Robert Joseph Huebner (February 23, 1914 – August 26, 1998), was an American physician and virologist whose research into viruses, their causes and treatment that led to his breakthrough insights into the connections between viruses and cancer, leading to new treatments, as well as his hypothesized oncogene, which was discovered to be a trigger for normal cells turning cancerous.

Early life and education

Huebner was born in Cheviot, Ohio, a western suburb of Cincinnati, on February 23, 1914.^[1] After attending a local parish elementary school, he attended Elder High School, graduating in 1932.^[2] He attended Xavier College (later Xavier University, where he majored in economics and English literature and took the prerequisites to attend law school.^[1] He decided he wanted to become a physician and did his premed undergraduate training at the University of Cincinnati.^[2] He attended the Saint Louis University School of Medicine starting in 1938.^[1] He was threatened with expulsion from the school after officials there discovered that he had taken outside work to pay for his education in violation of school policy — including a job as a bouncer at a brothel — but stayed in school and graduated in 1942.^[1] He graduated in June 1942, ranked in the top five of his class of 100.^[2]

After graduating, he joined the United States Public Health Service during World War II, and was assigned for a year to the United States Marine Hospital in Seattle, and then to the United States Coast Guard ship USS Hemlock in Alaska.^[1] The Public Health Service transferred him to a position as a researcher at the National Institutes of Health in July 1944.^[1]

Rickettsialpox

In June and July 1945, Huebner was asked to investigate an outbreak of cases of a spotted fever that struck more than 100 New York City residents, most of whom were residents of a single apartment complex in Kew Gardens, Queens.^[3] Local physicians hadn't initially reported the cases to authorities, as most presented with a rash and fever, but recovered within two weeks without any specific treatment.^[3] The New York City Department of Health was informed after a "minor epidemic" broke out at the Queens housing complex and individuals had been sent to hospitals with violent fevers and skin lesions.^[3] The seven known rickettsial diseases were all ruled out based on tests.^[3]

Visiting the complex with self-trained entomologist Charles Pomerantz, the two peeled back wallpaper to find the walls swarming with mites, so much so that tenants had described that "the walls had movement".^[2] Huebner's investigations on the site led to the conclusion that tenants had been bitten by a mite identified as Allodermanyssus sanguineus, found on mice that infested the storerooms and incinerator areas in the buildings. After culturing and isolating the organism in laboratory mice, the pathogen they named Rickettsia akari was identified as the ultimate cause of the disease now called rickettsialpox. The Department of Health announced a program to work with building owners to exterminate the mice that were the vector for the disease.^[3]

Huebner document his findings of the new disease in a 1947 paper published in the Journal of the American Medical Association.^[4] He was recognized by the American Society of Tropical Medicine for his efforts with the Bailey K. Ashford Award in 1949, which included a $1,000 prize from Eli Lilly and Company that he later used as a down payment for a farm in Frederick, Maryland.^[2]

Q Fever

Huebner's first work on Q Fever was a report he had done on an outbreak of 18 cases that occurred in early 1946 in an NIH laboratory, where he showed a correlation between a spike in cases and the preparation of antigens in yolk sacs, and he prepared another report on a group of 47 patients being treated for the condition at the Public Health Service Hospital in Baltimore. He was sent in spring 1947 to investigate an outbreak at milk farms in the Los Angeles area, in which there was a dense population of farms in which the animals had little space, creating what Huebner called "unpasturized cows".^[2] Huebner found the cause to be a member of the rickettsia family that was found in containers of unpasteurized milk.^[1] The cause was found to be Coxiella burnetii, with their findings published in 1948 in the American Journal of Public Health.^[2] Dairy farmers were upset by the insinuation that they were responsible for the outbreak and put pressure on local health officials to ask Huebner to leave the area.^[1]

Huebner found that the C. burnetii bacteria could survive temperatures of up to 60 °C (140 °F) in sealed containers for as long as 30 minutes, just below the levels used for vat pasteurization. This could mean that there was no way to verify that every particle within a vat was raised to the peak temperature and that pasteurization might not eliminate all of the bacteria in the milk being treated.^[5]

Adenovirus and oncogenes

While trying to grow common cold viruses, he and his colleague Dr. Wallace Rowe first tried to use adenoid and tonsil tissue, before using a culture based on tumor cells. From that culture they isolated cytomegalovirus, as well as the first of a large family of adenoviruses. Dr. Robert M. Chanock said the discovery "put him up there with [Dr. Albert Bruce Sabin (born 1906)]" (creator of the oral polio vaccine) as one of the "great moments in virology". Based on their observations, Huebner and Rowe hypothesized that these viruses could trigger an unknown gene that would cause cells to grow out of control.^[1]

In a paper published in the Proceedings of the National Academy of Sciences in 1969, Huebner advanced his theory that oncogenes, then only a hypothetical construct, could cause normal cells to mutate and become cancerous. A specific gene matching the theorized description was discovered and led to the development of treatments for cancer and other diseases.^[1]

In contrast to medical wisdom in the 1960s and 1970s, Huebner was confident that viruses were a cause of cancer in humans and convinced the United States Department of Health, Education and Welfare to provide $60 million in grants to fund research on the connection as part of the War on Cancer.^[1] This led to the discovery of the role that cytomegalovirus plays in opportunistic infections in patients with immunodeficiency.^[1] Research on retroviruses led to the development of a vaccine for hepatitis B, which has led to major decreases in rates of liver cancer, rates of some viral cancers, like that of the liver, have been sharply reduced.^[1]

He took a position in 1968 as chief of the National Cancer Institute's Laboratory of Viral Carcinogenesis, staying there until his retirement in 1982.^[1]

Awards and recognition

President of the United States Richard Nixon presented Huebner with the National Medal of Science at a White House dinner held on February 16, 1970, recognizing his "contributions to the modern understanding of the biology of viruses and their role in the induction of diverse diseases."^[6]

He was also inducted into and participated actively in the United States National Academy of Sciences. He also received the Rockefeller Public Service Award.^[1]

Personal

He bought a 300-acre (1.2 km²) farm for $4,000 in Frederick, Maryland where he raised his family, using the money he had received as part of an award for his rickettsial research to make the necessary downpayment. His children were each given the task of raising an Angus cattle bull to help pay for their college education. By the time of Huebner's death in 1998, the farm was operated by three of his children.^[1]

Huebner died at age 84 due to pneumonia on August 26, 1998, at the Veterans Administration Medical Center in Coatesville, Pennsylvania, where he had been a resident since 1991.^[1] He had been diagnosed with Alzheimer's disease in the early 1980s.^[1] He was survived by his second wife, Harriet, as well as by six daughters, two sons and 11 grandchildren.^[1] His first marriage had ended in divorce.^[1]

References

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• ^{a b c d e f g h i j k l m n o p q r s t} Noble, Holcomb B. "Robert Huebner, 84, Dies; Found Virus-Cancer Connections", The New York Times, September 5, 1998. Accessed July 23, 2009.

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• ^{a b c d e f g} Beeman, Edward A. "Robert J. Huebner, M.D.:A Virologist’s Odyssey", National Institutes of Health, 2005. Accessed July 23, 2009.

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• ^{a b c d e} Staff. "NEW FEVER TRACED TO MITE ON MICE; U.S. Health Service Roots Out Cause of Spotted Ailment That Struck in Queens NO CURE IS FOUND AS YET Victim Made Ill by Bite of Insect--Weinstein Urges War on Rodents Some Removed to Hospitals Blood of Patients Sampled", The New York Times, October 4, 1946. Accessed July 23, 2009.

• ^ MORRIS GREENBERG, M.D.; OTTAVIO PELLITTERI, M.D.; IRVING F. KLEIN, M.D.; ROBERT J. HUEBNER, M.D. "RICKETTSIALPOX—A NEWLY RECOGNIZED RICKETTSIAL DISEASE", Journal of the American Medical Association, 1947;133(13):901-906. Accessed July 23, 2009.

• ^ W.K. "NOTES ON SCIENCE; Aureomycin Is Effective Against Virus Pneumonia -- Acoustics", The New York Times, May 15, 1949. Accessed July 24, 2009.

• ^ "The President's National Medal of Science: Recipient Details - Robert J. Huebner", National Science Foundation. Accessed July 24, 2009.

'FOR half a century a small, persistent and intrepid brand of scientists insisted, often at the top of their decibel range, that cancer is caused by man's tiniest and most mysterious natural enemy: the virus. Very few scientists ever listened; if they did, they generally objected. How can a virus cause cancer when doctors don't seem to get it from their patients, or from research animals, or from tissue cultures?, the skeptics asked. Why do the old folks come down with cancer more frequently than the young? Why are there so many different agents‐1,000 chemicals alone at last count—capable of bringing about animal cancers in the laboratory? And why do Japanese males and New York Jews suffer more than other ethnic and cultural groups from cancer of the stomach, while the Chinese on Taiwan die more often from cancer of the nasopharynx?

Such thorny questions made life difficult for the virus theory proponents. But in the last few years number of leading scientists have recognized that a revolution in thinking may be brewing in their midst. Laboratory findings in molecular biology, biochemistry and immunology have begun to make scientific sense and have inspired a new wave of hope that mankind's No. 2 killer (No. is heart disease) may one day soon be effectively controlled. Meetings devoted to tumor‐producing viruses —how they work and behave—are being’ held with greater frequency than ever before and are drawing more distinguished investigators all the time.

In Bethesda, the National Cancer Institute, which controls the Government's cancer research budget, has doubled the allotment for virus research over what it was five years ago; in fact, this year's budget is twice the size of last year's, despite a general cut in research funding. The President's State of the Union message, which proposed an inspired, Apollo‐like effort to end the scourge of cancer, is likely to increase this budget even further. [Dr. Frank Joseph Rauscher II (born 1931)], who heads the institute's virus cancer task force, says that “the era of the seventies is the era of confrontation with the cancer mystery and will reveal more about the mechanism of cancer than any time since the inception of research.”

This extraordinary revival of interest in viruses can be laid in large measure to Dr. Robert J. Huebner, 57‐year‐old head of the institute's viral carcinogenesis branch, a recent winner of the National Science Medal and one of the nation's leading disease fighters. Huebner, marshaling the findings of the last few years, has formulated a theory of cancer that not only lays the disease at the door of the virus, but actually indicts a particular type of virus known to microscopists as the C particle.

Moreover, his theory diverges from those of other viral researchers on an even more critical point: he believes that the C particle is not an infectious virus that invades the body and generates disease, but a noninfectious virus that is a normal part of all living cells—and has somehow gone haywire. The Jekyll‐and‐Hyde behind diverse cancers in man—the C particle—turns out to be, in Huebner's opinion, none other than a form of RNA, one of the two main substances that govern heredity (although the particle, as we shall see, has a different function in the cell).

HUEBNER is an articulate man with the dominant air of one who has fathered nine children and with an Inspector Javert complex about getting his bug. He loves nothing more than to expound his ideas. “Let's be clear about one thing,” he says, “the cancer virus is definitely not the same kind of bug that causes such well‐known infections as measles, polio or the common cold. It isn't spread horizontally, that is, from person to person, or from an animal or a toilet seat. You don't catch it. The C particle, or rather the genetic material it carries, is something we all have in our bodies, and transmit vertically to our offspring, like a gene that gives you red hair or blue eyes. In fact, the cancer virus is itself a group of genes —one tiny package of inheritance units among the three‐quarters of million genes that make up the 46 corkscrew‐shaped chromosomes in the nucleus of the human cell.

“This doesn”t mean that the disease is inherited. What you do inherit is the specific group of genes that carry the potential of cancer, the oncogenes as they are known'What sets them off? That's the key question. One has to know something first about viruses and how they behave in living cells.”

Viruses are microscopic‐50,000 average‐sized ones can sit on the head of a pin—and come in a variety of shapes: some are spheres, others rods, still others come in groups of triangles. The basic composition, however, as Nobel laureate Wendell Stanley of the University of California first revealed in the nineteenthirties, is the same for all. A virus contains either deoxyribonucleic acid (DNA) molecules or ribonucleic acid (RNA) molecules, the chemical building blocks of all living things, held together by a coat of protein. Since this composition is virtually the same as that of the gene, it is not surprising that scientists have come to regard viruses as central to the study of genetics, indeed as the key to the secret of life.

They can be found anywhere, not only in the body but in the air, on the ground and in plants. According to one theory, viruses are really genes that escaped from cells. Several thousand of these “creatures” have been caught and examined in the electron microscope, and so far some 300 have been tied to disease in man and animal. In fact, a “good” virus is hard to find.

The virus exhibits the properties of a living system, but spends a good deal of its time in an inactive state. Unlike other somnolent biological units such as seeds or spores, it is not blessed with metabolic machinery; to grow and reproduce each virus must therefore latch onto host cell, with its built‐in chemical factory. Once inside the host, the virus suddenly makes up for its own deficiency by taking advantage of the cell's chemical apparatus and using it to make replicas of itself. The parasite subverts the host and reproduces at its expense, sometimes until the cell dies of exhaustion. The new viruses then stream out of the emasculated cell and invade a new cell, then another, spreading infection throughout the body—unless stopped by the body's own virus‐destroying antibodies or by a drug that prevents the virus from replicating in the host cell.

The cancer virus, the Huebner team's C particle, operates in a totally different manner. “It's been sitting quietly in the nucleus of the cell all the time, and suddenly takes command like a fifth columnist who feels the conditions are ripe,” Huebner explains. “Instead of reproducing itself, like the infectious virus does, the cancer virus programed to issue orders to the cell to grow and grow until it unhappily creates ugly cluster of cells known cancer, which invades other body structures and may cause death.”

In Huebner's thinking this virus is on hand, ironically, to serve a good purpose; it is a growth particle, perhaps one of the original growth commanders of the embryonic stage of life. “The particle really wants to go back to the good old times of its world—to grow more embryo, some arms, legs, eyes and other specialized products. In a way it wants to start again, to make the brother of the host cell. Unfortunately, in the prison of the complex, mature body structure, there is no longer an opportunity for such simplistic urges, and instead of a new and useful growth, the body grows a cancer. The particle, it seems, has the power to start us off, and the power to kill us.”

N its basics, this approach to cancer isn't altogether new, as Huebner will admit. Back in the nineteen‐forties Dr. Jacob Furth of Columbia, one of the pioneers of cancer research, performed an animal experiment which suggested that leukemia potential in mice was vertically transmitted from parent to offspring, and in the nineteenfifties Ludwik Gross of the Veterans Administration proclaimed the then outrageous idea of a latent cancer gene. In later years researchers who believed that cancer must have a genetic connection put the blame for the disease on defective chromosomes, defective genes and on certain mutations of the genetic material (or some combination of these factors).

Huebner's contribution, based on considerable new data, is the conclusion that the many different forms of cancer are all traceable to morbid change in the same virus, the noninfectious C particle. He thus came to call his conception the “unitary theory” because it purports to explain the origin of all cancers, whether they seem to arise spontaneously or are induced by carcinogenic factors in the environment, such as cigarette smoke.

“Excessive cigarette smoking, chemicals, radiation and old age are simply triggers that switch on the genome [the collection of genes that make up the virus],” he says. “So are a host of other environmental and hereditary factors that make the differences in cancers between one ethnic group and another — or among geographical areas. They're all contributory causes, not the real root of the trouble, which lies in the interaction of the C particle with the genes in the host cell.”

The hypothesis is a sweeping one, and not all members of the scientific community are convinced that Huebner has provided adequate proof. RNA virus particles have been found in animal cancers, but they are not easy to identify in the tumors of man.

Huebner himself has not isolated a C particle from a human cancer, but other observers claim to have seen it, especially in some cases of breast cancer. Observations from an electron microscope are open to some interpretation, however, and there is disagreement as to whether the observers truly saw what they professed to see.

Huebner shrugs off the entire argument by saying that it is not really necessary to observe the C particle in human tumors to know that it is there. For its existence is unmistakably indicated, he maintains, by the presence of a “chemical footprint” known as an antigen.

An antigen is any substance that inspires the release of antibodies which attack a particular virus. Most proteins are good antigens, and the protein coat of an infectious virus itself is often the body's best defense against illness. (Dead or weakened viruses are introduced into the body in vaccines to combat such diseases as polio and influenza.)

The presence of an antigen can be detected by various biochemical methods, and in the nineteen fifties Huebner discovered one in animal cancers induced by DNA viruses; he called it the T (or tumor) antigen and its discovery led to the understanding of this type of cancer. Several years later, he found the antigen of the RNA tumor virus, which he named the gs (or group specific) antigen. The presence of this gs antigen is evidence of the presence of the viral RNA.

“It's a little like the devil,” Huebner says about the particle, “you know it only by its works. Medicine doesn't always have laboratory proof of the cause of a disease, but we can move forward and deal with the disease without it.”

NONETHELESS, neither Huebner nor any of his colleagues has yet performed the definitive test so dear to the virologist's heart since the days of Robert Koch, the father of bacteriology: that would require isolating the virus from a human cancer, injecting it into man and animal, and consistently obtaining the same cancer. (Obviously human volunteers for such a test would be hard to find!)

In the absence of proof of this sort, Huebner's critics argue that it may well be other genetic mechanisms that produce cancer in the cell and not the morbid expression of the RNA particle he claims is the cause. Some scientists, for instance, hold firm to the mutation hypothesis—first enunciated in 1905 and still one of the most durable theories of cancer — which maintains that a chronic irritation causes in time a genetic change that may be transferred from one cell to its progeny. This means some genetic information must have been added to, or taken away from, the genes already there or some other modification must have occurred, creating a new situation in which the cell is dominated by instructions for producing cancer.

Huebner says the mutation hypothesis is losing support even from those who believed in it for years. He points to an interesting experiment in which an investigator replaced the nucleus of a frog's egg with the nucleus taken from a cancer cell in a frog's diseased kidney. The egg was fertilized. A healthy swimming stage larva emerged from the embryo, indicating that the cancer cell had all the necessary genetic information to cause the growth of a normal organism. Evidently the cancerous state had failed to take anything away or add anything to the nucleus.

Finally, a persistent argument against‐Huebner's theory stems from those experts, mainly pathologists, who insist that cancer is not a single disease but a family of diseases. If it's just a single disease—caused by one virus —why are there so many chemically different types of cancer and why do different chemicals act specifically against different tumors?

“That's a reasonable question,” Huebner replies, “but think the many faces of cancer have to do with the type of target cell in which the virus ‘turns on.’ The diversity of cancers should not dissuade one from believing in the common cause, especially at the molecular level. After all, we all sprang from one cell, which contained the information that made us all different.”

ALTHOUGH Huebner blames a vertical, noninfectious RNA virus for all cancers, work on ‘horizontally infectious viruses was important to the development of his theory. Back in 1911 Peyton Rous of the Rockefeller Institute ground up a tumor from a Plymouth Rock hen, dissolved it in a salt solution, filtered out the cancer cells and injected the resultant cell‐free “soup” into other chickens. To his intense fascination, they all developed tumors. Evidently the extract contained something that could transmit the highly malignant tumor from one hen to another.

Rous's findings, when first published, made little impact'Everyone said it was fine for the birds, but had no relevance to man. When studies of cancers in other species yielded no virus, the cancer‐virus infection theory fell into disrepute — the same kind of ignominy with which established medicine greeted the microbe theory of disease when it was first proposed. Rous himself, somewhat discouraged, turned to other fields of research. Interestingly, 55 years after Rous had made his discovery, the world of science took a second look at this feat and awarded him the Nobel Prize for Medicine.

During that half ‐ century, evidence of virus‐caused cancer slowly trickled in. The big breakthrough occurred in the nineteen‐fifties when Ludwik Gross, an Army surgeon attached to the Bronx Veterans Administration Hospital, showed by a brilliant series of experiments that leukemia, a cancer of the blood, could be transmitted in mice though only in the newborn.

Gross worked with two inbred strains of mice: the AKR strain, which shows a high incidence of inherited leukemia, and the C3H strain, which does not incur the disease naturally. He injected the leukemia fluid from the AKR mice into the low‐leukemia C3H strain and found that the latter developed the disease; in fact, the strain developed not only leukemia but a variety of other cancers. Gross was able to identify the killer virus, which is now known as the marine leukemia virus. A few years later researchers were able to see it in the electron microscope and over the years they found similar viruses in other species including — though this is in dispute—in man.

At first, Gross's monumental work was treated with the same skeptical disdain accorded early virus research. Denied working space on one occasion, he had to set up his laboratory in an unused military latrine. Nevertheless, his findings on oncogenic viruses stimulated a wave of research.

At the National Institutes of Health, for instance, Drs. Sarah Stewart and Bernice Eddy tried to duplicate Gross's experiment and found in the leukemic fluid a new virus which produced a group of cancers in newborn animals. So many cancers appeared in fact (23 in all) that the virus was christened polyoma (many tumors). More surprising, when injected into other species, such as hamsters, rats and rabbits,‐ this tiny spherical particle always yielded a display of tumorsThe virus, the first discovered which crosses species boundaries, proved to be made of DNA.

THE discovery of the polyoma virus created a good deal of excitement; it meant that a single virus might be the agent in a disease that has many forms. Huebner entered the search at ‘this point, asking himself whether the polyoma could also be found in animals in their natural state and could therefore be associated with naturally occurring cancer.

He had behind him a record of having tracked down the elusive Q fever and other mysterious diseases. To find the polyoma virus, he began hunting in the places where mice were most likely to gather—crowded urban areas. In Harlem, he trapped 450 mice on the top floor of one tenement and discovered that half of them carried the virus, but no virus was found in the human beings who lived there.

He also wondered whether the Harlem mouse's wild country cousin contracted polyoma. As the owner of a, cattle farm in Maryland where he raises prize Angus bulls, he had no trouble finding natural breeding places of mice in his own hay sheds and nearby granaries. Huebner soon found that polyoma was as widespread in the country as in the city.

Even in his travels Huebner couldn't get away from mice with polyoma. He remembers seeing a field mouse scurrying out of sight in the vicinity of Disneyland, a rather fitting place for a mouse. Huebner promptly climbed a small fence, traced the mouse to its lair and later determined that it was carrying the virnst.

Out of these forays Huebner discovered an important, fact while the polyoma virus is present in a good many of the wild mice, the animals were singularly free of cancer. This was also true of other DNA viruses, such as the adenoviruses found in throat and adenoids of man and animals, which do not produce cancers in their natural hosts.

It seemed that these infectious DNA viruses could produce tumors in newborn laboratory rodents by injection, but did not do so when harbored by wild mice, probably, Huebner thought, be cause they entered the mouse's body later in life after some immunological and other defenses had been thrown up.

How about the other great class of viruses, the hundred or so RNA's beginning with the chicken virus—the first C particle—discovered by Peyton Rous? Here Huebner and his colleagues hit pay dirt; RNA viruses, mainly C particles, were found in large numbers of animals with naturally occurring cancer. The scientists found them in thickens, mice and cats with tumors, though they found not the virus itself but the specific antigen of the virus. The big question was: Is the virus a harmless resident in the cell or an assassin in disguise?

TO answer this question huebner had to know more about the care and feeding of the C particle. In the next few months he and his team

“‘Let's be clear about one thing,’ says Huebner. ‘The cancer virus is definitely not the same kind of bug that causes such wellknown infections as measles polio or the common cold.” hunted down antigens of the C particle in virtually every vertebrate that could be trapped and hauled into the laboratory. The particle proved to be amazingly ubiquitous. Investigators found it in rats, swine, guinea pigs, monkeys, hamsters and, to show the evolutionary continuity, in snakes. Wherever there were malignant tumors, there was evidence of C particles.

Cats were discovered to be a particularly good laboratory subject for the study of C particles. Huebner and others found that the feline leukemia virus, present in 75 per cent of cats, crosses species barriers and grows well in dog, monkey and human tissue. In fact, this finding led to a rash of public worry over catching cancer from cats. To avoid panic, Huebner and his aides, [Dr. Murray Briggs Gardner (born 1945)] and Bernard Hanes of the University of Southern California, conducted a survey in the Los Angeles area last year and established, happily, “There is no statistically significant difference in cancer incidence in the number of households with pets … and since 70 to 80 per cent of the cancer case households denied any cat ownership, it is unlikely that cats would be a causal factor in the generality of human cancer.”

Early last year several investigators created a flurry of excitement when they claimed to have seen a C particle in human cancer tissue (it looks like a miniature Chinese fortune cookie). Huebner, however, wasn't sure, though he admits he would feel like Balboa sighting the Pacific if he could identify the particle for certain. “Actually,” he says, “it wasn't that important. By this time a lot of lines of evidence from laboratories were fusing, and I became convinced that the RNA viruses are not harmless but are behind most cancers in man and animal.”

One of the major pieces of experimental evidence had been gathered the previous year when Huebner's associates, George Todaro and Stuart Aaronson, attempted to prove a closer connection between the onset of old age — especially the so ‐ called “cancer years” (beginning, by most estimates, after 50)—and an increase in the pro duction of C‐type virus.

One of the striking facts of life is that no cell lives forever. Every normal cell is exquisitely timed from birth to live its assigned lifetime and then die. Only cancer cells seem to seek immortality.

Todaro and Aaronson grew embryonic mouse cells in a test tube until they reached the age that biologists agree amounts to dotage in tissue culture. What happened was that a number of the cells when they passed the grim boundary line of old age became cancerous — at which point most of them were starting to make the antigen of the C particle. Evidently the assembly of viral genes must have been in the cells before birth, to be released as C particles at the proper moment and with the proper trigger—in this case, some change that accompanies old age.

Numerous experiments in Huebner's own shop and elsewhere have tested cancer “triggers” other than old age. Typically, normal animal cells with and without active RNA virus have both been subjected to radiation, or have been chemically treated with known carcinogens. In one such experiment, the carcinogen produced tumor cells in a colony with RNA virus relatively quickly and in great number. A similar assault on the irusfree cells didn't transform them into cancer at all, strongly suggesting that the virus was the key factor in the cancer.

HUEBNER found another striking thing: he turned up antigens of C particles in all embryos. Perhaps nature had built the C particle into each cell for a good purpose—to produce the fast growth needed by the embryo for maturing. If the particle is associated with rapid growth, he theorized, then tissues that grow fast and thus have the highest turnover of cells should have more antigens than more slowly growing tissue. And so it proved to be. Huebner found, for instance, that the fast growing inside lining of the intestinal tract shows more footprints of the C particle than other tissues do, and indeed it shows even more antigen than can be found in most tumors. This is also true of the inside of the uterus and of the ovaries.

But some questions remained. If the cancer potential is already in the cell in the form of an RNA virus, how does one account for the transmission of cancer by the injection of the Rous sarcoma virus? Huebner worried over this for some time, but now gives this explanation:

“Rous dealt with young birds, and he forced in large amounts of the infectious virus which contained genetic information to change normal cells into cancer cells. We've shown that many chickens with C particles, unless killed by some other means, are likely to get cancer later in life, so it seems that Rous's injection of virus simply provided the disease‐causing level more quickly.”

There were even more intricate puzzlers: What, for example, causes the C particle, or indeed any other oncogenic virus, to make the cancer? And how does it actually go about its dirty work?

During the last decade, molecular biologists have successfully probed the mechanisms of the normal cell. They have shown how the DNA in the nucleus lays down chemical “orders” which are carried out by the RNA in the cytoplasm, directing it to build the living structure according to genetic plan.

At the Salk Institute in La Jolla, Renato Dulbecco has shown that a DNA virus particle can somehow incorporate itself into the genetic blueprint for a cell and cause it to behave abnormally. What happens, according to Dulbecco, is that the viral genes take up positions along the double helix of the blueprint, thus changing the genetic information passed on to the cell. (The double helix, of course, is the DNA that is known to be present in the cell; the virus particle is another form of DNA which either invades the cell or is also normally present —it is not yet clear which.)

Little was known of how the RNA virus subverts the healthy cells until last year, when Dr. Howard Temin of the University of Wisconsin and, independently, Dr. David Baltimore of the Massachusetts Institute of Technology, came up with some startling evidence. Temin and Baltimore discovered that the RNA of the virus can also replace the double helix and, by so doing reverse the transcription of information that guides the normal cell process. Here, the RNA is in charge, and, in a kind of man ‐ creates ‐ God operation, gives orders to make DNA which, in turn, creates replicas of itself. How this transfer of information goes on to cancer is still not known, but Temin's findings do indicate that the complexity of the mechanism is at last yielding to research.

HUEBNER is firm in his belief that the answer to the disease ultimately lies in somehow muzzling the viral cancer genes and forcing them to remain “silent” in the cell (until, he says, “the individual dies of something else”). This is not so fantastic as it sounds. As a result of recent work in molecular biology by Nobelists F. Jacob and J. Monod of France, each growthcontrolling gene in the cell is now known to be regulated by another gene that sits atop it and represses further cell division after the organ reaches its inherited shape and size. The tumor occurs when this “policeman” fails to do his duty, leaving the growth genes free to create the anarchy of cancer.

What Huebner envisions is that a substance can be found which will restore the repressor to its original position of control in the cell. At present he and several teams across the country are trying to find the specific natural repressor for the cancer genes of the C particle in a number of species.

Already, several virus scientists are reporting some extraordinary results in reversing malignancy in tissue culture, although they are not working directly with C particles. At Berkeley, for instance, G. S. Martin, in the famous virus laboratory of Wendell Stanley, experimented with a mutant of the Rous virus and found that he could turn a cell induced to grow abnormally by a virus into normal‐growing cell — and back again—by merely altering the temperature of the cell's environment a few degrees. At Princeton, in what may be a landmark experiment, Max Burger and Kenneth Noonan covered certain cancer cells with a plant protein called Conconavalin A and found that they suddenly grew like normal cells. He then removed the protein cover and the cancer growth took, off again!

In C particle investigations there have been similar promising findings. A team of scientists from the Cancer Institute and the Pasteur Institute in Paris isolated a chemical inhibitor from various types of mouse and rat tissue carrying cancer virus. They injected the material, along with cancer‐producing C‐type virus, into a colony of mice and found they developed fewer tumors than mice which were given the virus but not the inhibitor.

These and other experiments make Huebner and his colleagues more optimistic than they have been in a long time.

“I think the public will soon be able to cash the promissory note it has been holding for years from scientists working on a cancer cure,” Huebner says, adding reflectively: “You know, a few years ago that would have been enough to contemplate as a great end in itself, but now the skeptics question all values, and even ask whether it would be wise to have a cancer‐free society in view of the population explosion am old‐fashioned enough to believe that curing a disease that kills 250,000 Americans a year is a great plus for civilization — and that utopia will not be reached all at once, but step by step.”

Dr. Robert J. Huebner, whose genius as a medical detective in pursuit of viruses and other agents of disease became a major force in the battle against cancer, died on Aug. 26 at the Veterans Administration Medical Center in Coatesville, Pa. He was 84.

Dr. Huebner, who had suffered from Alzheimer's disease for 16 years and had lived at the center since 1991, died of pneumonia, medical authorities said.

Working with a colleague, Dr. Huebner correctly hypothesized that a gene he named the oncogene was implicated in the cause of cancer and focused science to look for and eventually find it. His discoveries and the oncogene theories he put forth in his years as chief of the Laboratory of Infectious Diseases at the National Institutes of Health in Bethesda, Md., led to the development of vaccines and treatments for a variety of widespread and deadly illnesses.

Among his major accomplishments were the discovery of viruses responsible for serious respiratory illnesses in children and the identification of the notorious cytomegaloviruses, which cause opportunistic infections in AIDS patients. Dr. Huebner (pronounced HYOOB-ner) is credited with galvanizing medical science in the late 1960's and 1970's into action on cancer and predicting, contrary to the medical wisdom of the day, that viruses would be linked to certain cancers in humans. He persuaded the old Department of Health, Education and Welfare, now Health and Human Services, to provide $60 million for cancer studies, and young scientists all over the country joined the crusade to conquer the disease.

''When I was growing up on the farm,'' he told a Life interviewer in 1965, ''I saw that land erosion was the result of little individual drops of rain, all adding up finally to a gully. Human erosion isn't a simple thing; it's the result of the interplay of many factors, many raindrops, but I strongly suspect that among them are the virus agents.''

[Dr. Murray Briggs Gardner (born 1945)], a virologist at the University of California at Davis, said Dr. Huebner ''was just what we needed to get people moving, a visionary who foresaw the importance of viruses, in particular retroviruses.''

Retroviruses, little sacs of genetic material, put out a kind of reverse code or defective blueprint causing cell overgrowth. Dr. Huebner put together a team of scientists to study them, Dr. Gardner said. ''And within 15 years it paid off,'' he said.

By then the existence of the oncogene was confirmed by others and it was clear that vaccines could be developed to prevent tumors. As a result of such vaccines, including one for hepatitis B, rates of some viral cancers, like that of the liver, have been sharply reduced.

Dr. Vincent T. DeVita, director of the Yale Cancer Center and former director of the National Cancer Institute, said, ''The guy was brilliant and unconventional -- he opened up the whole field of cancer viruses, looking at them in ways people had not looked at before.''

Robert Joseph Huebner, the first of nine children of Joseph and Philomena Brickner Huebner, was born on Feb. 23, 1914, in Cheviot, Ohio. He began premedical studies at Xavier College in 1937, finished them at the University of Cincinnati and enrolled in 1938 in the St. Louis University School of Medicine.

Lacking money, he was forced to violate a prohibition against outside jobs and was threatened with expulsion. The threat was not carried out, and he was permitted to graduate in 1942, when he joined the United States Public Health Service and went to sea in World War II as a medical officer aboard a Coast Guard vessel in Alaska. He returned in 1944 to join the National Institutes of Health as a researcher, still with the Public Health Service.

Shortly after V-J Day, he was the only Public Health Service officer on duty in his institute (senior officers were taking their first extended breaks in four years) when he received a call from New York City authorities puzzled by a disease among residents of crowded apartments in the Kew Gardens section of Queens. Victims had violent, body-racking fevers and skin lesions.

The cause could not be determined, but the disease had already killed an 11-year-old boy. A local exterminator, Charles Pomerantz, led Dr. Huebner to an apartment where the wallpaper appeared to be moving before their eyes, set in motion by billions of mites crawling around inside the walls. That led to the discovery of the first known case of rickettsialpox, a variety of the diseases caused by rickettsia, which are tiny microorganisms that in this case were spread by those billions of mites. The mites, infected with the previously unknown variety of rickettsia, were inadvertently brought to the United States in the luggage of Russian immigrants.

Once the findings were confirmed, Dr. Huebner called his new friend, the exterminator. ''Well, Charlie,'' Dr. Huebner said. ''We've made it! Bravo!''

''I was stricken dumb,'' Mr. Pomerantz told The New Yorker shortly afterward. ''That we included me.''

On the strength of that work, Dr. Huebner was sent to California on a new case, the mystery of Q-fever, which normally strikes cows but had apparently spread to people. Dr. Huebner found the villains hiding out in vats of unpasteurized milk. Again they were members of the rickettsia family, rare pathogens smaller than bacteria and larger than viruses. Once the cause was found, the outbreak ended. But laying blame on dairy farmers angered them, and they pressured state health authorities, who politely invited Dr. Huebner to leave California.

In 1953, Dr. Huebner was working with a health-service colleague, Dr. Wallace Rowe, to grow common cold viruses in cultures of human adenoid and tonsil tissue.

They tried to inoculate the cultures with nasal secretions from people with colds, but before they could the cultures began to fall apart. They took what remained and injected it into a new, more stable culture, one made of human tumor cells. There they first detected a virus later called the adenovirus. Since then, 47 varieties of the virus have been discovered and linked to human diseases, including acute respiratory illnesses. They also found in the culture the human cytomegalovirus, since identified as a great hazard for organ transplant recipients and people with AIDS.

''There were great moments in virology,'' said Dr. Robert M. Chanock, Dr. Huebner's successor at the Laboratory of Infectious Diseases, who added that the body of Dr. Huebner's work ''put him up there with Sabin.'' It was Albert B. Sabin who developed the oral polio vaccine in the 1950's.

Dr. Huebner and Dr. Rowe concluded that the viruses could trigger dangerous cell overgrowth -- that they could conspire with a specific but ordinary gene to interact and produce cancer. In 1969, Dr. Huebner proposed his oncogene hypothesis in the journal Proceedings of the National Academy of Sciences. He later updated and refined the theory, stating that a specific and normal human gene may mutate and cause cancer.

A gruff, warm hulk of a man, he and his wife Berdine and their nine children lived in Frederick, Md., on a 300-acre farm he had bought for $4,000. The farm had outdoor plumbing, but Dr. Huebner's Government salary as a laboratory director, he told colleagues, did not permit him to house his large family in affluent Washington suburbs like Bethesda.

To supplement their income, he and the children began raising Aberdeen Angus cattle and breeding the stock, with each child raising a bull to help pay for college.

The farm is currently run by three of his children.

In 1968 Dr. Huebner left the Laboratory of Infectious Diseases to become chief of the Laboratory of Viral Carcinogenesis of the National Cancer Institute, where he remained until 1982, when he retired.

He received the Presidential National Medal of Science, one of medicine's highest honors, and the Rockefeller Public Service Award, and he was a longtime member of the National Academy of Science.

His marriage to Bernine, who died seven years ago, ended in divorce.

He is survived by his second wife, Harriet, of Rockville, whom he married in 1974; eight children, F. Kay Huebner of Philadelphia, Elizabeth J. Pfeiffer of Great Falls, Va., Geraldine A. Wyman of Santa Cruz, Calif., R. James Huebner of Sanford, Fla., and Virginia R. Huebner, R. Sue Creamer, Mary Louise Barnard and R. Daniel Huebner, all of Frederick; 11 grandchildren; 3 brothers, and 4 sisters.