[Physicists] feel that the field of bacterial viruses is a fine playground for serious children who ask ambitious questions.

A lot of people ask, “Do you think humans are parasites?” It’s an interesting idea and one worth thinking about. People casually refer to humanity as a virus spreading across the earth. In fact, we do look like some strange kind of bio-film spreading across the landscape. A good metaphor? If the biosphere is our host, we do use it up for our own benefit. We do manipulate it. We alter the flows and fluxes of elements like carbon and nitrogen to benefit ourselves—often at the expense of the biosphere as a whole. If you look at how coral reefs or tropical forests are faring these days, you’ll notice that our host is not doing that well right now. Parasites are very sophisticated; parasites are highly evolved; parasites are very successful, as reflected in their diversity. Humans are not very good parasites. Successful parasites do a very good job of balancing—using up their hosts and keeping them alive. It’s all a question of tuning the adaptation to your particular host. In our case, we have only one host, so we have to be particularly careful.

A strong feeling of adventure is animating those who are working on bacterial viruses, a feeling that they have a small part in the great drive towards a fundamental problem in biology.

All living things need their instruction manual (even nonliving things like viruses) and that is all they need, carried in one very small suitcase.

Almost daily we shudder as prophets of doom announce the impending end of civilization and universe. We are being asphyxiated, they say, by the smoke of the industry; we are suffocating in the ever growing mountain of rubbish. Every new project depicts its measureable effects and is denounced by protesters screaming about catastrophe, the upsetting of the land, the assault on nature. If we accepted this new mythology we would have to stop pushing roads through the forest, harnessing rivers to produce the electricity, breaking grounds to extract metals, enriching the soil with chemicals, killing insects, combating viruses … But progress—basically, an effort to organise a corner of land and make it more favourable for human life—cannot be baited. Without the science of pomiculture, for example, trees will bear fruits that are small, bitter, hard, indigestible, and sour. Progress is desirable.

Because I was less tied to Parliament, because I was freer to travel and investigate and explore, I found myself often with the odd jobs which nobody else wanted or had time for. One of these, I remember, was a study of the myxomatosis problem. Myxomatosis was a disease fatal to rabbits and without a cure—there had been prolonged examination of it on the Continent where there were dreams of eradicating or anyway reducing the rabbit population. A French chemical scientist carried out a series of experiments in the park of his chateau, with a view to rabbit control. He let the virus loose, apparently unaware that it could be carried by birds and insects. Very soon myxomatosis had spread like wildfire through France.

But however secure and well-regulated civilized life may become, bacteria, Protozoa, viruses, infected fleas, lice, ticks, mosquitoes, and bedbugs will always lurk in the shadows ready to pounce when neglect, poverty, famine, or war lets down the defenses.

By teaching us how to cultivate each ferment in its purity—in other words, by teaching us how to rear the individual organism apart from all others,—Pasteur has enabled us to avoid all these errors. And where this isolation of a particular organism has been duly effected it grows and multiplies indefinitely, but no change of it into another organism is ever observed. In Pasteur’s researches the Bacterium remained a Bacterium, the Vibrio a Vibrio, the Penicillium a Penicillium, and the Torula a Torula. Sow any of these in a state of purity in an appropriate liquid; you get it, and it alone, in the subsequent crop. In like manner, sow smallpox in the human body, your crop is smallpox. Sow there scarlatina, and your crop is scarlatina. Sow typhoid virus, your crop is typhoid—cholera, your crop is cholera. The disease bears as constant a relation to its contagium as the microscopic organisms just enumerated do to their germs, or indeed as a thistle does to its seed.

E.W. Goodpasture showed that the virus of fowl pox could be grown in the tissues of the developing chick embryo. Nearly all the later practical advances in the control of virus diseases in man and animals sprang from this single discovery.

For the philosopher, order is the entirety of repetitions manifested, in the form of types or of laws, by perceived objects. Order is an intelligible relation. For the biologist, order is a sequence in space and time. However, according to Plato, all things arise out of their opposites. Order was born of the original disorder, and the long evolution responsible for the present biological order necessarily had to engender disorder.
An organism is a molecular society, and biological order is a kind of social order. Social order is opposed to revolution, which is an abrupt change of order, and to anarchy, which is the absence of order.
I am presenting here today both revolution and anarchy, for which I am fortunately not the only one responsible. However, anarchy cannot survive and prosper except in an ordered society, and revolution becomes sooner or later the new order. Viruses have not failed to follow the general law. They are strict parasites which, born of disorder, have created a very remarkable new order to ensure their own perpetuation.

He saw virus particles shaped like snakes, in negative images. They were white cobras tangled among themselves, like the hair of Medusa. They were the face of nature herself, the obscene goddess revealed naked. This life form thing was breathtakingly beautiful. As he stared at it, he found himself being pulled out of the human world into a world where moral boundaries blur and finally dissolve completely. He was lost in wonder and admiration, even though he knew that he was the prey.

I can’t say I’m particularly happy about all the spam and the viruses and the equivalent that we see on the Net, but I think technology can deal with many of the problems that we’re now seeing, whether it’s filtering or whatever, and laws may help a lot.

I would picture myself as a virus, or as a cancer cell, for example, and try to sense what it would be like to be either. I would also imagine myself as the immune system, and I would try to reconstruct what I would do as an immune system engaged in combating a virus or cancer cell. When I had played through a series of such scenarios on a particular problem and had acquired new insights, I would design laboratory experiments accordingly… Based upon the results of the experiment, I would then know what question to ask next… When I observed phenomena in the laboratory that I did not understand, I would also ask questions as if interrogating myself: “Why would I do that if I were a virus or a cancer cell, or the immune system?” Before long, this internal dialogue became second nature to me; I found that my mind worked this way all the time.

If the structure that serves as a template (the gene or virus molecule) consists of, say, two parts, which are themselves complementary In structure, then each of these parts can serve as the mould for the production of a replica of the other part, and the complex of two complementary parts thus can serve as the mould for the production of duplicates of itself.

Influenza is something unique. It behaves epidemiologically in a way different from that of any other known infection.

It is important to go into work you would like to do. Then it doesn't seem like work. You sometimes feel it's almost too good to be true that someone will pay you for enjoying yourself. I've been very fortunate that my work led to useful drugs for a variety of serious illnesses. The thrill of seeing people get well who might otherwise have died of diseases like leukemia, kidney failure, and herpes virus encephalitis cannot be described in words.

It is, I believe, justifiable to make the generalization that anything an organic chemist can synthesize can be made without him. All he does is increase the probability that given reactions will “go”. So it is quite reasonable to assume that given sufficient time and proper conditions, nucleotides, amino acids, proteins, and nucleic acids will arise by reactions that, though less probable, are as inevitable as those by which the organic chemist fulfills his predictions. So why not self-duplicating virus-like systems capable of further evolution?

My ambition was to bring to bear on medicine a chemical approach. I did that by chemical manipulation of viruses and chemical ways of thinking in biomedical research.

On opening the incubator I experienced one of those rare moments of intense emotion which reward the research worker for all his pains: at first glance I saw that the broth culture, which the night before had been very turbid was perfectly clear: all the bacteria had vanished…as for my agar spread it was devoid of all growth and what caused my emotion was that in a flash I understood: what causes my spots was in fact an invisible microbe, a filterable virus, but a virus parasitic on bacteria. Another thought came to me also, If this is true, the same thing will have probably occurred in the sick man. In his intestine, as in my test-tube, the dysentery bacilli will have dissolved away under the action of their parasite. He should now be cured.

One can ask: “If I crystallize a virus to obtain a crystal consisting of the molecules that make up the virus, are those molecules lifeless or not?” … The properties of living organisms are those of aggregates of molecules. It’s very difficult to draw a line between molecules that are lifeless and molecules that are not lifeless.

Parasites are not only incredibly diverse; they are also incredibly successful. There are parasitic stretches of DNA in your own genes, some of which are called retrotransposons. Many of the parasitic stretches were originally viruses that entered our DNA. Most of them don't do us any harm. They just copy and insert themselves in other parts of our DNA, basically replicating themselves. Sometimes they hop into other species and replicate themselves in a new host. According to one estimate, roughly one-third to one-half of all human DNA is basically parasitic.

Primates stand at a turning point in the course of evolution. Primates are to the biologist what viruses are to the biochemist. They can be analysed and partly understood according to the rules of a simpler discipline, but they also present another level of complexity: viruses are living chemicals, and primates are animals who love and hate and think.

Run the tape again, and let the tiny twig of Homo sapiens expire in Africa. Other hominids may have stood on the threshold of what we know as human possibilities, but many sensible scenarios would never generate our level of mentality. Run the tape again, and this time Neanderthal perishes in Europe and Homo erectus in Asia (as they did in our world). The sole surviving human stock, Homo erectus in Africa, stumbles along for a while, even prospers, but does not speciate and therefore remains stable. A mutated virus then wipes Homo erectus out, or a change in climate reconverts Africa into inhospitable forest. One little twig on the mammalian branch, a lineage with interesting possibilities that were never realized, joins the vast majority of species in extinction. So what? Most possibilities are never realized, and who will ever know the difference? Arguments of this form lead me to the conclusion that biology's most profound insight into human nature, status, and potential lies in the simple phrase, the embodiment of contingency: Homo sapiens is an entity, not a tendency.

So, let’s say you want to change the human body. You want to fix a mistake. You want to repair something. You want to improve something. Well, if you’re going to reprogram human genetic material, you need a delivery system, and nothing works better than virus. It’s like a suitcase. Yes, pack in genetic mutation infect the body and the vector loads into the target cells Getting it where you want it, how you want it, is the nightmare. Unless you have a map.

Suppose [an] imaginary physicist, the student of Niels Bohr, is shown an experiment in which a virus particle enters a bacterial cell and 20 minutes later the bacterial cell is lysed and 100 virus particles are liberated. He will say: “How come, one particle has become 100 particles of the same kind in 20 minutes? That is very interesting. Let us find out how it happens! How does the particle get in to the bacterium? How does it multiply? Does it multiply like a bacterium, growing and dividing, or does it multiply by an entirely different mechanism ? Does it have to be inside the bacterium to do this multiplying, or can we squash the bacterium and have the multiplication go on as before? Is this multiplying a trick of organic chemistry which the organic chemists have not yet discovered ? Let us find out. This is so simple a phenomenon that the answers cannot be hard to find. In a few months we will know. All we have to do is to study how conditions will influence the multiplication. We will do a few experiments at different temperatures, in different media, with different viruses, and we will know. Perhaps we may have to break into the bacteria at intermediate stages between infection and lysis. Anyhow, the experiments only take a few hours each, so the whole problem can not take long to solve.”
[Eight years later] he has not got anywhere in solving the problem he set out to solve. But [he may say to you] “Well, I made a slight mistake. I could not do it in a few months. Perhaps it will take a few decades, and perhaps it will take the help of a few dozen other people. But listen to what I have found, perhaps you will be interested to join me.”

That Brobdingnagian molecule, tobacco mosaic virus.

The entire range of living matter on Earth from whales to viruses and from oaks to algae could be regarded as constituting a single living entity capable of maintaining the Earth’s atmosphere to suit its overall needs and endowed with faculties and powers far beyond those of its constituent parts.

The fact that, with respect to size, the viruses overlapped with the organisms of the biologist at one extreme and with the molecules of the chemist at the other extreme only served to heighten the mystery regarding the nature of viruses. Then too, it became obvious that a sharp line dividing living from non-living things could not be drawn and this fact served to add fuel for discussion of the age-old question of “What is life?”

The nucleic acids, as constituents of living organisms, are comparable In importance to proteins. There is evidence that they are Involved In the processes of cell division and growth, that they participate In the transmission of hereditary characters, and that they are important constituents of viruses. An understanding of the molecular structure of the nucleic acids should be of value In the effort to understand the fundamental phenomena of life.
[Co-author with American chemist, B. Corey (1897-1971)]

These results demonstrate that there is a new polymerase inside the virions of RNA tumour viruses. It is not present in supernatents of normal cells but is present in virions of avian sarcoma and leukemia RNA tumour viruses. The polymerase seems to catalyse the incorporation of deoxyrinonucleotide triphosphates into DNA from an RNA template. Work is being performed to characterize further the reaction and the product. If the present results and Baltimore's results with Rauscher leukemia virus are upheld, they will constitute strong evidence that the DNA proviruses have a DNA genome when they are in virions. This result would have strong implications for theories of viral carcinogenesis and, possibly, for theories of information transfer in other biological systems. [Co-author with American virologist Satoshi Mizutani]

We think of something that has four legs and wags its tail as being alive. We look at a rock and say it’s not living. Yet when we get down to the no man’s land of virus particles and replicating molecules, we are hard put to define what is living and what is non-living.

When there are too many deer in the forest or too many cats in the barn, nature restores the balance by the introduction of a communicable disease or virus.