Lives of a Cell Read online

  Much better we work our way out of it on our own, without governance. The future is too interesting and dangerous to be entrusted to any predictable, reliable agency. We need all the fallibility we can get. Most of all, we need to preserve the absolute unpredictability and total improbability of our connected minds. That way we can keep open all the options, as we have in the past.

  It would be nice to have better ways of monitoring what we’re up to so that we could recognize change while it is occurring, instead of waking up as we do now to the astonished realization that the whole century just past wasn’t what we thought it was, at all. Maybe computers can be used to help in this, although I rather doubt it. You can make simulation models of cities, but what you learn is that they seem to be beyond the reach of intelligent analysis; if you try to use common sense to make predictions, things get more botched up than ever. This is interesting, since a city is the most concentrated aggregation of humans, all exerting whatever influence they can bring to bear. The city seems to have a life of its own. If we cannot understand how this works, we are not likely to get very far with human society at large.

  Still, you’d think there would be some way in. Joined together, the great mass of human minds around the earth seems to behave like a coherent, living system. The trouble is that the flow of information is mostly one-way. We are all obsessed by the need to feed information in, as fast as we can, but we lack sensing mechanisms for getting anything much back. I will confess that I have no more sense of what goes on in the mind of mankind than I have for the mind of an ant. Come to think of it, this might be a good place to start.

  THE PLANNING OF SCIENCE

  It is generally accepted that the biologic sciences are absolutely splendid. In just the past decade, they have uncovered a huge mass of brand-new information, and there is plenty more ahead; the biologic revolution is evidently still in its early stages. Everyone approves. By contrast, the public view of the progress of medicine during the same period is restrained, qualified, a mixture of hope and worry. For all the new knowledge, we still have formidable diseases, still unsolved, lacking satisfactory explanation, lacking satisfactory treatment. Why, it is asked, does the supply of new miracle drugs lag so far behind, while biology continues to move from strength to strength, elaborating new, powerful technologies for explaining, in fine detail, the very processes of life?

  It doesn’t seem to help to apply the inclusive term “biomedical” to our science, much as we would like to show that we are all one field of inquiry, share and share alike. There is still the conspicuous asymmetry between molecular biology and, say, the therapy of lung cancer. We may as well face up to it: there is a highly visible difference between the pace of basic science and the application of new knowledge to human problems. It needs explaining.

  This is an especially lively problem at the moment, because of the immediate implications for national science policy. It is administratively fashionable in Washington to attribute the delay of applied science in medicine to a lack of systematic planning. Under a new kind of management, it is said, with more businesslike attention to the invention of practical applications, we should arrive at our targets more quickly and, it is claimed as a bonus, more economically. Targeting is the new word. We need more targeted research, more mission-oriented science. And maybe less basic research—maybe considerably less. This is said to be the new drift.

  One trouble with this view is that it attributes to biology and medicine a much greater store of usable information, with coherence and connectedness, than actually exists. In real life, the biomedical sciences have not yet reached the stage of any kind of general applicability to disease mechanisms. In some respects we are like the physical sciences of the early twentieth century, booming along into new territory, but without an equivalent for the engineering of that time. It is possible that we are on the verge of developing a proper applied science, but it has to be said that we don’t have one yet. The important question before the policy-makers is whether this should be allowed to occur naturally, as a matter of course, or whether it can be ordered up more quickly, under the influence of management and money.

  There are risks. We may be asking for more of the kind of trouble with which we are already too familiar. There is a trap here that has enmeshed medicine for all the millennia of its professional existence. It has been our perpetual habit to try anything, on the slimmest of chances, the thinnest of hopes, empirically and wishfully, and we have proved to ourselves over and over again that the approach doesn’t work well. Bleeding, cupping, and purging are the classical illustrations, but we have plenty of more recent examples to be embarrassed about. We have been hoaxed along by comparable substitutes for technology right up to the present. There is no question about our good intentions in this matter: we all hanker, collectively, to become applied scientists as soon as we can, overnight if possible.

  It takes some doing, however. Everyone forgets how long and hard the work must be before the really important applications become applicable. The great contemporary achievement of modern medicine is the technology for controlling and preventing bacterial infection, but this did not fall into our laps with the appearance of penicillin and the sulfonamides. It had its beginnings in the final quarter of the last century, and decades of the most painstaking and demanding research were required before the etiology of pneumonia, scarlet fever, meningitis, and the rest could be worked out. Generations of energetic and imaginative investigators exhausted their whole lives on the problems. It overlooks a staggering amount of basic research to say that modern medicine began with the era of antibiotics.

  We have to face, in whatever discomfort, the real possibility that the level of insight into the mechanisms of today’s unsolved diseases—schizophrenia, for instance, or cancer, or stroke—is comparable to the situation for infectious disease in 1875, with similarly crucial bits of information still unencountered. We could be that far away, in the work to be done if not in the years to be lived through. If this is the prospect, or anything like this, all ideas about better ways to speed things up should be given open-minded, close scrutiny.

  Long-range planning and organization on a national scale are obviously essential. There is nothing unfamiliar about this; indeed, we’ve been engaged in a coordinated national effort for over two decades, through the established processes of the National Institutes of Health. Today’s question is whether the plans are sharply focused enough, the organization sufficiently tight. Do we need a new system of research management, with all the targets in clear display, arranged to be aimed at?

  This would seem reassuring and tidy, and there are some important disease problems for which it has already been done effectively, demonstrating that the direct, frontal approach does work. Poliomyelitis is the most spectacular example. Once it had been learned (from basic research) that there were three antigenic types of virus and that they could be abundantly grown in tissue culture, it became a certainty that a vaccine could be made. Not to say that the job would be easy, or in need of any less rigor and sophistication than the previous research; simply that it could be done. Given the assumption that experiments would be carried out with technical perfection, the vaccine was a sure thing. It was an elegant demonstration of how to organize applied science, and for this reason it would have been a surprise if it had not succeeded.

  This is the element that distinguishes applied science from basic. Surprise is what makes the difference. When you are organized to apply knowledge, set up targets, produce a usable product, you require a high degree of certainty from the outset. All the facts on which you base protocols must be reasonably hard facts with unambiguous meaning. The challenge is to plan the work and organize the workers so that it will come out precisely as predicted. For this, you need centralized authority, elaborately detailed time schedules, and some sort of reward system based on speed and perfection. But most of all you need the intelligible basic facts to begin with, and these must c
ome from basic research. There is no other source.

  In basic research, everything is just the opposite. What you need at the outset is a high degree of uncertainty; otherwise it isn’t likely to be an important problem. You start with an incomplete roster of facts, characterized by their ambiguity; often the problem consists of discovering the connections between unrelated pieces of information. You must plan experiments on the basis of probability, even bare possibility, rather than certainty. If an experiment turns out precisely as predicted, this can be very nice, but it is only a great event if at the same time it is a surprise. You can measure the quality of the work by the intensity of astonishment. The surprise can be because it did turn out as predicted (in some lines of research, 1 per cent is accepted as a high yield), or it can be confoundment because the prediction was wrong and something totally unexpected turned up, changing the look of the problem and requiring a new kind of protocol. Either way, you win.

  I believe, on hunch, that an inventory of our major disease problems based on this sort of classification would show a limited number of important questions for which the predictable answers carry certainty. It might be a good idea, when commissions go to work laying out long-range plans for disease-oriented research, for these questions to be identified and segregated from all the rest, and the logic of operations research should be invaluable for this purpose. There will be lots of disputing among the experts over what is certain and what not; perhaps the heat and duration of dispute could be adapted for the measurement of uncertainty. In any case, once a set of suitable questions becomes agreed upon, these can be approached by the most systematic methods of applied science.

  However, I have a stronger hunch that the greatest part of the important biomedical research waiting to be done is in the class of basic science. There is an abundance of interesting facts relating to all our major diseases, and more items of information are coming in steadily from all quarters in biology. The new mass of knowledge is still formless, incomplete, lacking the essential threads of connection, displaying misleading signals at every turn, riddled with blind alleys. There are fascinating ideas all over the place, irresistible experiments beyond numbering, all sorts of new ways into the maze of problems. But every next move is unpredictable, every outcome uncertain. It is a puzzling time, but a very good time.

  I do not know how you lay out orderly plans for this kind of activity, but I suppose you could find out by looking through the disorderly records of the past hundred years. Somehow, the atmosphere has to be set so that a disquieting sense of being wrong is the normal attitude of the investigators. It has to be taken for granted that the only way in is by riding the unencumbered human imagination, with the special rigor required for recognizing that something can be highly improbable, maybe almost impossible, and at the same time true.

  Locally, a good way to tell how the work is going is to listen in the corridors. If you hear the word “Impossible!” spoken as an expletive, followed by laughter, you will know that someone’s orderly research plan is coming along nicely.

  SOME BIOMYTHOLOGY

  The mythical animals catalogued in the bestiaries of the world seem, at a casual glance, nothing but exotic nonsense. The thought comes that Western civilized, scientific, technologic society is a standing proof of human progress, in having risen above such imaginings. They are as obsolete as the old anecdotes in which they played their puzzling, ambiguous roles, and we have no more need for the beasts than for the stories. The Griffon, Phoenix, Centaur, Sphinx, Manticore, Ganesha, Ch’i-lin, and all the rest are like recurrent bad dreams, and we are well rid of them. So we say.

  The trouble is that they are in fact like dreams, and not necessarily bad ones, and we may have a hard time doing without them. They may be as essential for society as mythology itself, as loaded with symbols, and as necessary for the architecture of our collective unconscious. If Lévi-Strauss is right, myths are constructed by a universal logic that, like language itself, is as characteristic for human beings as nest-building is for birds. The stories seem to be different stories, but the underlying structure is always the same, in any part of the world, at any time. They are like engrams, built into our genes. In this sense, bestiaries are part of our inheritance.

  There is something basically similar about most of these crazy animals. They are all unbiologic, but unbiologic in the same way. Bestiaries do not contain, as a rule, totally novel creatures of the imagination made up of parts that we have never seen before. On the contrary, they are made up of parts that are entirely familiar. What is novel, and startling, is that they are mixtures of species.

  It is perhaps this characteristic that makes the usual bestiary so outlandish to the twentieth-century mind. Our most powerful story, equivalent in its way to a universal myth, is evolution. Never mind that it is true whereas myths are not; it is filled with symbolism, and this is the way it has influenced the mind of society. In our latest enlightenment, the fabulous beasts are worse than improbable—they are impossible, because they violate evolution. They are not species, and they deny the existence of species.

  The Phoenix comes the closest to being a conventional animal, all bird for all of its adult life. It is, in fact, the most exuberant, elaborate, and ornamented of all plumed birds. It exists in the mythology of Egypt, Greece, the Middle East, and Europe, and is the same as the vermilion bird of ancient China. It lives for five hundred triumphant years, and when it dies it constructs a sort of egg-shaped cocoon around itself. Inside, it disintegrates and gives rise to a wormlike creature, which then develops into the new Phoenix, ready for the next five hundred years. In other versions the dead bird bursts into flames, and the new one arises from the ashes, but the worm story is very old, told no doubt by an early biologist.

  There are so many examples of hybrid beings in bestiaries that you could say that an ardent belief in mixed forms of life is an ancient human idea, or that something else, deeply believed in, is symbolized by these consortia. They are disturbing to look at, nightmarish, but most of them, oddly enough, are intended as lucky benignities. The Ch’i-lin, for instance, out of ancient China, has the body of a deer covered with gleaming scales, a marvelous bushy tail, cloven hooves, and small horns. Whoever saw a Ch’i-lin was in luck, and if you got to ride one, you had it made.

  The Ganesha is one of the oldest and most familiar Hindu deities, possessing a fat human body, four human arms, and the head of a cheerful-looking elephant. Prayers to Ganesha are regarded as the quickest way around obstacles.

  Not all mythical beasts are friendly, of course, but even the hostile ones have certain amiable redeeming aspects. The Manticore has a lion’s body, a man’s face, and a tail with a venomous snake’s head at the end of it. It bounds around seeking prey with huge claws and three rows of teeth, but it makes the sounds of a beautiful silver flute.

  Some of the animal myths have the ring of contemporary biologic theory, if you allow for differences in jargon. An ancient idea in India postulates an initial Being, the first form of life on the earth, analogous to our version of the earliest prokaryotic arrangement of membrane-limited nucleic acid, the initial cell, born of lightning and methane. The Indian Being, undefined and indefinable, finding itself alone, fearing death, yearning for company, began to swell in size, rearranged itself inside, and then split into two identical halves. One of these changed into a cow, the other a bull, and they mated, then changed again to a mare and stallion, and so on, down to the ants, and thus the earth was populated. There is a lot of oversimplification here, and too much shorthand for modern purposes, but the essential myth is recognizable.

  The serpent keeps recurring through the earliest cycles of mythology, always as a central symbol for the life of the universe and the continuity of creation. There are two great identical snakes on a Levantine libation vase of around 2000 B.C., coiled around each other in a double helix, representing the original generation of life. They are the replicated parts of the firs
t source of living, and they are wonderfully homologous.

  There is a Peruvian deity, painted on a clay pot dating from around A.D. 300, believed to be responsible for guarding farms. His hair is made of snakes, entwined in braids, with wings for his headdress. Plants of various kinds are growing out of his sides and back, and a vegetable of some sort seems to be growing from his mouth. The whole effect is wild and disheveled but essentially friendly. He is, in fact, an imaginary version of a genuine animal, symbiopholus, described in Nature several years back, a species of weevil in the mountains of northern New Guinea that lives symbiotically with dozens of plants, growing in the niches and clefts in its carapace, rooted all the way down to its flesh, plus a whole ecosystem of mites, rotifers, nematodes, and bacteria attached to the garden. The weevil could be taken for a good-luck omen on its own evidence; it is not attacked by predators, it lives a long, untroubled life, and nothing else will eat it, either because of something distasteful in the system or simply because of the ambiguity. The weevil is only about thirty millimeters long, easily overlooked, but it has the makings of a myth.

  Perhaps we should be looking around for other candidates. I suggest the need for a new bestiary, to take the place of the old ones. I can think of several creatures that seem designed for this function, if you will accept a microbestiary, and if you are looking for metaphors.

  First of all, there is Myxotricha paradoxa. This is the protozoan, not yet as famous as he should be, who seems to be telling us everything about everything, all at once. His cilia are not cilia at all, but individual spirochetes, and at the base of attachment of each spirochete is an oval organelle, embedded in the myxotricha membrane, which is a bacterium. It is not an animal after all—it is a company, an assemblage.