UnprovenMethodsof CancerManagement

tion to the US Food and Drug Administration (FDA) seeking to initiate humaninvestigational trials with IAT. Accordingto the FDA, subsequent questions aboutthenatureof theresearchtrialswere notfully answered and the FDA never approved any research trials.6 A publicationfrom the Immunology Research Foundation, Inc., however, stated that “¿�havingbeen granted the [INDI identifying number, certain clinical test trials may be begunon a very limited experimental basis.―3TheIND application was placed in an FDA“¿�inactivefile―in March 1976.'

A representative from the NationalCancer Institute (NCI) of the US Department of Health and Human Services visitedthe Immunology Researching Centre, Ltd.in l978.@ The NC! representative foundthat clinic records were inadequate to evaluate IAT. According to the NC!, Dr. Burton has revealed neither the compositionof the treatment materials nor the methodof preparing them.7

Recently, the NC! has been in correspondence with Dr. Burton again. The NC!has offered to screen Dr. Burton's materials to evaluate its antitumor propertiesand has suggested possible collaborationand approaches for evaluating his methods.7 Without knowing the composition ofthe treatment materials or preparationmethods, the NC! is prevented from participating in human trials since the NC!would not know what is being tested.

Therehavebeenlegislativeefforts,at

After careful study of the literature andother information available to it, the American Cancer Society has found no evidencethat treatment with Immuno-AugmentativeTherapy results in objective benefit in thetreatment of cancer in human beings.Lacking such evidence, the American Cancer Society would strongly urge individuals afflicted with cancer not to participatein treatment with Immuno-AugmentativeTherapy.

The following is a summary of information on Immuno-Augmentative Therapyin the American Cancer Society files as ofOctober 1983. No implication of agreement by the Society with the contents ofany proponent material is to be construedbecause of the Society's reference to thatmaterial.

Background

“¿�Immuno-AugmentativeTherapy,―or“¿�IAT,―is a method of cancer managementproposed by Lawrence Burton, PhD, andavailable at the Immunology ResearchingCentre, Ltd., Freeport, Grand Bahama Island, Bahamas.' The Centre, which openedin 1977, was preceded by the ImmunologyResearch Foundation, Inc. in Great Neck,Long Island, New York.2 The Foundationwas established in 1973 with the supportof a number of businessmen.3-5

In December 1974, the ImmunologyResearch Foundation, Inc. submitted anInvestigational New Drug (IND) applica

232 CA-A CANCER JOURNAL FOR CLINICIANS

Immuno-AugmentativeTherapy

both the state and federal level, to legalizethe use of IAT. One effort that failed wasHR 7936, a bill introduced in the US Houseof Representatives, 96th Congress, Secondsession (1980). The bill was intended toexempt for five years the “¿�bloodfractions―used in IAT from the Federal Food, Drug,and Cosmetic Act, the Act enforced by theFDA.8

In Florida, House Bill Number 747,short title “¿�CancerTherapeutic ResearchAct of 1981,―was passed on March 12.1982, by an override of Governor RobertGraham's veto. The bill authorized a Patient Qualification Review Board to permit“¿�qualified―patients to obtain “¿�unconventional―therapies for the “¿�controland cureof cancer.―The Patient Qualification Review Board has the authority to approvethe “¿�protocol―under which IAT or other“¿�unconventional―therapies would be provided.9

House Bill Number 1633, introducedin the State of Oklahoma House of Representatives, became law on March 2,1982.10 This specifically legalized the prescribing and administering of IAT by licensed physicians for “¿�thetreatment of anymalignancy, disease, illness or physicalcondition,― provided patients had signed a“¿�writteninformed request.―°

Proponents

The principal proponent of IAT is Lawrence Burton, PhD. Dr. Burton receivedhis PhD from New York University in 1955.His doctoral dissertation in the Departmentof Biology, New York University, is entitled “¿�CarcinogenicActivity of LarvalDonor Extracts in Drosophila.― Dr.Burton worked from 1955 to 1957 atthe California Institute of Technology,Division of Biology, then returned tothe Biology Department of New YorkUniversity (Washington Square Collegeof Arts and Sciences), and by 1959 wasat the Hodgkin's Disease Research Laboratory, St. Vincent's Hospital, New YorkCity.' 12—14

A publication from the ImmunologyResearching Centre, Ltd. states it is “¿�ANot-For-Profit Foundation Incorporated in

the Commonwealth of the Bahamas,―offers an “¿�experimental―IAT program forwhich “¿�contributions―are needed, andclaims that “¿�100percent of the contributions will go to the support of this research.―5An undated fee schedule fromthe Centre lists a fee of $350, “¿�payableattime of evaluation,― for a review of recordsand clinical laboratory work and “¿�immunocompetence testing―;a fee of $3,000,“¿�payableupon acceptance for four weekstherapy―; and a fee of $450 per week forthe fifth week and each week thereafter.―Patients “¿�mayexpect to remain a minimumof six to eight weeks―and, if they go home,“¿�toreturnforathree-to-five-dayperiodafter12 to 16 weeks.―5

Organizations have promoted IAT orlegislation favorable to IAT. A currentlyactive organization is IAT Communications, Inc. in Olathe, Kansas.'6

Proponent Claims

A publication from the Immunology Researching Centre, Ltd. states:

“¿�Immuno-AugmentativeTherapy isexperimentaland isbeingconstantlyimproved and refined. The therapy is the resuit of 20 years of painstaking research andtesting in laboratory animals including several strains of mice. Evidence gathered hasrevealed that Immuno-Augmentative Therapy can reverse the cancer process and thatthe immunological faults which exist inanimals with cancer also exist in humanswith cancer.

“¿�Continueduse of immuno-augmentation techniques can correct the faults inthe immune mechanism. Immuno-Augmentative Therapy restores the proper balance of the protein fractions which makeup the immune mechanism. This balancethus permits the immune system to destroytumor tissue.

“¿�Cancerpatients who have been treatedat the Centre with this therapy have responded with cessation of tumor growth insome instances, with no new tumor growthin others, and in many with actual reversalas well as the destruction of the cancerousgrowth. Many patients are now living nor

VOL.34. NO. 4 JULY/AUGUST1984 233

mal lives way beyond their previous prognoses.―

In describing the rationaleof the therapy the publication states the following:

“¿�Inaddition to discovering a blockingprotein which prevents the immune mechanism from working, Dr. Burton foundthe factors within the blood that have ananticancer effect. His therapy includesa deblocking protein (an alpha 2 macroglobulin), tumor complement (complement 3), and tumor antibody fractionswhich include the alpha 2 macroglobulin,IgG, 1gM, and IgA.

“¿�Theway in which the immune mechanism attacks cancer in the body can bedescribed in the following way:

“¿�Afterthe tumor cells, develop in thebody and begin to grow, the tumor cellssend out a signal which stimulates the bodyto produce tumor complement. The tumorcomplement activates tumor antibody. Thisactivation of the tumor antibody results intumor cell death. A by-product of tumorcell death is a blocking protein which signals the immunemechanismto shut down,by preventing the activation of the tumorantibody by the tumor complement.

“¿�However,the deblocking proteinunites with the blocking protein, therebyneutralizing it and permitting the reactivation of tumor antibody by tumor complement.―

According to a “¿�backgrounddocument― provided by the Bahamian government, the Immunology ResearchingFoundation, Inc. had tested two “¿�deblocking proteins―on 100 humans and found noevidence of toxicity.2 According to thedocument, the substances were also administered to 50 terminal human cancerpatients with the result that “¿�21showeddefinitive improvement: no detectable evidence of the disease; 22 showed arrest ofthe disease process; seven died after showing some improvement.― The documentalso says, the Foundation “¿�wasanxious toaccelerate the speed of such trials in manby treating 1,000 to 3,000 cancer patientsannually during a five-year period, at Freeport.―

In material distributed to the Floridalegislature in 1981 on behalf of legislation

favoring IAT, the following statementswere made:'7•¿�IAT can provide effective cancer treat

ment for all types of cancer.•¿�IATis safe, nontoxic, andhasno adverse

or destructiveside effects harmful to thecancer victim.

•¿�IAT can provide practical and effective cancer prevention (emphasis inoriginal).

•¿�IAT can provide the earliest possible typeof cancer detection.

•¿�IAT can provide the most advanced, individualized,and “¿�tailor-made―cancertreatment and treatment monitoring testsand techniques.

•¿�IAT can provide reliable cancer prediction.

•¿�IAT can provide a better quality lifestylefor the cancer victim during treatment.

•¿�IAT can provide less expensive cancertreatment.

The material also gives examples ofsituations where IAT “¿�isa more appropriate cancer treatment―than surgery, radiation therapy, and chemotherapy.

Evaluation

The American Cancer Society MedicalLibrary conducted a search of the medicaland scientificliteraturefortheyears1966 to 1982. This and additionalliterature searches produced a total of 24references to publications of which Dr.Burton was the principal author or aco-author. 12-14.18-38

Twenty-three of Dr. Burton's publications were found. 12-14.18-37As recentlyas December 1982, the American CancerSociety wrote to Dr. Burton requestingdocumentation of his work and referencesto relevantpublications.No reply has beenreceived to date.

The American Cancer Society doesnot know to what extent, if any, IAT asavailable at the Immunology ResearchingCentre, Ltd. is actually based on Dr. Burton's published work. Dr. Burton has notprovided the American Cancer Society withany information, nor was any found in thescientific literature that describes the details of the treatment methods available or

234 CA-A CANCERJOURNALFORCUNICIANS

the results of any studies that may havebeen conducted at the Immunology Researching Centre, Ltd.

Publications by Dr. Burton and relatedliterature were submitted to two consultants for evaluation. Sharing the opinionof the NCI, the consultants concluded thatavailable information is insufficient forevaluating the safety or effectiveness ofIAT.7@940

Literature distributed to the floridalegislature to support legislation favorableto IAT included 142 personal anecdotaltestimonials.'7 The testimonials did notcontain the adequately controlled and scientifically documented evidence needed toevaluate the effectiveness of IAT in thetreatmentof cancer.Twenty-fivepercentof the testimonials were given within lessthan two months of beginning IAT therapyand 70 percentwithinsixmonths of beginning therapy. This is not sufficient timeto measure the effect of IAT on cancer.4'

Testimonials are inadequate scientificevidence for several reasons. They are susceptible to biased reporting, the number ofcases tends to be small, and five-year follow-up data are often insufficient. Frequently, no or incomplete data are gatheredand presented for cancer patients who hadno effects or negative effects from a treatment. Such patients could outnumber thosewho claim to have benefited. Patients whoclaimtohavebenefitedmay havereceivedother therapies such as surgery, radiation

Referenc,es

therapy, or chemotherapy. These therapiesare often dismissed or ignored.

In the literaturedistributedto the Florida legislature in 1981 there is a referenceto a “¿�MetPathcontract.―7According to theliterature, this contract “¿�providesanotherpractical validation of the principles onwhich IAT is based.―However, the agreement with Dr. Burton was terminated inDecember 1980,42afterMe@Pathwas unable to develop a reliable technique to measure or identify the substance in the serum“¿�saidby Dr. Burton to be related to thepresence or absence of cancer.―42According to MetPath, “¿�notwithstandingDr. Burton's assertion to the contrary, our contractwas not ‘¿�anotherpractical validation of theprinciples on which IAT is based.' We arenot aware of the basis for the assertion thatthe results were ‘¿�spectacular'or that the‘¿�testsproved to be 100 percent accurateand identified the blood specimens of patients known to have cancer. “¿�42

No scientific evidence was found norhas any been provided to the AmericanCancer Society to support the claims thatin some situations LAT is a more appropriate cancer treatment than surgery,radiation therapy, and chemotherapy.Likewise, the American Cancer Society hasfound no scientific evidence supporting theclaimsthatIAT canprevent,detect,orpredict the occurrence of cancer and none wasfound indicating IAT is safe or effectivefor any or all types of cancer.

1. Immunology Researching Centre, Ltd. brochure. Freeport. Grand Bahama Island, Bahamas, Immunology Researching Centre, Ltd.undated.2.Proposedestablishmentofan ImmunologyResearching Centre for cancer at Freeport, GrandBahama.Nassau, Bahamas,Ministryof Health,Governmentof the Bahamas, undated.3. The ImmunologyResearchFoundation,Inc.informationbulletin number Olb. Great Neck,Long Island, New York, Immunology ResearchFoundation, Inc. undated.4. Yasgur SS: Can cancer be destroyed by thebody's own agents? Modern Medicine 43:40—45, 1975.

5. Widom RS: Dear Friends, letter. Great Neck,LongIsland, NewYork, ImmunologyResearchFoundation, inc. June 1975.6. Immuno-AugmentativeTherapy, FDA talkpaperT82—14. Rockville,Md, US Departmentof Health and HumanServices, Food and DrugAdministration, March 2, 1982.7. Dr. Lawrence Burton, form letter. US Department of Health and Human Services, National Cancer Institute, Cancer InformationService, October 14, 1983.8. Bill to exempt certain blood fractions fromthe Federal Food, Drug, and CosmeticAct forfive years. US Congress, House, 96th Congress, 2nd session, 1980, HR 7936.

VOL 34. NO. 4 JULY/AUGUST1984 235

9. Cancer Therapeutic Research Act. Statutes,section 402.36, Florida, 1982.10. Immuno-Augmentative Therapy Act. Oklahoma Legislature, House Bill Number 1633,1982.II. Burton L: Carcinogenic activity of larvaldonor extracts in Drosophila, PhD dissertation.New York, New York University, February1955.12. Burton L: Carcinogenic effects of an extractable larval tumor agent. Trans NY AcadSci17:301—308,1955.13. Friedman F, Burton L, Mitchell HK: A tumor-inducing factor in Drosophila melanogaster. I. Purification and action. Ann NY AcadSci 68:349—355,1957.14. Kassel R, Burton L, Friedman F, et al: Carcinogenic action of refined tumor factor isolatedfrom mouse leukemia tissue. Proc Soc Exp BiolMed 101:201—204,1959.15. Burton L: Immuno-augmentative approachto cancer control, form 7332. Freeport, GrandBahama Island, Bahamas, Immunology Researching Centre, Ltd. undated.16. Immuno-Augmentative Therapy, information packet. Freeport, Grand Bahama Island,Bahamas,ImmunologyResearchingCentre,Ltd.undated. (Available from IAT Communications, Inc. Olathe, Kansas.)17. Literature distributed to Florida legislature,1981.18. Friedman F, Harnly MH, Burton L: Theeffects of tu larval fluid and vitamins on tumorproduction in Drosophila melanogaster. Proc AmAssoc Cancer Res 1:15, 1954.19. Harnly MH, Burton L, Friedman F, et al:Tumor induction in Drosophila melanogaster byinjectionofe°tularvalfluid.Science120:225—227,1954.20. Burton L, Friedman F, Mitchell HK: Thepurification of an inherited tumor-inducing factor in Drosophila melanogaster. Cancer Res16:880—884,1956.21. Friedman F, Burton L: Benign and invasivetumors induced in Drosophila by an inheritedtumor-inducing factor. Cancer Res 16:1059—1061, 1956.22.FriedmanF,OstranderF,BurtonL,etal:A technique and collection cage for the acquisition of large numbers of specific-age larvae.Drosophila Information Service 30:161, 1956.23. Burton L. Friedman F: A technique for thetissue culture of Drosophila tumors. DrosophilaInformation Service 30:160, 1956.24. Burton L, Friedman F: Detection of tumorinducing factors in Drosophila. Science124:220—221,1956.25. BurtonL, HarnlyMH, Kopac Mi: The activity of a tumor factor in Drosophila devel

opment. Cancer Res 16:402—407,1956.26. Friedman F, Burton L, Mitchell HK: Characteristicsof an inheritedtumor-inducingfactorin Drosophila melanogaster. Cancer Res 17:208-214, 1957.27. Burton L, Friedman F, Mitchell HK: A tumor-inducing factor in Drosophila melanogaster. 11. Its characteristics and biological nature.Ann NY Acad Sci 68:356—365,1957.28. Kassel R, Burton L, Friedman F, Ctal: Augmented tumor-inducing potency of refined extracts from human and mouse neoplasms. ProcNY State Association of Public Health Laboratories 39:10—12,1959.29. Friedman F, Burton L, Kaplan ML, et al:The etiology and development of a melanotictumor in Drosophila, in Gordon M (ed): Pigment Cell Biology. New York, Academic Press,Inc. 1959. pp 279—299.30. Burton L, Friedman F, Kassel R, et al: Thepurificationandactionof tumorfactorextractedfrom mouse and human neoplastic tissue. TransNY Acad Sci 21:700—707,1959.31. Friedman F, Kassel R, Burton L, et al: Arapid (24 hour) bioassay for the detection ofhuman and mouse tumor factors. Proc Soc ExpBiol Med 103:16—19,1960.32. Kaplan ML, Kassel R, Burton L, et al: Actividad carcinogenetica dcl factor tumor aisladode neoplasias humanas. [Carcinogenetic activity of the tumor factor isolated from humanneoplasm.] La Prensa Medica Argentina48:3209—3213, 1961.33. Friedman F, Burton L, Kassel R: The extractionandrefinementoftwoantitumorsubstances. Trans NY Acad Sci 25:29—32,1962.34. Burton L, Friedman F, Kassel R: Methodsfor determination and alteration of titers of acomplex of factors present in blood of neoplastic mice. Trans NY Acad Sci 25:33—38,1962.35. Kassel R, Burton L, Friedman F, Ctal: Synergistic action of two refined leukemic tissueextracts in oncolysis of spontaneous tumors.Trans NY Acad Sci 25:39—44,1962.36. Kassel R, Burton L, Friedman F: Utilization of an induced Drosophila melanoma in thestudy of mammalian neoplasia. Ann NY AcadSci 100:791—816,1963.37. Friedman F, Burton L, Rottino A: Necrosisliquefaction and absorption of C,H mammarytumorsresultingfrom injectionof extractsfromtumor tissue. Proc Am Assoc Cancer Res 6:20,1965.38. Rottino A, Burton L, Friedman F: A humanfactor as a possible cause of spontaneous necrosis of malignant tumor. Presented at the 53rdmeeting of the NY State Association of PublicHealth Laboratories, 1969.

236 CA-A CANCERJOURNALFORCLINICIANS

39.HH Fudcnberg,MD, MedicalUniversityofSouth Carolina, Charleston, South Carolina,personal communication,August 1983.40. EF Osserman, MD, College of Physiciansand Surgeons of Columbia University, NewYork, personal communication,July 1983.41. Analysis by Joseph J. Zavcrtnik, MD (Con

sultant,FloridaCancerCouncil)of the evidencepresented by Dr. Burton to the legislators onIAT therapy, December 9, 1981.42. Letter from Paul A. Brown, MD (Chairmanof theBoard,METPATH,Teterboro,NewJersey) to Joseph J. Zavertnik, MD (Consultant,Florida Cancer Council), October 30, 1981.

VOL 34. NO. 4 JULY/AUGUST1984 237