Immuno-augmentative therapy (IAT) was developed by Lawrence Burton, Ph.D., a zoologist who claimed that it could control all forms of cancer by restoring natural immune defenses. He claimed to accomplish this by injecting blood serum proteins isolated with processes he had patented. However, experts have shown that the substances he claimed to use cannot be produced by these procedures and do not exist in the human body . Burton did not publish detailed clinical reports, divulge the details of his methods, publish meaningful statistics, conduct a controlled trial, or provide independent investigators with specimens of his treatment materials for analysis. During the mid-1980s, several of Burton's patients were reported to have developed serious infections following IAT. Burton died in 1993, but the Bahamian clinic he founded is still operating under the direction of Dr. R. John Clement, a British-trained general practitioner who joined with Burton in 1978. The IAT Web site falsely claims that "IAT may well be the best option available for cancer patients today."
Burton received his Ph.D. in zoology from New York University in 1955. He had no formal graduate training in immunology, oncology, chemotherapy, or radiation therapy. His research began with fruit flies (Drisophila melanogaster) and later included mice. His doctoral dissertation was entitled "Carcinogenic Activity of Larval Donor Extracts in Drosophila."  He was a biology research associate at the California Institute of Technology from 1955 to 1957 and at New York University in 1958. From 1959 through 1973, he held various research positions at St. Vincent's Hospital in New York City .
Although Burton claimed to have been a "senior oncologist" at St. Vincents, hospital documents indicate that only medical doctors were titled "oncologists." His work on fruit flies was also challenged. Burton claimed to have discovered a "tumor induction factor" (TIF) and a naturally occurring TIF inhibitor in fruit flies. Later, in New York, he reported findng the same inhibitor system in mice and concluded that all mammals have it. However, Burton's research was questioned at Cal Tech after someone discovered that the control fruit flies in his experiments had no injection scars, while their experimental animals did, although the research protocol called for injecting controls with an inert material. Burton's supervisor, biology professor Herschel K. Mitchell, Ph.D. -- who had co-authored two papers with Burton -- investigated and concluded that Burton's results were "meaningless."  As described by Saul Green, Ph.D., in the Journal of the American Medical Association:
When questions were raised about the research results, Mitchell presented Burton with coded samples and asked him to use his assay to identify those containing purified TIF. Burton could not distinguish between plain buffer solutions and [buffer] solutions containing TIF. Subsequently Mitchell tried to repeat Burton's tumor transmission experiments with Burton's own TIF preparations, but found no difference between control and experimental groups. Consequently, Mitchell concluded that the assay did not work and that Burton had failed to provide evidence that TIF existed in fruit flies. Because the results Burton was reporting from New York were based on the invalidated bioassay, Mitchell asked to be "forgotten" as a collaborator in the work Burton did at the California Institute of Technology 
Despite Mitchell's repudiation, Burton applied his theory to the treatment of humans. From 1974 to 1977, he operated as research director at the Immunology Research Foundation in Great Neck, N.Y., which had been established in 1973 with the help of several businessmen. The Foundation's major purpose was "to investigate and stimulate immunological research for the ultimate control of cancer through the victim's own defense system."  Treatment using Burton's methods was administered by affiliated physicians . In December 1974, the foundation submitted an investigational new drug (IND) application to the FDA, seeking to initiate human trials using IAT with Burton as the principal investigator. According to the FDA, subsequent questions about the research were not fully answered. Instead, Burton asked that his application be withdrawn, and the National Institutes of Health placed it in an "inactive" file in March 1976 . Although IND numbers are assigned for identification only, a foundation brochure claimed that the FDA had "awarded an IND number toward the furtherance of the Foundation's goals" and that "having been granted the identifying number, certain clinical trials may be begun on a very limited experimental basis."
In 1977, Burton left the United States and opened the Immunology Researching Centre, Ltd., in Freeport, Grand Bahama Island, Bahamas. Literature from the center described it as a nonprofit corporation. In 1978, representatives of the Bahamian Ministry of Health and the Pan American Health Organization (one of whom was a National Cancer Institute official) visited the facility and reviewed 49 charts that the center's staff considered to represent encouraging results. The report concluded that there was no objective evidence that IAT was beneficial and recommended that the facility be closed . However, except for a seven-month period beginning in July 1985, the Bahamian government has permitted the clinic to remain open. Another IAT facility licensed by Burton was opened in 1987 in Frankfort, West Germany. A third one, the Immune Therapy Clinic, opened in 1989 in Playas, Mexico, with a promotional office in nearby San Ysidro, California (a suburb of San Diego).
IAT is administered on an outpatient basis. The estimated cost of treatment at the Immunology Research Centre is $7,500 for the first four weeks and $700 a week after that, with an average stay of 12 weeks. After the patients return home, the maintenance program costs $50 per week . I can find no mention of the Mexican or German facilities in any directory or on the Internet, so I suspect they are no longer in business.
During the late 1970s and early 1980s, National Cancer Institute officials communicated with Burton and other interested parties about possible approaches for evaluating his methods. However, no agreement could be reached for collaboration.
In 1980, Burton received an enormous boost when CBS-TV's "60 Minutes" gave him favorable publicity. During the program, a prominent physician stated that one of his patients treated by Burton appeared to have miraculously recovered . The patient died within two weeks after the program was shown , but "60 Minutes" never informed viewers of this fact. In 1984, at a Congressional hearing held by Representative Claude Pepper, a pathologist from Alabama described how his father-in-law had been tricked into believing that IAT had cured him:
In 1982, my father-in-law was diagnosed as having unresectable, incurable, widely disseminated cancer of the lung, and advised that essentially his condition was terminal. As could be expected, the family was distraught, and we began to grasp at straws and looking into alternative modes of treatment. . . . Some of the local press carried stories about . . . so-called immuno-augmentative therapy. . . . Soon thereafter he went to the Bahamas to get the treatment.
His main symptom had been pain from the tumor. It had metastasized to the bones. When he went down there, he was told to go off pain medication and to begin the serum injections, and that . . . the serum injections, if they work and dissolve the tumor, will cause pain. So he went down there knowing he had a tumor growing in him and causing him pain, and through a pretty good ploy he came back convinced that the pain he was having was a cure. In addition, he was told the tumor was shrinking. The x-ray film they took was overexposed, which has the technical problem of making masses look smaller than they really are.
Upon his return, I encouraged him to go to Fox Army Hospital and have another chest x-ray made. Several radiologists corroborated that they could see no evidence of any shrinkage in the tumor. I was then faced with the unpleasant task of telling my father-in-law for the second time he was dying.
It was interesting that both he and his wife came back with total euphoria -- that he was cured. They told everyone they saw he was cured. When they realized that they had been fooled, it was really a shock, and, of course one doesn't usually go around telling people you have been fooled.
He died approximately two months after he returned. In addition to the emotional turmoil and being away from the rest of the family for essentially half the remaining life he had, this cost them approximately $10,000, including travel and lodging, for this phony cancer cure .
The American Cancer Society's medical library has identified 24 papers written or co-authored by Burton between 1954 and 1969. In 1982, the Society asked him for documentation of his work and references to relevant publications. No reply was received. Burton stated that after papers he wrote between 1964 and 1973 were rejected, he decided he was being "blackballed" and would submit no more papers to major journals .
In 1986, U.S. Representative Guy V. Molinari held a public hearing on IAT, after which he and 41 other congressmen signed letters asking the Congressional Office of Technology Assessment (OTA) to evaluate IAT. Subsequently, Representative John Dingell, chairman of the House Energy and Commerce Committee, asked OTA to investigate unconventional cancer treatments with IAT included as a case study. OTA then appointed a working group composed of technical experts and representatives of Burton to design a clinical trial to evaluate IAT. According to OTA's report, a protocol was designed in which colon cancer patients would be treated at an accredited medical center in the U.S. However, communication between Burton and U.S. government authorities broke down after he insisted that a "pre-test" be conducted at his clinic. The OTA report concluded that "no reliable data are available on which to base a determination of IAT's efficacy."  In 1991, after an extensive investigation, the American Cancer Society issued a position paper warning that it had "found no evidence that [IAT] was safe or resulted in objective benefit in the treatment of cancer." 
IAT has also been promoted by People Against Cancer (PAC), an organization that advocates "medical freedom of choice" and offers literature and counseling about "therapeutic alternatives." The organization's founder and president is Frank Wiewel, of Otho, Iowa, whose father-in-law was a patient of Burton. Regular membership, which costs $35, includes a subscription to Options, a newsletter that promotes questionable cancer treatments. PAC's "Alternative Therapy Program" in which Wiewel provides an "extensive report and consultation on treatment options," requires purchase of a "sustaining memberhip" for $350. Wiewel was also president of the IAT Patient's Association, Inc., which was formed in 1985 and later transferred its assets to People Against Cancer.
In 1981, when the Florida legislature was considering whether to legalize IAT in Florida, its proponents distributed literature stating that IAT could provide:
Burton claimed that his treatment "augments the patient's own immune system."  He postulated that cancers develop because of a breakdown in the immune system and that IAT restores the body's natural defenses. A brochure from the Immunology Researching Centre stated:
Tumor antibodies are "alerted to the presence" of tumor cells by a protein produced by the tumor cells themselves-tumor complement factor. . . .Tumor complement induces the tumor antibodies to destroy the tumor cells. If the tumor cells are destroyed in an unregulated manner, however, a person's liver may become overburdened. . . . To protect the body, blocking protein factors are produced to shield the tumor cells from attack by the tumor antibodies and thereby regulate the rate of tumor kill. The important balance of tumor kill rate is maintained by yet another blood component-de-blocking protein factor . . . which neutralizes the blocking protein and thereby permits antibodies to destroy tumor cells in a regulated manner. At times this dynamic process is upset and an over-supply of blocking protein factor exists, along with undersupplies of deblocking protein factors and tumor complement factor. When this imbalance . . . occurs, the individual is said to be immuno-suppressed or immunodeficient .
According to the brochure, Burton's laboratory made daily or twice-daily assessments of the levels and proportions of "tumor complement," "tumor antibody," "deblocking protein," and "blocking proteins." The patient was then given daily injections of "tumor complement factor" obtained from the serum of persons with cancer and "deblocking protein factor" and "tumor antibody" obtained from the serum of persons without cancer. Burton determined the dosages after analyzing these data with a computer program that he developed. The brochure stated:
Each therapeutic IAT intervention is prescribed with the most recent assessment of: (1) the status of the native immune system; (2) the status of tumor activity; (3) the effects of the most recent therapy; and (4) the accumulated effects of all previous therapy and response.
After the patient was considered stabilized, a computer readout was prepared for a daily program of injections administered at home .
Burton did not claim that IAT products attacked cancers directly. Therefore, failures would be attributable not to his treatment but to unresponsiveness of the patient's immune system due to damage by prior treatment or advanced disease. He advised patients undergoing IAT to stop other therapies "so as not to confuse other data." The brochure stated that Burton did not claim "cure," but did claim that many patients "prosper" by becoming symptom-free and resuming their normal life activities.
Burton conducted no controlled trial of his treatment and did not publish detailed case histories of his patients. The clinic brochure contained a chart of about 40 types of cancer in various stages and scores a "+" if half or more of patients "have responded to IAT with long-term regression of tumors and/or remission of symptoms." These data were scientifically meaningless . OTA asked Burton for the data or calculations upon which the chart was based but did not receive them .
The brochure suggested that double-blind experimentation would be immoral because it would deprive half the patients of active treatment. However, an NCI official who critiqued the brochure in 1984 noted that Phase III trials compare the experimental treatment with standard treatment, not a placebo. He also said:
I think [Burton] realizes that he could get his work published if he were able or wished to present the data in the form needed to make his case. Nothing is required of him that is not required of others who wish to report his findings. If worst came to worst, he could as a start, publish and circulate the "clinical data" that he implies his promotional brochure is based on just as easily as he published and circulated promotional material. He could also make available to the scientific community the laboratory and clinical records upon which his claims are based 
In 1987, IAT proponents stated that Burton "was experimenting with his mice and some select patients with what he calls 'immune replacement' rather than immune augmentation. . . . If results continue to show promise and be executed, it will mean more frequent and longer stays at the clinic -- but home maintenance shots could be discontinued." 
In 1979, Burton entered a contract with MetPath, the nation's largest biomedical laboratory. The documents presented in April 1981 to the Florida legislature called the contract "another practical validation of the principles on which IAT is based." The material also stated that MetPath thoroughly investigated the IAT early detection test and found "spectacular" results . However, MetPath had actually terminated the contract in December 1980 because it was unable to develop a sufficiently reliable technique to measure or identify the substance Burton claimed was related to the presence or absence of cancer. According to MetPath's board chairman:
Notwithstanding Burton's assertions to the contrary, our contract was not "another practical validation of the principles upon which IAT is based." We are not aware of the basis for the assertion that the results were "spectacular'" or that the "tests proved to be 100% accurate and identified the blood specimens of patients known to have cancer." 
The Florida legislators were also given binder containing testimonials, one section of which included 142 "cancer victims whose immune systems have responded successfully to IAT." Two of these patients did not have cancer, and six did not specify when their treatment began or the date the testimonial was signed. Of the remaining 134 patients, 39 (29%) had begun treatment less than two months before their testimonial had been obtained, and 50 (37%) had given their testimonial between two and six months after starting treatment . This is not enough time to evaluate a cancer treatment. However, Burton claimed that by monitoring the immune system of patients with his four tests, he could usually determine whether there was a positive response to IAT therapy within three or four days . Two of the 134 patients died of their disease at least two months before he presented their testimonials to the legislators .
Burton held patents [A, B, C, D, E] for extracting the alleged IAT proteins, but he kept his computer program secret. In 1985, consultants from the Pan American Health Organization asked whether they could observe the preparation and dispensing of his protein fractions. According to their report, Burton replied that if they wanted to see how these products were made, they could go to Washington and examine his patents .
Saul Green, Ph.D., a biochemist who did cancer research at Memorial Sloan-Kettering Hospital for 23 years, has examined the patent applications. Dr. Green concluded that Burton's postulated "tumor complement," "tumor antibody," "deblocking protein," and "blocking proteins" in fact, have "never been identified as components of human blood much less of the immune system in the human." Moreover, proteins with the molecular weights Burton attributes to these alleged substances cannot be separated by centrifugation of blood using the speeds and times described in his patents . A report to the OTA reached similar conclusions . Dr. Green also noted that Burton did not establish immunologic baselines for normal individuals that were verified by independent investigators. Nor did he use recognized scientific tests to determine the status of his patients' immune competence either before or after treatment. Moreover, even if Burton's postulated substances do exist, the amounts injected into the patient's bloodstream would be too small to change the level of any existing blood component significantly .
No independent analysis of IAT treatment materials has been done on samples provided by Burton himself. Nor did he publish the results of any analysis he did on the nature and contents of the protein fractions he says he used to treat patients. NCI scientists who analyzed treatment materials given to several patients concluded that the materials were dilute solutions of ordinary blood proteins, the major component being albumin. None were electrophoretically pure, and none contained the components that Burton postulated .
William A. Nolen, M.D., who visited Burton's clinic in 1982, reviewed many records and had follow-up conversations with at least ten patients and some of their doctors. Dr. Nolen concluded that most of the patients had never had cancer or had tumors that typically grow slowly, while some had undergone conventional treatment that was probably responsible for any positive results .
In 1986, NCI and the American Society of Clinical Oncology asked cancer specialists about their experiences with patients who had undergone treatment with IAT. Although 95 such patients were identified, the researchers concluded that for various technical statistical reasons their survey could not be used to draw valid inferences about the effectiveness of IAT .
A research team from the University of Pennsylvania Cancer Center led by Barrie R. Cassileth, Ph.D., collected data on 79 patients who had received IAT at Burton's clinic. The researchers' report, which was privately published, stated that its data did not enable meaningful comparison of IAT patients and conventionally treated patients and suggested that a well controlled prospective study was needed  Nevertheless, IAT proponents have circulated copies of the report and claim that the study demonstrates IAT effectiveness .
In 1987, the American Medical Association's Diagnostic and Therapeutic Technology Assessment (DATTA) asked an expert panel to evaluate IAT. Of 27 panelists who commented on effectiveness, none rated IAT "established," 6 (22%) called it "investigational," 16 (73%) "unacceptable," and 5 (19%) "indeterminate." Of 26 panelists who commented on safety, none rated IAT "established," 6 (23%) called it "investigational," 19 (59%) "unacceptable," and 1 (4%) "indeterminate." 
In 1990, Burton's literature included a booklet summarizing the experiences of 35 IAT patients and their status as of February 1988. . Wallace I. Sampson, M.D., a cancer specialist who analyzed the data, concluded:
The sampling of cases is not meaningful. To estimate prognosis accurately, the stage and grade of a tumor are needed. Only a few of these vignettes provide both of these. Any facility that treats large numbers of cancer patients will have some patients who survive a long time -- with or without treatment. It would not be possible to determine IAT's effectiveness without knowing how these outcomes compare with the rest of Burton's patients who had similar cancers. Moreover, 30 of the 35 received standard or near-standard treatment before undergoing IAT. All of these had a significant probability of living as long as was recorded in the booklet .
The U.S. Centers for Disease Control (CDC) has reported that from March 1982 to March 1984, 16 people treated at Burton's clinic developed skin abscesses where IAT materials had been injected. Nocardia asteroides was recovered from seven of these patients, one of whom also developed pneumonia. Based on a survey of patient charts, CDC estimated that between November 15, 1983, and March 1, 1984, the attack rate for abscesses at injection sites was 4.5 per 100 . At the Molinari hearing, Burton stated that the Nocardia infections had been caused by a problem in an air conditioning duct and that the problem had been eliminated .
In 1984, NCI examined unopened vials of treatment materials given to five patients of Burton and found contamination with various bacteria . During 1985, public health officials found antibodies to the human immunodeficiency virus (HIV) in vials of serum obtained from several patients and were able to culture the virus from one specimen-suggesting that blood infected with HIV had been used to prepare IAT treatment materials . Antibodies to hepatitis B were also found in IAT serum, and a few cases of this disease occurred following treatment at Burton's clinic [35,36]. Because of the public health risk involved, the Bahamian health authorities asked the Pan American Health Organization to send consultants to reinspect Burton's clinic. The consultants reported:
The visit to the clinic was essentially unproductive. . . . Some miscellaneous information was obtained, such as the fact that the clinic has treated AIDS patients . . . .The overall impression [of the report's writer] was one of dismay and concern for the lack of scientific knowledge displayed by the clinic staff, including the director, the unscientific atmosphere in the laboratories and the considerable potential for harm .
The consultants advised the Bahamian Ministry of Health to close the clinic. It was closed in July 1985 but was allowed to reopen in March 1986 after it acquired equipment to test for the AIDS and hepatitis B viruses.
In 1980, U.S. Representative Larry McDonald introduced federal legislation to exempt IAT "blood fractions" from FDA regulation for five years. His effort was not successful . McDonald, a urologist who used the quack remedy laetrile to treat cancer patients in his office, also introduced bills intended to exempt laetrile from FDA regulatory action .
Bills to legalize the use of IAT were passed in 1982 in Florida and Oklahoma. The Florida bill required that the treatment be administered with a protocol and that data be presented periodically to a patient qualification review board. The Oklahoma bill required that samples of the serum be submitted to the State Health Department before treatment. Burton did not open a clinic in either state. The laws were repealed in Florida in 1984 and in Oklahoma in 1985.
In 1986, the FDA issued an Import Alert to halt importation of IAT treatment materials used by Burton . Although the ban is still in effect today, I have seen no report indicating that it has been enforced.
In May 1988, a U. S. District Judge for the Western District of Michigan denied a widower's suit for payment by his insurance company of his deceased wife's treatment with IAT . The court arbitrator in the case had concluded:
Based upon the record before me, it does not appear that the [IAT clinic] is conducting a therapeutic program which is reasonably designed or intended to add to the general body of scientific knowledge. . . . Since the effectiveness of the therapy is unknown, and since it appears that its effectiveness will remain unknowable under the [clinic] program as it is presently designed, I cannot find that the treatments in question were "necessary." 
No evidence has been published showing that immuno-augmentative therapy is safe or effective against cancer in humans. Burton did not publish detailed clinical reports or meaningful statistics, divulge the details of his methods, conduct a controlled trial, or provide independent investigators with specimens of his treatment materials for analysis. The mechanism of action he postulated for his treatment involved substances that are unknown to the scientific community. Although Burton said that IAT treatment materials were produced with processes he patented, experts do not believe that these processes can achieve what he claimed. Several attempts to develop a protocol for a clinical trial of IAT were unsuccessful. Moreover, during the mid-1980s, cases were reported of patients of Burton who developed serious infections following IAT.
The information upon which this article was based was gathered with help from Joseph J. Zavertnik, M.D., Saul Green, Ph.D., and the American Cancer Society.