Infectious diseases are one of the greatest threats to mankind. With new genetic methods such as CRISPR and monoclonal antibodies, researchers are now developing weapons against newly emerging pandemics.
What makes pandemics so dangerous?
Mankind has feared the coming of the four horsemen of the apocalypse for millennia: war, famine, plague, and death. That disease is feared as much as the horrors of war is no coincidence. Infections can decimate just as many lives in a short space of time as armed conflict – and they can develop into global pandemics in the same way as an assassin’s bullet can start a war.
For instance, between 1347 and 1352, bubonic plague - the Black Death - accounted for the death of a third of the population of Europe and, only 100 years ago, between 1918 and 1920, over 50 million people around the globe succumbed to the Spanish Flu. From the war-torn trenches of Europe and Native American villages to the mega-cities of the USA and remote South Sea islands, countless victims died from this aggressive and highly infectious form of the influenza-A virus. It was not only weakened or older victims who were hit by Spanish Flu. On the contrary, this insidious infection, generally causing death by pneumonia, particularly affected young people between twenty and forty years of age.
In addition, recent years have also seen repeated outbreaks of infectious diseases that have spread like wildfire. Since the 1980s, for example, HIV has led to almost 40 million deaths from AIDS. The Ebola virus outbreak in West Africa in 2014/15 caused an epidemic that shook the world to its roots. In the case of Ebola, one to ten viruses were already enough to generate an infection and 50 to 90% of people infected died from hemorrhagic fever. By the time the epidemic had been contained, Ebola had already taken more than 11,000 lives. Ebola flared up again in August 2018, this time in the Democratic Republic of the Congo. 2,500 people in the rebel-held region in the north of the country died from the virus and, in mid-July 2019, a first case was reported in Goma, a city of more than one million inhabitants.
Just recently we were able to experience live how quickly a new virus has reached all parts of the world. The new virus SARS-CoV-2 causing the lung disease COVID-19 conquered all corners of the world in just a few weeks.
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Did you know?
deaths resulted from two pandemics, Spanish flu and AIDS – more than in both World Wars.
passengers fly with airlines every week. Pathogens can reach any place on earth within a few of days.
is the period scientists need to develop effective pandemic protection from the blood of a survivor.
Why is the threat from pandemics still growing?
Crowded living conditions in major cities increase the danger of pandemics. Urban populations will probably grow by more than three billion people by 2050, above all in developing countries and emerging economies. In Africa, the problems are compounded by insufficient healthcare infrastructures: In the Republic of Ghana, for instance, there are only two doctors per 10,000 inhabitants, while in the Democratic Republic of Congo, the figure is only 0.9 – in contrast, Germany has 42, the USA 26, and China currently has 18.
Another factor is global mobility: As around 80 million passengers board planes every week, a virus can strike almost anywhere on the planet within only a few days – and the number of passengers is expected to double within the next 20 years. In view of increasing mobility and global population growth, there is also an increasing danger of contact with animals that may be carriers of viral pathogens – for instance birds, apes, and bats. There is also a growing catalog of new threats, ranging from bio-terrorism to the shifting of vegetation zones as a consequence of climate change: Tropical mosquitos that carry malaria, dengue fever, or yellow fever have already begun to spread into Europe. Stefan Oschmann, Chairman of the Executive Board and CEO of Merck KGaA, Darmstadt, Germany, gets straight into the point by saying: “A global pandemic would be one of the major threats we face. Pandemic preparedness is a must. How well we are able to respond when the day comes depends on what we do today." (this quote was given during the award ceremony in July 2019, before the outbreak of COVID-19 happened)
The first "Future Insight Prize" Grant: one million euros for the category “Pandemic Protector”
So, what must we do? We have added protection against pandemics to the categories of our grant program, known as the “Future Insight Prize", that the company will be awarding annually for the next 35 years. The prize value is up to one million euros - higher than that of the Nobel Prize. “With this, we are drafting a future vision for ambitious dream products
that are important for humanity to have but cannot be realized with the current state of science and technology” explains Ulrich Betz, the initiator of the Curious Future Insight Conference and the "Future Insight Prize". “With this research grant we encourage scientific work in the areas of health, nutrition, and energy that creates the required scientific and technological basis for a later realization of these visionary dream products.”
Due to the extreme urgency of the issue, a call for submissions to the first "Future Insight Prize" in the category “Pandemic Protector” was made and the research grant to fund future research was presented in the course of an award ceremony and expert discussion at our Innovation Center in Darmstadt on July 9th, 2019. A jury of international experts from disciplines including tropical medicine, infectious diseases, vaccines and epidemiology, chose two leading researchers from the USA from the numerous submissions: Pardis Sabeti, Professor at the Broad Institute in Cambridge, Massachusetts, and James Crowe, Director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center in Nashville, Tennessee. “Their work underscores that science can be a force for good – that it can make a substantial and lasting contribution to human progress,” said Stefan Oschmann, honoring the recipients of the research grant. 2
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How can the human race be protected against pandemics?
The description of the dream product for protection against pandemics sounds simple. You start off with a blood sample from a person infected with an unknown pathogen and use it to produce an effective agent that cures the patient or prevents the infection of others - and all of this within a “clinically-relevant” time window. What is meant by this is an extremely short period of perhaps several days. Speed is the key to success. It has been calculated that, today, a virus similar to that of the Spanish Flu would claim the lives of 33 million people – and five percent of the global gross domestic product (GDP). That represents more than the economic performance of Germany.
Thanks to Sabeti and Crowe's results, a pandemic protector is no longer merely a vision, but now a realistic possibility. Sabeti, who, together with her team, contributed to containing the Ebola outbreak in West Africa, are concentrating on reading the nucleic acid sequences of disease pathogens as quickly as “New methods like CRISPR-Cas13, that precisely target genetic material (DNA or RNA) of a virus can be impactful,” reports the research scientist. “They can enable development of extremely specific tests to detect viruses for improved clinical diagnosis, and also methods to disable the virus for potential use in patient treatment”, says Sabeti.
Crowe’s lines of research ideally complement this: he works with people who have already developed immunity after recovery from a viral disease. His team has developed a technology for the extraction and replication of human monoclonal antibodies from the blood of these patients - as an extremely effective antidote. As Crowe explains, “Administering antibodies to at-risk people doesn’t offer lifelong protection, because the half-life of protection will only be a few months. But a couple of months of protection in the exposed population is usually going to enough to contain an epidemic”.
Antibodies that dock and lock on to and block important virus receptors have already been found in the case of Marburg, Ebola and Zika viruses. “Blocking attachment of virus to the susceptible tissues in the body with antibodies is the best way to combat these pathogens,” says Crowe. He also points out the particular speed of the process: “we’ve recently completed a discovery and testing process in only 78 days from acquiring a blood sample from an infection survivor to vaccination” - that’s only a little over 11 weeks that his team needs to be ready to combat a new virus. At the same time, the research scientist intends to play a role in preventive medicine with his AHEAD100 project: The aim of the project is the development of monoclonal antibodies for 100 known and dangerous virus types - namely before a new outbreak can happen.
What steps must still be taken?
Despite these successes, there remains a lot to be done to assure protection against a pandemic in an emergency, emphasized both the research grant recipients and the international experts during the presentation of the Future Insight Prize. In the opinion of Pardis Sabeti, the analysis of pathogens on the spot and fast development of vaccines is not enough: “It is also essential that knowledge is disseminated widely and quickly, and that the people affected are involved in order to gain their trust and to empower them on the front lines.”
This has only seen partial success in the battle against Ebola. The rVSV-ZEBOV vaccine, already under development for a long time, offered practically complete protection against infection, but only came into play in West Africa after a year - much too late - but, nevertheless: a fast ring vaccination was successful when the next outbreak came. Here, healthcare staff and initial contacts of infected patients and their immediate contacts were vaccinated. This enabled a new epidemic to be contained.
So far, this approach has failed in the case of the current outbreak in the Democratic Republic of Congo - despite the availability of several hundred thousand doses of the vaccine. As a consequence of armed conflict in the country, patients and their contact persons cannot be reached. What makes things worse is that rebel forces are reportedly destroying treatment centers and spreading rumors about how Ebola is being spread – adding the challenge of education as well as the delivery of vaccines.
“We aim to be prepared ahead of time for the emergence of pandemic threats, instead of chasing them in the midst of a major outbreak”
- Future Insight Prize: http://futureinsightprize.emdgroup.com
- Pandemic protection: https://www.emdgroup.com/en/research/open-innovation/futureinsightprize_streaming/pandemic_protection.html
- Lab of Pardis Sabeti: https://www.sabetilab.org/
- Lab of James E. Crowe: https://www.vumc.org/crowe-lab/
- Coalition for Epidemic Preparedness Innovations (CEPI): https://cepi.net/
- Future Insight Conference: http://curious2020.com
 Published by James E. Crowe, Jr Vanderbilt University Med Center Nashville, TN, USA during his speech during the award ceremony of the Future Insight Prize 2019 on July 9, 2019 in Darmstadt, Germany
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