When Pasteur died, he left his laboratory notebooks to his oldest male child, and his will stipulated that these notebooks should never leave the family and were to be passed on from generation to generation by male inheritors. In 1964, Pasteur’s last surviving direct male descendant donated his laboratory notebooks to the Bibliotheque Nationale in Paris. Scholars studying these notebooks found that Pasteur often cut corners in his work, sometimes did not describe exactly how experiments were done, and did not always publicly report results transparently. This straddling of ethical boundaries or, worse, fraud is severely punished by the modern scientific community. Indeed, as it should be, because the scientific edifice is built on the trust that scientists have described their studies honestly. Mistakes can happen, of course, but deceit is not allowed.
Pasteur’s straddling of ethical boundaries notwithstanding, he made groundbreaking advances that had a transformative effect. Vaccines designed using Pasteur’s methods have saved more lives than any other medical procedure. Vaccines that protect children from diseases are a major contributor to the dramatic reduction in childhood mortality. Today, we crave a vaccine against the ongoing COVID-19 pandemic, and hopefully, we will have one soon. Pasteur’s work is the foundation for this hope.
For his achievements, Pasteur received many honors and awards. Many streets around the world are named after him, and the Pasteur Institute in Paris is a famed medical research laboratory that Pasteur himself founded. He died in 1895, when he was 72, and his body is interred in the first floor of the original building of the Pasteur Institute. Visitors are welcome to see his tomb and the apartment where Pasteur lived at the end of his life. Pasteur did not receive a Nobel Prize because the first of these was awarded in 1901.
Koch’s and Pasteur’s work focused mainly on bacterial infections. But there are other organisms that can cause disease, like fungi, parasites, and viruses. Because viruses pose a special threat to humans, causing many recent pandemics, in the next chapter, and in most of what follows, we focus on these tiny organisms.
3 Viruses and the Emergence of Pandemics
When Pasteur was trying to make a vaccine for rabies, he was unable to find the causative agent. Filters were often used to trap and isolate bacteria that might be contained in fluids. These filters were unable to trap the causative agent of rabies. Pasteur reasoned that the microbe that caused rabies must be very small. Rabies is caused by a virus, and indeed it is very tiny. The virus that causes the COVID-19 disease is a member of a family of viruses called coronaviruses. These viruses are roughly spherical in shape and have a diameter of roughly 100 nanometers, which is a thousand times smaller than the diameter of a human hair. The influenza virus, which causes the seasonal flu, is also of similar size. In comparison, the bacterium that causes tuberculosis is rod-shaped, and its length is 20–40 times larger. Pasteur also failed when he attempted to culture the rabies virus using the procedure that Koch developed to grow bacteria. It was only in the twentieth century that methods to visualize and study viruses were developed.
In this chapter, we will describe why viruses need us, and plants and animals, to survive. We will also describe the different types of viruses that exist and how they function, as well as how pandemic-causing viruses emerge to wreak havoc. We begin, however, with a bit of history about our long war with viruses.
Our Eternal War with Viruses
Viruses are very simple ancient organisms that have probably existed since life began. For reasons that will become clear in the next section, viruses cannot reproduce on their own. They have to colonize bacteria, plants, and animals (including humans) in order to replicate and propagate their species. Therefore, viruses have specialized skills that let them invade other species and replicate inside them. When a virus invades the human body and replicates, it can damage our cells and tissues. The immune system, about which we will learn in the next chapter, tries to kill viruses that invade us to prevent and combat viral infections. This war between viruses and our immune system has raged since time immemorial.
Pre-agrarian humans contended with fewer types of viruses than we do. These ancient humans were also afflicted by viruses, but they were different in nature from the highly contagious ones that circulate today like those that cause flu, measles, or COVID-19. This is largely because of differences in the lifestyles of modern and ancient humans.
Many viruses that circulate today spread by casual contact between people. Infected people exhibit symptoms of disease and some people die because of the acuity of disease. Our immune system usually succeeds in completely eradicating the virus from our bodies, and we are cured. Remarkably, for a period of time, our immune system “remembers” that a particular virus had previously infected us. If the same virus reinfects us, the immune system can swat it away. For some viruses, this shield of immunity can last as long as a person’s lifetime.
Contagious viruses that kill some infected people, but which are normally eradicated from our bodies by the immune system, were unlikely to survive as a species in a pre-agrarian world. Our ancestors at that time lived as small groups of loosely connected people who occupied a large area. So, people encountered very few others in their daily lives. If a virus like that which causes COVID-19 infected a person, that individual would therefore infect very few others. The infected people would either die or recover and be immune to the virus. In a small population, over time, most would become immune, and a newly infected person would be very unlikely to encounter a susceptible individual during the course of disease. Therefore, the virus could not be transmitted to new people in whom it could replicate. Thus, over time, the virus would become extinct. If the virus caused a very lethal disease, it would kill everyone in a small community and become extinct because again there would be no one to infect.
This is why most viruses that circulated in pre-agrarian humans were probably not terribly contagious or deadly, and were not eradicated from the body by the immune system. These viruses adapted to coexist for the lifetime of the infected person, hiding out quietly most of the time. Periodically, they would rear their heads and infect new cells, causing recurrence of disease symptoms. The immune system would then suppress this recurrence, and the cycle would continue. Herpesviruses are an example of such an ancient type of virus that circulates in modern human populations.
Viruses like those that cause the flu, measles, and COVID-19 that were unable to thrive in pre-agrarian times became viable once human ingenuity led our ancestors to learn how to grow crops. In the agrarian society that emerged, people started living together in larger communities concentrated in smaller areas of land. In a dense population, a contagious virus can potentially be transmitted to many others by an infected person. So, the virus can replicate in many people. If the population is large, many individuals have to be infected and then recover to reach a point where a sufficiently large proportion of the population is immune. As this takes a long time, the virus can keep spreading to new people. Furthermore, in a large and dense population, new births provide a constant stream of new susceptible people. This is why highly contagious viruses that cause diseases that our immune system can usually clear from our bodies began to thrive in the agrarian era. Farming also led humans to domesticate animals and live closely with them. Viruses that infected animals and could also replicate in humans began to spread in the human population. Thus, it came to be that a great diversity of viruses began to circulate among humans.
The exchange of individuals between communities increased as travel became easier. These “immigrants” could bring diseases caused by viruses in their communities to others. For example, as mentioned in chapter 1, European immigrants brought a disease caused by a virus, smallpox, to the Americas. Immigration is also a source of new susceptible people for a virus that already exists in a community. When the industrial revolution began, people started to live in cities with even higher population densities than farming communities. Highly contagious viruses flourished even more. The human race
is connected today by our shared history of battling the same contagious viruses.
The transition from hunter-gatherer societies to agrarian ones, the industrial revolution, and the many technologies and innovations that followed have improved the quality of human life as measured by a myriad of metrics. For example, we live longer now and childhood mortality is much lower. But the accompanying changes to the way we live also made us more susceptible to infection by a greater diversity of contagious viruses that can cause acute disease. Yet in spite of how the changes in our way of life have favored viruses, we have been winning the war against them. This is because of human ingenuity. We learned to develop vaccines that protect us from many disease-causing viruses. But vaccines take time to develop. So, anytime a new virus emerges, we remain vulnerable to devastating pandemics. The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is only the most recent example.
Let us now dig into how viruses work, how they replicate, and why they cannot do so without us. But first we need a primer on the basic machinery that enables living organisms to function and replicate.
DNA, RNA, and Proteins
All living organisms try to replicate and propagate their species into the future. Since ancient times, people noticed that children share some traits with their parents, and the origin of heredity was hotly debated. But it was only in the nineteenth century that the Catholic monk and botanist Gregor Mendel’s careful studies while breeding peas provided the first rigorous basis for heredity. His work led to the concept of genes, which are inherited from one’s parents. But Mendel did not know what a gene really was. The discovery of genes had to wait until 1953 when James Watson and Francis Crick, two young scientists working at the University of Cambridge in the United Kingdom, first described what a gene really is. Informed by the studies of many others, including Rosalind Franklin, they had a flash of insight that has transformed how we think of ourselves as individuals and as a species, and indeed our understanding of all living things. Their discovery of how a molecule called DNA stores all our genetic information and faithfully reproduces it in our progeny also laid the foundation for modern medicine.
A DNA molecule is made up of two long strands, each comprised of four types of units that are connected together. The four types of units are called bases, and are labeled A, T, G, and C. The two strands of DNA wind around each other to form a double helix. This is made possible by the fact that A on one strand pairs only with T on the other strand, and G pairs only with C. Therefore, each DNA strand in the helix has a sequence of bases that is the complement of the sequence of the other. The sequence in which these four types of bases are connected in a DNA molecule encodes information about the organism. This is the information that is passed on to progeny.
Complex organisms, like us, are made up of many cells. Each cell contains a copy of our DNA within an enclosure inside the cell called the nucleus. The cells in an organism need to be continually replenished with new cells. This is accomplished by a process by which one cell divides into two identical daughter cells. During this replication process, the DNA double helix in the original cell is copied into two identical DNA molecules. First, the two strands of DNA are separated. Each original strand now serves as a template for the synthesis of a new complementary strand. This is accomplished by a cellular molecule called DNA polymerase, which joins the right complementary bases one by one to the growing new strand. The structure of DNA provides a mechanism to “proofread” the growing complementary strand of DNA. If the wrong base is added, it will not pair with the template strand, and so it is excised and the correct base is then added. In the end, we have the two old strands of DNA, each paired with a new complementary one. Each of the two new DNA helices becomes the DNA molecule in each daughter cell. Of course, errors do occur sometimes, and the errors are called mutations. The error rate for copying DNA in higher organisms is small—during each replication cycle, the probability that an erroneous base will be inserted into the new growing strand is roughly one in a billion.
Our cells work together to allow us to perform all our functions. The functions of a cell are carried out by proteins. Proteins make life work. If we imagine that a cell is like a car, proteins make up all the parts that allow the car to function. Proteins are long strands of units called amino acids. There are 20 types of amino acids. So, an enormous diversity of protein sequences can be generated by connecting these amino acids in different ways. For example, as there are 20 choices for amino acids at each position, a string of just three amino acids could be arranged in 20 × 20 × 20 = 8,000 different sequences. Proteins are much longer, with an average length of about 400 amino acids. The number of possible proteins, each with a different sequence, that can be created is therefore immense. The sequence of amino acids in a particular protein determines its function. Proteins with different sequences have different functions. Information about all the proteins we can have in our cells is encoded in our DNA.
Ingenious experiments carried out after the structure of DNA was discovered showed how DNA encodes information about the sequence of amino acids in proteins. Different sequences of three contiguous bases in a DNA molecule correspond to different amino acids. For example, AGC corresponds to one particular amino acid, while GCC corresponds to another, and so on. Given that there are four types of bases, there are 4 × 4 × 4 = 64 combinations of three bases. So, our DNA can encode information on 64 types of amino acids. In reality, there are only 20 amino acids. So, multiple types of three-letter strings of bases correspond to the same amino acid. The sequence of three-letter strings of bases in a stretch of DNA (a gene) corresponds to a particular amino acid sequence, and hence encodes information on a specific protein. So, you see that DNA, using only a four-letter alphabet, is a compact and ingenious way to encode complex information.
How does the information encoded in DNA get translated into making proteins in a cell? Just as a car needs many bolts to function, cells usually need to make many copies of a protein in order to enable their functions. The gene that encodes information on a particular protein’s sequence is first converted into a molecule related to DNA called RNA. RNA is a very ancient molecule, and almost certainly existed before DNA or proteins. An RNA molecule is usually composed of a single strand of connected bases, and looks very similar to a single strand of DNA. The difference is that RNA’s four-letter alphabet of bases is not, A, T, G, and C, but A, U, G, and C. So, U replaces T. A cellular molecule, called RNA polymerase, transcribes the DNA sequence that comprises a gene into many RNA molecules that have the complementary sequence. Each RNA molecule now contains the information on the sequence of amino acids in the corresponding protein. A large and complex machine in cells, called the ribosome, then takes each RNA molecule and translates its sequence of bases into the sequence of amino acids in the corresponding protein. The way in which the information encoded in genes in our DNA is first transcribed into RNA and then translated into the synthesis of corresponding proteins is called the “central dogma of molecular biology.”
Viruses Need Us to Replicate
Just like animals and us, viruses have to replicate in order to propagate their species. In fact, their principal function is to make copies of themselves. To carry out its functions, just like our cells, a virus needs proteins. Just like our cells, each virus particle also contains its genetic information. But, unlike each one of our cells, a virus particle does not have all the machinery needed to translate its genes to corresponding proteins. Viruses enter a person, animal, or plant and invade their cells. A virus then hijacks the machinery in the cell they have invaded (e.g., the ribosome) to translate its own genetic information into many copies of its proteins. This enables the assembly of many new virus particles that can go on to infect other cells. In a sense, viruses are parasites.
How Viruses Enter Our Cells
Cells respond to changes in their environment in order to carry out their functions. Each type of cell has specific proteins, called receptors, that stick out o
n their surface to sense the environment. A receptor on a particular cell binds only to a specific substance in the environment. If the receptor binds to this substance, the cell detects its presence and responds accordingly. Viruses have spikes on their surface made up of viral proteins. To cause infection, a virus’s spike must bind to receptors on the surface of cells in the tissues that it invades. Once a virus’s spike binds to a receptor, it can force its way in through the cell wall and then hijack its machinery to replicate.
The SARS-CoV-2 virus, which causes the COVID-19 disease, binds to a specific human receptor, called ACE2, that helps regulate blood pressure. ACE2 is abundantly present on the surface of cells in the lung. So, an airborne virus can enter through our respiratory tract and bind to ACE2 on our lung cells. This is why SARS-CoV-2 spreads through the air and infects our lungs. But ACE2 is also expressed on cells in the heart, intestine, and kidney, which may explain why other medical problems arise in COVID-19 patients.
Types of Viruses
Viruses, Pandemics, and Immunity Page 4
