Larry Corey, former President and Director of the Fred Hutchinson Cancer Research Center
Moderator: Tian Johnson
Complied by: Anna Matendawafa – with inputs from Wilfred Gurupira & Maaza Seyoum
Webinar Recordings & Supplementary Materials:
Date: 24 July 2020
Larry Corey, former President and Director of the Fred Hutchinson Cancer Research Center and in 1998, the founder of the world’s largest publicly funded international collaboration conducting clinical trials of HIV vaccines, the HIV Vaccine Trials Network (HVTN). Larry Corey is one of the leaders responsible for bringing together the expertise and infrastructure of HVTN, the HIV Prevention Trials Network and the Atlanta-based Infectious Diseases Clinical Research Consortium in a national collaboration to speed the development of a vaccine to stop this coronavirus – the COVID-19 Prevention Network, CoVPN. Larry also advises the current Director of the US National Institute of Allergy and Infectious Diseases, Dr Anthony Fauci. During this dialogue with civil society, Larry will share his insights and perspectives on what this new formation means to him personally, his lifetime work at the HVTN and shares insights into what he thinks the private sector, civil society and community advocates can contribute to the collective in advancing the global COVID19 response.
During this dialogue with civil society in the private sector, Larry shared his insights and perspectives on what this new formation means to him personally, his lifetime work at the HVTN and shares insights into what he thinks the private sector, civil society and community advocates can contribute to the collective in advancing the global COVID-19 response. He also spoke about what lessons this new network can learn from HIV research and what lessons need to be unlearned.
QUESTIONS AND ANSWERS
*This section contains a transcribed account of the Question and Answer Session
So Larry the optimism around, and I’m sure you wouldn’t be doing this work if there wasn’t any optimism. So what makes us optimistic that at least maybe this time we might get it even though we started a long time ago to pursue an HIV vaccine. Why should we be optimistic this time?
Science is one in which you make advances on the backs of the people in front of you. I think what we have here in the COVID-19 program is this 20-year history of working in this HIV vaccine trials, building infrastructure, and global infrastructure. That is one of the beautiful things I feel about being on this program and working with South Africa. South African scientists have been so much important in the HIV vaccine trials network Glenda Gray especially concerning her role in the MRC as well as the PI and Linda Gail, you know hundreds of really wonderful scientists in South Africa as well as in Sub Saharan Africa helped us in this. And we’ve been able to continue to use that infrastructure that educated nurses, clinicians, and community recruiters and created clinics, and pharmacies and the kinds of things that are needed to do the kind of clinical trials and the sophisticated clinical trials with new platforms that sometimes require refrigeration, just the infrastructure needed to do clinical research you know frankly the pivot is essentially assembling an army which is what we have assembled in the prevention network of trial sites. Not only in my own country were essentially every trial has about 80 sites, but as we start the vaccines programs in September, your country has already started COVID vaccine studies as far as with the Oxford vaccine. Occasionally a couple of other vaccines, this sort of group of investigators, this infrastructure that is both a human resource infrastructure and physical infrastructure, was able to pivot Covid-19 vaccines effectively and at least in the United States. I think soon globally, and we will have this unprecedented effort. Starting Monday, we start a first of five,30,000 person trials. One that starts in July starts in mid-August, one that starts at the end of September, starting in mid-October, and starts in mid-November.Each one is the individual trail is 30,000 people, so for us, the cumulative total in the network is to recruit 150,000 people in a 5month period. We are averaging 2months per trial into this unprecedented effort to see if these vaccines work, how well they work and how safe they are. And I don’t think I have ever experimented in my life that, where I feel the outcome is both personal and important. I feel that these trials are a necessity if you ask me the one thing that I worry about: some political process in my own country will upset the outcome and not allow us to do these trials because I think they are important for us to know whether they are safe. Some of these vaccines are new platforms like RNA and DNA and some of the factors like the Oxford vaccine, and you want to know how safe they are. We made these trials 30,000 persons, so double the size that we needed to do them because we wanted to make sure that we had a great safety base and made sure that the vaccines were safe and didn’t enhance disease. We doubled the size to answer sooner because the more people involved, the faster you get to the number of endpoints to determine whether the vaccines work. Knowing that they are safe and knowing how effective they are, they are equally effective or some more than the others. And the third part is that not every vaccine platform is likely to work best for every person. There are many women of childbearing in the healthcare professions, and we need to know the safest vaccines to give to women who can potentially fall pregnant. We need to know the vaccines that work in pregnant women, and we need to know the vaccines that work in children. Do we feel comfortable giving an RNA vaccine to children? Most of the vaccines we have are from a safety point of view children, its protein vaccine, the Hepatitis B vaccine, the HPV vaccine, the Rotavirus vaccines, these are the most commonly used vaccines in children. We already know a little bit about the RNA vaccines that the second dose has a lipid envelope that the RNA’s are in and has a little bit of immunogenicity. I would be honest with you. I’m not sure I would want my grandchildren to get in RNA vaccines. I want them to get a protein-based vaccine, so if it’s equally effective. So I want them to get an effective vaccine. Still, in essence, we are vaccinating children to protect their teachers, protect their grandparents, protect their parents’ children do outright with this disease, but you know it’s as much as a societal thing. So a vaccine can be, has to be very safe to move into children. So that’s been the goal, the goal is to try and license as any vaccines. The press is trying to say that this is a race and their whole print vs. marathon metaphor. I think it’s something that I don’t think it’s useful, nor do I think what this program is called in the United States operation, work speed is beneficial, so it sorts of suggests that its cutting corners, to get there quickly. I think people must understand that we are not cutting corners. What we expect is safety. And what is taking out the inefficiencies and time in the United States government is essentially paying the companies to do this. They take risks into buying the vaccines and manufacturers at risk and then distribute. So the realities are that we are cutting the time of decision-making. Normally, if we do a phase 1 trial, there are a few months to organize a phase 2 trial. You do a phase 2 trial you spend especially if it’s a commercial company, a long time figuring out ( a )whether we want to invest in many millions of dollars into phase 3 trial and (b) grading up the manufacturing process of the vaccine in order to be able to pass a SAPRHA audit or an FDA audit. So, all of this is being compressed we do the phase 2 trials and food and drug administration, it looks at the data, and 10 or 12 days later, they say “okay the data, it’s safe to go,” and if it’s not safe to go there obviously are going to stop it. So I mean, that’s the process that’s being compressed as well as nicely is it that the government is buying hundreds of millions of doses. Now you know what our government says and what our government is sometimes doing; fortunately, it’s different. Well, no one is advocating and certainly not me the stance with the WHO, etc. but within the program of Covid-19 vaccines, they are buying from 5 companies,2 to 3 million doses and that’s over a billion doses of vaccines, and our country has 220million adults and 110million children. Hence, billions of doses are way above what’s needed for just our citizens. We are hoping that it intends to allow vaccines to be made and get to the people of the world. We are a global community. And if we are to return to life and have global commerce and travel and move things, we need everybody on the globe to be immunized. And that’s again why we need multiple vaccines. No vaccine can be made to rapidly immunize 7 billion people, not even partially, not even over an extended period. So we need to have multiple vaccines because the company World’s entire manufacturing capability is needed to get the vaccines in the people’s arms if they were
What do you think is the role of this collective collaboration between private sector, civil society, and the researchers? What do you think is perhaps the advice and the need that you see within civil society, public sector and private sector in this collective collaboration for the pursuit of a vaccine? What role should they play?
Each has a unique role, and I couldn’t agree more with you are having; and each has a unique position, and we have an unprecedented problem. I don’t think in human history there has ever been a disease that has swept across globally and six months, well look today,14,12 million, 14 million people. You know this is unprecedented, so it requires all of our resources to get us out of this. One obvious issue is the private sector working with the major pharmaceutical companies, not even the smaller biotechnological companies. They are the only private sectors with the manufacturing capabilities to make 500million and a billion doses, and I see the Indian manufacturers’ involvement, Chinese manufacturers. We are going to need everyone’s global manufacturing capabilities and forget the politics and the borders because you know the virus doesn’t recognize borders, doesn’t recognize like I said, my country’s red or blue states, whatever the different colors are for various political parties and various countries’ around all our continents. So we need, we are battling a global pathogen, and we need to use our global resources, so that’s a private sector. There are expertise, and they are manufacturing capabilities, they are multinational aspects of things that we are essentially relaying of them, the US-based or the European based because they are multinational and distribution systems to use those distributions systems for the vaccines they will make to put them into the people’s arms because that’s really what we need. So then what is the academic sector, what is the public sector coming with. Both provide the expertise and the academic sector that is, you know, working to do the clinical trials and advising the government sector interpretation and data on who gets what. And the last part is the citizenry, and indeed, I’m starting Monday and at this point, we as the citizens of the United States and you for your clinical trials in South Africa and the citizens of South Africa to participate in the trials, to step up and be part of the process to be the kind of, the individual hero that went on the HIV process, HIV therapy process, the whole issue of joining all of the therapy studies and being involved and certainly joining the vaccine studies. And we have had such excellent cooperation and tremendous success with the citizenry of South Africa, and I’m sure they will come through for the Covid-19 vaccines. There is no other way to determine whether they work or how safe they are; the volunteers are the essence of determining whether the vaccines are safe or how effective they are and allow the investigators to do this. So science needs the citizenry, and the citizens need science.
Are there any lessons that we need to perhaps unlearn with the experience that we had with the HVTN trials network going to the Covid-19?
Well, I think transparency, we have always tried to be transparent and communicate. I believe communicating, what you are doing, what you are trying to do, sometimes it’s not easy, and I think it’s a learned process. I think we are a lot better at communicating about what we are trying to do, the mission that we have, and the issues that are associated with that to the public, and I think that HIV is a very complicated disease, COVID-19 is a very complicated disease, and so I think the issue of how to, how to communicate. I don’t think we have ever had the resources to communicate enough to the public on HIV, and I think we’ve been resource constricted in many ways in those areas, and now we are not resource-constrained in our programs. We are starting an advertising campaign; we use public service and social media to explain to the citizenry and its importance. We have a lot of vaccine hesitancy in the United States, the issue of trusting the government, and what’s going on with racism in the country. These are prevailing issues that affect all of us and affect science. So we can’t ignore the milieu that we live, and they have tried to explain what we are doing and how we are doing it and try to overcome some of this to involve the communities that are at greater risk. For us, that’s an incredibly important issue that we enroll the kind of African American and the Latin population that has suffered the most significant morbidity from the disease; density is the fuel in the virus. It is the difficulty for people who are acquiring that, and we see that globally. So I think the issues of being a good communicator being able to have the resources to communicate are why these webinars are so important it’s why journalism is so important. Again, this is unique. This is a virus that’s affecting all of us. The issue is to try to explain it, the importance of masks, the importance of social distancing, how do we balance that, and the fact that social distancing can accomplish something. Still, it cannot achieve the whole thing. And hence again, you know to get our way really out of this requires science, it requires a vaccine, it requires monocle biology, it needs better therapy, and we have to understand that reality and explain it.
How are you dealing with the scepticism and negative noises around vaccination amongst our people? How do we deal with those negative noises about vaccination other than this Corona virus vaccination there was a growing trend against vaccinations in general and do you think any of that will change now? Is there anything we need to change, and the language about this vaccine about this vaccination, about how quick it will come. What are your thoughts about that?
Well, I thought it’s a challenging problem. The internet creates all sorts of things that sort of has its strengths and has its weaknesses. We can put up a website asking for people to join a vaccine trial, and we have 176,000 people in a week but yet there are many articles even in the New York times about how I won’t take a vaccine, so there is vaccine denialism. Some people you will never convince, I think, some people you will have to be very straight forward and very transparent about the benefits and the risks. I also don’t believe that you can cohere people, we can strongly recommend it, but people will look at what’s safe and not for a little while. And these are risks that I think; this is where committees, this is where luminaries, this is where cooperation’s that are trusted play a role in helping direct the narrative associated with the vaccine. This is why I think the trials are so essential to create factual information, data as to how effective and who is effective, and how safe it is. If you have that data, you can communicate that data on a knowledge base, and eventually, I hope that knowledge wins out. You know, we’re scientists, we believe in knowledge, we believe that reproducibility and knowledge lead veracity to the results. And if we have that kind of veracity in there, that kind of reproducibility, we will be able to explain it to the populace, we will be able to explain it to the government and that the constellation of that will need to be happening here because, again, the virus knows no borders. We have to essentially vaccinate all of us, not within just the United States’ borders or the borders of South Africa. We have to care about our neighbors? Because that’s travel is one reason, I think we have such an epidemic in the United States, and we have an endemic disease, and we’re not able to control it. There are many reasons, but we have lots of people with lots of geographies and excellent transit. And in the use of automobiles, on highways and the contacts, you know, we’re seeing a rebirth of the outbreak in Seattle, where I live because the farming community 100 miles away Yakima, where most of the produce most of the agriculture is, there’s enormous traffic. That’s where the outbreak was, and it’s transported back. And I, so we are our neighbors’ keeper here, and we have to be mindful of that.
Looking at the demand for vaccines ,it is obvious that the resource rich countries are going to have the privilege of having the vaccine first .How do we ensure that there is equitable distribution to other resource challenge countries and not to leave this market forces.The flu vaccine is 50-65% effective(I stand corrected). What % efficacy would you be happy with to define it as a good vaccine?
Both of them are tough questions; the shorter answer is the second one. Our trials are powered at 50 or 60%. To me, I’d love it to be 75%. And there’s a complication when you say efficacy if it can prevent hospitalization and death. It led people to have mild disease and doesn’t prevent infection. That would be an accomplishment, but it also would likely not stop infectivity in the spread. And we still would have to be dealing with this disease but maybe not the hospitalized part of this, and indeed, if we can affect that would be a great thing. Let’s say that any, so 50, 60 70% reduction in death would be a significant accomplishment. The issue of access is fundamental. And here, I feel good about what the HIV vaccine trials network has done. I think the ability to have such strong investigators in South Africa and have the kind of leadership that Glenda, Linda Gail, and Helen Reese, and all the other people we work with have been so vital that we’re able to have them participate in the trials. And there’s always been this sort of moral sense that as well as the discussion before vaccines going in that that if a country is going to participate in a trial, there will be accessible as soon as possible. One of the crucial issues is that the excuse used for lack of access takes time to manufacture this? Some of that is going away because, you know, the US government is putting in this money to have companies manufacture hundreds of millions and almost half a billion doses. And I think the companies and the WHO need to sort of put the foot to the fire. There certainly are some things going on in Europe for funds to be made to have vaccines available and for manufacturing capabilities to be increased. I still think that, to be honest; there’s still a worry. I still have a great concern about access, and I, as a researcher, you know, have no way to build a plant. I know the flat philanthropies, and the World organizations and GAVI are starting to talk about that. But I think here’s where the advocacy groups need to keep track of talk versus doing. Too often everybody flies to Geneva and eats dinner and talks, and doesn’t do much.I think this is one area where there has to be watchdog monitoring of the organization that plants are brought online. That it’s visible as soon as a vaccine efficacy is reached with a particular vaccine, there’s a manufacturing plan, and frankly, a push to know where those vaccines are going, and how it can what’s the cost and where it goes. And I think that’s the most effective advocacy when people picked the companies, and I believe advocates need to look and direct themselves at the companies and hold them accountable. It’s not just NGOs who are the WHO that turns the factory’s crank and defines where the vaccines go, what the factory makes, and how many doses get appropriated, and that’s the primary issue. If you have the staff, then there is a powerful lobby to direct where it goes. And if you don’t have the stuff, that is a very theoretical argument, and it’s like saying you want something in the-wisp. So that’s my feeling, and it’s genuine anxiety, and I think that’s one of the things that will be in your camp anyway.
Given that we are getting a 94% recovery rate, very low mortality rate and given that most of the countries perhaps have seen most of their peaks would we still that vaccine when it comes and should we be focusing on the vaccine in this moment in time or should be focusing on case management given the case that most of the people who die actually would be dying in hospitals and the have got these comorbidities.What is your take on antibody testing in assessing past exposure? How long does immunity last if indeed it exists?
Yeah, well here I think that the academic community can sometimes raise issues that you don’t, you know, you can almost ask the question: What’s real here? I think the fundamental question you’re asking is if you get infected, are you? Are you protected against reinfection? This is a simple issue, but the real problem is if you get reinfected, are you going to be at risk of death? Or if you get reinfected? Are you going to be at risk of some severe complications, and you’re going to get a vaccine-enhanced disease? And the answer at the moment is on a scientific basis. On an encouraging basis, I think that it appears that reinfection, maybe if it occurs, is unlikely to lead to the highest rate of being on a ventilator or that you see with acquiring infection de-novo for people high risk. I think we sort of know that because we’ve seen a lot of viruses still circulating in Europe and Italy, in the United States in New York and Seattle. And there are many asymptomatic carriers, and you know, a lot of people have to be re-exposed. And you’re not seeing a vast number of case reports of people who said, “Gee, I had COVID-19, and I was in the hospital, and now, three months later, I’m back in the hospital now,” maybe we will have two years from now. You know, we do know antibody wanes, and we do know most viral diseases. Reinfection seems to occur; we see that roof spiral so efficient social virus, we see that with influenza, we see it all the time. At least for many of them. The second and third infections are not as severe as the first infection and don’t have reality, but each virus is different. And I don’t think we understand the paradigm here. So the sort of the first axiom of infectious diseases respect your pathogen, and this one deserves respect. It is a formidable foe. Now, I don’t think it’s as formidable a foe is HIV. Okay. But this is a formidable foe. So I, you know, I’ve given you a long-winded answer to say that, (a) I don’t know. I am cautiously optimistic that quote, there is such a thing as an immunity passport. That doesn’t mean you won’t acquire it and you couldn’t transmit it to your parents or your grandparent or something else. I mean, an immunity passport implies that, at best, you’re protected from getting this. It doesn’t mean that you’re not a vector of other people. Doesn’t mean that you know, hey, I can hang out in a bar. And I’m going to for sure that be able to transmit it, get it again and not transmit it. You may be able to get it also and not know it. And then you become a shelter and a transmitter. So we don’t know that.
Is there a different antibody response and duration that we see in the few cohorts in Africa? So how would you then structure some of the studies elsewhere? Would it be different for what you see in various parts of the continent because of the antibody responses you anticipate in the other strains that are perhaps being observed across the globe, Larry? is there a cause for concern? Should we be having different platforms because of these different antibody responses that we have seen?
There is always a cause for concern. I mean you can in the lab, you know, show that there you can mutate with monocle antibodies, where the virus attaches and where the molecule is. Now, whether these vaccines will induce the non-immune response to multiple places so that there are other antibodies will revert to the kind of genetic variations that will occur. I would say the molecule offers more significant potential for the virus to mutate a way from its effectiveness than a vaccine at the moment. And I guess again I will just say that we will have to wait and see if we vaccinate an enormous number of people and the virus mutates away from that. Just like influenza, and you know there are a lot of precedents for RNA viruses to do that. How long it will take, you know at the moment it’s only two base periods a month which is like, you know a few hours for HIV, you know, so it’s not doing it but, you know, the point is, it’s where there are changes. It’s a possibility, and I think that we again have to monitor and see what happens, but I don’t think it’s relevant to the vaccine trials we are undertaking in the next six to eight months.
Considering that vaccine development usually takes a long time and here whilst we don’t have time. When do we foresee a vaccine coming and also how would it define the success of that vaccine, as in what kind of efficacy are we looking at to prevent disease transmission and stop the pandemic?
Well, I think you are asking difficult questions, and I think some only time will tell, and you know collecting that data, we have to go on conscious optimism. I think the first vaccines will become available with luck. We will see whether they work with chance and at the end of January or February. Now I have to say that those are RNA vaccines, and there is a lot of issues about making RNA and how widely the lipid molecules can be manufactured and the cold chains and all the other things that go with it and the novelties. The next vaccine, the Ad vectors, and ChimpAd vectors, if they work and work as well, they may be more readily available and usable to be manufactured in more significant amounts for worldwide use. I think those wouldn’t know till March or April, so I am already giving you months of, gee, it’s July, you know, that’s another seven months in this. And I don’t think I can tell you to give you much more optimistically than to say that, that’s the situation of knowing, let alone how do I get that happening. But I think that South Africa is involved in these trials, not the RNA trials. Still, the ChimpAd and Ad26 vectors and I think one of the issues that whose, the government and the citizenry and the investigators who are doing that trial to make arrangements to essentially get this vaccine made available to South Africa at the same time that it’s going to be made available at the United States or Brazil.
Is there a price at all that you have in mind around affordability and scalability to have a vaccine for all. Is there such a thing that if only I get this vaccine under a dollar, I don’t know what the amount would be and then I know I’m optimistic that it may be perhaps available. Do you think of such issues at all?
First of all, I am not an expert in this. I am just here; here is only an opinion, not even me as a scientist, but me as just a person. I think that this epidemic has had devastating consequences, so that price is not an option here. The governments need to come up with respect with philanthropists all the globe, and governments need to chip in and make this available for all. Because we are all not protected as much as we should, unless we are protected with the vaccine, I also feel that price gouging is not what this is all about. I at least saw cooperation between pharmaceutical companies, and companies aren’t cooperating in this arena. Now I don’t think it’s just altruism; to be honest, I also believe it’s self-interest. Their business of healthcare has been decimating. No one wants to go to the hospital, no one wants to see the doctor, and they have big businesses that are taking a hit, and still, they are also motivated to get a vaccine, and essentially, now I think price gauge and do that in a way. It makes sense for the rest of their business, so I believe there is a lot of favorable economics and clear need, and again I believe citizens need to be watchdogs. There needs to be transparency and realism on both sides. Governments should come up with the money for their citizens for this. We are all being quarantined, we are all being, you can not go out to eat, you can’t do this, you can’t do that, why is it that you can’t fly an airplane, you don’t want to fly out in a plane, but you know, but why would they want this to persist. What else is more important?
Can you hazard an educated view, what is it that makes it so different, the viral spread. So you spoke earlier about density being a key factor in how the virus spread but Nigeria is one of the dense countries but hasn’t seen as much,India we also haven’t seen as much ,Brazil is dense and South Africa again so we can understand that. I’m just curious in terms of your thoughts.
My simple answer is no. And I’m puzzled that I would just say that. I don’t think I’ve ever seen a situation in my life where the virus has infected so many people that, in my mind, we know so little about the virus with the modern sciences that we have. To me, it’s very puzzling as to how infectious it has been and the sort of the differences in epidemiology that we see. We find that the virus has shed one and a half to two logs higher than we see with flu. And so tighter makes a difference, but yet it’s curious. You know, here’s a virus that infects the nose enough to stop your ability to smell, which then interferes with your taste, and it doesn’t appear to be neuronal. It’s not going into the brain. I mean, it can, but it doesn’t look like that; it’s the routine aspect of it. So, there is evidence that it replicates in high titers. Still, we don’t understand why someone of my age has a high death rate versus a three-year-old, what’s, and you can duplicate that in animals, old macaques. And old mice die of coronavirus, SARS-COV-2 more than young macaques and young mice, which has something to do with the native immunity. That is not figured out. And all this changing epidemiology of what’s recognized, what is asymptomatic, what is just under reported, I think there’s a lot of puzzling public things about the epidemiology and what I’ll call the underlying parthenogenesis as to why children do so much better than adults. So, or elderly adults, so, I don’t have an answer. I think we haven’t had much time. We’ve been so overwhelmed by the medical aspect of care. Yeah, that the ability to do the science is just starting to emerge, you have to be able to think you have to be able to, to master sort of the resources, your first resource has always been to take care of people. When you get done with that, you can start thinking about how you know, well, what, how do I investigate what I’m seeing takes time.
Do you think that it might be valuable to start changing some of the language just to allow maybe success of trial enrollment but even just the understanding of what the trial is about?
I think your perception is a really good one. You know sometimes as scientists you get immersed in things; you don’t see it as how other people see it. I’m listening to what you are saying, and I think those are good thoughts.
Is there global collaboration in vaccine research, in other words in the USA, Russia and China communicating and collaborating in COVID-19 vaccine research and is there global oversight of the quality of vaccine research?
Well, science is global, but that doesn’t necessarily mean communication is international. I think regulatory agencies play a critical role in countries, and I think regulators have great respect for them, and they are tied to each other. They’re connected to governments, and the rules of the game require anyone involving, you know, experimental implementation to interact with the regulator in a country. So, your regulators in South Africa will know a lot more about Chinese vaccines and Russian vaccines. And I would know, which are not entering the United States nor being tested in the United States. And so I just would stop there and sort of say, yes, it’s great to have a global effort. But scientific communication is pretty ad hoc and not always coordinated. And that can be both good and bad.
So any closing remarks to this audience that we have today that are so keen and eager, and they are saying go, Larry, go as you lead us hopefully, to March, April when we get a vaccine. Any closing remarks, Larry?
Well, thank you. It’s a pleasure and an honor to be with you. I learn every time I do one of these things. It’s terrific to enact and interact. I hope I’ve made some remarks with utility, and I also said the same thing. I am leaving you in great hands if not better hands of Professor Gray’s exceptionally terrific and quite knowledgeable. And again, it’s been a pleasure interacting with you