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Our War Against Killer Germs
Read by Jamie Renell
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In today’s world, it’s easier than ever to move people, animals, and materials around the planet, but the same advances that make modern infrastructure so efficient have made epidemics and even pandemics nearly inevitable. And as outbreaks of COVID-19, Ebola, MERS, and Zika have demonstrated, we are woefully underprepared to deal with the fallout. So what can — and must — we do in order to protect ourselves from mankind’s deadliest enemy?
Drawing on the latest medical science, case studies, policy research, and hard-earned epidemiological lessons, Deadliest Enemy explores the resources and programs we need to develop if we are to keep ourselves safe from infectious disease. The authors show how we could wake up to a reality in which many antibiotics no longer cure, bioterror is a certainty, and the threat of a disastrous influenza or coronavirus pandemic looms ever larger. Only by understanding the challenges we face can we prevent the unthinkable from becoming the inevitable.
When I was the state epidemiologist of Minnesota, a few people in the media started calling me "Bad News Mike" because often when public officials or corporate leaders got a call from me, I was unlikely to tell them anything they wanted to hear. In a story with that title by Kermit Pattison in Mpls St Paul magazine, the subhead read: "Headstrong and outspoken, the state's epidemiologist insists he's only a messenger from the germ front. Whatever he is, the message isn't good."
Well, I don't know about the "headstrong" charge, but I certainly have to plead guilty to being "outspoken." That's because I believe in what I call consequential epidemiology. That is, by attempting to change what could happen if we don't act, we can positively alter the course of history, rather than merely record and explain it retrospectively. Because of the accomplishments in the 1960s and 1970s of two of the giants of public health, Drs. Bill Foege and the late D. A. Henderson, aided by literally thousands of others, countless millions yet unborn will be spared the devastation of smallpox. Opportunities for such life-altering good are still out there, if we only recognize them and have the collective will to act.
This book results from my participation, observations, concerns, outbreak investigations, studies, programs, and policy development on the front lines of the major public health issues of our time. They involve toxic shock syndrome, AIDS, SARS, antibiotic resistance, foodborne diseases, vaccine-preventable diseases, bioterrorism, zoonotic diseases (those transmitted from or to animals and humans) including Ebola, and vector-borne diseases (those transmitted by mosquitoes, ticks, and flies, such as dengue and Zika viruses). Each experience or encounter—local, regional, national, or international—has informed and shaped my thinking, each has taught me a critical lesson about how we deal with our deadliest enemy, and each has focused the lens through which I approach public health.
Because, in fact, infectious disease is the deadliest enemy faced by all of humankind. True, infection is far from the only type of illness that affects each of us, but it is the only type that affects us collectively, and sometimes on a mass scale. Heart disease, cancer, even Alzheimer's, can have devastating individual effects, and research leading to cures is laudable. But these diseases don't really have the potential to alter the day-to-day functioning of society, halt travel, trade, and industry, or foster political instability.
If there is any particular theme to my career, it has been connecting disparate dots of information and making them into a coherent line to the future. For example, I both wrote and lectured as early as 2014 that the appearance of the Zika virus in the Americas was just a matter of time. Before a doubting professional audience at the National Academy of Medicine in 2015, I predicted that MERS would soon appear in a major city outside the Middle East. (It did, in Seoul, South Korea, just months later.)
I don't claim any unique skills. Foreseeing issues and potential threats should be a matter of standard practice in public health.
When I established CIDRAP, the Center for Infectious Disease Research and Policy that I now head at the University of Minnesota, I was mindful of the fact that without policy, research has nowhere to go. Another way of saying this is that we tend to go from crisis to crisis without ever anticipating them or finishing the job in the end.
Science and policy must intersect to be effective. Therefore, throughout this book, we will seldom talk about realized or needed advances in the science of disease prevention without always giving equal consideration to what to do with those advances.
What we aim to give you here is a new paradigm for considering the threats posed by infectious disease outbreaks in the twenty-first century. While we will deal with the broad range of communicable illness, we will concentrate on identifying and exploring those maladies with the potential to disrupt the social, political, economic, emotional, or existential well-being of large regions, or even the entire planet. And while morbidity and mortality are certainly prime considerations, they are not the only ones. The current reality is that a few confirmed cases of smallpox anywhere in the world would create more sheer panic than do many thousands of malaria deaths in Africa alone.
That is, we don't always make rational distinctions between what is likely to kill us and what is likely to hurt us, scare us, or simply make us uncomfortable. As a result, we don't always make rational decisions about where to put our resources, where to direct our policy, and, frankly, where to direct our fear. As we write this, much of the Western world is greatly worried by the spread of Zika virus and its association with microcephaly, other birth defects, and Guillain-Barré syndrome. Yet over the past few years, dengue virus, which is spread by the very same mosquito, has killed far more people in the same region with hardly a blip on the public radar. Why? Probably because there are few situations as dramatic and horrifying as babies being born with small heads and facing uncertain lives of disability. It is every parent's worst nightmare.
We will be invoking two metaphors for disease throughout this book. One is crime and the other is war, and both are apt because in various ways, our struggle against infectious disease resembles both of these horrors. In the investigation and diagnosis of outbreaks, we are like detectives. In our response, we must be like military strategists. Just as we will never eliminate either crime or war, we will never eliminate disease. And just as we engage in an ongoing war against crime, we are constantly battling disease.
In the first six chapters, we will present the stories, cases, and backdrop that will provide context for the rest of the book. From that point on, we will discuss what I consider our most pressing threats and challenges as well as practical means to take them on.
In 2005, I wrote an article for the journal Foreign Affairs entitled "Preparing for the Next Pandemic." I concluded with the following warning:
This is a critical point in history. Time is running out to prepare for the next pandemic. We must act now with decisiveness and purpose. Someday, after the next pandemic has come and gone, a commission much like the 9/11 Commission will be charged with determining how well government, business, and public health leaders prepared the world for the catastrophe when they had clear warning. What will be the verdict?
In the eleven years that have passed since I wrote those words, I don't see that much has changed.
We could try to scare you out of your wits with bleeding eyeballs and inner organs turned to mush as some books and films have attempted to do, but in the vast majority of instances, those images are a misrepresentation and not relevant. The truth and the reality should prove sufficiently concerning to scare us all into our wits.
I'm not trying to give either an optimistic or a pessimistic spin on the challenges in facing our deadliest enemy. I'm trying to be realistic. The only way we are going to confront and deal with the ever-present threat of infectious disease is to understand those challenges so that the unthinkable does not become the inevitable.
Black Swans and Red Alerts
There's something happening here.
What it is ain't exactly clear.
Who? What? When? Where? Why? How?
Just like reporters and police detectives, this is what public health epidemiologists—disease detectives—always want to know: as many pieces of the "How did this happen?" puzzle as possible; the components that help us tell the story. That's what epidemiology—in fact, all of diagnostic medicine—is about: connecting the dots and putting together a coherent story. And only then, once we sufficiently know and understand the story, can we begin to confront the problem or challenge. As medical detectives we can sometimes stop a disease outbreak cold without understanding all the pieces of a complex puzzle, like finding that a certain food item is making people sick even though we don't know how that food got contaminated. But the more we can find out, the better equipped we are to solve the mystery and make certain that similar disease problems don't happen in the future.
On a day I will never forget, there were about ten of us sitting around the table in the Director's Conference Room at the Center for Disease Control in Atlanta—later renamed the Centers for Disease Control and then again the Centers for Disease Control and Prevention. None of us knew what to make of the cases that had just been presented to us as we went through the mental checklist.
The what: in one cluster, Pneumocystis carinii pneumonia (PCP)—a rare parasitic infection that causes a life-threatening pneumonia and usually occurs only in people with compromised immune systems. And in the other, Kaposi's sarcoma (KS)—a disfiguring malignant tumor now known to be caused by human herpesvirus-8 (HHV-8) and also more frequent in people with immune system problems. It starts as little red and bluish black lesions on the skin or in the lining of the mouth, nose, or throat. The lesions grow into very painful raised tumors and often spread to the lungs, digestive tract, and lymph nodes.
The when: right as we sat there—June 1981.
The where: The PCP cases were being found primarily in the Los Angeles area and the KS cases in the New York City area.
The who: two clusters of young, otherwise healthy gay men on opposite sides of the country.
The why and how: Those were the mysteries.
Because, we all knew, these rare, arcane diseases shouldn't be happening in this patient population.
Dr. James Curran sat at the head of the table in the long, narrow room paneled in dark wood. He was with what was then called the STD Division—sexually transmitted diseases—and his team was working with the CDC's Viral Hepatitis Branch in Phoenix. I was interested in hepatitis B and was doing studies on how healthcare workers at a single hospital in Minneapolis had become infected. More than eighty such cases had occurred in a fourteen-month period, including that of a young physician who had died as a result of his work-acquired hepatitis infection.
Jim is one of the brightest guys in our business and someone never afraid to speak his mind. I had once considered taking a job in his division at the CDC. Now he was setting up a study on a new, not yet approved hepatitis B vaccine in gay men in several cities across the United States. Gay men were at high risk, due to the significant possibility of transmitting the virus through anal sex, a risk heightened for those with multiple partners.
Dr. Bill Darrow, an STD Division expert on the behavioral aspects of infectious disease, and Dr. Mary Guinan, MD, PhD, a leading virus expert with the STD Division, were also at the meeting.
Dr. Dennis Juranek of the Division of Parasitic Disease was there and had been quite involved with the early information gathering for these cases. Since PCP was so rare in the United States, the manufacturer of the chief drug used to treat it worldwide, pentamidine, had not wanted to go through the time and expense of the full Food and Drug Administration approval process. Therefore, the CDC was the only place in the United States that could stock it, as an investigational, unlicensed drug. Dr. Wayne Shandera, who helped monitor disease outbreaks from Los Angeles as part of the Epidemic Intelligence Service (EIS), was on the speakerphone. EIS is the CDC's training program for new epidemiologists and other public health professionals, who are sent around the nation and the world to investigate mysterious and potentially threatening disease outbreaks.
For a twenty-eight-year-old epidemiologist from the Midwest, working with such distinguished and dedicated people and being there at the CDC was like beaming up to the mother ship. I was grateful that Jim had invited me to this meeting, even as a small-bit player. As chief of the Acute Disease Epidemiology Section of the Minnesota Department of Health, I was actually at the CDC for another reason—a meeting on toxic shock syndrome (TSS), a condition I had been actively investigating for almost a year. Because of that, my experience with public health disease surveillance related to unexplained outbreaks, and the fact that I happened to be in the building, Jim invited me to help provide a perspective from the field. In addition, I had led our team at the Minnesota Department of Health in investigating several recent large outbreaks of another type of viral hepatitis in gay men. That illness is now known as hepatitis A.
It was against this public health backdrop and recent investigative experience that I faced the current mystery with the others in the CDC Director's Conference Room.
Details had been published, employing the dispassionate language of science, in the June 5, 1981, issue of MMWR—the Morbidity and Mortality Weekly Report—the CDC's dispatch of diseases important to the public:
In the period October 1980–May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection. Case reports of these patients follow.
The report described five men, ages twenty-nine to thirty-six, four of whom were previously healthy and the fifth having been successfully treated for Hodgkin's lymphoma three years earlier. CMV is a common virus that most carriers don't know they have, because it generally doesn't cause any symptoms. Since it spreads from person to person via bodily fluids—saliva, blood, urine, and semen—and because people share more fluids when they have multiple partners, and also because anal intercourse is much more likely to cause small abrasions and resultant bleeding than vaginal intercourse, it was often noted in sexually active gay men. The term of art in those days was MSM—men who have sex with men. But CMV was known to cause various health problems in individuals with compromised immune systems. The candida infection these men presented with could indicate some sort of immunosuppression. Patient 4, the youngest of the cohort and the one who had had Hodgkin's disease, was one of the two who had died. He had been treated with radiation. Had that suppressed his immune system? Had the cancer itself had some effect? What about the other four?
Particularly confounding was that these two conditions—Pneumocystis carinii pneumonia in LA and Kaposi's sarcoma in New York—were not "perpetrators" any medical detective would expect to discover at such a "crime scene." PCP was caused by a parasite that, in general, is easily neutralized by the human immune system. KS in this part of the world tends to show up in old, otherwise frail and sickly men.
As MMWR soberly noted:
Pneumocystis pneumonia in the United States is almost exclusively limited to severely immunosuppressed patients. The occurrence of pneumocystis in these 5 previously healthy individuals without a clinically apparent underlying immunodeficiency is unusual.
So why were we seeing these two medical anomalies in groups of healthy young men on both coasts? What were the known causes of immunosuppression?
We went through the list of usual and unusual suspects—what physicians refer to as the differential diagnosis.
There was some speculation that it could be related to Epstein-Barr virus (EBV), generally transmitted through oral and genital secretions and bodily fluids. Often, EBV causes no symptoms at all, but it is one of the prime causes of infectious mononucleosis, which when I was in school was known informally as the "kissing disease." EBV is also associated with more serious conditions, including Hodgkin's and Burkitt's lymphomas and a variety of autoimmune diseases. Some scientists have speculated that it triggers chronic fatigue syndrome, though the association has never been proven.
Theories were running rampant—everything from the idea that none of these cases were related to the appearance of a new, highly infectious disease.
"Most of us thought it was a sexually transmitted agent, but we didn't know what," Jim Curran recalled.
Could there be some blood-borne microbe that was promoting these conditions? Maybe there was a chemical these men had intentionally or inadvertently ingested. We thought it sounded like an infectious disease, but at that point, we couldn't be sure.
There was a significant cohort of the gay community in a number of major cities, New York and LA included, that was sexually active with numerous partners, often on the same day. So one of the favored methods for achieving and maintaining an erection, and enhancing sexual sensation, was through sniffing amyl nitrite "poppers." Were the chemicals lingering in the system and causing these weird effects? It didn't seem likely, but we weren't ruling anything out.
And the big question: Were these two clusters related, or was the commonality of sexually active gay men merely a fluke? Most people have heard the old diagnostic aphorism, Common things occur commonly. Uncommon things do not. When you hear hoofbeats, think of horses before you think of zebras. So was this a zebra, or simply two unrelated horses?
The first critical step would be what we call "case surveillance," and it is just as important as a police detective's surveillance of a possible suspect. Because of my own recent experience with toxic shock syndrome, the group assembled in that conference room asked me how I thought they could enhance surveillance in New York and LA and where else they should look for similar cases. Did it make sense to concentrate on clinics that handled a lot of sexually transmitted diseases? What about pulmonologists' offices for possible cases of PCP and dermatologists' for KS?
Those ideas made sense, but I thought we would likely get the most information quickly by conducting a survey among doctors in the areas of LA and New York City with large populations of gay men to see if any of them were seeing cases like these. Even if these cases were caused by a single infectious microbe or ingestion of a chemical that undercut the immune system and occurred in other cities and among heterosexuals, the "hot spots" for finding more cases seemed to be among gay men in LA and New York City.
I walked out of the meeting wondering if there was really anything to worry about or if these cases were just the kinds of random incidents that happen in our business. Would one or both of these small clusters turn out to be medical anomalies that quickly faded from view? Would they be mysteries with neat explanations? That was certainly what Jim was hoping for; as he said, "Identify. Treat. Over."
Or were we seeing a genuine black swan event, one that would become an all-hands-on-deck red alert?
The term "black swan" was introduced by Nassim Nicholas Taleb, author and scholar, to explain certain rare occurrences in financial markets. In his 2007 book, The Black Swan, he extended the concept to explain unusual high- or extreme-impact and difficult-to-predict events in the larger world.
None of us around the table that day in Atlanta realized that we were bearing witness to an epochal moment in history: the world's transition into the era of AIDS. Jim Curran would remain the CDC's point man on the disease, and it would transform his career.
Jim subsequently set up a CDC task force to explore this new condition, tentatively labeled Kaposi's Sarcoma and Opportunistic Infections. At about the same time as the establishment of the task force and the publication of the first MMWR report, the CDC began receiving an unprecedented number of requests from physicians for pentamidine to treat young men afflicted with PCP, especially in New York. Even though no one knew what was causing the condition, Jim and his colleagues knew it was time for the CDC to develop a case definition.
The case definition is critical in identifying a disease and trying to figure out what to do about it. Once a disease has been described in this way, the CDC's own investigators, state and local health department officials, hospital emergency room personnel, and all other physicians and healthcare workers can begin ruling in and ruling out individuals they see.
"The cases were so unusual," Jim recalled, "that we had to have a specific definition. Then we focused on very specific active surveillance, so we were able to say, 'This really is increasing. It's focal, but it's spreading.'"
As soon as the media picked up the story of these strange new disease outbreaks, the CDC was flooded with calls describing similar symptoms. By the end of 1981, 270 cases of severe immunodeficiency had been reported in gay men. Of those, 212 had died. In the first year or so of surveillance, the condition was seen mostly in gay men and intravenous drug users.
The next year, the disease estimate was in the tens of thousands. Jim says, "The problem was that the first few years, we were always underestimating but being accused of overestimating."
It was when symptoms started showing up in people who didn't fit the profile that the investigation turned a critical corner. Jim recalls, "We started seeing transfusion recipients with Pneumocystis pneumonia, and we were pretty convinced they weren't gay and had no other risk factors. We saw it in children with hemophilia. Then we were able to convince ourselves and others of the logic of who got it and who didn't. And that was really important. When we saw three hemophilia cases in one week, we knew the agent had to be in the blood supply, and it had to be a yet-unrecognized virus."
In September 1982, under Jim's leadership, the CDC first used the term "acquired immune deficiency syndrome," which was defined as "a disease at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known case for diminished resistance to that disease." Jim had pushed for the adoption of the AIDS acronym because he thought it was critical to have a name that was easy to remember and would have the same label throughout the world.
The next month, MMWR published its first guidelines on AIDS prevention, treatment of patients, and handling of specimens.
AIDS turned out to have all the elements of the greatest public health challenges: on-the-scene medical drama, in-the-lab discoveries, and huge financial, social, religious, ethical, political, and even military impact.
By 1983, lab scientists in the United States and France had determined that AIDS was caused by a retrovirus. On April 23, 1984, Health and Human Services secretary Margaret Heckler held a press conference to say that Dr. Robert Gallo and his colleagues at the National Cancer Institute of the National Institutes of Health had found the cause of AIDS: the retrovirus HTLV-III.
This would be followed in June by Gallo and Pasteur Institute professor Luc Montagnier's joint press conference confirming that the French lymphadenopathy associated virus (LAV) and the American HTLV-III were almost certainly identical and the likely cause of AIDS. It then took until 1986 for the International Committee on Taxonomy of Viruses to officially label the cause of AIDS as human immunodeficiency virus, or HIV.
HIV most likely began in the jungles of Africa as an infection in primates such as monkeys or chimps, and it lingered there for many decades before crossing over into the human population. As human populations grew in the jungles of Africa, the practice of hunting primates became more common and bushmeat a regular source of nourishment. The virus probably jumped species as people killed, butchered, and had extensive blood contact with infected primates. From there, human-to-human sexual transmission was probably the main means of spread, eventually making it out of the small, isolated groups in the jungle.
This is an instructive model for the proliferation of other infectious diseases as population growth and "progress" create better roads and more mobility while reducing jungle and forestland. As a result, microbes that may have stayed in their particular niches for centuries or longer are now emerging into far larger problems.
But to go back to the April 23 press conference, Margaret Heckler also announced development of a diagnostic blood test and expressed hope that an AIDS vaccine would be ready within two years.
The idea that an AIDS vaccine would be ready that soon struck me as wildly unrealistic. I couldn't fathom where she had come up with that estimate. Two years is a very short amount of time to develop any vaccine, and for the retrovirus that caused AIDS, the time frame seemed virtually impossible.
Once in the cell, the retrovirus hangs around indefinitely. HIV is present in the body fluids of infected individuals, and when the virus enters a person in the form of infected immune cells, for example, in ejaculate, it makes it virtually impossible for antibodies produced by a vaccine or other parts of the normal human immune response to win the earliest battle against the invading virus. With other viruses, vaccines trigger the immune system to identify the invaders and kill them. But the fact that this virus could escape the body's own defenders challenged all notions of how vaccines work.
"There was definitely some premature optimism with mention of the vaccine," Jim comments. "The honest question would be, not when there would be a vaccine, but if there would be a vaccine."
This didn't mean treatments couldn't be developed that would greatly handicap the virus once it was in the body. In fact, progress on the cocktail of drugs now used to control the disease has been truly remarkable and inspiring. But the key word here is control, just as we do with diabetes and other chronic diseases, not prevent or cure.
In the mid-1980s, while some in the public health community were laser focused on vaccine research, I kept saying in every forum I participated in that we couldn't afford to wait for a vaccine to stop transmission. Preventive measures were essential.
I had a personal stake in this. In 1983, before the American blood supply was routinely screened for HIV, my beloved sixty-six-year-old aunt, Romana Marie Ryan—a nun and teacher in San Francisco—broke her hip when she fell while taking her kindergarten class on a field trip. Her parish priest, Father Thomas F. Regan, often said that she was "magically gifted" in teaching young children.
Aunt Romana had come home to Iowa for a visit in August of 1984. We had a small family reunion at the motherhouse convent in Dubuque. I remember so clearly driving from Minneapolis to Dubuque for a wonderful Sunday afternoon get-together.
It was a beautiful day on the bluffs overlooking the Mississippi River. Sister was her usual joyful, fun, and loving self, the kind of person you cherish being with. But she had been sick lately and her doctors had not been able to pinpoint the cause. I remember she was wearing a long light-green skirt that day; she had given up nuns' garb years earlier. When she was sitting on a patio chair, I noticed she had these terrible-looking red and purple lesions on her lower legs.
- "Michael Osterholm is one of the best epidemiologists -- hunters of infectious diseases -- of our time. When Osterholm tells us that the potential for global pandemics is a life-or-death issue for every person on the planet, we need to listen. Deadliest Enemy is a powerful and necessary book that looks at the threat of emerging diseases with clarity and realism, and offers us not just fear but plans."—Richard Preston, author of The Hot Zone and The Demon in the Freezer
"This book will change the way you think. It is clear, well written, and has a narrative drive provided by a subtext worthy of Stephen King. It is also based on solid science--in fact, I wish the science weren't so solid, so I could dismiss its conclusions. If enough people--or the right people--read it, it will do what few books can do: it will save many, many lives."
—John M. Barry, author of The Great Influenza: The Story of the Deadliest Pandemic in History and Rising Tide: The Great Mississippi Flood of 1927 and How It Changed America
- "Osterholm and Olshaker calmly show us that Mother Nature is the 'greatest bioterrorist of them all.' Marshaling solid scientific evidence, they question why we have spent billions on the 'war on terror' and virtually nothing for an inevitable calamity that will kill millions. This stunning book is a clarion call to mount a Manhattan Project 2.0 that would prepare for the coming global pandemic. Someone should listen."—Kai Bird, Pulitzer Prize-winning historian and coauthor of American Prometheus: The Triumph and Tragedy of J. Robert Oppenheimer
- "As a former governor responsible for the welfare and health of my state, and a former United States Senator concerned with national security, I applaud Deadliest Enemy as a chilling and important wakeup call. Not only is it a fascinating human story and medical detective drama, it lays out the great public health challenges facing humanity and the actions that need to be initiated or enhanced to avert their life or death consequences."—Bob Graham, former Governor of Florida, U.S. Senator and Chairman of the Senate Intelligence Committee
- "Dr. Michael Osterholm is 'the Paul Revere of the Germ War.' To those of us who have peered over the horizon and seen the enemy, his work is heroic and critical. So I am extremely gratified that he and Mark Olshaker are now sharing that vital knowledge and insight in their compelling new book, Deadliest Enemy."—Michael Leavitt, former Governor of Utah, Administrator of the Environmental Protection Agency and Secretary of Health and Human Services
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