 You might as well get started. I'm delighted to introduce today's speaker, Professor Matthew Herter. I am Sheila Wildman. I'm a member of the Health Law Institute. Matt became director of the Institute a couple of years ago, I guess it is now. And he's facilitated many wonderful opportunities for scholars and students studying and researching in the area, including opportunities to build bridges and partnerships with others working in the field and with communities. So we're very grateful for the work that Matt does, born with us. He's also, along with Constance McIntosh, responsible for having set up this year's seminar series. So it's fitting then that he's the one to close it off. It's the last seminar for this year. And I, for one, have been thrilled with the quality and the variety of the speakers that we've hosted. So thanks for that as well to Matt. So Professor Herter is on faculty at the Department of Pharmacology, and he's cross-appointed with law. He also sits on the Patent Medicine Review Board, which is a very good thing for you and me. Matt's research is recognized as of national and international importance. It addresses drug regulation and biomedical innovation policy. It's focused particularly on intellectual property law and practices connected to the commercialization of scientific research, as we'll hear more about today. So please join me in welcoming Matt. Thank you, Sheila, Professor Wildman. Thank you all for coming today. It's my pleasure, although it sounds a little bit like I picked this spot for myself. There was a committee. That isn't the case. Anyway, it's a real privilege for me to share this work. It's something that I've been working on for the last five years, and it's an important story, as I think you'll come to appreciate. I should start by thanking the funder of the research. The Canadian Institutes of Health Research funded this project, and others related, as Sheila said, to my focus on the commercialization of academic science. And so that project's been ongoing. It's just wrapping up this month, actually, and this is probably the flagship piece of work connected to it. I'd also like to thank my collaborators on this particular project, a legal scholar at McGill, Richard Gold, and my anthropologist colleague in medicine, Janice Graham. Last, but not least, most importantly, I want to acknowledge the work of this person that you see on the screen. That's the late Dr. Julie Alamonte. Without her work, her contributions, I don't think we'd have the vaccine that is the focus of the work I'll talk about today. And so today, I really hope to surface her contributions, which I think have so far been buried in the backstory of this important public health intervention. With 973 suspected cases and 534 deaths to date, the current Ebola outbreak in the Democratic Republic of the Congo is the second largest Ebola outbreak in history. The largest, which occurred in 2014, 2015 in West Africa, tallied more cases of Ebola, more deaths due to Ebola, than all of the other Ebola outbreaks combined, since that virus was first identified in 1976. Over 28,000 cases of Ebola, including over 11,300 deaths, spread amongst the people of Ganea, Sierra Leone, and Liberia, not to mention the front line responders who tried in vain to quell that two-year epidemic. The period of interest for our study, though, actually predates that epidemic in West Africa. It spanned from May 2010 to March 2014, when the World Health Organization declared that Ebola outbreak a public health emergency of international concern. During that four-year period, only 54 cases and 21 deaths from Ebola were recorded globally. None of them were in West Africa. And yet that's the period I want to focus upon today, because that's the timeframe during which the government of Canada, specifically the Public Health Agency of Canada, entered into a patent licensing agreement with a private company known as Bioprotection Systems, or what I'll call BPS. The purpose of that deal was to commercialize an experimental Ebola vaccine known as our VSV-Z-Bov, I'll probably call it Z-Bov for short, which had in a series of promising preclinical studies involving animal models dating back to 2004 been shown to be up to 100% effective in protecting against Ebola. However, in 2014, October 2014, the New York Times ran the following story at the height of the West African epidemic. Suggesting that that company, BPS, had shelved this vaccine. We wanted to figure out if that was actually the case and if so why. The facts that we uncovered through our access to information requests will follow, but what we found calls into question the wisdom of licensing global health intervention such as this vaccine to the private sector. And at the same time, illuminate both the value yet precarious state of public sector science. The story of the Z-Bov vaccine powerfully demonstrates the need for new approaches to knowledge production such as open science. So the story I'm going to tell has three parts interrupted by key pieces of context around the war on terror, patent theory and from all of that, I'll distill some key insights by way of conclusion. There are lots of different actors in this story that one that is central is the National Microbiology Laboratory or NML in Winnipeg, which following the SARS crisis over 2002 to 2004 became the cornerstone of the newly formed Public Health Agency of Canada or P-HAC. The NMLs work on Ebola traces back to 1999 when the lab recruited Dr. Heinz Feldman to become chief of its special pathogens program. Feldman trained at the University of Marburg in Germany where the Marburg virus belonging to the same family of viruses, phyloviruses as Ebola was first discovered in 1967. To the 1990s, Feldman established himself as a leading infectious disease researcher both in the lab and in the field. Here he's walking the streets of Hong Kong with his junior colleague from the NML, Dr. Raymond Flick during the SARS outbreak. Within three years of arriving at the NML in Winnipeg, Feldman and his colleagues had developed an Ebola vaccine candidate, the Z-Bov vaccine, which essentially worked by taking a live attenuated recombinant stomatitis virus or R-V-S-V, that's the first half of the name, and replacing its glycoproteins that appear on its surface with the glycoprotein gene from the Ebola virus sourced from the former country known as Zaire. Today, the Democratic Republic of the Congo, or DRC. As required under Canadian patent law applicable to government scientists, Feldman and his colleague Stephen Jones and Ute Strohr disclosed the invention of the National Microbiology Laboratory's Intellectual Property Office. The Canadian government, Her Majesty the Queen in the eloquent writing of patent law, in turn filed a U.S. patent application in July 2002 entitled recombinant vesicular stomatitis virus vaccines, this is a struggle for me, for viral hemorrhagic fevers which include what is not limited to the Ebola virus. That patent was eventually granted in the United States, in Europe, in Canada, in 2010, 2011, 2013 respectively. Despite a series of publications indicating that this vaccine was highly effective in mice and non-human primates, there was initially no commercial interest in this vaccine. In 2005, P-HAC entered into a material transfer agreement with the U.S. Army Medical Research Institute of Infectious Disease, USA-AMRID. However, the agreement was for only non-commercial research purposes. To develop the vaccine, NML scientists instead secured funding under the Canadian government's Safety and Security Program, or CSSP. In 2006, in pursuit of two broad objectives, those are the papers that were showing the promise of this vaccine. The first broad objective of this funded research was to manufacture 1,000 to 2,000 doses of clinical quality or GMP grade vaccine for use in clinical trials involving humans. Second, the scientists sought to understand the immune correlates of protection for an Ebola virus infection so that they could develop treatment protocols and assays in order to obtain regulatory approval from a regulator like Health Canada, the U.S. Food and Drug Administration. A total of 5.9 million Canadian dollars, including in-kind contributions from the NML, as well as the U.S. Military Research Institute, I mentioned, was budgeted for that project between 2007 and 2013. The deadline to use those funds was later extended to March 2014. Neither the funding source nor the involvement of the military in this research should be surprising. Between 1997 and 2015, public funding contributed three quarters of over a U.S., over one billion U.S. devoted to Ebola and related research. The development of vaccines through government, academia, industry, collaboration also has a very long history, particularly during times of war. Kendall Hoyt writing on vaccine innovations during the Second World War recounts a number of important examples. The development of a vaccine against pneumococcal pneumonia that had stalled in the late 1930s after antibiotics were introduced onto the market. However, the military had a continuing interest in preventive population-based health measures, and that spurred the creation of a U.S. government commission that coordinated vaccine development work across a range of government agencies, universities, and pharmaceutical companies culminating in a massive double-blind, randomized clinical trial during 1944-1945 that involved over 17,000 military personnel, which demonstrated not only the effectiveness of that vaccine, but also arguably set the bar for all future clinical trials. The war that lay behind the funding that was secured by Feldman and his team in Winnipeg was a very different kind of war, however. The war on terror. In her 2008 book, Melinda Cooper traces how the language and concepts of emerging and infectious diseases found a welcoming host in U.S. security discourse through the early 1990s, all the way through the 2000s and beyond. She describes that as the biological turn in the war on terror. As Cooper, Steve Henchcliffe, Melanie Armstrong, and others have argued, I think persuasively, the uptake of infectious diseases and security parlance at that time happened at the same time that there was a neoliberal demolition of public health. In other words, at the very moment when the old model of mitigating public health risks through careful state planning was being dismantled, quote, in favor of more speculative forms of government. To put it differently, again, the perceived risks of bioterrorism rose just as the responsibilities of state agencies were being parceled out to private actors, claiming to serve but not yet having the capacity to actually perform public health functions. Fundamentally, public problems, problems that by their very scope threatened the citizenry as a whole, the thinking went, required private solutions. Even before the September 11th, 2001 attacks, U.S. government officials were invoking the quote clear and present danger posed by the daily threat of human and agricultural bioterrorism. A week after 9-11, the first series of letters containing anthrax spores were mailed to the media and politicians that infected 22 people and killed five. That galvanized the U.S. support for so-called biodefense research. Legislation and a rash of new funding followed. The money flowed through existing mechanisms such as national institutes of allergy and infectious disease, recently established agencies such as the Defense Threat Reduction Agency, within the U.S.'s Department of Defense, and new channels, entirely new channels such as the Biomedical Advanced Research and Development Authority, or BARDA. In 2004, Congress entrenched this new funding with the enactment of Project Bioshield, a law with the express aim of creating a biodefense industry to develop medical countermeasures against diseases deemed material threats to the United States. Between 2001 and 2014, over $78 billion was earmarked for biodefense research. The Canadian government, like many other nations, followed the U.S.'s lead, albeit on a much smaller scale. Defense R&D Canada, I live close to their building in Dartmouth, an agency with Canada's National Department of Defense was grant within our Department of Defense, was granted $170 million in funding in the 2001 federal budget to establish in our sort of more clunky Canadian way the Chemical, Biological, Radiological and Nuclear Research and Technology Initiative, or CRTI. It was this funding from the CRTI initiative and its successor program, the Canadian Safety and Security Program, or CSSP, that the researchers at the NML secured to support their work on Ebola vaccine. Within months of securing that funding, the NML began discussions over a patent license agreement with bioprotection systems. A small startup company founded in 2005, right, right after all that new money came through Congress, located in Iowa State's University's Research Park. BPS, like many other small to medium sized biotech turned biodefense companies chased those new sources of government funding in the name of fighting bioterrorism. And it just so happens that one of Feldman's colleagues, Dr. Raymond Flick, was now working at BPS. With no prior track record of bringing a vaccine to market, in December 2007, BPS submitted a development plan to PHAK, claiming that it and its development partners have the capability and capacity to manufacture, to bring drugs to the clinic and follow that drug all the way through regulatory approval. BPS may have been relying on the capacity of its partner New Link Genetics when it made that claim. However, New Link had at that time, nor since ever brought a product actually to the market. Nevertheless, bioprotection systems proposed a work plan in which it would, one, carry out additional preclinical vaccine testing, two, perform safety and toxicology studies, three, assist with manufacturing of the vaccine, and four, consult with and carry the product all the way through approval by the US Food and Drug Administration, the FDA. PHAK forwarded draft licensing terms to the company in 2008. Negotiations over the license proceeded over another two years, but all the while the NML continued its work on the vaccine. So in 2008, the NML oversaw the production of plasmids for the reverse genetic system used to generate the vaccine, a critical first step in the manufacturing process. The government lab also entered into a totally separate deal with a German contract research organization known as IDT Biologica that specialized in vaccine manufacturing to complete the production of the ZBOV eventually. There's the agreement with the German firm. In May, 2010, PHAK and BPS finally formally concluded the patent license agreement. The agreement provided BPS with a sole license agreement over the vaccine, but with specific carve-outs protecting PHAK's ability to use the patent rights for research and educational purposes and also to make the invention available in the context of a public health emergency, whether domestically or internationally. BPS was given the power to sub-license the patent to another company without the Canadian government's prior approval, but PHAK's protections, for example, to use it in the context of an emergency will continue to run with any kind of subcontract or sub-license. BPS furthermore agreed to make reasonable efforts to commercialize the vaccine, deliver written reports to the government of Canada about its progress in commercializing the vaccine, and the contract stated that if you shelved the vaccine, if you sit on it, you don't commercialize it, that is a fundamental breach of the contract. While the publicly available version of the license blacked out the financial terms of the arrangement, new links, regulatory filings show that BPS had agreed to pay for all of the costs of obtaining the patent. Remember, the patents weren't actually secured until 2010 and beyond, and paid milestone payments of approximately Canadian $205,000 when and if a product was approved by a regulator like Health Canada or the FDA. So at this point, it's useful for me to sort of unpack these deals and the patents that underlie them, at least from a theoretical perspective. To an economist, patents are needed to protect inventions because an invention is an information-based good. Information in economics discourse is a public good, meaning that it is both non-rivalrous and non-exclusive. Unlike a tangible good, your consumption of the information doesn't diminish my ability to do the same. Similarly, it's difficult for you to stop me from using the information once I have it. As a result, unless we find other ways to protect the information against free riding used by others, we would worry that no one would put in the effort in the first place to produce the information, and this information, right, is it vaccine safe? Is it effective? That's socially valuable information, so we want to encourage that kind of information production. So enter intellectual property rights, such as a patent right, to encourage that production of information. The problem is, is that in the context of universities, government labs, where many, if not most, socially valuable innovations, including drugs and vaccines, originate from significant incentives to produce that underlying information are already in place in the form of reputation-based awards, grants, other kinds of awards and prizes. So particularly in light of the additional transaction costs or inefficiencies that patents can introduce to knowledge sharing, many have argued that in the upstream or early stage research context, such as universities, we don't need patents to encourage information production. It happens in any event. This stronger argument in favor of patenting and licensing out to the private sector actually follows from the lengthy research and development process that follows the initial discovery research. Patents on drugs and vaccines are usually about half elapsed by the time those products actually reach the market. Patents are for 20 years, you file them very early on, maybe only half of that term is left if you get approved by a regulator. This argument in favor of patenting and licensing out has become known as commercialization theory. Patenting is justified not to encourage early stage research but rather direct and sustain the follow-on development that's necessary. If we don't provide those kinds of incentives, the argument goes, those inventions, that knowledge will lie follow in university labs because no one will have an incentive to pick it up. That the private sector is better to equip to do this follow-on work is nested in an assumption about who holds the expertise and capacity to do that later stage work. It is the case that large multinational companies sponsor products through regulatory approval in most cases but the pharmaceutical industry is far from a monolithic beast. It's segmented by a number of different business models and it's highly heterogeneous even within each layer of that industry in terms of resources, capacity, and track record. To put it bluntly, BPS is no GSK for people who know what the latter three letters mean. Clarkso Smith-Clarne. In keeping with the standard view that the private sector is better positioned to bring a product to market, the then federal minister of health, Rona Ambrose, claimed in parliament that BPS quote had the corporate capabilities to develop the Zbob vaccine into a fully regulatory approved product even though the company had never done so. At the time the agreement was signed back in 2010 the NML's internal capacity, however, to drive Zbob's development was actually diminishing. The scientists that had all played a key role in the basic and pre-clinical research including Feldman, Stephen Jones, Utti Strower they had all left the NML by late 2010. Further, scientists in the civil service at that time under the conservative government were subject to increasing constraints and resource uncertainties. Midway through the NML's Zbob project, for instance, the flexibility to carry over unused funds in a given fiscal year to the next was taken away. With financial and human resources in flux the NML contemplated canceling the project altogether. Judy Alamonte employed by the NML on a limited term contract volunteered to take over the project as a project manager. During 2010 through 2014, Dr. Alamonte worked through myriad challenges and delays with the NML and its partners. A poorly drafted contract with IDT Biologica that that's the German firm resulted in a constant stream of negotiations over who was responsible for each deliverable. Early on IDT struggled to create the Master Seed Virus Bank which is an important preliminary step in the manufacturing process. Near the end of the process Alamonte expressed growing frustrations with various delays on IDT's end, especially as the funding they'd secured from the Canadian Safety and Security Program was due to end in March 2013. On November 7th, 2012 Alamonte wrote to the IDT, I would like to see a priority put on this production. The grant funding for the project runs out in March and you would not be paid for it and we will be without a vaccine. November 26th of the same year, I haven't heard from you. I still have concerns regarding the delay in the downstream processing and bottling. I think this could have a negative impact on the final product and I would like to discuss it with you. The very next day, as you know the current production has been stretched out two months longer than it should be. You should have pushed to have your suppliers get the material you needed before starting production or you should have waited for everything before you began. After two failed attempts to generate the clinical trial material, that's the clinical grade quality version of the vaccine, IDT finally delivered 1,300 plus doses to the NML and Winnipeg in June 2013. Canada paid the German firm over $800,000 for that vaccine. BPS's contributions during the four years leading up to the West African epidemic are however less clear. Contrary to the terms of the patent license with PHAK, the disclosure package we obtained suggests that BPS failed to deliver a single written progress report during those four years. The documentation we obtained also betrays a pattern of delay. Originally, BPS had planned to use a 10 liter test batch of the vaccine produced by IDT for further preclinical testing. However, BPS decided to wait for the clinical grade vaccine. BPS's lack of alacrity in running preclinical experiments was matched by its lack of diligence in meeting with the FDA. So in May 2011, IDT suggested via Dr. Alamonte that BPS asked the FDA what types of adventitious agent testing would be needed to support an investigational new drug application. Lots of jargon there. That's the experimental stage for the vaccine that is still overseen by the regulator. What kind of testing needed to be done to start that application and to start a phase one clinical trial? According to the meeting notes that Alamonte prepared, IDT said that they would do so gently. This is in May 2011. The project meeting notes, or that's in June 2011, rather. They noted again, yes, I'm getting a little messed up here, in June 2011, BPS indicated they would do so gently in July. But an entire year passes before IDT, with Alamonte again acting as the bridge to BPS specifies a series of technical questions to be asked of the FDA. These are the questions coming from the German firm. Alamonte is passing on to the US firm to please ask the FDA about. Not until November 2012 does BPS report on what the FDA's view was back to Alamonte, who in turn fed that information back to the Germans. In terms of experimental contributions, BPS also failed to advance the file. It had planned in 2011 to proceed with both the vaccine and post-exposure protocols, seeing what happens when you give it before someone's exposed and after, for testing the effectiveness or efficacy of the GMP grade vaccine once it was in hand. Yet by the time IDT had delivered the vaccine to the NML in June 2013, BPS had decided that it wouldn't be doing those tests, leaving it to the NML to actually run that efficacy testing in the fall of 2013. So this figure here depicts just one of the many experiments that the group in Winnipeg ran under Dr. Alamonte, comparing the efficacy in animal models of the GMP grade vaccine they got from the German outfit to the sort of more crude version of the vaccine that they also had on hand. In short, none of the experimental objectives that BPS outlined in its development plan were actually completed by the company, save for the interaction with the FDA, and even that only occurred after a significant delay and the questions were actually supplied by Alamonte and the Germans to BPS. With the funding coming to an end, the NML prepared a final project report about the project, just as the Ministry of Health in Ghanaia reported tens of deaths. The outbreak was moving into an epidemic in West Africa. And yet the report was optimistic, emphasizing there was to be life after the project. The NML planned to transfer to BPS not only the immunological assays and accompanying treatment protocols, but also the GMP grade vaccine that the NML had secured from the German company IDT Biologica. BPS would then finally commence phase one, phase two clinical trials, not on its own, but in partnership with the US National Institutes of Health. The escalation of the Ebola outbreak over the summer of 2014 interrupted the knowledge transfer from NML to BPS. Instead of sending all the GMP grade vaccine to BPS, the Canadian government donated 800 vials of the Z-Baw vaccine to the World Health Organization for use in West Africa. Questions though began to be raised about the delay in the development of the vaccine that had been shown to be up to 100% effective as early as 2004. In November 2014, BPS sub-licensed the patent rights to Z-Baw to the company Merck, Sharp, and Dome. Meanwhile, using the NML-procured IDT Biologica manufactured clinical grade vaccine, the public sector paid for the first phase one clinical trials which began in the United States in October 2014, in Geneva, Hamburg, and Calife in November 2014. And the Canadian Center for Vaccinology also began a phase one trial of the Z-Bola vaccine right across the street at the IWK. BPS now owned by Merck, now owned by New Link rather, the other Iowa state company, received US $50 million from Merck for that sub-license agreement as well as an injection of almost $120 million from US government sources. A more than 10-fold increase in the contracts and grants it had received in the years before the epidemic. After assuming legal control of the Z-Baw vaccine, Merck earned recognition for its in-kind support of the clinical trials that were run during the 2014 and 15 epidemic, most notably the trial known as Ebola Sassoufi, phase three trial involving over 11,000 participants which found that the Z-Baw vaccine offers substantial protection against Ebola. Merck's role in that trial, however, was limited to providing permission to use the Canadian procured and financed Ebola vaccine. That's the acknowledgement, you probably can't read it. In fact, if you examine all the trials, you definitely can't read this, that were initiated during the 14, 15 epidemic, Merck and or BPS or New Link, which by that time owned BPS, were involved in only a minority. Moreover, the trials in virtually every case were run by and paid for by public sector entities and non-governmental organizations such as MedSense en Frontière. Eventually the epidemic subsided and through 2016, 2017 philanthropic and government sources continued to fund Merck's later stage development of the vaccine. Merck missed its target for submitting the vaccine to the US FDA in 2017, but with over 42,000 frontline workers in Ebola contracts vaccinated in the outbreak that's continuing to unfold today in the Democratic Republic of the Congo, Merck reportedly now has all the data it needs for regulatory submission. So what can we learn from this case study? On one level, I think the lesson is pretty straightforward. The agreements to commercialize need to be enforced. The patent license required BPS to deliver written reports on its progress. And from what we can tell, and I can tell you more about why we're confident in this claim, the Canadian government lab or PHAK above it did not enforce that term of the agreement. But I think the implications are much more profound. Our case study reveals how entrenched the conventional wisdom of that licensing out patents to the private sector for the purpose of commercialization has become as a practice. We have long known that diseases which disproportionately affect the world's poor command little industry attention. Yet even in that context, control over a promising vaccine is transferred to a company on the strength of the assumption that they are better positioned to take it to market. And yet the development of the Z-Baw vaccine suggests otherwise the NML performed the bulk of the experimental work, problem solve various technical challenges that the German company IDT Biologica encountered during the manufacturing process. Recall this figure of the two objectives of the project. The NML either performed or played a crucial role in assisting every single step in the pursuit of the two objectives of producing a clinical grade vaccine, developing the assays and treatments protocols necessary to get regulatory approval. All of that was done by the public sector alone or in collaboration with the German group. Beyond advising the NML scientists about the FDA's regulatory standards, BPS did little to advance the Z-Baw vaccine. Yet despite the contributions on the public sector side, we now know this Ebola vaccine as the Merck Ebola vaccine. At the same time, the public sector's invaluable contributions to the Z-Baw and its development occurred under conditions of precarity. The funding for the project took years to secure, only to later to be undercut by a federal government seeking to contain its civil servant scientists. The inventors of the Z-Baw vaccine all departed the NML by 2010 leaving Alamante, herself precariously employed to run the project. It appears with minimal institutional support, which brings me to the fundamental point I wanna make. These two aspects of Z-Baw's development that it was driven by the public sector, but that the work took place under conditions of and by scientists subject to precarity are not unrelated. They are mutually constitutive of one another. The NML chose to grant BPS a sole worldwide license without any track record of bringing a product to market. It disregarded BPS's failure to provide written progress reports and deliver on its developmental plan. The NML's decisions were at every turn clouded by the conventional logic of commercialization. And just as that conventional logic inspires licensing patenting rights out to the private sector, it can render precarious funding and labor in public sector science. While also obscuring the actual contributions of publicly funded research to therapeutic interventions, such as the Z-Baw vaccine. Put bluntly state funded and run science can in fact and in fact sometimes does more than it receives credit for. But so long as public sector sciences role is seen as de-risking promising therapeutic leads for industry, its capacity both fiscal and human is likely to erode or go under realized. So what then is the corrective? I think it has to start with educating university scientists, government labs and funding agencies about a broader range of options for pursuing translational research. To stop assuming that the only way to advance vaccines and other products is by patenting and licensing out to the private sector. Open science collaborations where publications and data are widely shared without restrictions imposed by intellectual property present one potentially disruptive alternative. Rather than supplying an additional market reward open science collaborations change the way that science is practiced and knowledge is generated. As legal scholar Amy Kepchinsky describes in depth, the global influenza surveillance network now known as GISTRIS is a decades old example of capital intensive globally distributed open science that is maintained through institutionalized norms of information sharing and more recently contract law in order to ensure that all participants in the global network enjoy some measure of the resulting benefits. As Kepchinsky puts it intellectual proper intellectual production without intellectual property that is IP without IP is not order without law. Other tools including contracts can be used to structure research collaborations define expectations and goals and enforce norms of information and benefit sharing. The challenge is that the very researchers who we might want to ask to experiment with those alternative modes of knowledge production quickly run up against a set of structures and practices that follow conventional commercialization norms are themselves uninterested and or otherwise too vulnerable to think critically about intellectual property, patenting and so forth. Heinz Feldman stresses he does not know anything about the patents on Zboth. He simply wanted to do his scientific work. His postdoc Raymond Flick journeyed from the NML in Winnipeg to the University of Texas at Galveston then up to Iowa where he had held his job with BPS for three years where he fundraised by fanning the flames of bioterror. His LinkedIn profile suggests he's still looking for work. And the hero behind the development of the Zboth vaccine leading up to the West African epidemic Dr. Julie Alamonte as the epidemic subsided, the NML decided not to renew her contract. Her last day at the NML was March 31st, 2015. She left hoping to find employment with BPS but landed instead at the National Research Council in Ottawa again on a limited term contract where she began to work on another vaccine against the Zika virus before she fell ill. These are not the folks who have the intellectual freedom much less the time to consider patent and licensing practices or to experiment with new approaches to knowledge production. And until we address those prior insecurities, employment and funding insecurity in our universities and government labs, I fear we are at risk of repeating the same mistakes that were made in Zboth and delay the introduction of that vaccine again and again. Here's another example of potentially the same thing happening which I'm happy to talk about or what little I know about so far. Thank you very much. Thank you Matthew. Sean's gonna have to make questions for that fascinating and depressing and discussion. So we've got time for questions. So if anyone has questions, please feel free. I mean, there's a whole audience but one of the places where that vaccine got tripped up was contracting to a company as you point out had no track record, et cetera, et cetera. But Merck obviously did and lots of other roads that we can make it come. Is there evidence that in fact the government looked for partners other than this little Mickey Mouse out there in the University of Iowa? You know that's what I was wondering. Great question. So let me tell you a little bit about the mechanics or what's behind this research and I'll just to do that all to be really transparent put up the requests that I filed in December, 2014. So we were interested in that very question. Did they try to source it to another manufacturer that might have more capacity? What other kinds of approaches were made? And so the wording of our actual request was not limited to bioprotection systems. Once I figured out that was the, because originally when those stories started to run a lot of this wasn't in the public domain but if you know where to look you can find some of it. Long story short and it is a very long story because we ended up getting two disclosures. The second one being one we should have gotten the first place but then came sort of in a different route. So we got about 2,000 pages worth of documents. Took a couple of years to get any of them and there was no evidence of anyone else being approached or approaching the NML. And the story or the response we get from the people in Winnipeg is that no one was interested. Not just in the private sector but the public as well. And so, and it's important to point out that so Merck wasn't interested then despite the promising early stuff. They became interested or were pushed to be interested as a manufacturer with the capacity in the midst of that epidemic which was obviously a great concern the world over. So if there is very little interest and that's sort of the point I'm trying to get at then why are we even trying to find these deals? Are there different, you know, and if the point is usually back, well they're the ones who have the expertise to do this work. And what I think the story nicely shows is yes there was some collaboration with other entities clearly with the Germans in particular but the public sector actually was capable of taking it much further than some might have thought. I don't know if that's helpful. And I think we forget that, right? Like I think we assume we can't. And maybe there are fault lines but I'm not sure where we are right now and the sort of logic of when we license out is required is the right spot all the time. The other vaccine that I sort of ignored a story just appeared in the Canadian Medical Association Journal in February is for a homophilus influenza type A. We have a vaccine for type B and I know there's some vaccine scientists in the room so feel free to jump in or correct anything I say. We don't have one for type A and it disproportionately affects indigenous folks in the North, in Canada. And because of the absence of the bigger market there are not companies clamoring to get involved in this. There's been a lot of research done at the National Research Council in Ottawa and yet they've licensed it to a very small company in the state of Washington again and they're waiting to see if they might start a clinical trial or can get funding to do a clinical trial. So I think there's a need to play with the model. And I've filed another one of these. But it'll take years to figure out what actually happened. Sure. I mean how much of this is driven because this is not a big money-making potentially, like it just wasn't seen as a sort of a big opportunity to make money, it's not a big market. I mean I think that's the reason why very few if any came forward. I think the company that did come forward came forward because of a connection to the lab. And so you don't get a lot of interest although what you see right with that piece of context I was trying to provide around the US funding that happened sort of post-911, post-anthraxcare was enough funding to support things like BPS but not necessarily enough funding to help them develop effective countermeasures but just to get those companies off the ground. That's essentially, BPS was founded to try to take advantage of those that new money. Query whether their goal was anything broader than that. So there's not a lot of market interest. We knew that then. The vehicles that benefited from the creation of Project BioShield, it's not clear to me that they had enough capacity to bring things forward so we need different approaches. I'm not saying that open science would solve this problem necessarily but I think it can disrupt or at least challenge the suggestion that the next step is always partnering. But to even pursue that kind of experimentation in the knowledge development process you need to give the folks who we would ask to do the experimentation. Dalhousie's faculty owns their IP here. Please go out and try different ways of trying to develop the knowledge you're generating. We need to make sure that some of those folks actually have some stability in their lives, some employment security to do that kind of work and you hear more and more in the faculty of medicine when you go to research talks that there are fewer and fewer jobs in academia so you've got to go to industry. And what I'm wondering about is whether you can take a critical or open-minded approach about what works best when you're vulnerable in terms of your job security. So I think this, I'm trying to make an argument for more state support for science obviously but then people also have to be willing to make different choices in how they use the knowledge they produce. There's nice examples on this morning but nice examples in small molecule development for cancer and other applications for chronic open-sighted. Is there an example to be more open? So there are people tinkering, that's what I would say, and having some success. The one I tried to use as an example that is old and a little bit more complicated than I let on, which is this global network which if we're talking about openness at the end of the day that's about information sharing and for those who may not know the global influenza system or research network involves countries around the world collecting data around what strains of flu are circulating and sharing that information so that we can both develop seasonal flu vaccines which many of us probably get every year but also against potential pandemic strains of flu that might be circulating. This network is critical and it's a very different approach than trying to contain that information and patent it with a view to sort of going your own way and developing for example a universal flu vaccine which there's of course a lot of interest in as well. So I mean I don't know if that's a satisfying answer because if there's a lot of history about how that network works and when however people remember avian flu from a few years back one country decided to stop sharing the country that was most affected by avian flu in Indonesia the information with the global network because they learned that some of the information they had shared had or they perceived some of that information was packaged into a patent application and they were pretty sure they weren't gonna benefit from any vaccine that might result so they just stopped sharing which provoked quite an international crisis and led to this reconfiguration of the network where they used contracts to sort of set floors of benefit sharing and information sharing and so the norms that were very informal for decades and decades after that network was set up were formalized and the scholar in the US has done a lot of work to sort of understand that and interview people in the network. So that's one large example that's very complex and there's some other ones that are using more open science models in the neglected disease space but I'm afraid I don't know them terribly well. I'm trying to do the background work of just introducing these possibilities to other folks but recognizing the challenges in terms of employment precarity to pursuing them. Yeah. So I mean so many answer is having open access and such like that it's impressive that the NML the Williams grade will publish anything in the science literature in the first place in terms of the closed system. Is there a way to change the understanding in the public sector about publishing and open up their access to publish some of this information? I'm sure they had much more than two articles of published on this vaccine. I could have gotten that one. Yeah. I mean Dr. Alamonte has tens of articles on it or she's involved in many of them but Heinz Feldman many more. So I don't think there was any constraint on their ability to publish although the intellectual property office in Winnipeg made sure that they were putting together their patent application first to my knowledge. I can't find a publication that precedes the patent application filing date. So, but I do think I know there was a lot of attention during the hard years to sort of scientists being muzzled at least we didn't see in the documentation in this case any evidence that the scientists that were doing this scientific work couldn't publish it because of that kind of political top-down interference but what is clear is that this sort of standard approach of filing a patent and hoping that attracts investment it was followed even when there's not a market at the end of the day or the kind of market that a bigger company like Merck is going to really go after as soon as it can. Yes, Max. I think you had a slide with all of the I think they're ongoing and completed kind of the trials you've done in this company. Yeah, you're just supposed to notice there's not very much rent which is the ones involving the company. Well, that's not true to follow up with us. I wonder if Merck or we just had funded any of that one or if the rent was simply they provided access there. So I'll tell you where this comes that's a great question because we're trying to figure that out. These are all emails that we got in our disclosure folks. There is it. So all of these are the trial identifiers. So if folks know of something called clinicaltrials.gov there's been a big push to make the research evidence much more transparent and at least in the US you're required by law to register trials. So how many people you're gonna involve in the study what are the end points details of the design so you can go and see them but there's not great consistency in how folks are identified when the information is updated. So who is a sponsor is a I think a loose term and the actual money changing hands is not transparent through this system. So we can't tell. We can then go to publications and look for a specificity in the acknowledgments and things like that. But again, like the one of the Ebola Sassoufi trial that was published in the Lancet that said thank you to Merck for providing the vaccine. But that vaccine, the 800 files of the vaccine that were donated to the WHO those came from Winnipeg from Germany to Winnipeg and then they went to the WHO. The vaccine used in that trial was the one from Winnipeg not Merck's. So Merck gave permission that didn't actually provide the physical thing. And from what I can tell all of the funding for research being done at Merck on this is coming from US government sources. So in 2016, they got a deal from the Gates-Gavi vaccine alliance people for five million bucks to continue working on it and stockpiling it. And to be fair, they've stockpiled a lot of it. Like they apparently have tens if not hundreds of thousands of doses now. So they've been doing that work. But in 2017, they got 40 million from the US government. So we're not clear when I talk to investigators if any of Merck's own money is being used. Their people are involved, right? So probably lots of being conned. But I think this is all funded publicly. Yeah, I think that the reason that's so interesting is that he sort of begs the question of does the commercialization of the Rewind Pads even apply to all of your companies is completely funded in everything all the way through. And you can see with a model where all the data you need to get regulatory approval and you just not exclusively open up a production under contracts with governments to supply this. So the Pads is really a windfall almost to PDS and regulation? Yeah, of 120 million dollars. Yeah, no, absolutely. I mean, and the common sort of policy response are like, what should we do about this? And people say publicly fund clinical trials? We are. We are. So we need to understand that. And so another piece that I could have gotten to in the terms of insights is to make a lot of this stuff more transparent, obviously. There was a lot of confusion in terms of what Rona Ambrose said in Parliament when she was questioned about this by the then minister of science, Kirsty Duncan, now a member of the government. She claimed there were no negotiations. We set the terms. There was two years of negotiations that we could see. So there, you know, and all of the deals that are done at universities, they're extremely rarely made transparent. And I think there's a lot of negotiation that happens in the dark and assumptions are made about what these deals should look like. The only reason I could find it back in 2014 and figure out BPS was involved is because it was an appendix to a financial disclosure in the US securities exchange commission's documents. And if you know where to look, you can get them. So I actually got the license without going through the access to information process. But these deals are seldom public. And so there's not enough scrutiny of them, I think. I suppose all of the public funding of the public funds and the trials to what extent of those organizations are providing response thinking about accessibility once the thing is approved and applications, which I guess it has been. The public money is funding these types of trials. There has to be some consideration of that. There has to be exclusively controlled product by firms who would love me. What's the commitment after that to making it accessible? Yeah, so the GAVI agreement, which was only for $5 million to Merck, supposedly requires them to make it affordable. No one can find the contract. I've talked to MSF regularly about it. We can't get it. So we don't know how strong that commitment is to make it affordable at the end of the day. I'm sure that will be very controversial if it becomes highly priced in some way or even a relative sense. The other piece here is that there's a paper by Stephen Jones and the scientific director at the time at the NML, Frank Plummer, in CMAJ in the last year. So where they're talking about Canada's Ebola vaccine and this has become a success story. And I think it is, but it's also too important to recognize how difficult this was on the inside. And if I couldn't do it justice, but the documents we looked at, I mean, without Dr. Alamonte, this thing would have stopped in 2010. All of the sort of more established researchers had other priorities or left. Heinz Feldman moved to the United States, Ute's store as well. So I really want to highlight the two things and think about them in tandem, which is that one, sort of the contributions that the public sector is making, but the other vulnerability of that system as well, so long as we think they can only take it so far. I mean, maybe if we realize we can go further, Dr. Alamonte and others might have been better supported and resourced. She had one tech, I think, helping her throughout this time. Speaking to our widow, he's talking about how she would pull over on the highway and talk to the Germans one minute and then call Iowa. Like, you know, this would not be where it got to by the start of the epidemic without her contributions. And yet she was extremely precarious. Are there any other questions? Thank Professor Herder once more. Thank you.