The Coronavirus Files: A Discussion with WHO Advisor, Prof John Mackenzie

Brett Crossley and eminent Zoonoses Expert, Prof John Mackenzie discuss the biological basis of the Novel Coronavirus, critically engage with the adequacy of the Public Health response by Chinese officials and explore the emerging research field that intersects Human, Animal and Environmental Health (a.k.a One Health). The following is a transcript from what was originally intended to be a telephone-based podcast – due to a number of audio difficulties only snippets from the conversation were salvageable. Recorded 14/2/2020

Brett:

For those of us who might not be familiar with your work, John, could you give us a background of how you got into Zoonotic disease research and anything up to your current role advising the World Health Organization?

Prof John Mackenzie:

I've been a consultant to the World Health Organization now for about 40 years. I initially got involved with my work with influenza. Most of that was to do with how to make new vaccines for influenza. Then I moved across to where the new influenza strains were coming ... [they were coming] from birds. So I became interested in Zoonotic diseases because of birds and influenza. And then later on, I got much more involved in mosquito borne diseases. Of course, mosquito-borne diseases ... most of them ... go between mosquito's and an animal reservoir of the virus. Humans are usually 'dead-end' hosts or 'occasional hosts’, depending on what the virus is. From there, I also had a student who was working on Hendra Virus. So, I got very interested in bat borne diseases and we also did some work on Bat Lyssavirus, which is very much like rabies. So I've had an interest in one way or another with Zoonoses for quite a number of years in different guises. A part of that also is I've been a foundation member of a group called the Global Outbreak Alert and Response Network or GOARN for short. This started initially because the World Health Organization was involved in outbreaks of diseases in different countries. If there was an Ebola outbreak, say in Uganda, every man and his dog would turn up.

Obviously the WHO are the main international health group, but also people would come in Portland, Antwerp, Belgium, Tokyo, Beijing, the CDC, USA and a whole lot of other groups would [also] turn up to help. But there's no one there to tell them what to do to help. In other words, it was very much a whole of people turning up without knowing what to do with themselves. So, the WHO decided that it should make this much more efficient. So they had a meeting and brought all the major partners together and said, "Look, we shouldn't just all turn up. We need to send the right people for the right skills that are requested by the country." Everyone agreed. So, we set up this network, GOARN. That has now been involved in about 220 or 230 outbreaks around the world in the last 20 years. They have sent experts with whatever area of expertise required by that country [to ensure that] they don't get flooded by others, shall we say. And that's worked very well. We do it in conjunction with the WHO. In fact, our Secretariat is embedded into the WHO now. So it's very close relationship with WHO, but, altogether we have about 200 major partners around the world who send people plus another 300-400 partners who are in networks associated with our network. We can have huge number of potential experts we can send who might be available. This all depends on different language groups, so if the country doesn't speak much English, French, Spanish etc. It needs to be linked not only to expertise, but also to cultural and linguistic support as well.

So, I've been involved WHO in that respect for quite a while. I also was the first person to take a team into China for SARS on behalf of WHO to try to find the origin of SARS. I was also the first ever chair of an emergency committee for WHO for a pandemic influenza. So I've had various involvements with WHO over the years.

Brett:

I guess for those of us who aren't aware, Zoonoses are diseases that move from an animal host to a human. Is that right?

Prof John Mackenzie:

Yes. That is not only simple, but it is correct.

Brett:

Okay. All right. And the coronavirus is a Zoonoses? It has jumped from an animal to a human?

Prof John Mackenzie:

Yes. So it has jumped from an animal to humans. Probably 2 animals, on the way. We think there is probably a natural reservoir of [Coronavirus] is in bats. Just as a digression for a moment. We have had two or three major novel diseases discovered in the last few years. But the one that's had the most effect was probably Nipah virus, which occurred in Malaysia. Which is very similar to Hendra, which we had an Australia. Hendra and Nipah were both shown to be bat-born. So that caused a huge interest in bats, bat diseases and what bats might carry. Then with SARS, that was also found to be from Bats. So there's been a massive effort to look at bats all around the world in terms of what kinds of diseases they may carry. They carry a huge plethora of viruses and other organisms. A quite unbelievable number compared to any other mammal. There are various reasons for this which I won't go into. But one of the major things about these Coronaviruses is there's a whole suite of Coronaviruses found in bats too. Some of them are very similar to diseases we know like SARS, MERS, and others very similar to this new virus, Novel-coronavirus.

So we're pretty certain that bats were the original source of the virus. But the bats seldom are in contact with humans. I mean, we see pictures of people eating bats, but nevertheless, those bats are an unlikely route. Because, the cooking of the bat would kill off the virus anyhow. Therefore it is unlikely that bats are infecting people from cultural eating. On the other hand, often these bats can be linked to other forms of wildlife. The virus can spread from the bats to different species, particularly if the bat and other wildlife has been kept close together. What we think probably happened in this instance was the bats infected pangolins, which are very popular in China as a food source. Basically, eating them is illegal, catching them is illegal. But nevertheless, we think the 'intermediate host' as we call it, was probably pangolins. So the virus jumped from bats to pangolins, from pangolins to humans.

An unimpressed Pangolin on its way to a lawyer to file for defamation should the accusations of hosting COVID19 be found untrue. Image source (and an interesting article): National Geographic

Brett:

Okay. So, how does having an understanding of the source of the virus help inform how we deal with, quarantine and prevent the spread of the virus?

Prof John Mackenzie:

That in itself doesn't. What it does do is tells us where it first arose. We need to understand how these things arise in terms of actual outbreak itself. Other than the fact that that's where it initiated, probably it has very little bearing thereafter.

Brett:

Right. That's a nice fact check there. And in terms of the media coverage on the virus, depending on what newspaper you read, you get a different story. This morning some Fairfax news articles were suggesting that potentially two thirds the global population could be infected by the virus. We're seeing all sorts of fear-mongering news thrown at us. Do you have any comment about what you imagine would be possible in terms of the spread?

Prof John Mackenzie:

Well, one thing that I think that is almost certain, is that what we're seeing in terms of numbers is the tip of the iceberg. We're seeing those that have severe cases rather than the many, many mild and/or subclinical cases that probably occur as well. So it's very hard to know just how many people are infected. There's been a lot of modelling done and some of the best modelling has been done from the Imperial College in London. They estimate that the number of cases is probably is at least 10 fold more than we are seeing.

In other words, there's a large number of cases and [the current estimates are] probably at the lower end. It's probably even higher than that. So it's very hard to say just how many people are infected and how many people have clinical disease. What's been interesting I think, is that if you look at the figures we see most of the cases still come from Hubei even though it's been locked down for the last two or three weeks. Despite the fact that the virus has been spreading elsewhere, we're not seeing a great spread elsewhere in China. I think the current figures today are something like 33,000 new case cases in Hubei compared to about 10,000 cases elsewhere in China.

The spread elsewhere in China is not as fast as one might have imagined. But at the same time, this might be partly dependent on the fact that only confirmed cases are being reported and the number of test kits available for testing ... Not nearly enough. There's a lot of murkiness about how important these figures are in a sense and how reliable they are. I think there's little doubt that the spread is much more widespread and far more cases - certainly of mild and subclinical cases than we are aware of.

Brett:

In terms of how people should respond to the fact that the amount of people infected by the virus could be higher than is reported. Should people be changing their behaviour? Stop travelling etc.?

Prof John Mackenzie:

It's a very good question. I would say, no. I mean we stopped flying to and from China for the moment. That doesn't please the Chinese. It probably doesn't please the WHO, either. But at the same time it's probably the best thing as far as we're concerned. If we can try and restrict it [from spreading] for as long as we can. So everyone else can become more [equipped] to cope with it when it does appear. It also gives us more time, of course, to try and find antivirals or work towards vaccine and all these things help. But I suspect that the virus is going to move much faster than we were able to stop it, should we say.

Brett:

All right. Have you had much contact with or access to information about how well the Chinese officials are responding to the World Health Organization's advice on how to control the spread?

Prof John Mackenzie:

That is a very difficult one to answer, as I am not aware of much of the information, I suspect. I certainly know that the WHO were very impressed by the speed of which China announced [the outbreak] initially. If you think about it, that's probably quite correct. When you have a new disease, the first few cases don't ring any alarm bells because they might just be natural occurrences of some other thing like influenza or pneumonia. It's when you start seeing clusters of cases, it's important. The first cluster of cases occurred in the second half of December - linked to the seafood market in Wuhan. That cluster raised public health alarm bells. When it happened I think they were quite quick to report an outbreak of 'pneumonia of an unknown cause.' Which they did on the evening of the 30th of December. That was really quite quick by any stretch of imagination and quite quick for China. It would be quite quick for Australia. In fact, I could think of other public health areas where it might take much longer.

In a sense, I think the WHO Director General is quite correct when he congratulated China for the speed with which they announced it. I think there are aspects around which you can quibble about. Some things weren't as fast as they should be, perhaps. Some things weren't communicated when they should have been, perhaps. Nevertheless that was an important feature. I think there was a kind of hiatus for a while - when nothing was reported at all for about 10 days. And that, that was a problem. Another thing that was a problem was that there was some evidence that this was a new coronavirus from Bronchial Lavages taken and sent off to commercial laboratories which came back with a sequence that was a Coronavirus. Now the first one of those was done on the 26th of December. There was some indication that that new disease of unknown cause might've had a Coronavirus cause associated with it. If you're a public health official, you probably wouldn't take that on board as something which is definite, on one sequence. So they probably would need to wait for one to two other sequences coming through. And sure enough, they did more Bronchial Lavages from other cases, around about the end of December - beginning of January. So, when they finally isolated the virus on the 7th or 10th, maybe of January. They sequenced it and sent out the sequence on the 12th of January. Had we had that sequence earlier from these other Bronchial Lavages, it might have been possible to produce diagnostic kits much earlier than we actually did. But you know, it's with all these things looking at it with hindsight, puts it out of proportion in the sense.

Brett:

I see, okay. And in terms of your experience with SARS. Obviously, it's a virus coming from the same country [China] as the current novel-coronavirus. Do you see any alignment between the two viruses?

Prof John Mackenzie:

No. There's a couple of interesting points about it. One is the fact that this new virus is very closely related, they are sister viruses. They are in the Betacoronavirus group and they share 80% of their genomes, which is closer than say Dengue 1 and Dengue 2. Or Dengue 2 and Dengue 3. So in other words, they're very, very similar viruses and in many respects they have very different characteristics nevertheless. One of the most important differences for instance is that this transmits early, much earlier than SARS. SARS did not transmit until about two days after symptoms started.

Before symptoms started and the first few days of symptoms, there was no transmission. Transmission didn't really occur until about four or five days after and symptoms started. This new virus however, is almost certainly transmitting during the incubation phase before the symptoms start as well as when symptoms first start. With SARS, once you knew what's happening it was quite easy to prevent it, because you knew all the cases. You could put them in quarantine or you knew who was infected, definitely. But this new virus, you don't, you're going to have sub-clinical cases, mild cases and you have other cases which are severe, but all of them are able to transmit, probably, before symptoms start and certainly the early part of the symptomatology period. So this makes it much, much harder to control.

Brett:

Hmm, it sounds quite horrifying when you put it like that.

Prof John Mackenzie:

That is certainly one major difference. There are other differences too, which I won't go into. What I am trying to say is that it's all very well saying, we know quite a lot about SARS. It doesn't always mean that we can then utilise that information usefully for a new virus and we can't in this particular instance. The other thing that has happened in China - was when we went into looking for SARS, the laboratories were very poor and there was no communication between Beijing and the provincial laboratories ... Or not enough. There was [also] no compulsion that the regional laboratories reported cases to Beijing. So there was a need for better communication, improving their requirements of surveillance and reporting back to Beijing and so on. When we gave our report to the Ministry in China after SARS, we pointed out to them that if they didn't improve this, there would be other outbreaks in the future, liable to occur in China. If they weren't able to improve their game, shall we say, and diagnose these quickly, then the rest of the world would held them in some kind of ... I won't say contempt, but they'd certainly be unhappy.

So, I went back three years later with an official mission, with the [Australian] Health Department and the differences were chalk and cheese. I mean, China had just taken off. I'm sure it wasn't our report. I think what had happened was they had really moved incredibly fast. They had superb laboratories. Completely whole new CDC was being built at the time - I think five buildings or something outside Beijing. Each of the provincial CDCs, had been upgraded enormously. Every one of them was linked by computer - everyone knew what was happening each other's province. All of this information was being fed back to Beijing and it was done instantaneously, almost. Certainly very quickly. And it was just so different. It was almost like a different country. China's capacity and capability is enormous compared to what it was prior to SARS. So, I think one of the reasons that China was able to associate this as a new disease, even if they didn't know what it was, so quickly, was due to the fact that this had been put in place by the Chinese government.

Brett:

Well that sounds quite hopeful and promising. I imagine post novel coronavirus, there may be some more extraordinary leaps in capability and capacity in the Chinese healthcare system. It might be quite interesting...

Prof John Mackenzie:

There are obviously weaknesses that are coming through and these weaknesses are not surprising given the scale of things. I think there were still some instances - like very early on when reporting wasn't being done fast enough, probably because of other activities that were going on. I gather there was some party meeting in Wuhan which they didn't want to upset the applecart beforehand. And there's other things which might affected some aspects of the ongoing outbreak. And I think that the large numbers of cases the lack of diagnostic kits and so forth, made it very difficult for China to be able to control it as well as they did. They took a draconian action obviously stopping traffic in and out of Wuhan. [This measure extended] after that to the whole of Hubei Province. That was a very brave decision to take to basically quarantine 60 million people, which is amazing. It reminds you to what happened in 1997 with Avian influenza. When Margaret Chan, who was head of the Hong Kong Health Department at that stage ordered all poultry in Hong Kong to be destroyed and no repopulation of poetry for three months. For three months in 1997, there were no chickens, no ducks, no geese, no quail, nothing, No poultry of any sort was allowed for three months. That was also draconian, but it might well have saved the world from an outbreak of pandemic influenza. It was a very brave decision to take in the possibility of a pandemic down the track. So I think that doing the same sort of thing here in a bigger scale is quite amazing. And my suspicion is that it can only happen in China.

Brett:

Well that's very interesting perspective on that. My last question, is about your more recent research into the One Health Program and the academic journal you've set up. I understand you're attempting to push for better recognition of the links between humans, animals and our shared ecosystems.

Prof John Mackenzie:

Correct. Basically they all interact - interface. Where they interface is what we call One Health, basically.

Brett:

The health of the ecosystem, the health of animals is part of the health of humans?

Prof John Mackenzie:

Exactly right. They all effect each other.

Brett:

Of course. And this global pandemic that we're currently experiencing is the result of that interface?

Prof John Mackenzie:

It is. And basically as the [WHO] Director General said yesterday in his ... Tweet, twit, twitters?

Brett:

[Laughs] Tweets.

Prof John Mackenzie:

... Was that the world to take to take a One Health actions in this. It's recognised worldwide, by the World Bank and others, that One Health is a crucial thing. One Health is a major issue when it comes to human health and animal health and environmental health. They all interrelate and we need to understand them all in context. That's the important part of it. So yes, I set up [the journal, One Health] with my colleague Martin, who used to be the director of Cicero's Animal Health Lab in Geelong. Martin and I set up the first of the One Health congresses here in Melbourne in 2011. We're now about to have a sixth Congress in Edinburgh in June of this year. So they've grown enormously. We've set up a foundation called the One Health Platform Foundation. We've worked closely with various other organisations around the world to promote and to teach One Health. There are major One Health institutes now set up in different parts of the world. There is a major one in California at the University of Davis. Which is looking, is helping to build a One Health workforce around the world in different developing and resource poor countries as well as more resource countries. That's been incredibly successful. There is a big USAID grant, $85 million to help do this. There's also, a number of other institutes, very similar ones. So the whole idea is to build up a One Health workforce who's able to go in, diagnose and to respond to outbreaks of disease where there's an animal-human interface or animal-human-environmental interface. It's becoming a really big, worldwide movement.

Brett:

Okay. If a young person was interested in this emerging field, how would they find out more?

Prof John Mackenzie:

Probably best through the web, I suppose. As everything else these days - Googling, One Health. If you want to have a career in it, there are so many different avenues you can go through – veterinary medicine, human medicine, environmental health aspects or things with our environment. If you're interested in the actual disease epidemiology, the best way to go is get a master's degree in Applied Epidemiology. And we have a very good course here in Canberra at ANU. There are [other good training locations] at the CDC in the U S and most countries now have these courses aimed at producing people who are able to go and respond to outbreaks. From a human disease and from an animal disease perspective.

Brett:

All right. Okay, John. Well, thank you very, very much for taking the time to talk to me today. I've learnt a lot and you have dispelled some of the misinformation that I've read in the media. It's been very helpful.

Prof John Mackenzie:

My pleasure.