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����VR��Ƶ’s CEO Dr Richard Hatchett shares his personal reflections on the year and looks ahead to 2025.

Let me begin by expressing to all ����VR��Ƶ’s partners, supporters and (dare I say) fellow travelers our thanks for your good will and endeavors and our warm best wishes for the holiday season.  The problems and challenges the world presents today will await us in the New Year, but for now I pray that circumstances will allow all of you a respite from work, time with your families and time to reflect on the year that has been, and on the year to come. 

As an organization that is international in scope but narrowly focused on the problem of epidemics and pandemics, ����VR��Ƶ has a privileged vantage point.  Like every organization, we have our biases and blind spots – and we can’t see or understand everything that is happening, even in the domains we know best.  But our positioning gives us a wide view of trends and developments that others might not perceive. I see my year-end note as an opportunity to share a little of our perspective: our optimism, where that is warranted, and our concerns, where these must be acknowledged. 

One can always choose to be discouraged.  The context in which we are working to prevent epidemics and pandemics is shaped by the polarization of our societies and pathologies of our geopolitics. And these are genuinely discouraging.  Some of the governments that have done most to support this work are in transition, with the uncertainty that all democratic change brings. Others are in disarray due to the splintering of governing coalitions or loss of public confidence. Others face elections in the coming year, at a moment when anti-incumbent sentiment is high.  All are grappling with serious fiscal constraints and security challenges that demand attention and resources.  Global health institutions are struggling to secure funding, and major initiatives are in jeopardy.  Just one example are the intractable differences between the negotiating parties on certain key issues that have stymied progress and paralyzed negotiations on the Pandemic Accord for months. The prospects for a successful conclusion to this critical process seem increasingly dim. 

All these facts acknowledged and notwithstanding, I have arrived at the end of this complicated year feeling upbeat.  Progress, particularly in areas driven by the evolution of science and technology, seldom follows a neat and linear course (think, for example, of the creative destruction that has characterized the growth of the internet and our digital economy over the last several decades).  Progress is organic.  It grows. Its roots extend continuously and often out of sight, even in the cold and bleak times. Progress materializes – emerges – in ways that can be surprising and sudden, like the spring after winter’s dreariness.  In my effort to describe the year that has been, I will point repeatedly at signs and signifiers of this global organic development. It is these, rather than the foam of political processes, that give cause for optimism. 

That optimism shouldn’t be misconstrued as complacency, however.  This has been a banner year for the viruses.   

In Africa, an epidemic of a new, more virulent form of mpox spread at an alarming pace.  Clade 1b mpox was first detected in the Democratic Republic of Congo in September 2023 and now may have caused as many as 50,000 cases and more than 1,000 deaths.  This virus diffused across the DRC border into Burundi (where it caused an especially large outbreak, involving thousands), Uganda, Rwanda and Kenya and individual cases in travelers have been identified in Canada, Germany, India, Sweden, Thailand, the United Kingdom, and the United States.  In mid-August, Africa CDC and the World Health Organization declared Public Health Emergencies of Continental Security and International Concern, respectively. 

In South America, large outbreaks of the vector-borne diseases Dengue, Chikungunya, Zika, and Oropouche fever occurred across the continent.  More than six million cases of suspected Dengue were reported in Brazil (the highest ever).  These diseases, transmitted by mosquitoes, are all considered to be climate-sensitive, as the range of the transmitting vectors will expand as global warming progresses.  Oropouche, for example, emerged this year in numerous locations where it had never previously been recorded. 

In North America, H5N1 influenza, first introduced to domestic poultry in the U.S. by migratory birds in early 2022, spread into dairy cows, with calamitous results.  The movement of infected cows through the nation’s livestock system caused the massive amplification of the epizootic as it spread to 16 States and involved more than 860 dairy herds.  By the end of the year, more than 60 people in the U.S., in any one of which the virus might mutate or recombine with human viruses to become more transmissible, had fallen ill with the disease.  On 17 December, with almost 650 dairies in his State impacted, the governor of California declared a public health emergency.  In sharply criticizing the Biden Administration’s handling of the outbreak, Zeynep Tufekci described a bird flu pandemic as “one of the most foreseeable catastrophes in history.” 

 These outbreaks, individually and collectively, were notable for their scale and geographic reach and for their diverse epidemiology and virology.  One wouldn’t be wrong to conclude that where viruses are concerned the world is on fire. 

Against this backdrop, the paralysis and trench warfare that have characterized the negotiations on the Pandemic Accord, while intelligible in the isolated terms of the debate, seem almost incomprehensible as the collective human response to a common threat.  Negotiators have been arguing for months over provisions relating to “PABS” (the Pathogen Access and Benefits Sharing System), intellectual property rights, technology transfer, and how to operationalize the “One Health” approach within the treaty framework.  The Intergovernmental Negotiating Body charged with drafting the Accord missed the self-imposed deadline of delivering a completed treaty at the World Health Assembly in May. They missed an aspirational goal to complete it by the end of the year, and they now seem on track to miss delivering it by next May’s World Health Assembly. 

To criticize the conduct and output of the negotiations is not to question the integrity, sincerity or intent of the negotiators.  I have no doubt they are negotiating in good faith, but they are missing the point.  They are negotiating a treaty for the past, in the terms of the past, not a treaty for the future.  What is missing crucially from the debates, it seems to me, is any fine understanding of the converging technologies that offer us a way out of the labyrinth – technologies that will enable us to respond more rapidly and more equitably to future threats.  The solution is not to untangle the Gordian knot but to cut through it – not to solve these unsolvable problems, but to reengineer the system in a way that puts them out to pasture.  Matters that have theological gravity in one context can evaporate when the material conditions change. 

The factors that will come together to change these conditions are several.  They are technological, institutional, and operational in scope.  These factors encompass the evolution and diffusion of technology, new ways of solving the biological problems that diseases throw at us, and new means of production – as well as the creation of new institutions, new coalitions of partners, and new patterns of collaboration, operating in tandem with but outside the multilateral context.  To be sure, managing future epidemic and pandemic risk will require much more than just the availability of countermeasures.  If we needed a reminder, the COVID pandemic taught us that countermeasures are necessary but not sufficient.  I am not (or not merely) a technology evangelist – but let me begin there. 

The pandemic was notable, from a technology perspective, in that it served as a tremendous accelerant.  Particularly in the field of vaccines, the race to produce countermeasures resulted in the validation and production at scale, across wide geographies, of an array of technologies that absent the pandemic might have taken a decade or more to mature and diffuse.  The most widely acclaimed of these technologies – the systems for producing safe and protective mRNA vaccines – averted millions of deaths and prompted the award of the 2023 Nobel Prize in Physiology or Medicine to Katalin Karikó and Drew Weissman.  But other technologies, such as the viral vector platforms underlying the AstraZeneca and Johnson & Johnson vaccines and the protein-based approaches of many others, were also validated, transferred globally  – including to manufacturers in the Global South  – produced at scale, and contributed to saving many more millions of lives.  Numerous manufacturers in the Global South, some for the first time, developed and licensed their own vaccines.  All of these trends are salutary.  Most of these platforms will remain available and can be leveraged in the event of future pandemics, and many are now being extended to develop vaccines against other classes of virus, which will make the case, over time, for their general safety and utility.  Our armamentarium has grown. 

In the long run, though, I suspect that the world will come to recognize that one of the most significant milestones – perhaps the most significant milestone – to be achieved in the pandemic was the licensure, in June 2022, of SK bioscience’s SKYCovione™ vaccine, which was developed in partnership with the Institute for Protein Design (IPD) at the University of Washington (full disclosure: with ����VR��Ƶ funding support).  SKYCovione™ was the first computationally designed medical product to be approved anywhere in the world, for any indication.   

To frame that in slightly oversimplified terms:  it was the first vaccine developed by AI.   

The adoption of the kind of AI-enabled molecular design tools that enabled the development of SKYCovione™ by academic investigators and by biotech firms has been phenomenally rapid and now is contributing to the development of a vast array of products, across almost every domain of medicine.  With respect to its own suite of tools, IPD is committed to making these globally available and democratizing access to them [1].  Dr. Neil King, an Assistant Professor at IPD, has spoken eloquently of the way in which these tools will “push the bottlenecks of product development downstream” to clinical testing and regulation.  Investigators in less resource-rich environments, with more constraints on equipment and benchtop resources, will now be able to participate in developing products to address locally relevant diseases and medical challenges.  And IPD is putting their money, time and commitment where their mouth is:  they have provided training, for example, to investigators from Institut Pasteur de Dakar (the other IPD) to enable them to begin using such tools independently, in an African context.  It was for these accomplishments, and the impact that the tools he has created will have on medical product development and protein design more generally, that Professor David Baker, the Director of IPD, was awarded the 2024 Nobel Prize in Chemistry, along with Demis Hassabis and John Jumper from DeepMind for their work in developing AlphaFold, which uses generative AI to predict protein structures with great accuracy and at incredible speed. 

As such tools become more widely disseminated and incorporated into scientific workflows, and as industry develops the capability to provide mRNA and synthesized proteins on demand, at lower and lower cost, innovation in the biosciences and in the bioeconomy will become truly global.  Manufacturers in more and more regions, and at wider scales of production, will be able to develop products to serve local or regional needs.  The current configuration of production, driven by concentration and economies of scale, will be upended.  This won’t happen next year, but it is the future, and it is coming faster than we think. 

At the same time, the intrinsic potential of the new plug-and-play platforms to pivot from one pathogen to another has promoted a convergence around the idea that for many viral families and genera, vaccine designs can be generalized.  Blueprints can be worked out in advance.  The scaffolding can be ready and waiting for the emergence of a new pathogen.  If we know how we need to modify the spike protein to develop a vaccine against one coronavirus, we can do the same with any new coronavirus and get on immediately with vaccine development.  This is, of course, exactly what we did in 2020, when developers working on SARS and MERS vaccines took what they already knew to leapfrog straight to the clinical development of COVID vaccines.  The foundational concept of developing exemplar vaccines against prototype pathogens from different viral families as a critical aspect of preparedness, first articulated by Barney Graham and Nancy Sullivan in a in Nature Immunology, has now been embraced by the global community of virologists and vaccinologists working on pandemic preparedness and response.  Building out a library of such exemplar vaccines is a critical precondition of ����VR��Ƶ’s 100 Days Mission; and conducting basic through IND-enabling translational research on prototype pathogens in nine high-risk virus families is the core justification of the $100 million that the U.S. National Institute of Allergy and Infectious Diseases has invested in its Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness Network.  

In an important normative development at the end of July, before an audience of hundreds at the Global Pandemic Preparedness Summit in Rio de Janeiro, Ana Maria Henao-Restrepo unveiled a WHO report, , that was more than a year in the making.  The prioritization work underpinning the report involved over 200 scientists from more than 50 countries, who evaluated the science and evidence on 28 virus families and one core group of bacteria, encompassing 1652 pathogens, and placing the viral families framework at the center of global discussions about preparedness. WHO also called for globally coordinated, collaborative research to prepare for potential pandemics.  To facilitate such research, WHO announced that it would enlist research institutions around the world to establish Collaborative Open Research Consortia (CORC) for each pathogen family, with a   acting as a research hub for each CORC. 

The emergence of a shared and generally accepted conceptual framework is important because it arrives in a period – triggered by the pandemic – of institutional ferment.  The establishment and global reach of the CORCs is only one of several emerging institutional arrangements that will create new opportunities for collaboration and collective action against epidemic and pandemic threats.   

Under a G7 initiative, for example, a number of Development Finance Institutions, led by the U.S. Development Finance Corporation, have worked on a (MCMs). The programme will provide timely support for the production, procurement, and distribution of vaccines, therapeutics, diagnostics and other MCMs for low- and lower-middle-income countries during unfolding public health emergencies, to address gaps identified during COVID, and to ensure a rapid and equitable response to future pandemics.  And this, of course, is not to mention the World Bank’s Pandemic Fund, which has now allocated grants of almost $1 billion, catalyzing an additional $6 billion in co-financing and co-investment.  

Since the pandemic, new institutions charged with the development of MCMs have been created by Canada, the European Commission, Germany, Italy, Japan, South Korea, and Singapore while existing governmental and private sector institutions have significantly expanded their capabilities in Brazil, the UK, France, Senegal, India, and probably many other countries.  ����VR��Ƶ has convened an informal MCM Funders Roundtable to foster the exchange of information, share best practices, and promote collaboration between these entities.  At its most recent meeting, in Geneva in December, the members of the Roundtable were joined by representatives from the CORCs and the Global Research Collaboration for Infectious Disease Preparedness to facilitate awareness of each other’s activities and explore opportunities for partnership.  These institutions are perfectly placed to embrace and accelerate the agenda laid out in the WHO Pathogens prioritization report. 

A final area of institutional change that is worth mentioning relates to the aspirations of different regions to enhance their manufacturing capabilities and capacity.  Some institutions, such as Bio-Manguinhos/Fiocruz in Brazil, Bio Farma in Indonesia, Institut Pasteur de Dakar, and the Serum Institute of India, have moved rapidly to expand capacity and acquire new plug-and-play vaccine platforms, including mRNA.  In June, Gavi launched a new mechanism, the , to support the sustainable growth of Africa’s manufacturing base through (1) milestone payments for achieving WHO prequalification and (2) a per dose “top-up” payment known as an “Accelerator payment” to be added to any payments received under a UNICEF tender.  South – South cooperation has been facilitated through the Regionalized Vaccine Manufacturing Collaborative, most notably in the area of pooled procurement, where PAHO, drawing on its long experience with the Revolving Fund, is assisting the efforts of Africa CDC to establish such a mechanism in Africa.  

The establishment of rapid response platforms at an increasing number of manufacturing facilities in the Global South, coupled with the democratizing features of the new molecular design tools and the groundswell of intellectual and institutional support for the viral families framework, will contribute critically to those liberating changes in material conditions that I spoke of above.  As these changes and new configurations of productive capacity take hold, the issues that are flummoxing us now – that are preventing progress on the Pandemic Accord – will become less and less relevant, until they evanesce away entirely, passing out of sight and collective memory as a new, more distributed, and more equitable capacity to respond to future public health emergencies takes root. 

Such advances won’t realize their full potential unless they are matched by operational capability when the crises come.  It is one thing to have the tools at hand, another to know how and be able to use them when they are needed.  The observation that “Amateurs talk strategy; professionals talk logistics” is sometimes attributed to U.S. General Omar Bradley, the first Chairman of the Joint Chiefs of Staff.  Whether Bradley said this or not, the observation rings true: actually delivering a result requires mastery of the mechanics, and the mechanics can be perfected only through practice.  If we are serious about responding effectively to future pandemic threats – if we even want to dream about preventing future pandemics – we must master the execution and mechanics of response. 

While many of the responses to this year’s crop of infectious disease emergencies do not give cause for optimism, one outbreak has been managed superlatively well, and I would like to conclude this year-end note by celebrating it.  Today marks the formal end of the Marburg virus outbreak in Rwanda, two full incubation periods (42 days) having passed now without the identification of any new cases.  As Rwandan Minister of Health Nsanzimana and I wrote in a in today’s Telegraph, Rwanda’s Marburg response could serve as a masterclass in how to prevent pandemics.  As soon as the outbreak was recognized, Rwanda immediately implemented a muscular response, including isolation of and initiation of aggressive supportive care for cases and testing and tracing of contacts along with enhanced infection prevention and control measures.  Within nine days of the declaration of the outbreak, the Rwanda Biomedical Center had initiated clinical trials of experimental therapeutics and begun an open-label Phase 2 clinical trial of an investigational vaccine developed by the Sabin Vaccine Institute.  Rwanda’s swift action saved lives, prevented significant damage to the Rwandan economy, and helped protect the rest of the world from the virus.  From the point that the vaccine trial was initiated, only nine additional cases were recorded, and the case fatality rate of the epidemic (<23%) was the lowest ever recorded for a Marburg outbreak.  Rwanda’s effective response is undoubtedly attributable to its having practiced over several years, including more recently with ����VR��Ƶ and other partners, how it would respond in the event of a viral hemorrhagic outbreak, even though such outbreaks had never previously been recorded in the country.   

Through its prompt action, and in addition to setting an example for the world, Rwanda has helped to illuminate aspects of what it will take to deliver ����VR��Ƶ’s 100 Days Mission.  For that, we at ����VR��Ƶ can be grateful and it is one of the reasons I am looking forward to 2025 with optimism. 

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[1] The Institute for Protein Design is also one of the leading advocates for the and has led the call for community-wide standards in this domain.