and maybe even in North America. It contains 11 laboratories or principal investigators and we work only on parasites – and that is the unique aspect and to me the enormous attraction. Everywhere else parasites get swamped out because they are not crucial medical problems here. So the fact that the University has maintained this institute for over 75 years makes it a treasure, a really unique resource in North America.

You work on what the WHO calls Neglected Tropical Diseases.

These are diseases that are understudied but very prevalent. Some are caused by bacteria; some are caused by protozoa or single-cell organisms; and some are caused by worms. We work on worms. Worms that are called nematodes or roundworms are very common in temperate areas, tropical areas, in soil. They’re easily acquired. Estimates are that at least one billion people are infected.

One of the worst is the hookworm. These reside in the intestine and they rip open little holes and eat blood. So anaemia is a consequence.The parasite larvae, the infectious stage, live in the soil, and they burrow through skin. They had been very common in the southern U.S, but we have pretty much got rid of them by investing in infrastructure. But when you don’t have the money to invest in infrastructure, what do you do?

Parasites don’t kill you generally, but they are debilitating. They provide a chronic morbidity. The big problem with these diseases is that they contribute to the cycle of poverty. So if you are growing more poorly, you don’t go to school because you’re sick, you’re productivity in agriculture is reduced. So we are trying to find new drugs that would be locally produced and locally controlled that would help to break that cycle.

Congratulations on this impressive grant.

I’m very excited about it. This is something that started more than 25 years ago when I was doing malaria research and I tested a collection of chemicals that were derived from African plants with a guy from Sudan called Sami Khalid. I lost touch with him when I worked in the pharmaceutical industry. After I came to McGill, I happened to meet him again and we re-awoke the idea of how we could screen the chemical bounty of Africa as contained in its biodiversity for problems that are locally important – parasites. I was also lucky to meet my partner here, Dr. Eliane Ubalijoro, a Rwandan who got her PhD from McGill in plant biotechnology. She is a person with fantastic vision and energy. She was the one who said, “you know what, we’re going to do this. We’re going to put together a program that will allow us to build up drug discovery capacity in Africa.”

Half the money, at least, will be spent in Africa. In projects like this we tend to overemphasize the importance of the Western partner. But the fact of the matter is that this is an African project. My goal is to be obsolete, that in a few years time I would be irrelevant. Our African partners are the ones who have to be the leaders of the project in the future, and this is a way to help them boost the local capacity to do this stuff.

How did you first seize upon the idea that the treatment for parasites might be found in African plants?

There are two kinds of drugs, some are synthetic and made by chemists, but others are natural products. Most antibiotics are produced by microbes or fungi. A whole bunch of drugs that were developed for parasitic infections come from similar sources – plants or microbes. We have not continued to invest in those at the pharmaceutical-industry level because they’re harder to work with than synthetic drugs. For parasites, however, they remain a tremendous resource. So the idea was that Africa has an enormous capacity for biodiversity, plants and microbes that haven’t been sampled. The strength of African chemistry is really in natural products – purifying compounds from botanical sources or microbes. What we wanted to do was build on that expertise and say, “let’s look for next generation cures in that kind of chemistry and let’s do it in Africa where these problems are of significant local interest and importance.”

How are these parasitic diseases currently treated?

The worms that we’re talking about mostly live in the gut, and there are some really cheap drugs that can be used for them. Countries in these regions have huge demands on health budgets. Some of them are a lot more serious than worms in terms of their immediate impact. So organized campaigns to try to limit the incidence and extent of infection have been relatively limited.

As those campaigns expand, we worry about developing resistance to these old drugs. We need new compounds in order to sustain the control we’ve already achieved. In addition, the adult parasites of the species that live inside us are quite significant in size and can live at least 10 years in a human. And we don’t have any drugs that kill them and can be easily used in the field. Right now, the programs that we have implemented are designed to minimize the transmission and the production of the larvae. And they are good at that, but the eradication campaign is going to be difficult if we don’t have new drugs that kill the adults.

Day to day, what will the work involve?

One of the things we try to do is try and identify proteins in the parasite that are susceptible to chemotherapeutic attack. We are trying to understand how the nervous system works to find the proteins that are good targets for these drugs. The drug acting on that target would cause the parasite’s demise.

A big part of this project will be the screening effort. We’ll be doing some of that here at McGill, in the department of biochemistry, a group led by Dave Thomas (the Chair of Biochemistry). They have a screening centre. So we’ll employ that to begin to look for hits or leads. We’ll be doing similar exercises at other academic institutions, including the University of Michigan and the University of California (San Francisco), where we can get very clear intellectual property agreements that aren’t going to entangle us so that we will have freedom to operate in the African context for these indications. So we’ve had to work out some of that stuff, too. It’s developing the screens, the targets, then implementing them. It’s a labour-intensive thing to do.