Deadliest Enemy: Our War Against Killer Germs

by Mark Olshaker

We must never forget that a dangerous microbe anywhere in the world today could be everywhere in the world tomorrow.

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.

There are only four events that truly have the power to negatively affect the entire planet. One is all-out thermonuclear war. Another is an asteroid striking earth. The third is global climate change. And the fourth is infectious disease.

Today, we live in a just-in-time-delivery economy where virtually nothing is warehoused for future sales, let alone stockpiled for a crisis situation. Not even the parts and components necessary to manufacture these critical supplies are warehoused or stockpiled. When a rolling global pandemic takes its toll on the working population of a city in Asia, for example, the products and supplies that come from that city—and perhaps nowhere else—that we need to respond to a rapidly growing pandemic will not be available. No amount of money can buy something that doesn’t exist. This is why the recently created World Bank Pandemic Emergency Financing Facility fund, which is intended to provide global financing for responding to a pandemic, will not work for a global emergency.

Without going into all the complex biochemistry of diversity, the important thing for us to remember is that microbes were here before us, have coevolved with us while we humans occupy the earth, and will be here after we are gone. In our superior human mind-set, we think of our species as being largely in control. But to understand the true biologic sense of the power of microbes, we must never forget that we are the ones trying to anticipate and respond to their evolution, not the other way around.

There are more microbes in the human gut than there are cells in the entire body, and there are microbes virtually everywhere within us. Yet our personal microbiome accounts for just about three pounds of our total body weight. So for the total of microbes on earth to outweigh all other life-forms, their predominance in our existence is staggering to contemplate.

Individual components of our blood, including B cells and T cells, seek out foreign invaders and use their various mechanisms to envelop or destroy them, or both. They stick around for some period of time, some of them for a lifetime, with the “memory” of the invader, so that if it strikes again, the immune system is ready for it without having to ramp up as much as it did the first time it encountered this invasive agent. This is the concept behind vaccines: introduce an attenuated or dead version of the virus so that the body can build up these defenses before the “real” one hits.

Each infectious disease needs a certain human or animal population to sustain itself. Measles, for instance, one of the more effectively transmitted infectious diseases there is, likely requires a contiguous population of several hundred thousand; otherwise, it dies out.

Statistically, the worst pandemic of the modern era occurred in 1918, when the so-called Spanish flu swept the globe. In reality, it was not Spanish at all. It was just that Spain, neutral in World War I and thus a country that did not censor its press, reported it honestly and therefore was erroneously stuck with the rap. Conservative estimates have traditionally pegged the worldwide death toll at 40 to 50 million, but recent analyses suggest it might have been twice that, dwarfing the toll of the brutal and bloody world war that immediately preceded it.

The significance of the fact that any person can end up anywhere else on earth in a matter of hours is obvious. But just as significant is the idea that because of the global supply chain and the just-in-time-delivery practices affecting nearly all products and components, the impact of a pandemic will be far greater than one of similar virulence would have been in the past. As just one example, we may have among the world’s best medical infrastructures in the United States, but virtually all of our generic lifesaving pharmaceuticals are manufactured overseas. Let’s say there is a major epidemic in a region of India where many of our drugs come from. Lives will be lost in our own major cities because the critical medications just won’t be available.

In contrast to a chronic condition, an outbreak, particularly one caused by a virus transmitted simply by breathing the same air as those already afflicted or suffering a mosquito bite we don’t even feel or notice, creates a sense of panic combined with the struggle to understand the science and control the situation. This naturally leads to disproportionate disruption and impact. In the wake of the 9/11 attacks, a small amount of powdered anthrax sent through the US Postal Service to Capitol Hill and media figures, causing only twenty-two cases, still took billions of dollars to fix, closed down the Hart Senate Office Building across the street from the US Capitol for months, and paralyzed the mail delivery in the area. And anthrax is not a communicable disease the way Ebola and smallpox are. You don’t catch it from another infected person.

A pandemic can shut down regional, national, or even international commerce, which in turn can lead to economic chaos, which in turn can lead to destruction of confidence in unstable governments. If a government’s authority is shaky to begin with, the stress of a pandemic can lead to a failed state, which in turn can lead to anarchism and terrorism. At the same time, while the pandemic is occurring, other endemic and noninfectious diseases are still affecting the population, the combination of which can eventually tax or even break the existing healthcare delivery system.

It’s hard to overstate the impact of vaccines on our history and on our lives.

So compelling was the case for the early vaccines that in 1905, the Supreme Court ruled in Jacobson v Massachusetts that the benefit of compulsory smallpox vaccination to public health took precedence over an individual’s personal agency to refuse.

With matter-of-fact modesty and a shy smile, Salk replied, “Well, the people, I would say. There is no patent. Could you patent the sun?”

So successful was the effort to curtail or eradicate the range of childhood diseases that the public started taking their absence for granted. This, among other things, has given rise to an antivaccine movement, whose members are wary of vaccines, particularly childhood vaccines, believing that they may cause autism, or even the diseases they are supposed to prevent. There is no scientific evidence to support these charges, but that doesn’t stop a good many sophisticated, educated people from backing away from vaccines that were once considered miraculous. Ironically, this resistance recalls the dawn of vaccines, when smallpox vaccinators were harassed and attacked by suspicious opponents. But they, at least, had the excuse of lack of established knowledge.

Let’s get one thing straight about vaccines: It’s not like in the disease outbreak thriller novels and movies. A bunch of scientists in a lab don’t suddenly find the magic formula, bottle it up, and have a medical flying squad race to the scene and inject it into the arms of the stricken, who, miraculously, recover in a matter of seconds or minutes. For one thing, vaccines are almost always for prevention rather than treatment. For another, once you’ve got the proof-of-concept “formula” that appears to work in the lab and then in animal models, you’ve got a long way to go before you can even submit the vaccine for FDA approval and then create and ramp up production facilities, not to mention figuring out how to pay for all of this.

Vaccines are not like other kinds of drugs, and comparatively speaking, they are hard to make. The production of the Lipitor you take for your cholesterol, the Metformin you take for diabetes, the Prozac you take for depression, or the Viagra you take for erectile dysfunction—all maintenance drugs of one kind or another—can be likened to building a Chevrolet on a General Motors assembly line. Production of a vaccine, on the other hand—particularly a new vaccine—is more like growing lettuce in a field in California. By the time the Chevy gets to your garage or the lettuce gets to your table, each is going to be pretty much what you expected. But the process for manufacturing the car is a lot more predictable, repeatable, and scalable than the process for growing lettuce, which is subject to weather, ground conditions, drought or flood, insects, and any plant-based diseases that happen to be circulating in the area.

Just as a vaccine is different from a maintenance drug in terms of manufacturing and makeup, it is fundamentally different from an economic perspective. A pharmaceutical company can count on a regular and predictable market for the maintenance drugs its customers will take every day, often for the rest of their lives. For the major noncommunicable illnesses like cancer, manufacturers know they will have a steady market because the diseases are not going away anytime soon, and they can charge a lot of money for their drugs as long as their patent monopoly lasts.

To be dispensed in the United States, vaccines have to go through the same sorts of FDA-mandated clinical trials as other pharmaceuticals. As vaccine development progresses, there are various internal tests, and then animal testing. Then there are three phases of human trials. Phase I tests safety. Phase II tests various dosage levels for safety and effectiveness. Phase III tests the actual effectiveness of the drug or vaccine on a large enough cohort of human subjects to allow for variations in response, factoring in considerations such as how the vaccine affects children, teens, persons over sixty-five, persons with an immunocompromising condition, pregnant women, and so on.

Generally, Phase III trials are double-blind, meaning that neither the subject nor the administrator knows which subjects are given the actual drug and which are given a placebo. At the end of the trial, that information is revealed and the outcomes are compared. Sometimes the trials are stopped early when an independent monitoring board determines that during the trial, the vaccine has clearly demonstrated it is or is not working, or there are patient safety issues emerging. Phase III trials can get extremely expensive, and pharmaceutical companies don’t like to undertake them unless they think they have a pretty strong prospect of obtaining FDA approval. Today a pharmaceutical company can expect that getting a new vaccine licensed will take more than a decade of work and a billion dollars of investment.

If you look at three diseases, the three major killers, HIV, tuberculosis and malaria, the only disease for which we have really good drugs is HIV. And it’s very simple, because there’s a market in the United States and Europe. —JIM YONG KIM, MD, PRESIDENT, WORLD BANK

tuberculosis, which, without treatment, kills about 45 percent of its victims. He points out that 4,100 people die every day from the disease. And yet this is one of those examples of our emotional disconnect regarding the most likely threats. We are terrified of Ebola but ignore TB on the same continent. And make no mistake; TB is a much more likely large-scale killer in the West than Ebola or Zika.

At that time (and as of today), transmission of H5N1 virus from humans to humans has been rare. However, it remains one of the bird-flu viruses that have the potential to become a human pandemic strain. If H5N1 influenza virus acquired the capacity for human-to-human transmission and an increased case fatality rate, we could face a worldwide pandemic of devastating impact.

the powerful lesson here is that if an influenza virus accidentally escapes or is intentionally released, expect that it will spread around the world in short order. This is the proverbial single match being able to light a global forest fire. The possibility for a DURC research study using a potentially dangerous influenza virus should scare the hell out of everyone.

Anthrax—Bacillus anthracis—is a particularly effective bioweapon. It doesn’t transmit person-to-person, but when dried out, the bacteria preserve themselves as tiny, virtually weightless spores that are hardy enough to last for decades or longer. Archeologists have even found evidence of them in Egyptian tombs. When those spores are inhaled and reach the moist, comfortable environment of the lungs and gastrointestinal tract, they germinate, reverting back to their active form and releasing three deadly protein toxins. Inhalation of anthrax in the lungs causes pneumonia that kills between 45 and 85 percent of untreated victims. In dried form, anthrax can be hidden in any white powder and will not arouse the suspicion of airport security workers or anyone else.

The late William “Bill” Patrick was a brilliant scientist and a friend to both Mark and me. He used to head up the American bioweapons program at Fort Detrick. Bill made a habit of carrying around a vial containing 7.5 grams of a harmless bacterial culture that looks just like anthrax under a microscope. In March 1999, testifying on Capitol Hill before the House Permanent Select Committee on Intelligence, he pulled out his vial, explained what it was, and declared, “I’ve been through all the major airports and security systems of the State Department, the Pentagon, even the CIA, and nobody has stopped me.” Seven and a half grams, by the way, would be just about the exact amount needed to kill everyone in a structure the size of a Senate or House office building.

Bioweapons are unlike any other of their brother weapons of mass destruction, and our response strategies for other WMDs will not work against them. As horrific as it is to think of two jetliners hitting and bringing down the World Trade Center towers, that was a readily “survivable” tragedy for New York City and the nation. At the end of the day on September 11, 2001, the terrorist act was over and the recovery could commence. With a bioterror event, the end of the day would be only the beginning, and no one would even know it yet. We likely wouldn’t recognize it for a week, by which time the initial victims would have carried their deadly infection to all parts of the United States and much of the world.

Number two on my list of the big three is smallpox. Despite the fact that it has harmed no one in almost forty years, smallpox remains one of the scariest monsters on earth. Its toll on human history tops a billion deaths, and an even greater residual effect of acute suffering and disfigurement. So powerful has been its cultural influence that it is perhaps the only disease that is represented by gods and deities in various cultures. Today we no longer attribute the virus to gods, but the mere thought of its reemergence haunts the fevered dreams of all responsible public health officers.

as the technology raced forward, the superskyscrapers of genetic engineering became more and more attainable. Today, it will soon be possible, if it is not already, to re-create the smallpox virus in a lab just as Wimmer re-created polio. In fact, in an October 2014 opinion piece in the New York Times entitled “Resurrecting Smallpox? Easier Than You Think,” a highly respected professor at the University of Southern California, Leonard Adleman, described how his lab or others might make smallpox virus using a similar approach. In other words, we can now build 1,600-story genetic buildings.

through gain-of-function techniques, terrorist-employed scientists might be able to modify or enhance their new variola virus so that we are not protected by our current vaccine.

the delay between release/infection and the onset of symptoms compounds and prolongs the terror and makes it that much more difficult to track, identify, and apprehend the terrorist.

Without ongoing commitment from the global public health community, progress toward getting vaccines for Ebola approved could falter as memories of the outbreak in West Africa fade. Near the beginning of the 2016 Zika outbreak, American lawmakers decided to take the remaining Ebola funds to fight Zika, thereby giving neither disease the attention it warrants.

We can take Ebola off the table as a major epidemic threat, even if it does mutate into a disease that can be transmitted by just breathing shared air with an Ebola case. The question is, Do we have the collective vision, leadership, and financial support to complete the job?

On March 29, 2003, he crashed and died, after eighteen days of intensive care in a hospital in Bangkok. He was forty-seven years old. Toward the end, he asked for a priest to administer last rites and directed that samples of his lung tissue be saved for scientific analysis. I fervently hope that Carlo Urbani will be remembered as one of the great heroes of modern epidemiology—a man with a noble mission who sacrificed his own life to care for others and alert the world to a vicious and imminent threat.

In suppressing reporting, China forfeited a critical opportunity to contain the disease in its earliest stage and later apologized to the WHO.

Perhaps the greatest medical mystery of the SARS outbreak was why some people, like Dr. Liu and Mr. Chen, gave the disease to so many people they encountered, even casually, while others who caught it became sick themselves but were hardly infectious at all to others. For reasons we still don’t completely understand, certain individuals with coronavirus become “superspreaders.”

Superspreaders break the reproductive rate rule. They transmit to many more contacts than other cases with the same infection. It’s unclear why superspreaders infect such a large number of those exposed. What we do know is that superspreaders can make coronavirus infections in humans into a very scary situation. These superspreaders are not obvious; they are not necessarily sicker, immunocompromised, older, or pregnant—all the conditions we normally associate with being more infectious.

As Dr. Anne Schuchat, principal deputy director of the CDC, put it, “The only tools we had to control SARS were ones we’ve had for hundreds of years.” Even so, two very different public health–based activities played critical complementary roles in stopping the SARS outbreak: first, elimination of the animal sources in China, and second, effective infection control. Once the civets and badgers were recognized as the likely source for transmitting the virus to humans, they were removed from the markets in southern Asia and people were warned not to eat or have any contact with them. This was, in a sense, “pulling the pump handle,” similar to what Dr. John Snow did with the Broad Street pump in London in 1854.

And here is the problem that distinguishes MERS from SARS or any of the other coronaviruses: The virus is now established in the camel population throughout the Middle East; it doesn’t even need the bats any longer to propagate.

Now, it’s one thing to kill all the ferret-badgers and masked palm civets; no one cares that much about them. Even if you have a real taste for this kind of exotic delicacy, it’s not an unreasonable hardship to give it up. But there is absolutely no way you are going to eliminate camels in the Middle East.

camel owners are not about to cull an infected herd showing few, if any symptoms, the way the Chinese and Americans have several times culled entire populations of chickens infected with various strains of avian influenza. So we can rule out the idea of eliminating the camels of the Middle East and Africa.

If you think you are too small to make a difference, try sleeping with a mosquito. —DALAI LAMA

with mosquitoes, it’s only the females that bite, through the slender, hollow, tubelike extension from the mouth, called a proboscis. In some species, the female needs the nutrients in blood to produce eggs, and in others the blood stimulates production of more eggs. When she bites, the mosquito injects saliva into the tiny wound; the saliva contains an anticoagulant that keeps the blood from clogging up her proboscis. The itchy red bump on the skin left after the bite is the result of a histamine compound fighting off the invading protein. It’s the saliva that contains the virus or parasite that then infects us. And we’re not the only species affected by mosquitoes. Various types will seek blood from humans down to small rodents and even reptiles.

For a mosquito to transmit an infectious agent, it has to become infected. Fortunately, only a small percentage of mosquito species are susceptible to infection with human disease pathogens. The main way they get infected is by feeding on a human or animal that is also infected. For example, early in the summer, a mosquito carrying West Nile or, say, Eastern or Western equine encephalitis virus, bites nestling birds that can’t yet fly. These young birds become infected and are now carriers. Other mosquitoes bite these immobile birds and then bite other birds and humans in a pyramid of infection that keeps building on itself.

Malaria, on the other hand, is largely a human disease that is transmitted to biting mosquitoes, which then transmit it back to other humans. More recently we have seen an increase in strains of a malaria parasite that primar...

Temperature plays an important role, too, because it affects the extrinsic incubation period: how quickly the mosquito becomes infected with whatever it has taken in through a blood meal, and then how quickly it becomes infectious. The warmer the temperature, the shorter the extrinsic incubation period for most vector-borne diseases. This...

That’s the challenge of proactive public health practice. If you prevent something from happening because of your actions, you’ll always be second-guessed as to whether the action was necessary. On the other hand, if you don’t act on the information you have and an outbreak occurs, you will be burned at the stake by the media, elected officials, and even your colleagues. I have always taken the position as a public health professional that I’d rather have to answer for something I did than for something I didn’t do.

On the outskirts of Havana, Reed had constructed two barracks-like buildings, which he dubbed Fomite House (fomite being a physical object that can carry and, when touched, transmit infection) and Mosquito House. Volunteers were offered money to sleep in one of the two buildings. Fomite House was truly disgusting, with dirty bed linens contaminated with the vomit, urine, and feces of previous yellow fever sufferers. Accounts recall visitors puking just upon entering the fetid atmosphere. But Reed made sure no mosquitoes got in.

Mosquito House, by contrast, was kept spotlessly clean, with good air circulation. Inside, a sleeping space was divided by a partition that went from the floor to the roof. One side was kept completely free of mosquitoes. On the other side, the bugs were intentionally introduced.