When the Covid-19 pandemic comes under control, “we are not going back to February of 2020”, in how we control other diseases such as tuberculosis and malaria, says Trevor Mundel, the president of the Bill and Melinda Gates Foundation. The pandemic has shown how government regulators, manufacturers and companies can innovate faster and continue to do so in the fight against other diseases, Mundel explained. “This is the new normal standard.”
This is the first time that a vaccine has gone from inception to phase 3 trials, which involve human trials, in seven-eight months. What is the kind of research and innovation needed to produce the solutions the world needs? And is the pace sufficient? We asked Mundel, who has been the head of development at Novartis and has worked in clinical research at Pfizer and Parke Davis. He is also a medical doctor with a PhD in mathematics from the University of Chicago.
Excerpts from the interview:
What happens when a doctor is also a mathematician? What really rules in this case?
Well, I have to say that a lot of the work in the biomedical sphere has taken a data science turn. And often, it is a question of looking for targets and new opportunities in terms of therapeutics – it could be vaccines all well. And that comes through dredging through a lot of data. Certainly, having a background in analytics is very helpful. I may not be a frontline practitioner anymore, [but] I am able to keep my teams on their toes.
How do you see data science contributing to innovation in health and medicine? Your own training in a different era is perhaps actually proving useful today. Do countries like India or young people in India, have an opportunity here, which they perhaps did not have earlier, to pitch for projects and build new collaborations?
Yes, indeed. I do see data science applied in the right way as very foundational to our enterprise. And it gets to the issue of the burden of disease and how that is differentiated in different countries and sub-nationally. Even in India, there is a great divergence between different states. And if you are not aware of the risk factors that are differentiated between different regions, then how do you intervene rationally? Then you are really just going in blind.
Assuming that one region is the same as another is a complete mistake. So, I would say, one of our biggest investments of the [Bill and Melinda Gates] Foundation, certainly since I started, has been in improving data science: Understanding at a very local level, from primary data as much as you can – not just extrapolation and models – what is the burden of disease and what are the local risk factors, so that we might know how to best intervene.
Let us talk about vaccines. We all know roughly where the world is in terms of rolling out vaccines, different countries are at different stages. What is your sense of the efforts so far and what more needs to be done to either speed up or ensure that whatever is finally rolled out is safe?
The vaccine enterprise has really shocked me, I would say, in a positive sense. And we are now getting to the phase where I think in the next few months we will get some “readouts” from the leading vaccines – leading in the sense of having started their phase 3 studies a little bit earlier – whether they are actually effective and we will get the first read on safety.
Probably first out of the gates will be mRNA vaccines [messenger Ribonucleic Acid]. The others in contention would be, for instance, the Oxford-AstraZeneca and the Serum Institute vaccine. There we may get some data as well. But, if you think about that enterprise, in October-November some time, we start to see what is happening, when this enterprise really started in March.
So, the concept of a vaccine going from scratch, from the design of the epitopes, the antigen, to something that has completed a substantial phase 3 study in eight months – if I would have told you that one year ago, that was even vaguely, vaguely possible, you would have said I am crazy.
So, I do think we have seen a sea-change in the vaccine enterprise of what is possible and we really have to capture these learnings. We have been struggling with vaccines for tuberculosis, for malaria, for HIV-AIDS for years and years, on timelines that seem to stretch for decades. Was that really necessary?
I know that we should absolutely be focused on the safety of these vaccines. And that would be a point of no compromise at the end of the day. But the studies that have been done are substantial – tens of thousands of individuals. And I think we will get a good read on that safety and then we need to introduce things. When you introduce new therapeutics, new vaccines, you need to have a decent system of pharmacovigilance. There may be unintended events that occur, but if you are not looking for them and tracking them carefully, then you might not know until it is far too late.
The Grand Challenges [of the Bill and Melinda Gates Foundation] effort supports innovation by offering grants, catalysing the system of innovators, researchers and scientists. Walk us through the over 3,000 grants you have given. When you look back now, what has it done and what it is doing?
It kicked off with an initial 14 grants back in 2005. And those were substantial grants around 14 different topic areas. I will highlight one of them, which was called Target Malaria, which actually ended up as an effort to attack the problem of dengue via vector control.
That, in the last two years, has delivered evidence that releasing bacteria-infected mosquitoes that replace the normal Aedes Aegypti mosquitoes – the main vector for dengue – can somewhat dramatically drop the incidence of the diseases spread by the Aedes Aegypti mosquito, which include dengue, chikungunya and Zika.
We had some studies in South America, a particular study in Indonesia, which looked very positive. That enterprise is now developing a model whereby it can distribute this to countries that have a dengue problem or other diseases related to the Aedes mosquito. I would say, for the initial investment, that alone, to my mind, is a great justification.
Since that time, we have made 25 other Grand Challenges – the larger Grand Challenges – and 110 of what we call Grand Challenges Explorations. You can write a very short application and you might get a few 100,000 dollars to explore your idea, with the prospect that the new ideas that come out can then go to the second stage, where you could get more substantial funding.
I have not been completely satisfied with the notion that people just get together and talk about problems. What can they do to solve them, particularly in a collaborative way? So, we have these scientists from diverse countries, at a particular venue, can they not come up with some new ideas for collaboration around some of the key problems that we face?
So we announced, this year for instance, that if you have your own idea, we would give you a $100,000 grant, if selected to explore that idea. But if you have a collaboration with somebody else, from a different part of the world, we would give you $200,000 to explore that idea. I will be excited to read what ideas came out of this meeting, of real solutions, as opposed to just “we got together and debated things”.
As you look back at all these ideas that you have catalysed, what does it tell you about the role of a catalyst in healthcare and medicine innovations?
What I found is that there is a tremendous passion around the world for global health problems, for problems that impact society at large. And there are a lot of scientists – it may not be their main direction and they may be doing research in some other directions – but they think about these problems.
And the barrier to them really applying their ingenuity to these set of societal problems at large is that they often do not have seed funding because they are not experienced or they do not have a track history in that particular area. So by giving them that seed funding, my intention is that we can have all of the best scientists working in whatever areas to come into the global health enterprise and solve these societal problems.
When you look at vaccines, there is also the issue of equitable distribution. The debate on this just seems to be beginning and it is likely to get fiercer. What is your sense?
That has been our point of departure, in all of the efforts – the vaccines, the therapeutics, the diagnostics – which is that we fundamentally believe that any of these tools or opportunities that are available in wealthy countries need to be accessible to people everywhere, on an equal basis, and there should not be a waiting line for access to these life-saving interventions.
So, on the vaccine front, I have to say, India has been a tremendous contributor because of the strength of the vaccine industry. As you know, GAVI [the global vaccine alliance] is the institution that we have invested in heavily to distribute vaccines to lower-middle income countries, which I think has been quite a successful venture. And 70% of the vaccines that go through GAVI actually come from India.
Of course, when we were thinking about equitable access to vaccines, we turned, in the first instance, to the very good Indian manufacturers. And you would have seen some of the work we have been doing with the Serum Institute of India but also the other manufacturers, BioE [Biological E], Bharat Biotech. All have strong vaccine efforts now towards Covid-19. So we really can expect the supply that we need to address the equity issue. By and large, a lot of it is to come from India.
You have talked about the time taken and how we have gone from start to roll out in barely seven-eight months – and the contrast with traditional or legacy diseases, such as tuberculosis. So if we were to put in the same kind of firepower and investments, are you saying that we could find vaccines much faster for some of these traditional diseases?
I am really hopeful of that. Often, when you attempt some new approach, whether it is mRNA [messenger ribonucleic acid] approach for a vaccine that has not been tested before, then the first effort that you make often does not work out as you intended, it may not work very well, it may need to be modified. And so you often have to go back and iterate.
But if the loop of iteration is five or six years, then how many times can you do that? If the loop of iteration is less than 12 months, within a few years we could have started with something and progressed from very difficult vaccine areas to a much better construct within that five-year span. So it is all about innovation in vaccines and in therapeutics as well – it is about iteration, if you want to get that innovation practically into use.
How do we calibrate our efforts? Let us say, vaccines begin to roll out in the first quarter next year and maybe by the middle and third quarter of next year, 2021, there is some sense of control over this pandemic. How do we recalibrate or refocus our efforts to fight traditional challenges, including all the ones that you have been fighting all these years – TB, malaria and so on?
I think that is exactly our opportunity and risk. My nightmare would be that we are starting again, with any of the work that has been delayed on slow-moving epidemics – HIV, tuberculosis, malaria and others – and we start again from where we left off in February. That would be a big mistake because since February, we have learnt a lot about how regulators, for instance, can jump in and accelerate innovation–not in an unsafe way but just by being available to companies for a real-time ongoing dialogue.
If the company has an issue or the regulator has an issue, you can send a note to the company for a meeting in two months or three months, the usual kind of process. Or, there might be an immediate phone call to address the issue. That saves a huge amount of time.
So just the interaction between the regulators manufactures and the companies to enhance innovation by improving that connection would in itself be transformational. Those are the kinds of events that have occurred now. We need to set the expectation–this is the new normal standard. We are not going back to February.
As a doctor yourself, though not a practicing one, what is your own learning from the way you have seen Covid-19 progress? What has been your personal journey through this entire period?
It has been, I think, difficult for everybody in terms of the massive change of lifestyle, of interaction with people, the isolation that has come out of this. With my own group now, everybody distributed, working from home, I know people have struggled a lot. I am not excluded from that group.
The amount that we have been able to accomplish and how we have learnt at the level of molecular biology of this infection, which has turned out to be vastly more complicated than anybody could have guessed. What is emerging now is that you almost have these two phases in people who progress to the more severe disease.
An early phase may be driven by viral replication but then a second phase that can emerge at some delay where it is an autoimmune reaction, an endogenous effect. We have seen that something as simple as dexamethasone steroid is helpful in the later phase but not in the early phase.
Now, none of these things we knew before, but the ability of the medical system to actually take these learnings and incorporate them into treatment and therapies – you have seen the death rates drop dramatically, not because we have some completely novel therapeutics but just being able to patients prone, for instance, and reduce the need to put people early on ventilators. There has been an acceleration of this learning being put into practice.
To stand on the sidelines and in some ways have some insights of what is going on, is an amazing journey for a physician. Almost an entire career’s worth of knowledge about a disease entity telescoped into these eight months. Amazing and inspiring but, at the same time, tragic for the consequences that have impacted so many people.
This article first appeared on IndiaSpend, a data-driven and public-interest journalism non-profit.