TOr Dra. Meiklejohy, Thompson and Waahburn, a Special Coamittee of the Faculty SRM Dat. hoger 8, Mitchell SUBJECT: A poosible Tepartsent (or Mivision) of Genetics at the Seheol ef Medicine T. Background: In searching for outstanding research talent, the Colorado Foundation for Negeareh in Tuberculoeis becase interested in Dr, Joshua Lederberg, Professor of Senstics, University of Wisconsin, ‘The possibility of a Departaent er Navision of Genetica in our concemed with beth research and teaching and sponsored and housed by the do Foundation for “seeearch in Tubercu- loeis, has eserged froaa conversations and corres;ondence with ‘Yr, Lederberg. TI, The general place of Ganetics in a “Medical Sehool:s Pablic discussion of genetic hasards of exposure to radiation has focused renewed attention on the genetic factor in acdicines the level of this discus- sion helps to eaphasize not only the saps in our sofentific imowledge but also in the effectiveness with which the Imowledge we have gained has penetrated to the profession and to the lay public alike, The attitude of misunderstend- ing or aystery that often attaches to cenetic issues nay be contrasted with the faniliarity with basle physiological ani b ochenical science that is a worka= day tool of every wall trained clinician, Inevitably, both cenetic research and medical practice must suffer frou this lack of rapport, where 1¢ pertains, There are several signs of a new direction and euplasis on medical genetics today, however, For oxaaple, several excellent texts have, for the first time, appeared (Sterny Harriss feel and Stull Sorety) and a nunber of medical schools (notably “ichigan, Gidahasa, Minnesota, Utah, Soman-Gray) are sponsoring research, teaching and clinice in this field, This reenrhasis may be agerlboed partly the natural grevth and differentiation of the medi- cal sciences, partly to the popular interest in genetic hygiene, an?! perhaps significantly to the increasing relative importance of “constitutional” dise eases ag nedical practice achieves effective control over contagious afflice tions, The introduction of a medical genetics center doses not necessitate a separate departments this is a decision that will depend on many lecel and personal considerations. for the desenis of clinical practice, it appsars that highly specialized training in research methods is relatively uninportant, ani the role of genetic etiology might be effectively integrated into all clinical teaching. fut the sase might bo said of other basic sciences, xperi- ments with integrated teaching are wider ways; their success may well depend on the availability of integrated teachers, and until they have been treined themselves, differentiated departmenta and courses say be an unavel able compromise e The effectiveness of the teaching of genetics in a ‘‘edical %chool would depend a great deal on effective collaboration with the clinical departuents oBu in the joint study of specific cases, wherever feasible. This collaboration should, ideally, extend beyond the classroany the medical genetics staff should serve as a foous of consultation ani provecation of interest in genetic aspects of diagnosis and therapy among the working faculty, a role thst is possibly sore critical than classrom teachinc. To accoaplish this effestively, the geneticiat should be, on the one hand, well acquainted with the liters ture in the various fields of medical genetics, and on the other, conversant with the day to day problems of his clinical colleagues, and effective in linking the tao, At a university where research in various aspecte of genetics is soundly developed, the clinical ceneticist may be the only new ataff appointment ree quired to round out a genetics progren, ‘lsewhere, a base may have to be built up gradually if « high quality of research and graduate education is te be anticipated, In such a cirounstance, whether to start with the "elint~ cal geneticist” or the basic reeearch group is open to debate, A coaprontse might be effected if an 4,5. or Pa. %, can be found who can casbine both roles, at least for the tine being, III. A proposed course in Medical Genetics eo second or third A, What 19 heredity 1. Twins, Natare and nurture, 2. Collection and interpretation of ‘amily data, Consanguinity analysis. Pedigrees, Single factor inheritance, “Zominance, Sex 3. The chromeecnes of man, Sex deteraination. B, Common hereditary factors la Plood groupe. Transfusion, Hesorrhagic disease of newborn, 6. ‘The hemoglobins end hereditary anenias. C. Rare mutants in wan, Te Mutation, Metabolic diseases with phywiologioal genetics etc,, as background, Phenylketomric oligo Ketabolde continued: give 8 : diseases continued: glycogen storage disease; galactouenic hepatenegaly; agacmaglobulinenia; hemophilias, Metabolic individuality, De Polygenic inher tance Ge enetic factors in infestious and constitutional diseases 10, Genetic factore in nental disease, Ee Genetic hygiene. di, Aims and fallacies of eugenicss social end "industrial" medical probless from radiation (and chesicals?), “3 F. Sxperinental genetic studies on memals, 12. xample--histooompatibility and acquired tolerance; the antibody respome, G, ‘Merobial cenetics, ve Mutation studies, 2eug resistance, e fegombination mechaniens, 15. Viruses (as organious and as genes), Some of these topics aay already be adequately covered in other course work, Evory effort should be made to correlate this with other offerings, Tt will be essential to seek the cooperation of clinical specialists 1) for appropriate case demonstrations, and 2) to ensure a balanced account of such topics as nental disease, eugenics and retiation hasards, If there are pro- nounced differences of opinion within the medical faoulty, it may be profit able to arrange for joint presentations or “scussi ons. Student laboratory exercises would pose nany problena, but might be worked out in collaboration with other courses (elinical patholegy; physio- logical chosistry; microbiology). Tt would be helpful to have same standardisation of preparation in gene- ties, If many premedical students will already have included a course, it would be wise to urge most of thea to do soy if not, more auphasis may be needed on the blood croups, The course is not designed to indoctrinate specialists, but to inculcate an appreciation for the role of the genetic fecter in the determination of ivesse and of noraal personal individuality, “Ath this background, the stu- dent may be better equipped to learn from his experience in the clinical years and his practice, Taxt: Fosaibly *HarriseIntroduction to ‘hasan Mochevical Genetics" feference Books: Sorsty-Clinical “enetics; Neel and Shull-itusan Heredity; Stern-iuman Genetics, IV. 7 epee outline of genetic research related in whole or in part te net A, HOMAN GENETTCS 1. Hereditary factors in diacase Statistical mothodology, Pedigree analysis, Population analysis, Twin studies, Clinical genetics ( Single factor syndrones Soke henophilia retinoblastoma xeroderma pignentation) Sra j ; Complex deternination (o.¢., e:ilepay; dlabutes) Mochenioal or developmental annlysis of genetic defects SiSEis call’ tnocia) ©" ervinwrerie oltgoptreniay anenda) Mutation retes, Ze Individuality Blood groups Transplantation speckiic ity sengory sodalitiaa (eer, phenylt:iourea taste) Moteabolic individ, ttyl Antivady reaps Anthropometre: @kin and hairy feabureas '-acet 3e Cytegensbics Counsell Jaw Lpoomntel modi cing? Detection of b:oterosyfous carriers he, SPRL MACMALTAN Gatley "Tos a * tg i» atation ani radiation effects Ze Sriagenetion 3e Developmental aralyaia of gane aff-cte be Bloo>endeal analysis of gone effects Se Experimental evolution & 7 ransplantablonesh!stoconpativiiity and aoquired tolerance Te Suscertibllityv te infectious discase 8 Cancer tesearch==tiost variations and genetios of tlewue arci sumer eella’, Ge MPO ConA TES Mutations adlation effects, Shenical mtagenesis. “echanians of klliing calis., iwolutionary pet ems in natural p.oalatione (espe of rathorena)e venetic factors in pathogenicity. Ganetic recombination acalysise Mabure ant origin of viruses. Footnotes to TW: Afids ts readily recorniged in annracteriatic metabolde digoa es tub mar be equally feportant 1 sergonal a:ffopentea, ap “ocar Wilifams hes ae hasised. Incttviduality may trae be reflected in ch.race terlatic pattems of exeretian of var'ous metabolites and nas « large, gertaial sot an acclualwe, genetic taste. Th ig also rufleetad in life ferences in | erapaubic reasoning, aeg., to feondacia, and mm a a naglected fastor in Lifesyncratic reg: ages to ouoer Arupae Ex Licit penmti> ane lysis of &e latter situations semains to be carrtad cube Por example, in ths pollo vaceination programy it has buen noted twat sone children maka @ poor antibody rear nsesg It iy so. known vbebher this has a ganetic mala, nor wool er tuis ig a gene al unves: consi veness or ® aperi 'ec unreactulvenses to t @ pelio virus. Fink (at Colom ») and aere@re Ge ctven exoorimmntel evidence for genetic variability in antle boly regeowe In eloa. Tate fiele gould be one af 62 more izportant’ arong of Sevelerment for cractical medical unce sleniinge The venoral cuection af ind’ vi-welined renstiong te onicageng is nob far aistanbe 3 cacce rated enpnesig on “gugenio" programs for the sterilisation of the go called "unfit® is largels ressonaiide for tow hind-red tavelo ment of Se medical genstics, Such negative controls are eacentially futile for the reduction in incidence of rare recessive mutations in eny event, and involve matters of public polioy that far overreach the authority of the me:tigal pro- feesion por se, “any moder students (cf, Neel and Shull) share the view that much more sclentific knowledge of hua genetics is needed before one can ade vyocate any far reaching social controls of human reproduction, of the human ceneticist is to inform his colleagues in medical practice and through thes the miblis, rather than advocate drestic interference ty society, especially when the calculated social effects are so suall, On the other hand, the public is entitled to have accase to phyeiciare who can intelligently advise their patients on genetic problems, Medicine any suseday be faced with formulating an attitude on ancther izsue where gonotic control uy be sore effective, namely the sex ratio, ‘Tris has not been the subject of auch work lately, but it is at least theoretically possible that techniques will ultimately be Cevelop:.i to enable the sex of offapring to be voluntarily controlled, “ost of we would hope that day to be deferred intefinitely, but this illustmtes the tresendous impact that human genetics is bound to have, ultimately, on medicine and on society. « Many schools have set up "Heredity Clinies" ae part of their progran in necfoal genetios, These are valuable centers for the col- lection of data, and there can be no question of public interest in these probleus, Such a service in which the genetic specialist deals directly with the patiomt is nut advocated, ‘The counsellor inevitably aust influence the patient's reproductive decisions, satters so involwed with his tetal person= ality that such consultation should ordinarily bo made with his own physician, meee should be in a position to const with physicians, and inevi- tably will, Stinviromental medicine” is taken here to enoaupass the genetic hasards from industrial and professional operations, as well as froa atomic beaks, Almest al] the exphasis so far has been spent on radiations (fran bembe, fluo- roscopy or aineral extrestion), and, except that seve hasard is involved, little enovgh is known, “Without minimizing the tremendous impertance of radie ation hasards fron, for example, fellout, it sceus there is a much broader problem of which radiation is only one part. atil recently, radiations were consi dered the only artificial aganoy by which mutations could be indueed, It ie now realived that a wide variety of checical reagents can induce mutations, “adlations udoubtedly have freer access to the gem sells, but the nutagenicliy of such compounds as hydrogen peroxide, formaldehyde, nitrogen mustard, asasorine, and caffeine raises the question whether genetic effects ehould be considered as ons aspect of chronic toxicity of coupoun’s which are part of the sveryday environment of modern aan, Sixporinental studies have now fimly established the immmogenstic basis of transplantation conpatibility in mamals, It is disheartening to ees how often these facters are ignored in surgical reports, Prenatal exposure of mice to heterologous tissue anticens provokes a tolerance to the postnatal transplantetion of eimiler tissues, Thie ie an laportant lead to the develop= mant of techniques for overcoming histecempatdbility barriers which hinder the potentially vast applications of orzan replacesent, These studies also prowise to give answers to one of the mysterious questione of imwumologys wig does the organisa: fail to produce antibodies to ita am antigans? ‘Most of the emphasis in genetic cancer research has been in the proper= ties of specific lines of micw, which are indeed indispensable research tools, ohm More recently, technical advances are leading to closer examination of the genetics of the tissue cell itself, as in the ascites tumor stucies of Hauschka and Mlein, and the axtramely promising tiasue culture findings of Puck, Ve c considerations on possible interrelations between the 'niversity of mada School of Medicina, the Calorn4o Souncation for Nesearch in Tuber~ culesie and or, Joshua Lederberg. ae The Foundation: the Foundation charter directs the pursuit of wedie cal x 1 @ eaphauils on tuborculoais, Our chief interest still reaaing in tuberculosie. Well established first class tuberculesis researchers ere very limited in number and appear to be unevailable to us so far, The Trustees as a consequence have agreed te co out of the fleld of? tubcrovlosis research, if nocessary, in order to aecurs *irct class research ab’ lity) 1.6. the quality of research is considered more invortant than the subject. 2 The creation of a Severtment of Jenetics in the School, supperte reeay or even entirely by the Toun‘ation, would be a nee ceparture on at least two courte: @) ‘4n increase rether than e further decrease in the mumber of departuents or divisions of the School, b) The now emphasis on the subject of cenetics, 3. Dr. lederberg: There is no question that this whole matter has cone up now because of a possible availability of a scientist of Or. Lederberg's caliber, (He is respongible incidentally, for the information contained in sections Ii, III, IV and VI). He will not be available, if at alJ, for from one to three years, He would bring with him his wife who is also an accomp- lished microbial ceneticist, His curriculum vitae follows: He was born in Nontelair, Hew Jersey in 1925, He rece!ved his B,5, degree fron Columble in 194) and his The% fron Yale in 1916. He case to the University of “isconsin as Assistant Professor of Genetics in the Collage of Agrieultur: in 1947, He hed risen to the rank of full Professor by 1953, He received the Fl4 Lilly award in 1953 for out~ standing work by a sclentist under 35 years of age. He has published over 50 papers on microbial genetics, a list of which is available for those interested, Among hie outstanding contributions are the desonstration of sex in bacteria and the clear demonstration that hac- terial resistance to chemotherapeutic acente is due to suatation rather than adaptation, -Y. Lederberg would not want to come here without considerable autonoy in planning his research and teaching, hence the sugcestion of a new mont, A division of a present departaernt (o.¢., Mecicine) might well meet the neods of the altuation efter further consideretion and ‘Mscuss! on, Ve Growth of a “apartment (or Division) of Genetics. If this proposal is initiated with a staf! of twe or three sicrobdial geneticists, workers (at least part tine) in maaualian ccnetica and in clinical genetics woul scon be desirable, especially the fomer, “acause of the interrelated probleas, same af tion with the Hleed Buuk aisht be a logi- cal dereloment. Presented here for the consideration of those “Medical School and Unt- versity officials concerned is a proposal for the creation of a new progren of teaching and research in Genetics at the Medical School, It revolves particularly around one aan, Dr, Joshua lederberg, whoee thinking is respon- sible for the plan presented. It is definitely exploratory at this point. Mere detailed information on the subject can be obtained from the writer if desired, efere going further, the Foundation desires sone official reaction fran the authorities of the Jchool and University. Roger 3, Mitehell, “.0., ‘Srecter Colerado Soundetion for ‘seearch in Tobereculosis ec: Dre, Darley ledorberg Steams Waring