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In conversation with Sachdev Sidhu

Molecular genetics professor wins award for protein engineering research
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Dr. Sachdev Sidhu, a professor in the Department of Molecular Genetics, recently won the prestigious Protein Society’s 2015 Christian B. Anfinsen Award for his cutting-edge research in protein engineering. Sidhu is also a founding member of the Centre for Commercialization of Antibodies and Biologics (CCAB), a biotech company established last November with the aim to provide new antibody-based therapies. This was a big boost for the Ontario biotech sector, and CCAB already has antibodies targeting cancer and other diseases in their development pipeline.

In this interview, Sidhu speaks to The Varsity about his biotech company and the rise of tech startup culture.

The Varsity: Antibody therapy is an emerging and effective method to target cancer. Can you explain how it generally works to kill cancerous cells in humans?

Sachdev Sidhu-courtesy of Sachdev SidhuSachdev Sidhu: It’s beyond emerging; it’s actually one of the major methods currently available to target cancer. There’s typically at least two ways that antibodies work. One is by targeting signaling pathways on the cell surface and then shutting down the signals … So you actually down-regulate signals that are causing cancer cell growth. The second one is interesting … you can turn on signals that induce cell death of B-cell lymphomas … And the third way is [when] an antibody acts as a marker for the natural immune system. As you know, antibodies recruit T-cells. There’s a fourth way, [using] an antibody to target cytotoxic drugs, [which] is a delivery mechanism. The nice thing is this gives you a lot of different ways to use antibodies, as opposed to small molecules, [which] are the other big sourceof drugs. [Small molecules are] much more limited and typically act inversely — they down-regulate and inhibit proteins.

TV: As the CEO of the Centre for the Commercialization of Antibodies and Biologics (CCAB), tell me a little about CCAB and what it hopes to accomplish.

SS: To make money from antibodies, which is a thing that’s done all over the world.

Antibodies earn more than $50 billion a year, and will probably get to $100 billion in a decade. Firstly, almost none of that is in Canada, so [CCAB is trying to] get commercial benefits from research in antibody therapeutics, which people in academics often forget that at the end of the day there’s only two sources of money: government or private pharmaceutical[s]. Canada does a good job at U of T, for example, [in] funding … but we have a very poor record of getting private funding. So in a nutshell that is the goal.

TV: Did you always know you wanted to do this aspect of research within biotech, as opposed to academia?

SS: No, not really. Especially in Canada … a lot of people aren’t even aware that [biotech] is an option. I went to Genentech to do a postdoc, which ended up being a lot longer. I wouldn’t say it was accidental, because, for example, even though U of T is a huge university, easily competitive to the best schools in the United States, students here and across Canada are much more naïve about biotech. It’d be very rare for somebody to have a plan in Canada to want to get into biotech. It’s been 20 years since I started and it’s rare to see that. In the Bay area, it’s typical for students to already be thinking about biotech, but I think in Canada it’s fair to say you have to kind of luck into it.

TV: What challenges have you had to deal with in developing CCAB from the ground up and how have you overcome them?

SS: It’s just attracting the business … I think we’ve had success recruiting people from Boston and San Francisco, which is actually very rare. So we have to get people to move from other places, which is not trivial. I’d say that’s the biggest thing. You need all the pieces of the puzzle, you can’t just say you have the greatest science. Another [challenge] is getting American investors to take Toronto seriously. We have to do a lot more work than a typical American company, to get the investors comfortable … It’s still kind of the beginning, so it’ll take another five years minimum to get stuff to work and commercialize. So people are relying on you to remain committed, and Toronto doesn’t have a good reputation for that. We do great science, but we’re not doing a lot of translation … Another thing is [that while] we have the money, you can’t train people in a reasonable amount of time; you need a [certain] skill set to actually attract people from very competitive cities.

TV: Do you believe Toronto can be a really good biotech hub in the future, like San Francisco or Boston?

SS: Yeah, anything is possible and things can change very quickly in the industry. You have to have a pattern of success, and one company can’t do that. But it’s actually quite exponential, if we get a few key pieces in place. And that’s the thing, to attract more money you have to get more people [with the skills to do it], then hopefully they’ll attract more people. So, it’s feasible but it’s not trivial … CCAB is one starting point but realistically, even if everything was successful now, we’re not going to be getting new drugs coming out of this for another [few] years, so we still need further funding, [which] we’re trying get the government to [commit to] … It has to be a sustained effort. Again, Canada has a tendency to think that once it’s done, it’s done, but this is something that doesn’t have an end to it. Especially in other cities — Shanghai, San Diego, Singapore — there’s a lot of competition. It’s not like Toronto is the only city that’s noticed that we should be doing more biotech. It has to be consistent, and we’ll see if that happens … I think the key is, will other groups do similar stuff? Otherwise, it’ll be very good for us and good press, but sustainability is key and we’ll see if other groups can take on the challenge.

TV: For students who are interested in the intersection between science and business, what are the necessary skills one should have in order to attain the kind of career that you have?

SS: … It’s only in the past couple of decades with genomics, ironically, that there’s been this disconnect between academics and so called industry. If you think about it, going back to [the discovery of] insulin … it’s not fundamental science or practical science, it’s obviously both. The polio vaccine, penicillin and Flemming… all of these are key examples of how there really wasn’t an intersection between academics and industry. I think that’s the mistake we all make: we do genomics, we do the academics, industry does this, and we occasionally have to intersect. … I mean, this applies in computer science and physics. Was Nikola Tesla a fundamental scientist or was he an engineer? This is not a sensible question to ask. And oddly in biology we ask this question, which I think is very self-defeating.

A lot of my colleagues in academics are quite guilty of asking students, ‘do you want to be in fundamental science or do you want to go into industry?’ If somebody asked Banting and Best that, we wouldn’t have insulin. I don’t think they were thinking ‘although now it’s getting practical, last week our research was fundamental, and a month from now it’s going to get industrial.’ If you read the history of insulin, none of these guys ask, “Am I doing hypothesis-driven science now or am I doing a fishing expedition?” All these words that have crept into science are completely self-defeating. It’s like somebody asking Bob Dylan if he’s a rock singer or a folk singer, but that’s going way back. These aren’t sensible questions. And it’s unfortunate that a lot of the faculty everywhere kind of imposes that on students … There’s literally hundreds of examples where the best science has never been practical or fundamental, basic research or applied research.

This interview has been edited and condensed for clarity and length.