Summary of CMS Seminar Club presentation on Friday, April 28, 2023.
Title: Pandemic preparedness – the importance of “One Health”
Speaker: Prof. Thomas C. Mettenleiter, Ph.D., President of the Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Greifswald-Insel Riems, Germany
On Friday, April 28, Prof. Mettenleiter gave a presentation at Fujita Health University. He told us about:
(A) the Friedrich-Loeffler-Institut, the oldest research center in the world specifically dedicated to viruses, and its founder Prof. Friedrich A.J. Loeffler;
(B) the ever-present risk of animal viruses adapting and becoming contagious for humans (through “viral zoonosis”), exemplified by COVID-19 and influenza;
(C) the “One Health” concept and how the “One Health High Level Expert Panel” established by the Quadripartite (WHO, FAO, WOAH, UNEP) aims to help prevent future zoonotic epidemics.
Recording: For members of Fujita University, a recording of the meeting (without the discussion part) will be available at our Manabi system. Unfortunately, we cannot open the recording for a wider audience.
There were 56 participants who enjoyed the meeting, and the reactions were very positive. One German guest wrote me afterward “war wie immer gut” (it was good as always), as he knows the quality of Prof. Mettenleiter’s presentations. Prof. Jim Kaufman wrote “The talk was great, pitched at a level that I have only glimpsed from time to time, WHO/FAO/etc policy and so on”—and that was the case indeed. In a down-to-earth and accessible manner, Prof. Mettenleiter told us about discussions at the world’s highest organizational level to help prevent future epidemics.
For me, personally—because he was my first boss in 1993-1997—it was a treat to talk to him again, and it felt a bit like time-traveling to a nice past. I am grateful for his time and excellent presentation.
The contents of the presentation
(A) Friedrich Loeffler and the history of the Friedrich-Loeffler-Institut
The Friedrich-Loeffler-Institut (FLI) on Insel Riems is not only one of the most modern and biggest institutes dedicated to the research of viruses but also the oldest. It was founded, under a different name, on October 10, 1910, by Prof. Friedrich A.J. Loeffler (1852-1915).
Friedrich Loeffler joined the laboratory of Robert Koch, one of the “fathers of bacteriology,” in 1879, and under his mentorship described for the first time the bacterial agents of glanders, diphtheria, and erysipelas (Fig. 1). In 1888, he got his own group at Greifswald University (only 12 km from Insel Riems), and there, in 1898, together with Paul Frosch he discovered that the infectious agent of Foot-and-Mouth-Disease (FMD)—a highly infectious, and often devastating, disease infecting cattle, pigs, sheep, and goats—was a virus, because it retained its ability to infect and replicate even after being passed through filters that trapped bacteria-sized particles, whereas its corpuscular nature was evidenced by being filtered out if an even finer mesh was used (by the Kitasato-filter, named after the famous Japanese bacteriologist Shibasaburō Kitasato). The discovery of a filterable BUT corpuscular infectious agent can, arguably, and at least in animals (there were other research developments in plants around that time), be considered as the first conclusive discovery of viruses as a distinctive type of infectious agent.
Both important publications on Tobacco Mosaic Virus (by Beijerinck) and Foot-and-Mouth Disease (by Loeffler and Frosch) appeared in 1898, so we celebrate 125 years of Virology this year!
Then, on 10-10-1910, for biorisk management reasons, Prof. Loeffler moved his institute to the nearby island Insel Riems. Location on an island reduced the chances of unwanted spread of infections and allowed the careful control of who visited the institute and how. Nowadays, the “Friedrich-Loeffler-Institut“—which got this name in 1952 at the centenary of Friedrich Loeffler’s birthday—belongs to the Federal Ministry of Food and Agriculture and its research is dedicated to the health of food-producing animals and, also, the protection of humans from zoonotic infections; its main location is still on Insel Riems, which remains mainly dedicated to the research of viruses, but research is also done at other locations in Germany (in Mariensee, Celle, Braunschweig, and Jena) and on other animal health issues. There are ⁓850 staff (of which ⁓650 permanent) working for the Friedrich-Loeffler-Institut. On Insel Riems, in 2008-2013, there has been a massive construction to build modern high-tech research facilities, including a core unit with the highest biosafety level (BSL4) where the most dangerous pathogens of animals and humans, including in large animals, can be studied.
(B) The ever-present risk of viral zoonosis, exemplified by COVID-19 and influenza
Viruses, by far, constitute the most abundant, variable, and rapidly changing form of life on earth. Therefore, viruses now and again mutate towards variants that can productively infect species different from their original hosts. Many pandemics (large epidemics) that scourged humanity are believed to have originated from viruses that originally were more specific for animals. To name just a few recent ones: Spanish flu (influenza virus, probably from pigs), AIDS (HIV virus, from monkeys), and COVID-19 (SARS-CoV-2 virus, probably from bats with or without an intermediate host).
Researchers of Insel Riems tried infection of SARS-CoV-2 (the COVID-19 virus) in a variety of animal species, including chicken, bats, raccoon dogs, ferrets, and pigs (Freuling et al. 2020; Schlottau et al. 2020), and together with findings reported by others, the observed susceptibilities were summarized in Fig. 3 (Michelitz et al. 2021). Interestingly, in raccoon dogs, they demonstrated infection, productive replication, and transmission to in-contact animals of SARS-CoV-2 in the absence of symptoms, suggesting this species might have been an intermediate reservoir for the virus on its way from bats to humans (Freuling et al. 2020). SARS-CoV-2 can also productively infect minks from humans, and was found to mutate within minks and then infect humans again (Oude Munnink et al. 2020); this prompted the government of Denmark, in 2020, to cull (kill and dispose of) all the 17 million farmed minks in the country. An example of a wild animal reservoir for SARS-CoV-2, initiated by multiple independent infections (“spillovers”) from humans, are the wild-tailed deer of North America (Hale et al. 2022; Kuchipudi et al. 2022); interestingly, and—even more so—frighteningly, the SARS-CoV-2 lineages circulating in this deer population include lineages that in the human population have already been replaced by faster replicating but less harmful lineages, and within these deer the virus undergoes its own unique evolution.
Spillovers of viral infections from animals to humans (Fig. 4) happen all the time. However, in most cases, this is a dead end for the virus because the virus is not well-adapted to humans. Only in the cases that it accumulates mutations that enhance its reproductivity in humans, it can become a “human virus” that can create an epidemic.
While the world is still dealing with COVID-19, another potential for a human epidemic by zoonosis is literally hovering over us. Namely, in birds, H5N1 influenza (“bird flu”), a potential source of human epidemics because it sporadically infects humans (the present form is not very good at that) with sometimes deadly consequences, is currently more prevalent than ever recorded before. It goes without saying that with its increased abundance the chance increases that H5N1 may acquire mutations that better adapt it for productive infection of humans. Worrying observations have been made in other mammals already, like seals dying from H5N1 infection (Schnirring 2023) and productive H5N1 circulation among minks (Sidik 2023). On Insel Riems, they found that pigs are refractory to experimental H5N1 infection. Professor Mettenleiter stated that the H5N1 situation is not an immediate reason for alarm, because these potential dangers are a continuous part of normal biology/life, but reason for concern and that we should try to implement measures for dealing with it.
A first important step is to try blocking the entry of H5N1 into our domestic poultry populations. Apart from that, the poultry can be protected by vaccination.
For example, in China, in the 2016/2017 season, there were >700 human infections, of which 39% deadly, with another avian influenza strain, H7N9, all through close contact with poultry. After China had implemented compulsory vaccination of poultry against H7N9, these human cases fully disappeared (Zeng et al. 2018).
Humans acquire most zoonoses from domestic and not from wild animals, simply because the kind of interfaces and number of interactions are much higher. In this context, Prof. Mettenleiter showed us a graph explaining that between 2005 and 2050 the combined world production of poultry, meat, and eggs, is expected to more or less double in size. Thus, not only the world human population will increase, but also their domestic livestock, which increases the number of animal-human interactions.
After the seminar, one of the participants wrote me that if people would switch more to aquaculture products like fish, that would reduce the risk of zoonosis, and he is probably correct (but then other ecological questions arise).
(C) The world’s “One Health” and the “One Health High Level Expert Panel”
The expression “One Health” refers to the interconnectedness of species and systems (biological, ecological, cultural, socio-political, etc.), as they all affect each other, and is often used to expand the concept of human health. In 2021, four global partners (now designated the “Quadripartite”), the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), established the interdisciplinary “One Health High-Level Expert Panel (OHHLEP)” to enhance their cross-sectoral collaboration. Prof. Mettenleiter is a founding co-chair of the OHHLEP together with Prof. Wanda Markotter from the University of Pretoria, South Africa.
The OHHLEP currently has 26 members, coming from all continents, who frequently meet. I recognize the member from the Netherlands (my nationality), Prof. Marion Koopmans, because she has important national and international advisory functions on COVID-19 and has often been on Dutch television. Also the other panel members, like Prof. Mettenleiter and Prof. Koopmans, have prominent functions in their country.
For a precise definition of One Health by the OHHLEP, see Fig. 5.
Foundational principles that the OHHLEP subscribes to in relation to One Health are explained in Fig. 6.
For the implementation of its ideas, the Quadripartite developed the One health joint plan of action (2022‒2026): working together for the health of humans, animals, plants and the environment. Its major focal points are protection against zoonosis, protection against antimicrobial resistance (AMR; the fact that pathogenic bacteria become less sensitive to antibiotics because of overexposure), strengthening health systems, integrating the environment in the One Health approach, and improving food safety.
An important task of the OHHLEP experts is to discuss and advise how the risk of zoonotic spillovers can be reduced. Professor Mettenleiter mentioned the triad of: Prevention, Preparedness, and Response. Especially prevention is a logical target and can be achieved by reducing risky animal-human interactions and by protecting livestock from infectious diseases (see the previous paragraph). Professor Mettenleiter believes that large improvements can be made in this area, and I trust that he and the OHHLEP can truly help with that development. The OHHLEP, in 2023, wrote the opinion piece Prevention of zoonotic spillover— From relying on response to reducing the risk at source, in which they explain their ideas.
Preparedness and Response to zoonotic infections involve medical care and biomedical research into vaccines and therapeutics.
During the Discussion section of the seminar, Prof. Mettenleiter got the question of how a reduction in risky animal-human interactions can co-exist with cultural freedom. Namely, people typically only want people other than themselves to reduce those interactions: Big farms point out the risk of small farms, point out the risk of hobby-farming, point out the risk of keeping exotic animals as pets; People in countries where only a few animal species are eaten point out the risk of countries where many species are eaten, point out the risk of eating bushmeat. Professor Mettenleiter gave a perfect answer to this question and said that people should become better informed (as opposed to being forced) so that they can keep doing similar things but in a less risky manner.
