Marion Koopmans & Mischa Huijsmans – A Virologist in a Changing World

 

Introduction

The morning light streamed in through the curtainless windows of my old room. I woke up reluctantly, having gone to bed late the previous night, still unsettled from a hastily arranged journey out of London and back to my parents’ house in the Netherlands. The first Dutch lockdown measures had only just come into effect, following a few local school closures and a ban on large gatherings. The sudden closing of restaurants and schools had taken the country largely by surprise and I’d joked with my friends about the sudden implementation, which had given cafe patrons half an hour to down their drinks before venues closed and led to massive queues of people stocking up at their local coffeeshop. After cataclysmic scenes in northern Italy, national lockdowns were rapidly being instituted across Europe and the prospect of a UK lockdown had shifted from unlikely to apparently inevitable. Figuring that a major metropolis would be a less-than-ideal place to be during a global pandemic, and with my parents instead in a nice, detached house near a forest, I’d decided to head to the Netherlands for a couple of weeks and wait for lockdown restrictions to blow over. I would end up staying for five months.

Flying was out of the question at that point. Partly due to mom’s job and partly due to our family’s penchant for disaster flicks, I’d watched just about every major pandemic movie, and it seemed like every single one began at an airport. I talked it over with mom and we figured that the safest option was to travel by boat. Taking no chances, I cycled to the train station, passing restaurants and pubs still bustling with people – London hadn’t gotten the memo yet. I boarded a practically empty train bound for Harwich, the English port from which an equally sparsely occupied ferry would sail to Hook of Holland. Despite its 1200-person capacity there were perhaps a few dozen people on board, each with a sizable corner of the ferry to themselves.

Dad was waiting for me when the ferry arrived. Because I’d just come from a major city and both mom and dad were at elevated risk due to their age, we would have to strictly distance within the house for the first couple of weeks. It felt surreal, not being able to hug, as if we were caught in some bizarre Hollywood fantasy. Once we came home, the three of us had sat outside and talked deep into the night about the events that had unfolded since January and what else might be coming.

That was two weeks ago now, and my quarantine was finally over. I got up, dug through my bags for a fresh shirt and headed downstairs. Voices ringing out through a tinny laptop speaker revealed that mom was in a meeting, and I tiptoed around to grab the coffee jug – dodging her webcam to avoid sharing my morning hair with the leadership of the World Health Organization. In what was to become a theme, the jug had been drained long before I made it to the kitchen. Asking mom through hand gestures whether she wanted more coffee, I quietly set myself to making a fresh pot. With the coffee maker sputtering, I tried to match the voices coming out of mom’s laptop with some of the faces I’d seen on TV. There was the voice of Tedros Ghebreyesus, his Ethiopian accent unmistakable after weeks of press conferences and WHO statements. Then there was the equally distinct Irish voice. What was the man’s name again? Something, something, Ryan? My pre-morning-coffee attention span exhausted, I poured two cups and went outside to make some sudokus.

Professor Doctor Marion Koopmans, whom I know as ‘mom,’ was a blur in those days. Running from one zoom meeting to the next and stopping only to grab a quick bowl of yogurt or piece of fruit to eat as she poured over the endless stream of new reports and insights. Usually there were two or three moments in the day when she could tear herself away from her work. She made a point of stowing away her laptop during dinner and, for half an hour, paying no mind to all but the most urgent phone calls. Late at night we’d all head upstairs for one or two episodes of Desperate Housewives, which was our designated pandemic entertainment. And then there were the walks. Once a day on most days, for  fifteen minutes or so – and occasionally for several hours during the weekend – we would walk through the forests near the house, clearing our heads and talking about her work, the uncertainties and manic pace of the pandemic, the mixture of joy and frustration that came with international cooperation, or just about anything else. This book is a result of those and many, many subsequent zoom meetings once I returned to the UK.

‘The novel coronavirus’ or SARS-cov-2, the virus responsible for Covid-19 infections, changed the direction and pace of lives across the globe. No doubt the pandemic will feature prominently in future history books, where experts will argue about the immensity of its impact. Yet, despite all of this, the first weeks of the outbreak were a familiar process for our family. My mom had begun working in public health long before I was born. Growing up, my sister and I had gotten used to seeing her work on other outbreaks, epidemics and pandemics, including norovirus, SARS, MERS, bird flu, pandemic flu, monkeypox, Ebola, and Zika. It meant that she’d be busier than usual for a few months, until the outbreak of the day was better understood and reigned in through public health measures or the development of vaccines. On the surface, based on the reports in early 2020, SARS-CoV-2 looked similar to the 2002 SARS outbreak – a disease caused by the ‘original’ SARS-CoV. With a high fatality rate of around ten percent, the 2002 outbreak had alarmed scientists and triggered a worldwide response before being contained. Just over 8,000 people would be infected worldwide by the end of the outbreak. The virus caused massive disruption and halted international travel in the areas where it circulated, but ultimately did not have any major impact on the rest of the world. The same is true for countless other small and larger outbreaks that have occurred in the last few decades. Even amid the Covid-19 pandemic, updates continued to trickle in on West-Nile virus cases in Europe, MERS in the Middle East, an international monkeypox outbreak, infections of humans in Malaysia with a canine coronavirus, H5N8 bird flu on a poultry farm in England, and H5N1 bird flu all over the world. Those outbreaks too remain – at least for the moment – limited in scale. How does that work? What makes Covid-19 different from other viral diseases? How did this particular coronavirus swell in mere months from a local anomaly to a global pandemic? How does virus and outbreak research take place? What lessons have we learned, or perhaps failed to learn, with regards to future pandemic preparedness? And what, in all this, is the role of our rapidly changing environment?

 

Ebola

 Once again, the first signs were hard to spot. In December 2013, a young boy from a small village in Guinea (West Africa) died from severe diarrhea. Sadly, as we’ve seen in earlier chapters, diarrheal disease is still one of the leading global causes of death, and the case was not initially recognized as anything unusual. When another five fatalities linked to diarrhea were recorded in the same area, a medical alert was issued to the local authorities. These early cases were still being diagnosed as other diseases like Lassa fever, which were known quantities in the area and could cause similar symptoms. A team from Doctors Without Borders arrived in Guéckédou on March 18th and started an epidemiologic investigation. They collected blood samples that were shipped to laboratories in Europe, where laboratory tests confirmed the Ebola virus outbreak. By the time of diagnosis on April third, the outbreak had already been underway for four months, and had been able to spread uncontrolled through three of the world’s lowest income countries.

Unlike, say, the MERS virus, Ebola was fairly well known at the time. The first cases of Ebola Virus Disease (EVD) were documented in 1976, during an outbreak in Sudan and the Democratic Republic of the Congo. Scientists knew that the virus circulated among Central African fruit bats and could occasionally resurface around the region. It had never before been seen in West Africa though, and since the DRC is about as far from Guinea as Spain is from Norway, Guinean doctors had not been looking for Ebola.

The Ebola virus causes a very severe disease that usually begins with fever and muscle pains, progresses to vomiting and severe diarrhea, and in the final stage can cause fatal internal bleeding. It usually presents as a severe stomach flu, which of course can be caused by numerous other viruses, bacteria and parasites. Most deaths from Ebola do not come from internal bleeding but from fluid loss, as patients can produce up to 8 liters of stool per day. It kills around half of all those infected, although the actual numbers have varied between 25% and 90% in past outbreaks – largely dependent on access to healthcare and safe drinking water.

Ebola, just like norovirus for instance, spreads through direct contact with an infected person, eating contaminated food, or via contaminated material like bedding or sewage. Around the region and especially in the rural areas where the outbreak began, the sick were usually looked after by their families. The lack of advanced medical and sanitation equipment meant that the carers were likely to get sick in turn. A detailed reconstruction showed the grim reality of the outbreak. Of the fourteen people who were initially infected with the virus, twelve died, including the sister, mother and grandmother of the toddler who is thought to have been the first patient. The first known patient in an outbreak is often called ‘patient zero.’

The few local specialist there were traveled from village to village, and the reconstruction suggested that the virus had spread outside Guéckédou through a visiting midwife. She was hospitalized in Macenta, a town of around 90.000, where a doctor and several of his relatives died of the disease in the following weeks. Macenta lies just north of Guéckédou, where blood samples from these patients were the first to be tested by Doctors Without Borders. The fact that it had taken so long to discover the outbreak was due to the total absence of any kind of syndromic surveillance system. The meager public health and laboratory infrastructure meant that the disease could spread quickly and undetected to neighboring Liberia and Sierra Leone.

Now that the epidemiologists working in the region knew the cause of the outbreak, they also understood how to respond. Finding active cases became the highest priority, as a quick medical response both reduced the risk of the patient dying and could help stop any further infections. Fortunately, no airborne infections with the Ebola virus have ever been recorded, including in laboratory experiments, so isolation, contact tracing, quarantine and thorough decontamination of places where patients had stayed had been successful strategies for containing other Ebola outbreaks. The plan was easy enough in theory but beset by logistical challenges. During the first months of the Covid-19 pandemic, ramping up the capacity to test and contact trace proved a persistent bottleneck even in the highest-income countries. Just imagine trying to do the same in a region with minimal infrastructure, very few doctors, nurses, epidemiologists and laboratories, and a recent history of war and other armed conflicts. Mistrust of the government ran deep, and most rural areas were difficult to reach besides.

 

International response to Ebola in West Africa

Despite the best efforts of local doctors and NGO’s, the virus kept spreading. On August 4th, with over 1100 confirmed cases, the WHO declared the outbreak to be PHEIC – Public Health Emergency of International Concern – and activated its collaborating centers. Marion held meetings within the department to discuss how the Erasmus MC could contribute. Several volunteers came forward, and she began looking for ways to connect them to aid organizations on the ground. She contacted a team of Belgian scientists who were preparing to set up an emergency hospital and lab in the region. While she discussed the possibility of teaming up with them, the Dutch government announced that it would be sending an emergency aid package to help fight the Ebola outbreak. A brand-new Dutch Royal Navy ship was to sail for the West African coast in three weeks’ time, loaded with shipping containers full of vehicles, medical supplies and other equipment.

Among the thousands of items listed on the ship’s manifest, a set of three ‘container labs’ caught Marion’s attention. She knew there were companies that built fully functional labs inside of easily transportable shipping containers but hadn’t heard of anyone building them in the Netherlands. Intrigued, she tried to find out where the containers came from and was eventually put in touch with the manufacturer. As it turned out, they had been looking for someone to consult on the layout and safety of the container labs. Over the course of the conversation, Marion realized that the company had previously built hospital facilities inside shipping containers but had no experience designing laboratories. She suspected there would be a few blind spots where her team could help and invited the manufacturers over to the Erasmus MC to discuss the project.

 

Chapter 7

On the 31st of December 2019, my mom was at home. Dad was out for his daily run, and she had just opened her laptop to fire off the last few emails of the year when she saw a message from The Program for Monitoring Emerging Diseases (ProMED). It read:

UNDIAGNOSED PNEUMONIA – CHINA (HUBEI): REQUEST FOR INFORMATION

The email reported that a number of people had come into various hospitals around the city of Wuhan with ‘pneumonia of unknown cause.’ The patients had been isolated and researchers from the Wuhan CDC were rapidly collecting samples. The first patient was believed to come from Wuhan South China Seafood Market, and several other patients were linked to the same location.

A follow-up email came shortly after. It stated that SARS had not yet been ruled out, but readers need not panic. If the unknown pneumonia was indeed SARS, the limited infectiousness of that virus would be no match for the protocols put in place after 2003. The market had been closed immediately and disinfection was already under way. Since ProMED is an open mailing list that experts and non-experts alike can subscribe to, it also listed the preventative measures one could take: wash your hands, ventilate well and avoid crowded spaces where possible.

She told my dad about the message from ProMED. He knew the drill; they’d had a version of this conversation at least a dozen times now.

‘So, it’s going to be another busy couple of months?’

‘Not sure yet,’ mom replied, ‘but it might be headed that way.’

As they prepared for the evening, she ran the standard list of questions in her head. The emails were not exactly encouraging. There clearly were more than just a couple of cases, and it seemed strange people were being told that all would be well, ‘even if it turned out to be SARS.’ The assurance did not exactly fit reports of emergency meetings and experts being flown in from Beijing. What were they dealing with here? Could it be a bird flu? Marion knew that, despite the name, these ‘seafood markets’ often traded in all sorts of animals. The Wuhan authorities insisted there were no live mammals like the civet cats that had been the source of the first SARS cases in 2003. If there was a zoonotic link, this kind of market was a perfect place for a virus to jump from one species to another. Contaminated meat and fish combined with often meager hygiene standards meant there was a real risk of contagion – even without the presence of live mammals. They would know soon enough – the Wuhan labs were exceptionally well-equipped and ruling out known viruses would not take long.

Marion wrote quick email to her colleague at the Guangdong CDC, Dr. Changwen Ke. She had known him for years, mainly through their collaborative work on emerging disease preparedness. Their collaboration had been a part of a larger project that involved the RIVM, VWS and the Guangdong CDC, and aimed to help the various Chinese CDCs prepare for and respond to future outbreaks. One of their projects was an environmental sampling program at various Guangdong markets, many of which were similar to the Wuhan Seafood Market. The sampling program aimed to better understand the role of wet markets in the spread of infectious diseases. These are traditional markets where fresh produce is sold, often including live animals that can be butchered on the spot.

The program was run by a veterinarian from my mom’s team, Reina Sikkema, as part of her PhD research. A junior scientist from Dr. Ke’s team tested the environmental samples. The team regularly found avian influenza viruses in their samples and discovered that the markets in Southern China were a melting pot for different avian influenza variants. Based on that research, Marion thought this outbreak might be some new influenza variant. She asked Dr. Ke for his thoughts and to update her when he could.

There was not much more she could do that evening. She put the questions aside, closed her laptop, and left with Ad to ring in the new year with her old friends from vet school.

 

Huanan Seafood Market

Naturally, the WHO team wanted to visit all the sites and institutions that had been involved in the initial outbreak investigations. The team wanted to speak with the market manager, the staff of the traditional Chinese hospital that had picked up the first patients and alerted the Wuhan health service, the dedicated hospital for Covid patients, the staff of the various CDC’s, the Wuhan institute of virology, and so on. These visits have received a lot of criticism from international media since then. Commentators sometimes suggested that the visits were merely part of some propaganda show, given that the team could not move around freely and that every step was extensively filmed and photographed. Of course, that was partially true, but Marion found the visits useful regardless as she got a much clearer picture of what the pandemic’s ‘ground zero’ really looked like.

The scientists walked around the now closed Huanan Seafood Market with a map that showed where the first cases had been found. They examined the layout of each different section of the market, the inventories of what had been sold in each of the stalls, the water supply and the drainage system, and so on. All in order to better understand the data that had already been collected. Several members of the WHO team had considerable experience in outbreak investigations, and a good chunk of the visit was filled with conversations with their Chinese colleagues and increasingly detailed questions for the local teams who had carried out the initial investigation a year earlier. The environmental investigation team showed where they had collected their samples and how they had chosen the sites for sampling. The stalls with price lists for different (animal) food items spoke of the busy trade that had taken place here.

Back at their hotel, the team discussed what they had observed, what had stood out, what they thought was credible information and where they had doubts. Then they prepared more detailed questions for the Chinese teams the next day. It was the kind of slow, painstaking, step-by-step process of discovery that my mom enjoys, and has been digging into for most of her career.

The Chinese team was led by Liang Wannian, the international team led by Peter Benembarek from the WHO. Not, as I initially thought, by three gentlemen named Peter, Ben and Barack. As per usual during meetings in China, each event began with a series of formalities. My mom, who generally prefers to get the ‘executive summary’ anyway, felt more impatient now because there was so little time to begin with. After all, they would only be in Wuhan for four weeks. It was unfortunate that the usual icebreaker social events, where the formalities could be relaxed, were impossible due to the quarantine rules, the huge media presence, and the short duration of the visit.

 

The findings

At the end of their visit, the origin investigation team drew up a 120-page document (plus 193 pages of annexes) detailing their findings. With a series of dense tables, charts and graphs, they explained their research, their methods and how they had arrived at their conclusions. The team surmised four possible routes:

  1. Introduction directly via a wild animal host.
  2. Introduction via wild animals through a second species with which humans come into contact more frequently.
  3. Introduction via the food chain, for example through contaminated meat.
  4. Introduction through a laboratory incident.

 

Now, as is hopefully clear from the rest of this book, the historical evidence overwhelmingly favors the explanations that involve spillover from an animal reservoir. SARS-1, MERS, monkeypox, H1N1 flu, HIV and many other diseases have come from animals.

To illustrate, we’ll briefly jump forward from spring 2020 to late 2022. What have we learned about SARS-CoV-2 over the past two years? We have a much better idea of which animals are and aren’t susceptible to Covid. We have learned that cats, dogs, hamsters and mink can catch the virus. It is now also circulating widely among white tailed deer in the United States and Canada. Mutations play an important role here. Whereas the early SARS-CoV-2 viruses could not infect mice, the late-2020 ‘Alpha’ variant very much could. The United Nations Food and Agriculture Organization did an overall risk assessment on animal infections, but such assessments must be re-examined with each new variant.

The team had combined the data from the many different genetic studies and could see that the viruses most closely related to SARS-CoV-2 had been found in bats and pangolin. If you were to sketch out the measure of genetic similarity to SARS-CoV-2 along a graph, you would see these viruses near the top, several other coronaviruses in the middle, and everything else at the bottom. The closest related virus found to date came from a bat but was still much too different to serve as conclusive proof of an animal origin. For the time being, the original source of SARS-CoV-2 remained unknown.

Why that question remains unanswered nearly 3 years after the outbreak is a topic of hot debate. Origin studies are difficult and often take years. For instance, for SARS, the first evidence came from studies looking for antibodies in bats, and from many subsequent studies in the years following the 2003 outbreak. That is why we know there are numerous SARS-like viruses in bats, some of which closely resembled SARS as it infected civet cats and humans. However, nearly 20 years later the identical parental virus still has not been found. This is a real case of looking for a needle in a stack of other needles with a slightly different design. By comparison, it took 8 years before there was proof of bats as a reservoir for Ebola where, as with SARS, no identical virus was ever found both in bats and humans. On top of all that, the burden of proof for the origins of the coronavirus pandemic is considerably higher.

 

The lab leak theory

To most virologists, the team’s conclusions seemed logical, but because their explanations partially resembled those put forward by the Chinese government, some in the media suggested that the team had buckled under pressure. While my mom did not agree with that suggestion, she did point out how important it was that the scientists stay neutral amid the – sometimes very loudly proclaimed – opinions and emails from researchers who sent in all sorts of unverifiable information. The team discussed these data as well but decided only to work with information that had either been published or could be independently verified. After weighing all available evidence, the team rated the first three explanations listed above variously between ‘possible’ and ‘very likely’

Another possibility, at least in theory, was the fourth option: that the virus had leaked from a Wuhan lab. Given the long list of infectious diseases that originated from animals, there are few virologists who consider it a likely possibility. In support of the lab leak theory, the WHO team noted that ‘although rare, laboratory accidents do happen.’ The question for the team was if they could find any evidence to suggest such an incident had occurred here. The members had planned interviews with each of the labs involved in the initial outbreak research in 2020. One of the CDC labs in Wuhan had moved on the 2nd of December, and of course such moves could be disruptive. But the viruses that were being studied in this lab were very different from SARS-CoV-2. So even if the hypothetical lab incident had occurred, there still was no evidence whatsoever that SARS-CoV-2 could have come from there.

Another lab the team visited was led by a researcher who studied viruses in bats. She had discovered SARS-like viruses in local bats, but had been openly sharing many of her results at international meetings and in scientific publications. The WHO team examined her data and looked at detailed studies mapping out the relationship between SARS-CoV-2 and the viruses studied in the labs, and again there was nothing bearing a close enough resemblance to SARS-CoV-2 to be considered a source. Based on the available evidence, the team therefore considered the lab leak theory to be ‘extremely unlikely.’

The main conclusions of the report were presented at a press conference in Wuhan. Right up until the event, the various teams were dotting the i’s and crossing the t’s on their conclusions and recommendations. This again was a painstakingly precise process. Images of that press conference, and of my mom, Peter Benembarek and her other colleagues, went around the world.

Of course, these kinds of studies – like any other – invite scientific criticism, but in this case, it seemed that many minds had been made up before the report was even made public. The media mostly ignored the 313-page report and fell over themselves covering the press conference instead. Literally – mom had press running after her taxi as if she was a rockstar. She explained the report’s tentative conclusions and calls for follow-up investigations, and what it all meant for the ongoing pandemic.

After a year and a half of Covid, tempers were running short all around. I had observed it in myself. A few friends were still holding out on getting vaccinated, and my patience on the topic had worn down to a stub. Adil, my housemate and close friend, still didn’t see the point.

‘I’m just not sure bro,’ he told me when I asked what was holding him back. ‘I don’t see anyone at work and I’m healthy anyway. I heard people get sick from the shot. I can’t be missing work you know.’

Another friend, Mo, told me ‘I still haven’t been vaccinated you know. I’m not antivax or anything, everyone in my family had the shot. So, if I’m around them… well they’ve had the shot. I wouldn’t stop anyone from getting it, it’s just that I personally don’t think I need it. If that makes sense.’

We talked about the individual versus the societal, if he didn’t get vaccinated that might be fine, but if too many people didn’t then nobody would be as well-protected.

‘I hear you man. Everything you’re sayin’ makes sense to me, but I don’t know…’ he said. ‘I do wear a mask if I’m in a crowd. Maybe I’ll get the vaccine if I have to travel.’ He mused for a moment. ‘Don’t you think you’re in kind of a bubble though?’ He asked. ‘Like, you’re telling me these antivaxxers are crazy, but I hear guys that would say the same thing about you.’

I had to laugh. ‘I’m sure they do. And I’m sure they’ll quote studies and things that support what they’re saying. But… well, have you ever met a flat-earther?’

He had at that. The conspiracy theory holds that the earth is in fact flat, and that NASA and the world’s leaders have conspired to keep this a secret. It is among the wilder conspiracy theories out there, but a 2018 poll found that 2% of over 8.000 respondents in the U.S. firmly believed that the earth was flat. If accurate and representative, that’s nearly 7 million people in that country alone.

‘Yeah man,’ he said. ‘Man, those guys are intense. But they really believe it.’

‘Yup. And they’ll say you’re crazy and deluded too for not believing it. Wake up sheeple.’

Mo chuckled. ‘You know I got two friends who are doctors yeah? One of them’s pro-vaccine, the other is antivax. Like proper antivax. I heard them argue one time, literally saying the same things to each other. Both sayin’ oh you haven’t read the studies, you’re a liar, it’s misinformation. They were standing across the room calling each other sheep.’

 

The Wakefield study

Ok so before we continue: when we use the word ‘antivax’ in this book, we explicitly do not refer to people who have doubts or questions about vaccination, or even to those who have made the personal choice not to get vaccinated. Rather, we refer to the very small number of people who actively discourage others from getting vaccinated, either based on ideology or – as increasingly seems to be the case – based on some conspiracy theory. Likewise, we use ‘conspiracy’ and ‘conspiracy theory’ here to refer to ideas for which there is little to no factual evidence, and which most people will recognize as unlikely to be true. A ‘conspiracist’ in this context is someone who uncritically adheres to such views.

As with lockdown resistance, reasonable people can disagree on vaccination, and we will elaborate on that before the end of this book. For now, we just want to note that those sides of the debate that ground themselves in baseless conspiracies appear to be by far the most problematic and seem to have contributed materially to social unrest, stagnating vaccination rates and to the threats and abuse aimed that my mom and her colleagues receive. Although the networks through which misinformation is spread have changed dramatically thanks to the internet, sowing confusion through questionable science is by no means new. Remember we wrote about the WHO’s efforts to eliminate measles? Vaccination campaigns were well underway, until the publication of a bombshell study in on February 28th, 1998.

British not-a-doctor Andrew Wakefield probably did more damage to vaccination efforts than anyone alive today. In his now-infamous study, Wakefield claimed to demonstrate a link between vaccination and autism, writing that ‘the onset of behavioural problems had been linked […] with measles, mumps and rubella [MMR] vaccination.’ (Wakefield 1998) and concluded that children could become autistic after taking the MMR vaccine. The article was published in The Lancet, one of the world’s oldest and most authoritative scientific journals, in a lapse of the usually critical peer review. The study and its conclusions were soon revealed to be seriously flawed, but that did not prevent Wakefield from publicly calling for a halt to MMR vaccines until more research could be done.

The Lancet retracted the study when it became clear that Wakefield’s data were seriously flawed. On top of that he had strong financial ties to the vaccine that should, according to him, replace the MMR vaccine. The litany of ethics violations and conflicts of interest, and the numerous subsequent large-scale studies that found no link whatsoever between vaccines and autism, did precisely nothing to lessen Wakefield’s popularity. Far from becoming the sort of pariah you might expect, Wakefield today is revered among antivaxxers. He has appeared on far right talk shows that get millions of visitors, and there decries his treatment at the hands of the medical establishment. During an interview on the influential ‘alternative media’ platform Infowars sometime in the 2010’s he said ‘whatever the media say about me, whatever the politicians say about me, it doesn’t matter, because I don’t matter. What matters is the future of this country, and the future of this country is its children.’

Since the study came out, there has been a resurgence of measles outbreaks across the Western world that continues to this day.

I don’t know whether my friends ended up getting the vaccine. While I wouldn’t say it’s a topic we actively avoid, it is one that leads to tough conversations. I also find it difficult not to take those conversations personally, given the ideas the misinformed can have about scientists like my mom. At the same time, they have made me optimistic. It really can help to hear someone out, have the discussion, and offer suggestions to get them out of the downward spiral of misinformation. But what do you do when someone is so far detached from reality that a normal, mutually respectful conversation becomes impossible?

 

Afterword

Now, nearly three years after the start of the outbreak, we’re in what Marion would call a transition phase. As of October 2022, there have been over 600 million cases of Covid-19, and more than 6.5 million people have died from the infection. Nevertheless, the acute crisis seems to be over. In many countries the majority of people have been vaccinated or have at least been offered vaccination. Walking around an overcrowded airport, festival or sports event, you would not say that we are still in the middle of a major infectious disease outbreak. Containment measures have mostly been scaled back or scrapped, and fewer people are being tested for Covid-19. Yet, as hard as it is to hear, the pandemic is far from over. By late summer 2022 there were still around 400 Covid-patients in Dutch hospitals, and that number has since climbed up to around a thousand, with what looks to be the start of a new wave of infections. There is a growing group of patients with post-Covid syndrome for whom the medical profession does not yet have much to offer. SARS-CoV-2 has spawned several variants that continue to evade immunity, like Omicron and an ever-growing number of other variants. We continue to see widespread infection and the impacts thereof both on healthcare systems and society at large. There are no signs that any of these impacts will disappear any time soon. And without reliable monitoring and prevention programs, we could easily be caught off guard again.

The global inequity with regards to medical care has been made painfully clear by Covid. Per September 2022, only around 20 percent of the population of Africa had received a vaccine, partly due to logistical barriers and partly because the first vaccines were immediately hoarded by economically rich countries, including the Netherlands. Unless and until there is global equity in access to vaccines and drugs, as well as ongoing global coverage in disease surveillance, we will continue to face waves of infection, probably with new variants, that will have an impact around the world. With the current monkeypox outbreak we (again) see the result of this ‘me first’ thinking: there are clear indications that this virus had been spreading around Nigeria for several years before the worldwide outbreak began. Vaccines for monkeypox exist, but instead of a targeted approach to stop the virus in Nigeria by making vaccines available, we are seeing the exact same run on scarcely available vaccines. As a result, we are now dealing with slow and painstaking containment efforts in more than eighty countries.

 One of the lessons mom had hoped – and still hopes – we might collectively learn coming out of the pandemic is the need for a serious societal debate on how we are going to deal with epidemics and pandemics in the future. Viruses are part of our world, but that does not mean we can’t affect how much they circulate. Our societal work ethic generally held that ‘you do not stay home for a bit of flu-like illness,’ even if that means potentially exposing others to your infection. Is that really the way forward in an aging society with a growing number of vulnerable people?

Early in 2022, when the Omicron wave began to subside, the now-minister of Health, Welfare and Sport, announced a change in strategy. He tasked the different sectors (education, hospitality, healthcare, transportation etc.) with drawing up their own mitigation measures that could be implemented quickly when and if we see significantly increasing circulation again – which is not unlikely. The idea of any new containment measures is met with a lot of skepticism, but with everything we now know, it would be mad if we did not prepare for the eventuality. At the end of the day, good preparation and basic measures can prevent the need for lockdowns and other last-ditch containment strategies. That means some tough decisions have to be made, but for Marion it’s not an option to just do nothing and leave it up to the most vulnerable people in society to ‘take care and hope for the best.’ Looking to the future, it seems clear that we will continue to see surprises. It is certain that there will be additional waves, possibly with new variants, and Covid currently is far from a predictable endemic disease.

In the future, the medical advice provided by the OMT would be balanced with expert advice on societal impact. Perhaps in the future there could be other bodies similar to the OMT, made up for instance of social scientists, psychologists and economists to come up with their own set of recommendations throughout the different stages of a crisis situation. The OMT’s role again is to review the epidemiological, virological, and clinical data on Covid-19, and come to a consensus advice based on those data.

 

PDPC

The pandemic has reinforced my mom’s belief in the importance of preparedness research. In her conversations with Ernst Kuipers, who at that time was still head of the board of directors at Erasmus MC, she’d stressed the importance of thinking about the future role the hospital would play. SARS-CoV-2 was at the center of everyone’s attention and given her past experiences with the funding systems in the Netherlands, she could see how the government would probably try to encourage a kind of free market thinking to push for innovation, while relegating other work to public institutions. Unlike in some other countries, where major investments would be made in academic pandemic centers led by recognized experts in the field, that kind of format went against the long-time Dutch policy of research investment. To help promote an alternative way of doing things, Marion joined Ernst Kuipers and Rotterdam mayor Ahmed Aboutaleb in 2021 for the launch of the ‘Pandemic & Disaster Preparedness Center’ (PDPC), which would bring together experts from Erasmus MC, Erasmus University and TU Delft.

Although my mom has been working within the complex, sometimes baffling funding system, it has never discouraged her. Over the course of her career, she has secured somewhere between 75 and 100 million euros in grant funding for the different teams and (international) consortia she has been involved in. She does however scratch her head when seeing the sometimes-astronomical sums of money that were spent during the pandemic on ‘promising technologies and studies,’ not always backed up by good research. The allocation of government funds happens partly based on earning potential and collaboration with industry – a model that in Marion’s eyes is not well-suited to preparedness research. It’s also a question of scale. She regularly mentions the ‘one billion euro’s’ spent over 6 months of experiments with the events sector into reopening with tests for entry – a sum that could have funded the PDPC with some 300 scientists for the next 20 years. And just look at the financial cost of the pandemic, which just in the Netherlands is estimated to be around 100 billion euros, while entire reference labs might get something like a hundred thousand to do their work. If the government were to invest more into scientific research that benefits outbreak prevention, it would see a huge return on that investment, even if it comes in the form of prevention rather than profit.

As my mom sees it, one of the most important lessons from the pandemic is the need for new types of research. In order to meet the complex and interconnected challenges of the future, she and her PDPC colleagues are promoting multidisciplinary national and international collaborations between experts from different fields. The problem is that such projects are hard to fund in the current climate, within a funding system that expects – if not encourages – competition rather than collaboration between institutions. Marion and her colleagues argue that there should be a non-competitive academic research agenda, perhaps modelled after the Dutch ‘Delta’ program. The program, launched after a series of disastrous floods in the mid-1900’s, funded the reinforcement of dikes and water management systems, but also invested in ambitious research programs that have landed us many of the Netherlands’ world-leading innovations in waterworks. Although floods were relatively rare, the Delta Works have always received plenty of funding.

The signs when it comes to research funding are not particularly positive. Conversations about investment have reverted back to the pre-pandemic priorities: investing in the public sector and in collaborations with industry. Marion does not have much faith in those collaborations, especially given the increasing societal concerns about conflicts of interest, the huge profits made by some companies during the pandemic, and of course the completely unequal access to vaccines, diagnostics and treatment. Extra funding for basic research has been announced, but again within the system that promotes competition and fragmentation.

None of this prevents my mom from throwing herself fully into the PDPC. She is very enthusiastic about the first collaborative projects, where complex topics are examined through new combinations of scientific expertise. What impact will climate change have on mosquito-borne infections? How do you measure airborne transmission? How can you protect the population and increase its resilience? How do you respond to a growing anti-science and disinformation movement? Is it possible to both measure biomedical and societal impacts of an event, and how would you do that in a fast-moving crisis? What will the surveillance systems of the future look like, and is there room for collaboration with the major logistical bottlenecks that need to start thinking about preparedness anyway, like Schiphol airport and the Rotterdam harbor?

 

Faith in science

Marion also stresses the importance of the societal impacts of a pandemic, and the position of scientists and science communicators. A crisis puts society under pressure, which leads to frustration and anger. That is all understandable, if painful for those on the receiving end of that vented anger. Even the fact that some people use these events to shamelessly plug misinformation – whether knowingly or in cynical furtherance of some social or political goal – is nothing new under the sun. But how do you ensure that scientists can still do their work safely? At what cost do scientists like my mom step into the public eye? What do you do when some from within the political establishment shamelessly plug misinformation? Are our democracies ready for the internet age? Can we have honest and respectful conversations about the issues of the day when there is so much misleading information out there, or when those trying to have the conversation are discredited and labeled the worst names under the sun? Probably not. This topic affects all scientific disciplines, and trust in science needs to be continually earned.

In the meantime, my mom will continue to study emerging disease. She unfortunately feels less optimistic about our ability to contain outbreaks than she did at the start of the pandemic, for the reasons mentioned above. Still, we must continue to invest in this, because the next outbreak is never far away. As things stand, investment often does not come until an outbreak is already happening – including the production of vaccines and diagnostics. Like continuing to bail out a boat that has been leaking for decades. Marion thinks we could be doing much more. The scientific community knows where most epidemics come from and what the high-risk areas are. With proper funding, that knowledge could be used to set up smart warning systems to help detect outbreaks before they get out of hand. Projects like PDPC and her own VEO – Versatile Emerging infectious disease Observatory – are her way of at least flagging that there can (and in her view, should) be a different way of doing things. In November 2019, a month before the first infection with the novel coronavirus was detected, Marion co-wrote an article in Nature magazine. It read: ‘we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world-especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow’s leaders in epidemic prevention and response.’

Marion tries to practice what she preachers in the national and international projects she heads. VEO and PDPC try to combine the expertise of ecologists, climatologists, economists, social scientists and many more disciplines to address the complex issues of our day. Climate change, sea level rise, extreme weather, changing travel patterns, habitat destruction and many other factors are literally changing the landscape of emerging disease preparedness. The Netherlands is at the forefront of these developments, because a densely populated country below sea level with rapidly rising average temperatures is feeling these changes sooner than some other countries and will have to adapt to the future.

How can we prepare, not just for the coming winter or for next year, but for the coming decades? What is coming our way? How can we predict that? How can we measure that? How, when we actually get there, can we communicate the information and get everyone on the same page? And what can we do as a society to reduce the risks of new outbreaks? During the Covid-19 pandemic, most countries by and large thought of their own populations first. Aside from the ethical issues with that distinction, it makes no epidemiological sense to divide these things country by country. The concept of borders is not one that viruses care about, and real preparedness will require more international cooperation. By breaking down the disciplinary and geographical boundaries, and by promoting cooperative research over an ‘every man for himself’ mentality, this kind of research might have a chance to flourish.

Utopian? Maybe. But that’s what it will take to truly prepare for the next Disease X.

 

 

Translation by Mischa Huijsmans