Interview with Ragon Institute Director
Dr. Bruce Walker
The following interview by Faculty Newsletter Editorial Board Chair Jonathan Alan King (JAK) with Dr. Bruce Walker (BW) was held on May 18, 2020.
JAK: You're part of the Ragon Institute and the Institute for Medical Engineering and Science [IMES] as well as the Massachusetts Consortium on Pathogen Readiness. What’s the relationship among them and your role within them?
BW: I’m the director of the Ragon Institute of MGH, MIT, and Harvard, which is my primary role. The Institute was established 10 years ago with the mission of harnessing the immune system to prevent and cure human disease. We have focused on specific goals, the initial goal being to develop an HIV vaccine, and that work is underway right now. We have an HIV vaccine in efficacy trials in South Africa, developed by Dan Barouch, one of the founding members of the Institute.
I also have academic appointments at Harvard and at MIT. At MIT, I’m in the Biology Department and also in the Institute for Medical and Engineering Science. I also have an academic appointment at Harvard in the Department of Immunology. In addition, I have a clinical appointment at Mass. General Hospital, where I am an MD in the infectious disease division. So I wear a number of different hats.
JAK: You do indeed. And at the Ragon Institute and MassCPR?
BW: The Ragon Institute was established to bring people together across disciplines to combat really important global infectious disease issues. HIV and TB are two that we were already working on when the Covid epidemic, soon to become pandemic, started. We knew that we had a lot we could contribute based on our knowledge from HIV and TB and Zika and other infectious diseases we had been investigating. And so, we sought to basically use the model of the Ragon Institute of bringing people together to see if we could do that on a larger scale, and we teamed up with other local scientists to establish the Massachusetts Consortium on Pathogen Readiness (MassCPR), which is, in a way, kind of a pop-up store. We set it up in very short order. We’ve been able to bring together people from the University of Massachusetts, MIT, Harvard, BU, and Tufts, and all of the academic hospitals and the Department of Health, to organize around trying to do something about the Covid-19 pandemic.
JAK: How is it structured?
BW: We have six different working groups that are comprised of 500 scientists from these different entities that are working on everything from epidemiology to pathogenesis to treatment to vaccines. I am co-leading the overall effort with Arlene Sharp at the Harvard Medical School [HMS], but in truth we see ourselves more as facilitators, helping to convene people around specific focus areas, bringing scientists together to have a bigger impact. But it’s been energizing to be involved with so many terrific scientists in this unprecedented, unmatched ecosystem that we have here in biomedicine.
JAK: Regarding funding. Are most of these people working on their existing NIH funding? Or did they get supplemental funding?
BW: We gave out $16.2 million in funding that was distributed among all 15 institutions involved in this consortium. Those funds were raised from the Evergrande Group in China and from Mark and Lisa Schwartz here in the U.S., as well as from a number of other donors. So, yes, we have given out funding. The Ragon Institute also gives out funding. We’re funded through a philanthropic gift from Terry and Susan Ragon, and we also support collaborative scientific projects that historically have been focused predominantly on TB and HIV, as well as basic immunology to try to understand the intersection between the immune system and various pathogens.
JAK: Faculty are not always aware of the interests, skills, and talents of their peers, especially in a big institution. And these are very big institutions. So if some research group, let’s say the Biology Department, thinks that they have some contribution to make to the MassCPR effort, can they join in? What’s the path?
BW: We welcome everybody. In fact, there are a number of MIT faculty that are part of the MassCPR already. MIT is very much a part of it. Jim Collins, for example, with his diagnostics efforts, and Pardis Sabeti, with diagnostic efforts at the Broad, and Michael Birnbaum at the Koch Institute are some of the MIT faculty who are very much engaged. All it takes is signing up, which can be done through our website (masscpr.hms.harvard.edu).
People can participate in weekly working group calls in their areas of interest. The working group calls have been extraordinary. There have often been 100 people per call, and I personally have come to know so many people in the Greater Boston area and at the University of Massachusetts in Worcester. So for me personally, it’s really changed the work environment here in that I have a much better sense of the extent of talent in all these different areas, and it’s really remarkable to be on these working group calls, and see the collaborations starting in real time.
JAK: Concerning virology, 20 years ago Don Wiley solved the flu hemagglutinin, Jim Hogel solved the polio structure, and sadly they’re no longer with us. Who is providing the structural virology input?
BW: There are a couple of people who are doing structural biology. Steve Harrison at Children’s Hospital, and Aaron Schmidt, who is part of the Ragon Institute, and also part of HMS, and Bing Chen, who is also at Children’s Hospital. Jonathan Abraham, an MD/PhD at the Brigham and Women’s Hospital, also an infectious disease specialist, is also doing structural work, which I see as a critical component of the MassCPR effort.
JAK: This kind of collaboration normally would be very difficult, given all the different institutions. But in this period of coronavirus, it sounds like you’ve managed to overcome the inability of people to physically travel and work together. But some of those things still must be rate limiting. Can you say a few words about some of the more difficult areas of concern?
BW: Actually, there might never have been a better time to try to set something like this up, because on the one hand, most people had extra time because their labs were partially shut down. And also because there was no alternative other than Zoom calls. This entire consortium got to know each other through Zoom calls, and didn’t feel deprived because the engagements were only electronic, but rather felt delighted to have social and intellectual interaction. So it’s a strange dynamic that I think really contributed to the success that we’ve achieved thus far, very open to everybody. Nobody has to travel to get to these things. They start on time and end on time when we do a call. [LAUGHTER]
And people really have participated. The buy-in has been really great. And I think most people would say that it’s dramatically changed the sphere of people they call their colleagues now, because they’ve gotten to know each other through the science, and through these calls.
JAK: What are some of the recent developments that you’re most excited about?
BW: I think our vaccine development efforts are really encouraging. Moderna is part of the MassCPR, and they have a vaccine that looks like it’s getting reasonable responses in humans. We have another vaccine, through Dan Barouch at the Ragon Institute and Beth Israel Deaconess Medical Center, that Jansen Pharmaceuticals has picked up and has made a commitment to making a billion doses of the vaccine. We have animal data that should be out soon in terms of protection. And so that’s on the vaccine front.
On the treatment front, Boston University and the National Emerging Infection Disease Laboratory, the NEIDL, has a BSL-4 high containment facility, which is required in our view in order to do experiments with live virus in animal models. The NEIDL also has significant BSL-3 laboratories, where they are able to safely screen with live virus for drug compounds effective against SARS-CoV-2. Together with investigators at the NEIDL, we have set up a platform for high throughput drug screening and for repurposing drugs and testing new concepts. We’ve also been able to generate a very large cohort of people who have been Covid infected and from whom we’ve been able to get specimens, and that has played a really big role in understanding how the immune system functions and malfunctions and is giving us insights that are going to be important for ultimately containing the disease and developing vaccines.
Diagnostics is another area where we’ve made huge progress. Jim Collins at MIT is developing a face mask that turns color if it’s exposed to Covid. So if you put it on, and you’re infected, it tells you that you’re infected, or tells at least the people around you that you’re infected.
There are others: Michael Springer at Harvard Medical School is developing a strip-based rapid test, and Connie Cepko is developing an assay that turns color when Covid is present. Both are intended to become point-of-care diagnostics that are going to be really important to starting back up our normal lives. And then we’ve developed antibody assays that allow us to rapidly determine who’s been infected and who has not yet been infected, which we see as critical to getting the whole economy up and running again.
So those are just some of the things that I think have been incredibly exciting about what people in the MassCPR have done. And it is worth noting that, even where you might expect that all the people working on diagnostics would be competing with each other, in fact it’s just the opposite. They’re sharing reagents. They’re giving each other ideas. And they’re all pushing forward. It is a remarkable degree of collaboration and a remarkable degree of commitment to solving the problems rather than worrying about publishing papers.
JAK: That all sounds very exciting. But let me be the Devil’s advocate for a moment. You mentioned a number of really public/private partnerships. Historically the industry has been very focused on intellectual property rights, and many times I've gone to a meeting and seen somebody I know withhold data because they hadn’t yet filed for their patent. Or require signing non-disclosure agreements by collaborators. Have you run into that? Are you requiring non-disclosure agreements?
BW: Of course not, though our working groups have been closed meetings and are not open to the public. And the IP [Intellectual Property] follows inventorship in this organization, and we have not had issues. In fact, everybody has been really interested in solving the problem and not worrying about the IP-related issues. Those things may come later, but as of now, really the engagement has been terrific.
JAK: Concerning President Trump's Operation Warp Speed: Are you going to be getting direct support from Operation Warp Speed? Is there anything you can say relative to that?
BW: We’ll be trying to get funding from all different avenues. Initially the vaccine-related work was being funded by Mark and Lisa Schwartz, and is being taken forward with funding from Jansen Pharmaceuticals. So there’s a clear path to development there. For other things that we’re working on, we’ll hope to get funding from additional sources. Including Warp Speed.
JAK: Again about the Warp Speed: Do you have any sense of how long it might take for any vaccines or treatment? Any level of it from your point of view rather than a political point of view?
BW: I can tell you that the vaccine that we’re developing at the Ragon Institute and BIDMC will go into people in August or September, or perhaps even sooner. And larger trials will be done in the fall, with the hope that by early 2021 we’ll have a vaccine that can be ramped up and deployed. The important issues to understand here include that it takes a while and an enormous capacity to be able to make the billions of doses that are going to be required. There are seven billion people in the world, and if all of them need to be immunized, then we’ve got a huge challenge in front of us.
Now, we know that it’s reasonable to think that an adenovirus-based vaccine, which is what we’re doing with Jansen Pharmaceuticals, can be scaled to that level. What’s less clear is the mRNA vectors and how you get to scale with those to be able to provide enough doses. But knowing that’s the target, and acting on that now to build capacity is how this is being approached, and that’s really important.
JAK: All the efforts around the world were kind of launched when the Chinese groups completed the sequences, the RNA sequence, and they shared it. How do you feel about the Trump Administration’s charges that the Chinese are trying to steal U.S. intellectual biomedical property? And does that impact on your collaborative work with the Chinese groups?
BW: I feel this is a global problem, and we’re trying to come up with global solutions. The discussions with the Chinese that we’ve had have been extremely helpful, because they are ahead of us in terms of the wave of this pandemic. So, they were able to start studying it sooner. And I think that their sharing of that information has been very helpful, including sharing of the sequence that allowed everybody in the world to get started on this. So I hope that we can find in our response to this pandemic a sense of global cooperation that is really necessary for us to effectively combat it.
JAK: I come from the biophysical side, former president of the Biophysical Society, and I work with structural virologists. I'm going to ask you to comment on the importance of key publicly-funded resources including the Protein Data bank, and Genbank.
BW: These are critical. In fact, we’re developing a T-cell-based vaccine that starts with structure and by applying network theory to crystal structures. Gaurav Gaiha at the Ragon Institute developed an algorithm that allows us to identify highly networked amino acid residues that are key targets for effective immune pressure, because they can’t mutate, so the virus falls apart. We published a paper in Science last year showing that concept actually identified residues in HIV that when targeted by the immune system caused the virus to become crippled if it mutated to try and escape. And it turned out that there are individuals who target those specific highly networked residues. So it kind of makes sense, and I can’t stress enough how important the crystal structural data have been for allowing those experiments to be done.
JAK: Thank you so much for your time, Dr. Walker. This has really been most illuminating.
BW: You're most welcomed.
Jonathan Alan King is a long-time Professor of Molecular Biology at MIT. His research group worked out the major steps in the assembly of double stranded DNA phages and viruses, including identification of the procapsid precursor in DNA packaging, and the critical role of recycling scaffolding proteins in virus capsid assembly. He currently chairs the Editorial Board of the MIT Faculty Newsletter. A former President of the Biophysical Society, Prof. King sits on the Society’s Public Affairs Committee, which has produced recommendations for coronavirus research as well as popular coronavirus exposition.