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JAl'V(ES Ho i~tIP{ «EY 150 EAST 70TH STREET NEW YC+RIC A1. MY. NEW ENGLAND INSTITUTE FOR MEDICAL RESEARCH RIDGEFIELD, CONN. March 1963 dical Research was founded porating other sciences with medicine and biology in order bette and cure of disease. Icy or disease occurs at cells of the human body. Only by und function in cells and body fluids can we understand a come disease. Molecular research has been greatly advanced by discoveries decades in physics, chemistry, mathematics and elcc- ach adding significantly to medicine a.nd biology. approach - termed "intc:rdisciplina,ry» b dation of the Institute's work, Since basic research at the Institute ular level underlying all life numerous other fields of science. Highlights of work at the Institute since our previous report noted on following pagcs., JOHN H. HE Executive The Trustees of the New England Institute for Medical Research cordially invite your inquiry into its work, preferably by a personal visit, so that you will be in a better position to recognize its merits and needs. Special group meetings can be arranged for daytime or evening. Gifts, grants and be- quests to the Institute qualify as charitable contributions under federal tax laws.

RF Effects on Cells and Chr RADIO WAVES ( r.f. ) , pulse effects, have powerfu shown at this Institute, and since wi R.£. causes single-celled organisms to in the electromagnetic field, and also a nside living cells. Application of r.f. fields to divi lls in the gro example, can - fete with the cell's repro upon physical parameters, we find inhi sion; a great variety of nuclear abnorma somal fragmentation, and loss of genetic materi latter changes eventually result in death of the cell. Implications of this type of cellular response to treatment with r..f. in malignancies are obvious. We are searching at this~ Institute for specific frequencies which may inhibit reproduction of malignant ce affecting normal cells. The r.f, effects we are studying are .non-ther.rn.al. Thermal effects have been known for years. Applying this energy in pulses is designed to reduce heat to a bi- ologically negligible level. To make sure of this special thermal controls are set up. Experiments to fine the range of temperature shocks in dividing cells of Drosophila have been publislaeds .pundarrzental changes in the hereditary mechanism appear ta result from treatment of germ cells with r.f. Experiments with the fruit fly, Dros6phila, have yielded both dominant and recessive as sex-linked recessive lethal ble mutations, as well male flies receiving tb.ex.o..s Furt ions which destroy r.£. induces "crossing over" in the germ cells of male Drosophila, a phenomenon occurring naturally only in the fer.aale fly. These genetic effects resemble those resulting from apµ plication of ionizing radiation, which has tremendously greater energy levels. However, the dose of X rays necessary to produce the same amount of crossing over in the male as does r.f. also produces many other sim,ul» taneous effects; r.f. does not. Treatment with r.f. and gamma radiation, either sequentially or simultaneously, appears t producing more mutations t sed independently, a pb.eno.m,enon now red further because of its obvious interest as a mbination therapy in malignancy. ch is being vigorously pressed to elucidate the processes controlling these phenomena and to ex- plore the range of genetic changes produced at different frequencies. Tissue cultures of mammalian cells (,in« cluding mouse, hamster, opossum, and man ), usi is Doctor ts on Non-Biological Systems . Developmental Genetics Studies at the Institute on the developmental patterns in heredity and growth by Doctor K. C. Sondhi have re~ sulted recently in publication of several analytical anc ical paper In an attempt to obtain a better understanding of th, mechanism of the effects of r.:f., experiments have re cur been carried out in non-biological systems b H. :b£eller and Doctor D. J. Wilkins. ical surface charae of colloids is rnarkedl hort times. In terrc nergy required to reduce this charge undf nt theory, r.f. falls short by an enormous factor. , the length of waves required to produce tl ite specific and discrete, depending upc ysical parameters for wb.icbh no known physic s additional materials aspects of this work ysical chemistry m ience. It has giv( geophysics. Becau physical studies, aj ntal rigor which th Advisory Cozncnict verre Petterssen, P of the Departm, sity of Chicago; Dr. Joseph Kaplan, Professo. ics, U.C.L.A.; Dr. Colin Pittendrigh, Profe of Biology, Princeton University; Dr. Walter Orr F erts, Director of the University Corporation for Atrr pheric Research, Boulder, Colorado; and Dr. Hel, Landsberg, Director of the Office of Climatology, L Weather Bureau. Increasing Resistance of the RES to Disea Research has been conducted for several years at Institute on methods of stimulating the primary de sive system of the body, the reticuloendotb.elial sys ( RpS ), to prevent disease due to bacteria, viruses, toxins.r1,xz.13.z4.r.s Recent studies have shown that a major increas o disease results from stimulation of the ' ipids (a group of organic compounds related to s) and is intimately involved witb the individ Under stimulation, the RES rnark is,1s,17 but stimulation of ph ide adequate explanation.

control over size, c these variables are klel This requires the synthesis characteristics through involved tec and organic chemistry. The colloids, .raugh.l ia,l dimensions, carry built-in electrical surface charges, fluorescent dye incorporated throughout their structure. The surface charge, applied as a"sk.i.n" oof macromolecules, can be varied at will. Other studies involving colloids, designed to de- velop a test of resistance in man, have produced unex- pected data which may throw significant new light on liver function in transferring certain colloids fr(an°lm the ~l1CJQC~ stream 18 New Aspects a f Immunity to Disease A system in many respects ideal for RES studies i fertilized hen's egg, which at the outset is devoi antibody-producing mechanism. In such a system we have shown that resistance to infection of embryonated eggs may be qualitatively modified by adding antibody and immunologically competent tissue (spleen) from an adult normal or immurlixedd chicken and an RES- imulating agent, or combinations of these, as judged survival to challenge by an infectious agent (Sal- monella typbimvrivrrz) which is lethal for eggs in doses of as low as one bacterial cell per egg.'9.2p to Cancer a ists are beginning an extensive new pro- rch into the possible role of RES rabbits has been in.- A livexs in corljunc- ion sckledule. ed by Doctor J. P. Collection of H. Heller quantities major stimul studies of embrqalxate whether the stimulation shark liver lipid against infec .tert the laost-tumo.t equilibrium in Doctor Ransom and Doctor Bliz the initial stages of this new i Microbial Intera We are growing several types of gether in a continuous culture requiring ela paratus to provide a constant excess of nutrient cornitlg into the culture and a constant effluent of microbial waste products. Intriguing in this work is the fact that eertaznn microorganisms inhibit the growth of others, by some unknown ,p;eecess.zl,2a In recent studies by Doctor Ransom with this system, a normal yeast inhabitant of the human intestinal tract markedly interfered with the .hh of certain pathogens causing intestinal disease. iments have sh.ownn that a similar in- New New Studies on Proteins Dr. Lloyd H. Reyerson is doing basic research proteins at this Institute, using a new technique studying their functions requiring the use of phy physical chemistry, and other sciences.'3,24 His findings may help science to understand the biological behavior of many different protein groups. REFERENCES TO TEXT investigatioa into radio frequency effects which ap to be active ES In whole•body irradiaeion. x. H. Heller and A. "~eixeiaa-Pintor lletin, 4:10, 1958, ethod of creating chxoaaosomal at+errations: 1. H. Heller into, Nature, 183aq05> 1959• unicellular or nlsms Ia an electtomagnetic field, A. A, T« I»1ef elski, ~r.,. ~. T.. Cutler, and J, H. Ffeller. Fxperi» sch, 20:548, of radio frequency ln_biolaSical systexns. ~. Ti. Heller igest. Intc in Dtosaphila resulting from temperature shocks, G, k7, 8-73, 1962. jtsh~ff5ar o~1V'ew~"lnoskm 1963H(in ~kes) Journal of t.tc~r,s 7. Patterns of gene nleiotrouv in anortrhoiseneric arocesses. K. C, . Sondhi, 8. The evolution of aa pattern. K. C, Sondhi, Evolution, 16:18G. 1961 9. The dynamics of pattern fpranatia m K. C. Sondhi and J. Maynard Smith, 10. Effects of radio frequency fields on the tteta potential of a colloldal suspen- sian. 7. fT, Heller, D. J. Wilkins, ], P. Preebara, Nature (London), 1963 (inpress). 11, lth"T1CU'LC71i1±Wo Nam York City, 196 12. Morphologic changes a the Ncw York Academy 13. The enhancement of he Cutler. Jouraal of fmmun 14, Nantotic 1t;laS stimulatory li Acaleaay of Sciences, 88:11b, 1960. 15. 1"xffect of ~yraasan an erythraphagacyrasia. _ plo8y. 8d.73, 1961. 16. Effect of a reticuloendothelial stimulatia~ ~al;eat (restim) on resistance of mlce. ~9S2ltanstmr. "V. ~. Pasternak, J. Fi, kTcUcr. Journal of Bacteriologq, 84;A~66, 17. New advances in seiaaulation of the RES, ~. ~. ~Ieller, J, P, Bansoar, V. 2. Pasternak, ProceedinSs of Syarposiuar, encre National dc Ia 17.echerche 5cientiG.que, Paris, June 20, 19 18. ltapid Pxoceedi (in press). 19. Action des agents stlarulants du sysans,e rfticulaeadoth€lial sur Ia rdsistance des eaabryans de Poulets portents d'une greffe dc rate adulte. J. k_ Ransom, 6, Cr. Hllxnalcov, V. 2a. f'asternak ec~.H. Heller, Compces rcn de la Socidrd de 13ialogie, Tome CL"VI« ao, 6, lr. 1022, 1961 20. Madifzcation of Salmonella typhirnuriuar infection of embryonated e~ggs by aatiseru:m, adult splenic tissue, and combinations of thesc agents. E. C7. Dliz. aakov, J. P. Ransom and ], FI. Heller, Proceedings of the Society for Eac- perituental HlolagY an 21. lnteracrion of continuously fed cultures of "Vihrio cholerae, eaterococci and lactobacllli. ~) P. Ransom, R. H. Ceder, and S, B. Pormu.l. Bacteriological Proceedings, 11.'7, 1961. 22, Interaction of v'ihrio cholerae, Shi ella dexaeri, enteroeocci, and lacto- bacilti in continuously fed cultures. t P. Ransonn. R. A. FInlcelstela, R. E. Ceder, and S. B. Farmstl. Proceedings of the Society for Ercperimenrnl Hi- alogy and Medicine, 107:332, 1961. 23. The sorption of H20 and L1s0 vapors by lyophilixed B•lactoglobulin and the dauteriuna cacchan~~e effect. Lloyd 1"1. Rey1erson and Wasyl S, ttnoiecryi. Jaurnal of Physical Gharnistry, 44:811-815, 960. 24. Furcher studies oa the sorption of k1 0 and 1~20 vapors by lpsaz~ yr.he and the deuterlu.m exchange effect. 'C~'asp1~. 1"lnoiewyj and l.loyd He Reyerson. Journal of Physical Chemistry, 6S:16h4, 1961, af iaiected fat in the gut of the rat, D. J. Wilkins& iety far Experimental Biology and Medicine, 1963

L Grove Street, Ridgefiel I r. BOARD OF TRUSTEES I,ieut. Gen. Leslie R,. Groves ( ret. ), Darien, Conn, George C. Haas, Jr,, President, Haas financial Corporation, New York, iwT. Y. Dr. John H. Heller, President, New England Institute for Medical Research, Ridgefield, Conn, Dr. Marjorie Knauth, Wilton, Conn, George M. McCorkle, Vice President, New American Library of World Literature, New York, N. Y. Paul .t1.. Peasley, Vice President, Fairfield County Trust Company, Stamford, Conn. Edward L. Schulz, Vice President, Galbreathwli,uff"tn Corporation, New York, N. Y. Robert T. Tate, Jr., Counsel, Esso Standard Division, Humble Oil & Refining Company, New York, N. Y. OFFICERS Dr. John H. Heller, Executive Director Robert T. Tate, Jr., Secretary William K. Hutson, Vice President G. W. Brown, Treasurer and Administrator SCIENTIFIC ADVISORY BOARD Dr. Walter L. Brown Dr. Clark Goodman Dr. Gerald W. Johnson Physicist Vice President Assistant to Secretary of Defense Bell Laboratories Prengle, Dunker & Crump, Inc. for Atomic Energy Dr. Charles A. Doan Dr. Albert S. Gordon Dr. Joseph Kaplan Dean of the Medical School, Emer. Professor of Biology Professor of Geophysics Ohio State University New York University U.C.L.A.. Dr. William Von E. Doering Dr. Robert J. Jeffries Dr. Leo Pospisil Director, Division of Sciences President Associate Professor of Anthropology Yale University Data Control Systems, Inc. Yale University ADVISORY COUNCIL CH.AIRM.AN: James L. Turrentin t, d, Conn. Charles D. Agnew Thomas R. Jones r Wilton, Co.on,. Vice Chairman Schlumberger, Ltd. Picker X.Ray Corporation Hon. Prescott Bush Murray Hill, N. J. White Plains N. Y. Greenwich Conn , , , Harold D. Lasswell Tyler P. Cobb Professor of :C aw Manager Sales Operations Yale University American Can Co. Francis D. Martin New York, N. Y. " Ridgefield, Conn, Karl S. Nash Moore & VicewAdm. George F. Hussey, J (Ret ) President, Acorn Press New Yor . Rid gefield Conn Norwalk, Conn. . , , George A. Nelson, Jr. John B. Jessup Vice President A.ttorney-at-Law Andrews, Nelson, Whitehead, l:ne. Wean Engineering Co, lnc. New York, N. Y. New York-, N, Y. Warren, Ohio DOCTORATE STAFF E. G. Bliznakov, M.D. *E, Clark Ph.D. *D, Fogel, M.17. S.. C. Harland, pla.D, J. H'. Heller, M.D, " i,t.esearCh Associate *J. M. CYBrien, x V. Z. Pasternak *A., Perks, y'h.D. W. R, Pistey, Ph.ZJ. J, P, Ransom, Ph,T7, Lloyd H. R.eyerson, Ph.D. #5, Soloway, P,h.D. D, J". Wilkins, Ph.D.