ASSOCIATION CONTINUES MEDICAL EDUCATION PROJECTSFrom your president:One of the major interests of youralumni association is the promotion 'Ofmedical education. Toward this end wehave participated in the recruitment ofpromising students for our medicalschool. Groups of high school studentshave been brought to our campus to hearour distinguished faculty discuss thefascinating accomplishments in the biological sciences, the physical sciencesand in medicine. The personnel 'Of ourlaboratories and hospitals arrange exhibits S'O that 'Our young guest mayobserve our research staff at work. Individual counseling is arranged for interested candidates. These career conferences are rewarding in interesting superior students in our profession (pp. 4-5).Medical education does not end atgraduation, for it is a continuing process extending throughout the professional lives 'Of our physicians. It 'Occurredto your president that our medicalschool should participate in a program of continuing education for ourown graduates. The best way to keepour alumni in touch with their medicalschool is to sponsor a graduate day.2 MEDICAL ALUMNI BULLETIN With this thought in mind we arrangedsuch a program this past year. Our faculty presented "What's New in Medicine." Fortunately for us our secretaryarranged for the recording of these informal presentations. The discussionsand comments proved so interestingthat we are certain that our alumni willenjoy reading them (pp. 6-36).I hope that you will agree with methat our initial effort in promoting continuing education has been most fruitful. We would be delighted to haveyour comments and suggestions. I thankour alumni for honoring me by allowingme to serve as your president this pastyear. It has been a pleasant and a mostsatisfactory experience which I shalltreasure. I hope that I have made asmall contribution to the growth anddevelopment 'Of 'Our association.M. EDWARD DAVIS, '22The Alumni Council has set Wednesday, October 16, 1963, for the secondMedical Alumni Day. As y'OU can see,an excellent program has been arranged:10:00 A.M. F. Howell Wright (Pe-diatrics) "Mechanisms of Respiratory Distress in the Newborn."10:30 A.M. Frederick Malkinson (Dermatology) "Effects of Radiation onHair Roots"11 :00 A.M. Richard J. Jones (Cardiology) "Cholesterol and CoronaryDisease" .11 :30 A.M. M. Edward Davis (Obstetrics & Gynecology) "Estrogen andthe Aging Process"12:00 M.-Lunch at Quadrangle Club2 :00 P.M. Richard B. Richter (Neurology) "Anticoagulants in the Treatment 'Of Stroke"2 :30 P.M. Allan T. Kenyon (Endocrinology) "N ew and Old Lessonsfrom an Old Syndrome"3 :00 P.M. John Kenward (PediatricPsychiatry) "Discipline"3 :30 P.M. Joseph P. Evans (Neurosurgery) "The Role of the 'Neur'Ological Surgeon"4:00 P.M. Albert M. Potts (Ophthalmology) "Instruments for Tomorrow"4:30 P.M. George Wells Beadle (Genetics) "Medicine and the New Bi'OIogy"5 :00 P.M. Cocktails at the Center forContinuing EducationNOTES AND COMMENTS ON THIS ISSUEOur cover picture of PresidentGeorge Wells Beadle and JohnDewey Watson was taken in Pathology117 by Archie Lieberman at our lastBio-Medical Career Conference. On pp.4-5 John L. Sommer, '53, describesthis year's event.The eight reports presented on thefirst Medical Alumni Day program areprinted in the order in which they weregiven:Hypertensive Disorders of PregnancyCHARLES P. MCCARTNEY 6What's New in DiabetesHENRY T. RICKETTS 8On Causation of Urinary StoneCORNELIUS W. VERMEULEN 9Control of ErythropoiesisLEON O. JACOBSON 11Perturbation in the Milky WayCHARLES HUGGINS 29Current Studies in OphthalmologyFRANK W. NEWELL 30 The Hurler's Syndrome and Connective Tissue DiseasesALBERT DORFMAN 32Some Advances in NeurologyDOUGLAS N. BUCHANAN 34We have included candid portraits ofthe speakers to complete the record ofthis day.Visiting alumni were entertained atlunch and after the program at cocktails at the Quadrangle Club.On page 37 is Dean Ceithaml's profile of the class of 1966 that has justcompleted its freshman year. With hisusual thoroughness he has given us anexcellent survey of the backgroundsand capabilities of the class.Four major appointments to the divisional faculty are described on pp. 40-41. The new appointments represent awide range of interests and reflect thecontinuing expansion of our medicalfaculty. Several young graduates, some on ourown faculty, have been honored thisyear by appointments to distinguishedchairs at this and other universities. Inour last issue we reported that PaulRussell, '48, had been called to the JohnHomans professorship of surgery atHarvard. On p. 42 there is news of thenew appointments of Charles F. Barlow, '47, to the Bronson Crothers professorship of neurology at Harvard andof John M. Beal, Jr., '41, to the chairmanship of the department of surgeryat Northwestern University. On ourown staff, Albert Dorfman, '44, hasbeen named the new chairman of thedepartment of pediatrics and Paul V.Harper has taken on new duties as theassociate director of Argonne CancerResearch Hospital.This year marks the fiftieth anniversary of the Ricketts Award. A description of the ceremonies commemoratingthis year's special event will be foundon page 43.MEDICAL ALUMNI BULLETIN 3BIO-MEDICAL CAREER CONFERENCEOur Fourth Annual Career Conference was held in November, 1962. Conceived in 1959 as an experiment in precollegiate orientation to medicine as acareer, the conference has been expanded to involve not only clinicalmedicine, but the entire Division of theBiological Sciences. In one eventfulSaturday, 200 selected high school juniors and their faculty sponsors weregiven a look at some of the problems,rewards, and excitement to be found inthe study of biology and medicine.An engagement to deliver a lecturefor the biochemistry department broughtJames Dewey Watson, the recentlynamed Nobel Prize winner in medicine,to the University of Chicago campus onthe day of the conference and he agreedto greet the young people assembledhere. Watson graduated from our College in 1957 and was awarded the honorary degree of D.Sc. at the inauguration of George Wells Beadle as Chancellor.At the opening of the Conference,President Beadle introduced the distinguished visitor and then, abandoning hisown notes, gave a brilliant explanationto his young audience of the molecularbasis for heredity and evolution, thework for which Watson was beingawarded the Nobel Prize. The discussion that followed was so lively thatquestions were still being raised whenthe time came for the students to leavefor the second half of the morning program.Divided into five groups, with graduate students as their guides, theymoved on to demonstration sessions.Lawrence Bogorad, Ph.D. '49, andWayne McIlrath of the Botany Department showed the growth of plantsby way of an illustrated lecture andtour of the controlled environment"phytotron" ; Clifford Gurney, '51,Department of Medicine (Hematology),used mice housed in low pressure chambers in a demonstration entitled "Miceon a Mountain-Techniques in Leukemia Research." The Departments ofPsychology and Pharmacology (John4 MEDICAL ALUMNI BULLETIN A. Harvey) presented "Reward Centersin the Brain." Cornelius W. Vermeulen, '37, of the Department of Surgery(Urology) demonstrated with illustrations from animal experiments that"urinary stones are an ancient but unsolved disease."After lunch in a dormitory dining hallas guests of the Dean of the Division,the students reassembled in P-l17 for aclinical conference. Sidney Schulman,'46, presented a neurologic patient suffering from an acute demyelinizing disease of the central nervous system. Theimportance of the history of the illness,the examination of the patient, the contemplation of the differential diagnosis,the formulation of a "working" diagnosis, and the rationale of treatmentwere carefully put across. A spiriteddiscussion followed, where the studentsdisplayed a surprising degree of comprehension and sophistication.The final episode was a "synthesis"of the day's activities by H. StanleyBennett, Professor of Anatomy and Biophysics and Dean of the Division ofBiological Sciences. He showed parallelsbetween the nervous system and ananalogous electronic circuit in a diagramwhich filled an entire blackboard.Measured in terms of the response ofthe students and their teachers and theenthusiastic cooperation of the facultiesand students, the Biomedical CareerConferences have been successful. Although it is too early to expect any ofthese students to be entering MedicalSchool, we find a number of them enrolled in the pre-medical program ofour College.JOHN L. SOMMER, '53Assistant Professorof UrologyThe date of the 1963 Bio-McdicalCareer Conference is Saturday, November 9. Richard K. Blaisdell, '47,assisant professor of medicine, is incharge of arrangements. Alumni are encouraged to let us know the names ofany young people to whom they wouldlike invitations sent.WHAT'S NEW IN MEDICINEHYPERTENSIVE DISORDERSOF PREGNANCYCHARLES P. MCCARTNEYProfessor and Secretary, Departmentof Obstetrics and GynecologyData pertaining to the hypertensivedisorders of pregnancy are contradictory as well as incomplete, and investigators in this field are mainly engagedin determining patterns of biologicchange. None of these patterns ofchange has evoked more interest thanrenal structure and function. Over ahalf-century ago, an abnormality termedthe toxemic glomerular lesion was described in patients dying from preeclampsia and eclampsia. There was disagreement concerning which of theglomerular components were involved,whether cellular proliferation occurred,and whether permanent glomerular damage evolved from this change. The autopsy findings in individuals with a history of preeclampsia and eclampsia tento forty years before their demise werereviewed. Many of these patients hadchronic renal disease, and these findingswere used to support the hypothesis thatchronic renal disease evolved from thischange. Renal biopsies obtained at theheight of the disease and during monthsimmediately following it afford a moreaccurate means for evaluating the renallesions in the hypertensive disorders ofpregnancy than retrospective autopsystudies. We began such a series in 1948.Many people arc participating in thiswork: Dr. Edith Potter, Dr. BenjaminSpargo, Dr. Yves Lefebvre, and Dr.Roger Newton. Initially these biopsieswere obtained by the transperitonealFIGURE 16 MEDICAL ALUMNI BULLETIN route at the time of cesarean section.In 1951 the introduction of the percutaneous biopsy technique by Iversonand Brun permitted us to extend ourstudies to individuals delivered vaginally. These biopsies are enlightening, andit is hoped that they will be of interestto you.Figure 1 is an illustration of the toxemic lesion. The patient had severe preeclampsia; the biopsy was obtained atthe height of her disease. The essentialchange is situated in the glomerulus. Allof the glomeruli are involved. They areswollen and ischemic as a consequenceof a thickened glomerular capillary wall.The PAS stain in Figure 2 demonstratesFIGURE 2the thickened glomerular capillary wall.The toxemic lesion is reversible, but itcannot be stated that this is invariablytrue since the material is limited. N evertheless, we have obtained no evidenceduring the past fourteen years to support the view that permanent glomerular damage evolves from this change.PRBBCUJIPSIA AlID TWO 9UBSBQUEJft' !fORMAL PREGIIABCIESPRO'fEU. BABY Ir'l'.� � B.P. KDmIA 01. �195' 15 120/75 ° z.c,'4.5 190/120'5 140/95 '.9 1183-A1h.-DieclllPP 125/70 ° °195' 12 120/60 Trao.� 1'5/90 0.02 2855-Al1v.1955 17 105/70 0� 110/70 0 ,05Q-oU.1 v.6PP 1'5/80FIGURE 3The previously normal primagravidain Figure 3 is typical of those with the toxemic lesion from whom we have obtained serial biopsies. The patient developed hypertension and proteinuria inthe last trimester of her first pregnancy;her subsequent pregnancies were normal.The toxemic glomerular lesion was present in her first pregnancy, but the renalhistology in her subsequent pregnancieswas normal.The following two cases illustrate theerror inherent in retrospective autopsystudies. The first, Figure 4, had no ante-B.E. «t« 68 80G I Age 19PROTEINWEEKS !&!. us. � �8 54 1201'70 0 016 55 110/70 0 024 56 120/80 0 026 56 130/85 0 028 55.5 150'/100 0.5 030 55 140/106 1.5 032 56 160/100 3.0 +33 55 160/100 5.0 0c.s. - 1200 - survivedRenal Biopsy -CG'fWEEKSP.P-1- 48 140/80 2.0 06 50 110/80 0.5 012 53 130/80 0 036 55 120/70 C 0FIGURE 4cedent history of renal vascular disease.She was referred to us as a case of preeclampsia, yet a renal biopsy obtainedfrom her at the height of her diseasedisclosed chronic glomerulonephritis.I&J1 - IniU.l .... _,.18 _.... - 55.6 - 170/100 - Ed. 0 - "'ot. 0Ey. - S.20-30 _... - 130/80 - 230/100 - Ed. + - "'ot. 1.5Seizur ••38 _.... - 66.6 - 230/130 - Ed. + - "'ot. 2.0C.S. JOOO Qoo.Laft IUcIne,. AtrophicSiop.y - Chronic _1 Die .... - Itiol"&1'110 daye p.r. - 56.6 - 145/90 - Id. 0 - "'ot. 1.0 -6 ....... - 56.0 - 170/110 - Id. 0 - "'ot. 0.' -• _tM - 57.0 - 210/120 - 141. 0 - "'oc. 0.0FIGURE 5......z.z. - Second PregnancyB.P. 140/90 - 210/130 - Prot. 2 Cha. - Ed ••£Y" - S; Renal Function - NOl"1II&lSe1&ur .. - Tr .... lent _tor veakne ..37 _ka - C.S. - 3300 Qu.FIGURE 6In the second case (Figs. 5 and 6),the patient had hypertension, proteinuria, edema and convulsions during twopregnancies. The renal biopsies wereidentical in each of these pregnancies;the histologic diagnosis was chronic renaldisease of uncertain etiology. These patients did not have the toxemic glomerular lesions, but chronic renal diseasewhich antedated their pregnancies. Nevertheless, if renal biopsies had not beenobtained, these findings could have beenused in a retrospective autopsy studyto support the view that preeclampsiaand eclampsia initiate permanent renaldisease.Owing to the limitations of light microscopy, the toxemic glomerular lesioncould only be placed in the non-specificcategory of acute membranous glomerulonephritis, and it became apparent thatthe resolution of electron microscopewas required to define this change moreprecisely. In 1957 Dr. Spargo establisheda clinical electron microscope unit, andanother series of renal biopsies were obtained from normal and abnormal pregnant patients for his evaluation. Therewere no abnormalities of the glomerularcomponents in normal pregnant patients.In every instance where the so-calledtoxemic glomerular lesion was presenton light microscopy, electron microscopydisclosed the presence of a uniquechange (Figure 7).Ultramicroscopy-Glomerulus-PreelampsiaElectro Micrograph. The glomerular capillary lumen is narrowed by an increase inendothelial cell cytoplasm.BOW SP = Bowman's spaceEND N = Endothelial cell nucleusEND CYT = Endothelial cell cytoplasmCAP L = Capillary lumenEPITH = Epithelial cellFP = Foot ProcessFIGURE 7The glomerular capillary lumens werenarrowed primarily by an increase inendothelial cell cytoplasm exhibiting avariety of changes: strands, particulatematter, vesicles and vacuoles. The foot processes of the epithelial cells were distinct, and there were no consistentchanges in the basement membrane.There was no cellular proliferation. Thesmall renal arteries and arterioles wereessentially normal and the tubular findings were non-specific in the light of ourpresent knowledge. Again, the reversibility of this lesion was demonstrated.The toxemic glomerular lesion is ofpractical value since it affords a meansfor validating the clinical diagnosis ofpreeclampsia-eclampsia. Its etiology andits relationship to the abnormal wateron electrolyte metabolism obtaining inthis disease are unknown. Nevertheless,the disorganization of the cytoplasmsuggests that there is a profound alteration in the metabolism of the glomerularendothelial cell in preeclampsia-eclampsia, and one is justified in postulatingthat the decreased renal blood flow,renal plasma flow and glomerular filtration rate in this disorder are due at leastin part to the narrow glomerular capillary lumens.The differential diagnosis of the hypertensive disorders of pregnancy is difficult and these renal biopsies suggestthat the incidence of chronic renal disease in this general group is fifteen totwenty times greater than current statistics indicate. In the recent series, onethird of the patients in whom we madea clinical diagnosis of preeclampsia hadchronic pyelonephritis or chronic glomerulonephritis. In our biopsies from ahundred patients with recurring hypertension in pregnancy, 40 per cent hadchronic renal disease. Of these, 14 percent had nephrosclerosis, 25 per centhad chronic renal disease other thannephrosclerosis, and 11 per cent hadchronic renal disease of uncertain diagnosis. It is our belief that the majorityof those in the last group had chronicpyelonephritis and its incidence exceededthat of glomerulonephritis. These findings, therefore, suggest that all data per-FIGURE 8 taining to the hypertensive disorders ofpregnancy must be interpreted with caution unless they are validated by somemeans. Currently, renal biopsies affordthe best means for this validation. Thisis illustrated by Figure 8.In this particular group, the tubularcapacity for the reabsorption of waterwas determined. On the basis of theclinical diagnosis it was thought thatthere were four groups of pregnant patients: a) normal, b) water storers, c)preeclampsia, and d) essential hypertension. On the basis of this clinicalclassification it was found that the glomerular filtration rate in preeclampsiacorresponded to the mean value obtained in the literature, and it was foundthat there was a relative decrease in theabsolute ability of these patients to reabsorb water. This agreed with previousreports suggesting that there was a renalconcentrating defect in preeclampsiaeclampsia. The values for patientsdiagnosed clinically as essential hypertension fell midway between the preeclamptic group and the normal pregnant patients. However, when renalbiopsies were obtained it was found thatthere were five groups of abnormalpregnant patients instead of two andthat in the individuals with preeclampsiathere was a marked decrease in glomerular filtration rate and that the tubularcapacity for the reabsorption of waterwas not impaired (Figure 9).·C, .. "III11·,.�.o,' 'I.'.!.!:&.!Il ..c,.Renal Structure and Function in Normaland Abnormal Pregnant Patients at TermA = NormalB = Excess weight gainC = PreeclampsiaD = Chronic hypertensive vasculardisease; no demonstrable renal histopathologyE = Chronic hypertensive vasculardisease with nephrosclerosisF = Chronic glomerulonephritisG = Chronic pyelonephritisCIN = Insulin clearanceTcm H20 = Maximum tubular capacity forthe reabsorption of waterFIGURE 9MEDICAL ALUMNI BULLETIN 7It was found that there were two groupsof patients with chronic hypertensivedisease. The group with normal renalhistology had normal renal function,and the group with nephrosclerosis hada significant impairment of renal function. Patients with chronic glomerulonephritis and chronic pyelonephritiscomprised the other groups. Therefore,if we had not obtained renal biopsies inthese patients we would have had anerroneous concept of renal function inthe hypertensive disorders of pregnancy.SUMMARYThere is a unique, reversible renallesion in preeclampsia and eclampsia,and we have obtained no evidence tosupport the view that permanent glomerular damage evolves from this<change. Chronic renal disease plays amore important role in hypertensive disorders of pregnancy than current statistics indicate, and all data pertaining tothis general group of disorders must beinterpreted with caution unless thesediagnoses are validated by means ofrenal biopsies.WHAT'S NEW IN DIABETESHENRY T. RICKETTSProfessor, Department of MedicineThe thing about diabetes that mostpeople are interested in these days is theoral hypoglycemic agents. This subjecthas been so well aired, and knowledgeabout it so widely distributed, that itdoes not require a good deal of time onmy part. These agents seem to be hereto stay. They are working extraordinarilywell if patients are properly selected;they continue to be dismal failures whenselection is improper. By this I meanthat they work only in patients with socalled maturity onset diabetes of moderate or mild severity, and they do notwork at all in people with diabetes whichbegan in childhood or adolescence. Thereason for this is that most of theseagents require some amount of endogenous insulin to be effective. The juvenile diabetic has no endogenous insulin;the person with diabetes beginning inmaturity does have endogenous insulin,and the oral agents are capable of releasing it from the pancreas. These drugshave been, as you might expect, ratherbadly abused in certain quarters, andwhen used improperly have led to somedisastrous results. Perhaps the best way8 MEDICAL ALUMNI BULLETIN of summarizing their effectiveness is tosay that on the average they take theplace of not more than 20 units of insulin, and patients who require muchmore insulin than this cannot as a rulebe managed with the oral agents alone.To go on to something that is newer,and, I hope, more interesting, I wouldlike to discuss what has come to beknown as pre-diabetes. This term hasgrown up in the last few years and articles about it have burgeoned in theliterature. What do we mean by prediabetes? It should not require a lot ofimagination for anyone to define it inthe abstract: every person who is nowdiabetic must have been pre-diabetic atone time. This is self-evident. But thereare certain things that we are learningabout the behavior of people who eventually do develop the disease which mayin time be used as predictors of impending diabetes, or latent diabetes, or diabetes that will manifest itself a goodmany years later.First of all, this disease is inheritedas a Mendelian recessive. If two parentsactually have the disease, all of theirchildren will be expected to develop itin the long run. Statistically this is notquite true, for a variety of reasons, but30 or 40 per cent of such children become diabetic eventually, in contrast toan overall incidence of diabetes in thegeneral population of perhaps 1.5 to 2per cent. At any rate, one looks with agood deal of suspicion on the child oftwo diabetic parents, and the chances ofhis getting it are quite good if he liveslong enough. Another pre-diabetic situation is the identical twin of a child whohas diabetes. The non-diabetic twin, ofcourse, having an identical inheritance,will be expected to show symptoms ofthe disease in time, and, indeed, in thevast majority of cases he does. Then, ofcourse, there are people with family inheritance of a less strong degree, whosechances of developing diabetes are great-er than those of people who have no suchfamily history. These facts have beenknown for a long time.In recent years it has been recognizedthat diabetic women have larger babiesthan non-diabetic women. Sometimesthese babies are excessive in size, up tothirteen or fourteen pounds; not uncommonly, they may be nine or ten pounds.The astonishing thing is that some women who are now diabetic give a historyof having had large babies as long astwenty-five years before the onset ofclinical diabetes. If you reverse this observation, you can predict that if any woman you see today in pregnancy, andpresently non-diabetic, has a baby weighing nine or ten pounds, her chances ofdeveloping diabetes eventually are fargreater than the chances of women whohave normal-sized babies. Actually, 17per cent of mothers who have babiesweighing ten pounds or more becomediabetic later on, and if the baby weighsthirteen pounds, 60 per cent of suchmothers develop diabetes in a matter ofyears. This is not a maternal monopoly;it has also been shown that the childrenof diabetic fathers are, on the average,heavier at birth than the children of nondiabetic fathers. Other things connectedwith pregnancy may warn of impendingor possible diabetes. High fetal mortality in successive pregnancies of a givenwoman is suggestive, although certainlynot conclusive, and fetal malformationsare much more common in the childrenof pre-diabetic women as well as offrankly diabetic women.Leaving the pregnancy scene, one ofthe most interesting developments is thefinding of abnormalities of the smallblood vessels and capillaries not only inpeople who have diabetes, but also inpeople who do not have diabetes but later develop it. We now have enough information to be reasonably sure thatcapillary abnormalities, as determinedeither by examination of the conjunctival vessels in the Jiving patient, or byelectron microscopy of biopsy specimens, give evidence of a disturbancewhich is characteristic of diabetes, andwhich, in a good many cases, clearly precedes the onset of frank glycosuria. Here,then, is another signpost of possible prediabetes, and we are gathering information on this rapidly as time goes on.Another indication is the occurrenceof hypoglycemia at the end of a glucosetolerance test. Fajans and Conn at theUniversity of Michigan have shown thatthis has been true of people with a family history of diabetes far more frequently than of people who have no suchhistory. These are presumably non-diabetic people, and what seems to happenis that the pre-diabetic overreacts to theingestion of glucose with an excessiveoutpouring of insulin. Terminal hypoglycemia in a glucose tolerance testought to arouse one's suspicion of a genetic predisposition and the possibilityof the disease itself appearing later on.Most of you, I am sure, have heard ofthe cortisone-glucose tolerance test(CGTT), which simply provides a littlegreater stress than the ordinary glucosetolerance test. It has been shown quiteclearly that abnormal responses to theingestion of glucose preceded by administration of cortisone pick out people witha diabetic inheritance with a fair degreeof specificity. One cannot look at an abnormal CGTT and say to the subject,"You are going to have diabetes byChristmas," but statistically it is truethat many individuals who have such anabnormal response to the test have developed frank diabetes within the following three or four years. This again is thework of Fajans and Conn of Michigan.We should be careful about using theterm pre-diabetes. I think that it shouldbe regarded as a concept now rather thana definitely determinable condition. However, it does broaden our horizon in considering the natural history of diabetes,and it has furthered the understandingof its pathogenesis.One of the most interesting developments is the advances that have beenmade in the measurement of blood insulin. This seems like an esoteric thingto do, but the importance of such measurements becomes apparent as you lookinto the matter. There is no chemicalmethod available for measuring insulinin the blood; the amounts present areextraordinarily small in the normal individual, as well as in the diabetic: 10to 100 microunits per cc of serum (amicrounit is a millionth of a unit). Failing a chemical method, one has to relyon biological assays. The first method tobe used was to inject the blood of a patient into a rat which had been depancreatized and from which the pituitaryand the adrenal glands had both beenremoved so that he was highly sensitiveto insulin. The fall in blood sugar thusproduced was compared with decreasesin blood sugar obtained with knownamounts of insulin. This method yieldedresults that indicated the presence ofinsulin, but the animal was such a labileorganism with all these organs removedthat quantitative measurements wereundependable and often not reproducible.A more recent development is the useof the rat diaphragm. In this system, thediaphragm of a rat is excised quickly andimmersed in a suitable solution in a Warburg flask containing glucose plus theserum sample whose insulin content is tobe determined; the flask is agitated fora certain period of time, and the disappearance of glucose from the solution istaken as an indication of the glucose uptake by the diaphragm. The glucose uptake thus determined is compared withglucose uptake when a known amount ofinsulin, instead of serum, is added tosuch a flask. With careful technique and meticulous attention to detail this method has been successful in determiningblood insulin in a wide variety of conditions, but it is a very demanding procedure and much can go wrong with it.A better method, developed at Bostonunder Reynold et al., uses the rat epididymal fat pad. This organ, in the rat, isvery curious; it is a discrete structure,about two inches long, and extends wayup into the abdomen. It is nearly constant in size and gives reproducible results in the Warburg. The fat pad is cutup into sections which, together with theserum to be tested, are placed in a flaskcontaining a solution of radioactivelylabelled glucose. The C1402 evolved as aresult of the oxidation of the glucose isa measure of the insulin content of theserum.Values for blood insulin by this method are much higher than by the diaphragm, sometimes two or three timesas high. What could explain this? Thepossibility was raised that insulin mightexist in the blood in a bound, inactiveform instead of a free, and therefore active, form, and the fat pad might contain an enzyme which released free insulin from its combination with the circulating proteins. This proved to be true,and for the first time it became established that insulin does circulate in botha bound form and a free form. The proofof the bound form and its dissociationby fat tissue was obtained when extractsof adipose tissue were incubated withserum and the mixture then allowed toact on the rat diaphragm. The rat diaphragm method now gave high levels ofinsulin just as did the fat pad itself inthe experiments quoted before.Next, using techniques of this kind,the behavior of insulin in normal anddiabetic people was investigated by Antoniades. He found that in a normal person there is a substantial amount ofbound insulin in the blood during fasting, but very little free insulin. If onethen gives glucose, the bound insulin goesdown and the free insulin goes up; aftera while, things are restored to their previous situation. This observation is fullof import, because it shows that glucose,as well as adipose tissue, releases freefrom bound insulin in a normal individual. In other words, in the fasting statemost of our circulating insulin exists ina bound, inactive form, and as soon aswe eat carbohydrate the inactive formis rendered active by the dissolution ofthe association with the accompanyingprotein. Now, what happens in the diabetic individual? In the mild diabetic thetotal amount of insulin is not very differ- erent from that in the normal-still morebound than free. This is contrary to theold idea that diabetes is always the result of deficient liberation of insulin fromthe pancreas. Some mild diabetics, indeed, have as much insulin circulating asyou or I, but it cannot do anything because it is bound to protein. Now, whenglucose is given to the diabetic, there is,in contrast to the normal, only a veryslow and almost imperceptible release ofthe free insulin from its bound form.This apparently means that there issomething about the diabetic that interferes with the release of free insulin fromprotein. This observation has far-reaching implications. It may mean that diabetes is attributable to the diabetic's inability to dissociate free insulin from itsbound form as well as to a defect in thepancreas which inhibits the productionof insulin.I will return now for a moment to prediabetes and the vascular manifestationsin the small vessels and the capillaries.With the advent of the electron microscope we are learning very rapidly a lotof interesting and important things. Inexamining a glomerular capillary of adiabetic we find a great thickening of thebasement membrane, some abnormalitiesin the endothelium, some distortion inthe foot processes, and some depositionof a non-specific substance in the epithelium. This thickening of the basement membrane has been found not onlyin the glomerular capillaries, but also inthe microaneurysms of the retina, in thecapillaries of the skin, in the capillariesand smaller arterioles of the muscles,and, in fact, in every part of the bodythat has been studied with electron microscopy. This is beginning to look likewhat we might term "basement-membrane disease." This is the earliest lesionthat has been found, and the extraordinary thing is that it is not only 60 common and pervasive in frank diabetes, butappears in pre-diabetes as well. It maybe, after all, a better guide to the prediction of diabetes than any glucosetolerance test we now have.CAUSATION OF URINARYSTONESCORNELIUS W. VERMEULENProfessor, Department of SurgeryUrinary stone disease is probablyone of the oldest diseases known toman. Yet its cause is not known in spiteof modern scientific advances and inMEDICAL ALUMNI BULLETIN 9spite of the fact that stones, after all,are relatively simple mineral things.Perhaps the reason for this is that thequestion, "What is the cause of stonedisease," is not really an entirely properquestion. For stone disease seems not tobe a unicausal condition. Rather, it ismulticausal, due to a large variety ofcontributing factors, many of whichmust be present simultaneously in orderto provide a situation suitable for stoneoccurrence. In this little piece I wouldlike to illustrate the complexity of stoneformation, using two little experimentswe have performed in the course of acontinuing study of laboratory stonedisease.It is first necessary to say a wordabout the technique. We have beenusing what we could call an artificial.laboratory model of the disease, a modelproduced in the rat using the foreignbody principal. We stimulate the occurrence of stone formation by the surgicalinsertion in the urinary bladder of ametallic foreign body consisting of asmall disk of zinc about 4 mm in diameter. If other conditions are suitable,the rat will, with reasonable rapidityand regularity, develop a stone uponthat foreign body. It is possible toquantitate the results obtained in anygiven experiment by weighing the littlestone and subtracting the initial weightof the foreign body. Before looking atthe two experiments, it is only necessaryfurther to say that with different kindsof rats (different genetic strain or sex)the stone-forming reaction may besomewhat different; different in boththe amount formed and even the chemical type of stone produced.Now for the first experiment: it hadto do with the influence of milk instone-formation. Everybody knows thatmilk is a rich source of calcium, andit would be natural to expect that byfeeding large amounts of milk onewould enhance stone formation. Itshould be said, though, that in our ratexperiment our milk diet-powderedwhole milk-did not differ significantlyin calcium content from our normalcontrol diet of Purina Laboratory Chow.Thus there really did not seem to bemuch reason for doing the experiment,for the calcium intake on the milk dietwould really be no higher than that onthe /control Chow. But we did the experiment anyway, and got some surprising results. Let me just show you thepart of the study using a particularstrain of female rats. On the controldiet they do not make much stone andat the end of a six-week period, as yousee, most of them had zinc disks in10 MEDICAL ALUMNI BULLETIN their bladders still essentially bare. However, as is not uncommon, appreciableamounts of calcium stone did appear ina few instances. But on a diet of powdered whole milk, very large stones appeared in all of the rats. Moreover, onthe milk diet, stones formed in most ofthe animals also in the kidneys andureters. Now during this experiment,urines were collected quantitativelyfrom the different groups and studiedfor their excretion of calcium, phosphorus, and magnesium. The only difference appeared with calcium. On themilk diet its concentration in the urinewas three times as great as that on thecontrol Chow. Thus, on the milk diet,though it contains no more calcium, calcium excretion in the urine was markedly enhanced and stone formation verymuch exaggerated.In order to try to get at the reasonfor this, we sought to develop a synthetic powdered milk diet, a diet madeup to mimic powdered milk not only inits electrolyte and mineral components,but also in its protein and its carbohydrate. No attempt was made to duplicate exactly the fat content for technical reasons. With this artificial powdered milk diet we were gratified tofind that stone formation was similar tothat resulting from the powdered milkdiet in our previous experiment: largestones on the foreign body and in theupper urinary tract as well. We werenow in position to manipulate the synthetic diet by altering one or another ofits components in order to see wherethe special milk factor might lie. Atfirst we thought it might be attributedto the special milk-protein casein. Buta study using a different protein gavethe same result. We next turned to thecarbohydrate content. Now the milkcarbohydrate is largely lactose. So asynthetic diet containing lactose wascompared with an identical diet exceptthat glucose was substituted for lactose.And with this single substitution, thestone-formation was completely wipedout.Milk, then, is a calculogenic food forthe rat not only because of its calciumcontent, but also, and importantly so,because of its very high content of lactose. Lactose apparently acts by facilitating the absorption of calcium fromthe gut in ways not yet understood.N ow though milk seems to be a calculogenic food for the rat, we shouldnot, of course, rashly extrapolate fromthe rat to man. But let us not considerthe question of practical application;this study is presented only to illustratethe complexity of stone disease. With it we see how such a far-out factor aseven the carbohydrate of the diet maybe a decisive contributing factor.The second experiment has to dowith the drug Diamox (acetazolamide),which is used rather widely in thetreatment of certain medical conditionsand a few instances of stone formationhave been reported in patients usingthis drug. This is not too surprising because Diamox makes the urine alkalineand also increases its ammonia, and decreases its citrate content. - All thesechanges would tend to favor development of stones composed of magnesiumammonium-phosphate. Now, we have akind of rat that makes stones of thistype and we thought it might be interesting to try the effect of Diamox onsuch rats. When this was done, it wasfound that Diamox results in muchlarger stones forming upon the zincnuclei. Moreover, large numbers of accessory stones also appear in the bladder. What is more interesting is thatmost of the animals also had stonespresent in the upper urinary tract, inthe kidney, or in the bladder. Now inan experiment like this, we ought tohave a third group of animals, animalswhere Diamox is given but where noforeign body is present, that is, where nooperation was performed. We have sucha group, but no stone whatever wasformed in those animals. This is strange,for consider: Diamox alone-stones noplace; Diamox in conjunction with aforeign body-stones every place, evenin the kidney, though the foreign bodyis in the bladder. How does the foreignbody work to produce stones in theupper urinary tract? Well, we took afourth group of animals and operatedupon them, placing the zinc foreignbody in the bladder. But then, as if wehad changed our minds, we immediatelyremoved the foreign body and thenclosed the bladder. Those animals had,then, a sham operation; they had theoperation but not the foreign body.When they were given Diamox, stonegrowth was quite like before-manystones in the bladder and stones in theupper urinary tract in most of theseanimals. Clearly the foreign body itselfwas not necessary-only the operationfor putting it in.We do not understand this, but a hintof the mechanism is obtained by microscopic examination of the urines of someof these animals. Whenever Diamoxwas given, a large amount of crystalsappeared, crystals of magnesium-ammonium-phosphate-hexahydrate. This wewould expect because of the changesproduced by the drug. But if an opera-tion was done upon the rats, whether ornot a zinc disk was left in the bladder,the crystals were of giant size. How anoperation (sham or otherwise) will induce this striking change in crystalhabit is not known. The local injury ofthe urinary passages is producing a generalized and remarkable alteration inthe crystallization process. Similarchanges are at present being observedin several other experiments, but innone of them do we really understandwhat exactly is going on.Well, perhaps the two experiments Ishowed are sufficient to illustrate thateven a relatively simple thing like stoneformation is not so simple after all.Much remains to be found out beforethe disease will be understood. And, webelieve, only when it is understood willwe be in a position to eradicate it.(ONTROL OF ERYTHROPOIESISLEON O. JACOBSONProfessor and Chairman, Department ofMedicine, Director of ArgonneCancer Research HospitalI am going to try to take you througha little story this morning about thecontrol of red-cell formation, and Iwant first to say that a large part of theearly work was done in my laboratoryby two medical students, Lou Plzak,who is now at Harvard, and WalterFried, who is here as a senior resident.These boys came to me when theystarted in the College here at the University and worked through all theircollege years as well as their medicalschool days. I also want to call yourattention to the work of William Bethard, who is now at the University ofCalifornia, and a visiting scientist namedNakao who spent a year with us andwho is head of medicine in one of theuniversities in Tokyo. I will refer toothers as I go along, who are involvedin the current work on erythropoiesis.When most of us begin to work at aproblem, we are aware that the problemwe are undertaking was initiated many,many years previously. In this particular instance, two people in France, Carnot and deFlandre, had discovered in1906 a very simple thing, namely, thatif they bled animals, something appeared in the plasma which had thecapacity to stimulate red-cell formation in another animal. On the basis ofthis observation they postulated thatthere must be a humoral substance orhormone which controlled erythropoiesis. Many decades went by and very little was done with this observation. Itis only in the last fifteen years that thefield has moved very rapidly. Plasmarich in the hormone can be obtainedvery easily. We sometimes refer to thismaterial as anemic plasma or cobaltplasma, but when I do so I am in factreferring to the hormone which has nowbeen described and called erythropoietin. One has only to bleed the animal,put it in low oxygen or give it cobaltouschloride and the plasma becomes richin this substance. One can store theplasma in the frozen state and retainthis activity indefinitely at -180• Thuswe know that this humoral substanceexists in the blood but the assay methods used over the years were insensitiveand qualitative. We decided to investigate methods of assay for the hormone,and perhaps find out something moreabout where the material was produced.its mode of action, etc.Here is where Dr. William Bethardand the Japanese professor, Kiki Nakao,came into the picture. Working together we studied the effect of anemicplasma on the iron uptake of the redblood cells in the peripheral blood ofrats. Radioactive iron (Fe':") providesa beautiful tool for studying red-cellformation, for the simple reason thatthe atoms of the radioactive iron injected go only into the newly formedred cell, and never into the older redcell population, and it is thus possibleto study the effect of a number of materials on red-cell formation. However,this method is not sensitive enough, because the difference between the uptakeof Fe:;1l in a normal animal and onegiven the hormone is only a few percent.Then, following the work by Dr. JohnH. Lawrence and his co-workers at theUniversity of California, the two medical students, Fried and Plzak, and Ibegan to experiment with the effects ofremoving the hypophysis on erythropoiesis. We found that if one takes outthe hypophysis of an animal, the redcell mass goes down approximately toone-half over a period of ninety days.But to us the interesting aspect of thissimple experiment was the first fifteendays after hypophysectomy. You allknow that the reticulocyte count of theperipheral blood is a rough index of redcell formation. The reticulocyte valueof normal human beings is usually 1 to1.5 per cent, and in rats usually 3, 4 or5 per cent. If one takes out the hypophysis, red-cell production falls toessentially zero by fifteen days asjudged by the reticulocyte count. Like- wise Fe,,1l uptake at a correspondingperiod was reduced fivefold below normal controls. Next we assayed anemicplasma in these hypophysectomized animals. We now found that if the hormone "vas given to these hypophysectomized animals, whether as anemicplasma or as the purified hormone whichhad been worked up in the laboratory,the animal responded in an exaggeratedmanner as compared to the normal; infact, in the hypophysectomized animalwe had an animal about fivefold assensitive as the normal animal. Thisprovided us with an assay method ofgreat usefulness in terms of studyingvarious physiological problems relatedto this hormone. It seemed that whenwe removed the master gland in thebody, which controls, for example, thegonads and the thyroids, and which thushas a great deal to do with metabolism,human or animal, we had reduced theoverall requirement of the animal foroxygen by about one-half. The red cellmass, on the other hand, had not fallenappreciably within fifteen to twentydays after hypophysectomy and theanimal was thus comparable to one thathad been hypertransfused. This led us topostulate that control of hormone production and thus control of erythropoiesis was controlled by tissue PO:.!, whichis another way of saying that productionof the hormone which controls red-cellfunction is related to the tissue oxygendemand and tissue oxygen supply butto neither alone.Our next method of attack involvedstarving an animal-a rat. In three tofour days after initiating starvation, theFe;;!) uptake by red cells and its reticulocytes was reduced nearly to zero. Inother words, since the oxygen consumption of a starved rat goes down (fromthe teleological point of view), his needfor red cells is reduced, so the production of the hormone more or less ceases,and red-cell production goes down tozero. We demonstrated, however, thatif one gave the hormone to these animals, red-cell production quickly increased to the normal range.We then considered the possibilitythat if one took animals-a mouse, arat, a human being-and hypertransf used them (elevating the red-cell massabove normal), then the PO:.! (partialpressure of oxygen) value of the bloodwould be increased, and since, teleologically speaking, such an animal reallyhad more oxygen going around the bodythan needed, the hormone productionwould be shut off and red cell production would cease. This is exactly whathappens. If an animal is made polycy-MEDICAL ALUMNI BULLETIN 11themic by hypertransfusion, red cellproduction comes down to zero andstays there as long as the animal ishypertransfused. This is almost a perfect assay condition, since, if we arestarting from zero, any increase in redcell production above zero can be attributed to hormone activity in the plasma or other preparation we are testing.These findings provided us with threeconditions which we could use for assayof hormone activity, namely, the hypophysectomized animal, the polycythemicanimal, and the starved animal. Today,the starved animal is used all over theworld as the standard assay. In our ownlaboratories, we use the starved rat forroutine assay but we use the polycythemic mouse assay for more quantitative studies since it is the most reliableand the most accurate. The hypophysectomized animal is still used in otherplaces.Parenthetically, I would like to tellyou about another use that has beenfound for this polycythemic animalpreparation. A medical student by thename of James Dahl, working here withR. K. Blaisdell and E. Beutler, wasinterested in polycythemia in the human being. He wanted to produce thisdisease and study it in animals, and hechose the rat. He found that if he hypertransfused the rat, 90 per cent ofthe animals developed ulcers of thestomach or duodenum. This was a fantastic observation, and it is still beingpursued by Blaisdell as to mechanism.Also, if one hypertransfuses the rabbit,45 per cent of them get typical pepticulcers, of the stomach or duodenum. Inother words, a readily available preparation for studying ulceration of thestomach and duodenum has been foundalmost accidentally.Now I want to talk about the workbeing done by Clifford Gurney, Associate Professor of Medicine, who isinterested in differentiation of the stemcells in the bone marrow. You will remember that if one hypertransfuses themouse, red cell formation goes to absolute zero in the marrow and in thespleen, which constitute active bloodforming tissues in mice. After hypertransfusion not a single red cell precursor is to be found in these tissues,whereas normally they are packed withthem. So Dr. Gurney thought that thiswould be a lovely preparation to studydifferentiation from the stem cell pool.He took the purified hormone which wehave in our laboratory and gave it tothe hypertransfused mouse. Withintwenty-four hours, he had induced amassive differentiation of the stem cells.12 ME Die A L A L U M NIB U LL E TIN These differentiated cells went on tomaturation of the red cell series. Finally,in six days, red cell production revertedback completely to zero, because in theinterim, you see, the animal had beenkept polycythemic. He now has a beautiful model for studying the stem cellpool, and the effects of various agentson the stem cells, which is a very important thing in hematology, radiobiology, and the like. In summary, if apolycythemic animal, who is at zeroproduction as far as red cells are concerned, is given a single injection of thehormone erythropoietin, differentiationof the stem cell begins, a little laternormoblasts appear in the bone marrow,and finally reticulocytes appear in theperipheral blood. But if polycythemia ismaintained, and if the mouse is onlygiven a single injection of the hormone,only one wave of stem cell differentiation occurs and the animals come backto zero again in six days. Dr. Gurneycan thus completely control differentiation of a cell population, which is aunique and important finding.Now, under what circumstances canwe increase production of the hormone?I have already told you that bleedingwill do this, and many of you will remember that back in the early 30's aGerman scientist found that he couldproduce polycythemia in rats by the useof cobalt (cobaltous chloride). Youmay also remember that W. Castle andF. Gardner and others treated some anemic patients, nephritics and others, withcobalt, and in fact, in two of these patients, as I recall, they actually produced a polycythemia. It was only logical, then, that we should consider thepossibility that cobalt produced polycythemia by increasing the productionof the hormone. Dr. E. Goldwasser,from our Department of Biochemistry,did this simple and beautiful work: hegave cobalt as cobaltous chloride tonormal rats. He then assayed the plasma of these animals and found an increase in the hormone. He thereforeproved that cobalt produces polycythemia in animals by virtue of an increasein production of the hormone. Since weknew that we could produce an increasein the hormone by bleeding, by low oxygen tension, and by cobalt, we couldlogically attack the next question:where is the hormone produced? Wetried several surgical extirpation experiments, but we found that bilateral nephrectomy alone eliminated the expectedincreased production of the hormone inresponse to bleeding, cobalt administration or exposure to reduced oxygen.These were very simple and exciting ex- periments; moreover, we found that ifwe tied off the ureters, and then bledthe animals, or gave them phenylhydrazine, or put them in low oxygen tension, hormone production was increasedeven though a severe uremia was present.In another group of experiments, wedid a bilateral nephrectomy on animalsand made them severely anemic bybleeding. We harvested the plasma fromthese animals and assayed it in polycythemic mice, which is the most sensitive assay method. We observed a veryslight response. This means that, whilethe kidney is probably the major producer of the hormone, perhaps 10 percent of the hormone is produced outsidethe kidney; this is comparable to theproduction of, let's say, androgens orestrogens outside the gonads.Now I forgot to emphasize the factthat this hormone acts in only one singleway, as far as we can tell: it acts toproduce differentiation of the stem cellin the bone marrow . We then wonderedwhether all anemic patients have thishormone in the blood. Well, we foundthat the highest titers of this hormonein the blood are found in patients withaplastic anemia or hypoplastic anemiain which red cell production for somereason or other is at a minimum. This isunderstandable, because, if a patient hasa hemoglobin of five grams but is unable to produce red cells, the low tissueP02 will stimulate the production ofmore of the hormone, which, since itcannot be utilized, will pile up in theblood and come out in the urine. Thus,a patient with hypoplastic anemia is avirtual oil well as far as production ofthis hormone is concerned. We havecalculated that a single person withhypoplastic anemia can produce a million or more units of this hormone in afew weeks-so if any of you has such apatient, you had better hang on to him,since the hormone currently costs thirtycents per unit.Then we wondered if the fact thatthis hormone is produced in the kidneyis the reason why patients with renaldisease often have anemia. So Dr. Gurney did a study simply assaying theplasma of a group of patients who haduremia because of renal disease of various types, and who were anemic. Thehormone in these people was found tobe low or absent. You have also readthat occasionally patients who are polycythemic have renal disease. This is especially true of patients with polycystickidneys, but there is a large variety ofrenal diseases in which the patient mayhave polycythemia, so that if you havea patient with polycythemia, and spe-cifically a pure red cell polycythemiarather than a polycythemia rubra vera,you must suspect renal disease andmake the appropriate diagnostic tests.Moreover, fifty-four cases have nowbeen reported of polycythemia associated with carcinoma of the kidney. Dr.Gurney had one such case, in which removal of the tumor cured the polycythemia. I have observed a patient withbenign renal cysts in one kidney andpolycythemia who was cured of the polycythemia by removal of the affectedkidney. We also had a number of patients with a hem aglo bin of the orderof 5-8 grams, diagnosed as anemia ofunknown origin, whose bone marrowshowed an arrest of the red cell series.One would expect that in these cases,the blood and urine would have a highhormone titer. When we transfuse thesepatients to normal values, the hormonetiter in the blood and urine return tonormal. In other words, as you raise thered cell count, the oxygen supply to thetissues of the body is increased andconsequently the production of the hormone is shut off or reduced to the pointwhere it is within the normal range.You may be wondering at this pointwhat value the hormone has, and whether it would help you in your clinicalpractice if we had it in quantity for youtoday. Well, we really do not know. Atthe present time, it would cost approximately $10,000 to treat a single patient,so its therapeutic value is completelyunexplored. We do have the hormone ina purified state, which we use for experimental purposes, and the PublicHealth Service is now about to go intothe production of this from humanurine sources, so that we may be ableto test its therapeutic value in a yearor two. If you have a patient with aplastic anemia and notify the Public HealthService, or tell us, we will assay theurine, collect it, and process it for usefor experimental or possibly therapeuticpurposes.In summary, red cell formation isunder the control of a hormone appropriately called erythropoietin. This substance, which has the chemical properties of a glycoprotein, is produced inthe kidney. It is not known whether thekidney is the major site of productionor is only a co-producer. The site ofaction of the hormone is in the bonemarrow where it is specifically requiredfor the initiation of differentiation ofthe stem cells into the red cell series.No red cell formation appears to bepossible without the hormone.The partial pressure of oxygen in one or more tissues of the body appears toregulate hormone production and thusthe rate of red cell production and thesteady state of the red cell mass.In a number of clinical conditions inwhich a severe anemia exists, the hormone titer in the plasma and urine maybe greatly increased. This obtains in anumber of disease states in which theprocess of differentiation and orderlymaturation of the red cell series is altered or interfered with such that thehormone produced to the anemic anoxicstimulus cannot be utilized.In other clinical anemic conditionssuch as occur in advanced renal disease with uremia it appears that underproduction of the hormone is relatedetiologically to the anemia. It is only inthis group of anemic states that therapeutic administration of the hormonemay have limited usefulness.The association of a pure red cellpolycythemia (erythremia) and suchrenal abnormalities as renal tumors, renal cysts, and hydronephrosis should beemphasized since these abnormalitiesmay be unilateral and thus early diagnosis and surgical intervention may becurative.Finally it may be stated that investigators have unearthed an essential hormone that is waiting for clinical application, and in so doing have learnedsome intriguing and basic facts relativeto the control of red cell production andthe factors maintaining the dynamicequilibrium of the erythron.PERTURBATION IN THEMILKY WAYCHARLES HUGGINSProfessor and Director, Ben MayLaboratory for Cancer ResearchWith the greatest reluctance I haveagreed not to ask the five causes ofhematuria today, the seven types ofscrotal enlargement, or the five causesof acute retention of urine.I suppose everyone goes through thestage of being a professor, but for thelast ten years we have been busy andhappy in a research institute called theBen May Laboratory for Cancer Research and life in an institute is quitea bit different. First of all one is busierthan before, and that is a privilege too.Secondly, the phone never rings. Nobody comes by. My mail each dayranges between none and one letter, andusually I put it in the drawer and in about a month it does not need answering, so the mail problem is solved. Theone great defect of being an institutefellow is that the Christmas liquor doesnot flow in, so I have to buy my own.At any rate, there is never a dull moment in the lab, and there is not a dullmoment in the problem of breast cancer either.As you probably know, breast cancerhas the highest rate of incidence of anytumor of either sex, and if you work inthis field you find that in each block inour city there is someone with this disease, someone who is coming down withit, or someone who has had a radicalmastectomy and/or metastasis and allthat that entails. But there are worsecancers than breast cancer, becausesomething can be done about cancer ofthe breast in the way of therapy. A fewthings are known about it. First of all,the incidence in our country is twentyeight per hundred thousand deaths peryear, .while in Japan it is three casesper hundred thousand deaths, so that itis predominantly a disease of Westernwomen; women who eat with sticks arerelatively immune to mammary cancer,but the food conveyors qua chop-sticksare not to be implicated as the protective agent. It is a disease of women andnot men, so obviously there is a sexrelationship, and the third thing that isof significance is that women with breastcancer are those who naturally havelate menopause. Women who have menopause at age SO to 53 are in the groupwhich is particularly vulnerable to development of breast cancer.Sir George Beatson, in 1896, firstfound that removal of the ovaries ofwomen with breast cancer very frequently induced the lesion to wither,and ovariectomy was done between1896 and 1904. That it was abandonedwas largely due to the contemporaneousdiscovery and rise of X-ray therapy tosterilize the ovaries. Whenever one hasfound something good, another comesalong who will make it worse and sellit cheaper (Emerson). Then in 1951,our friend and colleague, D. M. Bergenstal, conceived the idea that theremust be a component other than theovaries to sustain mammary cancer. Itis known that mammary cancer flourishes in postmenopausal women, and,secondly, that although one sees a profound regression occurring after ovariectomy, spontaneous regression in theclinic does not occur during the climacteric although the menopause causes adiminution of ovarian function. SoBergenstal conceived the idea that theME 0 I CAL A L U M NIB U L LET I N 13VERMEULENJACOBSONDORFMANadrenals are the gonads of the aged,and devised a method by which adrenalectomized man could be supported. Theadrenals were found to have been sustaining the disease, and since then therehas been great progress in the field.The Swedish authorities said: well, ifthey can get results from adrenalectomyand ovariectomy, we will now do a muchbetter job by hypophysectomy; andnext Dr. Loeser, in London, introducedthe administration of testosterone. Then,while the surgeons were going to verygreat efforts ro remove estrogens, Dr.A. Haddow in 1943 began to give estrogens, and it was found that both removalof estrogens and giving estrogens causedregression of appropriate cases of metastatic breast cancer. At this point, medicine found itself theoretically boxed. in. We were in a vexatious contretempsas far as theory was concerned.However, a significant aspect of thissituation is that the people who discovered these treatments, including Chicago,were all clinicians. The Ivory Towerhad nothing to do with it, and if youlook at the experimental cancer literature you will see why. More than SOper cent of it is involved with mammarycancer of the mouse, and none of thesethings could have been discovered inthe mouse because when a mouse getsbreast cancer the tumor is wholly autonomous, except in very rare cases. Sowhat happened was that, in one of thegreat flights of human imagination, itwas decided to try the rat instead ofthe mouse-and that made all the difference in the world.It seems that certain albino rats,when fed a single dose of a hydrocarbon(you can call it a polycyclic aromatichydrocarbon; we call it, 7, 12-dimethylbenz(a)anthracene for short), will immediately produce breast cancer. If onefeeds a single meal of this, 20 mg dissolved in oil, 1 cc, to ten female rats,three weeks later rat No. 1 has breastcancer, and fifty days after the feedingten rats out of ten have breast cancer.It approaches a 100 per cent incidenceof breast cancer. The remarkable thingis that the animal is given the hydrocarbon in the stomach; no stomach cancer develops; most of it passes throughthe liver, no liver cancer. And we knowit passes through the liver because it isfluorescent and can be seen. Well, fromthe theoretical standpoint, this bringsthe dining table into the problem ofbreast cancer, at least the dining tableof the rat, and, at least in theory, hydrocarbons in the diet might causebreast cancer in women. At any rate,30 M E 0 I CAL A L U M NIB U L LET I N on microscopic examination of a ratwhich, fifty days after receiving a doseof DMBA, had four breast cancers, itwas found that the cancer was mammarycarcinoma. The earliest cancer we havedetected with microscopic examinationby serial section showed thirty thousandcells eleven days after the feeding ofDMBA. This has destroyed a good dealof the theory of cancer which was accepted as fact until very recently. Theauthorities thought that cancer rose instages which were successive, but this isnot correct; cancer arises in a singlestep. We also tried feeding increasingamounts of DMBA from 1 to 20 mgto a group of ten rats; and we foundthat if 1 mg is given, 10 per cent ofthe rats get it, and if one gives 15 mg,100 per cent of the rats get it. This isa stoichiometric response curve.Perhaps at this point you would liketo hear a simple definition of cancer.Well, I'll let you in on a little secret.Cancer cannot be defined, by myself ormy friends who work in this field, in afew words. But I will make a stab at it.The cancer cells ferment in the presenceof air. Fermentation in microorganismsmeans production of ethyl alcohol; fermentation by animal cells means production of lactic acid. Fermentation under aerobic conditions is a commonquality of cancer.Further, certain cancers are hormonedependent, and this is a concept discovered at Billings Hospital. Five hormone-dependent cancers have been recognized: neoplasms of prostate, breast,thyroid, endometrium and certainlymphomas. 1£ one removes steroid hormones from a normal creature, the secondary sex characteristics undergoatrophy, but their growth may be reawakened by administration of the appropriate steroid; if the hormone injections are then stopped, atrophy of thetarget sets in. These cycles of growthand atrophy can be repeated manytimes, respectively by giving or withholding hormones. Hormone-dependentcancer cells are different. When supporting hormones are removed in a creature with hormone-dependent mammarycancer, the cell does not merely undergo atrophy; instead, the tumor cell dies.Therefore, in hormone-dependent cancers the hormones are of prime, cardinal and critical significance for thelife of the cells.Well now, with the new methods, thecancerologists have something withwhich to work, and the foregoing represents some of the things which keepus busy and happy in the lab. CURRENT STUDIES INOPHTHALMOLOGYFRANK W. NEWELLProfessor, Department 0/ Surgery(Ophthalmology)A large variety of studies are goingon in the ophthalmology group here involving both clinical and basic topics.Dr. Albert M. Potts, who is director ofophthalmic research, has major programs in the toxicology, electrophysiologic phenomena, and the transparencyof the eye. Dr. Klein, who is in chargeof ophthalmic pathology, for manyyears has correlated the ophthalmologicappearance of ocular lesions with theirpathologic anatomy. Dr. Alex E. Krillis carrying out a fundamental programin which visual defects in female carriers of color blindness are correlatedwith other systemic disorders transmitted on the X-chromosome. Dr. TiborFarkas, a resident in ophthalmology, isstudying transport mechanisms withinthe lens in diabetes, an extension of thetopic that was the subject of his Ph.D.dissertation. In the time we have, however, it is possible to describe only a fewof the studies being conducted by theophthalmology group, and I thought itwould be of interest to describe some ofthe clinical programs.Despite the fact that Dr. Ricketts hasalready spoken this morning about diabetes, I wanted to touch on the thingswe are doing in that area, because oneof the most interesting aspects of thedisease is the ocular complications.These vary from rectus muscle palsiesto hydrops of the iris pigmentation, toa highly specific diabetic cataract occurring almost exclusively in juvenile diabetics, to lipemia retinalis, to rubeosisof the iris. Interesting as these complications are, they fade to insignificancewhen compared to the incidence of diabetic retinopathy, a condition responsible for some 40 per cent of admissionsto institutions for the blind in the stateof Massachusetts last year.Most of us, I think, do not appreciatethe various manifestations of diabeticretinopathy. Some time in the course ofthe disease there is marked dilation ofthe retinal veins, the cause of which isnot known. It emphasizes, however, thefact that diabetic retinopathy affects inthe main the venous side of the vascular tree and not the arterial, as occursin hypertension and arteriosclerosis. Insome patients the disease is ushered inby preretinal hemorrhages which burstinto the vitreous with rapid deterioration of the eye with retinitis proliferans.In other patients the initial ocular signof the retinopathy may be flame-shapedhemorrhages; small, deep, round hemorrhages; hard lipid deposits; or scattered,small microaneurysms that can be diagnosed only histologically.The occurrence of microaneurysmsmay be suspected when minute ophthalmoscopic areas appear to be deep, roundhemorrhages, but remain constant, distant from blood vessels, and aftermonths or years tend to undergo hyalinedegeneration. Although they were described initially in 1887, their importance was not appreciated until Ballantyne and Lowenstein in 1943 again described their occurrence in diabetes.Friedenwald, in 1947, demonstrated thatthe microaneurysms contained an acidmucopolysaccharide and could be brilliantly demarcated in flat preparationsof the retina. Most recently David Cogan, who interned at the University ofChicago Clinics and who was just appointed chairman of ophthalmology atHarvard Medical School, developed atechnique of digesting the retina withtrypsin, permitting only blood vesselsto remain. It was then possible to stainthese thin blood vessels with customaryhistologic staining material. He foundtwo types of cells, endothelial cells andcells which he believed to be unique inthe retina: mural cells.In diabetic retinopathy, Cogan andhis co-workers have demonstrated several changes at the site of microaneurysms: 1) disappearance of the muralcell nucleus with the formation of ghostcells; 2) proliferation of the endothelialcells; and 3) outpouching of the basement of the membrane.Attention has been focused on microaneurysms because in many respectsthey are similar to the change occurringin intercapillary glomerular sclerosis ofKimmelstiel- Wilson disease. It is worthemphasizing, I suspect, that next tohemorrhages and deposits, microaneurysms are probably the commonestpathologic abnormality of the retina.They may occur following central veinocclusion, in glaucoma, hypertension, incongenital malformations of the retina,and in a variety of other vascular diseases. However, it is only in diabetesthat they occur in such large numberswith preferential involvement of theposterior segment of the eye.Together with Shinji Kurimoto, a research fellow in ophthalmology, during the past two years we have beensystematically studying, by histochemi- cal methods, the retina in normal ratsand rats made diabetic with alloxan. Themain finding has been the marked concentration of phosphorylase in the diabetic rat. This enzyme in vivo appearsto be mainly responsible for the degradation of glycogen. These studies suggest that there is a metabolic changeoccurring in the retina in diabetes whichmay contribute to the occurrence ofspecific vascular changes there.Another area in which the group inophthalmology has been interested, andin which Seymour Goren, our seniorresident, has been active, is the use ofradioactive isotopes as an ancillaryagent in the diagnosis of ocular tumors.The problem is that inflammations andhemorrhages resemble tumors, and wehave been trying to develop some technique that would help us to distinguishbetween them. It must be stressed thatthe use of radioactive isotopes is butancillary to the many other methods ofexamination available, but they do havea peculiar value in the diagnosis of intraocular tumors because of the virtualimpossibility of securing tissue for histological study.There are several mechanisms whichmay be involved in the preferential concentration of an isotope or radioactivelabelled compound by a malignant neoplasm. All of the tetracyclines concentrate in the mitochondria of tumor cellsand inasmuch as they fluoresce in ultraviolet light they provide a good diagnostic tool. Initial studies were carried outwith bone tumors and this technique hasrecently been widely used as a meansof diagnosing malignancies of the gastrointestinal tract. There are, however,problems connected with the use ofthese isotopes.We have found an excellent uptakeof tetracycline (Terracycin) in recurrent malignant melanoma of the orbit;however, the tetracyclines enter the eyepoorly, even when a tumor is present,and we have not been able to find fluorescence in malignant melanomas of thechoroid following enucleation, hemisection of the globe, and illumination withultra violet light.Phosphorus-32 is concentrated by thephospholipids of the cellular nucleus,and because of the mitotic activity oftumor cells, a preferential concentrationis found in malignancy. Phosphorus-Sz ,however, is a beta emitter and the mostenergetic beta particles penetrate but amaximum of 9 mm of tissue. Thusthere are relatively stringent geometricrestrictions upon the test and this limitsits usefulness in the posterior segment even when appropriately designed detectors are used.Diiodofluorescein, whIch was used initially in the study of brain tumors, concentrates in neoplasms because of abreakdown in the capillary permeabilitywithin the tumor. Its use in ocular tumors, when labeled with Iodine-131,is limited because of the deep penetration of the gamma rays which cause radiation from the cavernous sinus to obscure the radiation arising from a radioactive target within the eye.The experience with P-32 and 1-131emphasizes the limitations imposed ondiagnostic tests using radioactive isotopes. If a gamma emitter is used itmust be quickly excreted by the bodyand retained by the tumor so that thetumor solely is radioactive. Inasmuchas tetracycline fulfills this criterion wewere hopeful that it could be labeledwith lodine-131 and detected by meansof an externally applied radioactive detector. However, we were unable to prepare a stable 1-131 tetracycline becauseof the molecular degradation caused bythe intensity of the radiation. The compounds prepared were very toxic whenadministered to the rabbit.Recently we have become interestedin the use of an isotope of Iodine which,although known for many years, hasonly recently become a nuclear reactor,through a technique devised by Dr.Paul V. Harper of the Department ofSurgery. This isotope, Iodine-Iz 5, has ahalf-life of 60 days and its major degradation is by the emission of photonswhich have a half-depth in tissue of2 em, an almost ideal isotope for ophthalmic use, since it may be used inposterior segment tumors without radiation from the cavernous sinus penetration to the external detector.We have conjugated lodine-l25 todiiodofluorescein and have used it insome forty patients, of whom nineteenhave histologically proven malignantocular tumors. In these nineteen patients, there were false negatives in fourpatients, an accuracy of about 75 percent. In the remaining patients who didnot have neoplasms there were no falsepositives and the overall accuracy ofthe test was in the neighborhood of 90per cent. I do not believe that diiodofluorescein is likely to be the ideal compound to conjugate with Iodine-l Z 5 butI do believe that other compounds willbe developed which will be useful inposterior segment tumors as well as anterior lesions.One of the most important advancesin ophthalmology in recent years hasMEDICAL ALUMNI BULLETIN 31been the use of desoxyiodouridine in thetreatment of herpes simplex inflammations of the cornea. Until the wide useof steroids and antibiotics a decade ago,this was a painful but relatively uncommon disease. Since then this disease hasappeared to be more resistant to theusual methods of treatment and morelikely to involve the stroma of the cornea instead of being limited solely tothe epithelium. In some of these patients immediate relief is obtained bymeans of a corneal transplant in whichthe inflamed tissue is removed and cadaver cornea substituted. RecentlyKaufman, at the Massachusetts Eyeand Ear Infirmary, proposed using acompound common in cancer chemotherapy to prevent replication of thevirus of herpes simplex. Large concentrations may be achieved by frequentinstillation of the drug in the eye. Insome five hundred patients treated foracute herpes simplex of the cornea, thismethod of therapy has been effective inapproximately 85 per cent. In stromalherpes it has been effective in some 60per cent of the patients.Double blind studies are just beinginitiated and the role of this compoundand therapy is by no means established.It is effective, however, in experimentalherpes of the cornea of rabbits and it iseffective in tissue culture injected withthe herpes of the cornea of rabbits andin tissue culture infected with theherpes simplex virus. This seems to bethe first instance of effective treatmentof a virus infection by means of chemotherapy and has led, of course, to studyof a variety of compounds currentlyused in cancer chemotherapy.THE HURLER'S SYNDROMEAND CONNECTIVE TISSUEDISEASESALBERT DORFMANChairman, Department of PediatricsThe Hurler's syndrome is a diseasewhich, unlike Dr. Huggins' subject, doesnot occur in every block in the city ofChicago; I would estimate from ourown experience that there are approximately ten to fifteen patients in the cityof Chicago with this disease. Despite itsrarity, however, it is of interest thatthis syndrome is one of a large group ofheritable connective tissue disorders.This disease was probably first recognized in 1900 by Dr. Thompson in Edin-32 M E 0 I CAL A L U M NIB U L LET I N burgh. He named it Johnny McL. disease. He photographed his patient, buthis photographs were not published until1940 when Henderson, working in thesame institution, found the case recordswith photographs of three brothers thatdemonstrated a syndrome characterizedby a large head, flattened nose, a massive jaw, claw-like hands, and relativefixation of joints. The liver and spleenwere enlarged and hernias were present.A variety of defects of connective tissueswere present; indeed, almost every tissue of the body was affected. In 1917,Hunter, a Canadian who was in Englandduring World War I, presented to theRoyal Society of Medicine a descriptionof two brothers who demonstrated similar changes. Hunter's cases did not havecorneal opacities and they were said tohave had normal intelligence. The following year, Gertrude Hurler in Munichpresented two cases with similar findings,including severe mental retardation, corneal opacities and deformities of thespine. This disease has now been described by many investigators and hasbeen found in all races. Detailed pathological studies have been reported, aswell as characteristic x-ray findings. Thelatter include a characteristic "boot"shaped sella turcica, broadening of bones,deformities of vertebrae, and increasedsize of the head with occasional hydrocephalus.Histologically, the disease is characterized by distorted cells which appear tocontain large amounts of abnormal material. It is difficult to identify the original cell type because of this extremedistortion. Patients afflicted with Hurler's disease characteristically developheart disease, and, interestingly enough,the order of frequency of valvular involvement is mitral > aortic > tricuspid. The order is similar to rheumaticfever and suggests a hydrodynamic basisfor this order of involvement. The valvesare thickened. The coronary arteries exhibit piling up of abnormal cells, and,indeed, some of these children developtypical angina because of occlusion ofcoronary arteries. The liver and thespleen are massively enlarged with deposition of abnormal material in variouscell types.The clinical characteristics and thegenetics of this disease have been extensively studied. Two genetic types havebeen recognized. In one group of patients the disease is apparently inheritedas an autosomal recessive occurring inboth sexes, while in other families it appears to be inherited as a sex-linked recessive in the male. We have had oppor- tunity to study chemically an interestingfamily described by Beebe and Formelat Albany Medical School. In this family, the disease appears to be sex-linked.The affected individuals survive to adulthood, some of them living to forty orfifty years of age. It is said that they arenot mentally retarded, but I think theywould be more accurately described asless severely retarded than patients withthe autosomal recessive type of Hurler'ssyndrome. Dr. Formel, who first recognized this family when he was a resident,carried out a careful genetic study,tracing the disease back to a probablecarrier, a woman who lived in about1827. The family is of Dutch extractionand lives in the mountains outside ofAlbany, where there is a group of people,descendants of early Dutch settlers whomigrated to upper New York State.There has been a great deal of inbreedingamong these people, One interesting speculation that Dr. Formel and I entertained some years ago was the possibilityof a relationship between these men, whowere semidwarfed and crouched, andWashington Irving's description in RipVan Winkle of the little men with thebowling balls. Washington Irving livedin this general area and had a sister wholived nearby, and he actually visited thisregion before he wrote this story. Unfortunately, this was not very productiveresearch. It turned out that the storywas not original with him; it is an oldGerman folk tale that he had copied whenhe was desperately in need of money inEngland. The New York Public Libraryhas his original notebooks. After severaldays spent in their study, I learned thathe was afflicted with a venereal diseaseabout that time, but nothing about thelittle men with the bowling balls.Hurler's disease or gargoylism was fora long time classified as one of the lipidstorage diseases, by virtue of the factthat following customary pathologicalpreparation, large vacuoles appeared.This phenomenon was originally ascribedto solution of the stored material by lipidsolvents. However, in the 1940's, Rileyand Lindsay and several other workerscame to the conclusion that the storagematerial is probably carbohydrate. Atfirst it was thought to be glycogen.No conclusive identification was carried out until 1952, when an importantdiscovery was made by a Swedish clinical chemist named Brante. He isolatedfrom the livers of two patients with Hurler's disease a pure polysaccharide whosecomposition was typical of chondroitinsulfuric acid, a connective tissue polysaccharide. I had noticed this report,having become somewhat interested inHurler's syndrome during the time I wasa student intern with Dr. Buchanan.Later I became interested in chondroitinsulfuric acid for entirely different reasons. In 1957, one of our former residents, Dr. Eugene Diamond, mentionedto me that he had seen a patient withHurler's syndrome and asked if I hadany interest in studying this patient. Atthat time we had no autopsy materialavailable. We were working on the biosynthesis of mucopolysaccharides andhad come to the conclusion that theywere formed in connective tissue cells.This conclusion suggested that if thematerial which appeared to be a connective issue component was present in cellsthroughout the body, Hurler's syndromeprobably was truly a storage disease. Forthis reason we studied the urine of ourpatient and, much to our surprise andhappiness, it turned out that within aday or two we were able to isolate almost100 mg of acid mucopolysaccharidefrom one day's urine collection of thislittle girl. We suspected that this wasabnormal. A control sample obtainedthe next day from my daughter, who wasexactly the same age, showed us that thenormal level was about 5 or 10 mg.At about this time, Dr. Cifonelli wasstudying the structure of chondroitinsulfuric acid B, a polysaccharide whichoccurs normally in skin. Although similar in composition to chondroitin sulfuricacid of cartilage, certain properties indicated that it was a chemically distinctsubstance. Dr. Cifonelli established thatchondroitin sulfuric acid B contains Liduronic acid in contrast to the D-glucuronic acid of chondroitin sulfuric acid Aand C. Interestingly enough, no sugar ofthis configuration had been previouslyfound in nature except when Bertrand in1898 found iditol in the mountain ashberry. When we began to study the polysaccharides of Hurler urine in more detail, we were able to identify chondroitinsulfuric acid B. Surprisingly, however,the urine also contained another polysaccharide, hepartin sulfate, a close relative of heparin. Hepartin sulfate hadbeen discovered in 1948 in Sweden byJorpes and Gardell as a contaminant inheparin, but nothing more was known ofit.We were rather fortunate that wechose this particular patient as our firstone, because we have since examinedurines of about a hundred patients withthis disease and we have found thatwhile some patients excrete both compounds in their urine, others excrete either heparin monosulfuric acid or chon- droitin sulfuric acid B primarily. Numerous patients have now been studiedby other investigators. In all cases, acidmucopolysaccharide has been found inlarge amounts in the urine.More recently, studies have been conducted on tissues of patients with thisdisease. In all cases, the two polysaccharides that have been isolated fromurine were also found in tissues. So far,it has been impossible to establish a clearcut relationship between the pattern ofpolysaccharide excretion and the genetictype of disease.The discovery of two different polysaccharides, both of which occur normally, in abnormal amounts in abnormallocations, poses a difficult problem interms of the explanation of the biochemical defect. The study of inheritance ofthis disease seems to result in the conclusion that in both types of disease, inheritance is by a simple Mendelian mechanism involving a single gene. The rapidadvances of biochemical genetics in thepast several years have established withconsiderable clarity the mechanism forconveying genetic information both fromgeneration to generation and from thenucleus to the cytoplasm of the cell.Briefly, the scheme that has emerged isas follows: Genetic information is contained in the desoxyribonucleic acidmolecule of the nucleus. The specific sequence of purine and pyrimidine bases inthis long molecule represents the key tomaintenance of specific information.When cell division occurs, the DNAmolecules are replicated so that eachdaughter cell acquires the identical information of the parent.In order to instruct the extra-nuclearportion of the cell, the cytoplasm, toform proteins characteristic of the cell,a specific type of ribonucleic acid, messenger RNA, is formed in the nucleusunder the influence of the DNA, whichis transmitted to the site of proteinsynthesis of the cytoplasm, the ribosome.This messenger RNA then directs thesynthesis of specific protein of the cell.A change in the base sequence of theDNA results in a change in base sequence of RNA and a consequentchange in protein structure. Such achange then is the chemical definitionof a mutation. In the case of mutanthemoglobins, we know now that thesubstitution of a single amino acid bythis mechanism may result in a profound alteration of its properties. If theprotein is an enzyme, such a changemay interfere with its enzymatic properties. We know that in certain genetically determined diseases, such as ga- lactosemia or phenylketonuria, the pathology results from the absence of anenzyme activity, resulting in the inability to perform one step of a series ofmetabolic reactions. Consequently, anintermediate accumulates in abnormalamounts.In the case of the Hurler syndrome,as we have already indicated, we aredealing with a somewhat different situation. There is a large accumulation oftwo polysaccharides which ordinarilyplaya normal role in the structure ofconnective tissues. One possible explanation is suggested by the recent findings that in bacteria certain genes areconcerned not with the determinationof the structure of proteins, but ratherwith the control of the rates of metabolic reactions. Such genes have beencalled operator genes. It is possible thenthat the excess formation of polysaccharides in Hurler syndrome may resultfrom a mutation of such an operatorgene. There is no critical evidence atpresent to either support or refute thispossibility.Recently, we have attempted to determine whether the Hurler syndromemight not be explained by a more conventional genetic mechanism. It is nowwell established that the acid mucopolysaccharides are bound to proteins inconnective tissues to form large molecules. A number of years ago, JohnFrench and Earl Benditt in our laboratory showed that when slices of cartilage are treated with trypsin, the polysaccharide is rendered soluble. Morerecently, Lewis Thomas and his co-workers have demonstrated that the intravenous injection of papain into rabbitsresults in the destruction of cartilagematrix with a characteristic drooping ofthe ears. It can be demonstrated thatunder these conditions, the chondroitinsulfuric acid of the cartilage diffusesinto the blood stream and is excreted inthe urine.These findings suggested to us thepossibility that the defect in Hurler'ssyndrome might reside in the proteinportion of the mucopolysaccharideprotein complex. Dr. Klaus von Berlepsch, who worked in our laboratory,has recently isolated from the urine oftwo patients with the Hurler syndrome,chondroitin sulfuric acid B under conditions which do not destroy the protein-polysaccharide linkage. Such preparations were analyzed for amino acidsand were found to contain only a fewamino acids even when previouslytreated with proteolytic enzymes.M E Die A L A L U M NIB U L LET I N 33These data suggest the possibility ofa new approach to the understanding ofheritable diseases of connective tissues.Hurler's syndrome might be visualizedas follows: Some defect in the proteinto which the polysaccharides are normally attached results in an abnormalpolysaccharide-protein complex which isreadily diffusible. Such material is notretained in its normal location in connective tissue and does not thereforeinhibit further synthesis through normal feedback mechanisms. Excess synthesis therefore proceeds and the diffusible material is carried in the bloodstream to tissues throughout the bodyand is treated as foreign material withconsequent storage and urinary excretion.This hypothesis is still conjectural,- but has considerable merit since itbrings Hurler's syndrome within thescope of other heritable diseases. Furthermore, it affords a possible explanation for the many other heritable diseases of connective tissue, such as thechondrodystrophies.SOME ADVANCES INNEUROLOGYDOUGLAS N. BUCHANANProfessor, Department oi PediatricsThis is the story of three boys, allten years old, who died about six monthsafter the onset of their trouble. The setting is in Europe in the middle of thenineteenth century. William was theking of Prussia, Bismarck was fortyyears old, Beethoven had been dead fortwenty years, and Brahms was a youngman of twenty-one.The first scene is in Berlin, where onJuly 1, 1854, Carl Zeppner, ten yearsold, was placed under the care of Professor Frerichs. This boy had been welluntil the summer of 1853. Then, whileswimming, his friends held his head under the water in one of their games.Soon after this, he complained of headache and began to speak slowly and.with difficulty. Gradually he lost thepower of his arms and legs, and hewould spend days in bed because ofweakness. When he did move his limbs,an irregular tremor was disclosed. All ofthis gradually became more marked until by December, 1853, he was no longerable to speak and he had much difficultyin swallowing. Despite his physicaltroubles, however, he remained normal-34 M E 0 I CAL A L U M NIB U L LET I N ly intelligent. When examined by Frerichs he was unable to sit or stand orhold things in his hands. He had noactual paralysis, but all of his movements were slow and weak. His face hadan expression of indifference and he wasunable to swallow properly or to speak,but he was lucid and had no troublewith his hearing or his vision. After ashort episode of fever with convulsions,he died. He was found to have hadcirrhosis of the liver. The brain wasexamined, but not in detail. It was saidto be soft, particularly in the region ofthe fornix and corpus callosum. N othing else abnormal was described in relation to the substance of the brain, butthis is the first record of the illness nowcalled Wilson's disease.FRONtAL SBO!'ION.Frontal section of the brain with softening in the outer layer of the left lenticular nucleus.The scene now shifts to London whereon October 5, 1886, Sydney M. was admitted to the National Hospital, QueenSquare, under the care of Sir WilliamGowers. The boy was ten years old andfor some months had suffered fromstiffness and weakness of his limbs anddifficulty in speaking. Gowers describedthis as a changing spasm of tetanoidcharacter. Clumsiness with his knife andfork was the first thing which had beennoticed by the boy's parents. This awkwardness in movement gradually increased, and then spontaneous, irregularmovements developed which affectedhis arms and his legs. He had a continuous and silly smile. His mouth washeld wide open by a spasm of the depressors of his lower jaw. If asked toclose his mouth, he pressed the lowerjaw up with his hand beneath his chin.After a few moments the spasm gaveway and he then could close his mouth,but in a few minutes the spasm wouldappear again, and again his jaw wouldbe pulled down. His tongue was retracted and this interfered with his abil- ity to swallow and to speak, but heappeared lucid and had no difficultywith hearing or with vision. Elevenweeks after his admission, fever developed and he died about six months afterthe beginning of his trouble. Examination demonstrated cirrhosis of the liver.A portion of the brain and of the spinalcord was examined, but nothing unusualwas described. Two years later, on August 29, 1888, this boy's sister Charlotte, who was fifteen years old, wasadmitted to the hospital with this sametype of trouble. She too died after abouteight months and like her brother wasfound to have had cirrhosis of the liver.Examination of the brain and spinalcord was made, but no abnormality wasdescribed. These two children of a fam-SYDNEY M., age ten, in 1886ily of sixteen had an older brother whohad died some years before at the ageof fifteen from a similar trouble.Gowers recognized that these childrenhad suffered from the same disease andthat this was one which had not at thattime been described.Three years later, on September 20,1889, William S. Walter, ten years old,was admitted to St. Bartholomew's Hospital under the care of Dr. Gee. Thisboy had been quite well until about sixmonths before when without associatedillness or accident, weakness developedin his right hand and arm. His speechbecame slow and difficult to understandand he appeared silly and had difficultyin swallowing. Weakness then appearedin his left arm and in the left hand andhe soon became unable to speak. Heunderstood what was said to him andwhen he was forced or encouraged hewas able to produce a few words. Hewas not aphasic, he was mute. He became restless and had fever and diedabout eight months after the onset ofhis trouble. On examination cirrhosis ofS.F., age twenty, in 1898 before theonset of the illness.D.P., age sixteen, in 1903 before theonset of the illness. S.F., age twenty-six, in 1904D.P., age nineteen, in 1906Photographs of two of the patients in whom Wilson established the diagnosis ofhepatolenticular degeneration.the liver was found. His brain was examined and softening was found in boththe left and the right lenticular nuclei.This was the first report of the changesin the liver and in the basal gangliawhich are now recognized as the essential changes of hepatolenticular degeneration.The classic description of the diseasefrom which these children suffered waswritten in 1912 by Kinnier Wilson. Hewas then Registrar to the National Hospital, Queen Square, London, and hadbeen house physician to Sir WilliamGowers. Wilson's interest in this diseasecame originally from the description ofthe family M. and from the ideas aboutthem that he was given by his chief. Itis of interest to remember now thatGowers in speculating about this illnesssuggested that a toxic blood state wasthe cause of the signs and symptoms.Wilson followed the fate of the familyand observed himself three young people who ultimately died from this disease. In all three he found cirrhosis ofthe liver and degeneration of the len tic- ular nuclei. He called this new diseaseprogressive lenticular degeneration. Later, Hall of Denmark suggested the titlenow universally used, hepatolenticulardegeneration.During the period from 1900 to 1912,another classic description was made inmedicine which seemed to have no connection with the story of the three boys.In 1902 an ophthalmologist, Kayser,described a peculiar brown ring whichhe had seen in the cornea of a patient.This was a farmer, twenty-three yearsold, who had had unsteadiness andtremor since he was eighteen. A yearlater Fleischer described two examplesof this corneal ring in patients who hadin addition unsteadiness, stiffness, andtremor. One came to microscopic studyand was found to have had cirrhosis ofthe liver. The other was actually thefarmer who had been first described byKayser. He was followed until his deathin 1911. Examination of his brain wasmade and nothing abnormal described.However, after Wilson described lenticular degeneration this brain was exam- ined again by Spielmeyer in 1920 andthen was found to have the characteristic changes in the neurons and in theglia. It was after 1912 that understanding came of the relationship betweenthe Kayser-Fleischer pigmented ring inthe cornea and the changes in the liverand in the brain characteristic of Wilson's disease.Other observations which at the timeappeared to have no possible relationship to this whole story were made inthe last few years. There is a diseaseof sheep and of lambs which has beenknown for centuries. In Britain this isdescribed by shepherds as the blind staggers or as swayback. Lambs born withthis trouble most often die. After a verysevere epidemic of this in Australia attempts were made again to discover itsorigin and a group working in westernAustralia suggested that it was the result of a deficiency of copper in thediet of the ewes. There now seemsproof that this is true, but the problemis still complicated. This disease inlambs is common in Peru in the regionof the richest copper deposits in theworld. Various trace elements are needed in diet, but there is a competitiveaction among some of these, particularly between copper and molybdenum. Asa result there may be deficiency of copper in the body even when the diet contains copper in adequate amounts.About this same time many attemptswere made to discover any possible etiological factor which might contributeto the demyelinizing disease known asmultiple sclerosis. Chemical measurements of trace elements in such patients were made since there was avague feeling that the disease might beproduced by a toxic reaction to one ofthe heavy metals such as lead or zinc orcopper. In this study various patientswere used as controls who did not haveevidence of multiple sclerosis. Some ofthese had hepatolenticular degeneration.No abnormality in copper metabolismwas found with multiple sclerosis, butthe patients with Wilson's disease werefound to have an inability properly tohandle copper.Since then much biochemical studyhas been made of this whole problem.It is clear that the physiological abnormality is very complicated and there isas yet no simple or absolute test whichby itself will establish the presence ofthis peculiar disease. It is known forexample that Wilson's disease can existwithout a Kayser-Fleischer ring and thatthe ring may be present in the corneaM E 0 I CAL A L U M NIB U L LET I N 35without evidence of any neurologicalabnormality. It is also known now thatbiochemical Wilson's disease may appear with an acute hepatitis and disappear when the hepatitis resolves. It isprobable that these discrepancies resultonly from the absence of an absolutetest and that soon it will be possible toknow whether or not a given individualhas a dangerous abnormality in his copper metabolism. One fortunate result ofall this chemical study has been the introduction of a form of treatment designed to lower the amount of copperheld in the liver and in the brain. Thissometimes produces remarkable improvement, but there are occasionswhen it does not change the abnormality and some where it seems to makethe patient worse. This is not an unusual finding in medicine in the earlystages of study of a disease.Bernard Shaw said in The Doctor'sDilemma that every new discovery inmedicine is re-discovered every fiftyyears. In a broad sense this can be applied to Wilson's hepatolenticular degeneration.AOA LECTUREThe annual Alpha Omega Alpha lecture was given this May by Jerome w.Conn, Professor of Medicine at theUniversity of Michigan. Dr. Conn spokeon "Some Aspects of Aldosteronism inMan."CARLSON LECTUREEdward L. -tatum, under the sponsorship of the Department of Physiology delivered the second annual AntonJ. Carlson Memorial Lecture on November 13, 1962. Tatum, who in 1958 sharedthe Nobel Prize with George WellsBeadle for their profound discoveries inthe field of genetics, spoke on "Genes,Cells and Organisms."PHEMISTER LECTUREHarwell Wilson (Resident 1932-39)gave the 5th Dallas B. Phemister Memorial Lecture last November. Dr. Wilson, who is now professor and chairman of the Department of Surgery atthe University of Tennessee College ofMedicine, spoke on "Contributions ofSurgery to the Basic Sciences."36 MEDICAL ALUMNI BULLETIN ALUMNI WON'T GIVE UPFIGHT TO SAVE DUNESIt has been brought to our attentionthat a Chicago alumna and a formerresident in The Clinics are practicing atsome cost the individualism and personal responsibility which has become atrademark of this university.In 1948, Knute and VirginiaReuterskiold, '33, bought an old farmhouse and a few acres of land in theIndiana Dunes. They later augmentedand improved their property, and Virginia became a charter member of the10-year-old Save The Dunes Council, agroup of conservationists seeking to incorporate the entire dunes area into anational park. Last October, the retiredcouple turned down an offer of $100,000for their property from BethlehemSteel Company, which in six years hadbought up 3,300 surrounding acres fora possible mill. The Reuterskiolds manage comfortably on an annual incomeof about $3,100 and the non-monetarybenefits of their quiet and secludedhome.Now, however, they face the possibility that their land may be condemnedthrough the routing of a new railroadto serve the mills. But they do not consider reopening negotiations with Bethlehem Steel. "The dunes are an irreplaceable asset which belong to all thepeople," says Virginia Reuterskiold, andshe adds, "we're going to see if hangingon might not make a difference in saving this area." We hope their gamblepays off.NEW BUILDINGS NAMEDThree new buildings at Chicago havebeen named in honor of distinguishedmembers of the faculty of the biologicalsciences. Dallas B. Phemister (1882-1951) was memorialized by the newInterns and Residents Apartments at5715 Drexel Avenue, now called "Phemister Hall." The Interns and ResidentsApartments at 1401 East Hyde ParkBoulevard was named "Carlson Hall" asa memorial to Anton J. Carlson (1875-1956). The new animal behavior laboratory was named the "W. C. Allee Laboratory of Animal Behavior" in honorof Warder Clyde Allee (1885-1955),an internationally known authority onsocial life of animals, who was Professorof Zoology at the University from 1921to 1950. LEND US YOUR EARSThe Temporal Bone Banks Center,which is directed by John R. Lindsay,has received a grant from the UnitedStates Public Health Service to supporta national campaign for ear bone bequests from persons afflicted with hearing and equilibrium disorders. Bequeststo the ear bank will be used exclusivelyfor basic research on the pathology ofdeafness and vertigo. Such researchprovides essential information on theinner ear and its relation to the brain,information which it is impossible toobtain during life because of the inaccessible location of the inner ear.Prospective donors may obtain legalforms from the Temporal Bone BanksCenter, University of Chicago, Chicago37, Ill. A network of twenty-two earbanks has been set up in universities andhospitals throughout the country wherescientists are processing and studyingthe temporal bones.GELLHORN PRIZEE. Gellhorn, Professor Emeritus ofNeurophysiology of the University ofMinnesota, has made a bequest to theDepartment of Physiology to establishthe E. Gellhorn Neurophysiology Prizeand Lectureship Fund. Although he hasnot been associated with Chicago, it isat this University that he has chosen tooffer encouragement to medical andgraduate students to enter the field ofneurophysiology. The Department ofPhysiology has agreed to match theamount of the bequest by inviting giftsto the fund. An annual award of $200will be made to a candidate for theM.D. or Ph.D. in any department whoshows outstanding promise in neurophysiology, and the award will be accompanied by copies of Dr. Gellhorn's threebooks, the most recent of which is Emotions and Emotional Disorders. Whenno suitable candidate is available, theprize money for that year may be usedfor an E. Gellhorn Lecture in Neurophysiology.The first recipient of the E. GellhornPrize is Howard A. Nash, '61. Dr.Nash is a Ph.D. candidate in the Department of Physiology.Gifts to the E. Gellhorn Fund shouldbe sent to Professor Dwight ]. Ingle,Chairman of the Department of Physiology.PROFILE OF THE CLASS OF 1966The entering medical class which assembled for the first time on our campus on September 26, 1962, consisted ofseventy-four able and attractive youngmen and women from all parts of theUnited States and from two foreignlands. This class of 1966 consists of tensingle women and sixty-four men, ofwhom seven are married and none hadany children at the time he began hismedical studies.The Committee on Admissions, whichselected this class, reviewed 1,032 applicants in the process. The seventy-fourstudents come from forty different colleges and universities, and they are legalresidents of sixteen different states andWashington, D.C., as well as Canadaand Hong Kong. It is interesting to notethat the 282 medical students in ourcurrent four medical classes represent110 different colleges and universitiesand come from thirty-five differentstates, Washington, D.C., the VirginIslands, and six foreign countriesBurma, Canada, Hong Kong, Iran,Peru, and Taiwan. With such a widespread distribution of our students it isnot surprising that the majority of themembers of the class of 1966 are notresidents of the state of Illinois. However, the largest single complement(thirty-one) does come from this state,and, as might be expected, the largestcontingent from anyone school is thatfrom the undergraduate college of theUniversity of Chicago (seventeen).There is also an unusually large number(seven) from the University of Michigan as well as three each from Oberlinand the University of Pennsylvania. Thecomplete list of all schools representedin the freshman class is as follows:University of ArizonaBarnard CollegeBrooklyn CollegeEarlham College (2)University of California, Los AngelesUniversity of California, BerkeleyCarleton CollegeUniversity of Chicago (17)Columbia UniversityCornell UniversityFranklin and Marshall CollegeGeorgetown UniversityHanover CollegeHarvard University (2)Haverford CollegeUniversity of Hawaii Houghton College, N.Y. (2)Hunter CollegeUniversity of IllinoisIndiana UniversityUniversity of IowaKnox CollegeLuther College, IowaMiami University, OhioM.I.T. (2)University of Michigan (7)Mills CollegeMorehouse College, Ga.New York UniversityNorthern Illinois UniversityOberlin College (3)University of Pennsylvania (3)Providence CollegeUniversity of Rochester (2)Roosevelt UniversityStanford University (2)Swarthmore College (2)Utah State UniversityWesleyan University, Conn.Yale University (2)With regard to the age of its individual members, this was a most uniform entering class. The average agewas twenty-one years, and nine-tenthsof the freshmen were between twentyand twenty-two years old at the beginning of their medical studies. Threenineteen-year-old students, all bornwithin a few days of one another, arethe youngest members of the class. Twoof these are women, one from HunterCollege, the other from Cornell University; the third is a young man fromthe University of Chicago College. Theoldest student in the entering class is atwenty-six-year-old theological studentfrom Canada.It has long been the policy of theCommittee on Admissions to pay careful attention not only to each applicant's scholastic abilities and achievements, but also to his non-scholasticattributes. Nevertheless, of the seventyfour entering freshmen, only two hadC+ grade averages in college, whiletwelve had B or B- grade averages,and sixty, or four-fifths of the class,had compiled grade averages of B + toA in their undergraduate studies. As agroup the freshman class had a collective average college grade record ofB+, and one-third of its members graduated from college with honors. Overthree-fourths of the entering freshmen (fifty-seven) had received a bachelor'sdegree before entering medical school,while the remaining seventeen studentseach had a minimum of three years ofcollege premedical studies. Three members of the class also had had one yearof graduate studies prior to coming tomedical school.On the Medical College AdmissionsTest, which is required of all medicalapplicants, the freshman class as aunit scored high above the nationalaverage and higher than any previousentering class in the past ten years during which the MCAT has been required of applicants. The average scoreof the entering freshman placed him inthe top fourteen per cent of all medical applicants in the United States.Seven of the entering freshmen haveone parent who is an alumnus of theUniversity of Chicago. One of thesealumni is a Rush graduate; the othersare graduates of the College or Divisions. As might be expected, the familybackgrounds of members of the entering class are most varied and interesting. Eight of the members of the entering class come from homes where oneor both parents have less than a highschool education. At the other extreme,two-thirds (forty-nine) of the enteringstudents come from families where oneor both parents are college graduates.As in previous years, the occupations ofthe fathers of the entering students include a cross section of the professions,industry, and labor. Included are thirteen physicians, five lawyers, five engineers, five high school teachers, fourcollege professors, three dentists, achemist, and a university president, aswell as the usual variety of office workers, businessmen, merchants, and workmen. Twenty-two of the mothers havecareers in addition to that of housewife.Four are school teachers, two are elementary school principals, one a collegedean of women, one a physician, one anurse, and the remainder includes secretaries, bookkeepers, saleswomen, an interior decorator, a psychologist, andfactory and office workers.The present freshman class is currently completing its third academicquarter of medical studies and it, likeits predecessors, shows promise of becoming an outstanding medical class.JOSEPH J. CEITHAMLDean of StudentsM E 0 I CAL A L U M NIB U L LET I N 37FACULTY NEWSWilliam E. Adams and Huberta M.Livingstone presented lectures and surgicalconferences last winter at universities inCairo and Alexandria, Beirut, Bangkok,Hong Kong, Tokyo, and Honolulu, as wellas at the meeting of the American College ofChest Physicians in New Delhi. Dr. Adamsis an officer of that organization.David J. B. Ashley is Visiting AssistantProfessor in Pathology.Percival Bailey, director of research forthe Illinois State Psychiatric Institute, gavethe three annual Harris Lectures at Northwestern University in April. He spoke on"The Life and Works of Sigmund Freud."William R. Barclay is president-elect ofthe American Thoracic Society, the medicalbranch of the National Tuberculosis Association.John R. Benfield, '55, William E. Adams,Salvatore L. Nigro and Edwin T. Longwon a bronze award for the most originalwork on an exhibit entitled "Surgical Restoration of the Chronically Collapsed Lung,"at the annual meeting of the Illinois StateMedical Society.Ray E. Brown, former Superintendentof The Clinics, has recently received theAmerican Hospital Association's Distinguished Service Award for 1963.Paul R. Cannon, '25, Professor Emeritusand former Chairman of the Departmentof Pathology, received on his 70th birthdaya specially published collection of originalscientific papers by more than a score offriends and former students at Chicago andother institutions across the country. Thepapers subsequently appeared in the Octoberand November issues of the Archives ofPathology.F. Harold Entz, of Waterloo, Iowa, wasinstalled as president of the North CentralUrological Association last October in Detroit.E. A. Evans, Jr. has been appointed amember of the Division of Medical Sciencesfor the National Research Council and ofthe divisional committee for Biological andMedical Sciences of the National ScienceFoundation.Jerome Gans is head of ophthalmologyat Mt. Sinai Hospital, Cleveland, Ohio.Peter Geiduschek, Associate Professor ofBiophysics, received a medical achievementaward at the 47th annual assembly of theInterstate Post-Graduate Medical Association held in Chicago in October. Four otherjunior faculty members of Chicago medicalschools were honored by the association.Paul V. Harper has been appointed Associate Director of the Argonne Cancer Research Hospital.A. B. Hastings, Professor of Biochemistry from 1926 to 1935, received the BantingMemorial Medal of 1962 last June. Dr.Hastings, who is now head of research atthe Scripps Institute in La Jolla, spoke tothe 22nd annual meeting of the AmericanDiabetes Association in an address entitled"Ah, Sweet Mystery ... ," which he represented as, "a biochemist's myopic view ofmetabolism."W. Garth Hemenway has left The Clinics to become chief of otolaryngology at theUniversity of Missouri Medical Center, Columbia, Mo.38 M E Die A L A L U M NIB U L LET I N H. Close Hesseltine is a member of theHouse of Delegates of the American MedicalAssociation.Howard F. Hunt, former Professor andChairman of the Department of Psychology,has accepted an appointment at ColumbiaUniversity.Leon O. Jacobson, '39, received the Borden Award last October from the Association of American Medical Colleges for hiswork on blood formation, blood diseases,and the effect of radiation on living tissues.John F. Kenward, '44, accepted the chairmanship of the Diagnosis and TreatmentCommittee of the Project on Mental Retardation of the Mental Health Society ofGreater Chicago, Inc. Dr. Kenward has alsobeen elected to the American Academy ofChild Psychiatry.Heinz Kohut, Professorial Lecturer inPsychiatry, is President of the AmericanPsychoanalytic Association.Robert Levine, '53, Nancy E. Warner,'49, and Charles Johnson, '54, received the1963 First Award for a scientific exhibit entitled "Localized Cytomegalic Disease" atthe Annual Clinical Conference of the Chicago Medical Society in March.John R. Lindsay is president-elect of theAmerican Academy of Ophthalmology andOtolaryngology for 1964.James W. Moulder will direct a specialtraining program in virus research, financedfor the next five years by the United StatesPublic Health Service.Frank W. Newell has been named to theAdvisory Council for Ophthalmic Surgeryof the American College of Surgeons, and hehas been elected a trustee of the NationalFoundation for Medical Eye Care. He hasalso been named Associate Editor of theAmerican Journal of Ophthalmology.Frank J. Orland is editor of the Journalof Dental Research of the InternationalAssociation for Dental Research.Stephen Rothman, Professor Emeritus ofDermatology, was one of six dermatologistsmade honorary members of the AmericanDermatological Association at the association's annual meeting in April. It was thefirst time in its history that the associationhad so distinguished men pre-eminent in thespecialty.Florence B. Seibert, who lives in Clearwater, Florida, received the 1962 JohnElliott Memorial Award of the AmericanAssociation of Blood Banks. At the annualmeeting of the Association last Novembershe read a paper on "Pyrogens from a Historic Viewpoint," and received the awardfor the work she did here and at Yale University in reducing the dangers of intravenous therapy.Paul Talalay has left the Ben May Laboratory to accept the appointment of Director of Pharmacology and ExperimentalTherapeutics at the Johns Hopkins University.Andrew Thomson, former Assistant Professor in the Department of Medicine, recently announced his association for theprivate practice of internal medicine withRichard B. Capps and Philip N. Jones.J. Robert Willson, a member of ourfaculty from 1944-1947, is president-electof the American Association for Maternaland Infant Health. He is professor of obstetrics and gynecology at Temple University.Harwell Wilson, Chairman of the Department of Surgery at the University of Tennessee and a former member of ourfaculty, was elected treasurer of the American College of Surgeons at their annualmeeting in Atlantic City last October.Stanley Yachnin, Assistant Professor ofMedicine, has received a Markle Fellowshipfor 1963-1968.GRADUATE NEWS'34. James F. Regan, Los Angeles, is amember of the Board of Medical Examinersof California.'40. Omar Fareed is in the Punjab, supervising the distribution of multipurpose foodto Tibetan refugees with the financial assistance of the Carr Foundation, established byhis father-in-law, George Russell Carr.'43. John W. Findley, Jr., a member ofthe San Mateo Medical Clinic, is clinical assistant professor at Stanford. He is president of the San Mateo County Medical Society.'44. George L. Nardi, Associate VisitingSurgeon at the Massachusetts General Hospital and Assistant Clinical Professor ofSurgery at Harvard, has been awarded aresearch grant for this year by the MedicalFoundation, a United Fund agency. Dr.Nardi's research will involve the study offundamental physiological and biochemicalprocesses in the pancreas of dogs.'46. John Cashman has just completedtwo years as Deputy Medical Director ofthe Peace Corps and is now going to JohnsHopkins for work in public health.Victor J. Mintek, formerly medical director of the Chicago Board of Health, SouthSide mental health clinic, became medicaldirector of River Edge Hospital in ForestPark, Illinois, a new 269-bed hospital forshort-term treatment of persons with mentalailments, which opened last fall. Dr. Mintekintends to keep the environment from becoming institutionalized; to this end, thestaff will not wear uniforms in most sections and an open-door policy will be pursued.'48. J. Thomas Grayston, Chairman ofthe Department of Preventive Medicine ofthe University of Washington, is currentlyconducting field trials in Taiwan on a trachoma vaccine, under the joint auspices ofthe United States Navy and the Taiwan government. The results so far have been encouraging, according to Dr. Grayston.'51. William M. Smith is now chief ofmedical service at the United States PublicHealth Service Hospital in San Francisco.'53. Conrad G. Thurstone was marriedtc Phyllis Bailey in January of this year.'55. Marshall Edelson, now chief of inpatient psychiatry at the University of Oklahoma Medical Center, has been instrumentalin transforming the psychiatric unit into a"therapeutic community," an environmentin which patients are encouraged to lead normal, active lives much as they would outside a hospital.Dr. Edelson has recently completed a studyon "The Termination of Intensive Psychotherapy," which is being published by theAmerican Lecture Series.Sharon (Mrs. Herman) Mead, now themother of three children, does part-timework with radioisotopes and endocrinologyat Meadow Brook Hospital in Hempstead,New York.Nelson A. Moffat is practicing urologywith The Marshfield Clinic in Marshfield,Wisconsin.'56. C. Peter Rosenbaum is assistant professor in the psychiatry department at Stanford. He married the former Eva Johnson inJune, 1962.'58. Seth Haber is now a member of theDepartment of Pathology at the KaiserFoundation Hospital in Oakland, California.Eugene Thiessen was elected chairman ofthe Committee of Interns and Residents ofthe Municipal Hospitals of the City of NewYork last fall.'59. James Bennington is now a memberof the Department of Pathology at theKaiser Foundation Hospital in Oakland,California.Yoshio Oda is resident in internal medicine at Queens Hospital in Honolulu.Sue Smith is clinical fellow in hematology.'60. George Bennett Humphrey wasawarded the Ph.D. degree in biochemistryfor work done under the direction ofEugene Goldwasser. His studies involved avirus-like agent which causes lymphatic leukemia in mice.'61. Matthew P. Dumont is now associated with the Massachusetts General Hospital.Elizabeth Ford is research associate inthe Ben May Laboratories.Hallie Moore has been received by theMaryknoll Sisters at Valley Park, Missouri.She is now Sister M. Anne Christine.Robert L. Perlman is a Fellow at La Rabida.James L. Spratt, assistant professor ofpharmacology at the University of Iowa, hasbeen named a Markle Scholar. His appointment will begin in July.'63. Robert D. Woodson spent fifteenweeks last summer in a mission hospital inEthiopia.Woodson's grant was awarded by the Association of American Medical Colleges asone of a number of fellowships financed bySmith, Kline and French Laboratories forthe purpose of providing American medicalstudents with first-hand clinical experienceof the problems endemic to foreign landsand cultures.ADAIR AWARDEdith Potter, Professor of Obstetricsand Gynecology at Lying-In Hospital,recently received the Fred Lyman AdairAward, a biennial award sponsored bythe American Gynecological Society andgranted for "the best work of originalquality related to Human Genetics."The funds for this award are furnishedby Adair Charities, Inc., founded byFred Lyman Adair, '01, Ryerson Professor Emeritus of Obstetrics and Gynecology for the purpose of "helping toimprove mankind physically, intellectually, morally, and spiritually." �_P_R_O__M_O__T_'O__N_S I I� R_U_S_H__N__E_W_S__ �1962-63To Professor:Wayne J. McIlrath-BotanyPaul Meier-Statistics and Director, BSDComputation CenterPeter V. Moulder, Jr., '45-SurgeryCharles Niven-MicrobiologyJohn F. Perkins, Jr.-PhysiologyTo Associate Professor:Joseph A. Cifonelli-La Rabida; alsoResearch Associate (Associate Professor) in BiochemistryPeter Geiduschek-BiophysicsClifford Gurney, '52-Physiology (concurrent with appointment in Medicine)Howard G. Williams-Ashman-Biochemistry (concurrent with appointment in BML)To Assistant Professor:Francis L. Archer-PathologyPaul E. Carson-MedicineLouis Cohen, '53-MedicineGlen D. Dobben-RadiologyEdward N. Ehrlich-Medicine & ACRHGerald A. Mendel-Medicine & ACRHGeorge G. Meyer-PsychiatryBrian Quinn-OrthopedicsGaldino E. Valvassori-RadiologyPaul H. Ward-OtolaryngologyTo Research Associate (Assistant Professor) :Robert A. Butler-otolaryngology andPsychologyTo Instructor:Jerry G. Chutkow, '58-Medicine andACRHDorothy F. Cooney-RadiologyGeorge R. Daicoff-SurgeryJohn M. Frederickson-OtolaryngologyMarcel Frenkel, '58-OphthalmologyHerbert B. Greenlee, '55-SurgeryCecil W. Hart-OtolaryngologyJules M. Kluger-PsychiatryShoichi Kohatsu-SurgeryJoseph R. Lancaster, Jr., '58-SurgeryShutsung Liao--Ben May LaboratoryRichard H. Moy, '57-MedicineWilliam H. Olson-AnesthesiologyHideo Oshiro-OtolaryngologyNatividad F. Ozoa-La Rabida and Pedi-atricsDavid L. Proctor-UrologyStanley M. Sinkford-PediatricsFrancis Straus, '57-PathologyHernando Torres-Neurosurgery '20. Frank B. Kelly, on the medical staffof Presbyterian-St. Lukes in Chicago, wasamong thirty-four persons selected by theIllinois Club for Catholic Women to behonored at their ninth annual V.I.P. Showof the Year last October. Dr. Kelly, oneof two physicians present, was honored forhis service in the field of medicine.'24. Willis J. Potts, Professor Emeritusof Surgery, Northwestern University, wasawarded the William E. Ladd medal by theAmerican Academy of Pediatrics last October. Dr. Potts, famed for his development ofcorrective surgery for "blue babies," washonored for "accomplishments of outstanding merit in pediatric surgery."'26. Edward L. Compere is serving a semester as Fulbright Professor and Lecturerof Surgery at the University of Sao Paulo inRibeirao Prete, Brazil.'29. Grace Hiller has retired as Directorof Student Health Service at Goucher College, Towson, Maryland. She will continueto practice medicine part time in Towson.Dr. Hiller visited The Clinics a year ago,during the annual meeting of the AmericanCollege Health Association, and at that timeshe recognized as unchanged only the frontdoor, Billings lobby and rear hall.'32. Louis B. Newman, chief of thePhysical Medicine and Rehabilitation Service at the Veterans Administration ResearchHospital, Chicago, was awarded the Veterans Administration Commendation for hissuccess as Chairman of the 1962 Crusadeof Mercy Drive at the hospital. Dr. Newman is also Professor of Physical Medicineand Rehabilitation at Northwestern University.Ying Tak Chan, following a serious illness, has returned to the Physical MedicineService, Government of the District of Columbia.'34. Marie A. Hinrichs, of Riverside, illinois, has been made an alumni member PhiBeta Kappa at Lake Forest College.'37. Ralph Siegel is currently serving aspresident of the oldest medical organizationin the country. We congratulate Dr. Siegeland the Middlesex County Medical Society.'41. Col. John W. Wichman, M.C., isStaff Surgeon, Northern European Command, Oslo, Norway.RESIDENT NEWSEarl Shrago ('56-'57) has been doing fulltime biochemical work with Lardy's groupat the University of Wisconsin. Despite thefact that he has not seen a patient since heleft Chicago, he recently became a diplomatein Internal Medicine.Srichitra C. Bunnag ('59-'62) is ResearchAssociate in the Department of Pathology.William E. Furst ('59-'62) has joined theradiology staff of John Gaston Hospital,University of Tennessee.Robert Jones ('61-'62) is completing hisresidency in pathology in the United StatesArmy.M E Die A L A L U M NIB U L LET I N 39NEW APPOINTMENTSBOWMANJames E. Bowman, Jr., has beenappointed an Assistant Professor ofMedicine and Director of the BloodBank as of March, 1963. With this stephe formalizes a connection with theUniversity which pas extended over anumber of years and a wide range ofterritory.Dr. Bowman is a specialist in thestudy of blood disorders and hereditaryblood factors in special populationgroups, and his work is focused on thehereditary enzyme defect, glucose-6-phosphate dehydrogenase deficiency,which was first discovered in 1956 atthe University of Chicago Army Medical Research Project, Stateville, byPaul Carson under the direction of AlfAlving. Attention was first drawn toG-6-PD deficiency as a result of studiesof hemolytic anemia occurring in some(10%) American Negroes who had received certain types of anti-malarialdrugs. G-6-PD deficiency has beenfound in all races, but is rare in northern Europeans. It was discovered thatfava beans (known as broad beans inEngland), which are a dietary staple inthe Middle East and Mediterraneanregion, also could precipitate hemolyticanemia in many individuals with thisdeficiency. Dr. Bowman made extensivestudies of favism from 1955 to 1961,while he served as chairman of the Department of Pathology of the ShirazMedical Center at the Nemazee Hospital in Iran, a new teaching hospitalbuilt by a wealthy Iranian businessmanand operated with funds from the40 MEDICAL ALUMNI BULLETIN United States and Iranian governments.According to Dr. Bowman, who regards his population studies of Iraniangroups as an adjunct of anthropology,G-6-PD deficiency was probably introduced and spread through the majorpopulation of Iran during and since theIslamic conquests: one of his findingsis that the deficiency is virtually absentin the Armenian and Zoroastrian populations, which discourage intermarriage.Dr. Bowman believes that furtherstudies of blood-groups could shed lighton the genetic influence of other population movements, such as the Mongolinvasions of the 13th-14th century.To attack the problem from a different angle, Dr. Bowman entered theDepartment of Eugenics, Biometry andGenetics of University College, London,where for the past year he worked on aspecial research fellowship from the National Institutes of Health. There hewas involved in what he calls a "theoretic exercise" attempting to explainsome of the anomalies in the geneticpatterns of G-6-PD deficiency. He iscarrying on this work here at Chicago,where the chain of research originated.Dr. Bowman received his B.S. degreein 1943 from Howard University, andhis M.D. degree three years later atHoward Medical School; he is boardcertified in clinical pathology as well aspathological anatomy. He is married tothe former Barbara Taylor, and theylive with their six-year-old daughter atL234 Madison Park, in Kenwood.With the appointment of HumbertoFernandez-Moran (Villalobos) as Professor of Biophysics, we have added toour faculty a brilliant scientist and anauthority on the use of the electronmicroscope. Born in Venezuela in 1924,he now holds M.D. degrees from theUniversity of Munich and the University of Caracas and a Ph.D. degree inbiophysics from the University of Stockholm.The main body of his research hasbeen concerned with the ultra-fine structure of nervous tissue, particularly theso-called lamellar systems, a large groupof structures derived from cell membranes and known to have energytransforming functions. These systems,which include mitochondria, known asthe power plants of the cell, and the FERNANDEZ-MORANphoto-receptors in the eye, are composedof layers of membranes only a few molecules thick. A major contribution in thisfield was Dr. Fernandez-Moran's recentdiscovery of thousands of "elementaryparticles" lining the membrane of themitochondrion; related biochemicalstudies indicate that these particles arecompact enzyme units which playa vitalrole in the energy-transforming functionof the mitochondrion. Detection of theseparticles may provide a clue to thefundamental problem of biological energy systems. It is interesting to note thatit was Robert Bensley, former Chairmanof the Department of Anatomy, who in1934 first isolated mitochondria fromliver cells, thus stimulating research inthis area.The discovery of the particles wasonly possible following the developmentby Dr. Fernandez-Moran of a numberof new techniques, including thin-walled,vacuum-tight chambers for the examination of cellular materials at the molecular level in a condition approachingtheir hydrated native state, and alsocryogenic techniques using liquid heliumfor rapid-freezing of samples being prepared for microscopic analysis.He is responsible for a number ofother innovations in the use of the electron microscope, including the diamondknife and ultramicrotome for ultra-thinsectioning of tissues and metals. Whilehead of the Department of Biophysicsat the University of Caracas, he conceived and built the Venezuelan Institute for Neurology and Brain Research,NEW APPOINTMENTSSCHMIDserving as its director from 1954-58. Hehas also served as scientific and culturalattache to the legations of Venezuela inSweden, Norway and Denmark, 1947-54, and as Minister of Education ofVenezuela in 1958.Dr. Fernandez-Moran is married andthe father of two children.On October 1, 1962, the Universitywelcomed Rudi Schmid, an outstanding medical scientist in the field ofmetabolic and hereditary diseases, whohas been appointed Professor of Medicine and Director of the new ChronicDisease Research Laboratories.Dr. Schmid was born in Switzerlandin 1922 and received his M.D. degreeat the University of Zurich in 1947. Heis now internationally known for hiswork on basic biochemical problems ofdisease, and is the author of more thaneighty-eight published contributions toprofessional and scientific journals andtextbooks.Dr. Schmid's clinical and laboratoryresearch has centered primarily onproblems of the metabolic processes ofthe liver and the blood-forming cycle.U sing modern radioactive labelling techniques he has made important studiesof normal and defective porphyrinmetabolism in the bone marrow andliver. He has also studied the metabolism of bilirubin, a bile pigment whichis found in the blood stream in abnor- mal amounts in many liver disorders,including jaundice, hepatitis, and cirrhosis. At his new base in the Chicago laboratories he is continuing to explore themechanisms which produce jaundice,and investigating such phenomena asinfant jaundice and the means by whichfoetal bilirubin is conjugated.Dr. Schmid comes to the Universityfrom Harvard, where he was assistantprofessor in the Harvard MedicalSchool; while in Boston he also servedas assistant physician at Boston CityHospital and assistant physician in theHospital's Thorndike Memorial Laboratory.His wife is the former Sonja Wild ofSt. Gallen, Switzerland, and they havetwo young children, Isabelle, eleven,and Peter, eight. They live at 5533 University Avenue.Ronald Singer has been appointedProfessor of Anatomy as of July, 1962.Born in Cape Town, South Africa,Dr. Singer received his M.B. and Ch.B.degrees, the equivalent of our M.D. degree, from the University of Cape Townin 1947. He has been a member of theDepartment of Anatomy of the Facultyof Medicine there since 1949.A distinguished anatomist and anthropologist, Dr. Singer has investigatedthe genetic differences in such characteristics as hair form, frequency offingerprint-patterns, the age at whichcranial sutures close, head types, problems of bone-formation and development, biochemical patterns, the conformation of arteries, and the phenomenon of sickling in blood cells as agenetic response to malaria. To this endhe has worked with groups ranging fromwhite South Africans to the Hottentotsof the South African veldt, and he hascollected relevant information fromartifacts and fossil remains throughoutSouth Africa. By tracing the development of anatomical differentia, such research provides a rare opportunity tounravel the silent history of the peoplesof Africa, a history which has a greatshare in illuminating the evolution ofman. His thesis, "Discoveries in Southern Africa Contributing to Our Knowledge of the Ancestry of Man," won forhim South Africa's coveted Cornwalland York prize, and is being expanded SINGERfor publication as a textbook of physicalanthropology.Included in his current research is astudy of the relationship between somatic types, temperament and disease,and he makes a point of the fact thatall of his research does not bear on oneparticular problem. Fascinated as he iswith the history of human evolution(he declares that a man who is not interested in his own past must have a"wooden head"), he sees it as only oneof a number of puzzles which maytempt an inquiring mind.Dr. Singer lives with his wife andthree children at 5731 Kenwood Avenue.Recent new appointments in the Department of Psychology have established Eckhard H. Hess, Professor ofPsychology, as chairman of the department and Donald W. Fiske, also Professor of Psychology, as associate chairman.Hess is Director of the W. C. AlleeAnimal Behavior Laboratory. He holdsM.A. and Ph.D. degrees from JohnsHopkins and has been on our facultysince 1948.Fiske received both an A.B. degreeand an A.M. degree from Harvard, anda Ph.D. degree in 1948 in psychologyfrom the University of Michigan. Sincethen he has been a member of the faculty here at Chicago.MEDICAL ALUMNI BULLETIN 41DORFMAN TO HEADPEDIATRICSAlbert Dorfman, '44, Professor 'OfPediatrics and Director 'Of La RabidaInstitute, has been appointed Chairman'Of the Department 'Of Pediatrics. Hewill continue to direct the scientific pregram at La Rabida, assisted in his etherduties by Burton J. Grossman, '49,Associate Professor 'Of Pediatrics andAssociate Director of La Rabida, whohas been appointed Medical Director atthe Institute.A biochemist as well as a pediatrician(he received his Ph.D. in biochemistryin 1939), Dr. Dorfman is internationally known for his work on the treatment'Of rheumatic fever and en the chemistry 'Of collagen, or connective tissue,which is the body tissue affected byrheumatic fever and related rheumaticand arthritic diseases. We are fortunateto have, in another part 'Of this issue, aglance at his investigations 'Of Hurler'sSyndrome. It was for his disc every 'Ofthe connection between this disease andtwo 'Of the complex sugars known asacid mucopolysaccharides that he received the E. Mead Johnson Award forResearch in Pediatrics in 1957. He hasalso been honored with the Phi DeltaEpsilon Award for Contribution toMedical Education.The Department 'Of Pediatrics is currently planning the construction of anew 100-bed hospital for children withaccompanying laboratory facilities forresearch in children's diseases. Withsuch opportunities for the exercise 'Ofhis talents as clinician, administrator,and investigator, it is to be expectedthat Dr. Dorfman's contribution tomedicine will continue to prove noteworthy.O'LEARY PROMOTEDJames O'Leary, '31, became chairman of the newly organized Department of Neurology at Washington University School of Medicine on July 1.He has been on the faculty of Washington University since 1928 and professorof neurology since 1946.His research centers en electrophysiology and the problem of relating manifold aspects of the electrical activity 'Ofthe brain to its means 'Of operation.Dr. O'Leary earned his Ph.D. in anatomy here in 1928 and his M.D. in 1931.In 1952 he was one of the first recipients of our Distinguished ServiceAward, inaugurated to celebrate the25th anniversary 'Of The Clinics.42 M E 0 I CAL A L U M NIB U L LET I N BARLOW GOES TO HARVARDCharles F. Barlow, '47, has acceptedthe Bronson Crothers Professorship ofNeurology at Harvard. He is to establish a pediatric neurological service atBoston Childrens Hospital where hedid part of his residency in 1948-49.He finished his residency here underRichard B. Richter, '25, and is now anAssociate Professor of Medicine (Neurology). His research has been in clinical pediatric neurology and the bleedbrain barrier with isotope labeled cornpounds.Dr. Barlow has been living at theDunes with his wife and family of three.BEAL TO HEAD SURGERYAT NORTHWESTERNOn September 1, John M. Beal, Jr.,'41, will become chairman of the Department of Surgery at Northwesternand Chief of Passavant Memorial Hospital. He succeeds Dr. Loyal Davis, aneminent Chicago neurosurgeon who isretiring after thirty years.Dr. Beal is Clinical Associate Professor of Surgery at Cornell UniversityMedical College and attending surgeonat New York Hospital.His residency was taken at New YorkHospital and from 1949 to 1953 he wason the faculty 'Of the University 'Of California. For the last ten years he hasbeen associated with Cornell and theNew Yerk Hospital. His research hasbeen in surgical metabolism and gastrointestinal physiology.The Beals will be returning heme-orclese to home-Dr. Beal's father waschairman 'Of 'Our botany department fermany years and his wife, Mary, is thedaughter of Dallas B. Phemister. Theyhave three children.HARPER APPOINTED TOARGONNE POSTPaul V. Harper, Professor 'Of Surgery, has been appointed Associate Director 'Of Argonne Cancer ResearchHospital.Dr. Harper was educated at Harvard: A.B., '39, M.D., '41. He has beena member 'Of 'Our surgical staff since1949. His interests have been mainly inthe applications 'Of nuclear medicine toproblems in medicine and surgery. Recent studies with strontium-90 administered by a radioactive isotope needlehave been successful in alleviating pain in cancer patients by destroying thepain-transmitting nerve fibers in thespinal cord.Dr. Harper is 48 years 'Old and thefather 'Of four. No statement about himis complete without mentioning that heis a grandson of William Rainey Harperand an expert at jude.DEATHS \'97. George Ainslee, Portland, Ore., May28, age 87.'99. Edward W. Ewing, Spickard, Mo.,May 29, 1956, age 80.'00. Robert Williams, Moose Lake,Minn., December 26, age 89.'01. Gilman W. Petit, Chicago, June 15,age 87.'02. A. Gullixson, Minneapolis, Minn.,July 1, age 88.Albert C. Yoder, Goshen, Ind., October 3,age 95.'03. Claude G.· Dickey, San Clemente,Calif., August 30, age 86.Edward F. Maginn, Los Angeles, Calif.,January 4, age 82.John M. Weiss, San Mateo, Calif., March9, age 83.'04. Archibald Hoyne, Chicago, March 3,age 84.John F. Waugh, Glenview, Ill., August12, age 84.'09. Irving Perrill, Chicago, January 30,1962, age 77.'11. John Z. Brown, Salt Lake City,Utah, November 14, 1961, age 88.Audley Sanders, Palo Alto, Calif., July20, age 84.Robert L. Reynolds, Franklin Park, Ill.,September 29, 1962, age 76.Henry I. Wilson, Chicago, January 14,age 80.'13. Albion H. Heidner, West Bend, Wis.,September 17, age 73.James H. Mitchel, Chicago, January 14,age 81.'15. James E. M. Thomson, RanchoSanta Fe, Calif., May 24, 1962, age 72.George L. Rees, Logan, Utah, April 15,1962, age 78.'16. Philip B. Greenberg, Beaumont,Texas, February 23, age 70.Simon O. Lund, Cumberland, Wis., September 22, 1962, age 77.William L. Ross, Jr., Yakima, Wash.,October 13, age 70.Maurice J. Silver, Brookline, Mass.,March 26, age 81.Frank Lee South, St. David, Ill., March 1,age 77.'18. Isaac W. Allen, Moab, Utah, March26, age 71.DeWitt H. Garlock, Redlands, Calif.,March 9, age 73.Malcolm F. Rogers, Milwaukee, Wis.,May 22, age 71.'19. E. Eric Larson, Laguna Beach, Calif.,October 22, age 72. .Robert H. Stanton, Pasadena, Calif.,February 5, age 68.Carl T. Stephan, Chicago, June 20, age74.'21. C. H. Brush, Shenandoah, Iowa,August 24, age 70.( Continued on page 43)DEAN H. STANLEY BENNETI, DR. RICHARD E. SHOPE, AND DR. HENRY T.RICKETTS.RICKETTS AWARDDr. Richard Edwin Shope, internationally known virologist.iwas named the fiftiethanniversary recipient of the Howard TaylorRicketts Memorial Award.Dr. Shope is a member and Professor ofAnimal Pathology at the Rockefeller Institute, New York City. Through his life-longstudy of animal diseases he has made fundamental contributions to the understandingof infectious disease and to the study ofcancer. He received the medal here on May31, and spoke on "The Epidemiology of theOrigin and Perpetuation of a New Disease."The Ricketts Award was originally inaugurated as a University prize for outstanding student research in bacteriology andpathology. The first awards were given in1913 to Dr. Esmond R. Long, who becamedirector of the Henry Phipps Institute inPhiladelphia, and Dr. George L. Kite, apromising scientific investigator who diedwhen he was still a young man, in 1919.In 1948, the Ricketts prize was made anational award given to honor distinguishedachievement in medical science. To commemorate the fiftieth anniversary of itsestablishment, the previous award winnerswere invited to the ceremonies for Dr.Shope and the annual dinner that followed.Twelve earlier recipients, four from our ownfaculty, were present. The guests arrivedfrom points as distant as Texas and PuertoRico to help celebrate the event. The following list indicates the year in which thosepresent received the award.1917. Enrique Eduardo Ecker, Ph.D. '17,Professor Emeritus of Immunology at Western Reserve University and Research Associate in the division of pathology at St.Luke's Hospital in Cleveland.1918. Harry Lee Huber, Ph.D. '17, M.D.'18, private practitioner in Chicago and president of the Society for the Study ofAsthma and of the Association for the Studyof Allergy.1925. Gail M. Dack, Ph.D. '27, M.D. '33,Professor of Microbiology and Director ofthe Food Research Institute, University ofChicago.1928. James Roy Blayney, M.S. '28, Professor Emeritus and former Director of theWalter G. Zoller Memorial Dental Clinic,University of Chicago, and Director of theEvanston Dental Caries Study.1929. George W. Sruppy, Ph.D. '29, M.D.'32, Clinical Professor of Medicine, University of Illinois College of Medicine.1930. Arthur J. Vorwald, Ph.D. '31,M.D. '32, Professor and Chairman of theDepartment of Industrial Medicine andHygiene, College of Medicine, Wayne StateUniversity.1932. William Burrows, Ph.D. '32, Professor of Microbiology, University of Chicago.1933. James A. Harrison, Ph.D. '35, Professor of Bacteriology, Temple University.1941. George G. Wright, Ph.D. '41, Chiefof the Immunology Branch, United StatesArmy Biological Laboratories, Fort Detrick,Frederick, Maryland.1943. Howard C. Hopps, Professor andChairman of the Department of Pathology,Medical Branch, University of Texas.1947. Robert W. Wissler, M.D. '49, Professor and Chairman of the Department ofPathology, University of Chicago.1956. John C. Bugher of The RockefellerFoundation, currently Director of the Nuclear Center of Puerto Rico. (Continued from page 42)E. Bertrand W oolfan, Beverly Hills,Calif., December 26, 1962, age 67.'23. John A. Bigler, Highland Park, Ill.,January 12, 1962, age 65.Frederick T. May, Jr., Lathrup Village,Mich., June 25, age 65.Thomas W. Woodman, Phoenix, Ariz.,February 10, age 61.'25. Abraham I. Love, Chicago, January16, age 62.Warren B. Smith, Temple, Texas, October 4, age 71.'26. Truman S. Potter, Branford, Conn.,November 21, age 65.Ernest B. Zeisler, Chicago, December 27,age 63.'27. Reynold O. Bassuener, Milwaukee,Wis., May 18, 1962, age 61.Edward K. Martin, Frankfort, Ky., December 1, 1962, age 63.John P. Wood, Quincy, Ill., November17,1961, age 61.Robert W. Lennon, Joliet, Ill., October 3,age 58.'30. Lumir E. Dostal, Chicago, December6, age 57.'32. Philip O. C. Johnson, Seattle, Wash.,May 26, age 54.William M. Tuttle, Detroit, Mich., December 22, age 57.'33. Kurt E. Hohman, Fort Lyon, Colo.,November 16, age 54.'34. Dick Freriks, La Grange, Ill., June 29,age 56.Sara E. Branham (Mrs. Philip S. Matthews), Bethesda 4, Md., November 16, age74.'35. John P. J. Milroy, Lake Forest, Ill.,January 28, age 61.'36. Harold L. Rogers, Albertville, Ala.,January 31, age 53.'37. George L. Nicoll, Dover, N.J., January 30, age 57.'51. Robert D. Towne, San Francisco,Calif., January 26, age 35.'56. Walter E. Deike, Los Angeles, Calif.,April 18, age 41.'58. Martin E. Hanke, Jr., Los Angeles,Calif., May 6, age 36.FACULTYHarriet F. Holmes, '30-'43, AssociateProfessor Emeritus, Pathology, Batavia, 111.,1962, age 88.Horace G. Strickland, Resident '35-'36,Greensboro, N.C., January 25, 1962, age 57.BULLETINof the Alumni AssociationThe University of ChicagoSCHOOL OF MEDICINE950 East Fifty-ninth Street, Chicago 37, IllinoisVOL. 19 SUMMER No.1EDITORIAL BOARDJESSIE BURNS MACLEAN, SecretaryARCHIE LIEBERMAN, Art EditorWRIGHT ADAMS ROBERT J. HASTERLIKJOHN D. ARNOLD ELEANOR M. HUMPHREYSL. T. COGGESHALL HUBERTA LIVINGSTONERICHARD EVANS PETER V. MOULDERWALTER L. PALMERMEDICAL ALUMNI BULLETIN 43