The Thorn in the Starfish: How the Human Immune System Works
The great geneticist Theodosius Dobzhansky wrote that in nature nothing makes sense unless we bear in mind that natural selection reigns supreme. In Africa, one of the sources of poverty is a cattle disease caused by a parasite, the trypanosome. The disease is transmitted by the tsetse fly. When this fly stings a cow, the trypanosomes penetrate into her blood, where they are recognized as foreign invaders by some of her white blood cells. Alarmed by that signal, these particular white cells divide and multiply, and their descendants secrete antibodies into the blood that kill the parasites. Alas, not quite all of them. A few survive because genetic mutations have dressed them up in new coats unrecognized by the cow’s antibodies; these survivors now divide and multiply, and force the cow’s immune system to begin the fight all over again. The same battle repeats itself every few weeks.
The Dutch molecular biologist Piet Borst discovered the genetic mechanism that enables the trypanosomes to take up a multitude of different disguises. He found that their chromosomes contain a repertoire of genetic “cassettes,” each capable of directing the manufacture of a different protein coat; mutations can activate such cassettes in turn by inserting them into the same “cassette player.” None of these new coats can fool the cow’s defenses for long because early in life the genes that code for its antibodies have been shuffled in about a hundred million different ways, allowing the cow to make about a hundred million different antibodies, each secreted by a different population of white blood cells. This profligacy ensures that the cow can make antibodies not only against the trypanosomes in all their different guises, but also against all other conceivable infections.
The mutations that change the trypanosomes’ coats, and the shuffling of the genes that gives rise to millions of different antibodies, are chance events. Natural selection causes those of the cow’s white cells that by chance recognize the trypanosomes, and those of the trypanosomes that escape recognition at first, to divide and multiply. The Darwinian struggle between the white cells and the trypanosomes ensures the survival of the population of parasites and also that of their host, the cow, but she becomes emaciated and a poor producer of milk, to the detriment of the farmer.
White blood cells like those that respond to the trypanosomes are the soldiers that spring to an animal’s defense on infection. Robert S. Desowitz’s book introduces the layman to their different uniforms, weapons, and tactics, and to the systems of command that control them, including, surprisingly, our state of mind. The vicious cold that struck you just before your final exams may have penetrated your defenses because mental stress and exhaustion had already made your immune system crumble. Experiments on rats suggest that the immune response can even be suppressed by a conditioned reflex, as if, after a series of exams, the mere sight of another examination paper could suppress it.
The book introduces us to some of the classic experiments on the microorganisms that attack us and our natural defenses against them. Its title, The Thorn in the Starfish, is taken from a discovery made in 1882 by the Russian biologist Elie Metchnikoff. Here is his own account of it:
I was resting from the shock of the events which provoked my resignation from the University [of Odessa] and indulging enthusiastically in researches in the splendid setting of the Straits of Messina.
One day when the whole family had gone to a circus to see some extraordinary performing apes, I remained alone with my microscope, observing the life in the mobile cells of a transparent starfish larva, when a new thought suddenly flashed across my brain. It struck me that similar cells might serve in the defense of the organism against intruders. Feeling that there was in this something of surpassing interest, I felt so excited that I began striding up and down the room and even went to the sea-shore to collect my thoughts.
I said to myself that, if my supposition were true, a splinter introduced into the body of a starfish larva, devoid of blood vessels or of a nervous system, should soon be surrounded by mobile cells as is to be observed in a man who runs a splinter into his finger. This was no sooner said than done.
There was a small garden in our dwelling, in which we had a few days previously organized a “Christmas tree” for the children on a little tangerine tree: I fetched from it a few rose thorns and introduced them at once under the skin of some beautiful starfish larvae as transparent as water.
I was too excited to sleep that night in the expectation of the results of my experiment, and very early the next morning I ascertained that it had fully succeeded.
That experiment formed the basis of the phagocyte theory [phagocytes are the mobile cells he had observed], to the development of which I devoted the next twenty-five years of my life.
As so often, a discovery of great benefit to man was made by observing the humblest of creatures. Soon afterward Metchnikoff went to Paris in order to work out its medical implications in Pasteur’s new laboratory. He then found himself embattled with Paul Ehrlich, the German pioneer of immunology who championed the role of the antibodies in the body fluids and belittled that of Metchnikoff’s bacteria-devouring phagocytes. In reality both proved vital. (Desowitz tells us that Ehrlich’s work initiated a “novalike” explosion of research, which made me wonder if our senses have become so blunted by superlatives that an explosion of mere dynamite slides off unnoticed and only an event capable of blowing up the entire solar system provides a clichĂŠ powerful enough to stir us.)
Desowitz supplies health-conscious Americans with recipes for keeping their immune systems vigorous to a ripe old age by taking essential trace metals in addition to their vitamin pills but he warns that these measures will be to no avail to heavy smokers. In Britain, cigarette advertisements have to display the warning, “Smoking may damage your health”; Mrs. Thatcher is said to have dismissed one of her ministers because he prepared legislation that would have prohibited the advertisements altogether. Smoking is the prime cause of lung cancer and one of the prime causes of cardiovascular disease. Desowitz describes other consequences of smoking that are less widely known. One is a depression of the immune system that makes smokers more liable to contract infections; another is paralysis of the tiny hairs lining the windpipe and the lungs that push out dust and bacteria; yet another is perversion of enzymes meant to remove or repair damaged lung tissue, so that they destroy the lung tissue instead and cause the agonizing disease of emphysema.
Allergic reactions may have evolved originally to rid animals of parasitic worms. The antibodies elicited by their presence in the gut do not attack the worms directly, but cause the release of irritants such as histamine that make the host’s gut expel the worms. These same antibodies are activated “by mistake” in hay fever, asthma, and other allergic diseases that plague us. Smoking relieves two allergic conditions, asthma and ulcerative colitis, at least in some of the sufferers. Apparently these patients benefit by the suppression of the immune system that smoking produces.
Vaccination mobilizes the immune system against diseases before they attack us. Its inventor, the English physician Edward Jenner, first tried it in 1778, not on “informed volunteers” but on children recruited from the workhouse. He inoculated them with the cowpox, and afterward his nonphysician nephew Henry Jenner tried to infect them with smallpox pus to see whether they were protected; he also used a non-inoculated child as a “control.” Desowitz was perplexed by the contradiction between Jenner’s religious faith and such ruthless experiments on ignorant children, until an Oxford historian explained to him that these children would have been beyond the protection of the Established Church’s God because they had committed the sin of being born poor; paupers were then considered as fair game as guinea pigs are now. Desowitz writes that the government of Bavaria made vaccination compulsory as early as 1807. It took until 1871 for compulsory vaccination to be made effective in Jenner’s native England, and nearly two hundred years for it finally to be made available to virtually every man, woman, and child in the world. New ways of killing people have always been adopted with alacrity, but ways of preventing illness have sometimes taken centuries to be implemented.
Vaccination may have saved even more lives than antibiotics. The author writes:
In 1921 there were in America some 200,000 cases of diphtheria; in 1934, 250,000 cases of whooping cough; in 1941, 900,000 cases of measles; in 1952, 21,000 cases of polio; and in 1968, 150,000 cases of mumps. By 1982 the widespread immunizations given to children had reduced the yearly incidences to 3 cases of diphtheria, 1,500 cases each of measles and whooping cough, 5,000 cases of mumps, and 7 cases of polio (three of which were caused by the vaccine, a rare untoward occurrence). All this and more (tetanus and rubella are also included in the standard immunizing regime) for a total cost of about ten dollars per child for all immunizations. There has never been a greater bargain.
In 1974 the Surgeon General of the United States announced national goals for the continuing immunization of Americaâ€”goals that were projected to be achieved by 1990. That program is not only working, it is ahead of schedule. It is just possible that by 1990, or shortly thereafter, measles and polio will become extinct in the United Statesâ€”historical curiosities.
It is sad that this splendid program is now threatened by budget cutters and by huge damages awarded against pharmaceutical firms whose vaccines have accidentally caused illness or death. Courts should realize that it is no more possible to manufacture an absolutely safe vaccine than it is to make a faultless car, and the public must accept a minimum of risk in return for the immense benefits; otherwise pharmaceutical firms will give up the manufacture of vaccines, since zero risk can be bought only at infinite expense.
Further great advances in vaccination are now in the offing. By 1990 most children in the United States should be vaccinated against mumps, measles, and rubella, and measles might soon be eradicated worldwide, just like smallpox. There already exists a vaccine against hepatitis B, a widespread killer and cause of liver cancer, but it costs $100 a shot. Leprosy still affects about 12 million people. Large-scale clinical trials of vaccines against it are being carried out in Venezuela, India, and Malawi. Research on a vaccine against malaria has become possible since M.J. Friedman in America and G. Pasvol in Britain found out how to culture the malaria parasite in human red blood cells, but there are many technical difficulties still to be overcome. The brightest hope lies in genetically engineering the vaccinia (cowpox) virus, formerly used for vaccination against smallpox, so that it also displays on its surface the markers of other diseasecausing organisms, such as the hepatitis B virus and the malaria parasite. A single shot of this genetic composite should be cheap and would immunize against a variety of diseases. For the distant future, the author forecasts vaccination even against some of the more common cancers.