In memory yet green, in joy still felt,
The scenes of life rise sharply into view.
We triumph; Life's disasters are undealt,
And while all else is old, the world is new.
—Isaac Asimov (1920–1992)
WHEN I WAS about nine, my father would take me to the neighborhood Gemco. This being the 1970s, he would deposit me in the small sundry store near the front, and would go shopping for whatever he wanted, coming back to fetch me perhaps a half-hour later.
Invariably, during that time, I would find some interesting book, and I would sit down on the lowest shelf of the book rack, and read. Sometimes it was a How and Why book on optics, or biology, or whatever. Or it might be a puzzle book. Occasionally, my father would ask me if I wanted to have the book (I always did), and he would buy it for me.
Once, it was a book of science essays by Isaac Asimov, called The Stars in Their Courses. Having a kind of mania for astronomy, I eagerly opened it and began to read. I hadn't understood that the title referred to astrology and not astronomy, though it didn't matter; Asimov brought up astrology primarily as a foil for astronomy, his chief subject in the first several essays.
My father bought me that book, and I read and reread each of the essays. In addition to astronomy, they covered physics, and chemistry, and sociology, and much of what was in those pages went into my neurons and lodged there for good. At the time, that seemed the most natural thing in the world, but as it so happens, Asimov had a genius for presenting the history of science as an engaging narrative, as engaging a tale as any novel he ever wrote. (To this day, I prefer his essays and short fiction to his novels.)
And when I decided to write essays of my own—focusing specifically on astronomy, of course—I wrote them as I imagined he would: with a discursive and personal introductory anecdote, followed by a start from the very beginning (often as not with the ancient Greeks), and then a joyful meandering ride through the twists and turns of scientific discovery. For the longest time, I thought all science essays worked that way, and it was only to my later disappointment that I discovered that wasn't the case, that Asimov was the exception rather than the rule. So although I mention Martin Gardner, long-time author of the "Mathematical Games" column in Scientific American, as a seminal influence, it should be clear from my style (such as it is) that Asimov is no less a guiding force.
In honor of the hundredth anniversary of Asimov's birth, I dedicate this essay to him. In contrast to the others, this one will not be principally about astronomy. You see, Asimov's favorite writing was, in fact, his series of science essays for the Magazine of Fantasy and Science Fiction. He wrote one a month, without fail, till the end, and it was his hope to get to an even four hundred. Unfortunately, he fell one short; his last essay, "Of Human Folly," made three hundred ninety-nine. What follows is the essay I have liked to think (for the last few years) that he would have written, if he could have made it one month longer.
So, Isaac, this one is for you.
The earliest Greeks, with which many such stories begin, believed disease to be brought about by the gods and demons. Whenever they were upset with one person or another, they would visit the unfortunate human with an ailment, the type and severity being commensurate with whatever offense that person was guilty of. The role of the physician was to appease the god or exorcise the demon responsible, and if they were successful, the person recovered; if they weren't, then clearly the crime was too severe and the person hadn't deserved to survive.
The Greek physician Hippocrates (about 460–370 BC) and his followers were responsible for quelling much of the mystical speculation about disease. They carefully catalogued the symptoms of disease and recorded what treatments seemed to work and what didn't. Even though many of these treatments turned out in the end to be ineffective, the key takeaway was that disease was a physical manifestation, rather than a metaphysical one.
One of the diseases known to Hippocrates that remains with us today is pneumonia. Since pneumonia is defined clinically as an inflammation of the lungs that reduces their capacity, without reference to the underlying agent, we should not be surprised to find that multiple microorganisms can lead to pneumonia, and that turns out to be true. Most microorganisms that cause pneumonia are bacteria or viruses. Bacterial pneumonia has been recognized as such, for instance, since 1875, when the German-Swiss pathologist Edwin Klebs (1834–1913) found abundant bacteria in the lungs of people who had died from pneumonia.
Nevertheless, other agents are capable of causing pneumonia. One of these is a common fungus called Pneumocystis jirovecii, named after the Czech parasitologist Otto Jírovec (1907–1972), who discovered that it was endemic in humans. In fact, some studies indicate that it is present in about a quarter of all humans, and the pneumonia it causes (known as pneumocystis pneumonia, or PCP) can be quite severe, leading to death about 10 to 20 percent of the time.
This makes it sound as though Pneumocystis jirovecii is a dangerous killer and must be stopped. Fortunately, in human hosts, it is not a terribly robust fungus, and most people with normal, uncompromised immune systems manage to shrug it off without noticing any symptoms. Until about 1980, hardly anyone developed PCP, and most who did were either immunocompromised due to some pre-existing condition, or had taken immunosuppressants in preparation for surgery.
And then, starting in October 1980 and continuing into May 1981, five men in Los Angeles developed PCP, none of whom had any known reason for being immunocompromised. By the time the cases were combined into a single report in June 1981, two of the men had died. The report also noted that all five men were homosexual, and were also suffering from serious cases of cytomegalovirus (CMV), a form of herpes that is almost always harmless.
In a way, that clarified matters. Epidemiologists from the Center for Disease Control (CDC) reviewing the study suggested, cautiously, that sexual behavior might be associated with whatever mechanism was allowing PCP and CMV to take root. On the other hand, it wasn't clear what that mechanism might be, and the CDC had trouble deciding what to call the new condition in its efforts to convene a task force to investigate it.
The press had no such trouble. Latching onto the fact that the five men were homosexual, the term Gay-Related Immune Deficiency (GRID) was coined, and conversation around the condition took on a depressingly ugly feel. In short order, it was discovered that it infected many people other than homosexual men, and the alternate term Acquired Immune Deficiency Syndrome (AIDS) was adopted, but the usual taint of moralistic overtones persisted for several years.
None of this, however, served to shed light on the fundamental question: What was causing AIDS?
In order to better answer that, let's take up a separate topic whose connection will become clear shortly.
It's evident to anyone who looks at living things even cursorily that organisms "breed true": traits that are prevalent in one generation tend to persist to succeeding generations, this being more firmly true for defining traits than for occasional ones. Blond parents are more likely than non-blond parents to give birth to blond children, but they do sometimes give birth to brunettes. However, they always (more or less) give birth to humans. They do not give birth to potatoes, for example, or porcupines.
It would seem that this is just characteristic of each species in turn, and thus does not present any particular difficulty to anyone who believes that humans have always been humans, potatoes have always been potatoes, and porcupines have always been porcupines.
By the time Charles Darwin (1809–1882) and Alfred Russel Wallace (1823–1913) developed the theory of natural evolution by natural selection, however, scientists had a thorny problem on their hands. If humans had not always been humans, then what was it that led to any kind of continuity in the human species? What was the mechanism behind heredity, and how could it be both robust enough, yet flexible enough, to produce only a very slow evolution of the human species?
Whatever it was, it had to be fairly complex. Not only humans but any advanced organism contained too much information to be encoded into anything very simple. Immediately, attention was directed at proteins, which were the most complicated molecules to be found in the cell. If anything were capable of storing the blueprints for living things, it might well be proteins. The only other things to be found uniformly in cells seemed mostly to be too simple to encode living things.
To be sure, there was a dark horse candidate in an obscure substance, called nuclein, for it was to be found only in the nucleus. The Swiss physician Friedrich Miescher (1844–1895) had discovered it in 1869, in pus collected from discarded surgical bandages. He was also the first to suggest that it might play a role in heredity. Its location within the nucleus was a point in its favor, but initial studies into its structure suggested it was relatively simple. Proteins still looked like the best bet.
Over time, however, it became evident that what were thought to be indications of nuclein's simple structure were in fact properly attributed to its building blocks, called bases. It was hypothesized that nuclein was composed of long chains of these bases, and that increased the odds that nuclein was involved in heredity. It was also found to be acidic, and built along a backbone made up of deoxyribose sugar, so that it came to be called deoxyribonucleic acid, or DNA.
The final confirming nail that it was DNA, and not proteins, that carried hereditary information was an experiment conducted by the American geneticists Alfred Hershey (1908–1997) and Martha Chase (1927–2003) in 1952. The next year, geneticists Francis Crick (1916–2004) and James Watson (1928–) reported on work conducted with their colleague Rosalind Franklin (1920–1958) that showed the detailed structure of DNA. It was a coiled "double helix," a twisting ladder joining two strands of bases. Each strand contained equivalent heriditary information, with each base on one of the strands chemically matching the corresponding base on the other strand. Reproduction involved repeatedly splitting these strands and then copying them onto another strand, using the same coding scheme.
Amazingly, this overall structure had been anticipated a quarter century earlier by the Russian biologist Nikolai Koltsov (1872–1940), who in 1927 suggested that whatever substance was involved in heredity (he did not necessarily think it was DNA) would be a giant molecule made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template."
DNA, and its close kin RNA (ribonucleic acid, which is built upon the ribose sugar rather than deoxyribose), are just the blueprint molecules. The actual duplication work is done by enzymes, molecules that perform various actions on DNA and RNA. In most cells, DNA acts as the "safe copy," from which enzymes transcribe a working copy in RNA. Other enzymes then translate the genetic information in RNA to proteins, which actually carry out the functions of the cell. In these cells, DNA is to be found in the nucleus, while RNA is typically found in the cytoplasm, outside the nucleus.
In bacteria, which lack a nucleus, DNA and RNA are both contained in a loosely connected body called the nucleoid. This simpler structure is not suitable for large amounts of hereditary information and prevents bacteria from becoming too complex. They are not capable of much beyond consuming food and excreting waste. One shouldn't be too dismissive of this, though; through such simple consumption and excretion, bacteria perform a host of functions useful to the rest of the biological world. The Earth's atmosphere was composed mostly of hydrogen-based molecules until certain bacteria acted on it and made it a nitrogen-oxygen atmosphere, so let's hear it for the bacteria.
Bacteria go down in size to about 500 nanometers in size (1/2000 of a millimeter), and it's hard to imagine anything living getting much smaller than that. And yet, when the French biologist Louis Pasteur (1822–1895) went looking for the bacterium responsible for rabies, he found none. He made use of a filter, developed by his colleague Charles Chamberland, which allowed nothing the size of a bacterium or larger through. He verified that serum that had passed through this filter contained nothing that could be seen through a microscope, but could cause rabbits to develop rabies.
It was thought by some that this indicated that what caused rabies was not a microorganism, but a toxin, possibly produced by bacteria. This substance was called virus, from the Latin word for "poison," and even when the agent responsible for rabies was shown to be a microorganism, the name stuck.
Viruses turned out to be tiny indeed—on the order of tens of nanometers, small enough to pass through Chamberland's filter, and small enough to elude visual detection under even the strongest of microscopes. They consist almost entirely of RNA or DNA, with a protein shell, but even at that, they don't contain enough genetic material to be self-sustaining the way even bacteria are, as small as they are.
Instead, viruses must take over other cells as virus factories, using their ordinary reproductive functions against them. Viruses make use of the enzymes and/or proteins within the cell, employing them to transcribe the viral DNA to RNA (and then to proteins), rather than the cell's own DNA. The cell is thus commandeered to produce nothing but building blocks of more viruses: copies of the virus nucleic acid instructions, and the protein shell. Once these parts are ready, the virus copies self-assemble, the process repeating until the cell is incapable of building more viruses (its own workaday functions having been set aside for the sole task of virus production), and the virus copies burst forth from the dead cell.
Occasionally, the virus invades the cell with its own RNA, along with a special enzyme called reverse transcriptase. This transcribes the viral RNA into DNA, instead of the other way around (which is why it is called reverse transcriptase). This viral DNA is then integrated into the cell's DNA with another enzyme. The virus plants, in a sense, the seeds of its own life into the cell. From that point, the cell behaves just as it always does—except now it makes more viruses. Because the virus makes DNA from RNA, in the "wrong" direction, such viruses are called retroviruses.
It may be this quality that makes retroviruses seem so insidious, since as far as the cell is concerned, it is simply carrying out what it normally does—only now it is at the direction of the invading virus.
Around the same time that the CDC was busy trying to assemble a task force to deal with AIDS, scientists were discovering the first retroviruses in leukemia patients. The host cells were so-called T-cells (T for the thymus gland, where T-cells originate), and retroviruses seemed to be implicated in the unusual T-cell reproduction exhibited by the leukemia patients.
It turned out, after some investigation, that AIDS patients also exhibited unusual T-cell counts and reproduction, and it was speculated that retroviruses might be implicated in AIDS as well.
Two research groups started working on this basis, one under the American biomedical researcher Robert Gallo (1937–), and a second under the French virologist Luc Montagnier (1932–). Gallo's previous claim to fame was that he had worked on the human T-cell leukemia virus, or HTLV, a retrovirus that (as its name implies) causes a particular form of leukemia. It was the first retrovirus found in humans.
In the early 1980s, the Gallo team examined blood from a patient with AIDS and isolated a new retrovirus, which they believed to have caused AIDS in that patient. Based on its similarity to the original HTLV, they called it HTLV-III. (HTLV-II, discovered in the meantime, was another retrovirus associated with leukemia.)
Meanwhile, one of Montagnier's colleagues, Willy Rozenbaum, had asked his assistance in 1982 in establishing the cause of AIDS, on the assumption that it might be a retrovirus. Montagnier's team took samples from Rozenbaum's patients and discovered a virus in the lymph nodes. Montagnier, on the cautious side, decided to call it lymphadenopathy-associated virus (LAV), since he wasn't yet sure that it was the virus that caused AIDS.
Gallo and Rozenbaum's teams published their results a year apart in 1983 and 1984, both in the prestigious journal Science. Rozenbaum had been the first to press, but he had not been especially forceful in asserting that LAV caused AIDS. By comparison, Gallo and his team published a series of four papers that clearly established (in their minds) that HTLV-III was exactly the virus that caused AIDS, but he was a year later than Rozenbaum. There followed a weary and occasionally acrimonious dispute over priority that took several years to resolve. In the end, it was decided that: (1) Gallo's HTLV-III and Montagnier's LAV were indeed the same virus, which would now be called the human immunodeficiency virus (HIV); (2) Montagnier's team had indeed been the first to isolate HIV; but (3) Gallo's team was the one who had demonstrated conclusively that HIV caused AIDS.
In one way, research on AIDS had benefited from a stroke of luck. The cells in any organism that contains nucleic acid, whether human or potato, porcupine or virus, occasionally make transcription errors in copying genetic instructions from one molecule to another. When these errors manifest in a new organism, there is said to have been a mutation, from the Latin word for "change." Mutations occur from time to time in any act of reproduction, with the vast majority of them having no effect, the majority of the ones remaining having a negative effect, and the small remainder having a positive effect. One of the triumphs of Darwin and Wallace's work had been in recognizing the tremendous impact of those infrequent mutations that produce a benefit for the organism.
HIV, like most viruses, reproduces extremely rapidly, with the result that it frequently mutates. There might have been any number of mutations that caused LAV and HTLV-III to differ in many ways, preventing researchers from realizing that they were looking at essentially the same virus. It might have taken years before they could concentrate their efforts on remedies.
It later transpired, however, that some of Gallo's samples had apparently come from Montagnier's lab, in a mix-up that involved one patient's virus contaminating another patient's sample. There had been no time for the virus to mutate in between the two teams' tests, and the determination that they were looking at the same virus was consequently rapid.
HIV is thought to have originated in Africa in primates as a simian immunodeficiency virus, or SIV. Hunters apparently catch SIV occasionally from their kill, but in humans, SIV is a weak intruder that is usually suppressed in a few weeks. It thus had trouble navigating from human to human until the twentieth century.
From then, however, increasing population and activity in prostitution led to sexual interactions involving people who had been infected with SIV who also were infected with a sexually transmitted disease that produced lesions. These increase the surface area for transmission and the virus spread much faster. This also permitted the virus to mutate into a variant more targeted for humans—namely, HIV.
Today, HIV drug therapies permit individuals to survive for many years after infection. The basketball player Earvin "Magic" Johnson (1960–) famously contracted HIV (likely from sexual activity) in 1991, and an aggressive therapy of the anti-retroviral drug azidothymidine (AZT) has allowed him to live an ordinary life to the present time.
Sadly, AZT and its like were not available as medications in the early days of AIDS. Isaac Asimov had had a heart attack in 1977, and in the years immediately following, he began to suffer increasingly from the angina that also afflicted his father. He decided, therefore, after conferencing with his doctors, to have a triple bypass operation in 1983. He wrote up the incident in a number of articles, including his final autobiography, I. Asimov, neglecting not to affix his usual humorous reaction.
But an incident occurred during the surgery that Asimov did not write about, or even know about for some time afterward. During the operation, a blood transfusion was required as a matter of course, and the blood was infected with HIV. A few years later, the dangers of HIV infection from blood transfusions would have been well understood and the blood would have been screened and discarded.
This was not the case in 1983. The surgery concluded with apparent success, although Asimov had a brief, high fever immediately afterward. (This was the virus establishing itself in his body.) He then recovered and resumed his busy work schedule.
Over the next several years, however, Asimov began suffering from an array of unexplained symptoms, the most serious being a decrease in kidney function. His wife Janet, a doctor herself, had read up on AIDS and worried that his symptoms might be a result of the disease. In due course, Isaac was tested in 1990, and was found to be positive for HIV.
He considered announcing his condition, but his physicians, concerned about the anti-AIDS prejudice prevalent at the time (it was still associated in the popular conception with homosexuals and drug users), dissuaded him. He began a long, slow decline, throughout which he wrote as much as his body would permit him, then dictated to Janet for as long as his voice held out, but in the last few weeks, he was too weak to continue, and died on April 6, 1992.
After his death, his family again considered announcing his condition, since the more recent cases of people like Magic Johnson had removed some of the stigma around HIV and AIDS. But two days after Asimov's death, Arthur Ashe announced the he had contracted HIV, and the Asimov family felt it would be distracting to make their belated announcement then. That didn't happen until 2002, ten years after Asimov's death (by which time most of his doctors had also died), when Janet edited a compilation of his writings entitled It's Been a Good Life. She added, in an epilogue, a fuller story of his death, which had up to then be reported plainly as heart and kidney failure. That much was true, but it was not the whole truth. (Janet herself died earlier in 2019, less than a year ago as I write this.)
Asimov, as I have mentioned, loved sharing what he had learned with his loyal readers, and I think it must have pained him that he wasn't able to write an explanation of his condition and how he contracted it (and I suspect he would have found it difficult to write a dispassionate essay about HIV and AIDS that didn't involve himself in some way). After more than four decades of reading his essays and emulating him as well as I can, I can think of no better tribute than to attempt an essay in his style.
Copyright (c) 2020 Brian Tung