The next pandemic virus

"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.

Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.

GOF engineered boy and girl viruses? A moment’s confusion in a shopping mall.

On reading Which virus will cause the next pandemic? Gabriella Neumann & Yoshi Kawaoka. Viruses 2023, 15, 199.

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Looking into the future is fraught with difficulties. Yogi Berra captured this well with ‘It's tough to make predictions, especially about the future.' So, it’s not surprising that pandemic prediction is intrinsically tough, a point that has been made in many essays, the latest being Following the science.

The paper by Neumann & Kawaoka provides a list of potential viral springboards to the next pandemic.

In the abstract we find the observation, ‘all pandemics have found us unprepared, with enormous losses of human lives, tremendous costs for public health, and vast and potentially long-lasting economic losses.’ Given that pandemics are very hard to predict this observation is essentially a stark corollary. It’s hard to swallow and we’d all rather not. However, this reality is more honest than talking up preparations for the next pandemic as though we’re even close.

Just as a reminder, in the essay UK COVID report we discovered that The UK prepared for the wrong pandemic. The significant risk of an influenza pandemic had long been considered, written about and planned for. However, that preparedness was inadequate for a global pandemic of the kind that struck.

The present paper makes an ever-useful reminder that the 1977 H1N1 pandemic resulted from an ‘accidental virus release or a vaccine trial with an insufficiently attenuated live virus.’ It is estimated that this man-made pandemic resulted in approximately 700,000 deaths. However, as variants circulated as seasonal flu up to the 2009 flu pandemic this accident resulted in well over 10 million deaths (UK COVID report). This was the Chernobyl moment in infectious disease history. Accidents happen with viruses just as with nuclear power stations.

We read, ‘While much has been learned about the molecular virology of some viruses, we cannot predict the risk potential of newly emerging viruses simply by assessing their sequence.’ Finally, 13 years down the line, Dr. Kawaoka confirms you can’t predict the next pandemic which was the mantra back in 2012.

By the by Dr Fouchier, his GOF comrade in arms, said the same thing recently (Flu lobbying) although this paper is better argued.

We could have been spared a great deal of time, energy and printed words, especially as the virology was saying this back then. Anyway, those belated words are noted.

Meanwhile, the NIH hasn’t followed suit even though they considered Fouchier and Kawaoka’s work on flu to be a risk worth taking (Chilled virology).

Under the section ‘What will cause the next pandemic’ the discussion is confined to viruses that give acute respiratory disease. When it comes to the non-respiratory route, HIV burst onto the stage in the second half of the 20^th century – a pandemic by any other name - and then stayed for good. Ditto hepatitis C virus, although we still don’t know where it came from.

The logic that the next pandemic will be caused by a respiratory virus is correct if you list only past pandemics provoked by respiratory viruses like influenza or coronaviruses. In table form, the article provides an overview of major human respiratory viruses. Among other things, we learn that there are no vaccines for most of these candidates, which is a sobering observation.

Given there are reservoirs of look-alike human viruses in animals, many of which have been known for years, one of these viruses could spillover one day and lead to the next pandemic. Although we knew that years ago.

The article then gets sidetracked by a series of good points about pandemic preparedness. There is not a word about which of the long list of respiratory borne animal viruses might provoke the next pandemic, not even a single probability value anywhere. Yet the paper’s title is Which virus will cause the next pandemic? Which virus… singular. It’s all handwaving. Game to Yogi Berra.

Conclusion

Dr. Kawaoka has understood and cannot tell us anything about the next pandemic virus. Like everybody else.

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Aside 1

Concerning the 2009 H1N1 pandemic viruses we learn that it caused something like 284,000 deaths worldwide. While macabre, this is less than the death toll of some seasonal flu viruses. Key facts can be found on the WHO website, notably,

• There are around a billion cases of seasonal influenza annually, including 3–5 million cases of severe illness.

• It causes 290,000 to 650,000 respiratory deaths annually.

• Ninety-nine percent of deaths in children under 5 years of age with influenza-related lower respiratory tract infections are in developing countries.’

Pandemics have a sense of novelty, of sudden emergence, typical of acute infections. The consequences of the 2009 H1N1 pandemic are banging around in the form of seasonal flu variants that are every bit as dangerous in this case. For the record, there are two seasonal human influenza A viruses circulating, H1N1 and H3N2. The impact of each can vary with each season.

When it comes to other well-established microbes, notably the big three of tuberculosis, malaria and AIDS, they are still spreading remorselessly, not to mention antibiotic resistant bacteria. And with cuts in international aid, these pathogens will spread further.

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Aside 2

If we are lacking so many vaccines for here and now human respiratory viruses, why even contemplate making preventive vaccines for GOF 2.0 wannabe viruses?

Take a look at the WHO’s list of needy vaccines, November 2024.

Despite the COVID pandemic and On reading’s professional penchant for viruses these lists are worth perusing for they show the need for numerous non-viral vaccines (underlined). There is a convention to give the names of bacteria in italics.

Pathogens where vaccine research is needed

• Group A streptococcus

• Hepatitis C virus

• HIV-1

• Klebsiella pneumoniae

Pathogens where vaccines need to be further developed

• Cytomegalovirus

• Influenza virus (broadly protective vaccine)

• Leishmania species

• Non-typhoidal Salmonella

• Norovirus

• Plasmodium falciparum (malaria)

• Shigella species

• Staphylococcus aureus

Pathogens where vaccines are approaching regulatory approval, policy recommendation or introduction

• Dengue virus

• Group B streptococcus

• Extra-intestinal pathogenic E. coli

• Mycobacterium tuberculosis

• Respiratory syncytial virus (RSV)

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Simon Wain-Hobson is an emeritus professor at the Institute Pasteur, Paris, from which he retired in 2021. He and his colleagues were the first to sequence the genome of HIV, and Wain-Hobson has published more than 230 papers on virology and cancer.