by Sanjay Gupta
The first known virus we ever documented scientifically was not one that infected humans. It decimated tobacco plants, turning their leaves a mottled dark green, yellow, and gray. In 1857, farmers in the Netherlands reported a disease sickening 80 percent of their crops. It spread so easily that touching an affected plant with a watering hose could damage the plant next to it. Martinus Beijerinck, a visionary microbiologist and botanist, had long thought the source was an infection of something entirely different from bacteria or a fungus. He called it contagium vivum fluidum (contagious living fluid), noting that the pathogen had the ability to slip through the finest-mesh filters that could trap bacteria, giving it almost liquid properties.8 And this is how the word virus got unluckily attached to this peculiar class of germs. Beijerinck used the word virus from the Latin word for a liquid poison to label this new kind of pathogen. If it could pass through a filter normally used to capture bacteria, he knew he was handling something else—something much smaller. But he never deciphered the full virus story and never got a chance to glimpse them. Yet while he incorrectly thought viruses were liquid—they are technically particles—his results were nonetheless on target.
Beijerinck was known as a difficult, socially reclusive individual who refused to have his picture taken, verbally abused his students, and never dated or married; he believed that marriage would interfere with his work. But he was a scientific trailblazer with a keen ability for observation. He may not have earned points for his character, but he definitely earned his keep in the laboratory, conducting research until the very end when cancer took him at age seventy-nine. He is credited with being a prime mover in establishing general microbiology as a major field of study. Well before most universities recognized microbiology as a distinct discipline, he established the Delft School of Microbiology, which is now regarded as the ancestor for many such departments and institutions worldwide.
Plant pathologist Adolf Mayer, who was director of the Agricultural Experiment Station just east of Delft in the Netherlands’ Wageningen municipality, began researching the tobacco blight in 1879 and named it the “mosaic disease of tobacco.” Germ theory, the modern understanding that pathogens can make us sick, was slowly under development, but the concept of viruses would take time to be accepted and understood within a biological context. When Robert Koch, a German pathologist and one of the main founders of modern bacteriology, discovered the bacterial culprit behind tuberculosis in 1882, he developed a short guide for linking these bacteria to the diseases they cause. It would become known as Koch’s postulates—the rules for recognizing the role of bacteria in illness: the bacteria had to be present in every case of the disease; it had to be isolated from the host with the disease and grown in pure culture; the specific disease had to develop when a susceptible host was exposed to a pure culture of the bacteria; and, finally, the bacteria had to be recoverable from that infected host.9 (I should note that fewer than 1 percent of bacteria cause diseases in people.)
Mayer ran the experiments to see if this unidentified microbe met the criteria of Koch’s postulates, but something wasn’t right. Every time Mayer performed a cycle of germ isolations and reinfections to find the cause of mosaic disease, he failed. He could show that the sap from a sick tobacco leaf could pass the disease to a healthy leaf, but he couldn’t produce a pure culture of the germ and couldn’t spot the nemesis under a microscope. It was an invisible contagion.
Not being able to see viruses under an ordinary light microscope, like you can bacteria, made them elusive, confusing, unbelievable, and on the verge of fantastical. In 1929, American biologist Francis Holmes developed a method using the tobacco mosaic virus to prove that viruses are discrete particles and have stronger effects at higher concentrations. In essence, his method “made the virus visible” to some degree, but not like a photograph. It would take the invention of the electron microscope in 1931 to pave the way for imaging these exceptionally small microbes, which finally happened in 1935 by the American biochemist and virologist Wendell Meredith Stanley. He created a crystallized sample of the virus that could be “seen” with X-rays, earning him a share of the 1946 Nobel Prize in Chemistry.10 The first unambiguous photographs of the tobacco mosaic virus would not be taken until 1941 with the invention of powerful transmission electron microscopes, which revealed the pathogen’s skinny, rodlike shape. (Rosalind Franklin produced the clearest X-ray diffraction image of the tobacco mosaic virus in 1955, following her contributions to the discovery of DNA’s double helix.)11
The visual proof was a turning point in science, dispelling doubts and quieting skeptics who had questioned the very existence of viruses. The images showed that viruses are simple structures made of genetic material wrapped in a solid coat of protein molecules (or, in the case of COVID, the virus is spherical and wrapped in a fatty envelope that makes them especially vulnerable to soap when you wash your hands). Although bacteria and viruses are both too small to be seen without a microscope, microbiologists will tell you that they are as different as giraffes are from goldfish. Bacteria are more complex, single-celled organisms with a tough exterior wall and a squishy beach ball full of fluid inside that cell. Most importantly, bacteria can reproduce on their own and have probably been around for 3.5 billion years. Viruses are tiny by comparison and can reproduce only by attaching themselves to a cell. Killing a virus isn’t possible, because they aren’t really alive. They are the zombies of the microbe world.
Whether we should call viruses “microbes” at all is up for debate. They cannot live on their own, contain not a single cell, and do not perform any kind of physiological task we usually equate with animal or plant life, such as eating, respiring, reproducing, and even dying. They are more akin to bits of data that need another piece of machinery—a host—to replicate and carry on. They are sacks of code sometimes called, ironically, capsid-encoding organisms, or CEOs. They don’t grow or move; we help them get around. We are the giant computers that run their software programs in our system. And for COVID, it’s like a nefarious computer virus—a bad computer bug that takes over our controls and turns our system against us.
Son of SARS
Human evolution has been slow and steady. It took the genome of the human species 8 million years to evolve by 1 percent. But ask your fellow virus that wants to infect you how long it takes to make a few adaptive changes to its wardrobe, and it will say to wait a day. Viruses practically change with the weather. Many viruses that infect animals, including COVID, can evolve by more than 1 percent in a matter of days. Coronaviruses, which are single-stranded RNA molecules, accumulate mutations at a rate 1 million times faster than human DNA does. They are simple, small, and nimble, whereas we Homo sapiens are complex, large, and often clumsy.
For those who want to understand the difference between DNA and RNA, here’s the briefest explanation. The two molecules are the power couple in all living organisms to sustain life and carry hereditary information, but they are not structurally identical. RNA is single stranded, like a ribbon, while DNA is double stranded and therefore more stable and sturdier. DNA looks like a twisted ladder, the one you memorized from your high school biology text. The chemical makeup or “ingredients” of DNA and RNA are also not identical. RNA nucleotides—the basic building blocks—contain ribose sugars, while DNA contains deoxyribose. And every scientist who studies this knows that uracil is specific to RNA, while thymine is present in DNA (don’t panic: you will not be tested on this). The important point is that DNA and RNA are partners in serving the function of maintaining the blueprint of life, and their main job is to produce proteins, which are the key products in the support of life on Earth.12
In most organisms, DNA stores the genetic information for building living things and transmits those precious codes to offspring, while RNA is mainly involved in transferring the genetic code for protein synthesis—the body’s manufacturing of proteins to support life. Proteins are the body’s workhorses: They are required for the structure, function,
and regulation of all tissues and organs. Put simply, proteins drive the chemical reactions needed to keep cells alive and healthy. DNA is mostly found in the nucleus of cells, whereas RNA is found in the surrounding cytoplasm. Until recently, RNA was thought of as merely a messenger between DNA and proteins, but RNA can do far more. Because RNA can drive chemical reactions, as proteins do, and carry genetic information, like DNA, most scientists think life as we know it began in an RNA world—without DNA and proteins. RNA and viruses likely coexisted for a long time before the more complicated DNA molecule showed up in Earth’s life story, or memoir.
Because the mutation rate for the RNA in viruses is exponentially higher than DNA, they have an extraordinary ability to survive an assault from our immune system—they can quickly undergo a wardrobe change or alter their spike proteins to be able to bind tightly to a human receptor to enter our cells, as in the case of COVID. This is why we hear so much about variants—the mutant strains of COVID that have emerged and can render the virus more contagious or deadly. Viruses that spill over from an animal such as a bat to a human are called zoonotic viruses.
Today, three-quarters of all new infectious diseases affecting humans originate in animals, and at least thirty new infectious diseases have emerged in the past thirty years—including SARS, MERS, and now COVID. Collectively, they threaten the health of hundreds of millions of people. One of the more alarming reports by the United Nations states that on average, a new infectious disease appears in humans every four months.13 There are many reasons for this, but the confluence of climate change, population growth, genetic adaptations in microbial agents, international trade and travel, and changes in land use is chief among them.
Outbreaks of rare infections like Ebola often make headline news, but more problematic are the highly communicable ones that spread via breathing, talking, whispering, kissing, hand-shaking, hugging, and singing. Given that they evolve so much more quickly than we do, our natural immunity is unlikely to keep up. And since we’re increasingly encountering these viruses in nature, we have to get crafty at countering them with other strategies—vaccines being one powerful counterpunch, among others.
One feature of modern pandemics that makes them stand apart from those in previous centuries is that their origins are off the grid. For thousands of years, we owed the contraction of most of our infectious diseases to domesticated animals—livestock like pigs, birds, cows, and cattle. The common cold originated in camels, and many strains of flu come from pigs and birds, such as H1N1 and H5N1. Today, however, our pandemics spring from close encounters of the wild kind. Ebola has repeatedly jumped from bats to primates and humans in Central and West Africa. Middle East respiratory syndrome (MERS) leaped from bats to camels to humans in Saudi Arabia. In the United States, the CDC responded to an Ebola outbreak in imported macaques at a primate research center in Virginia in 1989 and to monkeypox in 2003 that spread in the Midwest from infected rodents imported from Ghana.14 The sick rodents were housed near prairie dogs sold as pets at a facility in Illinois, and thereafter infected people. The new coronavirus’s genome is 96 percent similar to a bat virus. How long ago it made the jump from a bat to a human, acquiring the mutations necessary to do so, is not known. The germ may have also hitched an intermediary ride through another animal such as a civet cat or pangolin before reaching human cells.
As a reporter, I have traveled to the epicenter of outbreaks in Southeast Asia and China, long known as hot spots for emerging infectious diseases. I saw how poverty, population density, changing agricultural practices, and proximity to wild animals can conspire to make outbreaks likely.
Proximity to birds has emerged as a major factor in the flare-up of diseases. Nowhere else on the planet do so many humans have such close contact with so many birds as in China. Ask any infectious disease expert where they’d predict the next outbreak’s origin to be, and they will unanimously say China. At least two flu pandemics in the past century—in 1957 and 1968—originated there and were triggered by avian viruses that evolved to become easily transmissible among humans. China is a hotbed for birthing modern pathogens. The comingling of multiple species cultivates ideal conditions for spreading disease through shared water, utensils, or airborne droplets of blood, saliva, feces, and other secretions. On Chinese farms, people and livestock often live close together, sharing their germs. Pigs can be infected by both bird flu and human flu viruses, becoming veritable mixing bowls for combining genetic ingredients and possibly forming new and deadly strains. The public’s taste for freshly killed meat and the conditions at live markets, where stressed wildlife are stacked in wire cages and slaughtered on-site for buyers, create ample opportunity for humans to come in contact with these new mutations. You couldn’t design a more perfect setting for the transmission of disease. It’s the ultimate germ fest.
When COVID was first identified in late 2019, a video of a woman eating bat soup circulated widely on the Internet, sparking rumors that bat soup consumption in China caused the outbreak and the beginning of a barrage of misinformation. (As it turns out, the clip was taken in 2016 in the Republic of Palau, a country in the western Pacific Ocean, and the woman in the video was Mengyun Wang, a travel show host.) Still, there is no doubt that bats are prime reservoirs for new viruses, and there are a lot of them: A whopping one in four mammals on the planet is a bat, and 50 percent of mammals are rodents.15 Hence, the source of most zoonotic infectious diseases are bats and rodents, with bats dominating. They carry more than sixty viruses that can infect us, including Ebola and rabies. They are the natural reservoir for the rare but grisly Marburg virus, and Nipah and Hendra viruses, which have caused human disease and outbreaks in Africa, Malaysia, Bangladesh, and Australia. Bats also carry more human pathogens than other animals. Why? Because like us, bats are highly social creatures that prefer to live close to one another, giving them plenty of opportunities to spread pathogens among them. They also often live in huge colonies in caves, where crowded conditions are ideal for passing viruses to one another. These caves are abundant in Southeast Asia and China.
What’s more, the ability to fly makes their power of infection wide ranging. It also may help them adapt to the viruses so they are unaffected by them. Indeed, the physiological requirements of flight amp up their immune systems, helping protect them from the viruses they harbor. Flight also causes bats to have heightened metabolisms that raise their core body temperature to about 38°C (or 100.4°F). This means that bats are often in a state that for humans would be considered a fever. Researchers have suggested this may be a mechanism which helps bats survive viral infections. As a result, these winged rodents often host these germs without suffering any health consequences. (You may be wondering why not just exterminate the bats, if they are reservoirs for so many terrible pathogens. It’s not that easy. They are important players in our global ecology: they pollinate plants and rid the world of many pests. On top of that, they are excellent subjects for studies on healthy aging, cancer prevention, disease defense, biomimetic engineering, ecosystem functioning, and adaptive evolution.)
Because we humans haven’t yet evolved an equivalent kind of biological technology to evade the effects of these potent viruses, human-preying germs like COVID are hugely damaging. When you die of an infection, it’s often the result of your body’s own inflammatory response—not the invading germ itself. It’s friendly fire run amok. This has been the case for scores of people who succumbed to COVID. The germ foments a lethal blaze in the immune system—called a cytokine storm—that cannot be contained before it does lasting damage to organs and tissues. The ongoing cytokine storm may also play a role in those long-haul COVID patients who cannot shake the illness months after clearing the virus. It’s like a hit-and-run accident. The virus invades the body, messes with its machinery and balanced functionality, and leaves it forever changed before it takes off in search of new hosts.
Coronaviruses are a family of viruses named because of their regal appearance with crown-like
spikes on their spherical surfaces (corona is Latin for “crown”). Although this family of viruses didn’t earn its name until 1968 when scientists finally isolated and glimpsed coronaviruses under the electron microscope for the first time, these infectious microbes have been around for millennia—possibly for hundreds of millions of years, predating us.16 The first reported case of a coronavirus was in 1912, when German veterinarians debated the diagnosis of a feverish cat with an enormously swollen belly. They didn’t know what was wrong with it, and further did not know that coronaviruses were also giving chickens bronchitis and pigs an intestinal disease that killed almost every piglet under two weeks old. The link between harmful pathogenic coronaviruses and these animals, humans included, remained a mystery until the late 1960s. Certain types of coronaviruses cause relatively benign common colds, while others mutate into more virulent forms, such as the coronavirus behind the quickly contained outbreak of severe acute respiratory syndrome (SARS) in the early 2000s. In fact, we didn’t think coronaviruses could be so deadly to humans until SARS emerged, which had a case fatality rate of 11 percent, killing over half of people sixty-five and older who contracted it.
SARS is also a reason to take seriously the possibility that the strain of COVID that took the world by storm also came out of a lab, not a Chinese market. Here’s why. In 2004, the SARS virus had been largely brought under control after only 8,098 reported cases worldwide and 774 known deaths.17 The Wall Street Journal published a piece about a small resurgence of SARS tied to a safety accident.18 Although the virus had natural origins, spilling over from bats to humans either directly or through animals like civets held in Chinese markets, some of the SARS infections were caused by escapees from research labs. SARS coronaviruses have a history of breaking out of laboratories in Singapore, Taiwan, and twice in Beijing. So what about COVID?
