Lives of a Cell Page 4
In fact, this level of technology is, by its nature, at the same time highly sophisticated and profoundly primitive. It is the kind of thing that one must continue to do until there is a genuine understanding of the mechanisms involved in disease. In chronic glomerulonephritis, for example, a much clearer insight will be needed into the events leading to the destruction of glomeruli by the immunologic reactants that now appear to govern this disease, before one will know how to intervene intelligently to prevent the process, or turn it round. But when this level of understanding has been reached, the technology of kidney replacement will not be much needed and should no longer pose the huge problems of logistics, cost, and ethics that it poses today.
An extremely complex and costly technology for the management of coronary heart disease has evolved—involving specialized ambulances and hospital units, all kinds of electronic gadgetry, and whole platoons of new professional personnel—to deal with the end results of coronary thrombosis. Almost everything offered today for the treatment of heart disease is at this level of technology, with the transplanted and artificial hearts as ultimate examples. When enough has been learned to know what really goes wrong in heart disease, one ought to be in a position to figure out ways to prevent or reverse the process, and when this happens the current elaborate technology will probably be set to one side.
Much of what is done in the treatment of cancer, by surgery, irradiation, and chemotherapy, represents halfway technology, in the sense that these measures are directed at the existence of already established cancer cells, but not at the mechanisms by which cells become neoplastic.
It is a characteristic of this kind of technology that it costs an enormous amount of money and requires a continuing expansion of hospital facilities. There is no end to the need for new, highly trained people to run the enterprise. And there is really no way out of this, at the present state of knowledge. If the installation of specialized coronary-care units can result in the extension of life for only a few patients with coronary disease (and there is no question that this technology is effective in a few cases), it seems to me an inevitable fact of life that as many of these as can be will be put together, and as much money as can be found will be spent. I do not see that anyone has much choice in this. The only thing that can move medicine away from this level of technology is new information, and the only imaginable source of this information is research.
3. The third type of technology is the kind that is so effective that it seems to attract the least public notice; it has come to be taken for granted. This is the genuinely decisive technology of modern medicine, exemplified best by modern methods for immunization against diphtheria, pertussis, and the childhood virus diseases, and the contemporary use of antibiotics and chemotherapy for bacterial infections. The capacity to deal effectively with syphilis and tuberculosis represents a milestone in human endeavor, even though full use of this potential has not yet been made. And there are, of course, other examples: the treatment of endocrinologic disorders with appropriate hormones, the prevention of hemolytic disease of the newborn, the treatment and prevention of various nutritional disorders, and perhaps just around the corner the management of Parkinsonism and sickle-cell anemia. There are other examples, and everyone will have his favorite candidates for the list, but the truth is that there are nothing like as many as the public has been led to believe.
The point to be made about this kind of technology—the real high technology of medicine—is that it comes as the result of a genuine understanding of disease mechanisms, and when it becomes available, it is relatively inexpensive, relatively simple, and relatively easy to deliver.
Offhand, I cannot think of any important human disease for which medicine possesses the outright capacity to prevent or cure where the cost of the technology is itself a major problem. The price is never as high as the cost of managing the same diseases during the earlier stages of no-technology or halfway technology. If a case of typhoid fever had to be managed today by the best methods of 1935, it would run to a staggering expense. At, say, around fifty days of hospitalization, requiring the most demanding kind of nursing care, with the obsessive concern for details of diet that characterized the therapy of that time, with daily laboratory monitoring, and, on occasion, surgical intervention for abdominal catastrophe, I should think $10,000 would be a conservative estimate for the illness, as contrasted with today’s cost of a bottle of chloramphenicol and a day or two of fever. The halfway technology that was evolving for poliomyelitis in the early 1950s, just before the emergence of the basic research that made the vaccine possible, provides another illustration of the point. Do you remember Sister Kenny, and the cost of those institutes for rehabilitation, with all those ceremonially applied hot fomentations, and the debates about whether the affected limbs should be totally immobilized or kept in passive motion as frequently as possible, and the masses of statistically tormented data mobilized to support one view or the other? It is the cost of that kind of technology, and its relative effectiveness, that must be compared with the cost and effectiveness of the vaccine.
Pulmonary tuberculosis had similar episodes in its history. There was a sudden enthusiasm for the surgical removal of infected lung tissue in the early 1950s, and elaborate plans were being made for new and expensive installations for major pulmonary surgery in tuberculosis hospitals, and then INH and streptomycin came along and the hospitals themselves were closed up.
It is when physicians are bogged down by their incomplete technologies, by the innumerable things they are obliged to do in medicine when they lack a clear understanding of disease mechanisms, that the deficiencies of the health-care system are most conspicuous. If I were a policy-maker, interested in saving money for health care over the long haul, I would regard it as an act of high prudence to give high priority to a lot more basic research in biologic science. This is the only way to get the full mileage that biology owes to the science of medicine, even though it seems, as used to be said in the days when the phrase still had some meaning, like asking for the moon.
VIBES
We leave traces of ourselves wherever we go, on whatever we touch. One of the odd discoveries made by small boys is that when two pebbles are struck sharply against each other they emit, briefly, a curious smoky odor. The phenomenon fades when the stones are immaculately cleaned, vanishes when they are heated to furnace temperature, and reappears when they are simply touched by the hand again before being struck.
An intelligent dog with a good nose can track a man across open ground by his smell and distinguish that man’s tracks from those of others. More than this, the dog can detect the odor of a light human fingerprint on a glass slide, and he will remember that slide and smell it out from others for as long as six weeks, when the scent fades away. Moreover, this animal can smell the identity of identical twins, and will follow the tracks of one or the other as though they had been made by the same man.
We are marked as self by the chemicals we leave beneath the soles of our shoes, as unmistakably and individually as by the membrane surface antigens detectable in homografts of our tissues.
Other animals are similarly endowed with signaling mechanisms. Columns of ants can smell out the differences between themselves and other ants on their trails. The ants of one species, proceeding jerkily across a path, leave trails that can be followed by their own relatives but not by others. Certain ants, predators, have taken unfair advantage of the system; they are born with an ability to sense the trails of the species they habitually take for slaves, follow their victims to their nests, and release special odorants that throw them into disorganized panic.
Minnows and catfish can recognize each member of their own species by his particular, person-specific odor. It is hard to imagine a solitary, independent, existentialist minnow, recognizable for himself alone; minnows in a school behave like interchangeable, identical parts of an organism. But there it is.
The problem of o
lfactory sensing shares some of the current puzzles and confusions of immunology, apart from the business of telling self from non-self. A rabbit, it has been calculated, has something like 100 million olfactory receptors. There is a constant and surprisingly rapid turnover of the receptor cells, with new ones emerging from basal cells within a few days. The theories to explain olfaction are as numerous and complex as those for immunologic sensing. It seems likely that the shape of the smelled molecule is what matters most. By and large, odorants are chemically small, Spartan compounds. In a rose garden, a rose is a rose because of geraniol, a 10-carbon compound, and it is the geometric conformation of atoms and their bond angles that determine the unique fragrance. The special vibrations of atoms or groups of atoms within the molecules of odorants, or the vibratory song of the entire molecule, have been made the basis for several theories, with postulated “osmic frequencies” as the source of odor. The geometry of the molecule seems to be more important than the names of the atoms themselves; any set of atoms, if arranged in precisely the same configuration, by whatever chemical name, might smell as sweet. It is not known how the olfactory cells are fired by an odorant. According to one view, a hole is poked in the receptor membrane, launching depolarization, but other workers believe that the substance may become bound to the cells possessing specific receptors for it and then may just sit there, somehow displaying its signal from a distance, after the fashion of antigens on immune cells. Specific receptor proteins have been proposed, with different olfactory cells carrying specific receptors for different “primary” odors, but no one has yet succeeded in identifying the receptors or naming the “primary” odors.
Training of cells for olfactory sensing appears to be an everyday phenomenon. Repeated exposure of an animal to the same odorant, in small doses, leads to great enhancement of acuity, suggesting the possibility that new receptor sites are added to the cells. It is conceivable that new clones of cells with a particular receptor are stimulated to emerge in the process of training. The guinea pig, that immunologically famous animal, can be trained to perceive fantastically small amounts of nitrobenzene by his nose, without the help of Freund’s adjuvants or haptene carriers. Minnows have been trained to recognize phenol, and distinguish it from p-chlorophenol, in concentrations of five parts per billion. Eels have been taught to smell two or three molecules of phenylethyl alcohol. And, of course, eels and salmon must be able to remember by nature, as the phrase goes, the odor of the waters in which they were hatched, so as to sniff their way back from the open sea for spawning. Electrodes in the olfactory bulbs of salmon will fire when the olfactory epithelium is exposed to water from their spawning grounds, whereas water from other streams causes no response.
We feel somehow inferior and left out of things by all the marvelous sensory technology in the creatures around us. We sometimes try to diminish our sense of loss (or loss of sense) by claiming to ourselves that we have put such primitive mechanisms behind us in our evolution. We like to regard the olfactory bulb as a sort of archeologic find, and we speak of the ancient olfactory parts of the brain as though they were elderly, dotty relatives in need of hobbies.
But we may be better at it than we think. An average man can detect just a few molecules of butyl mercaptan, and most of us can sense the presence of musk in vanishingly small amounts. Steroids are marvelously odorous, emitting varieties of musky, sexy smells. Women are acutely aware of the odor of a synthetic steroid named exaltolide, which most men are unable to detect. All of us are able to smell ants, for which the great word pismire was originally coined.
There may even be odorants that fire off receptors in our olfactory epithelia without our being conscious of smell, including signals exchanged involuntarily between human beings. Wiener has proposed, on intuitive grounds, that defects and misinterpretations in such a communication system may be an unexplored territory for psychiatry. The schizophrenic, he suggests, may have his problems with identity and reality because of flawed perceptions of his own or others’ signals. And, indeed, there may be something wrong with the apparatus in schizophrenics; they have, it is said, an unfamiliar odor, recently attributed to trans-3-methylhexanoic acid, in their sweat.
Olfactory receptors for communication between different creatures are crucial for the establishment of symbiotic relations. The crab and anemone recognize each other as partners by molecular configurations, as do the anemones and their symbiotic damsel fish. Similar devices are employed for defense, as with the limpet, which defends itself against starfish predators by everting its mantle and thus precluding a starfish foothold; the limpet senses a special starfish protein, which is, perhaps in the name of fairness, elaborated by all starfish into their environment. The system is evidently an ancient one, long antedating the immunologic sensing of familiar or foreign forms of life by the antibodies on which we now depend so heavily for our separateness. It has recently been learned that the genes for the marking of self by cellular antigens and those for making immunologic responses by antibody formation are closely linked. It is possible that the invention of antibodies evolved from the earlier sensing mechanisms needed for symbiosis, perhaps designed, in part, to keep the latter from getting out of hand.
A very general system of chemical communication between living things of all kinds, plant and animal, has been termed “allelochemics” by Whittaker. Using one signal or another, each form of life announces its proximity to the others around it, setting limits on encroachment or spreading welcome to potential symbionts. The net effect is a coordinated mechanism for the regulation of rates of growth and occupations of territory. It is evidently designed for the homeostasis of the earth.
Jorge Borges, in his recent bestiary of mythical creatures, notes that the idea of round beasts was imagined by many speculative minds, and Johannes Kepler once argued that the earth itself is such a being. In this immense organism, chemical signals might serve the function of global hormones, keeping balance and symmetry in the operation of various interrelated working parts, informing tissues in the vegetation of the Alps about the state of eels in the Sargasso Sea, by long, interminable relays of interconnected messages between all kinds of other creatures.
This is an interesting kind of problem, made to order for computers if they came in sizes big enough to store in nearby galaxies. It is nice to think that there are so many unsolved puzzles ahead for biology, although I wonder whether we will ever find enough graduate students.
CETI
Tau Ceti is a relatively nearby star that sufficiently resembles our sun to make its solar system a plausible candidate for the existence of life. We are, it appears, ready to begin getting in touch with Ceti, and with any other interested celestial body in more remote places, out to the edge. CETI is also, by intention, the acronym of the First International Conference on Communication with Extraterrestrial Intelligence, held in 1972 in Soviet Armenia under the joint sponsorship of the National Academy of Sciences of the United States and the Soviet Academy, which involved eminent physicists and astronomers from various countries, most of whom are convinced that the odds for the existence of life elsewhere are very high, with a reasonable probability that there are civilizations, one place or another, with technologic mastery matching or exceeding ours.
On this assumption, the conferees thought it likely that radioastronomy would be the generally accepted mode of interstellar communication, on grounds of speed and economy. They made a formal recommendation that we organize an international cooperative program, with new and immense radio telescopes, to probe the reaches of deep space for electromagnetic signals making sense. Eventually, we would plan to send out messages on our own and receive answers, but at the outset it seems more practical to begin by catching snatches of conversation between others.
So, the highest of all our complex technologies in the hardest of our sciences will soon be engaged, full scale, in what is essentially biologic research—and with some aspects of social science, at that.
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The earth has become, just in the last decade, too small a place. We have the feeling of being confined—shut in; it is something like outgrowing a small town in a small county. The views of the dark, pocked surface of Mars, still lifeless to judge from the latest photographs, do not seem to have extended our reach; instead, they bring closer, too close, another unsatisfactory feature of our local environment. The blue noonday sky, cloudless, has lost its old look of immensity. The word is out that the sky is not limitless; it is finite. It is, in truth, only a kind of local roof, a membrane under which we live, luminous but confusingly refractile when suffused with sunlight; we can sense its concave surface a few miles over our heads. We know that it is tough and thick enough so that when hard objects strike it from the outside they burst into flames. The color photographs of the earth are more amazing than anything outside: we live inside a blue chamber, a bubble of air blown by ourselves. The other sky beyond, absolutely black and appalling, is wide-open country, irresistible for exploration.
Here we go, then. An extraterrestrial embryologist, having a close look at us from time to time, would probably conclude that the morphogenesis of the earth is coming along well, with the beginnings of a nervous system and fair-sized ganglions in the form of cities, and now with specialized, dish-shaped sensory organs, miles across, ready to receive stimuli. He may well wonder, however, how we will go about responding. We are evolving into the situation of a Skinner pigeon in a Skinner box, peering about in all directions, trying to make connections, probing.
When the first word comes in from outer space, finally, we will probably be used to the idea. We can already provide a quite good explanation for the origin of life, here or elsewhere. Given a moist planet with methane, formaldehyde, ammonia, and some usable minerals, all of which abound, exposed to lightning or ultraviolet irradiation at the right temperature, life might start off almost anywhere. The tricky, unsolved thing is how to get the polymers to arrange in membranes and invent replication. The rest is clear going. If they follow our protocol, it will be anaerobic life at first, then photosynthesis and the first exhalation of oxygen, then respiring life and the great burst of variation, then speciation, and, finally, some kind of consciousness. It is easy, in the telling.