The Real Cause of Cancer
Glasser, Ronald J.
The Real Cause of Cancer by Ronald J.Glasser T o d a y we know that above all else cancer is a cellular disease. What causes it to develop happens down inside individual cells, at the levels...
...The changes that occur in exposed cells undergoing malignant transformations were irreversible...
...Ames felt it necessary to write an open letter to Dr...
...In 1940 I. Berenblum, one of the greatest cancer researchers of all time, beginning with Rous’ observation, painstakingly set about to prove or disprove the crucial point of Rous’ work, what was to become the crucial point of all cancer production-the precise importance of irritation...
...There was no way under the microscope of making a mistake, no way any longer of confusing those wildly growing malignant cells with anything else...
...It was only when the microscope began to be used and precise microscopic evaluation of diseased organs and pathologic tissues became possible that the confusion about what was and what was not cancer finally began to be cleared up...
...Benzopyrene has proved, as would be expected, to be mutagenic in the Ames bacterial system, as have aniline dyes and radiation...
...No company wants to have someone else label its products as carcinogenic...
...But if you keep the doses of radiation or carcinogen to less than the amounts needed to kill all the cells, a few cells in each of the culture mediums will eventually turn malignant, assume unnatural shapes, and, beginning to divide at unnatural rates, quickly overgrow the whole culture dish...
...T h e r e is, among all this bad news, one vital, hopeful sign in cancer preven tion...
...It has been proved through a decade of precise, laboriously controlled research that no matter what the carcinogens, chemical or physical, no matter how diverse or different they may seem to be on the surfacebenzopyrene or aniline dyes, asbestos or X-ray-they all share that one same basic property...
...Some malignant cells can even appear totally identical to their still normal tissues of origin Nor can you tell exactly how malignant a cancer might be from the form it takes...
...We also know that these struct ure s inter act c he mi cally and physically with one another to keep a cell healthy, and that any injury to these structures, any interference with their communal microscopic interactions or control mechanisms, natural or man-made, is not only the cause of cancer, but basically the cause of all other illnesses as well...
...And people are finally listening...
...o n e thing became obvious at the very beginning of the studies of carcinogens and how they work...
...The ability to recognize the various malignancies was only the beginning...
...He rubbed the skin with a low-critical, though apparently noncancer-producing, concentration of a carcinogen and then waited days, weeks, months, or even years before applying the irri-tant...
...Paracelsus gave classic descriptions of them well before the end of the 16th century...
...m Beginning in 1941 , in the name of patriotism, with the tacit agreement of the federal government and the wholehearted cooperation of the American Red Cross, almost every healthy young adult male between the ages of 18 and 26 in the entire U.S...
...Malignant cells invading lungs may cause asphyxia before they cause uncontrollable hemorrhage...
...and he has found carcinogens forming from chemicals that by themselves, out in the environment and not yet ingested, might not be dangerous...
...If the chemical gets into the bacterial cell, into the nucleus, and affects the bacteria’s nucleoproteins, it will cause mutations, and with the mutations a some of the bacteria will begin to grow...
...Eventually each new cell, an exact replica of the first malignantly transformed cell, breaks out into the bloodstream or lymphatics, spreading to the other organs of the body, lodging in them, taking them over as well...
...Remove not only the cancer but the whole lung of cancer patients, and 95 per cent will still be dead within a year...
...The original discovery that upset the theory that cancer production results from nothing more than a constant exposure of normal cells to a carcinogenic agent was made by Peyton Rous in the early 1920s...
...Yet, there is still reluctance in many industries to test already existing products...
...Bruce Ames of the University of California at Berkeley, did what everyone said could not be done: he developed a test to prove if a chemical could cause cancer...
...It is not far-fetched today to say that the cigarettes delivered month after month to the Marines on Guam and,Saipan, the airmen flying out of Tinip and Iceland, the Third Army pushing up through the Rhine Valley, the lOlst and 82nd Airborne in Holland and Belgium, would eventually prove as deadly to those young men as any German bullet or Japanese rocket...
...Data obtained with this test have shown that over 80 per cent out of 140 carcinogens tested show mutagenic activity while very few chemicals in general [ 100 noncarcinogen~] are mutagenic...
...Infected municipal water supplies are closed down...
...There are no new markers-no biologically active “antigens”-on their surface to be read as foreign by the body’s defense system...
...it was even too late for those who were not dead at the time of the discovery but had already been sufficiently exposed to be in risk of dying...
...Today we know that cells are divisible, that each cell is made up of subcellular ultramicroscopic stmctures...
...At a recent lecture at the University of Minnesota, a world expert on the experimental production of cancer struggled to define for his scholarly audience exactly what cancer is...
...The more colonies growing in the dish, the more active the chemical in causing mutation...
...The FDA Consumer had stated even before Ames’ letter that hair dyes “were specially exempted from the Federal Food, Drug and Cosmetic Act of 1938 by Cungr e s s after Industry persuasively argued that the dyes could not meet safety standards of the act but should nonetheless be sold to meet popular demands...
...Those cigarettes would eventually kill as many of them as any grenade or mine...
...He developed a strain of bacteria that cannot grow in a certain type of nutrient-deficient broth, one without an amino acid called histidine, but cap, with a slight change in its DNA-a mutation-begin to use the broth to grow...
...Using the Japanese method for producing experimental cancers, he was painting rabbits’ ears with coal-tar preparations, fully expecting to have to paint the same patch of skin for at least a year before any cancers became evident...
...Much of the confusion about what was and was not cancer, about spontaneous cures and remissions, almost all of the myths concerning treatments and prognoses, came about because for centuries cancers were confused with other diseases...
...Cancer is caused by injuries to minute subcellular structures, so small that they can barely be seen by our most powerful electron microscopes...
...We find that 150 out of 169 oxidativetype hair dyes tested, most of the semi-permanent type dyes tested, nine of the components of hair dyes, and several oxidation products of hair dye ingredients are mutagenic...
...We have developed a rapid and sensitive test using bacteria and animal tissue, for identifying mutagens, chemicals that damage the genetic material...
...He has also inlcorporated liver enzymes into the culture medium, which can convert certain inactive test chemicals into active mutagens, mimicking what happens to chemicals entering the human body...
...Inhaled and ingested asbestos particles were found to be carcinogenic, causing lung cancer as well as a rare type of malignancy-mesotheliomas of the chest wall...
...Antigenetically like any other cells, ignored by the body’s defense system, these malignant cells grow unrestricted, - uncontrolled by any of our body’s defense or reparative systems...
...There are industries today that resist the idea that their products may cause disease, just as in a former day the idea that illness could be caused by contaminated water was resisted...
...Livers turning malignant, lungs and stomachs eaten away, have always been a horrifying part of medicine...
...Like all living things, the nucleoprotein in their nucleus is, chemically similar to the DNA in all other living things, including the DNA in our own cells...
...Berenblum made an even more ominous discovery, one that had to do with the time schemes involved...
...To find out, Berenblum went on to devise what has become one of the classic cancer experiments of modern times...
...From the data we concluded that chemicals active in this test have a high probability of proving to be carcinogens...
...We are just beginning to understand how these injuries occur and what the damaged structures are, and how, once injured, they can cause these cells to become malignant...
...Like Snow more than a hundred years before him, and Paracelsus and Pare centuries before Snow, Ames has had to make a public fight for the public’s health...
...He could at will reproducibly initiate cancers in supposedly still perfectly healthy, though carcinogenicexposed, skin by the addition of nothing more than an irritating solution...
...It is the lack of control over the way a cell divides and grows that makes it malignant...
...What causes it to develop happens down inside individual cells, at the levels of molecules and membranes...
...In other words, the definition finally presented to the audience was simply that tissues become cancerous when the cells that make them up no longer respond to the external, or their own internal, subcellular controls, controls that restrain them and keep them in balance with all the other cells of the body...
...With the use of the Ames test, in a matter of two days at a cost of approximately $600, rather than the hundreds of thousands of dollars, the two to three years, and the huge facilities necessary to do the appropri- ate animal studies, a potentially dangerous chemical can now be quickly screened for its ability to cause mutation, to damage the genetic material of cells...
...The real question was not the what or even the how of cancer, but the why...
...Once a quiet, cloistered academician, he has had to do what concerned physicians and scientists making discoveries opposed by vested interests have always had to do...
...The implications of this discovery were terrifying...
...It had been known for years that croton oil applied to normal skin would cause irritation and redness but never cancer...
...So I started manipulating bacteria to see if I could sensitize them to detecting chemicals that can cause mutations...
...T h e test Ames finally devised is very simple...
...I believe Menkart’s letter is extremely misleading and irresponsible,” Ames wrote...
...The grim fact is that this has already happened...
...Once DNA is changed, once the genetic code is altered, that change is permanent, forever...
...Instead of dividing and forming more of themselves in a restrained and totally organized way, or simply staying where they are and doing what they should do-making proteins, carrying hemoglobin, fighting infections, or transporting fats-the malignant cells take off on their own...
...But the truly important experiments were only now to begin...
...Crippling p at ho 1 ogical fractures caused by bones filling with metastatic cells may be the first sign of malignant lymphomas...
...Physicians using their microscopes could definitively say this man died of cancer, that man of a bacterial infection...
...Since carcinogens are mutagens, he reasoned that if a chemical caused a cell to mutate, it would in all probability cause other cells to become malignant...
...This has made the test sensitive to chemicals that might otherwise not be able to get into the bacteria...
...These preexposed cells, rather than healing themselves after exposure to irritating substances as any normal healthy cell would, instead became frankly malignant...
...I In 1956 an international conference of scientists in Rome declared Red Dye Number 2 to be a suspected carcinogen...
...It is only within the last few decades that we have begun to understand how the different arrangements of the molecules that form the DNA act as genes...
...Looked at superficially, even today leprosy can easily be mistaken for the slowly eroding squamous-cell carcinomas of the face and hands, echinococcal cysts for hepatomas of the liver, tuberculosis for lung cancer...
...We know that in large doses, carcinogens kill cells...
...As a member of the National Institute of Environmental Health Sciences said recently: “This test system has proved its capability of identifying potentially dangerous chemicals in a quick and efficient way...
...For all the suffering it causes, it is nothing more than a loss of intracellular control, a genetic mutation induced by injury...
...They all affect the cell’s genetic material by getting into the cell, and once inside, work their way into the nucleus where they either bind to or simply destroy sections or parts of the cell’s nucleic acids...
...The USO, religious groups, friends and relatives, all made sure their young men, no matter where they were, received cartons of cigarettes...
...Yet until a few years ago no one knew what they were, where they came from, how they kill us...
...Hair dye components can be absorbed apparently through the human scalp...
...In Ames’ own words: “About ten years ago I got fed up reading the long list of chemicals on potato chip labels and wondering if they were safe...
...Astonishing as it is, the only difference in genes, the only difference in the structure of a nucleoprotein that tells one cell to turn into part of the liver and another into part of the brain, that keeps this cell in the lymph node making antibodies and that one in the stomach making hydrocholoric acid, that turns one fertilized egg into a fish and another into a child, is the sequences of the four simple carbon- and nitrogencontaining compounds that form the basic backbone of the DNA molecule: the bases adenine, guanine, cytosine, and thymine...
...Up until the 1920s all that was known about cancer was what the Japanese had already proved: that there were carcinogenic compounds which, when continually applied to tissues, would cause the cells of these tissues to become malignant...
...Bacterial or virally contaminated products when found are removed from the market or destroyed...
...In short, he started out to discover what exactly the connection was between normal cells, carcinogens, and irritants...
...The carcinogen absorbed by the cells, while not making them overtly malignant, had turned them instead into tiny time bombs, ready to go off at what appeared to be the slightest provocation...
...Indeed, the development of this test is potentially one of the most important environmental advances in modern-day preventive medicine, and could in time be to cancer prevention what the development of vaccines was to infectious diseases...
...We now know that all carcinogenic substances, whatever they are, bind to intracellular particles, and the particles they bind to most strongly and affect most are the nucleoproteins contained in the nucleus of the cellthe DNA, the proteins that contain the genetic code...
...Nor does it, like aflatoxin, injure the liver cells themselves, but the cells of the small blood vessels that line the liver...
...Patients died just as slowly and just as horribly with a correct diagnosis as those who had died misdiagnosed or with no diagnosis at all...
...Hippocrates and Galen, describing them under different names, wrote of malignancies 2,000 years ago...
...Cancers have been noted since antiquity...
...All the pain and all the suffering of cancer come from the continual invasion of the body’s still normal tissues by its own malignant cells...
...It was plain to the first cancer researchers that cells which become malignant undergo some kind of profound and fundamental change...
...He thought for a moment...
...However, unlike aflatoxin, it is not ingeste: and absorbed into the bloodstream through the stomach, but through the skin or mucous membranes...
...By the 1890s physi-cians were able for the first time in history to know exactly who had cancer and who did not and precisely what cell type was involved...
...No one was testing anything to see if there was a mutagen...
...But the change is still as permanent as any mutation in a fetal cell and will be passed on to all the cells that spring from it...
...In smaller doses, because of their unique affinity for genetic material, they do not kill cells, they cause them to mutate, and it is this mutagenic nature of carcinogens that causes cancer...
...Carcinogens to which normal cells are exposed are called the initiators, and the irritant causing the malignant transformation, the promoter...
...It took Ames a decade to develop his test...
...It is only our understanding of what does and does not cause disease that has changed...
...Indeed, there is a great governmental bureaucracy devoted solely to testing for bacterial contamination not only in foodstuffs but water supplies...
...He peeled off the cell walls around the bacteria that ordinarily keep out large molecules...
...10 Berenblum took the mice whose skin had been exposed to the low, apparently noncarcinogenic, doses of benzopyrene and rubbed the skin with croton oil...
...All he needed was a way to look for cellular mutations, and he found one...
...At any time something could creep into our diet that would significantly alter our genes and we would never know it...
...Ames has modified his bacterial strain genetically by selective breeding so that they cannot grow without histidine in the broth medium...
...To his 8 surprise, cancers soon began to develop around the punch sites, months before any cancers were expected to be produced...
...State health departments, city and municipal health officials, the Center for Disease Control in Atlanta, all are devoted to the control and prevention of communicable diseases...
...the surface of these malignant 16 cells stays the same as normal cells...
...Carcinogens are toxic chemicals which are absorbed by or diffused into cells...
...Yet the ability of anatomists finally to be able to say that in this case the primary cause of death was malignant melanoma, in that adenocarcinoma, gave physicians what they had been looking for: a place to begin...
...Whole generations could be wasted before we would even know we were in danger...
...no matter how long he waited, nQ matter how long the interval between exposure to the initiator and exposure to the promoter, the cancer always developed in the same amount of time following application of the promoter...
...What must be done is simple...
...They can and do arise from literally any kind of tissue cell...
...Companies that distribute salmonella- or botulismcontaminated products are allowed by a suspicious public to go bankrupt or lose substantial parts of their market, and everyone feels the loss is justified...
...At very low concentrations of the chemical, no cancers developed in any of the exposed animals...
...Rous’ discovery that cancers would develop much earlier in normal skin exposed to a small amount of a known carcinogen if that skin was exposed to a second, in itself noncancercausing, insult, even one as seemingly innocuous as a tiny cut, led to development of the important concept of cancer inducers and cancer promoters...
...There, in the submicro12 scopic world of cellular controls, one molecule of the carcinogen, or perhaps two or three at the most, physically couples with the bases or perhaps even the sugars of the nucleoproteins, and like a monkey wrench jamming the control gears of a complicated factory, destroys or interferes with two billion years of finely tuned evolution...
...A cell exposed to a carcinogen was apparently not only a time bomb, but a time bomb that continued to tick and would continue to tick until either it died a natural death or, exposed to an appropriate irritant, turned cancerous...
...Could irritants alone cause cancer and how, in one tiny world of cellular differentiation, could minute, not massive exposures to carcinogenscause normal cells to undergo malignant transformations...
...They can present themselves in any variety of cellular types ranging from a totally undifferentiated, primitivelooking group of cells to a wellorganized tumor practically identical to the still normal cells surrounding it...
...m In the late fifties it was discovered that workers involved in the production of asbestos-cement fireproofing materials and insulation had rates of cancer ten times that of workers in other industries...
...It is not that any of this is really 6 new...
...Food samples are tested all the time for bacterial contamination...
...This is precisely what happens to the cells in your own body when they are exposed to a carcinogen and turn malignant...
...It is this DNA, holding within its own molecular arrangement the genetic code that tells the cell what it will be, what it will do, and how it will do it, that is affected most by carcinogens...
...Cancerous thyroid cells flooding into the kidneys crowd out normal kidney cells, causing the slow death of chronic renal failure and uremia...
...1 f there is any one overriding concern that haunts physicians today, one great fear that drives cancer researchers and keeps them working and publishing their findings in the face of powerful industrial and at times political opposition, not to mention personal and professional abuse, it is that a low-grade but potent cancercausing substance may be introduced into the general environment unknowingly or uncaringly, to be consumed by vast numbers of people, dooming them before they even know about the inevitable and untreatable malignancies...
...T h a t is really what cancer is...
...If the mutation occurs in a fully matured cell, one that will not give rise to any other cell types, only that cell’s nucleoprotein will be altered...
...This concept of inducers and promoters is now central to the understanding of how cancers are produced, not only explaining what have been some of the most confusing aspects of cancer production, but pointing the way to an understanding of not only why cancers take so long to develop but why malignancies are themselves so deadly...
...they merely grow there until they interfere with some vital fuhction like breathing or heartbeat, and the patient dies...
...A gene in the cell’s nucleus is injured...
...As their microscopic abilities improved, so did the number of diagnosed malignancies: osteogenic sarcomas, hypernephromas, oat-cell carcinomas, histocytosis...
...F o r other kinds of cancers the deaths are slower...
...There is nothing particularly mysterious about this...
...Fred de Serres said the Ames test “would help industry establish priorities on which chemicals to develop, allowing industry to screen chemicals very early in development instead of investing hundreds of thousands of dollars in a substance only to find out later it causes cancer...
...This meant that once a cell is exposed to a low but critical level of a carcinogen, it becomes premalignant and stays that way, never reverting back to normal, always ready on exposure to some irritant-no matter how long into the future, no matter how distant in time from its original contact with the premalignant levels of carcinogen-to turn overtly malignant...
...But if proper protection is used, it is not too late for the children and adolescents who will someday work in those factories or even those adults who are starting today...
...Dividing the animals into groups, he constantly increased the concentration of the benzopyrene...
...With all this variation we now know that it is not the speed with which a cell divides, how fast it grows, what it does, or what tissue it comes from that makes it cancerous, but its independence...
...population was systematically if unknowingly exposed to a low-grade but potent carcinogenic...
...The test is that simple and that definitive...
...In an example of individual persistence combined with scientific ingenuity and human concern, one man, Dr...
...no one thinks anything of it...
...If just one malignant cell is left anywhere in the body, the cancer will recur...
...Scientists have given us an important clue-a definitive diagnostic testto determine what is a carcinogenic chemical and what is not...
...After the publication of Rous’ and others’ work on the production of malignancies, the real question facing cancer researchers was no longer whether chemicals could cause cancers, but exactly how long such exposures took, what exposure amounts were necessary, how carcinogens worked...
...Cancerous cells, unrestrained by their own or any of the body’s normal control mechanisms, go where they please, take over the body’s energy and fuels when they want, and in the process squeeze out or starve the body’s still healthy cells, causing not only the patient’s death but eventually their own as well...
...Recently Dr...
...Some of the most malignant and difficult-to-treat cancers are those that grow the slowest...
...Indeed, cancers, even among themselves, show a wide range of growth rates, from the very slow-growing tumors which do not produce symptoms for years after their known onset, to those that reach lethal size within a few weeks...
...Each colony of growing bacteria represents a salmonella that has mutated, one that the test chemical has entered, changing its DNA, so that under new control the bacterial cell can now manufacture its own histidine, and unlike its unmutated neighbor not exposed to the spots of chemical, grow and divide in the histidine-different medium...
...But so much pressure was brought to bear, so much opposition generated by consumer groups, that the agency subsequently reversed itself and late in 1975 banned further use of the chemical in new products, but allowed the continued sale of any products that contained the dye before the ban...
...We have now begun to realize that the problem of environmentally induced cancer is that the changes that are caused by the carcinogen are all internal, occurring in the cells’ DNA...
...With a continually growing awareness among the public of the environmental nature of cancer, more and more companies are overcoming an initial reluctance to use Ames’ methods and are beginning to apply his test to the evaluation of new products while those products are still in their early stages of development...
...The development over the last few decades of the ever more radical cancer operation, the increasingly bmtal mutilation practiced by surgeons and agreed to by patients as well as their families-the legs removed with the hip joints still attached, the radical mastectomies, the total gastrectomies -all are grim evidence of this fact...
...For a quarter of a century the mechanisms that caused the exposed cells to become malignant remained unknown...
...Within a four-vear period of virtually constant wok he proved what industry today still refuses to acknowledge-that small, even infinitesimal exposure of normal cells to cancer-causing chemicals can cause malignant transformations...
...What from World War I had grown into an individual habit became with World War I1 a national institution...
...It is still there in the food we are eating...
...At the end of two days the number of bacterial colonies that grow in the vicinity of the spots of the chemical are counted...
...By knowing what causes malignant transformation we can stop cancer as surely as knowing the cause of polio stopped the production of iron lungs...
...Using benzopyrene, a very potent carcinogen distilled from cod tars, Berenblum began his experiments by rubbing the chemical into the skin of hundreds of animals...
...Bacteria are single-cell organisms...
...Carefully choosing his words, the expert finally gave what with all his preceding qualifications was at least a precise if somewhat limited definition: “Cancer is an autonomous growth of tissue, no more, no less...
...For these cells to defy treatments, never to revert back to normal, to continue to grow despite dosages of chemical poisons that could and did kill off the normal cells sitting right next to them, indicated that these cells are changed at their very core, and in an absolutely and profoundly fundamental way...
...If you take a hundred cells, grow them in tissue culture and expose the whole culture dish to X-rays or immerse it in what we know are carcinogenic compounds, you can, by increasing the dose of radiation or the concentration of carcinogenic material, kill every cell in the dish...
...He soon found that no matter what he did, it always took exactly the same amount of time for a cancer to develop once the promoter was applied, no matter how long after the tissue had been exposed to the critical, though still outwardly noncancerous, level of the carcinogen...
...The Ames test begins with the addition of small nontoxic amounts of the chemical under investigation to the special histidine-deficient broth...
...It was an elegantly simple experiment, but it was to indicate the difference between life and death...
...The Ames test system consists of a small covered laboratory dish filled with broth-growth medium seeded with millions of bacteria called Salmonella typhimurium...
...In a chemical code a billion years older than life itself, the arrangement of these bases directs like a master computer the way the cell’s proteins are made and how they are put together, what the cell wall will look like, what the cell does, what it produces, and how it divides...
...We know today, and it makes absolute biological sense, that it is the nucleoproteins, with their bases seemingly so safely for billions of years locked away inside the nucleus of cells, that carcinogens injure...
...Polyvinyl chloride causes those small vessel cells to turn malignant, producing a particularly deadly form of cancer called angiosarcoma...
...Since all DNA, whether it comes from a microorganism, a mouse or a man, is basically the same, a chemical that damaged the DNA in the nucleus of a bacterium would in all probability damage the DNA in man...
...Once cancerous, they never reverted back to normal...
...Like the mutated salmonella that can then grow in histidine-deficient broth, the genetically damaged human cell, its controls changed, short-circuited, or suppressed, takes off in a new direction...
...The opposite is also true-different kinds of malignancies can at times arise from the same exact tissue, each cancer, even though beginning from the same cell type, showing different biological properties...
...The discovery of the carcinogenic nature of asbestos fibers, like the discovery of the malignant properties of polyvinyl chloride, was too late for the workers already dead...
...The list grew and grew...
...Today we know that what produces malignancies are the same events that cause fetal toxicities and congenital defects-cellular damage...
...Ames has given us a test, a first step in making sure we are not exposed to carcinogenic substances...
...Malignant cells are relentless...
...We completely Copyright 0 by Ronald J. Glasser, M. D. From The Greatest Battle by Ronald J. Glasser, to be published this fall by Random House In c. replace all of our red blood cells every 120 days, all our circulating white cells every six hours, and yet no one would say that this massive cellular turnover is cancerous...
...Ames continued to add variations to his test to make the system more applicable to humans...
...If, as he realized along with other scientists, the majority of human cancers are caused directly or indirectly by “substances in the environment, what was needed was a quick, reliable, and inexpensive way of identifying the chemicals involved...
...leave just one cell and it is the same as not having removed any of the cancer at all...
...Berenblum realized he had really proved nothing with his increasing concentrations of benzopyrene that had not been known before...
...Cells once docile and obedient begin to divide, Unrestrained, they begin to multiply, continually making more of themselves, until their sheer numbers squeeze out the still normal cells around them, and take over the organ in which they first began...
...We tend to think of mutations in terms of the whole person, the albino or the dwarf, but the basis of all overt observable mutations is cellular...
...The real issue was whether even minute exposure to carcinogens changed the exposed cells intepally so that despite looking and acting outwardly qormal, they were really premalignant...
...For cells that won’t revert back to normal, that once turned fanatic stay fanatic, there can be no half measures and in most cases no measures at all...
...The idea that small, virtually minuscule amounts of a known carcinogen-not the constant heavy exposure once thought necessarycould, if coupled or followed by some kind of irritant, produce cancers, had far-reaching implications...
...T h e experimental study of cancer began in 1901, when the Japanese researchers K. Yamagiwa and K. Ichikawa finally proved that skin malignancies would result from the continuous application of coal-tar preparations to what previously had been normal skin...
...By the end of the 19th century pathologists were able, by looking at diseased tissues, to identify any number of malignancies by the type of cells that made them up-malignant melanomas, rhabdomyosarcomas, astrocytomas, adenocarcinomas, hepatomas...
...The chemical to be tested is spotted on the broth, and the dish incubated at 37 degrees centigrade...
...The use of bacteria was just a convenient hay of studying the effects of chemicals on genetic material...
...Primary and secondary conditions only added to the confusion...
...Nor, for that matter,” he went on, “are cancers restricted to just certain organs...
...The researchers’ greatest fear has already come true, and examples abound...
...The fact is that the hair-dye industry had already guessed wrong once about the dangers of their chemicals, I Yet hair dyes containing this chemical were still on the market as late as 1971...
...From Guadalcanal on, the exposure was massive and continual...
...They are all basically intracellular poisons...
...That is why there is virtually no hope of survival for those who have smokinginduced lung cancer or asbestosinduced mesotheliomas...
...m a t Ames felt comuelled to write about was not rates of Gacterial mutation, or the reproducibility of his results, but human cancer and birth defects...
...Like aflatoxin, PVC injures the liver...
...It was the sudden appearance of a rare type of cancer that alerted health officials to the dangers of PVC, polyvinyl chloride...
...No one then could have realized that the search for what caused these malignancies, the search that .would give meaning to the names they were just beginning to catalog, would take others down into the very heart of life itself, into chemistries almost too complicated to be dreamed of, into areas too small even to be seen...
...A stomach filling up with malignant cells leads to nausea and vomiting and then starvation before the malignant stomach cells spreading to other organs cause death...
...If a mutation-damage to the nuclear DNA-occurs to embryonic cells during fetal development, the results show up as fetal deaths or congenital defects...
...Yet when he rubbed the oil into the supposedly still healthy skin, it suddenly turned cancerous and the malignancies produced were indistinguishable from those produced in animals exposed only to high concentrations of benzopyrene...
...For some malignancies even the PO wer ful anti-cancer drugs have proved ineffective...
...For centuries putrefication, rather than underlying cancers, was conjured up as the cause of liver enlargement, while diseased arteries and veins were invoked for the tissue damage caused by infiltrating tumors or metastatic malignancies...
...At a recent New York Academy of Science workshop, Dr...
...they have been with us from the beginning...
...Then, having to move his rabbits to another research area, he decided to renumber the animals by punching little holes in their ears so that they could still be identified even if there were two or three to a cage...
...Cancers are no more inevitable than is cholera or smallpox...
...the bonemarrow cells that make all our blood cells grow very rapidly...
...These researchers know that minute exposures of cells to carcinogenic compounds can lead to cancer, and that because of the uniqueness of malignant diseases, the long time lags between exposure and the development of overt cancers-in humans as long as 25 to 30 years-a carcinogen, if distributed among the general population, might well doom hundreds of thousands, perhaps even millions of people before the harmful effects of the chemical became obvious enough to stop any further distribution...
...The dead would be our first warning, and the dying would continue for decades, until those last to be exposed would themselves finally be buried...
...If the malignant cells undergo transformation in a necessary organ like the brain or heart, the cancerous cells don’t even leave the organ to kill the patient...
...John Menkart of the Clairol Corporation in response to a letter Menkart had sent out under Clairol’s letterhead challenging not only Ames’ conclusions about the carcinogenicity of hairspray products but the validity of the test itself...
...It was only when the amount applied reached a certain high and seemingly critical level that the first cancers began to be produced...
...For example, thyroid cancers may still produce thyroid hormone, even though the cells making the hormone are obviously malignant...
...once transformed, the cells stayed that way...
...But the names meant nothing...
...H e su cceeded...
...The Ames test and others like it must be made as mandatory and routine a health procedure as is the testing of our food products for bacterial contaminants and our water supplies for purity...
...Under increasing challenge in the United States as a cancercausing agent, this same dye was recently cleared by the Food and Drug Administration for unlimited use in foodstuffs...
...Nerves invaded by malignant breast cells produce excruciating pain long before the patient dies of disseminated tumor...
...Once inside, they work their way or are carried to the nucleus...
...He repeated his experiments with other mice and found the same thing...
...He had great difficulty and began first with what it isn’t: “It is not simply the rapid growth of cells...
...Unlike the crude, lowpotency coal tar Rous had used, only a few applications of the concentrated benzopyrene were necessary to produce malignancies...
...Kidney stones found mixed in with kidney cancers were invoked as the cause for renal failure, while the blood and pus of meningitis often obscured small tumors of the brain...
...Others, too, have been concerned about the dangers of hair dyes but they, for whatever reasons, kept the dangers secret...
...Once past that critical point, the number of animals developing skin cancer increased as the concentration o f b enz op yrene increased, until at very high concentrations of the carcinogen virtually every one of the animals developed skin malignancies...
...In most cases,” he added quickly, “cancerous cells maintain some relationship to their tissue of origin, so that sometimes, even though mdignant, they possess the functional abilities of the parent cells...
...By this time, two new scientific words-initiator and promoter-had been coined...
...What happens to bacteria exposed to carcinogens is what happens to human cells...
Vol. 8 • October 1976 • No. 8
