📷 St. Joseph Health Care London
Journalist: Jeryn Anthonypillai
Jeryn Anthonypillai:
Hello and welcome to SciSection. My name is Jeryn Anthonypillai and I'm a journalist for SciSection radio show broadcast on the CFMU 93.3 FM radio station. We are here today with Dr. Frank Prato, the founder of the Lawson Imagining Research Program. Thanks so much for joining us today.
Dr. Frank Prato:
Well, thank you for interviewing me Jeryn.
Jeryn Anthonypillai:
So to begin, could you talk about the Lawson Imagining Research Program you founded, how did it commence and what were some of the challenges you have seen at the very start?
Dr. Frank Prato:
Yes, I've been working at St Joseph's hospital, which later became St Joseph's Health Center since August 1976. And I was hired as a medical physicist to help grow the nuclear medicine program at that hospital. Some visionaries at the hospital decided that maybe we should have a wing of the hospital dedicated to medical research. And that started to be put together in 1980, 1981. And in 1982, I was the only medical physicist in the hospital, but I propose that a new technique called nuclear magnetic resonance imaging had a future for patients and that it would be an excellent platform to initiate a program within the Lawson Research Institute, which would eventually become a Lawson imaging research program. So, that's how we started. We got interested in something that would later be called magnetic resonance imaging. It was very early technology. We were fortunate enough to get sufficient funds from various sources, including the director of the nuclear medicine department at St Joseph's hospital. And also some funds controlled by the sisters of St. Joseph's, who at that time ran the administration of the hospital. So with those funds, we purchased and we got running, what is now called a magnetic resonance imaging system. It was very primitive compared to the systems today. It was running with a very low magnetic field strength of 0.15 Tesla. And right now, the MRI imaging is done at 1.5 Tesla. So let's see, 0.15 and 1.5. So it's about 10 times higher or three Tesla, which is 20 times higher and field strength. But the images even then were very promising. So we started a research program and we started what would become the imaging program among other programs at the Lawson Research Institute. And so that was back in December 1982, we produced the first image of a patient who had a small stroke and we could actually detect it. And I remember working with the nuclear medicine specialist, the MD, and we went down to coffee and looked at these images, he said, this is fantastic Frank. We can see this very small lesion in the brain, and we've not been able to see that in any other way. This is really exciting. And I was concerned that maybe, there was a glitch or somehow in a machine and it wasn't running properly. So, it was three more years we've worked before we started getting some funding from the Ministry of Health in Ontario to pay for scans to be done in patients for diagnostic purposes. So we had three years of a hundred percent research on the machine, and then we progressed and around that machine, we built the Lawson Imaging Research Program.
Jeryn Anthonypillai:
And like you said, your team produced the first human MRI in Canada, as well as the first human hybrid PET MRI in Canada. So how did people react to these new imaging technologies at the time?
Dr. Frank Prato:
Well, I was a young man at the time, 30 years old, and I was really pleased to get the first image, but you know, the group at Princess Margaret hospital under the directorship of Mark Henkelman and Mike Bronxville, got their first image on the same piece of equipment about a week later. And, when I was a young person, I was fairly competitive. And so I can remember pushing the construction to get things going. And we just made it by one week also, the group at the University of British Columbia got delivery of a unit, but they had a little trouble getting it to work. So I think we beat them by a month or two months or something like that. So, clearly, there were about three sites in Canada that were coming online at about the same time. So, with an MRI, we continued to progress. And as you know, MRI is extensively used now, clinically, and research keeps going, research keeps progressing, and it's an amazing technology with an amazing opportunity. It's very flexible in terms of how it makes an image and people are imagining always new ways and inventing new ways of making imaging. So MRI is very exciting, but MRI is limited in sensitivity, can do marvellous things, and doesn't expose anybody to ionizing radiation like x-ray does, but it has limited patients. If there's a change in your body, say a change in a cell that becomes diseased. That change has to be something like one change in 10,000 compared to the surrounding cells. So you say, well, that's a small effect, and that's a small thing that can be detected with MRI. That's great. But I became interested in positron emission tomography as the technology, which has the downside of exposing individuals to ionizing radiation like x-rays, but they're called gamma rays, but the advantage of positron emission tomography, instead of seeing one part in the 10,000 change, it is very sensitive. It can detect one part in a trillion, so many orders of magnitude, more sensitive and it's much more flexible because it's much more sensitive in MRI, if you want to detect changes by injecting a contrast agent, which changes the MRI parameters. So you see where that contrast agent goes. You have to inject grams of materials. If instead, you want to see a contrast agent that is injected for positron emission tomography, you only have to inject nanograms of materials. And because you have to, you can only inject such small quantities and positron emission tomography is very flexible and you can make new contrast agents that, you know, eventually will be approved for human use. Whereas new contrast agents in MRI are difficult to approve for human use because you have to inject so much when people are concerned about perhaps some unwanted effect caused by injecting so much material. But MRI doesn't use x-rays, MRI produces exquisite images, of high-resolution images of the body, you know, sub-millimetre. You can see about 60,000 cells in an individual image element. Whereas with positron emission tomography, the images are more blurry but extremely sensitive. So the idea was to combine MRI and PET. Where MRI would produce the high-resolution images and PET would produce the great sensitivity to the tech disease very early on. So putting those two together was very exciting for me. So we worked very hard to raise the money to do that. And we got a very large grant, it was a city-wide proposal I led and we got a very large grant from the Canada Foundation for Innovation. And we got basically about $35 million to introduce new technologies. Now with positron emission tomography. Unlike MRI, with MRI, if you have a contrast agent, you buy the contrast agent who stays on the shelf for a year or two years. It doesn't matter. Then you can inject it into a patient. And there is one approved contrast agent, basically, in MRI with positron emission tomography, we inject radioactive material, and that material is designed so that we reduce the radiation dose so the patient is designed to disappear very quickly, disappears so quickly that you have to make it locally. If we want to make it locally, we have to make radioactive material using a particle accelerator. So this large grant, a large part of it was to build or to buy a particle accelerator that we would install in the basement of St Joseph's hospital. So that's what we did. And, we started the project about 12 years ago and took a long time to get everything going. We had to get approval from Health Canada approval from the regulatory agencies in Canada that control the use of radioactive material. We had to hire a team, and then we started doing some experiments that no one else can do almost in the world. For example, because we have the PET/MR system right next to this particle accelerator, we can produce things that have a half-life that is half a bit disappears in two minutes. So, you can use something for about five or six half-lives. So you make it, you have to test that it's safe to be injected into the patients, into humans. And then they have to use it within 10 minutes and you have to inject it into the patient within three or four minutes, and then you'll have to collect the images. And everything's sort of done 12 minutes after the material is made. So this is not an easy thing to do. You have to have the chemists, you have to have, the people who know how to run the particle accelerator. You have to have testing to make sure that whatever you're going to inject is safe, and then you have to transport it to the PET MRI. You have to inject it and you have to be doing the imaging very quickly. So, that's the technology that I've introduced. So I was happy, pleased, fortunate to be able to introduce MRI into say, London, Ontario, and Canada. And then with PET MRI, we were fortunate to introduce that into Canada. We were the first in Canada and we remained for the first three or four years now, their instruments than other parts of Canada. And, it was about the fifth unit in the world at that point in time. And the unit has remained largely research. And we were doing research work that that many other people can't do, for example, there is a PET MRI in this Cedars Sinai hospital in Los Angeles, but they come up to our site here in London, Ontario to do research because I have been able to coordinate with the help of many, a unique infrastructure that allows us to do experiments, that really can't be done, in very few of any places in the world. So that's given us some excitement for things to do. I'm not doing all that work. I've been at St Joe's for 44 years. Over that period of time, I've been able to recruit some outstanding people, and I've been able to recruit people with different skills, different disciplines. You know, we have an engineer running our cyclotron facility. For example, we have people with appointments and physics appointments and medical biophysics appointments in cardiology, appointments in biomedical engineering. So I've been able to put a group together and I could show you some examples at some point in time, how it's important. The excitement for me right now as an old guy is we can do many sophisticated things because we have the talent and the mix of talent and the interdisciplinary talent. We can do things that, I couldn't imagine doing on my own when I first started out. I'm going off a bit on a tangent, old men tend to do that. And I apologize.
Jeryn Anthonypillai:
No, it's perfect. It's really fascinating. So thank you for that. And I know you've done an immense amount of research and some of them have included MRI in them, but what would you say is like your most recent research work?
Dr. Frank Prato:
I've given that some thought, and it's not an easy question to answer. I think the most exciting things I'm doing now are varied. They're not just in one area and that's because I have some outstanding people with interdisciplinary skills. So, for example, one of the things that happened recently, I went on a trip to China a few years ago and someone was talking to me and they said, do you know, so-and-so at your Institute? He's famous. He's developed poop transplantation that is saving people's lives, where, you know, the bacteria in their gut is resistant to all sorts of antibiotics. Do you know this guy, this guy is doing fantastic stuff. And I said, no, I don't know who he is. Well, he had an office two or three doors down from me. So then I met him and then we talked and he said, you know, that one of the greatest problems we have in our business, bacteriology businesses is we can't image bacteria. We don't know what's going on. We give bacteria to people. We put bacteria, probiotics in yogurt. We put billions of bacteria in the yogurt. We ask people to eat it. We don't know where it goes. We don't know if it stays in the body. We don't know if it just goes right through with the poop. And, you know, I was very surprised to hear that dried poop is 40% by weight bacteria. But anyway, so, we put a group together just before Christmas, the team. We were shut down for a while justifiably because of COVID, so we couldn't do any experiments, but we did recently. Finally, we got this theory, we filed a provisional patent and then I've been trying to excite companies to fund us and they want to see some results in animals. And so we got a farm pig and we were able to image the bacteria in the pig using PET MRI. And we gave them a probiotic that is often in yogurt. And we determined what percent stayed in the gut, which was less than a percent, in a week's time. We used the pig because the pig has a GI system similar to humans. They're omnivorous like humans are, you know, you couldn't use a dog, because dogs are carnivorous and stuff like that. And we wanted to use an animal that's large enough because what we do is we image large animals on the same equipment we do humans so that if we find something that can be used for humans, we can immediately do it for humans. If you're doing work in small animals, imaging doesn't always translate linearly to humans. So we do like to use larger animals like pigs. And, we found out what percent stayed in the gut. We found out that some leaked out a small percentage, and we found that some of it went to the liver and the kidney, but none went to the brain and the heart, and this is a healthy animal. So, we're very excited about that. Haven't published it yet. That's one excitement. I'm really excited about the work I'm doing with an outstanding scientist in the United States at Cedars Sinai in terms of heart. He's been coming up to do experiments at our site because he can't do them where he is in the United States. And, we've discovered ways of diagnosing heart disease. The present technique for diagnosing heart diseases requires a 24 hours one study. And then the person has to come back for another study, two injections of radioactive material, another injection of a pharmaceutical. And so days of imaging and three injections. And we've shown in an animal model that we can do it all in one hour without any injections. And this would affect Canada about 400,000 tests per year, moving them from three injections overnight to a one-hour study using no radioactive material. So that's exciting. That's exciting for me. I'm doing a lot of work supporting excellent work that's going on in cardiology in the city, trying to, for women with left breast cancer who received radiation therapy, they're living longer now it's just that the therapy is successful, but the heart sometimes is getting radiation. And later on, they sometimes run into heart problems. So we developed in a large animal, a technique for early diagnosis of any potential complications that might arise in later life. And we have a student now, and I'm not the leader of this project. It's an outstanding group at the London Regional Cancer Center and I think we'd done our fifth patient now trying to translate what we found in the animals to the patients. So that's one other thing we're doing. I'm very excited about another graduate student. I started something about 15 years ago to try to produce for animals, a contrast agent for MRIs. If it's for preclinical, it's not for human use where we take DNA from bacteria and program that DNA into cells, mammalian cells. So we're taking bacterial DNA and put it in mammalian cells. And then, we turn that set of genes on at a particular point when the cell is doing something so we can inject the cell, the cells can grow and they're all silent. We don't see them. And then all of a sudden, when a cell state changes from one kind of a cell to another kind of a cell, it could be a cancer cell. It could be moving from a stem cell to a cardiac cell, then all of a sudden it lights up. So we believe once we get this technology going, we'll be able to get MRI to a sensitivity, close to PET, positron emission tomography. Instead of having it limited to about 60,000 cells, we'll be getting down to 300 cells. So that's very exciting, but that's been a very difficult thing. I was naive when I got involved. I thought just like the other reported genes in optical imaging, like fluorescents and bioluminescence. Bioluminescence was taken from fireflies and modelled after that, that was only one gene. It's turning out that the bacteria produced this MRI contrast agent, just serendipitously to produce it. They produce it for other purposes, but we found out that they produce it. And it is the greatest and strongest contrast agent known in MRI. If we can get normal cells to produce this stuff, they'll just light up. So, but I didn't know. I thought it was just one gene at the time I started 15 years, 12 years ago, it was only one gene people thought, but it turns out to be a cluster of genes. So the problem has become much more challenging, but we have people working on this right now and we have our patents. And so that's exciting. So you asked me what I'm doing and I'm doing some exceptional things because I have an outstanding group of people with skills that fit together with each other, to do things that we just can't do really anywhere else in the world. So for me, that's a very exciting thing to be 74 years old, and now to be able to benefit from an outstanding team. And many people have stayed with me for 10, 20, 30 years now. With an outstanding team of scientists and technologists. You know, if we're doing animal work, we need outstanding people who know how to handle animals safely, keep them safe and need to tie them cause they won't stand still for imaging, and then recovering them, treating them well. It's a tremendous pleasure to be able to do things that are important. That is important for translation to patients. I often try to say, I got a statement here that, you know, we have a storage responsibility when we're doing research in a hospital-based research Institute. We have a stewardship responsibility to our patients to make available the latest and best technology for early diagnosis and treatment towards cures. We have a stewardship responsibility to translate new technology when possible from our academic centers to community hospitals, we have a stewardship responsibility to make available novel, new therapies, not funded by provincial healthcare. And I just really believe that research is an essential part of the patient care continuum.
Jeryn Anthonypillai:
Yeah, for sure. I feel like you guys have definitely done a lot of important research and you have a very accomplished and prominent career. And I guess that leads to my final question. So what do you think you did differently compared to others that helped you become who you are today?
Dr. Frank Prato:
Oh my gosh. That's a difficult question. A lot of people I know have been more successful than I have. And so I don't know really how successful I have been, I think to be successful one has to have a passion and dedicate time to a particular goal. And that means making some sacrifices. It doesn't mean that you can't have a family life, but it may mean that you don't do some other things that when you were younger, you might want to do, you know, maybe you spent a lot of time watching sports on TV or, or things like that. So, I think it was the opportunity to work at an institution that is not a large institution. St. Joseph's hospital is a teaching hospital, but it's not one of the smaller ones, but to be able to work with people that have supported me and supported my vision. And, I also believe that one of the advantages is I've not jumped around in my career. I've stayed at one place and I've been able to establish relationships and I've been able to establish what I would consider is integrity so that people understand my motives and my motive as I said, is to do good research that I'm excited about. I find it fascinating. I always like to know that I've got something that no one else in the world knows, that's an exciting thing. But, I think that's it. And one other thing that is occurring to me that that is important. Oh, I guess we'll get to the question of advice to students or advice to anybody. You know, it's occurred to me that if you do not own your failures, you cannot own your successes. So if you blame others for your failures, then why should you congratulate yourself for your successes?
Jeryn Anthonypillai:
Yeah. I think that's a beautiful piece of advice to give to students. And with that being said, that brings us to the end of the interview. Thank you again for joining me today. That's it for this week of SciSection. Make sure to check out our podcast, available on global platforms, for all of our latest interviews.