Pandemic Center

All known life is homochiral. DNA and RNA are made from “right-handed” nucleotides, and proteins are made from “left-handed” amino acids. Driven by curiosity and plausible applications, some researchers had begun work toward creating lifeforms composed entirely of mirror-image biological molecules. Such mirror organisms would constitute a radical departure from known life, and their creation warrants careful consideration. The capability to create mirror life is likely at least a decade away and would require large investments and major technical advances; we thus have an opportunity to consider and preempt risks before they are realized. Here, we draw on an in-depth analysis of current technical barriers, how they might be eroded by technological progress, and what we deem to be unprecedented and largely overlooked risks (1). We call for broader discussion among the global research community, policy-makers, research funders, industry, civil society, and the public to chart an appropriate path forward.

A new threat now looms. In a recent publication in Science, we joined an esteemed list of researchers in raising the alarm about risks of ongoing efforts to create ‘mirror life’. If created, mirror life could lead to the destruction of life, the environment and food systems across the globe, including exacerbating inequities that already exist in low- and middle-income countries.

Every year, more than one million people die from antimicrobial resistance. It is one of the most important global health threats, according to the World Health Organization. This sentiment was echoed at the recent Jeddah Conference, where representatives from more than 57 countries pledged to move towards decisive multilateral action on antimicrobial resistance.

Antimicrobial resistance is also fundamentally a matter of health equity. It disproportionately affects low- and middle-income countries: diseases caused by bacteria that are resistant to antibiotics spread more quickly, and are more lethal, in developing countries. At the same time, high-income countries disproportionately contribute to the overconsumption and overproduction of antimicrobial drugs that can cause and exacerbate antimicrobial resistance in the first place.

This pattern of global inequity extends beyond antimicrobial resistance, with the Global South (countries of the developing world) often suffering the consequences of problems predominantly created by the Global North.

A new threat now looms. In a recent publication in Science, we joined an esteemed list of researchers in raising the alarm about risks of ongoing efforts to create “mirror life”. If created, mirror life could lead to the destruction of life, the environment and food systems across the globe, including exacerbating inequities that already exist in low- and middle-income countries. We must ensure that scientists and policymakers from developing countries are included as part of the discussions and leadership about governing mirror life.

Mirror life refers to organisms created with “mirror molecules”. Mirror molecules have the same structure as natural molecules, except they are flipped, like how one’s left hand is a mirrored version of one’s right hand. Proteins are made up of amino acids that are normally found in a “left-handed” form, and DNA is made up of nucleic acids that are normally found in a “right-handed” form. Mirror forms of these molecules, such as right-handed amino acids and left-handed nucleic acids, are rarely used in nature, but can be artificially created in laboratory settings. By putting together mirror proteins, DNA, and other mirror molecules, scientists may be able to create entire mirror lifeforms.

Spread unchecked
We argue in our paper that mirror bacteria (the form of mirror life most likely to be created first) could evade human, plant, and animal immune systems, which have evolved to protect against microbes found in nature. Beyond getting past our immune systems, mirror bacteria also could evade natural predators like viruses that target bacteria (bacteriophages), which would enable mirror bacteria to spread relatively unchecked throughout nature, with potentially devastating effects on the environment and the world’s food systems. A pandemic caused by mirror bacteria would have catastrophic effects worldwide. For these reasons, in our paper, we argue that mirror life should not be created. We call, as well, for broader governance around mirror molecules.

Mirror life may create unprecedented, worldwide risks, and its effects would be felt by all countries. The severity and scope of its impact could be quite unlike anything that has been seen before. Luckily, few laboratories are actively interested in the development of mirror life — and none of them are in developing countries. However, it would be a grave injustice if the discussion of governance around mirror life included only stakeholders in high-income countries, as it is the low- and middle-income countries that could be the most affected if mirror life were ever to be created. Hard as it is to imagine, the proliferation of mirror life, and its devastating consequences on human and animal immune systems, might require isolating bunkers to house humans and their life support systems — an expensive enterprise.

Covid-19 has demonstrated that the effects of novel biological threats hit hardest in the Global South. These countries are less able to provide emergency healthcare to those affected, and if we were to succeed in developing new drugs to counter mirror life, they would probably be amassed and stockpiled by high-income nations. This is the same pattern we’ve seen in practically every pandemic. The 1918 Influenza — which killed up to 50 million people — began spreading in Europe, yet South Africa and India were two of the worst affected countries. A pandemic due to mirror life could be much more disastrous.

It is imperative that those driving the threat from mirror bacteria recognise their responsibilities and actively engage leaders from low- and middle-income countries in the discussions around governance. Ensuring representation of the Global South will enable transparency and accountability. Engaging appropriate global entities to provide oversight and accountability over research into mirror life would be essential to facilitate the protection of all countries.

Countries and organisations in the Global North should work with regulators in developing countries to create governance for any laboratory that develops an interest in working on mirror life in the future. This would also prevent laboratories from dodging regulations by moving their research to developing countries.

Fortunately, scientists who are engaged in the research that would serve as a precursor to the creation of mirror life are cognisant of the risks. The development of mirror life is something that can still be halted. While an entire mirror bacterium could pose a significant threat, the synthesis of specific mirror biomolecules on their own do not pose similar risks — and, in fact, could lead to new medicines.

Oversight
For instance, mirror proteins have been touted as an option for creating drugs to fight HIV, still an ongoing pandemic disproportionately affecting regions such as southern Africa. Innovation in this space needs to be diffused worldwide, so that low- and middle-income countries can benefit just as much as high-income nations. The peaceful and beneficial uses of such precursor research underscore the need to engage experts everywhere in discussions about oversight and to instill a hyper-awareness as to when to stop the research before it becomes dangerous.

With mirror life, the world has the invaluable opportunity to avoid repeating the mistakes of the past. Practices that have led to antimicrobial resistance are key examples where actions taken by high-income countries can have negative effects in low- and middle-income countries. Similarly, (industrial) practices that have led to climate change have been largely led by countries of the Global North, with disproportionate impacts on the Global South. Air pollution has largely been caused by industrial corporations and high-income nations burning fossil fuels, yet it disproportionately affects low-income communities and causes diseases like lung cancer to become more prevalent in vulnerable populations.

Global action wasn’t taken rapidly enough to prevent the devastating consequences of antimicrobial resistance, climate change, and air pollution. The risks posed by the potential to create mirror life are unparalleled and fall in a class of their own. However, when it comes to mirror life, we have the chance to act wisely — now — and prevent a damaging worldwide impact. Incorporating global perspectives into the governance of mirror life is the only way to ensure we are all safe. DM

Wilmot G. James is a Professor in the Department of Health Services, Policy and Practice and Senior Advisor to the Pandemic Center in the School of Public Health, Brown University, Providence, Rhode Island. Vaughn S. Cooper is Professor in the Department of Microbiology and Molecular Genetics and a founder of the Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

n 27 September 2024, Rwanda’s Health Ministry confirmed the country’s first ever Marburg virus outbreak. It was a distressing national moment: a filovirus like Ebola, Marburg is lethal with fatality rates of up to 88%. Symptoms are dreadful, including intense feverishness, acute headaches, vomiting and bleeding from the eyes, gums and elsewhere – “bad news wrapped up in protein” as Nobel Laureate biologist Peter Medawar put it in 1974.

Six weeks later, on 15 November 2024, Rwanda’s Minister of Health Dr Sabin Nsanzimana, announced the discharge of the last of the Marburg patients. The virus sadly caused 15 early deaths, but of the 66 cases, 55 patients recovered.

He noted that it had been 48 days since the first case was reported, two weeks since the last new case and a month without further fatalities. If no new infections arise 42 days after the last case tests negative, the outbreak will be declared over by December 21.

It is an admirable achievement by any measure. In a context where the recent US presidential election and the controversial cabinet and agency nominations drive the news cycle, it is important to heighten the visibility of Rwanda’s achievement, of how a lower-middle-income country in mid Africa managed to contain an outbreak caused by one of the world’s most feared high-consequence pathogens.

What happened in Rwanda is captured by Louis Pasteur’s famous aphorism that “chance favours the prepared mind” or, as in this instance, the prepared response system.

In 2008, when Nelson Mandela hosted Nobel Laureate David Baltimore to give a science lecture on the origins of HIV, Baltimore travelled to South Africa via Rwanda at the invitation of President Paul Kagame where he was asked — far-sightedly — to give the country’s leaders advice on how to ground development in science.

In 2018 Rwanda was one of the first countries to conduct the World Health Organization’s Joint Evaluation Exercises in pandemic preparedness and response, which assessed the most critical gaps in their human and animal health systems and prioritised opportunities for enhanced preparedness, detection and response within the framework established by the 2005 International Health Regulations.
A National Action Plan for Health Security, a roadmap to strengthen the International Health Regulations’ core capacities, followed the Joint Evaluation Exercises. The Rwandan government, through its Ministry of Health and Rwanda Biomedical Centre, worked tirelessly to tick all the points by ensuring the readiness and the resilience of the system for any outbreak. The implementation was smooth and ready.

Rapid response
When Covid-19 hit, Rwanda responded quickly. The authorities imposed a six-week lockdown and introduced contact tracing and other interventions — 82% of the population received at least one dose of a Covid-19 vaccine.

The Australian think tank the Lowy Institute ranked 98 countries for their Covid-19 response and found that smaller populations and capable institutions were the most important factors in managing the global pandemic. Rwanda was the only African country in the top 10 achievers.

Rwanda therefore had been working hard over the long haul to upscale their preparedness. The hospital-based surveillance system gave an alert that triggered the national public health institute — the Rwanda Biomedical Centre — to detect the Marburg virus, which in turn switched on contact tracing, diagnostics and case management.

Co-infection with malaria (Marburg/Ebola share symptoms with malaria) slowed down detection of the first case. However, diagnostics were quickly scaled up and 7,408 tests were administered with a focus on healthcare workers who suffered 80% of the infections.

Epidemiologists ultimately traced the first case back to a 27-year-old mining cave worker. He was exposed to the reservoir of Marburg virus, the fruit bat Rousettus, and subsequently infected his pregnant wife who was admitted to the King Faisal Hospital’s ICU in Kigali.

In the following days, many healthcare workers were infected and fell ill. Rwanda has a sizeable and growing mining industry, and is a major exporter of the so-called 3Ts — tin, tantalum, tungsten — and increasingly gold. Some of the mines are close to Rwanda’s extensive network of 52 caves, some 2km long, many of which have large bat colonies.

At King Faisal and the rapidly deployed Marburg Treatment Centre at Baho International Hospital, patients received prompt intensive care support; use of high flow nasal canula; and intravenous fluids to manage high fever, nausea, vomiting and diarrhoea. Intubation and life support were provided to patients experiencing multiple organ failure. Two Marburg patients were extubated i.e. taken off life support, the first time in Africa.

Infection control measures were implemented in hospitals, including personal protective gear distributed to all health workers. Rwandan officials monitored the health of more than 1,000 community members and engaged in door-to-door surveillance in exposed neighbourhoods.

Schools and hospital visits were suspended and the number of people who could attend Marburg funerals was restricted. Even with relatively prompt detection, most of the deaths were of exposed healthcare workers.

The WHO supplied 12,000 personal protective items, sufficient to run the specially built 50-bed Marburg Treatment Centre with its clinical isolation units for 30 days. A joint WHO and Rwandan Ministry of Health infection prevention and control team trained 520 healthcare workers in infection control and prevention.

Gilead Sciences, a global biopharmaceutical company that revolutionised HIV treatment and prevention, donated 5,100 vials of remdesivir, a broad-spectrum antiviral medication previously used to treat Covid-19, as an emergency treatment measure.

With support from the United States’ Biomedical Advanced Research and Development Authority, Mapp Biopharmaceutical deployed a monoclonal antibody MBP091 that targets the Marburg virus. Almost all the initial doses were given to healthcare workers.

‘Ring vaccination’ strategy
The Sabin Vaccine Institute donated more than 1,700 doses of an investigational Marburg Phase II clinical trial vaccine (manufactured by the company ReiThera) to administer to high-risk groups, including healthcare workers, mine workers (exposed to virus-carrying bats in caves in mining districts), and individuals in contact with confirmed cases. Half received the vaccine immediately, and the other half 21 days later to align with the end of the disease’s incubation period. The “ring vaccination” strategy was deployed.

Marburg vaccine efforts must be seen against the background of a major effort under way to establish Rwanda as one of Africa’s leading vaccine manufacturers. BioNTech opened its first modular messenger mRNA vaccine manufacturing facilities in Kigali in April 2024.

The Coalition for Epidemic Preparedness Innovation landed its 100 Day Mission there, working with IQVIA (clinical trials), Ginkgo BioWorks (wastewater surveillance), the Rwanda Biomedical Centre and the Rwanda Development Board on end-to-end vaccine manufacturing prospects.

Regionally, Africa Centres for Disease Control and Prevention dispatched a team of experts on 29 September to aid response efforts. In collaboration with Rwanda’s neighbours — Burundi, Uganda, Tanzania and the Democratic Republic of the Congo — Africa Centres for Disease Control and Prevention provided guidance on regional surveillance and containment strategies.

It cautioned against using travel bans and movement restrictions targeted at African countries as inconsistent with international health guidelines that undermine public health responses, deepen economic challenges, ignite inequities and prompt mistrust.

Instead, what is required is the harmonisation of regional and global policies when an outbreak like this occurs.

Finally, there is the critical asset of leadership, with President Paul Kagame and his cabinet members, and Dr Sabin Nsanzimana, an epidemiologist and former director-general of the Rwanda Biomedical Centre, in command of the effort.

WHO Director-General Tedros Ghebreyesus praised Rwanda for its response, noting that “leadership from the highest levels of government is essential in any outbreak response, and that’s what we see here in Rwanda”. To symbolise Rwanda’s partnership with the continent-wide public health technical support agency the Africa Centres for Disease Control and Prevention, Dr Nsanzimana held his press briefings jointly with its director-general, Dr Jean Kaseya.

Even so, we can do even better, and we must learn much more. Rwanda’s response was exceptional, but it wasn’t perfect. Disease detection could have been much faster. The virus spread in the hospital before being picked up.

We need to get on top of the ecology and migration patterns of the bat carrying Marburg and other viruses, and better understand the impact of rising temperatures, altered rainfall patterns and habitat loss due to mining and human incursions that drive bats to new areas in search of food and shelter.

Climate affects food availability and causes nutritional stress, disrupts hibernation and breeding patterns, and droughts and floods can drive bats closer to human settlements, all opportunities for greater viral transmission. Upscaled surveillance of the pathogens, the disease and the ecology of bats can create a knowledge base for better interventions.

It is not a stretch to say that the world — including the developed world — can learn a great deal from Rwanda. This is the true meaning of global health, an exchange of knowledge, expertise and best practice between North and South, not one-way traffic from North to South. DM

Wilmot James is a Professor at the School of Public Health and Senior Advisor; Craig Spencer a Professor in the School of Public Health; Anne Wang a Research Assistant; and Bentley Holt Assistant Director of Communications and Outreach at the Pandemic Centre, Brown University, Providence, Rhode Island, USA.

Edson Rwagasore is the Division Manager of Public Health Surveillance and Emergency Preparedness and Response, Rwanda Biomedical Centre, Kigali.

Jeanine Condo is an Adjunct Associate Professor at the University of Rwanda and Tulane University and CEO of the Centre for Impact, Innovation and Capacity Building for Health Information and Nutrition, Kigali.

The ongoing mpox outbreak in Africa is a stark reminder of the persistent threat of infectious diseases. It also highlights a game-changing opportunity to leverage artificial intelligence (AI) and digital health applications in response to not just mpox, but any future infectious disease outbreaks.

AI’s transformative potential, when integrated into digital health tools, can empower individuals and healthcare providers, enabling a more rapid, effective and equitable response to emerging health threats.

The rapid advances in AI over the past few years, particularly since the onset of the Covid-19 pandemic, offer a glimpse into a future where data-driven insights and intelligent tools can empower us to act swiftly and decisively against emerging health threats. AI-powered digital health apps can serve as critical tools in this endeavour.

Imagine two innovative applications: one designed for people to safely self-navigate infectious disease outbreaks and another tailored for community health workers to efficiently provide vaccinations and medical care. Both can revolutionise public health responses and enhance our ability to manage outbreaks proactively.

During an infectious disease outbreak, timely and accurate information is crucial for the public to make informed decisions. An AI-powered app that helps individuals and families self-navigate outbreaks by providing real-time, personalised guidance based on the latest information can radically improve infectious disease response and containment.

The consumer app would deliver easy-to-understand and concise summaries of the pathogen, the most vulnerable cohorts, local exposure risk factors, a person’s risk of death if infected, and the availability of vaccinations and infection treatment.

Such an app offers a single source of truth for informed infectious disease management tailored to each family’s circumstances. The actionable insights are a lens into prevention measures, symptom monitoring and when to seek medical care.

As of 28 July 2024, a total of 14,250 cases of mpox (2,745 confirmed; 11,505 suspected) and 456 deaths have been recorded in 10 African countries, including Burundi, Cameroon, Central African Republic, Congo-Brazzaville, Democratic Republic of Congo (DRC), Ghana, Liberia, Nigeria, Rwanda and South Africa.

The DRC outbreak, ongoing since 2022, accounts for more than 90% of the reported cases of severe mpox clade 1b. This year, the DRC identified 13,791 cases, with children under 15 accounting for 68% of cases and 85% of deaths.

Four countries – Burundi, Kenya, Rwanda and Uganda – previously unaffected by mpox, have reported cases since mid-July 2024 (at least 50 confirmed cases, with clade 1b now confirmed in Kenya, Rwanda and Uganda).

There is a vaccine that is effective against both clades, but it is not widely available. The resources to contain and avoid this unfolding crisis exist but must be brought to bear to contain the outbreak with the greatest urgency possible.

This zoonotic virus, endemic to the forested regions of east, central and west Africa, has shown increased human-to-human transmission, including by way of sexual transmission, which deviates from the historically zoonotic (animal) nature of the disease.

Kenya’s Ministry of Health confirmed an outbreak of mpox clade 1b on 29 July 2024, originating from a traveller moving through Uganda and Rwanda. The development underscored the urgent need for enhanced public health measures across east Africa, as the high mobility of populations through key transport corridors poses a significant risk for regional transmission.