After careful study of the literatureand other information available to it, theAmerican Cancer Society does not haveevidence that diagnosis by means ofeither the Intradermab Cancer Test, including the Tumor Skin Test, or theSchultz-Dale Reaction, is a reliablemethod of detecting cancer in humanbeings.

Following is a summary of the information on the Makari Tests in the American Cancer Society files:

The interest of Jack George Makari,M.D. in cancer tests first came to theattention of the public when he made areport on a modified Schultz-Dale Reaction to the annual meeting of the American Association of Bacteriologists andPathologists in 1955. At a press conference arranged by the American PublicHealth Association at its annual meeting in 1958, the first public announcement of Dr. Makari's interest in a newTumor Skin Test (TST) was made. Dr.Makari reported on a five-year preliminary study of this test to the New YorkAcademy of Sciences in 1965, and hasmade numerous other presentations concerning it. He has also developed an Intradermal Cancer Test, which combines•¿�theTumor Skin Test with an InvasiveActivity Test. This test is not availablefor general use and is being currentlyclinically evaluated under a “¿�NoticeofClaimed Investigational Exemption fora New Drug― DBS-IND 216, issued bythe Division of Biobogics Standards, U.S.Department @ofHealth, Education, andWelfare,

Tumor Skin Test (TST)

According to Dr. Makari's report tothe New York Academy of Sciences in1965, the original Tumor Skin Test

(TST) used four intradermal injections.'Three of these contained serum antibodies from the individual to be tested,combined with Tumor PolysaccharideSubstances (TPS) which were preparedfrom the tissues of three types of tumors—¿�carcinoma of the lung (TPS-Ca), fibrosarcoma (TPS-Fs), and lymphoma (TPSL). The fourth injection was a serumcontrol. The findings depended on a comparison of measurements of the erythema resulting from injections containing TPS with that resulting from theinjection of the serum antibodies alone.“¿�Aratio of 1.35 or less was taken toimply a negative test, while a ratioabove 1.35 constituted a positive test.One positive finding made the test positive. For the test to be negative, the findings with all three TPS antigens had tobe negative.― Later, a duplicate test, inwhich trypsinized serum (serum-T) replaced the untreated serum used in thefour original injections, was added,making a total of eight injections usedin the TST.

A news release discussing the TumorSkin Test, prepared and distributed in1960 by Fuller, Miele, Inc., a public relations firm in New York City, stated thatin a preliminary report on the originalseries, Dr. Makari claimed that “¿�apositive test of TST reaction was obtained inall cases of early carcinoma, 85 percentof carcinoma with local extension and 60percent. of metastasized carcinoma. Thetest also detected all cases of malignanttumors other than carcinoma, and all but8 percent of benign tumors.―

Referring to a later report, the releasestated that “¿�withthe trypsin method,only 3 percent of all carcinoma patientsshowed negative results (compared with31 percent in the previous two series).However, the new technique was con

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Unproven Methods ofCancer Treatment

The following statementconceruing tests for cancerproposed by Jack G. Maka.i'i, M.D.,including Intraderinal CancerTest, was recently distributedto the 58 Divisions ofthe American Cancer Societyfor their information.

Makari Intradermal Cancer Test

siderably less accurate than the originalin detecting malignant tumors other thancarcinoma, and in detecting benign tumors.―2

In closing, the release quoted Dr. Makari as concluding: “¿�Inhealthy youngerpersons, a positive TST reaction indicates a susceptibility to tumor, whereasin healthy older persons, a positive TSTreaction indicates the presence of eithera precancerous lesion or a latent tumor.―

In the report, made on November 8,1965 to a meeting of the Section of Biological and Medical Sciences of the NewYork Academy of Sciences, Drs. Makariand Hayton stated that the “¿�aimof thepaper― was “¿�toprovide a thorough evaluation of the Tumor Skin Test over aperiod of follow-up extending from 3 to7 years.― 1 This paper, reporting on 854subjects tested and studied between 1958and 1965, provided a great deal of complicated data, but no summary or statement of conclusions was made. In aninterview following the presentation ofthe paper, Dr. Makari was quoted asstating that “¿�thetest proved 90 to 100percent accurate in detecting early casesof carcinoma.' In a group of apparentlyhealthy younger persons, the test showed14 persons to have a positive skin test. Inthe five-year follow-up, he said 13 ofthe 14 developed cancer.―

IntradermalCancerTest(ICT)

In a personal communication to theAmerican Cancer Society in January,1968, Dr. Makari said that the TumorSkin Test, using untreated and trypsinized serum, alone and with the TumorPolysaccharidal Substances (TPS), wasat that time used to determine only thata tumor, benign or malignant, was present. A further test, which is still underinvestigation and not available for general use, called Invasive Activity Test(IAT), using heat treated serum, aloneand with TPS complexes, was used onserums giving a positive TST to determine whether malignancy was present.A decision ratio of 1.35 had been adoptedfor TST and a ratio of 1.20 for the IAT.Ratios greater than those constitutedpositive tests. These two tests used together are known as the IntradermalCancer Test.

ModifiedSchultz-DaleReaction

This test, originally proposed by W. H.Schultz of Germany and modified by Sir

Henry H. Dale, an English scientist, wasbased on the reaction of the womb of aguinea pig, which had been previouslyinjected with an extract made from human cancer, to the blood serum to betested.

In a report to the American PublicHealth Association in 1958, Dr. Makariclaimed that, using a modified SchultzDale reaction, he had found the test inmore than 500 cases of cancer to be 96.8percent accurate, with 4.8 percent falsepositives in normal subjects. Other investigators were reported to have obtained good results with the Makarimodification, but stated that more specific data would be needed before the testcould be evaluated fully.'

At the Tumor Immunity Conference ofthe New York Academy of Sciences in1962, Dr. Makari stated that technicaldifficulties encountered with the SchultzDale test had led him to the developmentof the Tumor Skin Test. Since that time,discussions of the Schultz-Dale test in hisreports have appeared to be primarilybackground information.

Proponents

According to the American MedicalAssociation Directory for 1967, Jack G.Makari, M.D. was born in 1917, and received an M.D. degree from the MedicalSchool of the American University ofBeirut, Lebanon, in 1941. He was licensed to practice medicine in NewJersey in 1962.

The American Men of Science, 1966,gave additional information as follows:British Council scholar, Royal College ofPhysicians & Surgeons, England, 1945-47, Diplomate, 1946; World Health Organization fellow, Harvard, 1950-51,S.M., 1952. From 1943-1950, he was associated with the Trans-Arabian PipeLine Co., first as Assistant Bacteriologistand Parasitologist, then as Instructor,and finally as Senior Physician and Director of the Hospital Laboratory. From1952-53, he was a fellow in medicine, Biological Division Johns Hopkins Hospital;from 1953-54, Research Assistant atJohns Hopkins and Physician at the Baltimore City Hospital. From 1954-56, hewas Associate Professor of Immunologyat the University of Texas and Immunologist at the M. D. Anderson Hospital& Tumor Institute. The last entriesshowed that from 1957 to 1963, he wasDirector of Research at the Muhlenberg

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Hospital, Muhlenberg, New Jersey; from1963 to the present, he has been Directorof the Makari Research Laboratories andTumor Clinic. According to informationreceived from Dr. Makari, he became anaturalized United States citizen in 1959.

In the paper presented at the NewYork Academy of Sciences in 1965, Dr.Makari was identified as the Director ofthe Makari Research Laboratories andTumor Clinic, Plainfield, New Jersey.1 In1968, the address of the Makari ResearchLaboratories was given on a letterheadas 223 South Dean Street, Englewood,New Jersey.

Dr. Thomas Hayton, who was associated with Dr. Makari in the 1965 study,is an Associate Professor of Mathematicsand Applied Statistics at Rutgers University. As of June 2, 1969, he wrote tothe Society that, although he had beena statistical consultant to the OrmontDrug & Chemical Company, Inc., sincelate 1965, and in that capacity had hadsome association with the Makari Research Laboratories, Inc., as of that date,his connection with both Ormont and theMakari Research Laboratories had ended.

In 1965, the Ormont Drug & ChemicalCompany, Inc., of Englewood, NewJersey, according to Drug News Weekly,was “¿�sponsoringDr. Makari's clinicalstudies.―5 The same article reported thatMr. Myron Pantzer was president ofOrmont, and the “¿�developmentof research on the skin test is being directedby the company's Panray division.―

Investigation

Preceding Dr. Makari's report in theTransactions of the New York Academyof Sciences, is another report by Dr.Joseph M. Miller et al. of the VeteransAdministration Hospital in Fort Howard,Maryland, on the same procedure, usinga carcinoma antigen supplied by Dr. Makari.1° In this study of 108 patientsknown to have carcinoma, “¿�diagnosisbythe intradermal test was right in 92 patients and wrong in 16 patients.The test was not satisfactory in the 31patients without malignant, new growthsin whom a right diagnosis was made in18 and wrong in 13.―A later report ona study by the same group in the MedicalWorld News in 1967, gave as “¿�theoverall results: right in 83 out of 87 patientswith malignant new growths, but falselypositive in 15 of the 54 patients withoutcancer.― This article closed: “¿�Notingthat the test is not suitable for use in

the doctor's office because of laboratorywork required, the Maryland researchercomments that ‘¿�itcould be adapted, anddoctors could be taught to give it.' Buthe emphasizes that several years of clinical study will be necessary to fully assessthe procedure.―

In response to an inquiry from theAmerican Cancer Society, Dr. Makariwrote, August 8, 1969, “¿�Earlyresultsof cooperative projects abroad and inthis country are showing a definite confirming trend to my original work withthe Tumor Skin Test,― but he did notgive any details as to where the testswere being conducted, or what resultswere obtained.

The Wall Street Journal for October27, 1967 carried an item stating that theOrmont Drug & Chemical Company “¿�saysthe British Ministry of Health has indicated an interest in testing its new ‘¿�antigens' cancer detection test,― which wasdeveloped by Dr. Makari. It added: “¿�TheEnglewood, N.J., company adds that ithas applied to the U.S. National Institutes of Health for permission to marketthe drug. . . .“

In October, 1967, in response to aninquiry, the National Cancer Institutereported that the Ormont Company hadfiled an Investigational New Drug Application with the Division of BiologicsStandards of the National Institutes ofHealth (NIH). In a further report onJune 17, 1969, they stated that theOrmont Company's application for licensure was still under review by theDivision of Biologics Standards.

References

1. Makari, J. G., and Hayton, T.: The tumor skintest: a five-year follow-up study. Tr. New YorkAcad. Sc. 28: 198-213, 1965.

2. Makari, J. C.: Recent studies in the immunology of cancer. 5. Detection of tumors in man bythe skin testing of polysaccharide-antibody complexes. J. Am. Geriatrics Soc. 8: 675-688, 1960.

3. Cancer test is developed. Gives early warning,Academy reports. The (Hackensack, N.J.) Record,December 27, 1965.

4. Ubel, E.: Blood test for cancer announced. Srientist claims 97% accuracy. New York HeraldTribune, October 31, 1958.

5. Randall, R.: Quick test for cancer? Drug NewsWeekly, November 15, 1965.

6. Miller, J. M.; McElfatrick, C. C., and Ginsberg,M.: Demonstration of an antigenic reaction to apolysaccharide-antibody complex by an intraderinaltest in patients with malignant new growths. Tr.New York Acad. Sc. 28: 194-197, 1965.

7. An early warning system for cancer? MedicalWorld News, March 24, 1967.

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