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.
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]
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]
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]
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 Sabin" (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]
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]
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 American Angus 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]
Q fever or query fever is a disease caused by infection with Coxiella burnetii, a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including cats and dogs. The infection results from inhalation of a spore-like small-cell variant, and from contact with the milk, urine, feces, vaginal mucus, or semen of infected animals. Rarely, the disease is tick-borne. The incubation period can range from 9 to 40 days. Humans are vulnerable to Q fever, and infection can result from even a few organisms. The bacterium is an obligate intracellular pathogenic parasite.
Rickettsia is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci, bacilli, or threads. The genus was named after Howard Taylor Ricketts in honor of his pioneering work on tick-borne spotted fever.
Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally made up of small spots of bleeding and starts on the wrists and ankles. Other symptoms may include muscle pains and vomiting. Long-term complications following recovery may include hearing loss or loss of part of an arm or leg.
Rickettsia rickettsii is a Gram-negative, intracellular, cocco-bacillus bacterium that was first discovered in 1902. Having a reduced genome, the bacterium harvests nutrients from its host cell to carry out respiration, making it an organo-heterotroph. Maintenance of its genome is carried out through vertical gene transfer where specialization of the bacterium allows it to shuttle host sugars directly into its TCA cycle.
Coxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever. The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C. burnetii is a small Gram-negative, coccobacillary bacterium that is highly resistant to environmental stresses such as high temperature, osmotic pressure, and ultraviolet light. These characteristics are attributed to a small cell variant form of the organism that is part of a biphasic developmental cycle, including a more metabolically and replicatively active large cell variant form. It can survive standard disinfectants, and is resistant to many other environmental changes like those presented in the phagolysosome.
Herald Rea Cox (1907–1986) was an American bacteriologist. The bacterial family Coxiellaceae and the genus Coxiella, which include the organism that causes Q fever, are named after him.
Rickettsialpox is a mite-borne infectious illness caused by bacteria of the genus Rickettsia. Physician Robert Huebner and self-trained entomologist Charles Pomerantz played major roles in identifying the cause of the disease after an outbreak in 1946 in a New York City apartment complex, documented in "The Alerting of Mr. Pomerantz," an article by medical writer Berton Roueché.
Sir Michael George Parke Stoker was a British physician and medical researcher in virology.
Orientia tsutsugamushi is a mite-borne bacterium belonging to the family Rickettsiaceae and is responsible for a disease called scrub typhus in humans. It is a natural and an obligate intracellular parasite of mites belonging to the family Trombiculidae. With a genome of only 2.0–2.7 Mb, it has the most repeated DNA sequences among bacterial genomes sequenced so far. The disease, scrub typhus, occurs when infected mite larvae accidentally bite humans. This infection can prove fatal if prompt doxycycline therapy is not started.
Rickettsia akari is a species of Rickettsia which causes rickettsialpox.
Rickettsia typhi is a small, aerobic, obligate intracellular, rod shaped gram negative bacterium. It belongs to the typhus group of the Rickettsia genus, along with R. prowazekii. R. typhi has an uncertain history, as it may have long gone shadowed by epidemic typhus. This bacterium is recognized as a biocontainment level 2/3 organism. R. typhi is a flea-borne disease that is best known to be the causative agent for the disease murine typhus, which is an endemic typhus in humans that is distributed worldwide. As with all rickettsial organisms, R. typhi is a zoonotic agent that causes the disease murine typhus, displaying non-specific mild symptoms of fevers, headaches, pains and rashes. There are two cycles of R. typhi transmission from animal reservoirs containing R. typhi to humans: a classic rat-flea-rat cycle that is most well studied and common, and a secondary periodomestic cycle that could involve cats, dogs, opossums, sheep, and their fleas.
Charles Pomerantz was a pest control expert and self-trained entomologist who played a pivotal role in identifying the etiology of a 1946 outbreak in New York City of what was later named rickettsialpox. In subsequent years, he spoke before audiences at colleges and other public forums about the menace from pests.
African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick. Symptoms may include fever, headache, muscle pain, and a rash. At the site of the bite there is typically a red skin sore with a dark center. The onset of symptoms usually occurs 4–10 days after the bite. Complications are rare but may include joint inflammation. Some people do not develop symptoms.
Rickettsia felis is a species of bacterium, the pathogen that causes cat-flea typhus in humans, also known as flea-borne spotted fever. Rickettsia felis also is regarded as the causative organism of many cases of illnesses generally classed as fevers of unknown origin in humans in Africa.
Barrie Patrick Marmion was an English microbiologist who spent the majority of his career in Australia. He is known for his work on Q fever, and led the team that developed the first vaccine against the bacteria that causes it.
Winston Harvey Price was an American scientist and professor of epidemiology with a special interest in infectious diseases, who made media headlines in 1957, when he reported details of a vaccine for the common cold after isolating the first rhinovirus. He was acknowledged by the director of the Public Health Research Institute at the time. However, other specialists in the field of vaccine research have disputed his methods and data.
Wallace Prescott Rowe was an American virologist, known for his research on retroviruses and oncoviruses and as a co-discoverer of adenoviruses.
Paul Fiset was a Canadian-American microbiologist and virologist. His research helped to develop one of the first successful Q fever vaccines, noted by The New York Times. Fiset was born in Quebec, Canada, and attended Laval University, where he earned a Doctor of Medicine degree in 1949. He subsequently attended Cambridge University, where he received a PhD degree in 1956. As a professor at the University of Maryland School of Medicine, he also researched other bacterial diseases such as typhus and Rocky Mountain spotted fever, in addition to Q fever.
Edwin Herman Lennette was an American physician, virologist, and pioneer of diagnostic virology.
Janet W. Hartley is an American virologist who worked at the National Institute of Allergy and Infectious Diseases (NIAID). A Washingtonian, she received degrees in bacteriology and virology research before graduating with a Ph.D. and joining the National Institutes of Health lab of Bob Huebner. Later becoming section head for the virology department, she would spend the next four decades researching a variety of viruses, discovering numerous species, and identifying new methods for quantifying viruses and the involvement of viral infection in cancer development.
