A highly contagious, highly deadly pandemic like the 1918 Spanish flu could kill 200-400 million people and hit the global economy with the force of the Great Recession.
In a globally connected world, a pandemic that invades every continent hits every sector, and continues in over several years will disrupt supply, demand, and the ability of business, nonprofits, and governments to operate.
ICV is pleased to present The Next Pandemic Fund which will allocate donated capital to innovative research dedicated to antimicrobial resistance (AMR), Methicillin-resistant Staphylococcus aureus (MRSA), and influenza.
In a public-private partnership between Stanford Medicine and Washington University in St. Louis School of Medicine, two of the top academic medical centers in the United States and ICV, we are putting people with capital on the front lines to wipe out some of the world’s deadliest diseases.
ICV will provide full transparency. Every quarter, ICV and select donors will sit with the Stanford and Washington University research teams to review progress in real-time.
“Those who cannot remember the past are condemned to repeat it.”
– George Santayana
The 1918 flu influenza pandemic, which originated from pigs in Kansas, infected 500 million people around the world, and resulted in up to 100 million deaths (3-5% of the world’s population), making it one of the deadliest natural disasters in human history. There was a combination of factors involved during this time, namely a strain of the virus that most people did not have any immunity to (no partial immunity having been through the flu); malnutrition after the war; and, lack of antibiotics.
“We have been averaging about 100 deaths per day, and still keeping it up. There is no doubt in my mind that there is a new mixed infection here, but what I don’t know.”
– A doctor stationed at Camp Devens, a military base just west of Boston, writes to a friend and fellow physician, September 29, 1918
The 2018 influenza season “set the record for the highest number of flu-related deaths in children reported during a single flu season (excluding pandemics),” according to the CDC. Severe complications and deaths from the flu were largely attributable to the 3-4 strains that spread during the 2018 flu season. In many cases, the flu virus changed genes with each other, mutated without correcting itself, and any vaccine administered was not the right key for the lock. This made for a more deadly virus, and for many who were exposed, the immune system went into overdrive, set off a chain reaction, caused respiratory distress and shut down organs.
“This doesn’t mean that we are having a pandemic, just that levels of influenza-like-illness are as high as what we saw during the peak of 2009.”
– CDC Acting Director Dr. Anne Schuchat, February 9, 2018
Today, we have 4x the population and 50x the travel as we did a century ago. We also have people who are older, which presents certain risk factors. On top of it, there are so many viral incubators around the world, such as chicken farms, where there is a possibility of gene swapping of viruses that can travel from migratory birds to chickens to humans. For different reasons, we may be just as vulnerable as those in 1918.
Today, we do not have enough intensive care facilities for when people do get a sea storm reaction of an over-exuberant immune system, and we simply cannot care for all them.
We need a universal vaccine that can detect the flu, without going to the doctor’s office and spreading it. We need better pharmaceuticals and diagnostics and barrier methods to control the vaccine. We need to get people engaged that understand that good government support is worth investing in. We know what we need to do to bolster resources, and we hope that the loss of so many children during the 2018 flu season is a loud cry that we need to move more quickly.
Influenza A virus (IAV) causes major morbidity and mortality worldwide, and is a major cause of infectious deaths in the United States. IAV infections cause seasonal flu, but can also sporadically emerge as pandemics that are much more devastating than seasonal influenza. An IAV pandemic resulting from a highly pathogenic strain with efficient airborne transmissibility would be very difficult to contain without highly effective antiviral agents. At present, vaccines must be re-engineered annually by guessing which virus strain will naturally emerge, take many months to develop and distribute, and often provide inadequate protection, especially if our “guess” was wrong. Moreover, viruses can be naturally resistant to currently available drugs. Finally, a purposefully weaponized strain, for which we are unlikely to have the requisite knowledge in advance of its genetic nature, can now readily be made to be both highly pathogenic and resistant to current drugs.
A universal vaccine capable of conferring protection against any strain of IAV represents a highly unmet need. It would protect against any circulating IAV isolate—regardless of resistance to current drugs or high pathogenicity. We would no longer be hostage to the current vaccine strategy, which keeps us a year behind IAV’s evolution, and often guesses wrong as to what antigens to use to prepare the vaccine. Ideally, such a universal vaccine could be administered at the last minute—even just days before exposure to the circulating IAV strain.
A universal therapeutic that targets an essential feature present in all isolates of IAV, and against which the development of natural or purposefully engineered resistance is thwarted, is also a highly unmet need.
Scientists at Stanford are developing just such a universal therapeutic that can be administered days after an otherwise lethal infection, or days before as a Just-In-Time UNiversal Influenza VACcine (JIT-UNIVAC), that has a high barrier to the development of resistance, and is effective against any strain of IAV, including those resistant to all currently available drugs.
In all parts of the world, antibiotic resistance is rising to dangerously high levels. According to the World Health Organization, it is one of the biggest threats to global health, food security, and development today.
By 2050, more than 10 million people could die each year from infections from resistant microbes, overtaking cancer, according to the Review on Antimicrobial Resistance.
The estimated cost to the world could be as high as $100 trillion, more than five times the annual GDP of the United States. The domino effect of the prevention of superbugs could ruin the economies of some countries and push nearly 30 million people into poverty.
Most experts outside of the food and drug industries believe the feeding of antibiotics to livestock is causing the problem of resistance bacteria.
Rising populations and wealth have led to a greater consumption of meat. According to the FDA, almost 80% of antibiotics used in the United States are used for industrial livestock production — to feed farm animals — not for sickness, but for growth promotion. Our consumption of meat could ultimately lead to our demise.
Ending routine use of antibiotics in animal agriculture is critical and containment efforts of resistance microbes must be implemented without delay.
“Each year, 90,000 Americans suffer from invasive MRSA infection. About 20,000 die. Many are children.”
– MRSA Research Center, The University of Chicago
In July 2018 Novartis joined other pharmaceutical giants like Pfizer, Eli Lilly, and Bayer in announcing they, too, will no longer research or develop new antibiotics. Even though Novartis’s announcement was largely lost in the headlines, it has implications for claiming many lives as society faces the expanding threat of antibiotic resistance.
Although occasional outbreaks of exotic diseases, such as Ebola or Zika, briefly remind the world of the importance of these drugs, society remains ambivalent to the increased number of reported cases of preventable diseases like whooping cough and diphtheria. This is also evidenced in the declining rates of immunization against childhood diseases and the re-emergence of infectious diseases in Europe, such as measles, that are beginning to gain momentum in the United States.
The rise and comeback of infectious diseases is attributed to an unfortunate combination of nature and business. An overuse of antibiotics in the past did allow bacteria in nature to gain resistance to certain drugs, causing society to lose confidence in their ability to prevent and treat infectious disease.
These trends have not been good news for public health and have led many experts to declare we now live in a post-antibiotic world.
As a result, declining profits provoked many of these pharmaceutical pioneers to stop antibiotic research and development in search of more lucrative markets. In fact, research taking place at Washington University in St Louis discovered that there have been more than 150 antibiotics introduced since the Second World War, with more than 30% of these drugs now discontinued, primarily due to resistance. Our research also found that the number of companies’ currently researching antibiotics has declined by more than 75% since the late 1980s. And for every new antibiotic created since the 1990s, three established antibiotics will no longer be available.
“Of the more than 150 antibiotics introduced since the second world war, more than 30% have been discontinued, primarily due to resistance.”
– Washington University in St. Louis
Some have argued a perceptive financial market will recognize new opportunities and address the crisis, but Washington University recognizes two major issues with this view. First, a new drug requires at least a decade of development before it is approved for public use, whereas a drug-resistant superbug can hop from one continent to another at the speed of a modern jetliner. Second, as bad as the public health situation has become, the market is clearly not yet positioned to recognize the impending disaster, as evidenced by Novartis’ July 2018 announcement.
Our continued failure to confront what could become a postantibiotic world threatens a return to incessant waves of otherwise preventable and treatable plagues that could hobble societies and economies throughout the world. In the absence of a governmental and pharmaceutical will to prioritize prevention and treatment of infectious disease, it falls to researchers at institutions such as Washington University to continue to meet the challenge of stopping what could quickly become a major crisis to our global health. It is our hope that the ICV Group will join us in addressing this challenge by marshaling resources from philanthropists who share our vision to eliminate the threat of deadly infectious agents.
We are facing a global crisis in drug development. Even though the flow of ideas from basic scientific research has never been more prolific, the ability to translate these ideas into breakthrough medical products is severely compromised due to dramatic changes within the pharmaceutical industry.
The implications for public health are enormous, exemplified by the dearth of new antibiotics to combat “super bugs” and the need for drugs to treat newly-arising infectious diseases such as Ebola and the Zika virus, as well as the need for improved treatments for cancer, heart disease, diabetes, Alzheimer’s and other major health threats.
As one of the nation’s leading biomedical research enterprises with vast scientific and medical expertise and one of the largest patient populations of any U.S. health system, Washington University is ideally positioned to fill the critical need for early stage discovery and research of new drugs and medical treatments.
Washington University has invested heavily in institutional resources to aid in the fight against infectious disease. The Center for Research Innovation in Biotechnology, along with the Center for Drug discovery identify and support research efforts as they identify new drugs and move them into the marketplace.
More than 70 principal investigators here, along with teams of staff scientists and PhD students, are hard at work probing the molecular underpinnings of bacterial and viral infections, the mechanisms of virulence, and how the body can combat bacteria, viruses, and other pathogens.
The purpose of The Next Pandemic Fund is to identify and fund projects that hold the greatest promise for anticipating, preventing, and treating deadly infectious diseases.
Washington University will issue an annual request for proposals to all Washington University investigators to solicit the most innovative ideas. The notice will be distributed to all schools and departments engaged in research, inviting faculty to apply for either a Pilot Grant or a Breakthrough Award.
Pilot Research Projects
Pilot Grants will provide $150,000 for a two-year research project. Early funding has an outsized impact because it enables great ideas to get off the ground when they would otherwise be unable to move forward. By allowing researchers to generate the preliminary data required for an application to the National Institutes of Health, pilot grants leverage large, multi-year grants ten or more
times the amount of the pilot grant. Budget justifications will be required. We anticipate awarding five to seven such grants each year.
Breakthrough Awards will provide substantial support to the most transformational projects. Although such projects will have a higher risk of failure and thus unlikely to receive funding
from the National Institutes of Health, they hold the promise of revolutionary advances. We anticipate awarding one or two $750,000 projects per year.
A committee of distinguished researchers will review the proposals and select projects that have the greatest likelihood of impact.
Review criteria will include exceptional innovation, the potential for transformative impact on infectious disease, the experience and track record of the investigator’s previous research projects, justification of project expenses, and whether support from the National Institutes of Health would be difficult to obtain due to the forward-looking or high-risk nature of the proposed research.
Washington University will provide an annual progress report outlining the advances made and challenges encountered by each funded research team. Donors will be invited to meet the investigators for an interactive exchange.
Challenges that threaten humanity require innovative responses and insights. The power of collaboration can ensure a prosperous future. Our experienced team with representatives from the cooperating organizations has the character, courage and commitment to solving the nature of the challenges we face today, and how to respond to and contain these threats.
Jeffrey Glenn, MD, PhD, is a Professor of Medicine (Division of Gastroenterology & Hepatology) and Microbiology & Immunology at Stanford University School of Medicine, and the Director of the Center for Hepatitis and Liver Tissue Engineering. He also heads a research laboratory focused on studying molecular virology and the translation of that knowledge into novel antiviral strategies, as well as the development of new treatments for liver diseases and cancer. He is the founder of Eiger BioPharmaceuticals, Inc. (NASDAQ:EIGR), co-founder of Riboscience LLC, and founder of I-Cubed Therapeutics, local biotechnology companies developing several new classes of antiviral and anti-cancer drugs. Glenn was born in Los Angeles, and grew up in Switzerland. He received his B.A. degree in Biochemistry and French Civilization from U.C. Berkeley from where he graduated summa cum laude. He received his M.D. and Ph.D. in Biochemistry and Biophysics from U.C.S.F.. He trained in internal medicine at Stanford University where he completed specialty training in gastroenterology, and joined the faculty in 2000. He is the principal investigator on multiple NIH grants including a National Institute of Allergy and Infectious Diseases Center of Excellence for Translational Research, an inventor on numerous patents, an elected member of the American Society for Clinical Investigation, and a member of the FDA Antiviral Drugs Advisory Committee. He has pioneered new approaches to antiviral therapy, including the concepts of targeting host functions upon which viruses depend and highly conserved viral RNA secondary structures. These have resulted in a pipeline of exciting novel therapeutics designed to target the worst form of human viral hepatitis, provide a cure for the common cold and paralyzing enterovirus infections of children, and yield a universal treatment for influenza virus including the most devastating pandemic strains. He is particularly passionate about changing the paradigm for drug development to make the next generation medicines he is developing affordable to those in greatest need through GDP-dependent pricing.
Pandemic viruses, such as influenza, are exceedingly difficult to predict and can have catastrophic consequences. New research from Jacco Boon, PhD offers details about flu viruses that could improve surveillance to detect and halt an emerging pandemic. Pandemic flu emerges when flu strains from different species, such as birds and humans, genetically mix to make a new virus that spreads faster and makes people far sicker than either strain alone. Boon and his team identified genetic features that control how well two viruses mix and how well they multiply. By focusing surveillance efforts on just these genes, public health authorities can focus their resources.
As dangerous bacteria grow more savvy at evading antibiotics, Gautam Dantas, PhD and his interdisciplinary team are designing new ways to counterattack. One of their recent successes is the design of a novel drug cocktail for defeating deadly staph infections, work that was featured on the cover of the prestigious journal Nature Chemical Biology. They showed that three antibiotics that, alone, are ineffective against drug-resistant staph (MRSA) infections can kill the deadly pathogen when administered in combination. Remarkably, the designed three-drug cocktail was effective at killing all of 73 tested diverse strains of MRSA isolated from patients at St. Louis area hospitals. Dantas and his team also showed that the drug cocktail completely cured MRSA bloodstream infections in mice within two days of treatment. They are now working to bring their discovery to human patients and exploring whether the same approach can be used to rescue other old antibiotics in clever combinations to defeat other deadly bacterial infections, such as those caused by E. coli, Pseudomonas, and Acinetobacter.
Victoria J. Fraser, MD is the Adolphus Busch Professor of Medicine and chair of the Department of Medicine at the Washington University School of Medicine in St. Louis. She joined theDivision of Infectious Diseases at in 1991 after completing a three-year fellowship in infectious diseases at what now is Barnes-Jewish Hospital. Her research focuses on the prevention and control of hospital-acquired infections. She has studied surgical site infections, blood stream infections and ventilator-associated pneumonia, and her team looks at risk factors, outcomes and costs of these infections as well as how to prevent them. This research and the work of the BJC HealthCare Infection Control Consortium have led to dramatic declines in the rates of hospital-associated infections at BJC facilities over the past decade. Fraser earned a medical degree from the University of Missouri-Columbia and completed a residency at the University of Colorado Health Sciences Center, where she also was chief resident. She has received numerous awards, including the Distinguished Service Teaching Award; the Academic Women’s Network Mentor Award; the Neville Grant Award; the SHEA Young Investigator Award and the Bi-State Public Health Award.
Juliane Bubeck Wardenburg, MD, PhD, is Associate Professor of Medicine Division of Gastroenterology at the Washington University School of Medicine in St. Louis. She is uncovering the mechanisms this bacteria uses to cause such destruction. She discovered that S. aureus hijacks a human protein called ADAM10 to cut apart tissues and thwart the immune response, rendering the infected individual highly susceptible to severe disease. She is now developing ways to minimize the severity of infection when it occurs, but more importantly focusing on disease prevention through development of a childhood vaccine that will enable broad, population-based protection.
“Friendly” bacteria profoundly affect human health
Mutually beneficial relationships between microbes and animals are a pervasive feature of life in our microbedominated planet. The vast majority of these microbes live in our gut (tens of trillions, belonging to all three domains of life plus their viruses) where they provide us with traits we have not had to evolve on our own, such as synthesizing Vitamin D.
Research at Washington University led by Jeffrey I. Gordon, MD, who is widely regarded as the “Father of the Microbiome,” focuses on the role of gut bacteria in defining our nutritional status in order to develop gut bacteriatargeted therapeutics to treat malnutrition in infants and children living in low-income countries as well as obesity in Westernized countries.
Curing infections without antibiotics
With the rise of antibiotic resistance, many believe that we are entering a ‘post-antibiotic era.’ To effectively treat bacterial infections, new approaches are desperately needed. One promising avenue is to target the different adhesive mechanisms that bacteria use to attach to host tissues to gain a foothold and cause disease. Washington University investigators Scott Hultgren, PhD and James Janetka, PhD are targeting the long, hair-like structures called pili that are tipped with an adhesin called FimH. E. coli uses this sticky substance to latch on to the surface of the bladder, causing urinary tract infections (UTIs).
Hultgren and Janetka developed a class of drugs called mannosides that block the ability of the FimH protein to stick. When mice were treated with mannosides, E. coli in their bladders and in the gastrointestinal tract reservoir were swept away, clearing the infection and eliminating the reservoir without antibiotics. Mannosides are now in late stage preclinical testing for UTI treatment. Hultgren has also developed a vaccine that targets FimH which has successfully completed a Phase 1A/B trial. Based on the promising results, the FDA has already allowed compassionate use in women suffering from recurrent UTIs and not responding to the standard of care. Hultgren and Michael Caparon, PhD, have developed vaccines that block adherence by other types of bacteria such as Enterococcus and MRSA. They found that the important adhesins of these bacteria attach to proteins that the body coats onto medical implants. Vaccines that prevent the bacteria from attaching and small molecule therapeutics, which prevent the assembly of the attachment proteins on the bacterial surface, show potential in treating infections.
Staying ahead of microbial resistance
Another innovative team of researchers is staying ahead of microbial resistance by developing re-sensitizing drugs before resistant bacteria have become a clinical challenge. Tetracyclines are a class of antibiotics widely prescribed for bacterial infections and used broadly in farming applications. Enzymes that destroy tetracyclines making the bacteria resistant have been identified, but are not yet a problem in human patients.
Foreseeing the coming challenge, Niraj H. Tolia, PhD, Timothy A. Wencewicz, PhD, Joseph P. Vogel, PhD and Gautam Dantas, PhD have employed chemical, structural, microbiological and genomic methods to identify the mechanisms responsible and develop compounds to block the microbes’ evasive maneuvers.
When the cause of an outbreak is unknown
Many thousands of viruses cause illness in people and animals, and making a diagnosis can be an exhaustive exercise, at times requiring a battery of different tests.Often the physician already needs to have a hunch of what virus the patient has. Gregory Storch, MD is developing a new test that casts a broad net to detect all viruses, even those present at very low levels. Such a test would be especially useful in situations where a diagnosis remains elusive after standard testing or when the cause of an outbreak is unknown.
Dr. Jonathan Quick (“Jono”) is an international leader on a mission to protect humanity from deadly infectious disease outbreaks and epidemics. He is the author of The End of Epidemics: The Looming Threat to Humanity and How to Stop It (2018 from St. Martin’s Press and Scribe Publications). A family physician and health management specialist, Dr. Quick is Senior Fellow at Management Sciences for Health (MSH) where he previously served as President and Chief Executive Officer from 2004-2017. MSH is a global health non-profit organization working in the world’s poorest places to build strong, locally led, locally run health systems. Dr. Quick has personally carried out assignments to improve the health and lives of people in over 70 countries in Africa, Asia, Latin America, and the Middle East. Dr. Quick also currently serves as chair of the Global Health Council, the leading membership organization supporting and connecting advocates and decision-makers to deliver life-saving services through equitable, inclusive and sustainable investments, and policies. Dr. Quick is Senior Fellow at Management Sciences for Health (MSH). Carried out assignments to improve the health and lives of people in over 70 countries. Dr. Quick also currently serves as chair of the Global Health Council.
Antibiotics | Antimicrobial Resistance
At the end of the day, at the end of our lives, we will ask ourselves whether we could have done more for the health and well-being of the planet, of humanity and all living things. Leverage your charitable giving to create systemic change with ICV’s Catalytic Philanthropy.
As a tax-exempt public charity as defined by the Internal Revenue Code (IRC) Sections 501(c)(3), ICV Group, Inc. is eligible to receive tax-deductible charitable contributions under IRC Section 170 and is qualified to receive tax deductible bequests, devises, transfers or gifts under Section 2055, 2106 or 2522 (EIN: 82-2698363).
“When we think of the major threats to our national security, the first to come to mind are nuclear proliferation, rogue states and global terrorism. But another kind of threat lurks beyond our shores, one from nature, not humans – an avian flu pandemic.”
– Barack Obama