Dr. Jerome Kim: Director General of International Vaccine Institute (IVI)

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I'm Geicawasaki and this is remarkable people. This episode's guest is Dr. Jerome Kim. He is the Director General of the International Vaccine Institute. The International Vaccine Institute was established in 1997 as an initiative of the United Nations Development Program. Its mission is to discover, develop and deliver safe, effective and affordable vaccines for Global Public Health. Dr. Kim has a BA from the University of Hawaii and an MD from the Yale University School of Medicine. He completed his training in internal medicine and a fellowship in infectious diseases at the Duke University Medical Center. He was the principal deputy and chief at the Laboratory of Molecular Virology and Pathogenesis at the Military HIV Research Program. He also served as the project manager for the HIV Vaccines and Advanced Concepts Evaluation Project Management offices. He led the Army's Phase 3 HIV vaccine trial, the first demonstration that an HIV vaccine could protect against the infection. He has authored over 200 publications. He was named one of the 50 most influential people in vaccines in 2004 by the Vaccine industry organization Vaccination. Another of his claims to fame is that we went to the same high school in Hawaii, Iolani. We even had many of the same teachers, which we will discuss in this episode. I'm Guy Kawasaki and this is remarkable people. And now bringing you the straight scoop on vaccines, here is Dr. Jerome Kim.

How did you go from Iolani to Seoul, Korea, running an institution like this? That's quite the transition.

Yeah, it was.

It's funny because my senior year in high school, my dad lost his job. So I didn't go out. I didn't go to the mainland for college. I stayed at the, uh, worked in his restaurant on Fort Street Mall and, and worked on the weekends as a ward clerk at Straub. And that was the, that was my introduction to medicine. And so I already had known. I knew that I wanted to go to medical school. So as soon as I could, three years, I graduated and left and went about as far away as you can get to Connecticut for medical school. But in those days, remember? Right. I mean, you didn't go on interview trips to the mainland. I mean, you looked at a catalog and you said, oh, yeah, this looks like a great place. This is where I want to go. So for medical school then, two of my Iolani classmates were at Yale, so I, Michael Ho and Alan Tanaka. And. And you know, it was great to be. To actually start medical school, but have friends that you knew from high school there. And in order to pay for it, I joined the Air Force. The Air Force has this program where if you're in medical school, they pay for four years. It was a great program. And then they said, okay, you can go and do your residency fellowship at Duke. So I did, and I got a grant and got an extension. So I wasn't in the Air Force. And I. And I got another grant and I wrote to them again and said, can I get another five year extension? Because, you know, I'm doing research and it's really great. And they said the first Gulf War had started, so 1990, I wrote to them and said, can I have another five years? And I got this email back, who are you and why don't I know about you? And so they brought me on to active duty. They didn't send me to the Gulf, but they sent me to San Antonio to be an infectious disease doctor, which is what I was trained as. And then the guy said, Neil Boswell, he said, we've got this program with the army and they do HIV vaccine research. I think, you know, I mean, you're qualified. You should. You should go there. So I did. And I went to work for Robert Redfield, who is now the director of cdc, and his deputy was Debbie Birx, who is now, you know, serving as the White House coronavirus.

Wow.

And we did HIV vaccine research in the military because at that time there wasn't a lot of work being done on HIV vaccines. And that's how I learned about vaccines. Spent 20 years in the army with a brief interlude at the University of Maryland working for Bob Redfield and Bob Gallo. And then I went back to work with, under Debbie Burks. And, you know, the army sent me to Thailand to do a phase three trial for the HIV vaccine, which is still the only one to have shown protection against HIV infection. In 2015, I was up at 20 years and I got a call from somebody who said, you know, this international vaccine institute is in Seoul. They work on vaccine development for diseases in developing countries. Would you like to interview? And I thought about it and my wife said, Absolutely. Oh, we. I interviewed and they offered me a job. So for the last five years, I've been here. And we work on everything, really, but hiv, all those diseases that you can get if you travel somewhere that really aren't found in the United States. So, you know, I mean, IVI is very small. We're not that well known, but we are an international organization, so we have all the flags of our signatory. And some of the countries fund us, so, like who, World Health Organization, some countries fund ivi, and then we get money from the Gates foundation, the Wellcome Trust, and others to work on different kinds of vaccines. And so, in a sense, we're like a little biotech company. We have a lab, we generate our own vaccine. Sometimes we help other people with their vaccines. And right now, if you hear about a cholera outbreak, so the cholera is a very severe form of diarrhea. That's our vaccine. So it started at ivi. We transferred the ability to make it to some companies. One in Korea, one in India. And whenever there's an outbreak, our vaccine made by these two companies is being used to help control the outbreak. So we are a bit. I mean, really like a little company, but we're also a research institute where we do research in the lab. We help. We do clinical research to evaluate vaccines, and then we actually take vaccines and vaccinate large populations to make sure that the vaccines are working the way we advertise. So.

Wow.

And what's your current activity vis a vis coronavirus?

Yeah. And so with coronavirus, actually, we made a really, I think, probably the right decision. We decided to help other groups to develop vaccines rather than to develop one of our own. And in that way, then we can facilitate multiple efforts. You know, there are over 150, I think over 170 now, different efforts to develop coronavirus vaccines. And we can help any of them without showing favoritism. So what we do is we help the companies to evaluate the defensive responses. So when you get a vaccine, your body makes a defensive response against the virus or the bacterium. And our group, our laboratory, helps the companies evaluate these responses. And that's really important. So the US FDA or the Ministry of Food and Drug Safety in Korea will look at these, and that will be a part of the package that goes into them for approval. So IVI is helping multiple companies with that. And then also yesterday, we were approved to go forward with a vaccine trial in Korea. Hopefully, it'll be the first COVID 19 vaccine trial actually performed in Korea. Although we're still waiting it has to actually formally start.

And why do these companies, many of whom are more money than God, why do they need you to help with this process?

So actually, we work with smaller companies in Korea. There are four groups now that are working with us. And we can do something very simple like take their vaccine injected to an animal and check to see if the animal, if infection is prevented in that animal model, or we can just measure the defensive or immune responses that are made to the vaccine. And so we are trying to facilitate efforts by smaller companies and groups, many of which have real development efforts and activity and have funding to do it on their own through venture capital or investors. We thought it would be important to try and move these products along as well, because we don't really know what's going to work in the end. And so with a bigger company, we can actually offer to help them if they'd like to test the vaccine in Africa or South America or South Asia, because, you know, in the end, this is a global vaccine. And the other thing is, if you thought you were going to be able to test the vaccine in Italy or in England, in the uk, with the rates of infection going down, you can't actually test the vaccine there, or it would be more difficult. You'd have to enroll tens of thousands of people. Or if you thought, if you were a Chinese company, you thought, well, we'll develop a vaccine and test it in China. Well, you can't actually test the vaccine in China now because there aren't enough infections. So in order to test a vaccine, you have to compare the vaccine to an inactive substance and see if the vaccine prevents infection. If you're not having any infections, you can't do the clinical trial. So you have to find parts of the world where you can do that, and an IVI can help in parts of the world that companies, big companies usually don't work.

Do you pick the companies you want to work for or are you buying or selling your services?

Yeah, so we go to some companies where we already have a relationship. Sometimes companies will approach us, but typically we go out to different companies and say, this is what we're the International Vaccine Institute. This is what we do and how we believe we can help you. And sometimes that kind of approach works pretty well. So I think, you know, particularly for, you know, say, a company in Korea where you can't test a vaccine in Korea either, because there aren't enough infections. So a big Korean company that's developing a vaccine may request assistance from IVI to help develop the vaccine. Outside of Korea. And so we offer services to a lot of people and you know, it is a bit of selling ourselves. Organization that could help you do the animal studies, can help you with the assays, can help you do a clinical trial. And if you need help, we can, as we do for the smaller companies. The Korean company that makes the cholera vaccine, this was their first vaccine and we helped them with Gates foundation funding through the whole process of testing and evaluation by the Ministry of Food and Drug Safety, approval by the World Health Organization. So we can help along the entire spectrum of getting a vaccine over the finish line, over the goal line.

As a layperson, how do I interpret this? That there are 170 efforts going on? Is that like the more the merrier or is it just a random luck? I mean what, what am I supposed to be happy that there's so many trial tests, possible drugs going on or how do I interpret that?

Yeah, so normally it would be invisible. I. There were a lot of groups that, that in the 30 year history of, of HIV that have started work on an HIV vaccine only to fall away because the vaccines never showed enough generation of protective responses in animals or didn't do well in human studies. Early human studies with COVID 19. Because of the publicity and the intense spotlight that's been put on trying to develop a vaccine, a lot of groups are saying, well, we can do this, we can grow up the virus and kill it, or take a bit of the virus, put it into something like an adenovirus and then grow it up. And oh yeah, it makes a great immune response. And so the thing is that most of those won't make it. So when you look at vaccine development in general, 93% of the products that start out in the lab don't make it to the end. So if you had 176 and not all of them are really serious efforts, there's a good chance that large number of them aren't going to make it into humans. So over what we call the first valley of death in tech. The valley of death where you have a great idea but it just doesn't get, doesn't get any, doesn't get any traction. So that's the first value. It happens in vaccines. It never gets out of the lab. And the last thing you want is a vaccine that protects mice against Covid. You really have to test it in humans in phase one and then, which is for safety, say phase two, which really looks at the protective responses and then phase three, which looks at protection against infection and disease. And then if it works, the company decides, okay, we'll take it forward to the fda. And FDA says, okay, go ahead. You can market it. Dropout rate is 93%.

I'm surprised it's that good. I mean. I mean, that 7% make it, because it seems to me that this is a very difficult process. So, speaking of difficulty, so you talked about cholera, and, you know, there's typhoid and strep vaccines and stuff. And it seems to me that, like, those took so long to come to fruition. Why do we have people saying, well, by January, we might have a coronavirus?

And that's an interesting thing. The spotlight and the number of deaths is really important. I mean, this is a disease that is not a disease that's found in Bangladesh or in Yemen or in Haiti. This is a disease on our doorstep. And, you know, so it's killing Americans and Brits and people in the European Union, as well as people in China and Korea. I mean, over 200 countries around the world. So the visibility of it and the intense spotlight that's been put. I mean, this is the biggest pandemic outbreak of the last 100 years. And so there's so much intense scrutiny on it that we're saying, okay, we have to develop a vaccine. Because, I mean, in the US People are on lockdown. You couldn't leave, you couldn't conduct your business. The economy took a huge hit, and I guess Hawaii has 22% unemployed. I mean, that's incredible. And that can you. And the best way to get back to normality, back to the way it was, would be for us to have an effective vaccine, for us to vaccinate enough people so that we have protective immunity in the community. And that will allow us to get on with our business, go back outside, go to the theater, have friends over for a graduation party. Those are the kinds of things that are needed. And so what normally would take 5 to 10 years has now been telescoped. So where we would normally do this first phase for safety and then wait and look at the data and decide if we have to fix anything, and then go to phase two. Right now, we're telescoping them. So we start phase one before phase one is done. We start phase two because we've looked at the protective responses. They look good. People haven't had any side effects that we can see. And so we move on to phase two. We will look at phase two, and after we analyze the protective responses in phase two, we can start phase three in a population. So we go from 50 people to several hundred people to thousands of people. And we go from is it safe? To in the very end, is it safe and does it actually protect against the disease? And we can do that fast, hopefully. And so by the end of the year, maybe beginning of next year, we'll know the vaccine works. But proving it worked is only the first step.

What's the next step?

Sorry, the next step would be making it. I mean, making billions of doses, right? If you think there's seven, there are actually more than 7 billion people in the world and everybody needs at least one shot, one dose. Sometimes depending on the vaccine, you need two or three. So that's 14 or 21 billion doses. We usually don't make that much. So. And we don't need it as quickly. Usually you can roll out vaccination to different populations at different times. Now, you know, everyone's going to want that vaccine. And how are you going to make that much so quickly and distributed around the world fairly? And so those are. That's going to be a big issue.

Coming up, what is the most promising new vaccine technology that you are aware.

Of for Covid or for, in general?

For. Well, both actually.

So if you could answer that both.

Ways, the most promising, I think that the RNA vaccines, which is what the US NIH is pursuing with Moderna and which a German company called CureVac has.

Got, and I think now one of.

The other big companies that purchased one, have a lot of really amazing potential because you can make them fast. Theoretically. You can make a lot of it in a very small space. I don't know if you've ever been to a vaccine manufacturing plant, but it's like the old dull pineapple cannery. I mean, it's these giant 2000 liter stainless steel fermenters with pipes that go everywhere and a series of rooms and clean rooms. You could make 50 million doses of a RNA vaccine theoretically, in a classroom.

Really theoretically.

I say theoretically because no one's ever had to do it because there's no licensed vaccine yet. So that's the technology. If we had to, if we knew that works. So say this COVID vaccine, the Moderna vaccine works, which we don't know that it will, it becomes a platform. And the next time we have pandemic influenza or Covid 23, we can very rapidly make the RNA, which is already a platform for COVID 19 and, and begin testing it very quickly. Moderna was the first out of the box. They got their trial started in mid March, I think March 17th. We had known about the virus, really had known the sequence since, you know, the first or second week in January. Two months later we're doing our first test in human.

That would be incredible.

I mean, and that's the speed that you can move when you have an RNA vaccine. The problem is we don't have a licensed vaccine yet. So we don't know that they, you know, it generates the right immune responses. We know, we think, but we don't know that those responses protect, you know, and it could be useful for cancer. It could be. I mean there are lots. You could actually personalize a cancer vaccine very quickly. You know, you know exactly what you want to make in a particular person with cancer and you create a boutique RNA for them for their own vaccine in a matter of weeks and you start their injection. So it has a lot of potential because it's fast and scalable in theory. We don't have an actual example.

Part of my ignorance about what does license vaccine mean.

Okay, so vaccines are highly regulated, in our case the Food and Drug Administration in Korea by the Ministry of Food and Drug Safety. But every country almost has a regulatory agency that allows vaccines to be used in a country medicines as well. So the FDA regulates medicines. The Europeans have their own organization that covers most of the European Union. The Brits now have their own used to. And once again, and usually they're charged, for instance, the US FDA is charged with safe and effective medicine. Not everyone has that same requirement. Sometimes it's mainly safe, not necessarily effective. But in the US it's safe and effective. And for vaccines safe and effective is very important because you know, as opposed to a medicine, if a person is sick and you're giving them medicine, it's one thing. But when a person is well or your child is well and you're giving them a vaccine, you want to make sure that pain that you inflict on them or any potential safety issues are for a very well defined and significant benefit. So the government looks at all the data from a phase one, from phase one, actually they look initially at the animal data, then at the phase one, the safety data, then the larger test in phase two of whether the vaccine's generating the right protective responses. And then the phase 3 efficacy data. These trials generate 100,000 pieces of paper in the old days. Now it's like a computer disk or a series of high density transfers to the Food and Drug Administration on an electronic format. But it's still hundreds of thousands of document equivalent pages. And the Food and Drug Administration goes through every one. They'll ask questions like if you have lost too many patients in follow up or if you, you know, they notice that you weren't following the protocol which happens, or that you didn't get consent forms from people, they'll note these things and they come back to you as a series of questions and you have to answer them. And the worst thing is when their statisticians go through your data and they say, we disagree with your conclusion. You used a very funny definition here. And that funny definition allowed you to show an effect which we don't think is in effect. And that is not what you want to hear from the FDA because you just invested, you know, 500 million, $1 billion in a vaccine. You're sitting in this meeting and people are asking you questions and disagreeing with whether or not the vaccine should be licensed or approved by the fda. And what the FDA approval does is it allows you to market the vaccine. And for a company, that's the bottom line, right? I mean, you don't make money until you actually can market it. And then in the US and actually most countries, there's another step. Just because you have a vaccine doesn't mean that doctors will use it. So usually the doctors wait until there's a recommendation from the Advisory Committee on Immunization Practices, acip, which is a US Organization that says it's run by cdc and they say this vaccine looks good. It, you know, it has a cost benefit analysis that is favorable, it will protect children against, I don't know if your children were vaccinated against meningitis. B, my children were. And so you should recommend vaccination. And then pediatricians around the country say, ah, we just got a recommendation to use this. Your child is in the right age range, you should get vaccinated. And that's how the, you know, it's the approval to begin to sell the vaccine. And for the company that's the key anyway.

And with the CDC and the FDA involved, are we in danger of those kinds of rigorous science and testing being politicized?

So the FDA is supposed to be independent and so is the Supreme Court.

Right?

I mean, yeah. So the fda, the drug companies call it, the agency, they talk about, they say the agency is really tough on this. So right now the FDA is saying, you know, in order for us to approve this vaccine, we are going to need to see, and it's a statistical thing. When you do a clinical trial, you get an upper and lower bound of confidence of the confidence interval. In the case of a really effective vaccine, they want that Confidence interval to be above 30% protection. If it's below 30%, then the FDA is usually okay, I think you probably need to redo this or I mean we're not going to prove it above zero, but less than 30. I mean that's highly suggestive, but it's not enough. So the question is, and they're right now they're saying that for COVID vaccine, that's the requirement. Whether they will come under political pressure or whether they'll grant emergency use is really not known. In fact, there's I guess some speculation in one of the editorials that that may be a surprise political surprise in October. The fda though, they take their jobs pretty seriously.

I mean it, it took a lot.

Even, I mean a lot of lobbying to even get them to allow AIDS drugs to be used before they were licensed. But because of the, you know, because essentially AIDS was a, back in the mid early 90s was a disease that you got and then died of. They allowed an accelerated pathway. But the same thing applies. You have to keep records.

You have to.

I mean it's really. We call it compassionate use of a.

Medicine.

And it's important for cancer drugs and for some of the back then, the age drugs that were coming out that had these amazing effects. So it was good that the FDA did that, but they were very uncomfortable because their job thing that they are tasked with doing is to. Is to ensure that the vaccines are safe and effective and they take it very seriously. So hopefully they won't fall prey to political influence. And I think you pointed out that we've been surprised.

What do you think of human challenge studies? Which just to be sure that I understand what a human challenge study is, that you give people the vaccine or placebo and you purposely infect them and see if it prevents itself. So what do you think of that?

I think they have a real use. I came out of, I retired from the US army in the vaccine development area. And the army really has pioneered some of these human challenge studies. So I mean, it's not well known, but the current licensed, I guess approved malaria vaccine actually came originally out of the army, was transferred to gsk, which is a huge company. The initial set of experiments on that vaccine were done with volunteers. I mean the proof that the vaccine was protective. So you would give the. These army or sorry, they're often civilian, but some in those days, probably some active duty who volunteered, you gave them the vaccine and then you gave them malaria, a malaria that you could cure with a drug. So once they develop fever and you know, you can see the malaria parasites in their blood. You treated them, and under those circumstances, it's quite safe. And the army's done challenges with things like dengue fever, which actually is occasionally in Hawaii. And there have been challenge studies with cholera, which is a very severe diarrheal disease. We know that people lost 23 liters worth of fluid from their bodies. But again, you know, you can replace fluid and you can treat them. So it's done under very controlled, experimental circumstances. There's recently been a vaccine for typhoid that's been tested that way. So we did a study. We showed that it made the correct protective responses. That was sufficient to gain approval. But people really wanted to know if the vaccine worked. And so some doctors at Oxford did a challenge study, and it protected. I mean, it really protected well. And now, two years later, a formal study was done in Nepal, and it actually does what we predicted.

So. Great.

So it has a capability to accelerate vaccine development. The problems here are for Covid in particular. You know, we can give it to. So if you were going to do this, theoretically, you'd actually have to first determine how much virus to give. So you'd have to take a. Probably a Covid person, a person who had been infected with COVID who had protective antibody, give them a dose, and see that they didn't get reinfected. Now, we think they won't, because, remember, theoretically, infection protects you. Then you'd have to lower it or raise it to the point where you're comfortable with that dose. And then we have to go, all right, now we're going to test it in people who are naive, people who've never had Covid.

So to do that, you probably have.

To lower the dose significantly, challenge them if they don't get infected, begin to raise it step by step till you reach a dose that causes enough infection in enough people, but not so much that, you know, it's an overwhelming challenge, because one of the things we fear is that it's the size of the challenge that may contribute to severity of disease. So we want to start low and work our way up. So you can imagine that takes time. And in the US that challenge stock is also regarded as a medicine. So it has to go through the same levels of quality control that any medicine has to go through. Of course, the FDA is watching and telling you that it's okay to go ahead with the challenge in other countries. For instance, in England, it's not considered a medicine. So actually, challenge studies are easier to do there than in The United States. In some countries in the world, like in Korea, it's not considered ethical to do that.

So again.

Different countries have different approaches to this issue. So once you determine the right dose, then you start testing your vaccine. So you give a person a vaccine, then you have to wait usually a month or so after the final dose of vaccine, and then you challenge. So the question is, you could get some very useful information, but right now we're anticipating having a vaccine maybe by the end of the year, or knowing a vaccine works by the end of the year and, and, or early next year. How much time would you save with a challenge model? I think that's one question. If the first set of vaccines fails, then yes, definitely challenge model. You might need, you might want to have it. And why, what does the challenge, what else does the challenge model tell you? Well, it tells you if a vaccine works or not. But also because we have them under very, very strict conditions, we can actually draw a fair amount of blood from the volunteers and find something we call a biomarker. What's the biomarker? So you give a person a vaccine and then you measure the protective responses. You might measure the level of antibody that binds to and neutralizes virus, or you might measure the killer cells that are in the blood. And then when you look in the end and some people are protected and some people aren't, you can find this biomarker. Say it's a level of antibody, a 1 to 10 dilution or 1 to 50 dilution of antibody appears to protect people against infection. Well, that becomes something you can use. Instead of doing a trial in 30,000 people, now you can do a simple trial in several hundred people and look for just the biomarker. Because the biomarker is the marker that shows that a vaccine is protective. And so it shortcuts the system, allows you to more rapidly develop a vaccine. And then, you know, the first vaccine, we rush to get it, you might want to optimize it. But if you have the biomarker, you don't have to do a big huge 10,000 person trial. Do a small quick trial, adjust the dose or the interval between doses and the biomarker. We call it a correlate, a correlative. Protection is the thing that we are looking for. And the challenge studies really help you to define those biomarkers.

In the examples you cited, though, there was an important caveat in that. Cholera, you put fluid back. Malaria, a mild form. If you purposely infect someone and the vaccine doesn't work, what do you do? With coronavirus.

Right. So a great. So typically you. You want to have backups. So the case of coronavirus, you take people who are young, so I would guess under 30, they wouldn't have any other risk factors. So no obesity, no underlying heart disease or other things. We know that Remdesivir, so this is a drug made by Gilead, decreases the duration of illness. So you'd have Remdesivir there as a backup. There's some thought that these antibodies, that they're collecting blood from people who had COVID infection, purifying out the protective proteins and potentially using that as a treatment. So you'd have all these things that would be available. The important thing is when you're doing a challenge study, I mean, the ethics and the science have to be really, really carefully done. The ethics means that when you are getting a volunteer, you have to tell them, okay, we are giving you an infection. You're very young. It should be fine. You know, we don't think it will be. You could get very sick, though.

You could need to be on a.

Ventilator or be in a hospital. We have medicine called Remdesivir that, at least in one trial, seems to show an effect. And so you have to really carefully document all the things that you've told people you're gonna do. It's easier for a disease that has a fatality rate for young people under 1%. Or actually, in the case of COVID 19, initially, when we were just still learning about it, there were almost no deaths in people under 30. And even now, unless you develop a severe, one of the rarer complications, you're in general going to do well. But you have to be very careful and you have to really carefully explain because people have to understand what they're getting into.

That's the ethical guide.

And on the scientific side and medical side, you have to be absolutely sure that you can diagnose infection early, that you can provide some form of symptomatic relief and treatment. And it can't cost the volunteer anything. And there are people. I mean, there are people who will.

Volunteer for this because what's their motivation?

It's usually altruistic. They feel like I'm sitting down at home watching Netflix all day. I want to do something that will potentially benefit all of mankind. And it's really kind of an interesting set of things, that motive, or they know someone who died and they say, well, okay, well, you know, I've seen someone die. I really think this is something I should do. So it's complex. There are actually people, I think, I don't know if they're on the Internet, but they've talked to newspapers and said, yeah, if there were a challenge study and this could advance vaccine development more quickly, I would do it. The question is, at least for now, it looks like the first set of vaccines, we should get a readout of safety and efficacy by the end of the year and it'll take that long to get the challenge models up and running.

Now I understand a challenge test. So how do you test a regular vaccine? You just give it to thousands of people and see if they get it, but they may have never been exposed.

So yes, you definitely have to pick people who haven't been exposed. So I can give you an example. In the phase three HIV vaccine trial that the army conducted in Thailand with the Thai Ministry of public health, 8,200 people got vaccine, 8,200 people got placebo. And it was, you know, 16,402 people.

Without HIV and passion.

And you watch them over time. So in a traditional trial, typically you watch them for months to years. In our case it was three and a half years of follow up. And we tally the number of infections in the vaccine group and in the placebo group and you know, in our case there was 30% reduction in the number of infections in the vaccine group compared to the placebo group. And that was a little disappointing. At month 12 we saw 60% and that amount, that protection decreased over time. So we thought, ah, maybe we need a booster. So you learn something during these tests. But they're huge. This trial cost $100 million to conduct the COVID vaccine trials. They're thinking, you've heard the, I don't know if the number that people are throwing around now is 30,000 people per tr. So we did 16,000 and it cost, you know, 100 million in Thailand. If you're doing a 30,000 person trial in the United States, you can just kind of imagine how much that's going to cost. So if you're a drug company or vaccine company and you had to pay for this yourself, you're thinking, okay, I really want to make sure that what I take into phase three has a pretty high likelihood of success because I'm about to plunk down several hundred million dollars to prove it. And sometimes we actually have to have a second phase three trial. So that's a lot of money. And the companies are going, well, let's go back and optimize this some more. Let's think about it, let's make it better, let's fiddle with it so that when we go into phase three and we spend all that money, we're going to be guaranteed of success. Right now, because of the pressure, we're assuming success. So several people have said, well, we can make, we can have 100 million doses of vaccine available in January. Well, to do that they're going to have to start manufacturing before we know it works. So there are a lot of things that we're doing now that we wouldn't normally do. Why are companies willing to take the risk? Because somebody else is paying for it. So Operation Warp Speed is giving companies a significant amount of funding in order to accelerate development and de risk it for them. I think at least one company has decided to go do it on its own with its own money. But many companies have accepted the several hundreds of millions of dollars from the US Government or commitments of millions and millions of dollars from cepi Coalition for Epidemic Preparedness Innovations in order to make sure that they can accelerate the timelines and to ensure that they're not going to lose money on this.

Does the United States have the capacity to make the vaccine without dependency on China and India?

Yes. So the US has actually invested in a lot of different kinds of bio preparedness starting after 9 11. The ability of the US to handle a big flu epidemic, for instance, is probably second to none anywhere in the world. So the government has these mechanisms to put into place large scale manufacturing. The companies also have a substantial capability to manufacture vaccines. So I think. And you actually have vaccine manufacturing in the United States. If unfortunately you were like Germany, most of the vaccine manufacturing has left Germany for other parts of Europe. So how does the German government do it? Well, they participate in a global effort called cepi. CEPI has contracts with a lot of different manufacturers and they'll depend on companies to fulfill obligations under other using different means. But for the U.S. you have this organization called BARDA, which is meant to help prepare the U.S. for pandemic, typically flu, because that's the one, the usual one, but in this case Covid.

What.

If the vaccine is created or discovered by a country or a company that doesn't want to share the intellectual property? What if China develops a vaccine and says we're taking care of China first.

And I think everyone's concerned about that. I mean everyone is. So one of the things is that this organization of I think now 13 or 14 countries, the gates foundation and the Wellcome Trust, it's called CEPI Coalition for Epidemic Preparedness Innovations. The US is Not a part of it. CEPI was actually the first funder of a lot of these companies. So Moderna, which is an RNA company, Inovio, all of them were funded by cepi. Even this vaccine made by Oxford University got initial funding from cepi. In the CEPI contract it says that as a result of this, you commit to making the vaccines accessible and affordable. So there, at least for the non Chinese vaccines, because China is also not a part of this. There are commitments to CEPI for access. But yeah, I mean if China had a vaccine, they could in fact hold it back. I think that the president of China, Xi Jinping actually made a statement in the World Health assembly that China considers a vaccine for COVID 19 to be a global good and would be, would be willing to share the vaccine and make it available around the world. Now it's easy to say on the one hand, on the other hand, China doesn't have much disease right now.

So they won't have a market.

Well, they for instance, for a Chinese company now say there are several Chinese companies now in the second stage of testing. Some of them are huge. One of the companies manufactures 70% of the vaccines used in China. It's a large number of vaccines. So they're in phase two. Can they test the vaccine in China? No. So they'll have to form international collaborations in order to test the vaccine. So again, just the nature of the epidemic will compel certain groups to work with others, which is important. I mean this is a global pandemic. The solution is a global solution. I mean it's like this is a fire and you know, like all these seven alarm fires, there are seven engines pumping. You really don't want one of them to leave. You really need cooperation, collaboration. And so like these big companies are going around the world and talking to other manufacturers about potentially transferring technology to other manufacturers. I mean some of the these big companies and maybe I haven't been around long enough, but are talking about no profit vaccines again. I think now it'll be important to see what happens when the vaccine is actually there one hand. On the other hand, I think right now, even in the biggest companies there's really a commitment to this global health good.

You kind of have to say that the US has done a pathetic job, right? Of the 220 countries in the world, we're number three, 13 or something. And I think I looked at the statistics and normalized for population. The US has about 30 times the infection rate that South Korea has now. Why is that?

That's a, that is an important question. And you know, it's really hard to watch what's happening in the US from, from Korea. So you can actually. And I had the opportunity to hear someone from Australia talk about what they did. And actually the Korean experience and the Australian experience are not that different because they've both been successful at controlling the outbreak initially. And the first is that, you know, there is top down command and control now. So as a former military person, you know, command and control is very important. And a pandemic is like a war. And so to have a single unified chain of command. Korea did that. So once you reach a certain pandemic level, the person in charge of the outbreak, of the response, the government response, becomes the prime minister. And that means that everything flows down from there. And his deputy, his technical. Actually, the person really running the campaign is the director of the Korea CDC Centers for Disease Control. So you have an expert really embedded in this structure that is designed to make sure that decisions are made with data. They're made on the basis of science and not emotion. I mean, the things that were put into place, the changes that were made to tweak the process and make it better, are all things that are decided and implemented through the country. The US doesn't have that. The US has a state system. Now, they could pull things together, but that would require special legislation, special effort, special coordination. And that's been difficult because we don't have the structure in place. Korea set this up because of previous experiences. So they have the Infectious Diseases Prevention and Control act that puts all of this into place. And it's a law that was passed not during an epidemic, but when we could reflect calmly on, on what the best practices are. Australia did the same thing. They have a similar thing they were able to pull. Australia is federal, so it's like the United States. Each of the states is separate. The heads of all those states joined the cabinet, the national cabinet, in order to create unity of governance. So that means messages are consistent, governance is consistent. The information that's flowing down is clear and unequivocal. And both countries practiced. So they did tabletop exercises like war games for pandemics. Korea had one, right? In December, two people went on a tourist, Korean tourist went to China, came back with pneumonia, unknown cause, and they ran a tabletop exercise in December. And what happens in January? Outbreak. Pneumonia from people who had visited China. And so they had already practiced the scenario. The Australians had done exactly the same thing. Korea had the test kits available. Australia, when they found out about the outbreak, they looked at their stockpile and said, we have 20 million masks. We think, let's see, the estimate is a billion. How are we going to get a billion masks? They found a single mask manufacturer in Australia. The army and the Ministry of Industry built it up so it could make enough masks for Australia. I mean, so control.

Well, we do have a commander in chief, but are you saying the US's problem is a systemic problem or a leadership problem?

So it's a bit. So again, you have a federal government with responsibility and you have state governments. And right now there isn't an ability for the federal government. So, you know, the U.S. can nationalize, the National Guard, can federalize the National Guard. There is no ability to pull all these state departments of health into one group that thinks. And the data that is reported to the US center for Disease Control differs from state to state. So the CDC compiles data, but the data may not be the same. So it's, you know, you get apples from California and oranges from Georgia. You know, it's difficult. So that complicates, you know, data is important. Then there's the question of leadership. So you're seeing leadership at the state level. And the federal government has taken its role in a particular way. It has more authority. It could exercise authority. And you've seen it. Operation Warp Speed. They pulled all these federal agencies together, put a pharmaceutical executive and an army general together and said, you need to get these vaccines. So they've now picked five companies. They've given them $2.2 billion. I mean, the federal government has tremendous capacity to organize. And the thing is that they need to take control. And with the abilities that they have now, they don't have the authority that the Korean government has during a pandemic, during a. Actually, it's any natural disaster, these response things are set in place. There isn't an equivalent law in the United States that allows them to do that.

Then maybe you can explain this mystery to me. So my impression of Singapore is that it is as organized and, you know, as possible, Right? And yet they are very high on the list of normalized infection rates. So how come somebody, Lee Kuan Yew's great grandson, didn't say this is the way and what happened in Singapore?

So this is the problem with special populations. Singapore has a large number of migrant workers, and this population is not like the regular Singaporean population. The ability of the government to track and control it is less than is the case outside of the tenements where these migrants live. They're critical to the economy. Yet they're a weak spot. And as you would expect, as has happened in multiple countries, the COVID 19 virus has targeted the weak or found the weak spot and exploited it. You know, in Korea, the outbreaks were in churches. Actually, they continue now to be in churches. It's a very religious society and people get together and you know, it's difficult to control social separation. Now, a month ago, churches really weren't gathering. I mean, for instance, our church is still online, but other churches are gathering. And as you would expect, there's been transmission. You open up the bars and tell people, okay, it's fine. And all of a sudden you've got hundreds of, of 20 to 30 year olds milling around in a, in a club and you know, you'll have transmission one case to 300 cases.

So I can probably guess your answer to this, but the US is now getting about 20,000 new cases per day and 1,000 deaths per day. And if you look at those statistics, would you say now is the time to open up again?

So, you know, I think it's so you're. I think the important thing to think about is Korea never had to close. It was never a lockdown. We could go to the supermarket. Actually, we never ran out of toilet paper. It's amazing. I mean, through all this time, I mean, we wore masks. The supermarkets were less crowded, the restaurants were less crowded because most people did takeout and ate at home. A shutdown like the one in California or like, I mean, most of the US has devastating consequences. And so the purpose of the shutdown, the flattening of the curve, was really temporizing. It was only to gain you enough time to put into place the kinds of things you needed. The testing, the tracing, the strengthening the hospital system, getting more protective equipment, masks and gloves and face shields for people. It was only meant to be a temporary measure. At some point, no country can exist on lockdown, so you had to let it go. And so ideally you would have put into place all those things that would allow you to control the infection at a lower level. And to some extent, some states have been successful at it. And I think everyone's concerned two weeks from the Labor Day weekend that we're going to start seeing the numbers trend upward again. And 20,000 infections means there's still a lot of infection out there. And if you're not, I don't think the case fatality rate, the mortality rate is above 10, I think it's probably closer to 2 to 3%, which means that in the United States. There are millions of people who've been infected. We have no idea who they are, and they're spreading infection.

So it doesn't sound like you think we should be opening up here.

No.

So, again, you have to understand the outbreak. You need to be ready to pounce on major outbreaks. So you have to protect the people in nursing homes. You should protect healthcare providers. And the messaging around, you know, masks, distancing, have to continue. And when you open up the schools, it's gonna entail particular risk. You have to anticipate them, and you have to put into place a system that will make sure that if we start to see things, will be able to act really quickly. And people need to be reminded because, you know, in Korea, they've forgotten we were. It was difficult. I mean, there were days when we would. We went to a mall, beginning of April, a really, you know, big mall. It was the first time we could find parking on the, you know, first level. Parking. I mean, that's the extent to which people were really following. You only went shopping for things that you absolutely, you know, that you needed. And only when you needed it, you just. You didn't. People weren't going to coffee shops. And basically in Korea, there's like two or three coffee shops per block. I mean, it was really you, you got your coffee and you took it outside and you, you know, finished it somewhere else. But now you see people in restaurants and in shopping malls.

Would you catch a commercial flight in America today?

Would I, if I had to? If it was essential. How is my daughter going to get to college? I don't know. We haven't come to that decision yet. But, you know, if I had to, I would. And it's actually difficult for us. For instance, I mean, we work in a lot of countries in Africa and now in South America and South Asia. And sometimes some things we can do by video conferencing, some things like if you're setting up a new site to do a COVID vaccine trial, I mean, you want to actually see what's there, what people can do, where they are. You know, there are a lot of things that have to be done in person. So we're thinking about how we're going to protect the staff from IVI who have to travel to these sites, how we're going to get them in and around quarantines because we can't send a person. They're quarantined for two weeks before they get there. Then they come back to Korea and they're quarantined for two weeks. And how do we, how do we do that? So, I mean, I would travel if I had to, but if, but for vacation. No.

Let'S pretend that Donald Trump calls you up and says, we need help.

I'm going to make you the Coronavirus.

Czar of the United States. Okay, so you're in charge. You're the, you know, command and control. You're at the top of the thing. What would you do?

Ah, interesting question. So first, I think I would, I. So again, just thinking, like, I would divide the country into regions and appoint regional committees of states, because it's not only a New York problem, it's a New York, Connecticut, New Jersey problem, including Pennsylvania. We would come up with a set of rules that were based on best practices. And actually the CDC did come up with some recommendations that were subsequently modified. So I don't think I've seen the original recommendations. I would put into place much more effective tracing. I would strongly encourage the use of these handshake tracking apps, which aren't exactly what the Korean government has done. I think I would push Congress a bit to challenge them on the question of privacy versus the ability to know where the infection is. You know, so, I mean, I understand the need for privacy and I, on the other hand, understand that, you know, we have to control this pandemic and we have to prevent, you know, our grandparents and elderly neighbors from contracting an infection that has a 50% mortality. So, and I understand the impact on privacy. And I think that we as a nation are going to have to have a reasoned discussion on what these pandemics do and what the government can and should be able to do in the context of a pandemic. So, for instance, you all have been on lockdown, which I think is a real restriction on your freedoms. I mean, you can't go out of the house. I mean, in Italy, where my wife is from, the police will stop you and ask for your papers, your permission to be outside. That's a real restriction on your freedoms. So in exchange for that, in Korea, there was no lockdown. The Korean government, which again may be one of the extremes in a democracy, has the ability during this kind of pandemic to track your GPS signal for your cell phone. So when they found that single case in Itaewon, they immediately knew who had activated their cell phone between midnight and three o'clock in the morning on the following dates. And they use that cell phone information to send texts to people to say, you could have been exposed. Why don't you Come in and be tested. And when only 2,500 people responded, they said fine, we'll make it anonymous. We'll just send us your number, come in and get your test and we'll fact, we'll, we'll send you your test result. But if you're positive, you need to consider, you need to be under quarantine and you know, you shouldn't, will put you under observation actually in a government hospital if you're exposed then you should self quarantine. But they use this information now, anonymous testing to really try to contact all of the original 10,000 and then later much larger population of people who are exposed. So that's a discussion that Congress has to have and that the states have to have and, and it's really tough to do it in an outbreak. But you know, I think that's something that we need to start thinking about more practically. These tracking teams have to be trained and so you know, we have significant unemployment. Let's start utilizing people, training them to do the kinds of things that are necessary in order to try to really. And you can use these tracing teams for other things. They can educate, they can give, you know, they can provide some relief. Do we need teams of people who understand how to control infection, who can go and visit the houses of people who are elderly and really, you know, help them get the things that they need? I mean there are lots of things that you can do that will keep people busy, that will engage everyone in the fight. And again, you know, one of the things that Korea did and in Australia, I mean everyone was a part of this. So your contribution was important to help control this and defeat it. And I don't get that feeling. I mean, so it's difficult because I'm watching the US from afar. But this was an opportunity to unite us in something that unite us against a common threat. You know, you saw George W. Bush do it after 9 11. It was reasoned, it was careful, it was, you know, we're going to, you know, we're going to get out of this. But it also made very clear what the threat was. So again, I think the coronavirus task force, the daily briefings have stopped. I mean people really respect Tony Fauci and Debbie Birx and they got a lot of useful information from them and it informed the way people were thinking and that's important. We went back and forth on, so if we had a vaccine, would Americans use it? And there's one study that said only 50% would and another one recently that 70% would you know, there has to be really much more consistent messaging around. This is the threat. This is how we are going to get around the threat. These are the things that we're looking at. Drugs, vaccines. If you look at the countries that did well, somebody pointed out that a lot of them have female leaders. Korea doesn't. Well, so. But what they did was the people in charge stepped back and let the public health folks do what they do best. The same way. The same way in a war. The president doesn't direct the war. I mean, he's the commander in chief. But the generals do the planning and the execution and the training and the logistics. That's what they know how to do. So again, I would try to. If you were going to make me the king of COVID for a day, I would try to put into place things that, respecting the fact that the United States has 50 states and that we don't have a system for making them all work together, at least make them consistent, make sure that the reporting is consistent, make sure that states all equally recognize the necessity to understand how big the pandemic is.

What happens if only 50% of the people take the vaccine, or 70? I mean, what, what are the ramifications of something like.

So, I mean, we talked a lot about social distancing, right? So stay 2 meters apart. What a vaccine does is it creates immunological distance. It actually, so once you get to around between 60 and 70% of the people being vaccinated, you have herd protection, herd immunity, which is like what you see. If 60 to 70% of people in the United States were to come down with COVID at one point, enough people would be protected so that the individual cases would no longer propagate. So they, an individual person could be infected, but they wouldn't spread it to others efficiently. Well, a vaccine does that it creates by having 70% of people vaccinated. Individual cases, which will continue to occur, won't spread. And I think that's ideal.

But trying to achieve herd immunity without a vaccine, isn't that like saying, oh, well, 30% of you are gonna get it and 2% of those people are gonna die. But that's the brakes, because we want herd immunity. I mean, is it essentially. Is that what you're saying?

Yeah, and so. Right. I mean, so herd immunity, basically. Now, I think people call it the Swedish experiment using just social distancing without any lockdown, without actually, you know, I think the person in charge said, yeah, yeah, it's not been a success there. You know, we were unable to protect the elderly. So they conducted that. They took that path. And their mortality, again, adjusted for the size of the population, is much higher than even the United States.

I've taken up a lot of your time. I have two more questions for you. Okay, so question number one is, who was your favorite Iolani teacher?

Ah, that's a hard one.

We had the same teachers.

We.

We probably did. You know, I. So I had some teachers that I. I took multiple classes from. Captain Slate, Mr. Keebles. I took three classes from Mr. Keebles, actually. You know, actually, there are. There are a large number. Mr. K. And although I only had him for one year, Mr. Braden, because he. Larry. Math teacher. Yeah. So. But I. And a lot of them influenced me. I majored in biology and history. Maybe you see, Mr. K and Captain Slate there. A lot of what I do is writing. I mean, you can't be a scientist and not write. And for that, know Mr. Keebles, Harold Keebles.

As I look back of the arc. On the arc of my life, Harold Keeble was the singest, biggest influence. I think that. Well, I mean, Steve Jobs influenced me too, but Harold Keebles taught me how to write, essentially, and taught me how to think. And I hated that class was so hard.

You know, I don't. It's. It's. Mr. Keebles was quite a remarkable teacher. I did creative writing, advanced creative writing and AP English with him. And, you know, it was really. I learned a lot, and it was tough. And I can still correct people's grammar.

So. Yeah, no, no, you know, between two independent clauses, a comma and all that.

No passive voice.

Okay.

And my very.

My very last question is, we all heard the recommendations, but just in case you talked about everybody can do something. So what. What should everybody do? I mean, you know, we're not all. We're not all scientists or doctors, but just the random person listening to this says, okay, this is my contribution. What would that contribution?

So the most important thing is, is not only to protect yourself, but to protect others. I think sometimes we forget. We think that the masks are protecting us against infection. Actually, the masks are protecting other people. The US Government, in recommending that everyone wears masks, is actually saying, we can't tell who's infected. You may be infected and not know it. And rather than, you know, let your grandma or grandpa or the. Your elderly friends or your neighbors get infected, in protecting yourself with this mask, you're also very importantly protecting others. And so all the other things during the loosening of restrictions, still Apply if you have to be in a close setting, indoors, wear a mask, wash your hands frequently. If you're coughing or have a fever, get checked, stay home. Those are the kinds of things that are going to. You're going to. You have to remember that this is not over, that especially in the United states, there are 20,000 infections, as you said, a day. And so it could be your neighbor, it could be the person passing you in the street, the person standing in line with you, you know, so social distancing and use of masks and hand washing is going to be important. And we really need to remember that. I mean, this is our part. And so, you know, I, as an infectious disease doctor, you know, masks are not something. Masks have a particular purpose. And so I'm wearing a mask now, outside part of it is, I think people in Korea feel uncomfortable when you're not wearing a mask. And they'll tell you. They'll point to you and point to their mask. And actually, someone gave me a mask once, and I didn't say no, I don't believe it works. But it. But it does. In fact, there is data that would suggest that if you have. If you're sick, that it does prevent transmission. There's less data that would support in a general population that the mask actually protects you against infection. But there are some data that say it does. So, you know, again, and the mask reminds us that we're still in it, that it's still around, and that we still all have to participate in helping to control it. So it doesn't. So we can carry on at least with a bit of what we used to do before.

Well, I hope we can get to a place in America where, as you say, that if you're not wearing a mask, it's socially unacceptable because we are not there at all yet. Not. Not even close. I. I'm in Santa Cruz right now, and if you were to walk down at the beachfront, I'd say 5% of the people have a mask.

Yeah. And, you know, I mean, when I go running in the morning, I can't run with a mask on. It's just, you know, there, I'd say about 20% of people who are walking. So I'm running on a path are wearing masks. But when you start to look in, for instance, in the subway here, everyone has mask on. So in a closed setting, people wear masks depending on the workplace. We went to Seoul National University Hospital to announce that the trial was going to. We agreed to start the trial for the vaccine against Covid we wore masks during the meeting. And actually, the picture of us, we're all wearing masks with this standing with the sign in the backdrop in the background. So, I mean, they take it seriously here, and. But it reminds you. It's a constant reminder that it's not over.

Meanwhile, you know, our vice president goes to the Mayo Clinic and doesn't wear a mask. I mean, I. I don't get that at all.

I mean, yeah, you know, there's a bit of leadership by example. And I understand if a politician's at the podium, they make a sign, they take off the mask and speak, because it does. It's difficult to understand people sometimes when they're conquering behind a mask on the one hand. On the other hand, when they're out interacting with people, masks are important, and it's an important thing. Again, this consistent messaging is very important. If the government is saying that you need to do something, it's a government. You know, this is a thing by inclusion and by example, not by exception.

Well, thank you very much. I will sleep better tonight knowing that you and Ivi are working on this, and I now know more about vaccines than I ever thought I would. So I hope to meet you face to face sometimes someday when it's safe in Korea or Hawaii or California.

Well, thank you, Guy, and it was great to talk to you and reminisce about you.

Well, thank you.

All right.

And Yolani. No koi.

No koi.

Review time. Social influences get a lot of attention nowadays. Their job is just that, to get attention, not necessarily make a mark on the universe by doing something. Hey, it's a living for them, I guess. Good for them. Guy connects me in these conversations with people who are truly remarkable. These people have made a mark. They have taken action, done some good, made stuff and. Or changed minds. These are exemplars I want to be more familiar with. I'm grateful Guy is having these conversations and bringing attention to the real social influencers. Thank you, Chad. That made my day. I feel better with people like Dr. Kim being involved in the development of a coronavirus vaccine. As you heard, the creation of a vaccine is a complex and difficult process, and the medical industry is doing things very differently this time around. Let's hope that Dr. Kim and his colleagues around the world are successful in the near future. I, for one, would probably not fly commercially until there is a vaccine. By the way, at the very end of the podcast, you heard both of us say Iolani. No ka oi. That's Hawaiian for Iolani is the best I'm Guy Kawasaki and this is remarkable people. My thanks to Jeff C. And Peg Fitzpatrick for their remarkable work to make this podcast as good as it is. Until next time, wash your hands, maintain a social distance of 2 meters or 6ft. If someone coughs or sneezes near you, hold your breath and get away. Take care and mahalo.

This is remarkable people.