By the time that December 2019 was drawing to a close, the world had witnessed a year of milestones and firsts.

In sporting terms, it had been a vintage year. From Lewis Hamilton clinching a sixth Formula 1 Drivers’ World Championship to Tiger Woods’ roaring return to glory as he won the Masters yet again – his 15th career major and fifth Green Jacket – and South Africa’s dominant Rugby World Cup victory in Japan, it was a year of major sporting highlights across football, rugby, tennis, F1, golf, cricket, boxing, athletics, gymnastics and so much more besides.

In entertainment and specifically at the box office, it was a year of epic film releases as the waiting public flocked to cinemas the world over to indulge in top-grossing releases ranging from The Lion King, Frozen II and Toy Story 4 to Joker, Star Wars: The Rise of Skywalker, and Avengers: Endgame. In fact, 2019 became the first year to have nine films cross the billion-dollar milestone1, surpassing 2015’s and 2018’s record of five billion-dollar films. Additionally, Disney (not counting Marvel Studios or Lucasfilm) saw four films cross $1bn, the studio’s highest amount in any calendar year.

Had we ever had it so good in film, entertainment and our social freedoms?

Meanwhile, the clean energies movement continued to gather pace and break barriers around the world too, with a notable highlight in Britain by the year’s end, as zero carbon electricity outstripped fossil fuels in 2019 for the first time. Confirmed by National Grid, the year was the cleanest on record for Britain as zero carbon technology such as wind, solar and nuclear exceeded electricity supplies from polluting fuels such as coal and gas.

Whilst wind and solar may have been at the forefront of that milestone, alternative energies such as biogas (biomethane), hydrogen and LNG continued to move forward at increasing pace, while carbon capture technologies continued to gain both profile and capacity worldwide at the other end of the net zero circle of sustainability.

Unfortunately, it was a year of less than glamorous firsts, politically. Across the UK, for example, the year may have concluded with clarity around Brexit and with Parliament voting overwhelmingly to formally exit the EU by 31st January (2021), but it had been yet another tumultuous 12 months of societal and political struggle to get there and with clear divisions in opinion still existing across the constituent countries. Likewise, for all those countries still actively participating in the EU and pro-union, the debacle had undoubtedly been both a distracting, resource-intensive and unedifying experience in 2019.

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Across the Atlantic, an equally distasteful political spectacle was unfolding in the US. Whilst President Donald Trump had made international history on 30th June when he became the first sitting US president to set foot in North Korea, engaging in a meeting in the Demilitarised Zone for potentially groundbreaking nuclear (warhead) talks between the two countries, those same talks appeared to stall soon after. Less constructive rhetoric resumed across high-profile social media channels in the days and weeks thereafter, at a time when the Trump Administration was also deeply embroiled in terse trade tariffs and political stand-offs with another perceived ‘threat’ in the Asia-Pacific region – China.

Against this backdrop and with the US election year pending in 2020 and, some would argue, a campaign to more than besmirch the outspoken Republican president, an anonymous whistleblower alleged in August 2019 that Trump had used the powers of his office to pressure Ukraine into investigating Democratic frontrunner Joe Biden and his son in a call on 25th July. A political storm that deepened Democratic and Republican divisions, by 24th September it had progressed to a formal impeachment probe. The House voted on 31st October to hold public hearings; those hearings opened in mid-November; and by 18th December, the House had voted along party lines to approve two articles of impeachment against the sitting president.

On one hand, it could be argued that many had never had it so good in 2019, with rapidly advancing technologies at our disposal, flourishing social freedoms, and all the music, film, programming and sport we could need to entertain us. We were gradually moving towards a cleaner and most sustainable way of living, even if progress still felt slow.

Yet on the other hand, the world was arguably a tinder box of geopolitical and societal tensions, distracted by growing tariffs, trade wars and thorny turf wars (think the US-Iran conflict, the Saudi oil refinery attacks), as well as escalating domestic political dramas. One might even question, were these more serious than turf wars? Were they in fact proxy wars, and representative of efforts to exert global influence? Meanwhile, at a time when many people around the world had more choices than ever, many others were in the midst of drives for greater democracy and freedoms; think of pro-democracy protests in Hong Kong, political protests in Algeria and Iraq, and inequality protests in Chile as strident examples.

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Source: Jimmy Siu / Shutterstock

Crisis in the making?

Then, almost overnight, it would be a temporary case of exit stage left for many of these issues, as a once-in-a-century global pandemic would so unexpectedly and irrevocably change the world.

Did those issues, however, really just subside? Did that terse political battleground at home and overseas actually facilitate the unchecked rise of an indiscriminate virus in so many countries? Did world leaders take their respective eyes off the ball, in the name of short-term political posturing?

How prepared were our healthcare systems, supply chains and societies for a crisis unlike any other over the last 100 years?

Here in this series, we will explore a playbook of political, social, scientific and economic constructs that underpinned one of the most devastating public health emergencies in a century and oxygen supply chain shortages that ultimately failed to prevent the loss of many thousands of lives. There will be no conclusions, there will be no opinions, only presented facts and perspectives of a story – we must remind ourselves – that has not yet reached its concluding chapter. This is the story of Covid-19 (coronavirus) and oxygen shortages.

A new threat

As the year closed and revellers around the world celebrated into the small hours of 1st January 2020, it’s fair to say almost no-one knew what kind of year they were ushering in. Just over 100 years since the ‘Spanish flu’ pandemic raged across the globe and took the lives of an estimated 50 million people2, a new virus was about to be unleashed on the world to strikingly similar and devastating effect.

The 1918 influenza pandemic was the most severe pandemic in recent history. Though termed ‘Spanish flu’ there is no universal consensus regarding its place of origin, only the knowledge that it was caused by an H1N1 virus with genes of avian origin.

The virus spread worldwide in various waves throughout 1918-1919 and through to April 1920, during a period of major international conflict, most notably World War I, and it is estimated that around 500 million people – one-third of the world’s population at the time – became infected with it. The number of deaths was estimated to be at least 50 million worldwide, though interpretations vary considerably given dynamics such as misdiagnosis, the wars being fought at that time and a lack of accurate data compared to today. In fact, estimates range from a conservative 17 million to a possible high of 100 million3.

Just over a century later, the world was rapidly gripped by a new virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – or Covid-19 as it soon became known.

On 31st December 2019, the World Health Organization (WHO) was informed of cases of pneumonia of an unknown cause in Wuhan City, China4. A novel coronavirus was identified as the cause by Chinese authorities on 7th January 2020 and was temporarily named ‘2019-nCoV’. Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases. A novel coronavirus (nCoV) is a new strain that has not been previously identified in humans.

By 30th January, the outbreak was declared a Public Health Emergency of International Concern by the WHO and was subsequently named the ‘Covid-19 virus’. By 11th March it was officially recognised as a pandemic. Yet the exact origin of the virus still remains uncertain today and there are various theories in circulation concerning natural versus synthetic emergence.

Some claim and make very plausible arguments for synthetic emergence; that this was a man-made virus manufactured in a lab, quite possibly in Wuhan itself. Others argue, and this is apparently the basis of widespread scientific reason, that this was a story of natural emergence; most likely from a bat, to a civet or other animal, and into contact with humans via the wet markets of Wuhan. Whether of synthetic emergence (manufactured) or having jumped from wildlife into the human ecosystem, it is argued in some quarters that the political agendas of governments and scientists ‘have generated thick clouds of obfuscation, which the mainstream press seems helpless to dispel’.5

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The synthetic argument

The argument for a virus of man-made origin is not necessarily that it was deliberately unleashed upon the world for malintent, but more that it may have been created, studied, manipulated and further studied for research purposes, and subsequently managed to escape from the confines of that lab.

The most likely reason for any lab experiment with such viruses is something called Gain of Function (GOF) research. This is a term used to describe any field of medical research which alters an organism or disease in a way that increases pathogenesis, transmissibility, or host range (the types of hosts that a microorganism can infect). This research is intended to reveal targets to better predict emerging infectious diseases and to develop vaccines and therapeutics6. In other words, this is the modelling and study of a virus or organism to understand how it functions, what the worst-case scenario of human infection might be, and develop the treatment for that disease or prevent against it before it actually happens.

GOF research is big business and, clearly, carefully used in such a way – in the right hands – is to the benefit of us all. It is arguably the pinnacle of mankind’s (medical) scientific endeavour and understanding. It is also, however, associated with both controversy and questions over its efficacy.

Back in May 2014, an article from the Center for Infectious Disease Research and Policy (CIDRP) explained how the ongoing debate over the appropriateness of experiments that increase the transmissibility of H5N1 and other avian flu viruses in mammals had heated up again7. It cited two experts who argue that there are safer and better ways to investigate how the viruses could turn into a pandemic threat.

As the article explains, this was largely based on continuing controversy over H5N1 studies that first began around 2011/12. One of the studies in question used a combination of genetic engineering and serial infection of ferrets to develop a mutant H5N1 virus that could spread among animals without direct contact. Another took a different approach and created a H5N1-H1N1 re-assortant virus that was capable of airborne spread in ferrets.

When news of these studies leaked in late 2011, it triggered a review by the US National Science Advisory Board for Biosecurity (NSABB), given the 60% fatality rate in known human H5N1 cases. According to an article published by The Lancet in February 20188, the concern was that ‘malign actors’ could replicate such works to deliberately cause an outbreak in human beings. After much debate, the studies were published in full in 2012.

Guidelines have subsequently been issued for funding decisions on GOF experiments likely to result in highly pathogenic H5N1 viruses transmissible from mammal to mammal via respiratory droplets. These were later expanded to include H7N9 viruses too. Yet there were reported to have been several breaches of protocol at US government labs in 2014 and such research has been mired in controversy ever since. October 2014 saw the US National Institutes of Health (NIH) implement a moratorium on certain GOF experiments, stating it “will be effective until a robust and broad deliberative process is completed that results in the adoption of a new US Government gain-of-function research policy.” 

That process concluded and the moratorium rescinded by 19th December 2017, with the NIH promptly resuming the funding of gain-of-function experiments involving influenza, Middle East respiratory syndrome coronavirus (MERS), and severe acute respiratory syndrome coronavirus (SARS)9. This is a topic that remains clouded in scientific division, conjecture, conspiracy theories and counter-claims – as any such search engine query will demonstrate – and only fuelled by the devasting impact of the Covid-19 pandemic since January 2020.

Indeed, the NIH was compelled to issue a statement10 on misinformation about its support of specific GOF research on 19th May 2021, during which it made clear that the NIH and the National Institute of Allergy and Infectious Diseases (NIAID) “have for many years supported grants to learn more about viruses lurking in bats and other mammals that have the potential to spill over to humans and cause widespread disease. However, neither NIH nor NIAID have ever approved any grant that would have supported ‘gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans.”

The statement added that the NIH strongly supports the need for further investigation by the World Health Organization (WHO) into the origins of the SARS-CoV-2 coronavirus and urged the WHO to ‘begin the second phase of their study without delay’.

“The question for many is, did it enable an emerging virus to escape and avoid all subsequent control for well over 12 months?”

Given that GOF research is such a big and established area of science, it is plausible that such a novel virus could be manufactured in a lab and especially so considering a history of outbreaks related to the coronavirus family of genomes. Think here of the SARS1 and MERS viruses, for example. Better understanding and protecting against these viruses is a reasonable reason for such research, it could be argued.

Equally, that lab could feasibly have been in any number of locations around the world. The argument bringing it back to the Wuhan Institute of Virology, however, is that this is renowned for being a leading world centre for research on coronaviruses – and of course, that the first known cases of Covid-19 were reported in Wuhan itself. When the pandemic first broke out in December 2019, Chinese authorities reported that many cases had occurred in the wet market of Wuhan, a market selling wild animals for meat and the subsequent focus of the world’s media when the epidemic became a pandemic.

The Wuhan Institute of Virology has by its own admission been designated a home of research for viruses and infectious diseases, biosafety and virus culture collection. Its website states that when the SARS virus broke out in the country in 2003, the state and the Chinese Academy of Sciences promoted the prevention and control of newly emerging diseases to a new strategic height, with the Wuhan Institute of Virology adjusting its discipline layout in a timely manner11.

“On the one hand it was to have the advantage [of] integration for the traditional pre-ponderant disciplines such as insect virology, aquatic animal virology, biological control, analysis of biotechnology; on the other hand, through the training and the introduction of talents, it was to lay out a series of medical virus-related discipline groups, engaged in the researches of HIV, influenza virus, hepatitis virus, tumour virus and zoonotic virus and virus replication and antiviral drugs,” it explains.

In 2004, the Chinese and French governments signed a cooperation agreement on fighting and preventing new diseases, stressing the active cooperation between China and France in the construction of high-level biosafety laboratories and the systematic construction of biosafety laws and regulations. In order to implement the spirit of the Sino-French agreement, in 2005 the Wuhan Institute of Virology undertook the task of building a national biosafety laboratory of Wuhan, Chinese Academy of Sciences. The lab facilities were completed in January 2015.

Interestingly, the laboratory aims to carry out scientific research on the prevention and control of new infectious diseases and biosafety in order to meet the needs of early warning, detection, research and biosecurity prevention system for emerging infectious diseases in China. It was expected to become the prevention and control research and development centre for China’s emerging infectious diseases, virus culture collection centres and a WHO reference laboratory, which would play a basic and technical role in China’s emerging infectious diseases prevention and control, and biosafety.

The question for many is, did it enable an emerging virus to escape and avoid all subsequent control for well over 12 months?

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The case for natural emergence

The counter answer to that question focuses on the theory of natural emergence, currently the commonly accepted ‘route to market’ for Covid-19.

There is still not yet any conclusive evidence to prove this, however. Further still, no firm conclusion about the role of the Huanan market (the so-called wet market in Wuhan) in the origin of the outbreak, or how the infection was introduced into the market, can currently be drawn, according to the WHO-convened Global Study of Origins of SARS-CoV-2: China Part (14th January – 10th February 2021)12.

In May 2020, the World Health Assembly in resolution WHA73.1 requested the Director-General of the WHO to continue to work closely with the World Organisation for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO) and countries, as part of the One Health approach, to identify the zoonotic source of the virus and the route of introduction to the human population, including the possible role of intermediate hosts.

The aim is to prevent both reinfection with the virus in animals and humans and the establishment of new zoonotic reservoirs, thereby reducing further risks of the emergence and transmission of zoonotic diseases. In July 2020, the WHO and China began the groundwork for studies to better understand the origins of the virus. Terms of Reference (TORs) were agreed that defined a phased approach, and the scope of studies, the main guiding principles and expected deliverables. The WHO selected a multi-disciplinary team of international experts to work closely with a multi-disciplinary team of Chinese experts in the design, support and conduct of these studies and to conduct a follow-up visit to review progress and agree upon a series of further studies.

The joint international team comprised 17 Chinese and 17 international experts from other countries, the WHO, the Global Outbreak Alert and Response Network (GOARN), and the World Organisation for Animal Health (OIE). The Food and Agriculture Organization of the United Nations (FAO) participated as an observer. Following initial online meetings, a joint study was conducted over a 28-day period from 14th January to 10th February 2021 in the city of Wuhan, People’s Republic of China.

The summary of the report, published on 30th March 2021, explains that an epidemiology working group closely examined the possibilities of identifying earlier cases of Covid-19 through studies from surveillance of morbidity due to respiratory diseases in and around Wuhan in late 2019. It also drew on national sentinel surveillance data; laboratory confirmations of disease; reports of retail pharmacy purchases for antipyretics, cold and cough medications; a convenience subset of stored samples of more than 4,500 research project samples from the second half of 2019 stored at various hospitals in Wuhan, the rest of Hubei Province and other provinces.

In none of these studies was there evidence of an impact of the causative agent of Covid-19 on morbidity in the months before the outbreak of Covid-19. Furthermore, surveillance data on all-cause mortality and pneumonia-specific mortality from Wuhan city and the rest of Hubei Province were reviewed. The documented rapid increase in all-cause mortality and pneumonia-specific deaths in the third week of 2020 indicated that virus transmission was widespread among the population of Wuhan by the first week of 2020. The steep increase in mortality that occurred one to two weeks later among the population in the Hubei Province outside Wuhan suggested that the epidemic in Wuhan preceded the spread in the rest of Hubei Province.

The report states that many of the early cases were associated with the Huanan market, but a similar number of cases were associated with other markets – and some were not associated with any markets. Transmission within the wider community in December could account for cases not associated with the Huanan market which, together with the presence of early cases not associated with that market, could suggest that the Huanan market was not the original source of the outbreak.

Other milder cases that were not identified, however, could provide the link between the Huanan market and early cases without an apparent link to the market. No firm conclusion therefore about the role of the Huanan market in the origin of the outbreak, or how the infection was introduced into the market, can currently be drawn.

With a firm conclusion yet to be drawn on the source of the virus in terms of specific location, what of the host animal or medium that could have brought this into the human ecosystem?

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The molecular epidemiology and bioinformatics working group examined the genomic data of viruses collected from animals. “Evidence from surveys and targeted studies so far have shown that the coronaviruses most highly related to SARS-CoV-2 are found in bats and pangolins, suggesting that these mammals may be the reservoir of the virus that causes Covid-19,” the report states. However, it adds that neither of the viruses identified so far from these mammalian species is sufficiently similar to SARS-CoV-2 to serve as its direct progenitor.

The high susceptibility of mink and cats to SARS-CoV-2 suggests that additional species of animals may act as a potential reservoir, yet there is further inconclusion when the report goes on to state that there has still been no evidence of wider animal infections in China despite ‘extensive testing’.

It explains, “The animal and environment working group reviewed existing knowledge on coronaviruses that are phylogenetically related to SARS-CoV-2 identified in different animals, including horseshoe bats (Rhinolophus spp) and pangolins. However, the presence of SARS-CoV-2 has not been detected through sampling and testing of bats or of wildlife across China. More than 80,000 wildlife, livestock and poultry samples were collected from 31 provinces in China and no positive result was identified for SARS-CoV-2 antibody or nucleic acid before and after the SARS-CoV-2 outbreak in China.”

“Through extensive testing of animal products in the Huanan market, no evidence of animal infections was found.”

The joint international team behind the report made a series of recommendations for each area and in doing so assessed the likelihood of different possible pathways for the introduction of the virus. It conducted a qualitative risk assessment across four scenarios for the introduction or ‘pathway’ of Covid-19, considering the available scientific evidence and findings.

The joint team’s assessment of likelihood of each possible pathway was as follows:

  • Direct zoonotic transmission to humans (spillover) – Considered to be a possible-to-likely pathway 
  • Introduction through an intermediate host, followed by spillover – Considered to be a likely-to-very-likely pathway 
  • Introduction through the (cold) food chain – Considered a possible pathway 
  • Introduction through a laboratory incident – Considered to be an extremely unlikely pathway. 

Despite these pathway assessments and the apparent lack of confidence in a synthetic emergence via a laboratory incident, there is still no conclusion on the origins of a natural emergence of Covid-19.

It is a widely held belief that civets (considered a delicacy in China) may have played a role as intermediate host in the outbreak of SARS from 2002 – 2004, and an initial theory had been put forward about a similar role of pangolins (a prized meat delicacy in parts of China and Vietnam) as intermediate hosts in the outbreak of Covid-19. The joint report acknowledges, however, that “subsequent epidemiological and epizootic studies have not substantiated the contribution of these animals in transmission to humans. The possible intermediate host of SARS-CoV-2 remains elusive.”

Elusive is an interesting if not appropriate term upon which to close this opening part of our playbook. By definition it describes something that is difficult to find, catch or attain, or perhaps difficult to remember. As we now know with the story of Covid-19, there is an incredible juxtaposition with the term ‘elusive’.

This is a virus that has proven anything but, having ravaged the world due to its sheer transmissibility; and yet it was so often described as the invisible enemy for the very same reason. It’s a virus that has eluded countless control measures, track and trace systems and preventative actions; yet it has been such a searingly painful and poignant experience, that we will never forget it. Science, virus history and GOF research arguably suggests we should have been better equipped to handle and understand this pandemic; yet the origins of Covid-19, whether natural or otherwise, remain elusive. 

Sources

1. https://en.m.wikipedia.org/wiki/2019_in_film

2. https://www.cdc.gov/flu/pandemic-resources/1918-commemoration/1918-pandemic-history.htm

3. https://en.wikipedia.org/wiki/Spanish_flu#cite_note-:17-3 

4. https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov

5. https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ 

6. https://en.wikipedia.org/wiki/Gain_of_function_research

7. https://www.cidrap.umn.edu/news-perspective/2014/05/experts-call-alternatives-gain-function-flu-studies

8. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30006-9/fulltext

9. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research

10. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-misinformation-about-nih-support-specific-gain-function-research

11. http://english.whiov.cas.cn/About_Us2016/Brief_Introduction2016/

12. https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part