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>aEWSREK Apri1.22, 1963 'The Niles Cluster' Smallpox, yellow fever, polio• mumps, fld, me~:!r•s-one by one, a host of in- fecrrous diseases have been proved to be raused by vinrses. At a seminar in Lu Joila, C:odif., last week, some of the nateon's top virologists heard the most imprrssive r~•idenee so far that vinrses may be responsible for the most feared d:sense of all-cancer. The evidence, which does not rule out other possible causes of cancer such as heradiq- or environmental factors, was Freseutrd in the form of a report on what h:s become know•rr among cancer e.perts as "The Ndes Cluster." The tosvu of Niles, llbnois, is an or- dm;:n, middle-class suburb of Chicago with a population of around 25,000. But in March 1961, the U.S. Public Health Sendce's Communicable Disease Center in Atlanta, •v!rlch routinely keeps track of infectious disease outbreaks reported throughout the country, received an ex• traordinary report. four Niles children had died within the space of three months of acute leukemia, an incurable Lype af cancer that floods the blood- st-aam with abnormal white cells. Aiore• over, nther voungsters had come down witl: 3eukemia in recent years, all within the same 2-square•mila neighborhood. Dr. Clark Heath Jr. of the CDC's Epidemic Intr lligence Service was quicki% otderer; to Niles. lnten•iewinf, parents, family physi• cians, and lo,:al health officials, Heath learned that eight Niles youngsters, 3 to 14 years old, had developed leu• kemia since 1957. These cases gave NJe: an annual leukemia rate five times higher than the national average. Familiar Partprnr Heath also noted "a concentration of cases among families usinF a particular school, and a periodic pattern of onset." Seven of the children either were going to St. John Breberd, a parochial school, or had older brothers or sisters at the school. And the disease cropped up in two distinct periods- three cases between the fall of 1957 and spring of 195b, and five between winter 1959 and summer 1900. All this suggested to the CDC invesli- gator (and to a team from Cook County Hospital in Chicago) a familiar pattern; the lerrkemur was acting like an infee• tioes disease. Niles seemed to be in• c:.ded by a °cancer virus " E,:t on the cthrr hM.i HP,th found that none of lhe• stricken children came trom the same famdc, nor, in foct, were the youngsters or their families even acquainted. As the summer wnre on, hawevcr• Heath came upon two more flndrr.gs suggesting that the Niles leuke- min cases were infectious in origin. First he leamed thut the two leukemia emp- tious rMCurred at about the same time as MEDICINE two outbreaks of rheumatic fever•like ill- ness. Second, a survey of death certifi- cates for the same period revealed an abnormal number of Nile~ youngsters had died with congenital heart defects. What could be the connection be- tween leukemia, the rlreumatic•like illne5ses, and malformed hearts? Sum- marizing his report on the case at the American Cancer Society seminar in La Jolla, He.rth pointed out that the paral• lel outbreak of rheumatic-like disease suggests that both it and acute child• hood leukemia may be a sequel to a milder infection going the rounds, just as acute rheumatic fever itself may fol• low a strep throat. As for the heart de• fcrts, he added, the% "crommonly occur in infants whose mothers n,tch Cerm•m measles [rubella] in early pregnancy:" Tying all this together, conceivably the rubella virus might lie dormant in a child infected before birth, only to awaken years later to produce leukemia, or to activate a leukemia virus. Stealth,r Nolrr Nor does the ab- sence of direct contact between the Niles victims rule out the possibility that viruses play a stealthy role in the dis• ease, Heath noted. The polio virus, for example, infects many people, but rela- tively few actually become sick or para• lyzed. Similarly, some scientists believe, leukemia could be caused by a'tiveak" virus, infecting many children, but trig• gering malignancy in only a few. Further evidence that a virus may have been at work in the Niles leukemia cluster is offered by the Cook County Hospital team of Dr. Steven Schwartt. Several years ago, Schwartz reported that volunteers inoculated with extracts from the tissues of leukemia patients produce antibodies• as they would after a polio shot, and he concluded that the injected tissues contained viruses. Re- cently, he tested blood samples taken from relatives of the Niles leukemia vic• tims "A certain number of the somples•" Heath The rirrimrlmd sornething in rommon H TflJ034U11 Schwartz told NEwswr.etr, "rontaured antibodies to leukemic extracts." The interest of some cancer experts who heard Heath's report was tempered with caution. "Until more cluster out- breaks are studied in detail," said Dr. Sidney Farber, research director of Bos- ton's Children's Cancer Research Foun- dation, "I prefer to think of the Niles case simply as an unusual occurrence that deserves special note." And the experts were careful to emphasize that. the question of infection aside, there is no concrete evidence that leukemia is "catching," the way a cold Is. Already, however, epidemiologists at the Com- municable Disease Center and the Na- tional Cancer institute are Investigating other reported leukemia drrsters. Had the Niles incident occurred a Adr•no.•irus 12 A garden rvrrirh• rarned ranter

decade ago, it might well have been overlooked. Its significance today is largely attributable to the surge of re- search interest in viruses as a cause of cancer, which started with Dr. Wendell M. Stanley's pronouncement in 1956 that "the time has come when we should assume that viruses are responsible for most, if not all, kinds of cancer, includ- ing cancer In man " The Nobel Piize winner's assertion, of course, was grounded on solid evidence of the role viruses play in some animal cancers. At least three kinds of leukemia in mice can be vjrus•induced, as well as one type of breast tumor. Working with hu- man blood samples under an electron microscope, investigators have found particles in leukemic cells that are indis- tinguishable from the mouse leukemia vinrses. But no one has yet seen a virus from a solid human cancer. Neo- ApproaeHr Searching for the viruses that may be at work in human malignancy, Prof. John J. Trenttn of Houston's Baylor University College of Medicine is using a new approach. In- stead of looking for airoses in human caneer cells, he is looking for human viruses that cause cancer. The Texas re- searcher has taken various types of adenovirus-many of which cause re- ap vatory• infections in man-and inlerted them, one by one, into baby hamsters and mice. Two types, adenoviruses 12 and 18, produced highly lethal tumors in the test animals, he reported last week. Both types, he noted, infect hu- mans (nearly half of the persons tested have antibodies to adenovirus 12), but they do not actually produce ill- ness. "No one knows whether they cause human cancer;" Trentin added, "but we should test all the garden- varietv viruses we can." When invesligating the role of vinrses In cancer, scientists are constantly amazed by ;he cunning and versatility of their prey. Bacteria, which harm the Hi®0034072 body by creating in9ammation or by secreting poisons, are clumsy by coar- parison to vinises. Because they per- form their subtle mischief within the cell, virus behavior is as complex-and mysterious-as the process of life. In- deed, a virus is only a submicroscopic speck of nucleic acid-the same sub- stance that makes up the eell's genetic material, delertoines its characteristics, and controls the production of enzymes, hormones, and other essential proteins. chemlcst Naehlnerva Once inside the cell, the virus may take over its host's chemical machinery in many ways. It may destroy the cell outright, after forcing it to produce more vinues, in- stead nf normal proteins. Or it may, as Dr. Jonas Salk, famous developer of the killed-virus polio vaccine explained, "cause malignant cell changes." We should, Salk says, think of viruses a.' "infectiors molecules," chemicals on the threshold of Bfe. External factors may also have an im- portant bearing on the ability of cancer viruses to spread infectimr. Dr. Harry Rubin of the University of California reported at the seminar the Rous sar- coma virus, which infects chickens, can cause the growth of malignant cells but cannot fome the cells to produce other Rous viruses without the help of another viral agent. The "helper" virus, which causes a form of leukemia in chicken 9ocks, helps the Rous virus acquire the protein covering it needs to become a complete infectious particle. "It is no longer suf6cient to think of a virus in terms of simple infection and multipBcation," concluded Nobelist Stan- ley. Thus, as the relationahip between viruses and cancer becomes clearer, the picture of viruses themselves grows more complea. Stanley ARumP N+at rdrnu3 are reifronaible