BIOMEDICAL CAREER (ONFEREN(Total Ph. D. 's20,00010,000••••••••••••••1,0001920 19» 1940 1950 1900Medical graduates andPh. D. 's: 1920-58 and estimates to 1970Medical schoolgraduatesPh. D. 's inphysical sciencesPh. D. 's inbiologicalsciences1970In the following pages we give a detailed description of theFifth Biomedical Career Conference conducted in November1963 under the presidency of Emmet B. Bay, Rush 1923.A crew of volunteer photographers was assembled under thedirection of Archie Lieberman to record the entire program.Picture credits and our grateful appreciation go to ArchieLieberman for the cover picture (of Dr. Otto Gago-B andDarlene Rothman of Morgan Park High School), photographson pp. 3, 12,22, and demonstrations #1,3,6, and 17; and tothe following students, alumni and friends for the followingdemonstration pictures: Bill Brath, '64-#20, 22; Tom Butter­field, '64-#2, 21; Donald Chow-#7, 11; Julius GinsbergRush '31-#5, 12; Joan Hill-#13, 14, 16; Robert Hillman'65-#4,8; Mickey Pallas-#9, 10; Enrico Sarsini-#19; andJoel Snyder-#15, 18.ROM IDEA TO ACTIONIn a way, the Biomedical Career Con­ferences began with this graph, showingthe relative decline of medical schoolgraduates. The figure, which appeared inthe 1959 Bane Report*, caught the eye ofDr. Richard Evans, '59, then an intern,who brought it to the attention of Dr.John Arnold, '46, at that time a memberof the medical faculty. The graph con­firmed their own observations that medi­cine was no longer attracting its share ofthe ablest minds. They reasoned that ifyoungsters were made aware of the newkinds of opportunities and rewards ofcareers in medicine, more of them wouldchoose to go to medical schools.This was in October 1959.By November, after frequent huddleswith the ever-accessible Mrs. JessieMaclean, Executive Secretary of theMedical Alumni Association, plans fora program had been given the enthusi­astic endorsement of Dean Lowell T.Coggeshall.On January 30, 1960, the first Bio­medical Career Conference lured 250eager high-school students, accompaniedby their science teachers, from the Chi­cago metropolitan area. The immediateresponses were most gratifying and inspite of the speed with which the confer­ence was conceived and planned, itseemed to have attained its "naturalform" at its debut.In order to meet the nation's need forphysicians, the Bane Report had pro­jected that by 1970, at least 20 additionalmedical schools would be required. Butthe number of qualified applicants toexisting medical schools was going down,not up. Why? Four factors seemed to bedeterring the flow of bright aspirants intothe medical professions: (1) competitionfrom other fields, (2) prolonged periodof training, (3) lack of opportunity, and(4) high cost to the student. The confer­ence planners realized that while theirprogram could not hope to alter someof these deterrents, it could present fulland accurate information on them; itcould also demonstrate the powerfulappeal of lives devoted to biomedicalresearch, teaching, and patient care.* Report of the Surgeon General's Con­sultant Group on Medical Education, Physi­cians for a Growing America, U.S'p.H.S.Publication No. 709, 1959. Thus, from the beginning, the full-dayprogram has usually taken the followingformat:-Laboratory demonstrations by fac­ulty for small groups of conferees-Luncheon with medical studentguides and faculty participants-Explanation of admission require­ments, the structure of the variousdegree programs, and the financingof biomedical education-A clinical session in which the toolsand results of research are broughtto bear on a patient's illness.Throughout, the emphasis has been onpersonal, intimate contact between thevisiting prospective biomedical scholarand his host, the dedicated scientistin the challenging setting of his ownlaboratory.In terms of the original goals, howeffective have the conferences been? Wehave no parallel controls, but the follow­ing figures, based on responses from 305who attended the first three conferencesin 1960 and 1961, are reassuring:Present status No. Per centMedical school ......... 26 9Pre-medicine ............ 88 29Graduate in biologicalsciences .............. 12 4Undergraduate in biologi-cal sciences ........... 54 17Nursing ................ 13 4193 63Especially revealing were comments,such as this one from a pre-medical stu­dent: ". . . a most enriching experience... it was the first and most influential... I am presently applying to The Uni­versity of Chicago."The true measure of the conferences,of course, will be found in the long-termtranslation of the inspiration, so eloquent­ly voiced above, into meaningful andproductive careers in biology and medi­cine. A recent inquiry indicates that othermedical institutions have started similarcareer conferences, but of those with acontinuous tradition, The University ofChicago is the first. EVANSARNOLDCOGGESHALLMEDICAL ALUMNI BULLETIN 31. GAGO AND DELGADO3. MOULDER AND DAICOFF 2. FITCH, ,4. FERNANDEZ-MORAN5. FRIEDMANN" MEDICAL ALUMNI BULLETINNEW LUNGS FOR OLD DOGSPHOTO #1The feasibility of transplanting alobe of lung from one mongrel dog toanother was demonstrated in full-dresssurgical operating procedure by EmilioDelgado, Otto Gago, and Louis Kolb,'62, of the Department of Surgery. Im­mune-suppressive drugs were given toimpair the capacity of the recipient dogto reject the foreign tissue. Factors in­fluencing success or failure of the graftwere discussed in relation to the pos­sibility in the future of replacing dis­eased lung tissue in man.SELF-NOT SELF: PROBLEMSOF ANTIBODY FORMATIONPHOTO #2Frank Fitch, '53, of the Departmentof Pathology, began the demonstra­tion with a brief discussion of the im­portance of antibody formation, bothin the body's defense against infectionand in the- rejection of transplantedorgans. Knowledge of the control ofantibody formation is needed for thepreparation of more effective vaccinesagainst harmful viruses and bacteria.If the regulation of the immune re­sponse could be understood, it mightbe possible to interfere with it selec­tively so that kidneys, lungs and otherorgans might be transplanted from oneperson to another.These goals are still a long way off,but many new techniques have beendeveloped to aid in the search forknowledge of how the body reacts toforeign or "not-self" materials. Dr.Fitch demonstrated the fluorescent anti- DEMONSTRATIONSbody technique, which makes it pos­sible to study the location of antibody­forming cells; and immunoelectro­phoresis, a method used for separatingthe different kinds of antibody mole­cules as well as for analyzing complexmixtures of antigenic materials. Healso explained several techniqueswhich make it possible to study the de­tailed structure and the metabolism ofindividual antibody-forming cells. Itwas emphasized that significant dis­coveries do not necessarily requireelaborate equipment, but simply askingthe proper question which will providea clear answer.HEART VALVE SURGERYPHOTO #3Correction of faulty heart valves byreplacement with prostheses made ofplastic, rubber and/or metal materialsis now a reality for certain forms ofhuman heart disease. How such devicesare designed and inserted, and theireffects on the circulation were shown byPeter V. Moulder, '45, James Covell,'62, and George Daicoff, of the De­partment of Surgery, in operations ondogs.ELECTRON MICROSCOPYOF CELLSPHOTO #4Mitochondria, the minute particlesin cells which provide for the releaseof energy from food, are so small thata thousand of them could fit into thespace of a grain of sand without touch­ing each other. The secrets of the mito­chondria are now being probed with the use of the electron microscope anda number of intricate mechanical de­vices developed by Humberto Fer­n&ndez-Mor�n, of the Department ofBiophysics, and demonstrated by himfor the students who attended the con­ference. These included the diamondknife, a metal alloy specimen holderwhich expands, when precisely heated,just enough to accomplish the exactfeeding process over the knife's cuttingedge, and a graphite chamber to pro­tect the specimen while in the vacuuminside the electron microscope.THE RADIOACTIVEAUTOBIOGRAPHYOF A VITAMINPHOTO #5Vitamins, by definition, are sub­stances that are required but are notmade by animals such as human be­ings. Plants and sometimes bacteriamake them for us. For Vitamin B12,which is not synthesized by plants, wehave to rely on the bccterlo in ourintestines. Many details concerning theenzymatic pathway by which bacteriaput together the complex B12 moleculeremain to be determined. In this dem­onstration Herbert C. Friedmann, ofthe Department of Physiology, usedthe techniques of radioactive tracersto follow the fate of a benzimidazole,one of the ingredients of this vitamin,when acted upon by a bacterial en­zyme extract. The bacteria used areknown as Propionibacteria. They pro­duce compounds related to the vita­min, and are perhaps better known bythe fact that they are indispensable forthe manufacture of Swiss cheese.MEDICAL ALUMNI BULLETIN .56. KIRSTEN8. HASELKORN 9.-GARBER 7. HUBBY10. GRIEM11. LEVENETUMORS PRODUCED BYPOLYOMA VIRUSPHOTO #6Polyoma virus is a small animal viruswhich has been shown to cause mul­tiple benign and malignant neoplasmsin a number of laboratory animals.Tumors develop only when newbornanimals are inoculated with potentpreparations of this virus. The varioussteps in the formation of such viral can­cers can now be analyzed by in-vivoand in-vitro experiments. First, themultiplication of polyoma virus in tis­sue-cultured cells of embryonal miceand rats were illustrated by electronmicroscopy by W. H. Kirsten, of theDepartment of Pathology. Then theeffects of this virus during carcinogene­sis in tissue culture as well as in theliving animal were shown. This tumor­producing virus requires undifferenti­ated embryonal or neonatal cells inorder to cause cancers but multipliesin tissues of any age.SEPARATION OF PROTEINMOLECULES IN GENETICSTUDIESPHOTO #7John L. Hubby, of the Departmentof Zo�logy, demonstrated the electro­phoretic separation of proteins in solidmedia. Various applications of thistechnique to indicate molecular differ­ences in proteins between geneticstrains of Drosophila me/anogasterwere presented. Another technique waspaper column chromatography alsocalled "fingerprinting," which revealsamino acid substitution in proteins. DEMONSTRATIONSMISCHIEVOUS MESSENGER:VIRAL RNAPHOTO #8Robert Haselkorn, of the Depart­ment of Biophysics, demonstrated thetechnique of sucrose gradient centrif­ugation. In this type of measurement,a small volume of the material beinganalyzed such as viral RNA, is carefullylayered over a column of sucrose con­tained in a plastic tube. The tube iscentrifuged for a fixed time, and thenthe bottom of the tube is pierced andthe emerging drops collected in a seriesof fractions. A number of measure­ments is made on each fraction, in or­der to locate the material being ana­lyzed. The position of the substance inthe centrifuge tube tells us its sedi­mentation coefficient, which is relatedto the mass, size and shape of the mole­cule being examined. The results of thisprocedure were compared to those ofconventional analytical ultracentrifuga­tion.MUTANTS, ENZYMES,AND ROTTEN ORANGESPHOTO #9Edward Garber, of the Departmentof Botany, demonstrated experimentswith the rot of oranges which providea model for relating genes with specif­ic enzymes and pathogenicity. The rotis caused by one of two fungal patho­gens, Penicillium italicum and Penicil­lium digitatum, which produce tissue­macerating enzymes: pectinase andcellulase. Mutant fungi resulting fromultra-violet light irradiation did not in­duce rotting, but rather necrosis at thesite of inoculation into oranges. Whenextracts of healthy, rotted, or necroticorange tissue were assayed for pectin­ase and cellulase activity, it was found that pectinase was responsiblefor the rot and cellulase for the nec­rosis. Genetic analysis indicated thatthe ability of fungi to induce rotting isgenetically determined, and that muta­tion may involve different genes.HIGH ENERGY RADIATION INTHE TREATMENT OFCANCERPHOTO #10Melvin Griem, of the Department ofRadiology, demonstrated the rotatingcobolt''" machine and how it is usedto deliver ionizing radiation in a con­centrated fashion to a tumor. Follow­ing this demonstration, the two millionvolt constant potential Van de Graaffgenerator and the linear electron ac­celerator were shown, and specific ap­plications to the treatment of patientswere discussed.RHEUMATIC FEVER, LEATHERAND EMULSIONPHOTO #11Charles Levene, of the Departmentof Pathology, demonstrated the versa­tility of collagen, a major componentof normal connective tissues. Collagenis the basis of the leather industry and,when denatured by heat, it formsgelatin, which is important in the glue,gelatin and photographic industriesand in food technology. In man, col­lagen holds the body's tissues together."If it were not for collagen," said Dr.Levene, "we'd fall like ashes into ourboots." But too much collagen in thewrong places can also cause trouble.For example, if" disease processes suchas rheumatic fever, deposition of col­lagen can result in deformity of theheart valves.MEDICAL ALUMNI BULLETIN 712. MOSCONA 13. MC CLEARY AND15. NlDEN 14. STUDENTS16. MULLAN17. LESTEREXPERIMENTALCONSTRUCTION OF TISSUESFROM SINGLE CELLSPHOTO #12One of the fundamental problemsin biology and medicine is that con­cerned with organization of cells inthe embryo into tissues and organs.It has been shown that various embry­onic tissues can be disassembled intotheir constituent cells and that the dis­persed cells can be compounded andre-synthesized into new tissues. By suchexperimental procedures, much can belearned about the mechanisms involvedin developmental processes at the lev­el of cellular activities, about molecularrequirements, and about conditionsthat affect the expression of the geneticpotentialities of cells. Aaron Moscona,of the Department of Zoology, illus­trated some of the factors that affectthe reconstruction of tissues from singlecells in such synthetic systems andcontrol the differentiation of cells intodeveloping structures. Emphasis wasplaced on possible mechanisms bywhich cells "communicate," "recog­nize" each other, and become associ­ated in a manner conducive to pro­gressive development. Interferenceswith such mechanisms have been sug­gested as possibly significant in variouspathological disturbances of develop­ment.EXPERIMENTAL BRAINSTUDIES OF FEAR INTHE CATPHOTOS #13 AND 14Robert A. McCleary, of the Depart­ment of Psychology, showed behav­ioral test-equipment and neuro-surgicaltechniques employed in the study ofthe contribution of the brain's limbicsystem to behavior. Open surgery ofthe cingulate gyrus and septal regionwas demonstrated, and several proce­dures were shown for studying fear­motivated behavior in the cat. DEMONSTRATIONSPULMONARY HEMODYNAM­ICS: BLOOD FLOW INTHE ISOLATED PER­FUSED LUNGPHOTO #15Albert H. Niden demonstrated therelationship of pressure and blood flowin the dog lung. The pulmonary circu­lation separated from the dog's sys­temic circulation was artificially per­fused, while respiration was maintainedand controlled in a negative-pressurerespirator box. [The effects of varyingrespiratory pressures was shown, aswere the effects of both blood pres­sures and flow rates.] The influences ofvasoconstrictor and vasodilator drugson the circulation were demonstratedand their usefulness in various diseasestates were explained.USE OF A RADIOACTIVENEEDLE IN BRAIN SURGERYPHOTO #16John F. Mullan, of the Section ofNeurosurgery, discussed the develop­ment of stereo-tactic surgery. By thismethod, small areas of the brain whichare not functioning properly may bedestroyed by means of a needle giv­ing off radioactivity. The needle iscarefully guided to the right point bymechanical means, thus replacing thelarge opening in the skull necessaryfor conventional free-hand surgery onthe brain.The problem in developing a needlewhich, by beta emission, could makethese small irradiated lesions was thatbeta-emitting isotopes with the great­est penetration have the shortest half­life. Paul V. Harper solved this prob­lem by creating what is in fact a mini­ature nuclear reactor. The parent iso­tope, Strontium90, decays to Yttrium90,giving off weak beta rays on a virtuallycontinuous basis (29-year half-life). TheYttrium90 further decays to Zirconiumf", giVing off stronger beta rays with ahalf-life of only 21h days. The net resultis that the Strontium is the starting andcontinuous source of the strong beta ofYttrium. Fifty-four millicures of Stron­tium are permanently sealed in theend of a steel needle. By allowingthe needle tip to come in contact withthe right spot of tissue for an appro­priate time, fifteen minutes for exam­ple, a predetermined volume of sur­rounding tissue may be destroyed. Thisneedle has now been used to destroypain fibers in the spinal cord in pa­tients with advanced painful cancer.Another painful condition (trigemi­nal neuralgia) may be treated by in­serting the needle into a small openingat the base of the skull and destroyingthe trigeminal nerve in that situation.The needle may be inserted into thepituitary gland through the nose, forit has been found that destruction ofthe pituitary gland will help a greatmany patients who have breast cancer.The needle has also been insertedthrough a drill hole in the skull in thetreatment of Parkinson's disease, cer­tain forms of epilepsy, and a few raretypes of pain which cannot be dealtwith by the more simple needle injec­tion in the neck.WHERE DOES THE "RED"OF THE REDBLOOD CELL GO?PHOTO #17When red blood cells are destroyed,the cellular pigment, heme, is de­graded to a yellow pigment, bilirubin.The liver excretes bilirubin into the bile,and in doing so produces an importantchemical modification. Roger Lester,of the Department of Medicine, dem­onstrated the nature of this modifi­cation by intricate biochemical pro­cedures, and discussed the relationshipof bilirubin and conjugated bilirubinto the clinical syndrome of jaundice.MEDICAL ALUMNI BUllETIN 918. ROWLEY 19. POTTS-GLOCKLIN MODEL OF THE EYE20. WEISS 21. SIMMONS22. WOOL10 ME 0 I CAL A L U M NIB U L LET I NSEX AND THE"HOT" X-CHROMOSOMEPHOTO #18Janet Rowley, '48, of the ArgonneCancer Research Hospital, demon­strated how differential labelling ofchromosomes by radioactive isotopeshelps us to understand the biologicalfunction of these structures in the cellnucleus.When cultures of dividing white cellsfrom the blood of a normal womanare incubated with radioactive thymid­ine, one of the two female sex (X)chromosomes incorporates consider­ably more of the isotope, and later,than the second X-chromosome andthe 44 non-sex autosomes. Thus, thetwo X-chromosomes are not identical;and because one becomes more heav­ily labelled later, it is called the "hot"or late-labelling X-chromosome.Some women patients with the Turnersyndrome (short stature, amenorrhea,reduced secondary sex characteristicsand mental retardation) have onlyone X-chromosome; others have twoX-chromosomes, but one of the twois morphologically abnormal. Analysisof the cells from these two groupsof women with the Turner syndromeshows that in the former group thesingle X-chromosome is not "hot" orlate-labelling, while in the latter groupthe morphologically abnormal X-chro­mosome is always the "hot" chromo­some.Cells from a congenitally malformedboy revealed four X-chromosomes anda Y (male) sex chromosome. Afterthymidine labelling, three of the fourX-chromosomes were found to be "hot."The results support the Lyon hy­pothesis that the two normal femaleX-chromosomes are different; the "hot" DEMONSTRATIONSX-chromosome is probably geneticallyinactive, but may be associated withcertain abnormalities; the other X-chro­mosome is probably gentically active,accounting for X-linked disorders.MORE THAN MEETSTHE EYE: TRICKS PLAYEDBY THE ORGAN OF VISIONPHOTO #19The working of the eye representsan exquisitely adapted optical, photo­chemical and electronic system. AlbertPotts and Vera Glocklin, of the Sec­tion of Ophthalmology, demonstratedsome details of this system by ana­tomical dissection with the excised eye,and showed the process of imageformation with television ophthalmos­copy.However, the act of vision embracesfar more than the functioning of thisorgan. Vision requires transmission ofimpulses to the opposite end of thebrain, analysis of the picture, interpre­tation of the picture, and correlationwith past experience. Some remarkablefacts about these processes were shownby a number of optical illusions dem­onstrated in special apparatus.GENETIC CONTROL THROUGHRNA SYNTHESISPHOTO #20Samuel B. Weiss demonstrated thevariety of physical, chemical and mi­crobial instruments and techniques usedto study the mechanisms by which thegenetic material of the cell (DNA) con­trols protein synthesis. Of special in­terest to Dr. Weiss is a major inter­mediate step, the enzymatic transcrip­tion of RNA from the DNA template.He explained for example how experi- ments in his laboratory have shown thatthe instructions for synthesis of ribo­somae and transfer RNA occupy lessthan 0.2% of the message space on theDNA molecule.SAVING LIFEAGAINST ATOMIC DEATH:MARROW TRANSPLANTATIONPHOTO #21Eric L. Simmons, of the ArgonneCancer Research Hospital, showed howthe lives of lethally-irradiated animalscan be saved by the injection of cellsof blood-forming tissues which colo­nize and re-populate the damaged tis­sues. These techniques are of practicalimportance in making possible higherdoses of radiation therapy for medicalpurposes, and in providing a method oftreatment for victims of accidents in­volving nuclear reactors.HORMONES AND MUSCLESPHOTO #22Ira G. Wool, '53, of the Departmentof Physiology, began with a short"chalk-talk" outlining the biosynthesisof protein and the means by whichregulation of that synthesis might beachieved. An experimental approachto the study of one aspect of regula­tion, amino acid transport, was thendemonstrated. The method of perfusingan isolated rat heart in a closed circuitsystem was shown and its applicabilityto the problem of the influence ofinsulin and diabetes on the process waspointed out. The method of analyzingthe perfusate and the heart musclefor each of the twenty naturally-oc­curring amino acids by automatedcolumn chromatography was also dem­onstrated.MEDICAL ALUMNI BULLETIN 11BLAISDELLHASELKORNBOWMANSINGER12 ME 0 I CAL A l U M NIB U II E TIN BAY CEITHAML STRANDJORDCLINICAL CONFERENCEDR. RICHARD BLAISDELL:This afternoon's clinical discussionwill focus and then enlarge on a case ofsickle cell anemia, the first disorder towhich the term "molecular disease" wasapplied. Here to participate in the dis­cussion are four members of The Univer­sity of Chicago faculty in the Division ofthe Biological Sciences, whose specialinterests reflect the various aspects ofthis fascinating disturbance. First, on myleft, Dr. Robert Haselkorn, who bringshis talents in physics and chemistry tobear on basic biological problems, assome of you learned this morning. Nextto him is Dr. James Bowman, a pa­thologist and human geneticist, who isdirector of the hospital blood bank. Onthe far side, is Dr. Nels Strandjord, aclinical radiologist who devises new kindsof radiographs, not just X-ray films, and­whose highly-trained eyes detect thesubtlest of changes in these pictures.Then we have Dr. Ronald Singer, pro­fessor of anatomy and anthropology,whose specialty is the whole breadthand scope of human variation.N ow we would like to introduce ourpatient, Gwendolyn Bolton. Would youbring her in, Doctor? (The patient enters.)Good afternoon, Gwendolyn.A: Good afternoon.Q: Please sit down. It is nice of youto be with us this afternoon.A: Thank you.Q: How old are you, Gwendolyn?A: Seventeen. Q: And how are you feeling today?A: Fine.Q: Do you have any restrictions at allin your physical activity?A: Well, I can't do what my otherclassmates do, like play games.Q: What happens if you do?A: Well, I get tired easy.Q: I see. Do you get out of breath atall?A: Yes.Q: Now, we understand that you havehad some serious illnesses in the past.About how many times have you been inthe hospital?A: About twenty times.Q: And can you tell us a little aboutthe kinds of illnesses you have had?A: Well, I had pneumonia twice, andI have had pains in my joints and se­vere pains in the abdomen.Q: What sorts of treatment have youhad?A: I had transfusions; I had abouttwenty of them.Q: What year are you in high schoolnow, Gwendolyn?A: I'm a senior.Q: And what are your plans for thefuture?A: Well, I want to go to nursingschool._Q: That's very nice, Gwendolyn. Per­haps we can help you in that respect,and maybe when you become a nurseyou can come back and help us here inthis hospital. Thank you for coming.(The patient leaves the room.)Well, here is a high school youngster,very much like yourselves, but, on theother hand, very different. For, after verycareful questioning of the patient andher parents, a thorough physical exami­nation using our eyes, our ears, and oursense of touch, then certain laboratoryprocedures, and careful study of all ofthis information, the essence of the storyis that since the age of five monthsGwendolyn has had a severe, relentlessanemia. Against this background, shehas had serious episodes of pain in herabdomen, in her chest, in her bones andin her joints, two bouts of pneumonia,heart failure, and bleeding from her di­gestive system.These illnesses have been so gravethat on several occasions she has beenon the edge of death. Indeed, few chil­dren with this disorder survive intoadulthood.What is sickle cell anemia? The term"sickle cell" refers to the peculiar con­figuration which the red cells, in theblood of patients affected, assume undercertain conditions, such as the relativedeficiency of oxygen in the blood of theveins as opposed to the arteries.Fig. 1 is a photograph of blood froma normal person. We see that the cellsconsist of round red discs.Fig. 2 is a smear of blood from ourpatient, Gwendolyn. Notice the fairnumber of cells that have a peculiarcrescent or sickle shape. Such cells arevery fragile, so that they are readily de­stroyed in the circulation. Normal redcells survive about four months, in thecirculation. Sickle cells die very early,lasting only a few days, perhaps onlya few hours. Because of this, there isa reduction in the circulating red cells,a condition which we call anemia, andthis is demonstrated in Fig. 3.The tube on the left contains bloodwhich was taken from the arm vein of anormal person. We see the deep red colorof the hemoglobin, the red pigment inthe red cells of this blood. Next is a tubecontaining blood from Gwendolyn's arm,which is paler.When we centrifuge the tube of nor­mal whole blood, we find that the redcells become packed in the lower portionof that tube, so that about 40 per cent ofthe volume of this specimen consists ofthese packed red cells. In comparison,the volume of packed cells in the bloodtaken from Gwendolyn is appreciablyless, about 20 per cent of the volume ofthe whole blood in the tube. This, thenrepresents a severe anemia. She hasabout half the red cells in her circulationthat you and I have. Fig. J. Microscopic appearance of red cellsfrom a normal person. Fig. 2. Blood smear from patient showingsickle-shaped red cells.UN' CENTRIFUGEDNORMAL SICKLE CENTRIFUGEDNORMAL SICKLEFig. 3. Tubes of blood from a normal individual and from the patient with sickle cell anemia.The relative pallor of the sickle blood (second tube) is a reflection of the decreased volume ofpacked red cells as is evident in the centrifuged specimen (fourth tube).Notice also the pronounced yellowishdiscoloration of the fluid in which thesered cells are ordinarily suspended. Thisfluid is called the plasma, and the yel­lowish pigment is, as some of you learnedthis morning in Dr. Lester's laboratory,bilirubin. Bilirubin is excreted by wayof the liver into the bile ducts and gallbladder, and may give rise to gall stones,which Dr. Strandjord will refer to.Sickle cells are not only readily de­stroyed, but, because of their shape, theytend to clump and occlude small vessels.The involved tissues are deprived oftheir normal blood supply, a state which we call ischemia, and this may give riseto pain. If the deprivation is severeenough, the tissues may die, and, in criti­cal areas, blood vessels may rupture, withresulting bleeding. If this occurs in thelungs, blood may appear in the sputum.Bleeding from the kidneys may berecognized by blood in the urine, . andwhen the trouble is in the bowel, bloodmay be seen in the stool.Sickle cell anemia gives rise to a widevariety of clinical disturbances. Some ofthese can be readily detected by X-rayprocedures. Will you tell us about these,Dr. Strandjord?ME 0 I CAL A l U M NIB U II E TIN 13FIG. 4FIG. 7DR. STRANDJORD:I would like to follow the course ofGwendolyn in this hospital by use ofX-rays and also show you how we canmake the diagnosis of certain pathologi­cal and physiologic processes whichoccur in patients· who have sickle cellanemia.The first X-ray, Fig. 4, is the initialchest film on her admission to this hos­pital, and you can see in the right lowerlung field a large dense area which repre­sents pneumonia. The patient was admit­ted at this time with a fever caused bythis infection. You will also see scatteredthroughout the rest of her lungs someother densities.Now, in a normal subject, pneumoniais a severe disease, but in Gwendolyn'scase it posed an even greater threat toher health. In order to help her breathe,a tube had to be placed in her tracheawhich then was connected to a positivepressure respirator. In Fig. 5 we seethroughout her entire lung fields veryextensive pulmonary edema, which is ourterm for fluid in the lungs.14 MEDICAL ALUMNI BULLETIN FIG. 5FIG. 8Due to excellent care, the patientgradually improved. Fig. 6 shows anX-ray taken eight days following heradmission, and at this time she still hasa tracheotomy tube in place. The pneu­monia in the right lung is improving,though there are scattered areas of infec­tion throughout other portions of herlungs.In Fig. 7, taken two and a half weekslater, we see that her pneumonia haspractically disappeared, but now we seeanother troubling sign: her heart is largerthan that of a normal subject.Can we understand why this patient'sheart is enlarged? In persons with severeanemia the output of the heart is in­creased to compensate for the diminishedoxygen-carrying capacity of the blood.This increase is accomplished by aug­mentation of stroke volume, as well asincrease in the heart rate. Her heartbeats faster and it attempts to put outmore blood per st.roke.Cardiac hypertrophy, or enlargementof the heart, occurs, then, in patients FIG. 6Fig. ..tI. X-ray film of chest of sickle patientshowing pneumonia in right lower lung field.Fig. 5. Diffuse edema throughout both lungsand tracheostomy tube in place.Fig. 6. Regression of edema and pneumoniawith treatment.Fig 7. Tracheostomy tube removed, furtherclearing of the pneumonia, but enlargement ofthe heart now clearly apparent.Fig. 8. Patient now symptomatically recoveredand only residual scars evident in right lowerlung field.who have long-standing severe anemia,as compensation for this increased work­load.Fig. 8 shows a chest X-ray taken aftershe had recovered. She has some mini­mal residual scars in her lung, but herlung fields are essentially clear. However,in addition to the lung trouble, we foundthat the increased destruction of bloodhas led to increased excretion of bilirubinand the formation of a gall stone, whichis quite unusual in a girl of this age.Another characteristic of this diseaseis changes in the bones which contain theblood-forming tissues of the body. In anattempt to increase the number of redblood cells circulating, there is hyper­trophy, or expansion, of the blood-form­ing organs, or hematopoietic system, andthis is reflected in a distinct widening ofthe marrow of the bones of the forearm,seen clearly in Fig. 9. The bones have be­come softer and are very thin in theircortex.Now, you have also heard that thesered cells, when they are deprived ofFIG. 9oxygen, assume a peculiar sickle shape.In capillaries, particularly in the bone,the clumps of sickle cells impair the flowof blood. There is further hypoxia, orreduction of oxygen; rupture of bloodvessel walls with hemorrhage, and, insome cases, actual death of tissue. Thesechanges we call infarction or necrosis.In Fig. 10 you can see this process ina patient who has sickle cell disease.There are occluded or thrombosed ves­sels in the bones. A portion of the bonehas died and, in the reparative phase, hasbecome calcified: this is called a boneinfarct.In Fig. 11 we see destruction of thehead of the femur, or thigh bone, in apatient. This tissue death, or necrosis,occurs in about 12 per cent of the pa­tients who have sickle disease and leadsto severe arthritis. The head of the femurhere has been almost totally destroyed,leading to severe crippling.Our final X-ray, Fig. 12, demonstratesanother phenomenon. Bacteria are fre­quently present in the blood stream. They FIG. 10FIG. 12get into the blood stream daily in everyone of you. The simple process ofsqueezing a pimple or brushing yourteeth vigorously causes bacteria to bedislodged and sent into the blood stream.If the patient has an area of infarctionor dead bone, the bacteria find a place tolodge and grow and multiply, producingan osteomyelitis, or an infection of thebone. This film shows very severe osteo­myelitis.This is the way in which we use X-raysto follow the course of the patient and,in many cases, to make a diagnosis.Dr. Blaisdell: Thank you, Dr. Strand­jord. We have seen how diverse the clin­ical expressions of this disorder can be,and we ask ourselves: How does a childcome to have this kind of disorder? It issaid to be inherited and yet Gwendolyn'Sparents, Mr. and Mrs. Bolton, seem tobe well. In fact, we can see for ourselves,because they have consented to be herethis afternoon. (Parents enter.)Good afternoon, Mr. and Mrs. Bolton.Please sit down. We have been talking FIG. 11Fig. 9. The ulna and radius exhibiting widen­ing of the marrow space and thinning of thebony cortex.Fig. 10. Irregular radiolucency and smallareas of dense calcification representing in­farction of the distal femur.Fig. 11. Aseptic necrosis of the femoral head.Fig. 12. Bacterial infection and destruction ofdistal forearm bones, a complication of thesickling phenomenon with ischemia.about Gwendolyn and we would like toask you a few questions. Have either ofyou had such serious illnesses as yourdaughter, Gwendolyn?Mr. Bolton: No, I haven't ever beensick a day in my life, no more than Ihad a finger amputation in 1960 and Iwas in the hospital ten days.Q: How about you, Mrs. Bolton?Mrs. Bolton: No, I was only in thehospital twice, for the birth of my twochildren.Q: You say you have two children?Mrs. Bolton: Yes.Q: Are there any others in your fam­ily, children or otherwise: who have beenill like Gwendolyn?Mrs. Bolton: Well, I have a son, 15,and he has the same disease, but not asserious.Q: Anyone else in the family with thistrouble?Mrs. Bolton: No, I have no knowl­edge.Q: Dr. Bowman, do you have anyquestions to ask Mr. and Mrs. Bolton?ME 0 I CAL A L U M NIB U L LET IN 15Dr. Bowman: No.Q: Thank you very much for coming.We will be conferring with you later.(Parents leave.)Dr. Bowman, how is it that Gwendo­lyn and her brother have this disease andyet their parents do not seem to beaffected?DR. BOWMAN:Before I begin this discussion, Ishould define a few terms for you. How­ever, the laboratory demonstrators thismorning have informed me that your·questions have been so astute that it ismore than likely you already know thedefinitions that I am about to put beforeyou. But, in the event there are somewho do not, I will proceed.Within the nuclei of cells are struc­tures termed chromosomes, which existin pairs. Along the chromosomes areunits of heredity called genes. Each geneon one of the pair of chromosomes hasan opposite at a similar place (calledlocus) on the other member of the pair,which is either like or unlike its partner.Genes which occupy similar places orloci are alleles. Since genes may be likeor unlike and are in pairs, there are threepossible paired combinations analogousto the result of the simultaneous toss oftwo coins many times. If two heads fallface up, we would say, in genetic terms,that the coins are homozygous heads; ifthere are two tails: homozygous tails;and if there is one head and one tail thecoins are heterozygous head, tail.Now, there are thousands of genessituated along threads of chromosomes;it is thus clear that all are not oppositeeach other. Genes which are not op­posite are non-allelic.In Gwendolyn's case, as we will show,both her father and mother are hetero­zygous: each carries one normal geneand one defective gene. Gwendolyn her­self, however, is homozygous, abnormal:she inherited two defective genes. Exam­ination of her blood and of her parents'blood revealed the erythrocytes to havea sickle shape, as previously shown. Thisphenomenon is induced by various tech­niques which lower the oxygen environ­ment of erythrocytes of subjects who arehomozygous or heterozygous for thesickle cell gene. However, with this testwe may not be able to distinguish thepatient's blood from the parents' blood.Fig. 13 illustrates a test which enablesus to make this distinction: electrophore­sis. Some of you have seen demonstra­tions of electrophoresis this morning. Inthis test, specimens of lysed blood, that16 ME 0 I CAL A L U M NIB U L LET I N HEMOGLOBIN PAPER ELECTROPHORESISG Direction of Migration eORIGINtI CONTROL Hb AI CONTROL Hb SI PATIENT Hb SI MOTHER Hb S AFATHER Hb S AFig. 13. Electrophoretic identificotion of theparents as heterozygotes (Hb A-S) and the pa­tient as a homozygote-affected (Hb S).is, hemoglobin solution from red cellsare placed on paper and in a suitablebuffer, and an electrical current is applied.The hemoglobin then migrates towardsthe anode (positive electrode) . You willnote that the migration of the normalcontrol hemoglobin (HbA) has proceeded-farther along the strip of paper than thatof the hemoglobin S (HbS). The patient'ssample is similar to that of the homozy­gous HbS standard. However, there aretwo distinct bands of hemoglobin onstrips containing hemolysates from themother and father. One band migrateslike that of H'uA and the other like thatof HbS; thus, the mother and father areheterozygous A-S (Normal hemoglobin/Sickle hemoglobin).We will now demonstrate various pos­sible combinations of parents and off­spring with respect to a pair of genes,assuming one-of- the genes to be "ab­normal." As we have said before, theaiternate gene (allele) may not be defec­tive. (Fig. 14).You now see before you our volun­teers. Five students in the front rowstand and face the audience. The two onyour left are mother and father and thenext three are children. Now, let the firstchild represent the homozygous normalA-A, the second child the heterozygousA-S, and the third one the homozygousaffected child S-S. 1. If the mother and father are bothhomozygous normal then it is clear thatall children will be homozygous un­affected.2. If the father is homozygous normaland if the mother is heterozygous it isexpected that the offspring will be one­half homozygous normal and one-halfheterozygous. Clearly, since children in­herit only one gene from each parent, itis impossible for these parents to have ahomozygous affected child.3. If the father is homozygous normaland if the mother is homozygous affected,all children will be heterozygous. Thismating is very important clinically as faras the sickle cell gene is concerned. Withbetter medical care it is quite possiblefor a homozygous affected S-S motherto have children. She may ask the physi­cian, "Will my children be sick as Ihave been most of my life?" The mothercan be assured that although all of herchildren will have a sickle gene, theywill be heterozygous and can live a rea­sonably normal life.4. The fourth mating of heterozygousfather and heterozygous mother is themost important source of transmissionof the sickle cell gene and is like that ofthe case presented today. Both parentsare apparently healthy, yet they mayhave severely affected children. Fromthis mating, one would expect one-fourthof the children to be homozygous nor­mal, one-half to be heterozygous andone-fourth to be homozygous affected.Now odds, as you know, do not alwayswork out like this. The parents of ourpatient today are so unfortunate as tohave two affected (homozygous) chil­dren. The homozygous normal and theheterozygous children may go to theirphysicians, deeply concerned about chil­dren that they may have at some futureThe Sill Types d Fornilies with Respect to One Pair dAutosomal Genes��;x.��.x.o Unoffected c! or «() Heterozygote cJ or ,• Homozygote • or ,Fig. 14. The possible modes of inheritance ofthe sickle gene.date. After all, they have seen brothersor sisters ill or even dying. The homo­zygous normal child may be assuredthat no matter who he or she marries, achild with homozygous sickle cell diseaseis impossible. The heterozygote may beinformed that, provided the prospectivemate is not heterozygous or homozygousaffected, the children will not havehomozygous sickle cell disease. This in­formation is very important. No doubtmany couples have gone through lifefearing to have children, whereas thesituation could have been avoided withproper advice.5. The mating of a heterozygousfather and a homozygous affected motherwill produce one-half heterozygous andone-half homozygous affected children.6. Finally, (a most unlikely mating)a homozygous affected father and ahomozygous affected mother can produceonly homozygous affected children.Dr. Blaisdell: Thank you, Dr. Bow­man, and thank you, our model family,for your togetherness.N ow we would like to ask some otherquestions about this inherited disorder.Dr. Bowman has referred to adult hemo­globin (HbA) which is normal, and asecond kind, sickle hemoglobin (HbS),which is abnormal. The questions wewould like to ask are these: How doeshemoglobin S, an abnormal hemoglobin,lead to sickling of the red cell, and,secondly, what is there about the hemo­globin S molecule that is responsible forthis peculiarity? The last question is:How are these properties geneticallycontrolled?Tough as these questions may be, theycan be largely answered through thework of people like Dr. Haselkorn, whoapply the methods of physics and chem­istry to biological problems. Dr. Hasel­korn.DR. HASELKORN:I shall start by trying to fill in the gapbetween the gene and the gene product,which, in this case, is the protein hemo­globin. First I'd like to make sure thatyou all know what a protein molecule is.A protein is a large molecule containinga linear array of units called aminoacids, in a particular sequence. There aretwenty naturally-occurring amino acids.Each protein has a unique amino acid se­quence which determines the way it willact biologically. Amino acids can be di­vided into three classes: those with apositive charge; those which are neutral;and those which are negatively charged. Of the twenty amino acids, two, lysineand arginine, have positive charges; six­teen have no charge; and glutamic acidand aspartic acid are negatively charged.Some proteins are structural. Theseare the proteins that are found in skin,bone, hair, and muscle. Others are en­zymes, which carry out all the chemicalreactions in living cells.The job of hemoglobin is to carryoxygen from the lungs to the rest of thebody. The hemoglobin molecule consistsof four peptide chains of amino acids.There are two "kinds of peptide chains,called alpha and beta. The alpha chainhas 141 amino acids and the beta chainhas 146 amino acids; the two are verysimilar in amino acid sequence. Eachpeptide chain has on its surface a large,flat structure called heme. It is the hemeof the hemoglobin that binds and carriesoxygen in the blood.I think the next question is, "Howare proteins made in a living cell?" Forthis we have to start from scratch withDNA. For those of you who read Scien­tific American regularly, this is old hat,but in case you missed a couple of issues,I should like to say a few words about it.There are four kinds of base units inDNA: adenine, guanine, cytosine, andthymine. The unique property of theseunits is that simple physical forcesgovern the attraction of adenine withthymine, so they will always bond toeach other, and the same physical forces,hydrogen bonds, govern the associationof guanine and cytosine. These nitrogen­containing base units, called nucleotides,are displayed along a linear sequence,and this linear sequence comprises agene. Now in theory, proteins could bemade directly on such a DNA mold ortemplate, although this has never beenobserved to happen either in a cell or atest tube, to date. What the cell does isto make a copy of one of the DNAstrands in the gene. This copy is RNA,which is chemically very similar to DNA.It differs only in a minor detail, and thebase thymine is replaced by uracil. Thisuracil has the same property as thymine:it bonds with adenine exclusively.This particular RNA molecule, whichhas been termed "messenger RNA,"leaves the gene and stretches itself outon the surface of cytoplasmic particlescalled ribosomes. Ribosomes look ratherlike small viruses. They are made up ofabout 60 per cent RNA and 40 per centprotein, and they are the machinery onwhich proteins are made in cells.Now we have a nucleotide sequence,an RNA molecule attached to a ribo- some, which carries the same informa­tion that one of the strands of DNA inthe gene had. How are we going to makea protein? We have to convert thenucleotide sequence into an amino acidsequence. This is done by a set of smallmolecules called soluble or S-RNA.There are probably forty kinds of S-RNAin every cell, and these S-RNA mole­cules are the translators of the geneticcode. They have a dual specificity. Theyrecognize given amino acids which attachto one end, and they have nucleotidetriplets on another end which recognizea sequence of nucleotides in messengerRNA. An enzyme sitting on the surfaceof the ribosome makes the bond betweenthe amino acids, and it is there thatmesenger RNA determines amino acidsequences.Next, let us consider the consequencesof mutation. Mutation is the change ofone of the naturally-occurring nucleo­tides in DNA to a wrong one. A wrongnucleotide in DNA puts the wrong nu­cleotide into RNA, and, finally, a wrongamino acid in the protein. That's asmuch as we have to know.You may ask what the evidence is forthis scheme of gene action in terms ofprotein synthesis. In reality, this came aslittle more than the filling in of the de­tails of the one-gene-one-enzyme propos­al of Beadle and Tatum, two decadesago. I should mention that much of theevidence for this scheme has been ob­tained in the past few years, and, indeed,Samuel Weiss of the biochemistry de­partment here is one of the discoverersof the DNA-RNA synthetic reaction.E. Peter Geiduschek in our departmentworks on the product of that reaction,and my own laboratory is concerned withthe association of RNA with ribosomes.So this is work that is going on at pres­ent in many laboratories, including thoseof The University of Chicago.The first clear-cut evidence that genesact in this way came from a study ofhemoglobin. The story goes back to1945, and in connection with it I'd liketo read you a little of the history ofscience. This is written by Linus Pauling,who is describing the initiation of a chainof experiments that led to the discoveryof the origin of sickle cell hemoglobin.He says:"I remember very clearly some occa­sions when I have seen a new way oflooking at a part of the world. One eve­ning, early in 1945, I was having dinnerin New York with a small group of menassociated with the medical schools ofthe country. We were members of aME 0 I CAL A L U M NIB U L LET I N 17Medical Advisory Committee appointedby Dr. Vannevar Bush to help him pre­pare replies to a series of questions posedin a letter sent to him by PresidentRoosevelt. That evening, one of themembers of the committee, Dr. WilliamB. Castle, of the Harvard MedicalSchool, began, in the course of thedinner conversation, to talk about thedisease, sickle cell anemia. This seemedto be a disease of the red corpuscles ofthe blood, which were twisted out oftheir normal shape in the blood of thepatient. The disease seemed to involve apathological state of the red corpuscle,but the red corpuscle is so large com­pared with molecules, and it contains somany hundreds of kinds of molecules,that there seemed to me to be little pos­sibility that an understanding of the.disease could be obtained in terms ofmolecules. However, when Dr. Castlesaid that the red cells of the blood aretwisted out of shape in the venous bloodof the patient and resume their normalshape when the blood passes through thelungs and enters the arterial circulation,the idea burst upon me that the mole­cules of hemoglobin in the red cellsmight be responsible for the disease­that the disease might be a moleculardisease involving an abnormal sort ofhemoglobin, manufactured by the pa­tients because of their possession of ab­normal genes in place of the normalgenes that control the manufacture ofnormal hemoglobin molecules. This idea,the idea of molecular disease, seemed tome to be such a sound one that I had nodoubt that it would ultimately be foundto be correct."Now, this is the birth of an idea in1945. Dr. Pauling suggested that some­body else do an experiment, and thatperson turned out to be Harvey Itano,who performed the experiment that wasdemonstrated in the slide that Dr. Bow­man showed: the electrophoresis ofhemoglobin. Molecules that are chargedmove in an electric field, and when thistechnique was applied to hemoglobinfrom people with sickle cell anemia, itwas found that the electromobility ofhemoglobin S was different from that ofnormal hemoglobin, which implies thatthere is some difference in the number ofcharged amino acids on the surface of themolecule. That discovery was madearound 1950, and it took another five orsix years to show exactly what the changein hemoglobin S was.You remember that each chain ofhemoglobin has about 140 amino acids.When the amino acids of hemoglobin A18 MEDICAL ALUMNI BULLETIN and hemoglobin S were quantitativelyanalyzed, no difference in compositioncould be found: a more sensitive methodof analysis was required. Such a methodwas developed by Vernon Ingram, ofthe Massachusetts Institute of Technol­ogy, using techniques described bySanger for the determination of aminoacid sequences. A molecule of hemo­globin A was to be compared with amolecule of hemoglobin S, and he knewthat the small difference between themwould not be detectable when analysiswas done on the whole molecule. Theexperimental error in quantitative analy­sis of amino acids is 3 to 5 per cent, andwith 140 amino acids, one amino acidchange would not be picked up. What heneeded was a reproducible way of cuttingthe molecule into small pieces and com­paring the pieces. The answer to the firstproblem was found in the enzyme tryp­sin, which has the lovely property ofbreaking peptide chains next to lysineand arginine, the positively chargedamino acids. Next he needed a method ofcomparing the pieces. To do this frac­tionation, a technique was developedwhich is known as fingerprinting. Finger­printing consists of paper chromatogra­phy and paper electrophoresis performedin perpendicularity.This experiment is shown in Fig. 15.This is a comparison of the two-dimen­sional fingerprint of hemoglobin A andhemoglobin S. Each of the spots corre- sponds to one of the peptide fragmentsproduced from hemoglobin upon diges­tion with trypsin. Notice the tremendoussimilarity. However, here peptide fourcan be seen to be in a new position. Ithas a different electrophoretic mobility.Also, note that all the other peptides arein the same position. It's a simple mat­ter to take a pair of scissors and cut outthe new spot, then subject the peptide toamino acid analysis. When this was done,it was found that a glutamic acid ofhemoglobin A is replaced by a valine inhemoglobin S.Fig. 16 shows part of the beta chainof hemoglobin A and hemoglobin S. Thesixth amino acid from the end of thebeta chain, glutamic acid, is replaced byvaline in hemoglobin S, and that oneamino acid replacement is enough toaccount for Gwendolyn's illness.So the story is essentially complete.The mutational alteration in the DNAof the hemoglobin gene leads to an al­tered messenger RNA, the altered mes­senger RNA leads to an altered aminoacid in the hemoglobin, and this, in turn,causes the sickle cell anemia.Dr. Blaisdell: Thank you, Dr. Hasel­korn.We have now traced the illness of ouryoung lady, and have observed the variedmanifestations resulting from a single,genetically-controlled molecular defect(Fig. 17). The flaw in nucleotide se-FINGERPRINT OF Hb A AND Hb 5+ElectrophoresisHb A t t>-£.o�0'o'0Eo�s:U>­.s::.Q.o�0'o'0E�uElectrophoresisHb 5Fig. JS. The difference between hemoglobins A and S is seen to reside in a single peptidefragment (#4).BETA CHAINPEPTIDE 42 3 4 5 7 86HbA+ +Hb 5+ +Fig. 16. The defect in the hemoglobin S molecule is pinpointed-the substitution of a singleamino acid valine (Val) for glutamic acid (Glu) in peptide 4 of the beta chain. The difference inthe charge 'of the two amino acids accounts for the altered electrophoretic mobility.quence in the DNA of the inherited geneis conveyed by messenger RNA to thecell ribosomes, where proteins are made;this error in transcription leads to theinsertion of a wrong amino acid in thebeta polypeptide chain of the synthesizedhemoglobin molecule; the resulting ab­normal hemoglobin, HbS, is responsiblefor the sickling of the red cell, especiallyin veins where the oxygen content of theblood is reduced; occlusion of blood ves­sels, bleeding, and susceptibility to in­fection result. Thus, most of the impor- tant gaps between the gene and the dis­tress of the patient are filled in.But man is more than an assembly ofmolecules. We are also interested in therelationships of man to man, and man tohis past, in order to understand man inthe future. The sickle cell story helps usto understand some of these relation­ships. For example, we may ask: howand where did the sickle gene arise, andwhy has it persisted? To answer theseand other questions is Dr. RonaldSinger.S -RNA + amino acidsQene (DNA) ---- m-RNA L Hb S (Yz f3;al 6) ].02_,RBe Sicklinv��RBe clumpinvR7�t-- a------/ -. (eor�. ., ocHvhyvall stones jcaJndic. weakness thin banes inbane lunvs vut�\/ischemia/��pain infection bleedinvFig. 17. The pathogenesis of sickle cell anemia from an abnormal gene to the diverse clinicalmanifestations of the disease. DR. SINGER:It's left to me to tie up all these high­voltage data into some sort of story. Thesickle story had its genesis on this cam­pus, in fact. Just about fifty years ago,in 1910, Professor James Herrick notedthe occurrence of sickled red blood cells,or erythrocytes, in a smear from a WestIndian Negro student with chronicanemia. Some seven years later, this con­dition was reported in a father and in ason, and, in another five years, thehereditary nature of the sickling phe­nomenon was established as a Mendeliandominant, variable in its effects. In 1927it was demonstrated that susceptibleerythrocytes sickled only when deprivedof oxygen, as you have been told here.In this country, numerous investiga­tions were carried out to determine thefrequency and distribution of the sicklingcondition. It was found to be virtuallyconfined to the American Negro, inwhom approximately 10 per cent exhibitthe trait. Only twenty years ago the cleardistinction was drawn between sickle-cellanemia and the sickle-cell trait or carrierstate.In Africa, it was well after World WarII that large scale surveys in search ofthe sickle cell were made. Prior to this,there had only been occasional reports ofsickling from the Sudan and West Afri­ca. In 1945 the condition was reportedfrom East Africa, from Kenya and Tan­ganyika, and in the same year the ab­sence of this trait was noted amongBantu-speaking Negroids from SouthAfrica. In 1946 an investigator reportedthat there was an incidence of 12 percent in Northern Rhodesia; he also no­ticed that south of the Zambezi Riverthere was a much lower incidence thanon the north side of the Zambezi River.He believed that this great river wasacting as a barrier to the spread of thesickle gene from the north.In 1949 Beet and N eel independentlypropounded the currently accepted the­ory of the genetic mechanism of thesickle cell condition that Dr. Bowmanso clearly pointed out to you. The traitoccurs in those heterozygous for thesickle cell gene, while the anemia resultsf rom the presence of the gene in thehomozygous state where the sicklingtendency has been inherited from bothparents.The prognosis, or future outlook, forpatients with sickle cell anemia is notdefinite. Some young children die; fewercases are seen in older children, andsome rare cases in adults where the con­dition is rather mild. Occasional patientsMEDICAL ALUMNI BULLETIN 19with the anemia may reproduce, thoughnot all cases claimed have been ade­quately identified. A relatively smallnumber of pregnant women with sicklecell anemia has been reported, andamong these the maternal mortalityamong the mothers was 16 per cent, andthe total fetal loss among the newbornwas one-third.Taking all the available evidence intoconsideration, it may be stated that it isexceptional for a homozygote to reachadult life and reproduce. So you mightask: If the disease is so lethal, so de­structive, how is it possible that it doesnot wipe itself out?A striking feature of the distributionof the gene for hemoglobin S is its al­most total occurrence among Negroesand Negroids of the African tropics. Itsessential predilection for Negroes is in­dicated by its discovery in areas whereAfrican Negroes were taken as slaves;for example, North, Central and SouthAmerica, where the condition has notbeen found among pure Indians. How­ever, hemoglobin S is also reported fromcenters in the Mediterranean countries,in the Middle East and in South India.A Negroid admixture is a part of thebiological history of some Mediterraneanpopulations at least since Roman times,and there is also considerable evidenceof fairly large Negroid populations inIndia. However, some of the reports ofsickling in these areas are clearly amongpeoples in whom Negroid genes are notevident. Thus, although sickling is pre­dominantly associated with the AfricanNegro, it may also be found in othergeographical populations.When one examines the frequency ofthe trait in Africa more carefully, oneis impressed by the patchiness and lackof conformity of the distribution of thegene, as is shown in the map (Fig. 18).Marked frequency differences (varyingfrom 0 to 45 per cent) may exist be­tween tribes living adjacent to one an­other within a single territory. Theaverage for all the African tribes is ap­proximately 20 per cent.Various aspects of the distribution ofthe hemoglobin S gene have been ac­counted for by migration and mixture,but at an early stage of the numerousattempts to solve the sickle cell distribu­tion problem, it was recognized that thescattered high frequencies required amore cogent explanation. The gene flowaspect, that is, the natural spread of thegene across populations, will be referredto again, but it is now advisable to dis­cuss the development of the remarkable20 M E Die A L A L U M NIB U L LET I N correlation between the distribution ofthe sickle cell gene and the severity ofmalaria. I will just say a word aboutmalaria relative to this condition.Malaria is a widespread disease whichproduces a significant number of deaths,among infants in particular, and the ex­tent or incidence of the disease is higherthan that of any other disease known.Malaria is caused by protozoa of thegenus Plasmodium, which grow in anddestroy red blood cells. Transmissionfrom one vertebrate host to another iscarried out by mosquitoes. In man thereare recognized at least four malarial in­fections, of which one is caused byPlasmodium falciparum, the most recentspecies to parasitize man. The distinctiveability of the Negro race to toleratethese infections perhaps points to Africaas the origin of these protozoa.Neel first pointed out that there aretwo possible major factors which tend tomaintain and increase the number ofsickling genes in a population: either thegene is arising frequently by mutation,or the heterozygote state confers a selec­tive advantage over the disadvantage ofthe homozygote for the anemia; that is,there exists a condition of "balancedpolymorphism. "To put it in simpler words, if a geneticGAMBIAFrequency of Sickling :Over 300/••21 - 30% •II -20%.1-10% •< 1%0The II Sickle Belt II -== trait protects individuals against malaria,either against death or by conferring ahigher fertility on the carriers in malarialareas, then such persons would enjoy adistinct biological advantage. But if sucha genetic trait also has harmful effectsand causes illness and diminished fertil­ity, then an equilibrium gene frequencywill be reached at which the beneficialand the harmful effects of such a genewill balance each other, and this systemis known in population genetics as bal­anced polymorphism.Several workers have demonstratedthat it is reasonable to exclude an in­creased mutation rate as the explanationfor the remarkably high frequencies ofthe heterozygotes that are known tooccur. Moreover, there is direct evidenceavailable that a person with the sicklingtrait has an increased resistance to falci­parum malaria; that is, the heterozygotepossesses a selective advantage overeither homozygote.After some important cause-and-effectobservations in East and South Africa,between 1944 and 1952, malaria becamefirmly established as a selective agent inregard to sickling with the publicationof a series of important papers by Alli­son in 1954. He pointed out striking dif­ferences between sicklers and non-sick-Fig. lB. Map of Africa showing wide variations in occurrence of the sickle gene, with high fre­quency in the mid-region of the continent and in Madagascar, but sharply reduced incidence southof the Zambezi River. The arrows indicate the migration of the shert-hern Zebu cattle.lers in susceptibility to experimentally­induced malaria.However, the interpretation of theobservations is complicated by the factthat all his subjects derive from an areahyperendemic for malaria and they allmust have acquired a considerable im­munity in childhood. He concluded thatindividuals with the sickling trait will, inall probability, suffer from malaria lessoften and less severely than those with­out the trait. Hence, in areas wheremalaria is hyperendemic, children havingthe trait will tend to survive, while somewithout the trait are eliminated beforethey acquire a solid immunity to malar­ial infection. He believed that the pro­tection against malaria might also in­crease the fertility of the possessors ofthe trait. Thus, the proportion of indi­viduals with sickle cells in any popula­tion would be the result of the balanceof two factors: the severity of malaria,which will tend to increase the frequencyof the sickle gene, and the rate of elimi­nation of the sickle cell genes in indi­viduals dying of sickle cell anemia.However, as plausible and as attractiveas Allison's hypothesis is, it seems likelythat there are additional factors at playor that an alternative hypothesis mayhave to be postulated. Some workershave supported his findings while othershave not. Most authors agree on thecomplexity of the problem and the lackof essential data as direct evidence.Evidence is accumulating that geneflow, transmission of genes across popu­lations through migration, may supplythe major explanation of the distributionof the sickle cell gene.Some of us have been interested in themigration concept for some time. Ourwork in Southern Africa and Madagascarhas certainly had some interesting impli­cations. As you can see from the inap(Fig. 18), Madagascar is a large island,some 300 miles in length and only 150miles from the African coast across theMozambique Channel. The interestingthing about Madagascar is that, despiteits proximity to Africa, its culture, lan­guage and mode of living are completelyIndonesian.VVe have seen that there is a sharpdrop in the sickling incidence in theregion south of the Zambezi River wheremalaria is as prevalent as in the north.Now I would like to discuss the remark­able resemblance that the distribution ofsickling bears to the distribution of theshort-horn Zebu cattle. The day wouldn'tbe complete without your seeing a Zebu(Fig. 19). These cattle migrated acrossAfrica by two routes, which, as you see Fig. 19. Short-horn Zebu cattle, whose distribution in Madagascar and Africa resembles that ofthe sickle gene.from the map in Fig. 18, are the majorareas of sickle cell distribution. The cat­tle are also present in Madagascar, inwhich they equal the population in num­bers. South of the Zambezi there are noshort-horn Zebu cattle at all.We know a lot about migration ofcattle and the approximate times atwhich they probably arrived from theMiddle East and spread down the eastcoast of Africa. This may give us infor­mation about the date of mutation ofcertain genes and the time it takes forthese genes to spread and develop in thepopulation.VVe also know that great numbers ofAfrican Negro slaves were taken toMadagascar from the 12th through the19th centuries. VVe find that in thosetribes in which there is the greatestNegroid affinity, the incidence of sicklingis higher than in those which are Indo­nesian in appearance. Because of this,and because of the high frequency amongthe Madagascan people of the typicalAfrican blood groups, it seems highlyprobable that the gene was brought toMadagascar from Africa and not fromIndia or other parts of the east. Theseobservations are also compatible with thetheory that the sickling gene was intro­duced into or arose in Africa in compara­tively recent times, perhaps about the7th century A.D.; that is, after theSouth African Bantu-speaking Negroids,who are non-sicklers, had crossed theZambezi. Furthermore, it is possible thatthe people who introduced and firstspread the sickling gene prior to theestablishment of the selective advantagewere the people who were accompaniedby the short-horn Zebu cattle. These cattle are highly successful in tropicalareas and possibly the fact that thepeople who herded them had a selectiveadvantage in respect to malaria, or someother environmental advantages, led totheir migratory success. This would alsoaccount to some extent for the peculiardistribution of the sickling gene.Furthermore, the spread of the sicklecell gene in West Africa seems to be re­lated to the manner of the spread ofagriculture: by cutting down forests andburning clearings, an ideal environmentwas created, within the last few hundredyears, for the propagation of the mostrecent species of malaria to parasitizeman, Plasmodium jalciparum.Thus, in summary of the appliedgenetical situation, one can say that thereis a certain impressive amount of indi­rect evidence that the sickling polymor­phism is balanced by a differential sus­ceptibility to malaria, but that what islacking is direct evidence.There can be no doubt that naturalselection occupies a focal point in thecourse of human evolution. However,our concepts of the operative mechanismof natural selection have advanced littlebeyond Wallace's views stated in 1871in his classic paper on "The Action ofNatural Selection in Man." In this re­spect, it becomes a vital matter to solvebeyond doubt the problems inherent inthe balanced polymorphism of the sicklecell gene, because it provides the onlyavailable experimental material obviousat present. The problems present an ex­citing challenge not only to the physicianand biochemist but also to the serologist,the physical anthropologist and the popu­lation geneticist.M E 0 I CAL A L U M NIB U L LET I N 21Dr. Blaisdell: Thank you, Dr. Singer.Are there some questions from the audi­ence?QUESTIONS FROM THEAUDIENCEQ: Why was it that Gwendolyn'sbrother didn't get the disease as serious­ly as she did?Dr. Bowman: In biology, one must ex­pect variability; there is no absolutecertainty in this field. Gene effects arenot necessarily the result of the action ofthe primary gene alone, but may havebeen modified by other genes which canincrease or decrease the action of the ab­normal gene. So the physiological en­vironment, and oftentimes the externalenvironment, may modify the effect ofthe primary gene. When we put all ofthese together, we should expect to see ahigh degree of variability.Dr. Blaisdell: Thank you, Dr. Bow­man. Do we have another question?Q: Would you say that a sickle cellgene is a dominant?Dr. Blaisdell: Dr. Singer referred tothe sickling phenomenon as dominant ininheritance whereas Dr. Bowman re­ferred to sickle cell anemia as a homo­zygous state, that is, resulting from thepresence of two allelic genes, one from 'each parent. This would suggest reces­sive inheritance. How do we answer thequestion, Dr. Bowman?Dr. Bowman: Dominance, recessivity,and intermediance are relative terms. Wecould probably best look upon the sicklegene as one of intermediate dominance,because the heterozygotes (HbA-S)occasionally have difficulty. For exam­ple, if Gwendolyn's mother or fatherwere to get into an unpressurized air­plane and the plane suddenly ascended tohigh altitudes, the reduced oxygen in theatmosphere might cause their red cells tosickle and they would develop a sicklecell crisis with pain and even anemia.When they were brought back to theground, someone who knew nothingabout their history might say, "This issickle cell anemia." So heterozygotes canget into difficulties, too.Dr. Blaisdell: A question has beenasked about the treatment of sickle cellanemia. The treatment at the presenttime is mainly correction of the anemiaby the transfusion of normal cellswhich contain hemoglobin A. But thequestion might be asked, "What is theultimate treatment for this type of dis­order; is it possible, for example, to ad­minister to these patients the right kindof gene or the right kind of messenger22 M E 0 I CAL A L U M NIB U L LET I N RNA that might correct the difficulty?"How about that, Dr. Haselkorn?Dr. H aselkorn: The practical diffi­culty of using nucleic acids for treatmentis that enzymes in the blood plasma de­stroy nucleic acids of both kinds as fastas you can get them into the body.If you've been thinking of the schemeof protein synthesis that I outlined, I'dlike to point out that more than one geneis involved in the synthesis of any pro­tein. In addition to the structural gene,described extensively today, which pro­duces messenger RNA, there are othergenes that make S-RNA, and there aregenes that make the enzymes that putamino acids on to S-RNA. If you had amistake in messenger RNA, you mightcorrect it by making a complementarymistake in S-RNA, or in the activatingenzyme which puts the amino acid on tothe end of S-RNA. These types of mu­tations are called suppressor mutations.Dr. Blaisdell: Thank you, Dr. Hasel­korn. We really should take a break now,a five-minute intermission, after whichwe will reconvene here for some con­cluding remarks by the president of theUniversity.INTERMISSIONDr. Blaisdell:We are privileged to have with us thisafternoon Mr. George Wells Beadle, 1958Nobel Laureate in physiology and medi­cine and president of this University.MR. BEADLE:Thank you very much, Dr. Blaisdell.I'm very happy to be here with youpeople. It won't be many years, youknow, until you will be doing what thesepeople were doing today. It may seem along way off, but time goes pretty fast.I know you have listened to a lot andseen a lot, and you don't want to hearmuch more talk, but I'd like to say justa few things. First of all, you have prob­ably heard so much and seen so many complicated pieces of apparatus today,that you think medical science and othersciences both enormously difficult andvery complicated. Actually, it isn't nec­essarily so.Ideas in science add up to making itsimpler. I like to think of some aspectsof science as a very complex telephoneexchange. The machinery looks so com­plicated that YO!J might think that no­body could possibly understand it, butactually, the individual component partsare very simple. And so it !s with sci­ence in general; biology in particular. Ican remember talking about how genesact when I was a post-doctoral fellow,and nobody had the slightest idea whatthey were. Now we know what they arein chemical terms; we know what theydo and how they do it; and much ofgenetics and the aspects of biology whichdepend on it have become very simple.Principles replace, a large collection offacts.Many of you are thinking about ca­reers in science, or medicine in partic­ular; that's why you're here today. Per­haps you have heard of a book calledListen to Leaders in Medicine. If youhaven't, I would suggest that you urgeyour high-school library to get thisbook. It is part of a series on careeropportunities for young people. Listento Leaders in Medicine was written bysome dozen and a half outstanding peo­ple in medicine, and it gives a great dealof information about what medical ca­reers are like and what kind of prep­aration is needed.In this connection, I'd like to empha­size something that Dean Ceithaml said:you should not give up a career in sci­ence or medicine or anything else youare interested in for financial reasons.Perhaps I can point out something aboutThe University of Chicago that willmake this a little clearer. I just lookedat some figures for last year's budget inThe University of Chicago and discov­ered that the income from tuition andother fees paid by students adds up toten million dollars. The amount of schol­arship and fellowship aid that goes tostudents, the loans which Dean Ceithamlmentioned, and the employment, add upto $9,500,000. In other words, there isa very small difference between the totalamount that students pay for their edu­cation in the form of fees and theamount they get back one way or an­other. Now, of course, part of this theyearn by working, and part of it repre­sents loans that have to be paid back.But since a pretty large fraction of stu­dents don't need any help, those who doneed it get a greater proportion. So ifyou have financial need, don't give upuntil you have explored all the possibili­ties, because if you have ability you willfind a way to go ahead and do what youwant to do.Now I'd like to clear up another com­mon misconception about scientists.Many people feel that you have to be akind of genius to do anything in science.This really isn't so at all, and historyshows it. Darwin, for example, was thedespair of his father because he wasn'tbright in school, he wasn't bright in col­lege, he wasn't even very interested inanything. His father practically gave up.He said he wasn't interested in anythingbut shooting and chasing rats-but lookwhat he did.Or take Gregor Mendel, who contrib­uted one of the great ideas to biologyof the last century. He couldn't pass theexaminations to teach high school. Infact, I believe he failed them twice-butlook what he did. The only trouble isthat he didn't get any credit for it, be­cause he was ahead of his time. It tooka third of a century for people to acceptwhat you were told today: that geneticsis really simple.This suggests another idea: many ofthe great ideas in science are simple, sosimple that people can't accept them.The so-called one-gene-one-enzyme hy­pothesis was actually proposed over fiftyyears ago, but people said, "Well, it can'tbe that simple." So it wasn't until tenyears ago that it was finally accepted.Science doesn't have to be difficult.You don't have to be a genius, and itdoesn't have to be complicated, and itdoesn't have to take a lot of expensiveequipment. Let me give you some ex­amples of that. Mendel worked in hislittle cloister garden, where all he hadwas some garden peas. Anybody couIdhave done the experiment he did, withno expense at all-all it took was time.Or take Fleming, who discovered peni­cillin in a little Petri dish culture ofbacteria which got contaminated with apiece of mold. The total expense for thisexperiment was perhaps fifty cents, butlook what came of it.Or take Watson and Crick, whoworked out the structure of DNA. Theyread the literature and found out whathad been done, and then they just satdown and thought about it. Then theygot some atomic models, just like tinker­toys, and started putting them togetherto see if they could make a structurethat would explain all the known factsabout DNA. And the basic idea for thisstructure, as Dr. Haselkorn pointed out, is that the base components are alwayspaired: adenine to thymine, cytosine toguanine.Now, it had been observed by otherpeople that if you tear nucleic acid downinto its component parts you find ade­nine, guanine, cytosine, and thymine.There is always one A to one T, and oneG to one C, but the A's and the C's arenot necessarily equal. This was the cluethat Watson picked up. He said, "Whatdoes that mean?" Well, the way youcould explain this is that they're pairedin a double structure, specifically, andthere always has to be an A to a T anda C to a G. Simple as anything. Actually,I don't think Jim Watson had a veryphenomenal record in high school. As amatter of fact, he was an undergraduateat The University of Chicago, and hedidn't have a phenomenal tecord here,either. In addition to that, he was anearly entrant; he came before he fin­ished high school. But he had a lot ofinterest, a lot of originality. He didn'talways like what his teachers taught him,so he didn't learn it, but when he wasinterested he was good.You may wonder, after hearing aboutall these discoveries, what there is leftto do. Well, mostly people tell youwhat's known; they don't say muchabout what's not known. But that's theinteresting part, because that's whatyou're going to discover.That brings me to a thought aboutscience which is true of any intellectualactivity-it gives you the opportunityto discover something that has neverbeen known before. Until you have ex­perienced finding something completelynew, you can't appreciate what a satis­faction it is. And you can have thatsatisfaction. You may have it in a verysmall way, but in any area, if you digdeep enough you can find out somethingthat has never been known before. Onediscovery isn't necessarily as importantas another, but there's always a greatsatisfaction in making the discovery.Let me mention to you some of thethings that are not known today. Whydoes a red blood cell make hemoglobinand not much else, whereas another cellof the body doesn't make any hemo­globin? We believe that the DNA in­formation in all cells starts out equal.Why do some cells do one thing andsome cells another? This is the field ofdifferentiation, and it's largely an un­known field. Why do the nerve cellsdifferentiate and do what they do? It'sa little bit like a cookbook. A housewifepicks a cookbook off the shelf, and al­though it's got a lot of information in it she only uses one piece today. But shecan go to the same book tomorrow andpick out a different piece, so that thefirst day she may make an angel foodcake and the next day an apple pie, butit all came out of the same set of infor­mation. And so it is with your cells.They all have the same information, webelieve, but different parts are used atdifferent times, and we don't know howthis selection is made. The answer maybe very simple; that's for you, the nextgeneration, to find out.And the discoveries that you makewill make the following generation alittle different from what it would other­wise have been. Not many people influ­ence the next generation, but you peoplehave a special opportunity.Let me mention one other area inwhich we need a lot more knowledge.You learned quite a lot about biologicalinheritance today. Each of your cellscontains five billion units of DNA.That's the total genetic information thatmakes you out of that little cell fromwhich you developed. Dr. Haselkorn toldyou about the two little bits of it thatmake the two chains in the hemoglobinmolecule. There are perhaps fifty thou­sand times that many in all. If you tookall the information out of one cell anddivided it, you would have five billionunits-l ,700,000,000 of these little three­letter segments that specify amino acids.They would make a protein molecule1,700,000,000 amino acids long. To putthis another way, there are twenty kindsof amino acids; there are twenty-sixletters in the alphabet. You could leteach of those three-letter sequences rep­resent a letter of the alphabet (andyou'd have some extra ones) and thenyou could encode a DNA message writ­ten in letters of the western Europeanalphabet, and how much informationcould you get out of the DNA of onecell ? You could get the equivalent of athousand printed volumes, six hundredpages per volume, five hundred wordsper page, if the words were five-letterwords.And all of that information is sub­microscopic. In fact, it is so small thatif you took all of the DNA out of allthe cells that have given rise to all thepeople on earth-that's three billionpeople, roughly-and stacked it up likecordwood, it would make a cube aboutan eighth of an inch on each side. Eachperson carries the equivalent of a thou­sand printed volumes; three billionwould carry three trillion printed vol­urnes; that is, about 60 thousand timesas much information as has been printedM E 0 I CAL A L U M NIB U L LET I N 23in all the different books since Guten­berg invented the printing press. That'spretty good miniaturization.Now you know something about thatkind of information, about how it's trans­mitted from generation to generation,how it mutates and how we evolvethrough mutation. But there's anotherkind of information in us that's tre­mendously important, and about whichwe know very little, and that's the infor­mation that is stored in the brain. There'sa lot of it there; it has been accumu­lating in your brain since the time youwere born. In fact, you probably ac­quired a good deal before you wereborn. Some people think it might be putthere like DNA code. I don't happen tothink that's very probable, but we don'tknow. Other people think it's kind of aselective pathway of nerve cells that,once established, gets used preferentiallyagain.We don't know how much informationis stored that way because, as you know,a good deal of it is subconscious. If yougot it all out, sense, nonsense, and allthat, how much would it be? Nobodycan answer that question.These problems are particularly im­portant in our species because our spe­cies is characterized both by a biologicalinheritance and by information stored inour minds, which is transmitted fromgeneration to generation by word ofmouth and printed word. Your teachersgive it to you, you give it to each other,your parents give it to you, and it accu­mulates generation after generation. Itis this which makes cultures different:they transmit different kinds of infor­mation. Some of it is information youdon't even know about, very, very subtlekinds of information not transmitted bywords but by what you see, what youhear, all sorts of ways.Well, that's a very exciting field, par­ticularly in this world, where new na­tions are trying to change their culturesrapidly. Since cultural patterns aretransmitted from generation to genera­tion, to change them rapidly you've gotto break this chain of communicationsomehow. Changing a basic culture issociology, but it's related to science andmedicine because it deals with what'sinside you.I think that's enough. I just wantedto tell you that science can be veryexciting; it can be rewarding; and I hopesome of you will think about it, and Ihope a lot of you will think about com­ing to The University of Chicago. Thankyou.24 M E Die A L A L U M NIB U L LET I N Dr. Blaisdell: Thank you, Mr. Beadle,for your encouraging words suggestingthat careers in biology and medicine maynot be so difficult after all; indeed, notonly may they be fun, but only whenthey are, are they worth while.The hour is late; we have had a fullday. Our parting word is thank you foryour participation and good luck.Rogrr iA.armon1931'1961Roger Harmon was a native of Mich­igan, and attended the State College inEast Lansing. After three years he cameto The University of Chicago Schoolof Medicine and in 1962 received theM.D. degree.He distinguished himself as a swimmerwhen he was a student. He was a memberof the Big Ten Championship relay teamin 1958, and in 1960 he held four Uni­versity of Chicago swimming records.He chose pediatrics as his specialtyand won the Wyeth Resident FellowshipAward for 1963-64.At the time he began his residency hedeveloped a malignancy but he continuedto work until the following spring whenhe moved his family to Elmhurst andentered practice with two pediatricianswho had been residents at Bobs Roberts­Richard Mueller and James Stuart. Hesoon became a great favorite with hispatients and continued to practice untila few weeks before he died on August 25.His wife, Nancy, and their two daugh­ters, Merri Kristine, three years old, andLindsay Jane, nearly two, will continueto live in Elmhurst.In tribute to his great courage in liv­ing with the knowledge of his illnessand planning for his family and caringfor his patients, his classmates and col­leagues have contributed to a fund in hisname. Their contributions, most of themmodest, are sufficient to start a scholar­ship fund. Mrs. Harmon and Dean Ceit­haml have agreed that the fund shall beknown as the"Roger Harmon Scholarship Fund toprovide scholarship aid for worthy stu­dents in the School of Medicine, particu­larly for those indicating an interest inpediatrics." fACULTY NEWSWilliam E. Adams and Huberta M.Livingstone were guest professors at theUniversity of El Salvador in October afterattending the international meeting of theAmerican College of Chest Physicians inMexico City.Paul R. Cannon, Rush '25, became thetwelfth recipient of the Gold Headed Caneof the American Association of Pathologistsand Bacteriologists, one of, the highestawards in medical science, on March 6.Since his retirement in 1957, Dr. Cannonserved for four years as chairman of thefirst National Institute of Health study sec­tion on environmental toxicology and hasremained active on the Food ProtectionCommittee of the National Academy of Sci­ences-National Research Council.Lester R. Dragstedt, Rush '21, has beenawarded the Henry Jacob Bigelow GoldMedal of the Boston Surgical Society andhe has been elected an honorary fellow ofthe Royal College of Physicians and Sur­geons of Canada and of the Royal Collegeof Surgeons of England. He and Mrs. Drag­stedt spent a very active summer travelingtwice to California, once to Mexico City,and once to his old home in Montana. Dr.Dragstedt addressed medical meetings inmany cities along the way.C. Wesley Eisele, '34-'51, associate deanfor postgraduate medical education of theUniversity of Colorado, presided over aweek-long general practice review in Jan­uary. Fifty-five members of the MedicalCenter faculty served as lecturers, discussionleaders, and demonstrators for three hun­dred physicians from Colorado and neigh­boring states.Isidore Gersh, professor of anatomy, hasleft the University to join the anatomyfaculty at the University of Pennsylvania.W. Garth Hemenway, '52-62, is nowassociate professor and head of the divisionof otolaryngology at the University of Colo­rado Medical Center.Paul C. Hodges will continue as profes­sor of radiology at the University of Floridafor three years.Duncan A. Holaday, '43, is a memberof the committee on anesthesia, Division ofMedical Sciences of the National ResearchCouncil.Charles Huggins received the 1964 GoldMedal award of the Rudolf Virchow Medi­cal Society in New York. His lecture on theoccasion of the presentation was on "Con­trol of Human Cancers with Hormones."Dwight J. Ingle, chairman of the De­partment of Physiology, was awarded theOutstanding Achievement Award of theUniversity of Minnesota at the Mayo Cen­tennial Convocation in September. He washonored as well when the American Medi­cal Writers' Association conferred theirAward for Distinguished Service in MedicalJournalism to Perspectives in Biology andMedicine in the category of specialty andresearch journals. Dr. Ingle is editor ofPerspectives.Hideo Oshiro, instructor and fellow inotolaryngology, has entered private prac­tice in his native Hawaii.Benjamin Spargo, '52, holds a ResearchCareer Award of the United States PublicHealth Service in pathology. Melvin Griemand Lester Skaggs, both in radiology, holdsimilar awards.Robert C. Stepto, '49-'53, has been ap­pointed to the Chicago Board of Health. Heis an obstetrician and pathologist on thestaffs of Provident and Mercy Hospitals andon the faculty of Stritch School of Medicine.Paul H. Ward has left The Clinics tobecome professor and chairman of the Divi­sion of Otolaryngology at Vanderbilt Uni­versity in Nashville.Guy Williams-Ashman, professor of bio­chemistry and in the Ben May Laboratory,has joined the faculty as professor of re­productive biology in the division of urologyand as professor of pharmacology and ex­perimental therapeutics at the John HopkinsUniversity.GRADUATE NEWS'31. Egbert Fell and Mrs. Fell left thiscountry in February for three years of serv­ice at the Presbyterian Mission Hospital inKuwait, Kuwait.'37. Charles H. Rammelkamp has beenappointed to a four-year term on the Na­tional Advisory Heart Council beginning inOctober. Dr. Rammelkamp is professor ofmedicine at Western Reserve University anddirector of medicine at Cleveland Metro­politan General Hospital.Leo Rangell is president-elect of theAmerican Psychoanalytic Association. Heserved as president of the Association oncebefore, in 1961-62. He is also currently presi­dent of the Los Angeles PsychoanalyticSociety.John M. Weir has been elected directorfor the medical and natural sciences of theRockefeller Foundation. This internationalprogram is mainly concerned in problems ofpopulation, nutrition, and the developmentof better health care for people in ruralareas of underdeveloped countries. Dr. Weirjoined the staff of the Rockefeller Founda­tion in 1939 as a field staff member of theInternational Health Division and servedin Jamaica and Colombia until 1942. Onstudy leave at the end of the war, in whichhe served as a malariologist, he took anM.P.H. degree at Hopkins in 1946 and thenrejoined the field staff in 1947 for a five­year assignment in Egypt where he helpeddevelop local health services in rural areas.In 1953 he came to New York as assistantdirector for medical education and publichealth. He was made associate director in1955.Dr. Weir received his undergraduate train­ing from The University of Chicago andearned both the M.D. and Ph.D. degrees herein 1937. He has received many honorarydegrees and awards from United States,Colombian, and Chilean institutions for out­standing contributions in the fields of pub­lic health and medical education.'49. Ernest C. Siegfried has been ap­pointed director for the Phoenix IndianHealth Area Office of the United States Pub­lic Health Service. '53. Edward A. Stemmer has left Stan­ford to accept a position as assistant pro­fessor of surgery at the University of Utah.'54. Erwin Whitman is associate directorof clinical pharmacology for Hoffmann-LaRoche, Inc., in New Jersey.'55. John R. Benfield, who was chiefresident in surgery in 1963-64, has joinedthe faculty of the University of Wisconsinas assistant professor of surgery.'56. Leonard B. Achor has been namedassociate director of clinical research ofSandoz Pharmaceuticals.'57. Henry O. Kandler is on the attend­ing staff of Albert Einstein College of Medi­cine on the adult in-patient psychiatricservice. He reports that Sander Abend,'56, and Ted Jacobs, '57, are also on thepsychiatric staff at Einstein and RussellGardner, '62, is a second-year resident.'58. J. Michael Whitman resigned asmedical director of the South Side MentalHealth Clinic in order to obtain additionaltraining in child psychiatry at the Institutefor Juvenile Research.'60. Kenneth S. Brown is at the NationalInstitute of Dental Research working on thegenetics of congenital malformations, par­ticularly deafness and cleft palate.Lloyd Ferguson completed his residencyhere in pathology and has started a medicalresidency at the Massachusetts General Hos­pital of Boston.Melvin Vinik served in the U.S. AirForce in 1962 and 1963 and is now a residentin radiology at the Jackson Memorial Hos­pital in Miami.Mark Hoffer has completed his tour ofduty with the Navy and is taking an ortho- his paper, "The Press and Hypnotism." Hill­man spent a year in Paris in 1962-63 onthe first Logan Clendening Travelling Fel­lowship in the History of Medicine.'66. Wesley D. Ulrich has been awardeda Smith Kline & French Laboratories for­eign fellowship which will enable him toassist for thirteen weeks next summer at amission hospital in Zambia (NorthernRhodesia).RESIDENT NEWSThe three clinical fellowships awarded inChicago for 1964-65 by the Illinois Divi­sion of the American Cancer Society allwent to residents at The Clinics: JeromeIrwin Bookin in radiology, Willard Ar­thur Fry in surgery, and George WatersSleight III in pediatrics.James A. Esterly, '63, received the 1964Hektoen Award from the Chicago Patho­logical Society.Wilfred Finegold, '42-'44, has publisheda book on Artificial Insemination, the firston this subject by an American author. Dr.Finegold is on the faculty of the Universityof Pittsburgh and in private practice inPittsburgh.M. M. Hipskind, '33-'37, has beennamed chairman of the Department ofOtolaryngology and Peter J. Talso, '48-'51, has been made chairman of the De­partment of Medicine at Stritch School ofMedicine, Loyola University.Shoichi Kohatsu '57-'64, is an instructorin surgery at Stanford University.Ibe Hliversl1J Of ChtcagO cltnta"''''-i'r.<"'1-0 "'I<��_"-.pedic residency at the Ochsner Clinic in NewOrleans.'61. Charles E. Attig has been appointedmedical director of anesthesiology at theRiverside Hospital in Kankakee, Illinois.Lauren Pachman has continued her in­terest in research with lymphocytes at theRockefeller Institute after having completedher residency at Babies Hospital, New York.'63. Phillip S. Epstein is doing researchin neurochemistry in the Department of Bio­chemistry of the Institute of Psychiatry,the Maudsley Hospital, London, as a Ful­bright Scholar.Paul Hoffer is Lieutenant in the Navy onduty in Rota, Spain.'65. Robert Hillman has won the Illi­nois State Psychiatric Society's annual es­say award in the medical student group for BULLETIN ,of the Alumni AssociationThe University of ChicagoSCHOOL OF MEDICINE950 East 59th Street Chicago, Illinois 60637VOL. 20 WINTER 1965 No.2EDITORIAL BOARDJESSIE BURNS MACLEAN, SecretaryARCHIE LIEBERMAN, Art EditorWJUGHT ADAMS ROBERT J. HASTERLIKRICHAlloK.BLAISOELL ELEANOR M. HUMPHREYSL. T. COGGESHALL HUBERTA LIVINGSTONERICHAJU> EVANS PETER V. MOULDEJlWALTER L. PALMERMEDICAL ALUMNI BULLETIN 25Wilbtr E. �ost-2lo 2lpprtdatiooThe long and distinguished life ofWilber E. Post came to an end on De­cember 22, 1963. The majority of themen of medicine of his generation hadpreceded him in death; few of the presentgeneration are aware of his contributionsto the University of Chicago, Rush Med­ical College, the Presbyterian Hospitalof Chicago, and to Chicago medicine.Born March 20, 1877 in Lowell, Mich.igan, Post began teaching at the ageof 15 in the district schoolhouse nearhis home. Later, he was Superintend­ent of Schools for two years in August,Michigan. In 1898 he graduated fromKalamazoo College, and two years laterreceived the Ph.B. degree from the Uni­versity of Chicago. It is interesting tonote that for some unknown reason Wil­ber Post was present at a conferencebetween President William Rainey Har­per, Ephraim Ingalls, and Frank Billings,in which plans were made for the estab­lishment of a medical school on thecampus of the University of Chicago. Anaffiliation between the University andRush Medical College had been effectedin 1898. The University in 1901 accededto the request of the Trustees of RushMedical College to permit Rush studentsto do their first two years of medical workin the Hull Laboratories of the OgdenGraduate School of Science. Dr. Postwas a member of the first class, togetherwith David]. Davis, later Dean of theUniversity of Illinois College of Medi­cine, Ernest E. Irons, later Dean of RushMedical College and President of theAmerican Medical Association, and Dal­las B. Phemister, the first Chairman ofthe Department of Surgery of the Uni­versity of Chicago School of Medicine.Dr. Post dedicated his life to threeinstitutions: The University of Chicago,Rush Medical College, and the Presby­terian Hospital. All three were closelyinterrelated throughout his active years.His association with Rush began as a26 M E 0 I CAL A L U M NIB U L LET I N student and continued throughout hislife as he filled one position after another,including a Clinical Professorship ofMedicine. He was the last Dean of RushMedical College, serving from October1939 to June 1942, when the last studentwas graduated. Technically, a friendlycourt decision had ended the union ofRush with The University of Chicagoin June, 1941. Rush then leased its prop­erty to the Presbyterian Hospital, whichin tum entered into an agreement withthe University of Illinois. Rush haspersisted in name and in organizationbut without a Dean and without students,except as these come through the Uni­versity of Illinois. The faculty membershave continued as Rush Professors. Afterretirement, Dr. Post cherished the titleof Rush Professor of Medicine Emeritusof the University of Illinois.Presbyterian Hospital for over fiftyillustrious years was the active teachinghospital of Rush Medical College. Dr.. Post served an interneship there underDrs. Frank Billings and Arthur DeanBevan from January 1904 to October1905; in later years he was proud to benumbered among the disciples of Billings.For 10 years after internship he workedwith the Billings group which includedDrs. Joseph A. Capps and Joseph L.Miller, who were members of the staff ofSt. Luke's Hospital and who later becameProfessors of Medicine of the Universityof Chicago; George Coleman of theSt. Luke's staff and Dr. William A.Thomas of the Presbyterian staff werealso members of the group. Dr. Postbecame chief of medical service at Pres­byterian Hospital in 1919, and in 1941was elected Chief of the Medical Staff.From 1912 to 1918 he was a memberof the attending staff of Cook CountyHospital, a position achieved at that timeby competitive examination.Hospital residencies in Internal Medi­cine had not come into existence whenDr. Post was a young man (they werealmost a generation away) but foreignstudy was in vogue. Dr. Post worked fota time in Vienna and then in Freiburgwhere, under Professor Aschoff, he in­vestigated the pathology of the cardiacnode. Upon his return to Chicago he be­gan a long series of studies on nephritis­a confused and poorly understood sub­ject on which he and his generation shedgreat light. Dr. Post participated in theestablishment of the concept of focal in­fection, especially its relationship toarthritis and endocarditis. He was greatlyinterested in the effects of drugs and onmany occasions told of a patient sensi­tive to aspirin, to whom the administra- tion of one five-grain tablet had causeddeath.In addition to the associations withThe University of Chicago already men­tioned, Dr. Post in 1919 became a mem­ber of the Board of Trustees and con­tributed greatly to the deliberations ofthat body during the years when theSouth Side Clinical Department was be­ing organized. John Post recalls that,when the blueprints for Billings Hospi­tal were being drafted, Lyman Flookwho at that time was head of the Uni­versity Department of Buildings andGrounds breakfasted with his father reg­ularly for many weeks in order to dis­cuss with him such details as the locationof the elevators, laboratories, and nursingstations. He resigned from the Board ofTrustees in 1939 when he became Deanof Rush, because he saw a conflict of in­terest in his loyalties to the two institu­tions. As a Trustee, Dr. Post was instru­mental in obtaining for the Universitythe Louis B. Kuppenheimer Fund, theZoller Fund, the A. D. Thompson Fund,and the Anna Louise Raymond Fund. Thecurrent value of these endo.wments, ac­cording to Miss Hortense Friedman, As­sistant Treasurer of the University, isestimated as in excess of eleven milliondollars.Dr. Post's extra curricular activitieswere numerous. In 1917 he was a memberof the American Red Cross Mission toRussia, headed by Dr. Frank Billings, tosurvey the medical needs of that coun­try. In 1918, under Harry Pratt Judson,President of The University of Chicago,he was a member of the Commission forRelief in the Near East, especially forfamine relief in Persia. In 1926 Dr. Postwas President of the Chicago Society ofInternal Medicine; in 1943 he was Presi­dent of the Institute of Medicine of Chi­cago. He was an enthusiastic golfer andloved to play with his old companions,David J. Davis, Ludwig Hektoen, Wil­liam H. Wilder, Joseph A. Capps, JosephL. Miller, Basil C. H. Harvey, H. GideonWells, Oliver Ormsby, and many others.On June 1, 1910, Dr. Post marriedLouise Morrison of Springfield, Illinois,who survives him. Their 53 years of mar­riage were happy years with mutual de­votion and the rearing of one son, John,who graduated from The University ofChicago School of Medicine and thenserved an internship in Billings Hospi­tal as well as in Barnes Hospital of Wash­ington University in St. Louis.Dr. Post's dedication to medicine wasa reflection of his broader dedication tothe service of his fellow man. To theBaptists of his youth, education was aj ostph 5Ilmarin «tapps1872-1961On September 16, 1964, Joseph Al­marin Capps, one of the grand old menof medicine, died at the age of ninety­two in the Winnetka home of his son,Dr. Richard B. Capps. His wife, ChristyBrooks, had died in 1942. He is survivedby another son, Robert, and a daughter,Mrs. David Cogan of Boston.Dr. Capps was born and grew up inJacksonville, Illinois, where he attendedIllinois College. After spending one yearat the medical school of Yale Universityhe transferred to the Harvard MedicalSchool, joining Harvey Cushing and Elli­ot P. Joslin, as chance would have it,in the class of 1895. His life long interestin clinical investigation was manifestedearly. During his fourth year at Harvardhe demonstrated that leukocytosis oc­curred during convulsions and publisheda paper on the subject in the AmericanJournal of the Medical Sciences. Follow­ing a term as "House Pupil" (now in­tern) at the Massachusetts General Hos­pital and house officerships at the Mc­Lean and Boston Lying-in Hospitals, heset up offices in Boston, prepared topractice obstetrics, but, with businesssomething less than brisk, pulled upstakes after a time and in 1897 arrivedin Chicago, where he forsook the forcepsfor the stethoscope. He set up "an officeover a drug store" and soon obtained anappointment at Rush Medical College.There he became associated with anillustrious group which included Billings,Sippy, Herrick, Hektoen and Woodvatt.His introduction to this galaxy �ameabout, no doubt, through Dr. Billings,who was so impressed by Dr. Capps'energy and ability that he invited himto live in his home and to assist him ina thriving practice. Thus began the Chicago phase, span­ning more than half a century, of a dis­tinguished career of medical practice,teaching and clinical investigation. Dr.Capps rose from instructor to professorof medicine at Rush, became chief ofthe medical staff at Cook County Hos­pital in 1912, served as visiting physicianto St. Luke's Hospital for forty yearsand latterly as Trustee, and in 1926 wasappointed Professor of Clinical Medi­cine at the University of Chicago, aunique position in an otherwise full timestaff. He shared offices with Dr. JosephL. Miller, with whom he was to be as­sociated all his life and later was joinedby Dr. George H. Coleman.Dr. Capps' researches were concernedchiefly with clinical medicine and physi­ology. Soon after his arrival in Chicagohe identified the first case of hookworminfestation in the city. In 1903 he devel­oped the "volume index," essentially thesame as the modern hematocrit, whichhe used in the study of anemia. In 1911,in association with Dr. David Davis, hetraced to its source (the udders of a fewcows) a severe epidemic of streptococcalsore throat which had taken more than500 lives. This work led to legislationwhich made compulsory the pasteuriza­tion of milk in the Chicago area. Hemade the interesting discovery that thesacred trust and Dr. Post, throughout hislife, strove to uphold this trust as ateacher and an administrator. His kind­nesses to students and to other youngmen were unnumbered and unsung, buthe kept the Hippocratic Oath, "that byprecept, lecture and every other mode ofinstruction, I will impart a knowledge ofthe art to my own sons and those of myteachers and to disciples bound by astipulation and oath according to the lawof medicine."His patients were devoted to him andhe returned their devotion in full meas­ure. With dogged and inspiring determi­nation he continued in the active prac- tice of medicine, in spite of the infirmitiesof age and ill health, until he was 84 yearsold and then, with great reluctance,stepped aside. I knew him as mentor, col­league, neighbor and friend, and shall al­ways remember him with admiration andaffection. As Francis H. Straus has said:"His was a long life; a useful life; anda good life. We are all of us enhanced instature because of the 86 years in whichhe lived it."We may paraphrase the Oath of Hip­pocrates and add that, "with purity andholiness" he did indeed pass his life andpractice his art.WALTER L. PALMER, M.D. blood of a leukemic patient who hadbeen treated with X-rays destroyed thewhite blood cells of another leukemicpatient both in vitro and, transiently, invivo. He is best known for his studieson the reflex and sensory pathways fromthe pleura, pericardium and peritoneum.These investigations were carried on inpatients over a period of twenty yearswith the collaboration of Dr. GeorgeH. Coleman and were published as amonograph in 1932.Two prolonged visits to Europe inter­rupted Dr. Capps' accustomed activities.In 1902 he studied for a year in Viennaunder Oppenheimer, Ghon, Neusser, Ko­vacs and Turck, and in the first WorldWar he served as Major and LieutenantColonel in the Medical Corps and con­sultant to the A.E.F. His capacity forleadership is attested to by the role heplayed in local and national scientificsocieties. He was a founding member ofthe Central Society for Clinical Research,a founding member and president of theAssociation of American Physicians, theInstitute of Medicine of Chicago, theChicago Society of Internal Medicineand the University Club of Chicago.The annual Joseph A. Capps Award forthe best original investigation by ayoung graduate of a Chicago medicalschool was established by Dr. E. R.LeCount in his honor in the Institute ofMedicine.It was Capps the man, of course, whomade Capps the superlative physician.I never remember him but with pleasure.He was the personification of Osler's"equanimitas." Serenity emanated fromhim, but enlivened by humor. His ruddyface with its bushy brows and mustache(later, becomingly white), the cock ofhis head when he was especially inter­ested, the twinkle of his eyes at a goodstory, his cheerful disposition, his gentlemanner and dignified but unassumingbearing, all combined to make him atonce an attractive and an impressivefigure. The picture did not fade with age.He never failed to live up to the promiseof what the eye beheld in him and theear heard. Behind this pleasant aspectthere lay a keen intelligence, sound judg­ment and unassailable integrity. He wasgiven a long life and he left it as hewould have wished, suddenly, quietly,and, probably, without pain.HENRY T. RICKETTSProfessor of MedicineThe writer has drawn heavily on adelightful and longer sketch of Dr.Capps' life written by his son-in-law, Dr.David Cogan of Boston. H.T.R.M E 0 I CAL A L U M NIB U L LET I N 27DEATHS'93. Nicholas B. Bartz, Grand Rapids,Mich., May 15, 1964, age 94.'94. Erasmus M. Hill, Chicago, Ill., April2, 1964, age 95.'95. Charles Bolsta, Ortonville, Minn.,April 14, 1964, age 92.Walter J. Price, Tremont, III., Decem­ber 2, 1964, age 93.'96. Willard D. Brode, Vero Beach, Fla.,May 11, 1964, age 94.Frank A. Grawn, Ypsilanti, Mich., May31, 1964, age 94.Henry B. Hogeboom, Bethel Park, Pa.,November 11, 1964, age 91.'97. Newton M. Otis, Palo Alto, Calif.,March 24, 1964, age 91.'98. Harry Wallace Horn, Wichita,Kans., December 11, 1964, age 90.George R. Reay, Onalaska, Wis., Sep­tember 9, 1963, age 87.Ralph L. Whidey, Osage, Iowa, August26, 1964, age 93.'99. Charles J. Carson, Chewelah, Wash.,March 22, 1964, age 88.'00. Robert C. Kayler, McCloud, Okla.,September 19, 1963, age 88.'01. Duncan S. MacKenzie, Havre,Mont., November 17, 1962, age 83.'02. Howard J. Barry, Sun Prairie, Wis.,November 10, 1964, age 85.James H. Fowler, Lancaster, Wis., March24, 1964, age 93.'03. Don A. Vanderhoof, ColoradoSprings, Colo., April 12, 1964, age 85.'04. Leon A. Baldwin, Omaha, Neb.,June 21, 1964, age 86.Charles K. Barclay, Joliet, Ill., May 21,1961, age 82.'05. Roscoe L. Sensenich, South Bend,Ind., January 18, 1963, age 81.John P. Spooner, Toledo, Ohio, March 4,1964, age 88.Sidney H. Wetzler, Juneau, Wis., August5, 1964, age 81.'06. Harry R. Beery, San Francisco, Octo­ber 4, 1964, age 82.'07. Edward Niles, Chicago, May 26,1964, age 80.Joseph B. Winnick, St. Paul, Minn., May14, 1964, age 82.'08. Frederick A. Olson, Pomona, Calif.,July 10, 1964, age 80.Hollis E. Potter, Stuart, Fla., October 15,1964, age 84.'09. Ernest M. Johnstone, Santa Cruz,Calif., November 19, 1964, age 82.'10. Arthur N. Aitken, Newfield, N.Y.,September 13, 1964, age 81.'11. Harry L. Dale, San Francisco, No­vember 14, 1964, age 78.28 M E 0 I CAL A L U M NIB U L LET I N Albert H. Good, Denver, Colo., May 24,1964, age 82.'13. John D. Fowler, Los Angeles, March27, 1964, age 80.Ralph H. Kuhns, Chicago, September 10,1964, age 75.Linn F. McBride, Evanston, Ill., July 31,1963, age 75.Virgil H. Moon, Coral Gables, Fla.,April 16, 1964, age 85.'14. Emil Bunta, Chicago, February 1,1965, age 78.Lowell M. Campbell, Minneapolis, June1, 1964, age 78.Julian F. DuBois, Sauk Center, Minn.,March 31, 1963, age 76. ,Perry G. Snow, Douglaston, N.Y., March19, 196.3, age 85 ..Ottar A. Thomle, Everett, Wash., May6, 1964, age 81.Emmett C. Troxell, Sarasota, Fla., No­vember 20, 1962, age 73.Henderina V an de Erve, Los Angeles,August 31, 1964, age 77.'15. Herbert R. Booth, Hamilton, Mo.,April 29, 1964, age 77.Elmer Funkhouser, Indianapolis, August23, 1964, age 79.Peter O. C. Johnson, Watford, N.D.,May 26, 1962, age 79.'16. Ralph W. Carpenter, Geneva, Ill.,September 10, 1964, age 74.Charles A. Cibelius, Rockford, Ill., Au­gust 24, 1964, age 72.Jacob D. Mulder, Grand Rapids, Mich.,October 13, 1964, age 80.'18. Vincent J. O'Conor, Chicago, Janu­ary 26, 1963, age 70.'19. Clarence A. Barnes, Waukegan, Ill.,June 14, 1964, age 71.'20. James A. Howell, Shreveport, La.,March 22, 1964, age 72.Ora A. Rawlins, Park Ridge, Ill., No­vember 6, 1961, age 85.John L. Reichert, Chicago, September 19,1964, age 68.'21. Gardner Black, Kamuela, Hawaii,January 3, 1963, age 67.Wendell A. Potter, Springfield, Mo.,October 8, 1964, age 74.Clarence W. Spears, Jupiter, Fla., Feb­ruary 1, 1964, age 70.'22. William W. Davies, Jr., Kendall,Fla., November 17, 1964, age 73.Alvin G. Foord, San Marino, Calif., No­vember 13, 1964, age 69.John E. Nienhuis, Lamar, Colo., July 4,1964, age 70.A. Howard Shan berg, Chicago, Decem­ber 17, 1964, age 66.Lawrence J. Wilhelmi, Joliet, III., Octo­ber 4, 1964, age 72.'23. Earl E. Carpenter, Superior, Wis.,July 13, 1964, age 65. Clarence K. Schubert, Waunakee, Wis.,August 7, 1963, age 65.'24. Benjamin M. Gasul, Chicago, April.1964, age 64.'26. Harry A. Gussin, Chicago, October30, 1963, age 68.'27. Gladys K. Dolan, Tulsa, Okla., Jan­uary 15, 1964, age 69.'28. Edward M. Dorr, Chicago, October25, 1964, age 62.Gilbert J. Rich, Roanoke, Virginia, April12, 1963, age 70.'29. John W. Foster, Winston-Salem,N.C., November 7, 1964, age 70.Ralph McBurney, Tuscaloosa, Ala., June21', 1964, age 81.Frank Curtis Spencer, Honolulu, May 3,1964, age 65.'30. William Perry Wheless, SpringHope, N.C., March 12, 1964, age 59.'31. Alfred L. Burgdorf, Bloomfield,Conn., October 15, 1962, age 60.Lloyd Catron,· Akron, Ohio, September14, 1964, age 57.Homer S. Parker, Park Ridge, Ill., Au­gust 10, 1964, age 59.Irving B. Shulak, Detroit, July 6, 1964,age 60.'32. Joseph Berlin, Donora, Pa., January25, 1965, age 59.'33. F. A. Musacchio, Laredo, Tex., May15, 1964, age 58.'34. Jerome A. Megna, Milwaukee, No­vember 13, 1964, age 53.Abe M. Meltzer, San Jose, Calif., May22, 1964, age 59.'35. Charles G. Polan, Huntington,W.Va., June 13, 1964, age 54.'37. John M. Hoffman, McMinnville,Ore., March 22, 1964, age 53.Thomas M. Leonard, Washington, D.C.,July 12, 1964, age 54.'39. Edward E. Cannon, Chicago, Decem­ber, 1964, age 49.Oscar L. Entin, Granada Hills, Calif., Au­gust 7, 1964, age 48.John E. P. Hyland, Phoenix, Ariz., May13, 1964, age 52.John R. Snavely, Jackson, Miss., June12, 1964, age 51.'41. Harry P. Maxwell, Milwaukee, Sep­tember 2, 1963, age 46.'43. Arthur A. Hellbaum, Ardmore,Okla., September 4, 1964, age 60.Paul W. Siever, Glencoe, Ill., November29, 1964, age 45.'62. Roger N. Harmon, Chicago, August25, 1964, age 27.RESIDENT STAFFWilliam W. Ornduff, Resident '38-'40,Portland, Ore., October 5, 1964, age 54.