Lives of a Cell Page 7
Although it is, as I say, a temptation. I have never really been satisfied with the operation of my brain, and it might be fun to try running it myself, just once. There are several things I would change, given the opportunity: certain memories that tend to slip away unrecorded, others I’ve had enough of and would prefer to delete, certain notions I’d just as soon didn’t keep popping in, trains of thought that go round and round without getting anywhere, rather like this one. I’ve always suspected that some of the cells in there are fluffing off much of the time, and I’d like to see a little more attention and real work. Also, while I’m about it, I could do with a bit more respect.
On balance, however, I think it best to stay out of this business. Once you began, there would be no end to the responsibilities. I’d rather leave all my automatic functions with as much autonomy as they please, and hope for the best. Imagine having to worry about running leukocytes, keeping track, herding them here and there, listening for signals. After the first flush of pride in ownership, it would be exhausting and debilitating, and there would be no time for anything else.
What to do, then? It cannot simply be left there. If we have learned anything at all in this century, it is that all new technologies will be put to use, sooner or later, for better or worse, as it is in our nature to do. We cannot expect an exception for the instrumental conditioning of autonomic functions. We will be driven to make use of it, trying to communicate with our internal environment, to meddle, and it will consume so much of our energy that we will end up even more cut off from things outside, missing the main sources of the sensation of living.
I have a suggestion for a way out. Given the capacity to control autonomic functions, modulate brain waves, run cells, why shouldn’t it be possible to employ exactly the same technology to go in precisely the opposite direction? Instead of getting in there and taking things over, couldn’t we learn to disconnect altogether, uncouple, detach, and float free? You would only need to be careful, if you tried it, that you let go of the right end.
Of course, people have been trying to do this sort of thing for a long time, by other techniques and with varying degrees of luck. This is what Zen archery seems to be about, come to think of it. You learn, after long months of study under a master, to release the arrow without releasing it yourself. Your fingers must do the releasing, on their own, remotely, like the opening of a flower. When you have learned this, no matter where the arrow goes, you have it made. You can step outside for a look around.
ORGANELLES AS ORGANISMS
We seem to be living through the biologic revolution, so far anyway, without being upheaved or even much disturbed by it. Even without being entirely clear about just what it is, we are all learning to take it for granted. It is a curious, peaceful sort of revolution, in which there is no general apprehension that old views are being outraged and overturned. Instead, whole, great new blocks of information are being brought in almost daily and put precisely down in what were previously empty spaces. The news about DNA and the genetic code did not displace an earlier dogma; there was nothing much there to be moved aside. Molecular biology did not drive out older, fixed views about the intimate details of cell function. We seem to be starting at the beginning, from scratch.
We not only take it for granted—we tend to talk about the biologic revolution as though expecting to make profits from it, rather like a version of last century’s industrial revolution. All sorts of revolutionary changes in technology are postulated for the future, ranging from final control of human disease to solutions of the world food and population problems. We are even beginning to argue about which futures we like and which we prefer to cancel. Questions about the merits of genetic engineering, the cloning of desirable human beings from single cells, and even, I suppose, the possibility that two heads might actually be better than one, are already being debated at seminars.
So far, we don’t seem to have been really shocked by anything among the items of new knowledge. There is surprise, even astonishment, but not yet dismay. Perhaps it is still too early to expect this, and it may lie just ahead.
It is not too early to begin looking for trouble. I can sense some, for myself anyway, in what is being learned about organelles. I was raised in the belief that these were obscure little engines inside my cells, owned and operated by me or my cellular delegates, private, submicroscopic bits of my intelligent flesh. Now, it appears, some of them, and the most important ones at that, are total strangers.
The evidence is strong, and direct. The membranes lining the inner compartment of mitochondria are unlike other animal cell membranes, and resemble most closely the membranes of bacteria. The DNA of mitochondria is qualitatively different from the DNA of animal cell nuclei and strikingly similar to bacterial DNA; moreover, like microbial DNA, it is closely associated with membranes. The RNA of mitochondria matches the organelles’ DNA, but not that of the nucleus. The ribosomes inside the mitochondria are similar to bacterial ribosomes, and different from animal ribosomes. The mitochondria do not arise de novo in cells; they are always there, replicating on their own, independently of the replication of the cell. They travel down from egg to newborn; a few come in with the sperm, but most are maternal passengers.
The chloroplasts in all plants are, similarly, independent and self-replicating lodgers, with their own DNA and RNA and ribosomes. In structure and pigment content they are the images of prokaryotic blue-green algae. It has recently been reported that the nucleic acid of chloroplasts is, in fact, homologous with that of certain photosynthetic microorganisms.
There may be more. It has been suggested that flagellae and cilia were once spirochetes that joined up with the other prokaryotes when nucleated cells were being pieced together. The centrioles and basal bodies are believed in some quarters to be semiautonomous organisms with their own separate genomes. Perhaps there are others, still unrecognized.
I only hope I can retain title to my nuclei.
It is surprising that we take information like this so calmly, as though it fitted in nicely with notions we’ve had all along. Actually, the suggestion that chloroplasts and mitochondria might be endosymbionts was made as long ago as 1885, but one might expect, nevertheless, that confirmation of the suggestion would have sent the investigators out into the streets, hallooing. But this is a sober, industrious field, and the work goes on methodically, with special interest just now in the molecular genetics of organelles. There is careful, restrained speculation on how they got there in the first place, with a consensus that they were probably engulfed by larger cells more than a billion years ago and have simply stayed there ever since.
The usual way of looking at them is as enslaved creatures, captured to supply ATP for cells unable to respire on their own, or to provide carbohydrate and oxygen for cells unequipped for photosynthesis. This master-slave arrangement is the common view of full-grown biologists, eukaryotes all. But there is the other side. From their own standpoint, the organelles might be viewed as having learned early how to have the best of possible worlds, with least effort and risk to themselves and their progeny. Instead of evolving as we have done, manufacturing longer and elaborately longer strands of DNA, and running ever-increasing risks of mutating into evolutionary cul-de-sacs, they elected to stay small and stick to one line of work. To accomplish this, and to assure themselves the longest possible run, they got themselves inside all the rest of us.
It is a good thing for the entire enterprise that mitochondria and chloroplasts have remained small, conservative, and stable, since these two organelles are, in a fundamental sense, the most important living things on earth. Between them they produce the oxygen and arrange for its use. In effect, they run the place.
My mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me. Looked at in this way, I could be taken for a very large, motile colony of re
spiring bacteria, operating a complex system of nuclei, microtubules, and neurons for the pleasure and sustenance of their families, and running, at the moment, a typewriter.
I am intimately involved, and obliged to do a great deal of essential work for my mitochondria. My nuclei code out the outer membranes of each, and a good many of the enzymes attached to the cristae must be synthesized by me. Each of them, by all accounts, makes only enough of its own materials to get along on, and the rest must come from me. And I am the one who has to do the worrying.
Now that I know about the situation, I can find all kinds of things to worry about. Viruses, for example. If my organelles are really symbiotic bacteria, colonizing me, what’s to prevent them from catching a virus, or if they have such a thing as lysogeny, from conveying a phage to other organelles? Then there is the question of my estate. Do my mitochondria all die with me, or did my children get some of mine along with their mother’s; this sort of thing should not worry me, I know, but it does.
Finally, there is the whole question of my identity, and, more than that, my human dignity. I did not mind it when I first learned of my descent from lower forms of life. I had in mind an arboreal family of beetle-browed, speechless, hairy sub-men, ape-like, and I’ve never objected to them as forebears. Indeed, being Welsh, I feel the better for it, having clearly risen above them in my time of evolution. It is a source of satisfaction to be part of the improvement of the species.
But not these things. I had never bargained on descent from single cells without nuclei. I could even make my peace with that, if it were all, but there is the additional humiliation that I have not, in a real sense, descended at all. I have brought them all along with me, or perhaps they have brought me.
It is no good standing on dignity in a situation like this, and better not to try. It is a mystery. There they are, moving about in my cytoplasm, breathing for my own flesh, but strangers. They are much less closely related to me than to each other and to the free-living bacteria out under the hill. They feel like strangers, but the thought comes that the same creatures, precisely the same, are out there in the cells of sea gulls, and whales, and dune grass, and seaweed, and hermit crabs, and further inland in the leaves of the beech in my backyard, and in the family of skunks beneath the back fence, and even in that fly on the window. Through them, I am connected; I have close relatives, once removed, all over the place. This is a new kind of information, for me, and I regret somewhat that I cannot be in closer touch with my mitochondria. If I concentrate, I can imagine that I feel them; they do not quite squirm, but there is, from time to time, a kind of tingle. I cannot help thinking that if only I knew more about them, and how they maintain our synchrony, I would have a new way to explain music to myself.
There is something intrinsically good-natured about all symbiotic relations, necessarily, but this one, which is probably the most ancient and most firmly established of all, seems especially equable. There is nothing resembling predation, and no pretense of an adversary stance on either side. If you were looking for something like natural law to take the place of the “social Darwinism” of a century ago, you would have a hard time drawing lessons from the sense of life alluded to by chloroplasts and mitochondria, but there it is.
GERMS
Watching television, you’d think we lived at bay, in total jeopardy, surrounded on all sides by human-seeking germs, shielded against infection and death only by a chemical technology that enables us to keep killing them off. We are instructed to spray disinfectants everywhere, into the air of our bedrooms and kitchens and with special energy into bathrooms, since it is our very own germs that seem the worst kind. We explode clouds of aerosol, mixed for good luck with deodorants, into our noses, mouths, underarms, privileged crannies—even into the intimate insides of our telephones. We apply potent antibiotics to minor scratches and seal them with plastic. Plastic is the new protector; we wrap the already plastic tumblers of hotels in more plastic, and seal the toilet seats like state secrets after irradiating them with ultraviolet light. We live in a world where the microbes are always trying to get at us, to tear us cell from cell, and we only stay alive and whole through diligence and fear.
We still think of human disease as the work of an organized, modernized kind of demonology, in which the bacteria are the most visible and centrally placed of our adversaries. We assume that they must somehow relish what they do. They come after us for profit, and there are so many of them that disease seems inevitable, a natural part of the human condition; if we succeed in eliminating one kind of disease there will always be a new one at hand, waiting to take its place.
These are paranoid delusions on a societal scale, explainable in part by our need for enemies, and in part by our memory of what things used to be like. Until a few decades ago, bacteria were a genuine household threat, and although most of us survived them, we were always aware of the nearness of death. We moved, with our families, in and out of death. We had lobar pneumonia, meningococcal meningitis, streptococcal infections, diphtheria, endocarditis, enteric fevers, various septicemias, syphilis, and, always, everywhere, tuberculosis. Most of these have now left most of us, thanks to antibiotics, plumbing, civilization, and money, but we remember.
In real life, however, even in our worst circumstances we have always been a relatively minor interest of the vast microbial world. Pathogenicity is not the rule. Indeed, it occurs so infrequently and involves such a relatively small number of species, considering the huge population of bacteria on the earth, that it has a freakish aspect. Disease usually results from inconclusive negotiations for symbiosis, an overstepping of the line by one side or the other, a biologic misinterpretation of borders.
Some bacteria are only harmful to us when they make exotoxins, and they only do this when they are, in a sense, diseased themselves. The toxins of diphtheria bacilli and streptococci are produced when the organisms have been infected by bacteriophage; it is the virus that provides the code for toxin. Uninfected bacteria are uninformed. When we catch diphtheria it is a virus infection, but not of us. Our involvement is not that of an adversary in a straightforward game, but more like blundering into someone else’s accident.
I can think of a few microorganisms, possibly the tubercle bacillus, the syphilis spirochete, the malarial parasite, and a few others, that have a selective advantage in their ability to infect human beings, but there is nothing to be gained, in an evolutionary sense, by the capacity to cause illness or death. Pathogenicity may be something of a disadvantage for most microbes, carrying lethal risks more frightening to them than to us. The man who catches a meningococcus is in considerably less danger for his life, even without chemotherapy, than meningococci with the bad luck to catch a man. Most meningococci have the sense to stay out on the surface, in the rhinopharynx. During epidemics this is where they are to be found in the majority of the host population, and it generally goes well. It is only in the unaccountable minority, the “cases,” that the line is crossed, and then there is the devil to pay on both sides, but most of all for the meningococci.
Staphylococci live all over us, and seem to have adapted to conditions in our skin that are uncongenial to most other bacteria. When you count them up, and us, it is remarkable how little trouble we have with the relation. Only a few of us are plagued by boils, and we can blame a large part of the destruction of tissues on the zeal of our own leukocytes. Hemolytic streptococci are among our closest intimates, even to the extent of sharing antigens with the membranes of our muscle cells; it is our reaction to their presence, in the form of rheumatic fever, that gets us into trouble. We can carry brucella for long periods in the cells of our reticuloendothelial system without any awareness of their existence; then cyclically, for reasons not understood but probably related to immunologic reactions on our part, we sense them, and the reaction of sensing is the clinical disease.
Most bacteria are totally preoccupied with browsing, altering the configurations of orga
nic molecules so that they become usable for the energy needs of other forms of life. They are, by and large, indispensable to each other, living in interdependent communities in the soil or sea. Some have become symbionts in more specialized, local relations, living as working parts in the tissues of higher organisms. The root nodules of legumes would have neither form nor function without the masses of rhizobial bacteria swarming into root hairs, incorporating themselves with such intimacy that only an electron microscope can detect which membranes are bacterial and which plant. Insects have colonies of bacteria, the mycetocytes, living in them like little glands, doing heaven knows what but being essential. The microfloras of animal intestinal tracts are part of the nutritional system. And then, of course, there are the mitochondria and chloroplasts, permanent residents in everything.
The microorganisms that seem to have it in for us in the worst way—the ones that really appear to wish us ill—turn out on close examination to be rather more like bystanders, strays, strangers in from the cold. They will invade and replicate if given the chance, and some of them will get into our deepest tissues and set forth in the blood, but it is our response to their presence that makes the disease. Our arsenals for fighting off bacteria are so powerful, and involve so many different defense mechanisms, that we are in more danger from them than from the invaders. We live in the midst of explosive devices; we are mined.