Mapping future viral threats

Bette Browne speaks to Dr Jonna Mazet of the Global Virome Project about how the initiative was established to
identify and characterise zoonotic viruses in order to better predict and respond to future viral pandemic threats

“Virus hunters”, determined to stop the next lethal pandemic, are hoping world leaders will row in behind their project to track down over half a million undiscovered animal viruses that can transmit deadly diseases to people. The virus experts are part of the Global Virome Project, which aims to compile a genetic atlas of all the viruses circulating in animals.

“It’s still in the foundational stages, but we’ve shown it is worth doing and is not too expensive,” Prof Jonna Mazet, Professor of Epidemiology and Disease Ecology, University of California Davis, US, and Implementation Director of the project’s leadership board, told the Medical Independent (MI). An estimated 1.6 million viral species are yet to
be discovered in mammal and bird populations and, of those, about 650,000 to 840,000 can infect and cause disease in humans.

Indeed, viruses and other microbes are the oldest form of life on earth and together comprise 60 per cent of its living matter, according to experts at the Harvard Global Health Institute. Most are considered beneficial or cause no great harm to humans and their livestock, but some are regarded as a major and constant challenge to humanity. According to the World Organisation for Animal Health, 60 per cent of pathogens capable of causing symptoms in – and even killing – humans originate in animals. The 2018 Prince Mahidol Awards Conference in Thailand noted global trends that indicated new microbial threats will continue to emerge at an accelerating rate, driven by growing populations, expanded travel and trade networks, and human encroachment into wildlife habitat.

A single lethal microbe can emerge suddenly and spread rapidly to every household and community without regard to national borders, experts have warned. The Sars, Ebola, and Zika outbreaks did little to prepare the world for the Covid-19 pandemic, the Virome Project website emphasises. These serve “as a clarion call that we are vulnerable to emerging viral threats”.

The Global Virome Project was conceived five years ago at an international conference of health experts, including the WHO, in response to the repeated emergence of viral epidemics and pandemics threatening the health and lives of millions of people around the world. The three core benefits, which the virome project aims to provide are: Early warning of future threats; data to improve prevention and reduction of these threats; and advance preparation of responses for unexpected outbreaks of unknown diseases.

The Covid-19 pandemic has slowed the progress of the project and it has yet to see experts on the ground, Dr Mazet told MI. “It’s up and running, but not as far yet as boots on the ground and finding the viruses. That’s had to take a break with a moratorium on research work because of Covid.”

PREDICT and Deep VZN

Before Covid-19 hit, US scientists and researchers had progressed the initiative as part of the country’s PREDICT programme, which has seen its work boosted since the Biden administration took over in January. Dr Mazet explained that the US contribution had proved the Global Virome Project could work successfully on a global scale. “I feel very confident that we’ve laid the groundwork for it,” Dr Mazet stressed. Dr Mazet ran the virome element of the PREDICT programme for 11 years and that aspect is now set to be re-launched as Deep VZN (Discovery and Exploration of Emerging Pathogens – Viral Zoonoses), she said.

“The US-funded phase of the Global Virome Project will be Deep VZN and this will contribute the data for the global virome initiative.

“Our team will be bidding for Deep VZN in May, but there will be many others bidding as well and I don’t know who will lead it, but I feel very confident that we’ve laid the groundwork for it, so all the foundation is ready for whoever is successful.”

Dr Mazet is heartened by the support for the US contribution to the project from the new Biden administration. “I’ve been very encouraged that they’ve made it a priority and are following through by making sure the resources are available,” she said.

President Biden’s Chief of Staff Mr Ron Klain has commented that “a three-pronged agenda focused on mitigating that risk – pushing for better and faster vaccine development and deployment, a stronger emergency response infrastructure, and a more robust global health security system – can make us safer.”

Supporters of the project also say characterising the global zoonotic viral diversity and ecology would result in a range of advances in human and animal health, including the development of new technologies and diagnostics, risk mitigation strategies, and eventually advances in vaccines and therapeutics.  With global support for the Global Virome Project, scientists say the world will be better prepared to deal with the consequences of escalating ‘spillover’ of deadly viruses in about 10 years.

Some have compared the Global Virome Project to the work of the Human Genome Project in the 1980s, which led to new technologies that ushered in an era of personalised genomics and precision medicine. Similarly, they say the Global Virome Project could spur development of pathogen discovery technologies, provide a wealth of publicly accessible data and lead to unanticipated discoveries, perhaps viruses that cause cancers, mental health or behavioural disorders. It could also enhance the ability to identify vulnerable populations and prevent global pandemics.

But for that to happen the Global Virome Project needs leadership and support from world leaders, Dr Mazet emphasised. “The 11-year-old US PREDICT project is really the first contributor of data in a large-scale way to the Global Virome Project,” she explained.

“That foundational work allowed us to do the calculations on how much time it would take to find all the viruses.
“So now it’s up to the global policy community to take it to the next level and that is happening, but there hasn’t been a start yet to the 10-year clock. The rubber hits the road when people have to put their resources into it.

“When you’re talking billions of dollars it means the big donor countries have to commit to it. We’re saying this is possible and now the world should get on top of it. Unfortunately, it took the Covid tragedy for people to really focus on it.”

G7

A big test of global commitment and support will come in June at the G7 summit of the world’s major industrial nations, which will be asked to back the work of the virome project. The summit will be held in the UK.

“(Former British prime minister) David Cameron is championing the project and is now taking it to the G7 in June. It will also be discussed at the meeting of the G20 nations in October.”

The G20 brings together the G7 major industrial countries plus 13 other countries, including Australia, China, India, and central bank governors and the European Union. “Covid-19 has demonstrated how one microscopic virus, 1,000th the width of a human hair, can engulf an entire planet. In doing so, it has exposed both the strengths and weaknesses in countries’ abilities to respond to such outbreaks. And one clear weakness is the capacity to detect such diseases early and, therefore, to act quickly,” Mr Cameron declared last June.

“It wasn’t until the end of December 2019, a considerable time after the first patient suffered symptoms, that China alerted the WHO to an increase of pneumonia-like cases in the province of Wuhan. It was then a whole month again before the WHO declared a public health emergency,” said the former Prime Minister. A new international body was needed to sound the alarm more promptly, he said.

Dr Mazet is hopeful that Mr Cameron’s support at the G7 and G20 meetings this year will provide fresh momentum for the project, which still has no multi-lateral funding pulling it together. Cost estimates for the Global Virome Project range from an initial $1.2 billion (€1 billion) to $3.4 billion (€2.8 billion) over a 10-year period. While countries like the US have contributed to the project through the work of the PREDICT programme, there is no consolidated central effort and there may never be, Dr Mazet said.

Individual countries may just take on the work on their own, possibly supported by the Global Fund, until there is a larger initiative from the G7 or G20. The Global Fund invests more than $4 billion (€3.3 billion) a year to support humanitarian programmes run by local experts in more than 100 countries. 

“It may be that different countries, China, Australia, and others, all start working on the project in their own countries and then it won’t be over 10 years. It will be over different timelines in different countries,” said Dr Mazet. But whatever way the virome project progresses, “the world needs to come together and collaborate and share the data, find the viruses and share the information.”

“Both Thailand and China were starting their viral projects before the pandemic. But the pandemic has put this work on hold and has also reduced our ability to collaborate. We had a lot of momentum. It’s ironic that the Global Virome Project stalled because of Covid, the result we were trying to prevent. But I do think that in the end this terrible tragedy will fuel progress with the project. When this pandemic is over hopefully we can be scientists again,” she commented.
But scientific progress also needs funding and investment. In this context, the Global Virome Project makes huge financial as well as humanitarian sense.

Preventing outbreaks can cost far less than reacting to one, as has been learned from the Covid-19 disaster. The Global Virome Project estimates that discovering most of the remaining viral threats and characterising their risk of spillover would cost less than 10 per cent of responding to just one major outbreak, such as the West African Ebola epidemic. The economic, health, and social costs of the 2014–15 Ebola outbreak are estimated to be over $53 billion (€44.4 billion).

The economic cost of pandemics of novel influenza or other readily transmissible viral diseases has been conservatively estimated at $80 billion annually when averaged over a century, according to The Lancet. World economies are also reeling from the financial toll of the Covid-19 pandemic and will continue to do so for some time. Millions of people have lost their jobs or have seen their incomes cut and unemployment rates have soared in major economies.

Millions of workers have also been put on government-supported job retention schemes and pandemic payments, like those in place in Ireland, as essential economic drivers like tourism and hospitality have come to a virtual standstill.
Indeed, some experts fear it could be years before levels of employment return to those seen before the pandemic. The International Monetary Fund, for example, estimates that the global economy shrank by 4.4 per cent in 2020. It described the decline as the worst since the Great Depression of the 1930s.

“To escape from the age of pandemics, we’ll need to treat them as a public health issue and start working on prevention in addition to responses,” Dr Peter Daszak (PhD), a disease ecologist and President of EcoHealth Alliance in New York, wrote in the New York Times on 27 February 2020.

“Our first goal should be to broaden our armory against potential mass epidemics. Pandemics are on the rise, and we need to contain the process that drives them, not just the individual diseases.”

Yet the world’s strategy for dealing with pandemics is woefully inadequate, Dr Daszak wrote. “Across the board, from politicians to the public, we treat pandemics as a disaster-response issue. We wait for them to happen and hope a vaccine or drug can be developed quickly in their aftermath. But even as Covid-19 rages, there still is no vaccine available for the Sars virus of 2002-3, nor for HIV/Aids or Zika or a host of emerging pathogens. The problem is that between outbreaks, the will to spend money on prevention wanes, and the market for vaccines and drugs against sporadic viral diseases isn’t enough to drive research and development.”

With a smaller investment, Dr Daszak believes we can also try to get ahead of pandemics by working with communities in hot spots of emerging diseases. “Disease surveillance should be focused on farmers, rural communities and anyone who has extensive contact with wildlife, to look for unusual illnesses, test for novel pathogens and work with people to develop alternatives to high-risk activities such as the wildlife trade.”

A radical shift is also needed in the way that tests, vaccines and drugs are designed, Dr Daszak stressed, in order that entire groups of pathogens are targeted instead of individual pathogens that are already known.

‘One Health’

With world attention focused on the spread of the coronavirus, infectious disease experts are redoubling their efforts to show the connection between the health of nature, wildlife and humans through the decade-old global initiative known as ‘One Health’, of which Ireland is a member. Backed by the WHO, One Health recognises that human health, animal health and a healthy ecosystem are inextricably linked. Dr Mazet pointed to it as a model for how the Global Virome Project could work, but said the project will also need to evolve and be fuelled by new thinking.

“The model for how we do this virome project needs to evolve and thinking needs to evolve,” she told MI.

“We can’t do what we’ve done in the past. We need to bring the scientists together, we call it the One Health approach, so we don’t have these terrible tragedies where people politicise health. We really need the world to grow and evolve to protect our health but it’s going to take global political leadership.”

While the One Health concept is now widely accepted by health officials, many governments have not factored it into policies that underscore the threat that wildlife-borne pandemics pose to people and the global economy. Dr Cristián Samper (PhD), President and CEO of the Wildlife Conservation Society, America’s oldest conservation organisation, speaking at the One Planet Summit on 11 January, declared that the world is facing three major crises today: The loss of biodiversity, climate change, and the pandemic.

“They are all inter-related, with many of the same causes and solutions,” he told the conference. “We know that pandemics of zoonotic origin such as Covid-19 are directly tied to wildlife trade and the increase in the human-wildlife interface caused by deforestation and forest degradation. What we need is higher ambition, political commitment and financial resources to implement actions over the next decade.”

The work of the Global Virome project is clearly urgent. The growing invasion of natural environments as the global population soars makes another pandemic a matter of when, not if, and it could be far worse than Covid-19. The spillover of animal or zoonotic viruses into humans causes some 75 per cent of emerging infectious diseases. This calls for a new model of “funding and sharing”, Dr Mazet believes. She said the Global Virome Project does need a big injection of cash.

However, she added “it doesn’t necessarily need to go into one pot or be administered centrally”.

“I think this is how this type of work has often been done in the past by international organisations but the world might be ready now for a new model, driven by global equity, where we collaborate and share data and maybe contribute to a central data base hub in which countries do the work themselves and own the data themselves.

“I think that projects like this should evolve and contribute to de-colonising global health.”

Global Virome Project deliverables

The Global Virome Project team says the success of the initiative will be measured by its deliverables. In the course of its 10-year lifespan, these are expected to include:

• Detecting and identifying at least 99 per cent of potential zoonotic viral threats to human health and food security;
• Characterising the host range of the detected viruses (reservoirs and transmission hosts);
• Determining the geographic distribution and ecologic scope of nearly all zoonotic viruses to inform on risk and surveillance in humans and animals;
• Promoting the monitoring of the movement of detected viruses across hosts and regions;
• Improving the assessment of the risk of spillover and epidemic potential;
• Prioritising high-risk viruses for further characterisation, surveillance targeting, research, and mitigation development;
• Strengthening global surveillance networks through local and global capacity enhancements (eg, surveillance, field biology, lab proficiencies, biosafety);
• Enabling in-country/regional laboratory and surveillance capacities to monitor for high-risk viruses across animal-human interfaces;
• Establishing sample biobanks for further research;
• Creating open-access databases that include sequence and metadata;
• Making data and samples available for public health risk assessments and mitigation, as well as further detailed pathogen studies;
• Providing new insights into virus and host biology, conservation and ecology;
• Identifying markers for transmission and pathogenicity for high-risk viruses; and
• Establishing an ethical framework for sample, data, information, and benefit sharing, including authorship and intellectual property.