by Isaac Asimov
Many biologists believe that human beings have introduced a number of new cancer-producing factors into the environment within the last two or three centuries. There is the increased use of coal; there is the burning of oil on a large scale, particularly in gasoline engines; there is the growing use of synthetic chemicals in food, cosmetics, and so on. The most clearly guilty of the suspects, of course, is cigarette smoking, which is accompanied by a relatively high rate of incidence of lung cancer.
THE EFFECTS OF RADIATION
One other environmental factor that is certainly carcinogenic is energetic radiation, to which human beings have been exposed in increasing measure since 1895.
On 5 November 1895, the German physicist Wilhelm Konrad Roentgen performed an experiment to study the luminescence produced by cathode rays. The better to see the effect, he darkened the room. His cathode-ray tube was enclosed in a black cardboard box. When he turned on the cathode-ray tube, he was startled to catch a flash of light from something across the room.
The flash came from a sheet of paper coated with barium platinocyanide, a luminescent chemical. Was it possible that radiation from the closed box had made it glow? Roentgen turned off his cathode-ray tube, and the glow stopped. He turned it on again—the glow returned. He took the paper into the next room, and it still glowed. Clearly, the cathode-ray tube was producing some form of radiation which could penetrate cardboard and walls.
Roentgen, having no idea what kind of radiation this might be, called it simply X rays. Other scientists tried to change the name to Roentgen rays, but this was so hard for anyone but Germans to pronounce that X rays stuck. (We now know that the speeding electrons making up the cathode rays are strongly decelerated on striking a metal barrier. The kinetic energy lost is converted into radiation that is called Bremsstrahlung—German for “braking radiation.” X rays are an example of such radiation.)
The X rays revolutionized physics: they captured the imagination of physicists, started a typhoon of experiments, led within a few months to the discovery of radioactivity, and opened up the inner world of the atom. When the award of Nobel Prizes began in 1901, Roentgen was the first to receive the prize in physics.
The hard X radiation also started something else—exposure of human beings to intensities of energetic radiation such as they had never experienced before. Four days after the news of Roentgen’s discovery reached the United States, X rays were used to locate a bullet in a patient’s leg. They were a wonderful means of exploring the interior of the body. X rays pass easily through the soft tissues (consisting chiefly of elements of low atomic weight) and tend to be stopped by elements of higher atomic weight, such as make up the bones (composed largely of phosphorus and calcium). On a photographic plate placed behind the body, bone shows up as a cloudy white, in contrast to the black areas where X rays have come through in greater intensity because they have been much less absorbed by the soft tissues. A lead bullet shows up as pure white; it stops the X rays completely.
X rays are obviously useful for showing bone fractures, calcified joints, cavities in the teeth, foreign objects in the body, and so on. But it is also a simple matter to outline the soft tissues by introducing an insoluble salt of a heavy element. Barium sulfate, when swallowed, will outline the stomach or intestines. An iodine compound injected into the blood will travel to the kidneys and the ureter and outline those organs, for iodine has a high atomic weight and therefore is opaque to X rays.
Even before X rays were discovered, a Danish physician, Niels Ryberg Finsen, had found that high-energy radiation could kill microorganisms; he used ultraviolet light to destroy the bacteria causing lupus vulgaris, a skin disease. (For this he was awarded the Nobel Prize in physiology and medicine in 1903.)The X rays turned out to be far more deadly: they could kill the fungus of ringworm; they could damage or destroy human cells and were eventually used to kill cancer cells beyond reach of the surgeon’s knife.
What was also discovered—the hard way—was that high-energy radiation could cause cancer. At least one hundred of the early workers with X rays and radioactive materials died of cancer, the first death taking place in 1902. As a matter of fact, both Marie Curie and her daughter, Irène Joliot-Curie, died of leukemia, and it is easy to believe that radiation was a contributing cause in both cases. In 1928, a British physician, George William Marshall Findlay, found that even ultraviolet radiation was energetic enough to cause skin cancer III mice.
It is certainly reasonable to suspect that the increasing exposure of human beings to energetic radiation (in the form of medical X rays, nuclear experimentation, and so on) may be responsible for part of the increased incidence of cancer.
MUTAGENS AND ONCOGENES
What can all the various carcinogens—chemicals, radiation, and so can possibly have in common? One reasonable thought is that all of them may cause genetic mutations, and that cancer may be the result of mutations in body cells. This notion was first suggested by the German zoologist Theodor Boveri in 1914.
After all, suppose that some gene is changed so that it no longer can produce a key enzyme needed in the process that controls the growth of cells. When a cell with such a defective gene divides, it will pass on the defect. With the control mechanism not functioning, further division of these cells may continue indefinitely, without regard to the needs of the body as a whole or even to the needs of the tissue involved (for example, the specialization of cells in an organ). The tissue is disorganized. It is, so to speak, a case of anarchy in the body.
That energetic radiation can produce mutations is well established. What about the chemical carcinogens? Well, mutation by chemicals also has been demonstrated. The nitrogen mustards are a clear example. These compounds, like the mustard gas of the First World War, produce on the skin burns and blisters resembling those caused by X rays, and can also damage the chromosomes and increase the mutation rate. Moreover, a number of other chemicals have been found to imitate energetic radiation in the same way.
The chemicals that can induce mutations are called mutagens. Not all mutagens have been shown to be carcinogens, and not all carcinogens have been shown to be mutagens. But there are enough cases of compounds that are both carcinogenic and mutagenic to arouse suspicion that their relationship is more than coincidental.
Beginning in 1960, scientists began to search for nonrandom changes in chromosomes in tumor cells, as compared with normal ones. Changes were indeed found and were pinpointed more surely when techniques were developed to form hybrid mouse/human cells. Such hybrid cells would contain relatively few of the human chromosomes; and if one of those suspected in activating tumors was included, it would give rise to a tumor when the hybrid cell was injected into a mouse.
Further investigations pinned the cancerous change to a single gene on such a chromosome, when a group at the Massachusetts Institute of Technology, under Robert A. Weinberg, successfully produced tumors in mice, in 1978, by the transfer of individual genes. These were called oncogenes (the prefix onco-, from a Greek word meaning “mass,” is commonly used in medical terminology for “tumor”).
The oncogene was found to be very similar to a normal gene. The two might differ, in fact, in a single amino acid along the chain. The picture therefore arises of a proto-oncogene, a normal gene, which exists in cells and is passed along with every generation of cell division, and which, through any number of different influences may, at any time, undergo some small change that will make it an active oncogene. (One may well wonder about the purpose of having a proto-oncogene hanging around a cell when the potential danger is so great. There is no answer yet, but at least we have a new direction of investigation and attack, and that is no small thing.)
THE VIRUS THEORY
Meanwhile, the notion that microorganisms may have something to do with cancer is far from dead. With the discovery of viruses, this suggestion of the Pasteur era was revived. In 1903, the French bacteriologist Amedee Borrel suggested that cancer might be a virus disease; and, in
1908, two Danes, Wilhelm Ellerman and Olaf Bang, showed that fowl leukemia was indeed caused by a virus. However, leukemia was not at the time recognized as a form of cancer, and the issue hung fire. In 1909, however, the American physician Francis Peyton Rous ground up a chicken tumor, filtered it, and injected the clear filtrate into other chickens. Some of them developed tumors. The finer the filter, the fewer the tumors. It certainly looked as if particles of some kind were responsible for the initiation of tumors, and it seemed that these particles were the size of viruses.
The tumor viruses have had a rocky history. At first, the tumors pinned down to viruses turned out to be uniformly benign; for instance, viruses were shown to cause such things as rabbits’ papillomas (similar to warts). In 1936, John Joseph Bittner, working in the famous mouse-breeding laboratory at Bar Harbor, Maine, came on something more exciting. Maude Slye of the same laboratory had bred strains of mice that seemed to have an inborn resistance to cancer, and other strains that seemed cancer-prone. The mice of some strains rarely developed cancer; those of other strains almost invariably did, after reaching maturity. Bittner tried the experiment of switching mothers on the newborn mice so that they would suckle at the opposite strain. He discovered that when baby mice of a “cancer-resistant” strain suckled at mothers of a “cancer-prone” strain, they usually developed cancer. On the other hand, supposedly cancer-prone baby mice that were fed by cancer-resistant mothers did not develop cancer. Bittner concluded that the cancer cause, whatever it was, was not inborn but was transmitted in the mother’s milk. He called it the milk factor.
Naturally, Bittner’s milk factor was suspected to be a virus. Eventually the Columbia University biochemist Samuel Graff identified the factor as a particle containing nucleic acids. Other tumor viruses, causing certain types of mouse tumors and animal leukemias, have been found, and all of them contain nucleic acids. No viruses have been detected in connection with human cancers, but research on human cancer is obviously limited.
Now the mutation and virus theories of cancer begin to converge. Perhaps the seeming contradiction between the two notions is not a contradiction after all. Viruses and genes are very similar in structure; and some viruses, on invading a cell, may become part of the cell’s permanent equipment and may play the role of an oncogene.
To be sure, tumor viruses seem to possess RNA every time, while the human gene possesses DNA. As long as it was taken for granted that information always flows from DNA to RNA, it was hard to see how tumor viruses could play the role of genes. It is now known, however, that there are occasions when RNA can bring about the production of DNA that carries the RNA pattern of nucleotides. A tumor virus, therefore, may not be an oncogene, but it might form an oncogene.
For that matter, a virus may be less direct in its attack. It may merely play an important role in bringing about the conversion of the proto-oncogene to the oncogene.
It was not till 1966, however, that the virus hypothesis was deemed fruitful enough to be worth a Nobel Prize. Fortunately, Peyton Rous, who had made his discovery fifty-five years before, was still alive and received a share of the 1966 Nobel Prize for medicine and physiology. (He lived on to 1970, dying at the age of ninety, active in research nearly to the end.)
POSSIBLE CURES
What goes wrong in the metabolic machinery when cells grow unrestrainedly? This question has as yet received no answer. One strong suspicion rests on some of the hormones, especially the sex hormones.
For one thing, the sex hormones are known to stimulate rapid, localized growth in the body (as in the breasts of an adolescent girl). For another, the tissues of sexual organs—the breasts, cervix, and ovaries in a woman; the testes and prostate in a man—are particularly vulnerable to cancer. Strongest of all is the chemical evidence. In 1933, the German biochemist Heinrich Wieland (who had won the Nobel Prize in chemistry in 1927 for his work with bile acids) managed to convert a bile acid into a complex hydrocarbon called methylcholanthrene, a powerful carcinogen. Now methylcholanthrene (like the bile acids) has the four-ring structure of a steroid, and it so happens that all the sex hormones are steroids. Could a misshapen sex-hormone molecule act as a carcinogen? Or might even a correctly shaped hormone be mistaken for a carcinogen, so to speak, by a distorted gene pattern in a cell, and so stimulate uncontrolled growth? It is anyone’s guess, but these are interesting speculations.
Curiously enough, changing the supply of sex hormones sometimes checks cancerous growth. For instance, castration, to reduce the body’s manufacture of male sex hormone, or the administration of neutralizing female sex hormone, has a mitigating effect on cancer of the prostate. As a treatment, this is scarcely something to shout about, and it is a measure of the desperation regarding cancer that such devices are resorted to.
The main line of attack against cancer still is surgery. And its limitations are still what they have always been: sometimes the cancer cannot be cut out without killing the patient; often the knife frees bits of malignant tissue (since the disorganized cancer tissue has a tendency to fragment), which are then carried by the bloodstream to other parts of the body where they take root and grow.
The use of energetic radiation to kill the cancer tissue also has its drawbacks. Artificial radioactivity has added new weapons to the traditional X rays and radium. One of them is cobalt 60, which yields high-energy gamma rays and is much less expensive than radium; another is a solution of radioactive iodine (the “atomic cocktail”), which concentrates in the thyroid gland and thus attacks a thyroid cancer. But the body’s tolerance of radiation is limited, and there is always the danger that the radiation will start more cancers than it stops.
The increasing knowledge of the last decade offers hope for some method of treatment that would be less drastic, more subtle, and more effective.
For instance, if viruses are involved in some fashion in the initiation of a cancer, any agent that would inhibit virus action might cut down the incidence of cancer or stop the growth of a cancer once it has started. The obvious possibility here is interferon; and now that interferon is available pure and in quantity, it has been tried on cancer patients. So far it has not been markedly successful; but because it is an experimental procedure, it has been tried only on patients who are far along in the disease and may be beyond help. Then, too, there may be subtleties to the method of use that have not yet been worked out.
Another approach is this: Oncogenes differ so slightly from normal genes that it seems reasonable to suppose that they are forming frequently, and that the production of a cancerous cell is more common than we suppose. Such a cell would have to be different in some ways from a normal one, and perhaps the body’s immune system may recognize it early on and dispose of it. It may be, then, that the development of cancer means not that a cancer cell has formed, but that a cancer cell, having formed, has not been stopped. Perhaps cancer is the result of a failure of the immune system—in a way, the opposite of autoimmune disease, where the immune system works too well.
Prevention and cure may rest then with our increased understanding of the manner in which the immune system works. Or, until such an end is achieved, perhaps the body may be given artificial aid in the form of compounds that will distinguish between normal cells and cancer cells.
Some plants, for instance, produce substances that react with certain sugars, as antibodies react with certain proteins. (The purpose of such sugar-distinguishing substances in plants is not yet known.)
The membranes that enclose cells are made up of proteins and fatty substances, but the proteins usually incorporate into their structures certain moderately complex sugar molecules. Because the nature of the sugars in the membranes are different, blood cells are of several different types that can be distinguished by the fact that some types agglutinate under some conditions and some under others.
The American biochemist William Clouser Boyd wondered whether there might be plant substances that can distinguish between one blood group and another. In 1954, rathe
r to his own surprise, he found such a substance in lima beans, which was among the first plants he tried. He named such substances lectins, from a Latin word meaning “to choose.”
If a lectin can choose between one kind of red corpuscle and another, on the basis of subtle differences in surface chemistry, some lectins might be found that can distinguish between a tumor cell and its normal cell of origin, agglutinating the tumor cells and not the normal ones. Thus, these lectins might put the tumor cells out of action and slow or reverse the growth of cancer. Some preliminary investigations have yielded hopeful results.
Finally, the more we learn about oncogenes and their method of production, the greater the chance of our learning ways of preventing their appearance or of encouraging their disappearance.
Meanwhile, though, the fear of cancer and the apparent hopelessness of cure frequently causes the public to yearn after pseudo-scientific cures such as those attributed to the substances called krebiozen and laetrile. One can scarcely blame people who clutch at straws, but so far these substances have never helped and have sometimes prevented patients from seeking out more hopeful treatment.
Chapter 15
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The Body
Food
Perhaps the first great advance in medical science was the recognition by physicians that good health calls for a simple, balanced diet. The Greek philosophers recommended moderation in eating and drinking, not only for philosophical reasons but also because those who followed this rule were more comfortable and lived longer. That was a good start, but biologists eventually learned that moderation alone is not enough. Even if one has the good fortune to avoid eating too little and the good sense to avoid eating too much, one will still do poorly on a diet that happens to be shy of certain essential ingredients, as is actually the case for large numbers of people in some parts of the world.
