Written Nov 2001

Preface

For several decades immediately afterWorld War II Federal researchbudgets increased exponentially everyyear. If one had reasonable ideas itwas possible to get funding. Itpermitted somebody like me, whowas trained in a relativelyunspecialized way as an MD, to doresearch in a variety of fields. This isone way of describing a checkeredcareer.

I have told stories about my researchexperiences to people in variousstages of post-prandial torpor. Mywife, Abby, insisted that I write themdown, presumably so she wouldn’thave to listen to me telling themanymore. I do so in more or lesssequential order, sticking to the factsas I remember them. I hope that they don’t differtoo much from the recollections of thoseinvolved at the time.

Chapter 1. Sweating at Fort Knox

I was in medical school in 1943 at NYU when wegot put into the Armed Services Technical Program.The medical students continued on as before exceptthere were no summer vacations. Since I startedmedical school after the 3rd year at Columbia (I missthat 4th year to this day), which I entered at age 16, Iwas a ripe old 22 when my M.D. was awarded.Abby and I were married when we were both aged21, so I was somewhat grown up.

I had 2 research experiences in medical school.The first was when I walked the halls outside ofMilton Levy’s lab in the chemistry Department. Iwas trying to get up enough nerve to go in to askhim to let me work on an idea. I thought that amixture of ionized chemicals could be separatedin an electrical field. This is conventional now,but had not been discovered then. I did not getup the courage and that is why I never became abiochemist.

The second research experience was in AlbertKeston’s laboratory. He was the model of a“mad”scientist: wildly enthusiastic, bubbling with

Memoir of a Mostly Research Career in Environmental Health

Roy E. Albert MD (January 11, 1924 - March 25, 2002)Jacob G. Schmidlapp Professor Emeritus of Environmental HealthDirector Emeritus, Department of Environmental HealthCollege of MedicineUniversity of Cincinnati

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ideas, gulping handfuls of thyroid tablets and waxinglyrical about pastrami sandwiches. He talked so fastthat I couldn’t understand what he was doing. Itwas something about acetylcholine and he usedleech muscles because of their exquisite sensitivity toacetylcholine. He sent me down to the bowery torestock his supply of leeches from some really oldtime pharmacy stores that were down there at thetime. When I told him that I was getting married, hesaid, “I’ll never see you again.” He was right.

The military took over the medical schools because they wanted to ensure a supply of doctors. Probably as a payback for not being put in the infantry, they required 2 years of military service after internship. I took my internship in Internal Medicine at the Bellevue Third Medical Division which was run by NYU. We were then assigned to Fort Sam Houston in Texas for orientation. The only thing I learned there was how to grade beef.

When asked, I told the Army that I wanted to do research, so they assigned me to the Third Amored Division Research Laboratory at Fort Knox, Kentucky. That laboratory was set up because of the high incidence of heat stroke among tank crews fighting in the North African desert. The Army had assembled a bunch of academic stars at the lab including Norton Nelson, Ed Palmes, Rollo Park, Bill Ashe, Tony Lanza, Bill Machle, Ludwig Eichana and Ted Hatch. All went on to distinguished academic careers afterwards. They literally invented thermoregulatory physiology in humans and developed a rational way to prevent heat stroke. It was an early example of combining physiology and engineering to produce a new field.

When I arrived all of the stars except Ed Palmeshad left for universities. So I worked with himand Herman Schachner, another MD serving his2 years. The lab I worked in was a “hot room”, bigenough to hold a tank (minus the cannon) andequipped with machinery that could regulate thetemperature up to 120 degrees F and control thehumidity to whatever level one wanted. Ed Palmes

had just finished an experiment with Rollo Park onthe thermoregulatory changes in humans whendeveloping fever. They gave each other andvolunteer GI subjects an i.v. shot of typhoid vaccine(ugh!).

The subject lay nude inside a coffin-like box, on awebbed cot with Saint Saens third piano concertobanging in his ears. Thermocouples werestrapped onto the skin at various spots. Therewas a recording rectal thermometer, a rig tomeasure oxygen metabolism, and a set up tomeasure the amount of sweat the subjectproduced. Dry air was pumped into the box andflowed over the subject, evaporating the sweat.The moisture laden air then went out through anotherpipe to an infrared gas analyzer that measured thewater vapor content in the air. The more sweatingthe higher the water vapor content, so a continuousrecord of sweating was obtained. Ed and Rollowere struck by the fact that the sweating from theirsubjects, as measured by the water vapor content ofthe air leaving the box was not constant and theywondered why.

It seemed to be a good idea to look at sweatingwith the same method but from a small skin area.I don’t remember whether this was my idea orEd’s. I think it was Ed’s. He was prone to comeup with something so simple and elegant that itwas a genius of an idea. For example, he thoughtof a way to sample gases in the atmosphere thatrequired only an open tube with one end closedand coated with an absorber at the bottom closedend. The gases would be picked up in theabsorber and the amount analyzed after acollection period. The rate of sampling wasdetermined by the length and diameter of thetube. No power was needed to run the sampler.It could be worn on a lapel. There areinternational meetings now that are being held todiscuss new applications of Ed’s idea.

He also did a notable science project for one ofhis kids. It was common for fathers to do themfor their children in those days. I did one. His wasa stand that held a metal ball that fell on a holder on

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which was placed a cookie, thereby breaking thecookie into pieces. There were a series of sieves ofgraded hole sizes under the biscuit that captured thefragments and thereby permitted them to be countedaccording to size. The title of the project was,“How the Cookie Crumbles”.

So we made a small cup that was shaped like astove pipe hat, but not so tall. It had a tube inthe side near the brim and another tube comingout of the top of the cup. The opening of the cupwas about 2 inches across. The open face of thecup was applied to the skin. Again dry airentered the cup and evaporated the sweat on thesurface of the skin and the moisture-laden airexited the cup and went through the infrared watervapor analyzer. The water vapor content wascontinuously recorded by a pen held against themoving paper of a strip chart recorder. The higherthe deflection of the pen, the greater the water vaporconcentration, i.e. the more sweating, and theconstancy of the sweating was indicated by thedegree of flatness of the tracing.

We were astonished to see that the line drawn by the pen was anything but flat. It went up and down continuously which suggested that the sweating from the skin was not constant for reasons unknown. At that point Ed Palmes left to go to NYU where he joined Nelson and Lanza in the Department of Industrial Medicine. This is the Department I joined in 1959. Herman Schachner was out of the picture because he shot himself not long after I arrived at Fort Knox. He was a German-Jewish refugee who was chronically depressed. He had a Teutonic need to control things. He tried to do that with a horse that had thrown him and was kicked in the face as a result. This caused a depressed fracture of the cheek bone that displaced an eye. That was the last straw for his depression. There went a fine person and a bright academic career. In any case, I was left alone with the sweat study because Ed and Herman were gone.

Everybody loves simple experiments that open newworlds like the old Greek observation of adding salt

to a full cup of water without its overflowingdemonstrating that apparently solid matter is full ofholes. Then there was the one by Otto Loewe, theNobel prize winner, who gave us a lecture in medicalschool. He discovered something he called, in histhick Prussian accent, “Vagus-shtuff”. He told ushow he woke up one night with a great idea but, tohis horror, forgot it in the morning. In desperation, heput a pencil and paper at his bedside in case the ideacame back to him at night. Sure enough severalnights later, he awoke with the same idea and wroteit down. This was the idea: he put a beating turtleheart with its attached vagus nerve in a beaker ofsaline. He stimulated the vagus nerve electricallyand the expected slowing of the turtle heartoccurred. They he discarded the slowed turtle heartand put a fresh beating turtle heart with its attachedvagus nerve in the same beaker that held the firstturtle heart. Lo (Loewe) and behold, it sloweddown like the electrically stimulated heart butwithout any stimulation of the vagus nerve.Something got into the beaker of saline when hestimulated the heart. He discovered that nerves,when stimulated, produce their effects by releasingthe chemical, acetylcholine. With that experiment herevolutionized neurophysiology.

I never did a revolutionary experiment that gotme a Nobel prize, but I did an inspired thing withthe sweating experiment. I went over to thestockroom and got another infrared water vaporanalyzer. Amazingly enough, they had one on theshelf. I duplicated the initial setup including a secondcup just like the first one. In short I had 2 identicalsetups for measuring sweating and I got a strip chartrecorded that had 2 pens, one for each sweatmeasuring setup. I had the hot room turned up toabout 110 degrees F so that I was sweating briskly.I then put one cup on my forehead and the other onthe front of my chest. Lo and behold, the 2 pens onthe strip chart recorded went up and down as if theywere tied together! No matter where I placed thecups on different parts of skin the same thinghappened. I had discovered that sweating occurs insquirts synchronously over the surface of the body.

The next question was whether there was

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something inherent in sweat glands that made themfunction intermittently or whether it was the nervoussystem that made them discharge periodically. Itwas known that sweat glands are under the controlof the autonomic nervous system, which are twostrings of nerve cells that lie along each side of thespinal column, discovered by the great WalterCannon of Harvard. This system controls thebody’s vegetative functions like digestion andsweating as well as keying up the body foremergencies by releasing adrenaline, the “fight orflight” response. Cannon gave a series of lectures atthe NYU medical school. People were hangingfrom the rafters at his first lecture. But he was sodull that there were only a few diehards in theaudience at the end of the series. He had a badcase of radiation dermatitis because he usedunshielded -ray tubes in his studies of the nervouscontrol of the GI tract. So he just scratched andmumbled. I can’t remember anything he said. Itwas like being there when Jesus gave his Sermonon the Mount but you couldn’t hear a wordbecause he just scratched and mumbled.

In any case, I knew that sweat glands were stimulated by Otto Loewe’s “vagus-shtuff”(acetylcholine), so I slaked up some acetylcholine in a gauze pad and applied it to the skin of my forearm. The skin is impervious to water soluble chemicals so I had to drive the chemical into the skin electrically (iontophoresis). One electrode was put on top of the gauze pad and the other on the other side of the forearm. A voltage across the electrodes was applied for about 10 minutes. Then the sweat cup was applied to the skin site. There was plenty of sweat being produced but there was not a bit of fluctuation. So there was nothing about the sweat glands themselves that made for intermittent sweating. The pulses had to be produced by the nervous system because the sweat pulses were synchronized over the whole body, and the nervous control had to be centralized.

What about other factors? The sweat pulsesoccurred about once every 8 seconds. Thatexcluded the heart beat from having anything todo with them. What about breathing? I sat

down in the hot room with the sweat cup on myforehead watching the strip chart recorded. I heldmy breath and the pulses continued. I breathedirregularly and nothing changed. Then I triedbreathing deeply and rapidly and got dizzy fromrespiratory alkalosis. As I got dizzy sweatingstopped and when my head cleared, sweatingstarted again. I could turn sweating on and off byoverbreathing intermittently. Hyperventilationeliminated carbon dioxide from the blood and madeit alkaline. That caused blood vessels in the brain toconstrict, hence the dizziness. Presumably it shutdown the autonomic nervous system which stoppedthe sweating. If hyperventilation is severe enough,the blood gets so alkaline that calcium in the blood isinactivated and the muscles go into spasms (tetany).I never dared to hyperventilate that much. Butabout that time I visited the Army QuartermasterGeneral’s headquarters in Natick, Massachusetts.They also had a big hot room for experimentalpurposes. They told me about an experiment inwhich they put GIs in the room at a temperature of110 degrees F and 100% humidity. Under theseconditions, there is no way for the body to lose heat.They aborted the experiment when the subjectsinternal temperatures rose rapidly. They were ontheir way to getting heat stroke. I asked if thesubjects were hyperventilating. They said that theywere hyperventilating so hard that they were stiffwith tetany. So there was one mechanism forinducing heat stroke: hyperventilating and shutting offsweating so the body temperature rises until thebrain gets cooked.

By then I was convinced, having repeated theexperiments on a bunch of GI “volunteers” thatpulsatile sweating was due to the intrinsicrhythmicity of the autonomic nervous system.This rhythmicity is there for anyone to see. Ifyou look in the mirror, you can see that eachpupil gets larger and smaller as the iris contractsperiodically. That is called hippus. Anothermanifestation of the rhythmicity of the autonomicnervous system is that the blood vessels expandand contract at the same rate as the sweatingpulses. This is called the alpha rhythm of thevascular bed. I was getting set to see whether the

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Chapter 2. The Bellevue Bloats

In 1949, I was back at NYU Medical School for afellowship in Cardiovascular Hemodynamics withLudwig Eichna. This was in the early days of theNational Institutes of Health (NIH) which had a totalbudget of only a few millions. Now the budget is athousand times larger. I got an NIH fellowship to workwith Eichna which was no mean achievement. I ranyelling up and down the Bellevue corridors when theannouncement came.

Eichna (Ike), of Estonian descent, looked likeCharles Lindbergh and had the same monomaniacalbent. He was a product of the Johns Hopkins MedicalSchool in the 1930s. The Flexner report on medicaleducation, or the lack of it, gave rise to revulsionagainst the medievalness of medicine with its foot-thickpharmacopeia filled, to the druggists delight, withprescriptions like the witch’s brew in Macbeth. Thenew passion was for scientific medicine: to understand

the mechanisms and treatment of disease. The watchword was “what is the evidence” and the evidence had to be in the form of numbers of scientific measurements. No more the great clinician who walks into the ward and says “I smell typhoid fever” while his minions swoon with admiration.

Ike carried the torch of scientific medicine with a passion. He brought to NYU the Fort Knox experience where the mix of medicine and engineering was so successful in understanding how the body copes with heat stress. At NYU he was going to apply the same medical-engineering approach to heart disease, which was all a matter of blood flows and blood pressures. Ike was a confirmed bachelor who was entirely absorbed by his work. In earlier times he would have been the ‘Abbot of a monastery. His office was on the 5th

floor of the A&B wing of Bellevue Hospital. He refused to have a telephone on his desk. His secretary was way down the hall at the other end of the building in a conference room that served as a small library. If you wanted to phone Ike, you had to call the library and his secretary had to go and get him. He didn’t answer many calls. On his desk he had a sign that said “Go away but don’t go away mad”.

Ike had a few rooms for his laboratory off the corridor connecting the 2 medical wards at either end of the 5th floor. The two medical wards were jammed, each with 50-60 patients in the winter. The beds ran down the two walls and the center of each ward and out into the connecting corridor almost to the elevator in the center of the building. The word “busy” was invented to describe the activities of the nurses and house staff. In those days, the interns drew bloods, did the blood counts, the urinalyses, the stool examinations, set up the i.v. infusions and lugged the patients back and forth to the x-ray department. They, of course, did and wrote up (by hand, no dictating) the histories and physicals, wrote up the nurse’s orders, and presented the cases to the attendings: “No looking at the chart, doctor, if you please”. Often at Bellevue, other patients had to be used as interpreters for new admissions, but regional dialect differences amongst Chinese was a vexing

alpha rhythm of the blood vessels synchronized withthe sweat pulses when my 2 year Army service wasfinished.

We went back to New York, first-born Danny in tow, where I had a fellowship at NYU. So I never did the final experiments at Fort Knox and I never did any more research on sweating. I wrote up the experiments with Ed Palmes for publication in the American Journal of Physiology in 1950. Years later, I saw with pleasure that Roth’s dermatology textbook, on the Pathophysiology of the Skin devoted 2 pages to the experiments. But, I picked up a book, not too long ago, on the physiology of sweating that came out in the 1990s that had no reference to my work even though they went into intermittent sweating. I was forgotten! My first and finest research gone to oblivion. But I knew, sadly, that in order to cut a current figure in a field, one has to keep publishing. Nobody bothers with ancient papers. The idea that one’s papers are there forever, because the bound journal volumes are on the library shelf doesn’t jib with reality. Sic Transit Gloria.

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problem particularly in the wee hours of the morning.

Bellevue was a trove of good diseases. Joseph Bunimtook me in tow to line up cases of Boeck’s Sarcoidfor a clinical conference. In short order we hadenough cases to illustrate every important aspect ofthe disease. He was the one who taught me to takea history in medical school: from the patient’scomplaints, you list all the possible diagnoses.Clinical questions rule each possibility in or out untilyou have the diagnosis. The physical exam and labtests should only be confirmatory. Bunim went onto be the first Director of the NIH’s newly formedNational Institute of Arthritis and RheumaticDiseases.

In those days, the full time faculty was there to doresearch. The Chairman of Medicine, WilliamTillett with Sol Sherry developed streptokinase andstreptodornase to dissolve the pus in lung abscesses(empyema) in order to facilitate draining. Now,similar agents are used to dissolve blood clots instroke and heart attacks. Tillett didn’t know muchmedicine, but he was adept at identifying patientswho were Russian because Russians, at least atBellevue in those days, always had perfect teeth.For the fun of it, I sometimes responded with “alittle better” when asked how I am feeling becausethat was Tillett’s response to similar enquires fromthe house staff at Monday morning rounds whonoted the tremorous after-effects of a bibulousweekend. I don’t know what became of Tillett butSol Sherry went on to the May Institute inCincinnati as research director, where he was regardedas a genius.

Most of the clinical teaching was done on avoluntary basis by practicing physicians in NewYork, many of whom were fine clinicians. These days,most clinical teaching in medical schools is done by full-time faculty who do not do research but spend theirnon-teaching time seeing patients in a clinical officefacility provided on campus by the medical school.Part of their income goes to the medical school where itforms a significant part of its budget. The decline inclinical incomes with the advent of Managed Care hasput a serious fiscal crimp in medical schools particularly

since HMOs are not interested in supporting the costsof clinical teaching.

Ike’s lab was a 2 room affair. One room was forpatient studies. It had a bed equipped with afluoroscope and all the gear needed for measuringarterial, venous and intracardiac pressures andoxygen content and oxygen consumption. Theother room was for blood gas analyses and otherpurposes. This was in the early days of cardiaccatheterization; hence the need for the fluoroscopeto guide the catheter into the heart from one of thearm veins. Cardiac catheterization is now routine inhospitals for diagnosing heart conditions. At thattime it was Cournand and Richards downstairs atBellevue in the Columbia Division studying shockand us upstairs in the NYU Division of Bellevuestudying heart disease. They got the Nobel prizefor their efforts while we discovered high cardiacoutput failure in cases of the Bellevue Bloats.

AQ miracle drug works miracles. Such was the case with adrenocorticotrophic hormone (ACTH). This hormone causes the adrenal glands to secrete cortisone which suppresses allergic reactions. The first case at Bellevue was a man dying of asthma in spite of being in an oxygen tent. He got a shot of ACTH at night and was up shaving in the morning. A lot of asthma patients got ACTH shortly thereafter. It made them so rambunctiously cheerful that I thought ACTH should be called “happy-gen”. However, ACTH causes retention of salt and water and it made patients very edematous, i.e. the Bellevue Bloats. Some of them became very short of breath as if they had heart failure. We studied them and found that their blood volumes were markedly elevated and unlike the usual forms of heart failure, the cardiac output was high. This“congestion of the circulation”, which is what we called it, put them into a form of near failure where digitalis was not effective because there was nothing wrong with the heart. The problem was fluid retention and the treatment was to get rid of the fluid. I got to be the lead author of the journal publication and presenter of the paper at meetings. The reception in both modalities was good.

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In those days there were no Institutional ReviewBoards to decide whether a proposed clinical studywas safe and scientifically justifiable. Nor werethere consent forms. Ike’s position, and I agreedwith him, was that patients at Bellevue were beinggiven the best of medical care free of charge andtherefore it was reasonable to ask them tocontribute to the advancement of medical science.We didn’t hurt anybody even though some patientswere studied repeatedly over substantial periods oftime. Some enjoyed the attention. One of themwas an old time New Yorker with an accent. Heinsisted that the proper way to make coffee was toput the cream in “foist”, then add the coffee; notthe other way around. We discussed thethermodynamics of the 2 scenarios amongstourselves and didn’t see any difference, but wenever actually determined if there was a difference.

With the advent of health insurance, Ike’s argumentthat the patients getting free medical care owed acontribution to medical research, was no longertenable and a few flagrant abuses by sloppy clinicalinvestigator put the quietus to this era of laissez-faire clinical research.

Although we didn’t get a Nobel prize for theBellevue Bloats research, we did get localrecognition in a 1993 issue of the NYU Physician, aMedical Center publication. The issues wasdevoted to the history of heart research at NYU.There for all to see was a triptych of me, WilliamGoldring and Homer Smith as NYU researchpioneers in cardiology. Not bad for a 2 year fellowwho never did any more cardiac research thereafter.

Chapter 3. Atomic Energy onColumbus CircleThe NYU fellowship was over in 1951 when Iwas 27 years old. It seemed that we had been inNYC forever and I wanted to get away with myfamily, now including a red-headed Julie, andfinish my internal medicine training elsewhere.So I eschewed a residency at NYU and went tothe NY State University Hospital in Syracuse,NY. Syracuse is a place where it begins to snowwhen the leaves turn and stops when theyreappear. The sky is sometimes blue but onlyalong the horizon. Not surprisingly, theuniversity students excelled at ice sculpture.

The hospital patients were middle-class which was a culture shock to someone brought up at Bellevue. A curious phenomenon was the mass exodus of patients from the hospital at Christmas time, even the seriously ill. I enjoyed doing medicine but practice meant taking care of patients which, although lucrative, was not going to satisfy my intellectual leanings. A faculty position in academic medicine in those days did not pay enough to support a family and we already had 2 children, with a third one on the way. I didn’t think it was possible to combine medical practice and research.

Norton Nelson at NYU told me that they werelooking for someone like me at the AtomicEnergy Commission (AEC) in New York. Therewas a log of excitement in atomic energy at thetime and plenty of opportunity for research, soback to NYC we went for the princely salary of10 grand a year.

The AEC was an independent governmentalagency that was responsible for the developmentof weapons, nuclear power, space applicationsand biomedical research. The AEC oversaw theatomic energy industry, which was the largestindustrial complexes in the country. In additionto industrial facilities, it had a string of nationallaboratories, university laboratories and a majorresearch grants program of individual scientists.

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The operations offices in various parts of thecountry were the AEC’s administrative arm. Theone in NYC had responsibility for uraniumproduction. The Health and Safety Laboratory(HASL) of New York Operations office had theresponsibility for worker health in uraniumproduction. It had 2 floors in the U.S.Immigration building just off Columbus Circle.HASL had nothing to do with Immigration, but Irode down the elevator with Boris Karloff,listening to his deep melodious voice. My firstencounter with Karloff was many years earlier asa child seeing his movie. “The Mummy”. Whenthey began to unwrap Karloff (the mummy), Iwas out of the movie house like a shot. My 2little daughters, Julie and Lucy did the same thingwhen the snarling face of the Wicked Witch ofthe West filled the screen. HASL was a largeRadiation Health/Industrial Hygiene group.When a field is new, nobody is trained in it.HASL had chemists, physicists, engineers,instrument developers all focused on measuringradioactivity in places and people. The enterprisewas run by Merril Eisenbud, an electricalengineer who got involved with industrial healthproblems when he worked for the Liberty MutualInsurance Company. When radioactive falloutfrom atomic weapons began to be noticed,Eisenbud seized the opportunity of expandingHASL’s activities from the work place to thegeneral environment and thereby became apioneer in environmental health. His book onEnvironmental Radioactivity is a classic, but thiscame later when he was at NYU.

Atomic weapons fallout first came to light whenEastman Kodak found that its film was beingruined by radioactive dust. Radioactive cloudsfrom atomic detonations in the Nevada Test sitewere entrained in air currents that went toRochester, NY. Intense efforts were made totrack the radioactivity through the food chain andinto people. Radioactive iodine and strontium inmilk were chief culprits that put children at riskfor cancer of the thyroid and bone. This was themain reason for the eventual ban on atmosphericweapons testing. HASL was busy analyzing

radioactivity on a global scale even in Laplandwhere radioactive cesium got into lichens andthence into reindeer and caribou which weresources of meat.

I was the first full time M.D. at HASL so we did some epidemiology. My first study was the Lindsey Light and Chemical Company in West Chicago. They imported a thorium/rare earth ore from Brazil. The thorium went into making Welsbach mantles, the invention that made the gas light era of the 19th century possible. Mantles are still used in Coleman lanterns for camping and in ornamental street lights. The rare earths, with names like yttrium, cerium and lanthanum were separated and sold for various industrial uses such as making glass.

It was my first introduction to a quintessentiallydirty chemical plant with floors, walls andequipment crusted with chemicals. The workersshoveled piles of brilliantly colored rare earthchemicals producing clouds of dust. I thoughtthis was picturesque until we got some of theautopsy tissues from a worker that had died of acoronary. His liver was stuffed with particles ofcerium. I was told that workers at the MallinkrodtCompany in St. Louis were known as the “greenhornets” because they were covered from head tofoot with the green uranium salt, uranyl nitrate. Thechemical industry in those days had little concept ofhealth hazards and exposure standards and theywere loath to spend money on even rudimentaryindustrial hygiene. The motto of the old timechemical industry should have been, “if you arenot making a mess, you are not makingchemicals”. I have been told by union peoplethat this is still true in small companies in Ohioand presumably elsewhere.

Uranium and thorium metals are pyrophoric, i.e.they can burn in the air. It was interesting to see (atFernald) the uranium and thorium metal shavingsfrom lathe work in the machine shop catch fire andfall smoldering to the floor where they wereeventually swept up, but without urgency.

Fernald figured heavily in the monograph that I8

wrote on thorium, commissioned by theAmerican Industrial Hygiene Association(AIHA). There was a lot of interest in breederreactors in those days. The reactors would makemore nuclear fuel that they used. The conceptseemed to suggest getting something for nothing,which is appealing. Thorium was the breedermaterial of choice because it absorbed neutronsand thereby converted to a fissionable isotope.The monograph was my “tour de force” becauseit covered the industrial hygiene, health physicsand biomedical aspects of thorium. I wasdisappointed that the AIHA insisted that it becalled the Industrial Hygiene of thorium becauseit was more than that. But it didn’t matter,because enthusiasm for breeder reactors wasshort-lived because of technical difficulties andtherefore, so was the interest in thorium. Themonograph has been the definitive book onthorium for the last 3.5 decades because nobodyhas written another. Assyriology would havebeen a more dynamic field to write about.

It was clear from the findings at the LindseyLight and Chemical Company that the employeeswere heavily exposed to chemicals and radiationand that a long term follow-up program wasneeded to determine the effects of such exposure.The Argonne National Laboratory took over thiswork but I believe it fell into desuitude and nothingcame of it. The AEC had no control over the plantinsofar as cleaning it up was concerned.

Although Lindsey illustrates the consequences ofthe old time industrial ignorance, there has been arelatively modern example in the USSR and itssatellites, of full knowledge of health hazards,very stringent exposure standards and completedisregard of both. I visited, in the 1990s, for theWorld Bank, a Trebca lead mining, smelting, andbattery manufacturing operations in theAutonomous Republic of Kosovo near Pristina inYugoslavia. This is the area that has beeninvolved with genocide by Serbs and Albanians.The lead mine is the largest in Europe and hasbeen in operation since Roman times. Thecurrent plant had been built by the British in the1930s. It had a bag house to collect the lead dust

and a plant to convert the sulfur dioxide tosulfuric acid for commercial sale. The dustcollector no longer worked permitting some 12tons of lead to escape into the atmosphere everyday and coat the surrounding towns with leaddust. The pipes in the sulfuric acid plant weretoo full of holes to permit operation so that tonsof sulfur dioxide escaped each day.

The conditions in the smelting plant were evenworse than the Lindsey company with thick leaddust everywhere in the ancient Dickensian brickbuildings. Workers were scraping the fumingarsenic slag off the tops of vats full of moltenlead. Of the 2000 smelter workers, 400 camedown with acute lead poisoning each year. Theywere given 3 months of chelation treatment toremove lead from the body and then sent back towork. None of the workers in the battery plant hadteeth since they were dissolved by the sulfuric acidmist. They were issued plastic teeth every 3 monthswhich is how long the false teeth lasted.

The operation was run by a workers commune.The managers said that they knew all about thehealth hazards, industrial hygiene controls andexposure standards, but they had no money andwould starve if they shut the plant down. Theywanted 500 million dollars from the World Bankand they got it. I have been told that thisdeliberate disregard of health in favor ofeconomics produced an environmental blight inEast Europe.

I did get a chance to visit Oak Ridge and see the biggaseous diffusion plant that used the UF6 thatFernald made to separate U-235 from U-238. Butis was even more interesting to watch themanufacture of hydrogen bombs but disquieting tosee the long line of bombs down each side of thewarehouse. I went up to one of them and gave ita kick.

When I was at HASL in the early 1950s, radonand the threat of lung cancer was a seriousproblem in our domestic uranium mines on theColorado Plateau where the radon levels werevery high. The naturally occurring parent isotope

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of uranium, U-238, undergoes a series ofradioactive decays ultimately to stable lead. Oneof the radioactive elements in the decay isradium-226 and it decays to radon which is a gasthat diffuses into the atmosphere.

Ever since the Middle Ages, in the silver mines ofmiddle Europe, many miners died early from alung disease called Bergkrankenheit, whichultimately proved to be lung cancer. Theevidence that radon caused lung cancer in thoseold silver mines and in many other types of minesis conclusive. The unanswered question was andstill is, what is a safe level of radon exposure.

The AEC had connections with the South Africanmining industry, whose gold mines also yieldeduranium ore. We thought that it might be usefulto measure the radon levels in the South Africanmines and relate them to their lung cancerexperience. We also planned to stop off to lookat the uranium mine in the Belgian Congo whoseore, consisting of almost pure uranium, wasextracted by Madame Curie to isolate radium. Atthe beginning of World War II Belgium sent itsstockpile of high grade uranium ore to the USAto keep it out of the hands of the Germans. Itwas warehoused in New Jersey and then sent toFernald for storage in silos that leaked radon ingreat quantities.

Our team consisted of Duncan Holiday of thePublic Health Service who had done studies ofuranium mines on the Colorado Plateau, and BillHarris, HASL’s senior industrial hygienist, andme. Holiday and Harris were to measure radonand I was to examine the health records for lungcancer.

Our first stop was in Brussels to visit theheadquarters of the Union Meniere de HauteKatanga, the mining company that ran thevarious mining operations in the Belgian Congo.We were taken to lunch at the Taverne Royale. Itwas my first excursion into haute cuisine. We atehors d’oeuvres for an hour before the maincourse which in my case was roast mutton and

endives, followed by a dessert of crepes. Therewas sluicing of various fine wines. By the end oflunch I thought this was the finest 2 hours of mylife. Our host asserted that Belgian cooking wasthe best in Europe and to prove it, he said, one needonly to note that the incidence of arteriosclerosis inBelgium is the highest in Europe. I believed him.

We then took a sleeper plane to Johannesburgwith stops in Tunis for an awful lemon gaseous(soda pop, pronounced, gassoos) and thensomewhere in the jungle of central Africa forfuel. Johannesburg is situated on theWittwatersrand, a tilted saucer-shaped ore depositthat has layers of gold ore alternating with ones thatcontain uranium. The city is surrounded bymountains of slag. Uranium began to be recoveredfrom the slag when it became valuable. Mining onthe Wittwatersrand is the largest operation in theworld that, at the time, employed about a quartermillion people in 60-70 mines. Much of theworld’s gold came from South Africa. That wasthe reason for the Boer War.

Because of the tilted nature of the ore body,many of the mines were as deep as 2 miles.Tremendous amounts of ventilation were neededto remove the heat and to keep the levels of silicaat acceptable levels, since silicosis has been animportant occupational disease in the miners.

One trip down the deep mine was enough for me.We got into an open-topped metal coffin-shapedtrolley attached to a cable on a steeply inclinedshaft. A Zulu crouched at the bottom of thetrolley so we could rest our feet on him. A bellrang and down we plummeted in the pitch dark,zipping past occasional landing lights until wefinally ground to a halt at the gallery that wewere to visit. We watched a gang of Zulus liftinga platform loaded with batteries. They had awonderfully complicated chant that synchronizedtheir hoisting efforts. There were miners on theirbacks in crevasses in the galley walls hackingaway at the ore with 2 miles of rock over theirchests. I was glad to get back to the surface.

Most of the miners were Zulus who signed up for10

contract periods of 6 months alternating with time athome to spend money on cattle and wives. Therewere a large number of white supervisors who werefull time and much easier to follow health-wise,particularly since most had autopsies when theydied, because the heirs were interested to see if theycould get compensation if there were evidence ofsilicosis.

Harris and Holiday found levels of radon thatwere not too high, and I found no evidence of anincidence of lung cancer. Our South Africanhost, a radiologist by the name of Dr. O., had agorgeous wife and a beautiful house with lionskin-covered sofa cushions. He insisted that wekeep our data secret because it might cause laborunrest and possible disruption of the uraniumsupply to the USA from South Africa because ofmeasurable levels of radon in the mines. Wewere totally bamboozled. Shortly thereafter, therascal presented our results, as though they werehis, at an international conference on the peacefuluses of atomic energy. I was glad to hear that hisstomach ulcer bled every morning.

The blacks in Johannesburg were a ragged groupthat flattened themselves against building walls togive us sidewalk room. Early every morning atthe hotel I was awakened by a giant Zulu whoslammed open the door, slammed a tray of tea onmy bedside table and slammed out of the room.It was a startling way to wake up but starting offthe day with tea in bed was a luxury.

The whites in Johannesburg included theAfricaaners and the English, the former tryingtheir best to politically disenfranchise the latterand the latter trying their best to shut out theformer from industrial and financial control of thecountry. The real tension at the time wasbetween the Africaaners and the British. Theblacks seemed too cowed to be a threat.

The country club that we were taken to was elegant, as was the service by Indian waiters. No colored or black guests were to be seen. The whites lived just as well as one might expect when lots of servants are available at

negligible cost. A minor government official couldeasily afford 3 full time servants. Racial strictures,like Apartheid and the Nuremberg laws, have solidroots in avarice.

We visited Kruger National Park and sawassorted cats, elephants and giraffes. We walkedthrough the bush to a river to see rhinos. Ourguide carried a rifle for protection but it had atuft of grass sticking out of its breech.

So off we went to Elizabethville, now Kinshasa,in the Belgian Congo. We were put up in theguest house of the Union Meniere de HauteKatanga. It was a baronical establishment thathad a hammer-beamed dining room ceiling with atable that could seat 30. There we were, the 3American peasants, at dinner with liveriedservants lining the walls.

Holiday and Harris went to see the uranium minewhich was nothing much since the ore was gone.There were no medical records to look at so Ichatted with the Medical Director. He said thatthey (the Belgians) fully expected to be thrownout of the country but he was sure that theywould retain control of the mining industry. Hewas wrong.

With nothing to do, I wandered around town.The natives were a big contrast with the down-trodden blacks of South Africa. Here they werewell nourished and full of life. The women worebeautiful fabrics with African designs. Iwandered into the museum. They had acollection of moth eaten lions and other stuffedanimals. There were bronze statues of Congonatives being looked at by Congo natives in theflesh.

There was a small wood carving on top of adisplay cabinet. It was a horse with a face like aduck-billed platypus. The eyes were orangebeads and the expression was beatific. It had acrest for a mane and its flanks were carved tolook like wings. It was weirdly reminiscent of anarchaic Greek statue. I knocked at the director’s

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door and obviously woke him up because he cameout stuffing his shirt into his pants. I told him Iwanted to buy the carving and he said it wasworthless. He got it from some native out in thejungle to the north. He gave it to me for 2 dollarsand it has been smiling at me from my desk eversince. African wood carving is the most imaginativein the world.

I parted with Holiday and Harris and flew toCairo while they went home. I saw the Pyramids,the Sphinx, the City of the Dead, rode a cameland was suitably stupefied by the treasures in theNational Museum, all in 24 hours without sleep.I was careful to drink only bottled water. But itcame from Bulgaria, so, I got sick and went toRome in dire straits. I ordered fettucini at thegreat Alfredo’s and to the shock of the waiters,couldn’t eat it. Like MacArthur, I said, I shallreturn. And so home, where being young, Irecovered quickly.

I did some laboratory research at HASL as wellas epidemiology. Since the main route ofexposure to airborne radioactivity is byinhalation, the question was, where in therespiratory tract does the inhaled dust go andwhat happens after it deposits? From the windpipe on down, the lung is like an upside-downhollow tree. The trunk (trachea) and thebranches (bronchi) are the air passages. Theleaves are tiny hollow sacs (alveoli) jacketed withblood capillaries permitting the exchange ofoxygen and carbon dioxide between the bloodand the inhaled air. The dust, entrained in theinhaled air, passes down the bronchi into thealveoli. It was known in general terms that,because of the physical factors, the largerparticles plate out in the large bronchi and onlythe fine particles reach the alveoli. The innerwalls of the bronchi produce a mucus film thatrides on top of microscopic cellular hairs (cilia)that beat like small oars and move the mucus upthe air passages to the trachea and over thelarynx where the mucus is swallowed. Dustparticles deposited on the bronchi are entrainedin the mucus and swept out of the lung. Dust

deposited in the alveoli, where there are no cilia,remains in the lung longer.

The question was, how is particle size related tobronchial and alveolar depositions and how longdo particles remain in the bronchi and alveoli?There was no information because no methodswere available to make the necessarymeasurements.

Just at the time I was at HASL, a new radiationmeasuring device was invented that made suchmeasurement possible. It was called ascintillation detector and consisted of a block ofsodium iodide (NaI) placed against a lightmeasuring device called a photomultiplier tube.Gamma rays are released by radioisotopes.These rays are similar to x-rays. When gammarays enter the transparent NaI crystal, theyproduce flashes of light. The bigger the flash, thehigher the energy of the gamma ray. Theseflashes are convered by the photomultiplier tubeinto electrical pulses which are sorted for sizeand counted. Isotopes have unique gamma rayenergies so the scintillation detector will measurethe isotope of interest to the exclusion ofotherwise interfering background radiation.Thus, the gamma rays emitted by radioactive dustin the chest will pass through the chest wallwhere they can be measured by a scintillationdetector.

Harry Levine, HASL’s instrument maker had justbuilt one of the early NaI scintillation detectors,so all we needed was some radioactive dust. Wegot some very fine iron powder and sent it to theAEC’s Brookhaven laboratory where it was putinside a nuclear reactor and made radioactive.Then we took a Waring Blender, put theradioactive dust inside and turned on the motor.The propeller threw up a cloud of dust which weinhaled through a pipe in the lid. The subjectthen gargled to get rid of dust in the mouth andthe throat and sat down with the scintillationdetector pressed to the front of the chest. Thedetector was shielded with lead so that it was onlyradiation coming from the lungs or from the stomach

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when it was held against the upper abdomen.

After about a half hour, the radiation countszoomed up and then dropped away. This was theradioactive dust being gathered to the center ofthe chest by mucociliary transport, and then upthe trachea where it was swallowed and appearedin the stomach. After the clearance was done,there was little dust left in the chest indicatingthat most of it had been deposited on thebronchial tree.

We reduced the size of the inhaled particles byshutting off the blender motor and waiting untilthe large particles settled out before inhaling. Asimilar wave of mucociliary clearance occurredbut this time about half of the dust remained for along time in the alveoli of the lungs, from whichit was slowly removed. We noted that alveolarclearance was slower in the subjects who werecigarette smokers indicating some damage to thelung.

So we had made the first-ever demonstration ofmuco-ciliary clearance in man or beast andshowed that the method could measure therelative amounts of bronchial and alveolardeposition, and the rates of bronchial andalveolar clearance including an effect of cigarettesmoke. I presented our paper at a meeting atSaranac Lake expecting a lively reception for ourexciting new findings. It met with no comment.Sourly, I realized that if you have nothing to saynobody will listen; if you have something to say,they will listen, but they won’t believe it untilother people confirm the findings. Scientists,particularly young ones, are resistant to ideas thatare not their own and they make mercilessreviewers of other people’s research grantproposals.

Several years later, I resumed the inhalation workon a much more sophisticated level but this wasback at NYU and is described in Chapter 6.

Chapter 4. Atomic Energy onthe Potomac

After 2 years at HASL, I got a call to work at theAEC Headquarters in Washington, D.C. I wasintrigued by the possibilities of researchadministration on a national scale. So we packedour stuff at Parkway Village, where we had apleasant apartment in the United NationsHousing Development in Queens, and went toWashington.

The AEC Headquarters was on Constitution Ave.in World War I “temporary” buildings. It was thetime of the Cold War and the hearings to oustRobert Oppenheimer, the Chairman of the AEC’sGeneral Advisory Committee. This happenedbecause he opposed the development of the H-bomb; it was done on the flimsy grounds that hewas a security risk. Oppenheimer was crushedby the loss of governmental prestige and power,something sought by many an academic. I hadnothing to worry about, having neither. Not longafter, the Russians detonated their own H-bomb.

The Division of Biology and Medicine, where Iwas Assistant Chief of something or other, wasresponsible for research in the NationalLaboratories like Brookhaven, Oak Ridge, LosAlamos, and various universities. I did a lot oftraveling to these laboratories in venerable DC3s,Lockheed Electras and TWA’s 3-tailedConstellations, whose engines (disconcertingly)glowed bright red at night. I was an ardentadvocate of bigger research budgets and so wastreated royally by appreciative scientists: Farberof Harvard’s Dana-Farber Institute expounded onhis collection of medieval weapons lining thewalls of his elegant private dining room. IsaacAsimov, also at lunch, told me he couldn’t affordto do biochemistry anymore, because he madetoo much money writing science fiction. Therewere all sorts of dinners, including a clam bake atMIT and a steak and corn-eating contest at the Uof Rochester which I almost won.

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There were also a number of trips to the NevadaAtomic Testing Ground to watch the A-bombsgo off. The spectacularly colored mushroomclouds would make the best of fireworks, but theshock waves, even miles away were teeth-jarring,and there was the radioactive fallout.

There was a trip to the Pacific Test site at Bikiniin the South Pacific. None of the Federalagencies involved in weapons testing talked toeach other so the AEC had to send out its ownpeople as observers, and my turn came up. Weflew across the Pacific in a MATS plane (MilitaryAir Transport Service). We were handed a lunchbox containing shriveled chicken and a life vestwith a packet of shark repellant and a waterproofsignal lamp whose filament barely glowed when Iturned it on. We made our way to Eniwetokwhere I was housed in a barrack. The island wascontracted out to a big construction outfit thatused food as a morale builder to make up for thelack of amenities. We were awakened eachmorning at 5:30 AM to go to the beach where wewatched really big A-bombs being shot off whilewe had excellent pastry and coffee. Withnothing to do, I wandered the beaches looking atremnants of old Japanese and US militaryequipment partially buried in the sand, collectingcoral, and reading Huckleberry Finn.

After a few days, we flew to Bikini and got on aNavy ship that was the control center for detonatingan H-bomb. It was my first experience with a NavalOfficer’s mess with table linens, silverware andwhite-jacketed waiter-seamen. I liked it.

The following morning was set for the shot. Upon deck, just before dawn, in the pitch darkness,we were very nervous because this was one ofthe first H-bombs. At 30 miles distance, we werethe closest to the bomb. At the end of the countdown, there was a huge fire ball on the horizonthat grew steadily as it rose into the atmosphere.Unlike the fireballs of the A-bombs in Nevadathat last only a few seconds, this one didn’t seemto die out as it rose. We felt the heat but heardno sound which bounced over us. At Eniwetok,

300 miles away, they heard it and the sky was litup like noon. When the sunrise began shortlyafter the detonation, we could see that half thesky was covered by a jet black cloud. At 12megatons, the bomb had lofted an entire island.And the Russians have shot off a 50 megatonbomb! We were a subdued group of observers,having just been given a preview of doomsday.

Back at Eniwetok, with another few days to goon my tour of duty, I went for the usual post-prandial bit of beach combing and heard a racketcoming from a nearby hut. Inside there wereradiation detectors that had flashing lights andregisters that were clacking away. I realized thatwe were experiencing a radiation fallout and lostno time in collecting my gear and getting to theairstrip where a plane was just about to leave forthe States. So much for the South Pacific.

Besides biomedical research, the AEC had someexciting projects. One of these was a nuclearairplane. It was supposed to stay aloft for yearswithout refueling. Passengers would reach it byshuttle aircraft. It had to be huge. I saw theengine which was being built at the GE plant inCincinnati. It was as big as a colonial-stylehouse. No way, I thought, could that thing fly,and sure enough the project was cancelled.

Years later, at a dinner party, I told the story to astranger. He was indignant, saying that, as anengineer, he worked on the plane at GE, and itcertainly would have flown except for thosedamn politicians.

Another AEC project was a nuclear rocket beingtested in New Mexico. The engine was a bundleof fuel rods about the size of a large garbage pail.Hydrogen gas was pumped down channels in thehot fuel rods to give the engine thrust. However,bits of highly radioactive uranium got into theexhaust gases and into the atmosphere. Wecalculated that one tiny particle on the neck of achild could destroy its thyroid gland. Theproject was shelved, but such rockets might stillbe used in deep space.

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One AEC project that did work was the nuclearbattery that powered many space probes forflights to other planets. The core of the batterywas a chunk of Plutonium-238, an isotope soradioactive that it generated intense heat that wasconverted into electricity by thermocouples. Wecalculated that if the plutonium was released in arocket explosion on takeoff, the residence ofDaytona Beach would have to be quiteconcerned about getting lung cancer. However,the battery case was thought to be proof againstany mishap so away they went without anymischance so far.

Life in Washington was easy. We bought a housein Hollin Hills, a post WWII development ofglass-walled, shed roofed, modern houses onlandscaped, fenceless grounds, just south ofAlexandria, VA. It was populated by youngprofessionals and their college-educated wiveswho, in those days, didn’t work. There wasmuch partying, chit-chatting at the communityswimming pool and gossiping about occasionalinfidelities. The children roamed free, in packs,stopping off for peanut butter sandwiches atwhichever houses they happened to be atlunchtime. Somebody said it was the largestsorority in the country. It was a fine place tolive with small children.

When the AEC moved to Gaithersburg, MD., whichwas an impossible commute from Hollin Hills, wedidn’t go. I took a faculty position at GeorgeWashington University Medical School inWashington, to run their RadioisotopeLaboratory, do some cancer chemotherapy anddo a study, supported by the AEC, on tumorinduction in the rat skin by radiation. So for afew more years, things proceeded as pleasantly asit was professionally vacuous. Then a call camefrom Norton Nelson to come back to New Yorkand join his Department at NYU. I was delightedto be done with the vacation in Hollin Hills, and Idragged my whimpering family back to life in thereal world. This was in 1959 when I was already35 years of age.

Chapter 5. Inhalation Studies

We came back to New York and bought a bigTudor house in the northern reaches of NewRochelle. This was in the postal zone ofScarsdale. When we wanted to act classy, wesaid that we lived in Scarsdale. Otherwise, wetold the truth. I rode the N.Y. Central with thestockbrokers from the Scarsdale Station toGrand Central and hoofed over to 32nd and FirstAve where the NYU Medical Center was.

The Department of Industrial Medicine didn’thave much space and was scattered in variousbuildings. Eisenbud and I both arrived at thesame time because Nelson got some Rockefellermoney to support us until we could get our own.

Eisenbud had arranged for a whole body counter(WBC) to be installed at NYU at the AEC’sexpense. It was a chamber that could hold oneperson sitting or lying down. The walls, roof anddoor were made of 6 inch thick steel plates thatwere cut from an old battleship. The purpose ofthe WBC was to shield out cosmic radiation andprovide a very low radiation background so thatsmall amounts of radioactivity in people could bemeasured. The WBC weighted 20 tons. It wastoo heavy for normal floors so it had to be placedin the basement sitting on top of one of the pilecaps sunk in the bed of the East river. LikeVenice, the NYU Medical School was built onpilings, but in this case, in the Kips Bay landfillon the East river. Old naval steel was ideal forthe WBC because modern steel is contaminatedwith small amounts of radioactive cobalt since itis used in the steel-milling process. So withclean steel and no granite under the WBC with itsburden of uranium and thorium decay isotopes,we had about the lowest radiation backgroundavailable anywhere.

The initial justification of the WBC was to do a“last roundup” of the old radium dial painters.These were the young women who, during WWI,painted aircraft instruments with luminous radioactivepaint so that they could be read in the dark. They

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ingested a lot of radium because they tipped thebrushes on their tongues so they could paint finelines on the dials. Radium is chemically similar tocalcium, so the radium lodged in bone where itcaused cancer. Newspapers gave the dial painters agreat deal of publicity calling them the “Legion of theLiving Dead” The first case of bone canceroccurred in the jaw and came to the attention of adentist in northern New Jersey near one of the dialpainting companies. Harrison Martland, the MedicalExaminer for Newark, New Jersey did the classicstudy linking the cases of bone cancer in theseworkers with the radioactive paint used by theJersey dial painting companies. Martland, asuspender-snapping, cigar-chomper gave us ahair-raising lecture with graphic slides in MedicalSchool on modes of suicide and murder.

The radium dial painters provided the only sourceof information in people on the relationshipbetween the amount of radium in the skeletonand the risk of bone cancer. From this data thecancer risks from plutonium and strontium couldbe inferred. It was important to get as muchinformation as possible from these cases and theonly accurate way to measure the radium in theskeleton was to do it in a WBC. So we set upour WBC with an 8 inch NaI scintillationdetector and did the study in conjunction withMIT and the Argonne National Laboratorybecause similar cases occurred near plants inMassachusetts and Illinois. We found measurablelevels of radium in all of them, which was grist forthe quantitative mill.

After this project was over, the WBC was thenfree for other uses. We decided to continue theHASL lung clearance study on inhaledradioactive particles using the WBC so that wecould make do with tiny amounts of radioactivity.By then, Universities were getting leery about thedangers of radiation and the free wheeling HASLstudy would not have been allowed.

This time we wanted to do the study withuniform sized particles so we could accuratelyrelate particle size to where in the lung they were

deposited, i.e., whether on the bronchial tree wherethey would be cleared from the lung rapidly or in thealveoli where they would stay for a relatively longtime.

These particles had to be insoluble and also hadto be tagged with radioactivity that would stickwith the particles. We worked unsuccessfullywith a variety of approaches and were gettingsomewhat frantic when in popped a visitor fromEngland, who was well known in the aerosolfield. After listening to our woes for a fewminutes, he said, “Try a spinning top. Whitby hasone”, and out he popped. We call it a spinningdisk. The English call it a spinning top. It wasthe shortest and most productive visit I everexperienced.

After finding out who and where Whitby was(University of Minnesota) I was there the nextday, breasting the herds of students changingclasses, while making my way to the engineeringschool. Whitby showed me the device and gaveme a set of blueprints. We duplicated it in 10days flat.

The basic part of the instrument was a sort ofhigh speed dental drill motor, mounted in avertical position, rotating a horizontal one inchdiameter disk at about 100 thousand revolutionsper minute. Liquid, run through a hypo needleonto the center of the disk, flowed to the rim andcame off as uniform sized drops so that whenthey dried, whatever was dissolved in the dropswould be solid particles of a single size.

The question then was, what insoluble materialthat was perfectly safe to inhale, could we use tomake the particles? Just about then, HenryPetrow, an industrial chemist came to thedepartment as a graduate student. He hadrecently developed a commercially successfulmethod of making a stable iron oxide colloid byextracting a solution of ferric chloride with a highmolecular weight amine. So with his method, wecould now make an aerosol out of uniform sizediron oxide (rust) particles, which is safe to inhale in

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small amounts. Furthermore, the aerosol wasproduced in a ready-to-breathe condition andavoided the headaches of trying to collect particlesand resuspend them into air in an unagglomeratedform. By adjusting the concentration of the colloidin the feed liquid and the speed of the spinning diskwe could make an aerosol of any specified diameterfrom about 0.7 microns to 7 microns with only abouta 10% variation in the size. This size range wasperfect for our needs. It was easy to salt theparticles with any of a variety of radioisotope tracerswith the desired characteristics. We chose to useradioactive technetium and gold for our tags. Sowith generous dollops of good luck we hadachieved a breakthrough in aerosol technology.

Just about then, Mort Lippmann arrived fromHASL as a graduate student to do his PhDresearch. He was a first rate engineer andindustrial hygienist who readily adapted himselfto biomedical studies.

We were ready to go hammer and tong tocharacterize the regional deposition of particlesin the lung and patterns of bronchial clearance.However, the problem was to find volunteersubjects. The Medical School didn’t permit us tosolicit medical and graduate students as researchsubjects. We were stumped until I thought ofErnest Wynder. There was a man who knew hisway around town. He was one of the first to linkcigarette smoking and lung cancer. He foundedthe American Health Foundation with its strongresearch program in epidemiology and laboratorywork and he squired some of the most beautifulwomen in New York. I once asked him to give alecture to the freshman medical students. Hestunned them by showing up with a magnificentblond (a Finnish doctor) on his arm, swathed infurs from eyeballs to toes. So I put the questionto Wynder and he said to advertise in the VillageVoice because all the unemployed actors read itfor jobs. We did so and could follow the deliveryroute of the paper through Manhattan by thestream of telephone inquires that came in. Wedidn’t lack for subjects after that.

Each study was a pretty substantial affair, lasting allday and into the night and finishing the next day. Butwe did a large number of them. Mort’s thesis wasthe cornerstone of what we know today about theregional deposition of particles in the human lung.

The Science section of the NY Times (10/02/01)had an article on factors that could affect successof a terrorist attack on the USA using a spray ofanthrax bacilli. One of those factors described inthe article was the particle size of the spraybecause the bacilli have to reach the alveoli tocause disease. They made the point that theinhaled particles would have to be 1-3 microns indiameter because larger ones would either notget into the lung or be deposited on the bronchiand swept out of the lung. That was our 40 yearold data that we got with the spinning diskgenerator and the WBC!

The total time required for the completion of theclearance of particles from the bronchial tree wasrelatively constant in repeated studies on thesame individual but varied widely amongstdifferent individuals. The times ranged from 2hours to 24 hours. I had the impression thatphlegmatic people were slow clearers and highstrung types were fast clearers but we neverproved that. The speed of clearance isundoubtedly due to the rate of mucus productionon the lining of the bronchi and the beat rate ofthe cilia which transports the mucus.

One observation suggested that the bronchialmuscles may play a role in emergencies. Wewere looking at the acute effects of cigarettes onclearance. Jack Berger, one of the graduatestudents, a non-smoker, did the study on himself.He normally completed bronchial clearance inabout 6 hours. After about an hour into clearance, hesmoked a cigarette for the first time in his life andthrew up. We were amazed to see with thesubsequent measurements starting a few minuteslater that his bronchial tree was completelycleared of particles. We didn’t do a systematicstudy on the effect of vomiting on clearance but theobservation couldn’t have been a fluke. The

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bronchial tree has circular, spiral and longitudinalmuscles. When they go into spasm, the individualsuffers an asthma attack. But the normal functionof the muscles is not known. Maybe, theysqueegee particles up the bronchial tree duringvomiting like an internal Heimlich maneuver.

Mike Foster, another graduate student looked atthe effect of isoproterenol, a drug used to treatchronic bronchitics to clear the mucus out of theirlungs. There was also a dramatic acceleration ofclearance. Maybe it was the same mechanism.

We studied chronic bronchitics and found thatthey clear their air passages mainly by coughing.Bill Briscoe, a distinguished pulmonaryphysicial-physiologist worked with us for a while.He was a heavy smoker with a chronic cough.We studied his clearance and found that hismucus would slosh up and down his trachea andlarge bronchi until it finally made it up over thelarynx to be swallowed. We called that“refluxing” of mucus. It was evident that anoverproduction of mucus by irritants such ascigarette smoke eventually overwhelms thetransporting ability of the cilia so coughing is theonly way to get rid of the mucus.

We did find that clearance was very slow insmokers before the first cigarette of the day.Once the first cigarette was smoked, clearancegot going. This gets with the commonknowledge that smokers need that first cigarettein the morning to clear out their lungs. Wecalled this “mucosal addiction”.

As an inveterate snorer, I was curious to seewhat the effect of snoring might be on thedeposition of particles in the lung. The noise ofsnoring is due to turbulence of the air in the backof the throat. Turbulence should enhance particledeposition. I found that inhaling particles thatwould normally go deep into the lung, did not getinto the lung when they were inhaled whilesnoring. They were either deposited in the backof the throat or in the trachea where they wereswept out in a few minutes. So snoring could be a

protective mechanism. This suggests that, if caughtin a germ warfare attack without a mask, it might beworth snoring.

We were interested in following the changes thatoccur in bronchial clearance during chronicinhalation of irritating pollutants such as sulphurdioxide, nitrogen dioxide and cigarette smoke.This couldn’t be done in humans so we needed ananimal model. Late one night, I saw a SwissColony wine ad on TV with its signaturecharacter, the “Little Old Wine-Maker” pulling aminiature donkey. I thought that that was theanimal model for us. It is bred to stand still in theteeming market place for hours on end. It hasbig enough lungs for inhaling and measuringradioactive particles, and is stoical enough toinhale irritants.

Our chief technician on the radiation cancerstudies had a farmer-husband who was availableto set us up with miniature Sicilian and Sardiniandonkeys. They were named alphabetically andaccording to sex. The first female was namedAbby and there was Bob and Charlie, etc. Mywife, Abby, didn’t appreciate having a donkey asa namesake.

The department had by then acquired laboratoryfacilities in Sterling Forest near the town ofTuxedo about 50 miles north of NYC. SterlingForest was in the foothills of the Rampomountains. The Empire State building was justvisible 50 miles away. Sterling Forest is a largetract of woods and lakes abutting the gatedcommunity of Tuxedo, the home of Wall Streetmoguls and the origin of the garment of the samename. Averill Harriman, our ambassador to theUSSR during WWII had a father who was themagnate that founded the Union Pacific Railroad.Old man Harriman wanted to live in Tuxedo buthe was turned away because they considered himto be a roughneck from out west. So he boughta huge tract of wilderness land around Tuxedoand gave most of it to NY State as the HarrimanState Park. He set up his mansion in Harriman,New York, about 20 miles north of Tuxedo. It is

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now a conference center belonging to ColumbiaUniversity. He also sold 30 thousand acres to theCity Investment Corporation. This land, SterlingForest, was to be an industrial research andresidential park. Sterling Forest Gardens wasoriginally set up as an outlet for Dutch tulipgrowers to exhibit their wares. The Gardens hada summer theater and there was a mouse thatregularly occupied front stage left. We thoughthe might be a drama critic.

The City Investment Corp recouped theirinvestment in a few years by the sale of peat mossfrom the numerous bogs on the property. As anattraction to industrial research laboratories, theCity Investment Corp gave one thousand acres toNYU to develop an exurban campus. NortonNelson, our Departmental Chairman, who hadserved as provost of NYU’s Bronx campus,University Heights, was tapped to be head of theSterling Forest campus. Sterling Forest had beenthe main iron mining center of the country sincecolonial days, reaching its peak at the time of theCivil War. The great chain that stretched acrossthe Hudson River during the Revolutionary Warwas intended to stop (it didn’t) the British Fleet fromreaching Albany. The chain was forged at SterlingForest. Some of the links, weighing 400 poundseach, can be seen at the West Point MilitaryAcademy.

There was an attempt to revive the miningindustry in Sterling Forest during WWI. Mrs.Harriman built a school house in anticipation ofthis revival and remnants of mining cottages canstill be seen in the woods. The revival failedbecause of the discovery of the Mesabi ironmines near Lake Superior at Duluth, where theore was almost pure iron. Duluth was the placewhere moose chased newsboys up trees in thewinter.

The Union Carbide Company acquired the schoolhouse and made it into a staging laboratory whileit built its new facility in Sterling Forest equippedwith a nuclear reactor to produce radioisotopes formedical use. When this was completed, Union

Carbide gave NYU the school house, which wasnow renovated into a laboratory building and Nelsonacquired it for the Department. The name of theDepartment had been changed in the 1960s fromIndustrial Medicine to Environmental Medicinebecause of our broadened interests and because wegot a National Institute of Environmental HealthSciences (NIEHS) Center Grant award. TheNIEHS had just been formed and because it wassmall, it needed university Centers to give it morestature. Harvard and Cincinnati were other earlyCenters of Excellence. Since our Departmentwas very crowded at the Medical Center weeagerly expanded into the additional SterlingForest space and got NIH funds to build a largelaboratory wing onto the old school house.

So we had plenty of room for a donkey corral inthe woods adjacent to the laboratory. Thegymnasium of the old school house had beenconverted into an inhalation chamber facility bySid Laskin to study the effects of inhaledcarcinogens on cancer induction in rats.

Laskin had previously built the inhalation facilityat the University of Rochester where most of theinhalation studies on uranium had been doneduring the days of the development of the atombomb. At NYU Laskin worked with MarvKushner, one of the country’s leadingpathologists, who was a legend at the MedicalSchool for never having taken any notes as astudent. Laskin and Kushner demonstrated thecarcinogenicity of a number of chemicalsincluding chromium, formaldehyde,bischloromethyl ether and sulfur dioxide incombination with benzpyrene.

We used a corner of the inhalation chamber labfor the donkey studies. We had a spinning diskgenerator in a cabinet on wheels to deliver theradioactive aerosol and a saddle for the donkeysthat held the scintillation counters against thechest for the measurements of bronchialclearance. The donkeys were marvelously patient.They stood quitely for hours without restraint orsedatives. The only thing that aroused a flicker of

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interest was the sight of a package of cigarettesbecause they loved to eat tobacco.

However, donkeys are social animals and whenalone for the first few times in the inhalationlaboratory, the females, particularly, got anxious.When we finished studying Donkey Abby for thefirst time and removed the detector saddle, shepaced up and down at the laboratory door almostwringing her hooves until Mort Lippmann startedher back to the corral to which she raced brayingand dragging the struggling Mort.

Animals that feed on the ground, unlike humans,have specially adapted nostrils to avoid inhalingdust. The nostrils of these animals direct theinhaled air at high speed directly to the nasalseptum where the air then makes a right angleturn to go up the nose. The inertia of the inhaledparticles prevents them from following theturning air stream and they impact on the nasalseptum to be cleaned out later by snorting.Because of the nostrils, we had to expose theanimals to inhaled material through a plastic tubein the nose which was easy to insert andapparently comfortable for the animals.

We did exposures to cigarette smoke and variouspollutants for many months but without much inthe way of sustained damage to the clearanceprocess. We certainly did not see evidence ofthe kind of chronic bronchitis that occurs sofrequently in human cigarette smokers. Perhapsit takes years for this to happen or the donkeysare more resistant that people. In any case, at theend of the project, the donkeys were no worsefor wear and they resumed their careers of givingrides to children and country fairs.

Although we published over 40 paper on theinhalation studies, which was a source ofsatisfaction, I was somewhat disappointed withbronchial clearance as a biological process,although it is somewhat arrogant to criticize MotherNature. Internal body functions are normallycontrolled within a relatively narrow range as withblood sugar or even blood pressure. The fact that

bronchial clearance rates could vary by a factor often in normal people seemed to mean that theclearance rate was just not that important. Inaddition there is a pretty effective backupmechanism in coughing. But we never did find outwhy the clearance rates can be so different inpeople. So far, nobody else has either.

Mort Lippmann by now had become a facultymember in the Department, and took over theprogram while I moved on to other things. He isnow one of the authorities on particle depositionand air pollution effects and has served for manyyears on EPA advisory boards.

Chapter 6. RadiationCarcinogenesis

While in the AEC, it became apparent to me thata critical aspect of radiation protection is theestimation of cancer risks at low levels ofexposure because low exposures are usually whathappens in the work place and in the generalenvironment. A critical aspect of estimatingcancer risks is knowledge of the shape of thedose response curve at low doses. This curvetells us the lifetime probability of getting cancer(over and above the normal background risks)given the level of mechanisms that operate toproduce cancer. To this day, the problem ofdefining the shape of the curve is unsolved eitherfor radiation or chemical carcinogens. Toparaphrase General MacArthur, old problemsnever die, but unlike old soldiers, they never fadeaway either.

While at the AEC, I resolved to enter the fraywith my own research effort based on a previousstudy at the Argonne National Laboratory thatinvolved dosing the rat skin with shallow-penetrating beta radiation. The rats respondedbeautifully with a large assortment of various typesof skin tumors that could be produced with even asingle brief exposure. The advantage of betaradiation is that only the skin is exposed and there is

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no danger of killing the animals by damaging thehighly sensitive bone marrow. We argued that theskin is a simple organ and that you can see whenand where the tumors arise, follow their growth ratesand examine the pathology of each tumor. The AECbought these arguments and awarded a grant to dothe research first at George Washington University inWashington, D.C., after I left the AEC and later atNYU. Fifty publications and many decades later westill didn’t know what the shape of the dose-response curve was at really low doses, i.e.,whether any tumors were induced, but welearned more about radiation skin tumorinduction in the male Sprague-Dawley rat thananybody on the planet.

The first problem was how to expose the rats andto what. We settled on radioactive Yttrium asthe beta ray source incorporated into a saddle-shaped polyethylene sheet. The rats surprisinglysubmitted without protest to being taped onto awooden tongue depressor blade held in a rig thatpermitted the radiation source to be applied tothe back and held there for the time required todeliver the required radiation dose. We foundthat when the rats were handled as friskyadolescents, they became quite tame. The stay atGW, before moving back to NYU, accomplisheda dose-response experiment that showed notumor formation at low doses and a sharplyincreasing tumor yield with increasing doses to apeak and subsequent decline with higher dosesbecause of increasing amounts of skin damage:i.e. dead cells don’t form tumors. Themalignancy of the tumors increased with doseand those at barely tumorigenic doses were nomore than benign sebaceous cysts.

When we moved back to NY in 1959, the AECallowed us to move the grant to NYU from GW.About that time, Fred Burns arrived from thephysics department at Columbia to be a PhDstudent in Environmental Medicine. He greatlystrengthened the program in radiation physics,mathematical analyses and experimental design.Our first project was a study of tumor inductionin the rat skin by proton radiation. Columbia had

a proton accelerator and they agreed to do the studywith us.

The exposure apparatus was designed and built atColumbia by Leon Lederman who later became adistinguished director of the Fermi Laboratory atthe Argonne National Lab. We weren’t allowedto carry the rats into the physics building throughthe front door so we passed the cages through awindow from the street into the accelerator lab.We did a wide range of doses and to ourastonishment there was no tumor formation ;atall even at very high doses. It dawned on us thatbecause protons penetrate only a very shortdistance into the skin that the tumor forming cellsmust be deeper.

We had a Van de Graff electron generator at the Sterling Forest lab which was left by the Union Carbide Company. This device permitted us to radiate the skin down to any depth that we selected. We obtained dose response curves for tumor formation with shallow, intermediate and deep penetrations. The curves were different in terms of the surface dose. But there was one level in the skin where the dose-response curves were the same for all the penetration depths. That clarified matters by indicating that the tumor forming cells were at that depth. It corresponded to the location of the stem cells part way up the walls of the hair follicles. These stem cells provide the reservoir for replacing cells in the surface epithelium, the sebaceous glands and the hair bulb at the bottom of the follicles where the hairs grow. It has since been generally accepted that the stem cells in the various organs are the ones that form tumors.

A complication arose when we were able todeliver the radiation to the stem cells withoutirradiating the rest of the hair follicles and foundthat no tumors formed. The whole follicle had tobe irradiated in order to get tumors even thoughthey were formed in the limited region of the stemcells, because repair of the radiation damage to thefollicles suppressed tumor formation.

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We soon got involved in studying damage to thehair follicles. The hair follicles could be examined enmasse by digesting the skin with trypsin and lifting offthe epidermis with the attached hair follicles. Whenmounted on a glass slide, epidermis down, stained,and embedded in a gel and cover slipped, thefollicles, under a microscope, were seen to be linedup in rows like so many picket fences.

After radiation, the hair follicles were irreparablydamaged and reduced to atrophic stumps, wherethe proportion of atrophic to normal folliclesincreased with dose in the same fashion as tumorinduction. In fact, one could see small tumorsgrowing out of some of the atrophic follicles.The ratio of tumors to atrophic follicles wasconstant, regardless of dose, at about 1 tumorper 2000 atrophic follicles. The atrophic folliclesseemed to be necessary for tumor formation, andthe progressive wiping out of follicles above thedose that yielded a peak incidence of tumorsexplained why the tumor incidence declined.

One might think that the mouse is merely a smallrat but that is not true for skin tumor formation.Rather than forming partially killed follicles afterradiation as in the rat, the mouse either hadnormal follicles or the follicles were completely wipedout, depending on the dose. So the mouse didn’t formhair follicle tumors like the rat but only a fewtumors at high doses, where no follicles survived;such tumors had the pattern of the surfaceepidermis (squamous tumors). Why the mousedid not get atrophic follicles is still a mystery.

Nuclear power in the USA accounts for onlyabout 20% of energy production compared to80% in France. The commercial deployment ofnuclear power in this country has been impededby the public concern about the dangers ofradiation stirred up by anti-nuclear scientists,often on flimsy scientific grounds.

Our work on the relationship of damaged hairfollicles to skin tumor formation is a case inpoint. The “hot particle problem” relates to the

cancer risk of radioactive particles in the lung. Eachparticle lodged in the alveoli radiates a very smallvolume of lung tissue at a relatively high dose.Based on our atrophic follicle-skin tumor data, itwas claimed by Arthur Tamplin that the cancer riskwas 1 in 2000 for each particle. Since radioactiveparticles are microscopic in size it would be easy toinhale thousands of them. According to thisestimate, such an individual would be certain todevelop lung cancer. There was enough publicinterest about the matter to cause the NationalAcademy of Sciences to convene a panel toevaluate the claim, which I chaired. The paneldismissed the approach and ultimately experimentaldata showed that the cancer risk from individualradioactive particles was small.

In the 1970s, NYU was given a 30 acre estate onGreenword Lake, New Jersey, called Timberhill.It had 900 feet of lakefront, a lodge house, 2cottages and a boat dock. It was about a 15minutes ride over the mountain from the SterlingForest lab. We used the estate for a 10 weeksummer program for medical students to do aresearch project at the lab. Abby and I werehouse parents and we invited distinguishedscientists in cancer research to spend a week withtheir families living with the students and givinglectures. We also had Manny Farber, Director ofthe Fels Research Institute and his family inresidence for the 10 weeks. The Farber’sdaughter, Naomi, and our youngest, Lizzie, wereavailable as playmates for the visiting scientistschildren. There was Henry Pitot, Director of theUniversity of Wisconsin’s MacArdle CancerLaboratory with his nine children, all in same redshirts, lined up in size order. Mass hysteriaensued when one of them lost his toothbrush.There was Hilary Kaprowski, the Director of theWistar Institute demonstrating the pronunciationof a seven syllable Polish word that had novowels. It was a good imitation of a grand malseizure, or a prodigious sneeze. There was HenryKaplan with the giant finger, one of the world’s greatradiologists, who developed the cure for Hodgkin’sdisease, and who was a passionate jig-saw puzzler.

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We actually got an NIH Training grant to support theprogram. It put food on the table, provided a cookand house cleaning, paid for the visiting scientist’stravel, a little research money, and a modest stipendfor the students. It went on for 6 years until NYUgot into financial straits and sold Timberhill and theUniversity Heights campus. A great time was had bythe students and the visitors. The program wasprobably beneficial but we didn’t try to get objectivemeasures.

Dan Albert (my son) studied tumor induction inthe rat skin by a chemical carcinogen to seewhether, like radiation, there would be anassociation with atrophic follicles. There wasn’t,even though the same kinds of hair follicletumors were produced. There went a finegeneralization that was done in by a cruelobservation.

Flushed with our success in using a large and unusual experimental animal in Sterling Forest, namely, the miniature donkey for inhalation studies, we took another wild excursion, this time using the white-tailed deer. Every spring the 2 antler pads of the male deer sprout under hormonal stimulation. This undifferentiated tissue produces the bone, blood vessels and skin with hair that forms the antlers. It is the fastest growing tissue in the animal kingdom. Cell proliferation has always been considered to be essential for tumor induction, so we thought that if we irradiated the antler pad just as it began to sprout, we would get an antler covered with tumors like a Christmas tree. When the antler fell off in the Fall, the deer would be no worse for the experience. So we tried it out, getting 3 male deer from the Catskill game farm. We began by irradiating one antler pad of the one deer and watched the antler develop. No tumors formed. The effect of the irradiation was to stunt the antler by making it thinner and shorter with fewer branches. Later in the summer, as the rutting season approached, the deer began to tussle and the irradiated antler broke off. Not being able to defend himself, our subject was killed by the other 2

deer. It was an experiment with an unforseen andtragic ending that did not seem worth repeating. Sowe returned the survivors to the Catskill game farm.I was thinking of doing skin tumor studies in snakes,but we never got around to it.

Fred Burns by now had reached faculty rank and gradually took over the program with my role being mostly a sounding board for ideas. He continued to take the rats to the elaborate radiation machines in various national laboratories around the country and got important results on the differences in tumor induction amongst different types of radiation, some of it being related to the health hazards of space travel. The program started at GW in the 1960s is still going on but the original AEC grant lasted for 30 years, which amounts to 10 renewal proposals. That might be a record for an individual investigator grant.

Chapter 7. Epidemiology

Ringworm Radiation: Ralph Baumring showedup in the Department late in the 1960s. He hadto serve 2 years in the Public Health Service.They didn’t know what to do with him so theysent him to us. Nelson didn’t know what to dowith him so he turned him over to me. I thoughtthat since he was an M.D. and in the PublicHealth Service, he should do some epidemiology.

We were interested in radiation-induced skin cancer. X-rays used to be used to treat acne in adolescents. We thought there might be a good epidemiology study on that subject. We went to see Rudi Baer, head of Dermatology. We hardly started to talk when he held up his hand saying that he had the perfect study for us. He went to a closet and came back with a cardboard carton filled with small black appointment books. He said that they had been treating cases of ringworm of the scalp in children with x-rays since before WWII and he thought that somebody should see what happened to them healthwise in later years. In the hopes that such

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a study might be done, he gathered the appointmentbooks that listed the names of all the patients that hadbeen treated, about 2000 of them.

The treatments had been administered over theyears by a single technician, supervised by onedermatologist, Earl Brauer, using x-ray machinesthat were periodically calibrated by the PhysicsDepartment at NYU. The irradiation procedurehad been standardized by Adamson and Kinebocksince 1910. The purpose of the radiation was tomake the hair fall out temporarily so that thescalp could be cleaned of the fungus. This wasimpossible with the hair in place. Before thedepilation by radiation was introduced, the hairwas pulled out manually. No wonder that theradiation approach was received enthusiastically.

The children became bald for several months during which time they typically wore a knitted cap. Although this was embarrassing for the patients, the hair grew back normally in a few months, and all was well except for the possible late consequences of the radiation, the nature of which were not known.

We were of course stupefied by the unexpectedluck of being handed a perfect study population.The records of the irradiated patients were in thefiles of the NYU Skin and Cancer Hospital, runby the Dermatology Department. In the samefiles we also had access to an equal number ofcases of ringworm that were not treated byradiation who could serve as controls. Most ofthe cases occurred during WWII when there wasa world-wide pandemic, but radiation was useduntil 1958 when the drug Griseofulvin was introduced,which did not require removal of hair.

There was only one possibly fly in this gorgeousointment: could we locate these people after somany years, particularly when they were treated aschildren? We got a pilot project grant to give it a tryon 200 cases. We hired a Public Health nurse whowas very interested in radiation effects because shehad had a botched treatment for facial acne with x-ray and had several skin cancers removed with

subsequent scarring. She lead a small staff that didthe tracking under her guidance. For a while thingswent well until the staff became restive when theywere not being given any work to do. On inquiry, itturned out that their leader had dropped the usualmethods of locating people in favor of using ESP.We wondered whether radiation to the headscrambled the brains. We were later startled to findevidence for this.

With the ESP maven out of the loop, wesucceeded in locating 95% of the pilot cases andso we were soon in business with a full scalegrant to do three things: a questionnaire surveyof illness experience, relying on physician andhospital records for accurate diagnoses, a clinicalexamination of a subset of the populations and adosimetry study of the radiation dosage to thevarious organs in the head.

It was my first experience with large scale data handling. In those days it was done with key sort cards. Each patient had a card that had many holes along each of the 4 edges. The outer rim of the hole was punched out, for example, if the patient was irradiated. If one picked up a batch of cards and stuck a long needle through that hole and shake the cards, the irradiated cases would fall out on the table, on the floor or through the door depending on the wind direction. Each hole could be assigned a characteristic and the analyses done by needling, shaking, picking up the fallen cards and counting both them and those that didn’t fall.

One night, in the wee hours, under pressure tofinish an analysis, I finally separated 4000 cardsinto little piles that filled the entire office. But tomy anguish, I had lost track of what the pileswere for. Consigning key sort cards to hell, Iresolved to use the computer. It cost real money toget all that data entered into IBM key punch cards,and to get the computer worked up for dataanalysis.

We took the punch cards down to the main framecomputer at Washington Square and one half an

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hour later, we had a 700 page print out, each pagecontaining one table. Faced with the prospect ofevaluating 700 tables, I wished we were back withthe key sort cards, but there was no turning back.

In my career, I started with the lever-operated adding machine, as the only tool available for data analyses, except for log tables and the slide rule. Then came the Marchant electric calculator. If you set it to doing a long division problem, there was time for a beer before it finished. Then came the calculators that had programs on cards that told the machine how to analyze the data. Now there are hand held calculators and desk top computers that outclassed them all. Do we do better science because of it? Yes, indeed.

When the methodological dust had settled, we found that the irradiated cases had an increased incidence of skin tumors, brain tumors, leukemia, and thyroid tumors, and a higher incidence of hospitalized cases of mental illness in early life. At later ages the controls caught up, as if the radiation were an accelerating factor in mental illness. Maybe it had to do with being bald as a child. Maybe there was some selection factor that made for a higher likelihood of getting irradiated for ringworm.

Thy physical examinations showed that the scalp did not recover completely since there was spotty baldness quite unlike the normal male baldness pattern. It occurred as much in women as in men. The individual hairs were thinner in the irradiated cases. There was some damage to the lens of the eye but not enough to impair vision. The evaluation of mental status was not decisive. The psychologists opted for the Minnesota Multiphasic Personality Index (MMPI). The psychiatrists insisted on an interview. We did both. The interviewer tended to rate the females as neurotic, and the black males as personality disorders. This might have had something to do with the interviewer. The MMPI didn’t necessarily agree with the interviews. One MMPI evaluation rated a case as a very sound

personality, but the interviewer learned that he had 2suicide attempts.

Bob Schultz did his doctoral thesis on theradiation dosimetry of the Adamson-Keinbocktreatment. Since the average age of theirradiated cases was 7 years, we had to get aseven year old child’s skull as the basis for atissue-equivalent wax phantom that he used tomeasure the doses to various parts of the head.I don’t remember how we got the skull, but itcertainly didn’t come from the corner store.

The doses to the scalp were very high becausethat is what is required to make the hair fall out.There were overlap areas of higher dose on thescalp since the x-ray machine was positioned in 5different locations in order to irradiate the wholescalp. These overlap areas corresponded to areasof partial baldness. The doses to the brain weresubstantial at the surface dropping off to lowerlevels at the base of the brain in the region of thepituitary gland and the eyes and ears.

We were the first to demonstrate the deleterious effects of the ringworm radiation but not long afterwards we were upstaged by the Israeli study. Many of the immigrants to Israel in the 1950s came from North Africa where ringworm was rampant. X-ray machines had to be set up in the reception camps and ultimately 25 thousand children were irradiated. Israel has a comprehensive health care system, so it was feasible for Modan, a Hopkins trained epidemiologist, and later the Minister of Health for Israel, to pull the records and demonstrate an elevated incidence of brain tumors and thyroid tumors in the irradiated population.

Israel has had one of the highest incidences of braintumors in the world because of this irradiatedpopulation. In epidemiology, you can’t argue withthe power of numbers. The Israel study had tentimes more people than ours, so their data on brainand thyroid tumors is the definitive data. However,they couldn’t get skin tumor data from the recordsbecause it is not a reportable disease, so ours is the

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definitive data in that area. The cumulative incidenceof skin cancer of the scalp has now reached thehorrendous level of 4% in our population. Most ofthe cancers are at the hair line indicating that there isinteraction between ultraviolet radiation of sunlightand the x-radiation.

We resolved from the beginning of the study to follow the cases until they or we died first. The project is still going on 35 years later. Although it all started because of Ralph Baumring, other people have participated, notably Abdel Omran, previously from Egypt, who moved on to a distinguished career at the University of North Carolina. Roy Shore has inherited the project and he has become a national authority on radiation epidemiology.

Lead Poisoning: During the 1960s, lead poisoning in small children, who ingested leaded paint by chewing on windowsills or eating chips of lead paint, became a racially charged issue in NYC. There were protest marches that demanded the removal of leaded paint from the slum buildings where most of the cases of lead poisoning came from. This would have cost several billion dollars to accomplish.

Our involvement began with a radiation devicethat Jerry Laurer built that could be pointed at awall and would measure the amount of lead inthe paint. We progressed to a full scaleepidemiological study to relate health effects tothe cumulative amount of lead exposure asmeasured in deciduous (milk) teeth. This was anapproach that had been used to measure theamount of radioactive strontium, from atomicfallout, that had been taken up in children’s bonesand constituted a cancer hazard. Lead andstrontium behave like calcium in the body and aretaken up in the bones and teeth, so that tooth levelscan be used as a measure of exposure to bone.

We sent field workers into the slums to find thecases, whose names we had gotten from a NYCregistry of blood lead levels, in order to persuadethe parents to bring the children in for an

examination. There was a high turnover of fieldworkers, because they were frequently beaten up.We played tooth fairy and offered one dollar pertooth to be delivered to a school teacher. Thelittle rascals collected teeth in the neighborhoodand passed them off as their own. Lead mayimpair intelligence, but not that much. We had toask the teachers to match the tooth to a hole inthe child’s jaw before paying up.

We did a battery of elaborate psychomotor tests thatproduced a wealth of mushy data. I yearned for asimple decisive test-like throwing a lead brick at thechild. If he ducked, he passed. If not, he didn’t.

My wife Abby, made an innovative evaluation ofbehavior by use of school records. Teachersgenerally don’t record behavior as bad unless itreally is. So we had a reliable measure of abnormalbehavior with which to relate lead levels.

We did find that children with elevated toothleads showed impairments, but Herb Needlemantook matters further and demonstrated that evenlightly elevated levels of tooth lead wereassociated with reduced IQ. This gave animportant impetus to the banning of lead ingasoline which has had a big effect on reducinglead exposure in children. Needleman took theidea for using tooth lead from us.

BCME Epidemiology: We got into the epidemiology of bischloromethylether (BCME) as a carcinogen when the Rohm and Haas Co.(R&H) managers came to us at NYU. BCME is used to harden ion exchange beads. R&H became aware of an unusual number of lung cancer cases that had occurred in Building 10 of their Philadelphia works. They had made a list of the more than 100 chemicals used in that building. Ben VanDuuren, our organic chemist-carcinogenesis man saw BCME on the list as the likely carcinogen because he had been working on chemicals like that. We offered to do an epidemiological study of the plant to which they agreed with the proviso that we couldn’t publish the results without their approval.

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This of course was unacceptable so we saidgoodbye.

Laskin and Kushner then did an inhalation experiment on rats with BCME and found that it was the most potent airborne carcinogen ever studied. Armed with this information, Nelson called a meeting of the 7 manufacturers and users of BCME together with representatives of the National Cancer Institute, the National Institute of Occupational Safety and Health, and the National Institute of Environmental Health Sciences. It was the ugliest meeting I have ever attended, but the industry people were check-mated and couldn’t say no to an industry-wide epidemiological study, which we proceeded to carry out.

The R&H plant was a typically dirty chemical operation. When they were first setting up to use BCME, they carried it (a very noxious liquid) around in open buckets. This method of moving BCME was called “using the R&H pump”. BCME was held in open unventilated vats. One quarter of the workers in the pilot plant died of lung cancer.

When the manufacturing process was finalized,they made BCME by loading several two-storytanks with the necessary chemicals. Fumespoured out of the tanks and into the general airbecause the tank was essentially unventilated. Iwas told that the foreman usually yelled foreverybody to get out of the building while thereaction was taking place but the macho workersstayed. Testimony before Congress about thisoccupational hygiene massacre played animportant role in the passage of the ToxicSubstances Act.

Of the six other plants using BCME, only one had asimilarly high incidence of lung cancer. This wasDiamond Shamrock on the west coast, and theyalso made BCME. The others used BCME invarious ways to treat ion exchange resins and theworker exposures were much lower. So it provedto be possible to use a very potent carcinogen safely

if the exposures were low enough.

To R&H’s credit, once they got wind of the lungcancer trouble, they wasted no time in building anentirely new production facility for BCME that wascompletely enclosed and automated with no accessfor any worker so the exposures to BCMEmanufacture were zero.

Meanwhile, the lung cancers caused by BCME were uncovered by Dr. Figueroa, a physician who worked at the Germantown Dispensary inPhiladelphia. He had a case of lung cancer whowas 38 years old. Since it is rare to have such ayoung case, he asked him where he worked andwhether there were any co-workers who hadgotten lung cancer. The answers were R&H and14. So he worked up this group and published inthe New England Journal of Medicine. R&Hwouldn’t let him inside the plant and his findingswere on the same population that we studied, andessentially duplicated ours. But it illustrates thefact that one way or another, and in spite ofefforts to the contrary, the cat will emerge fromthe bag.

BCME is now on the NIH’s Congressionallymandated list of carcinogens and classed as oneof the 32 chemicals “that is generally recognizedto be a carcinogen for humans”. It was a terrificsuccess story and Norton Nelson deserves thecredit for being the guiding genius behind thewhole enterprise.

The curious thing is that because BCME breaksdown in the air to hydrochloric acid andformaldehyde, we did an inhalation studyinvolving exposure to these two agents thatturned out to be positive for lung cancer in rats.A subsequent inhalation study on formaldehydealone showed that it was the carcinogenic agent notthe hydrochloric acid. This became importantbecause urea formaldehyde foam was widely usedas an insulating material in homes. In fact, after theOPEC oil embargo in the early 1970s, Canadaurged its citizens to insulate the walls of their homeswith urea formaldehyde foam. It was a poor

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product and broke down releasing formaldehydeinto the indoor air.

A class action suit for several billion dollars wasbrought against the manufacturers and installers ofthe foam in Canada. The trial was held in Montrealwhere the Code Napoleon ran the courts. The leadlawyer for the plaintiff was a beautiful dynamo by thename of Nicole Hessler (pronounced “ess-lair”).She asked me to testify that formaldehyde was acarcinogen, which I was willing to do.

The center of the courtroom was a long table, the head of which was a dial where sat the presiding judge (Hurtebise) in his French judicial porkpie hat and robes. Down each side were the opposing attorneys in wigs and robes and at the opposite end of the table from the judge stood the testifying witness, me. Behind the lawyers on each side of the table were their minions in quantity. The court was like a Marx Brothers movie, in continuous uproar with nobody having a chance to talk without interruption and with the judge vainly trying to keep order. I did my bit but the plaintiffs finally lost the case which lasted for years. Nicole H. wound up becoming a judge, herself, and I will bet she keeps a courtroom in proper order.

ENGLAND: In 1970, at age 46 with wife and 2kiddies (Lucy age 17 and Lizzie, age 7) off wewent to merry England for a sabbatical at theRoyal Cancer Hospital in Sutton, Surrey. LenLamerton, famed for his work on cellproliferation, was my host and a really charminggent he was. We rented a cottage in Banstead, inthe green belt that surrounded London. Theowner was a fastidious gardener and showed upon Saturdays with his small son to tend to rosebushes, which bloom until January. They shareda giant Cadbury’s chocolate bar for lunch therebyadding to the National Dental Service deficit.

We had a great social setup, since 2 of our bestcouple-friends from Westchester were living inLondon, the Bleys and the Kaufmans. I playedtennis with Lou Bley several times a week at thefamous London Queens Club where tennis balls

come in a sensible 4 per can instead of 3. But thecourts had wooden floor (too fast) and wereunheated (too cold in winter). We saw theKaufmans often but sadly they got divorced.

Lucy and Lizzie went to school but majored inhorseback riding (Lizzie) and dancing (Lucy).Lizzie’s thick British accent disappeared at homein the same 3 week period it took to acquire.Tom, Lucy’s future husband, showed up on avisit. Abby did rubbings of church bronzes. Weframed one of Sir John D’Abignon, a dapper gentin armor with his feet tip-toed on the neck of a lion.

At the royal Cancer Hospital lab building, Inoticed a memo signed “Harry” with no surname.On inquiry, Harry turns out to be Duke ofsomething, Chairman of the Board. I got my firstwhiff of British caste.

We were so taken up by the things to see and doin England that I didn’t get much research done.I did try to get a method for measuring cell lossin the liver. Previously we had radiolabeled liverDNA and demonstrated how a carcinogen killsoff the liver cells replacing them with tumornodules of progressively severe malignancy. Thistime I labeled mouse liver DNA with a non-radioactive tag, BUDR, and hoped to follow cellloss by a reduction in the density of ultra-centrifuged DNA. However, the DNA repairenzymes busily chopped out the BUDR withoutthe cell loss, so the method didn’t work. It mighthave been a method for studying DNA repairenzymes, but I let it go.

I joined the Sutton Symphony Orchestra(amateur). Attendance at rehersals was spotty asusual with such groups, but one day we had nocellos. The conductor, with typical English aplombsaid not to worry, because we still had the best ofthe strings. We were to perform at the SuttonCounty fair, but the stage wouldn’t hold the wholegroup. So who was left behind? With typical JohnBull spirit, the whole group voted unanimously that ifthe whole orchestra couldn’t go, none of us wouldgo. When I was to return to the States, theycomplained that, “We have just gotten you trained.”

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We had a new Austin America waiting for us at the Southampton dock after the QE II crossing. It was the first front-wheel drive auto and was cleverly engineered but built of foil and tape. Before returning home we took it on tour of France and Italy. It developed a terrific banging noise in the engine. We were in a small town on the French Riviera where we took it to a small garage. The owner listened to the engine and then fetched his teen aged son. The lad also listened to the engine but with a stethoscope. He announced that it was a broken distributor gear. The owner said it was lunch time, and to come back in 2 hours by which time they would have located a new distributor gear and be ready to replace it. With 2 hours available, we opted for a consultation at the Austin-America dealer in Cannes. There, 4 professors in white smocks diagnosed a broken cylinder with a repair tab ($400) equal to 24% of the purchase price of the car, which was only a year old. In response to my howls of pain, they got the Austin America plant in England on the phone. The reaction to my tale was, “Oh dear,” After consultation, they said that we shouldn’t rely on French mechanics but drive it slowly to Le Havre and put the car on the QE II and take it to their dealer in NYC. We did that to the outrage of innumerable horn-honking French drivers. We got the car to the Austin America dealer in NYC where they listened to the noise for a minute and said that it was a broken distributor gear, and it would cost $25 to fix. Some time later, we got a post card from the little garage on the Riviera that said, “What happened? We got the gear but you never came back”.

USSR: In 1974, when Nixon and Brezhnevengineered a USA-USSR detente, a USA-USSRCooperative Program in Environmental HealthResearch was organized. They wrote up a seriesof projects that, when translated, we didn’tunderstand and what we wrote up, they didn’tunderstand. The 2 documents were put togetherwith a cover sheet that was duly signed by bothparties.

Everything is big in Russia. The Hotel Russia

(Roo-see-yah) on the huge Red Square had 8000rooms and every one was bugged. At least ourwas. That was flattering. Russian is a difficultlanguage. Lizzie, aged 11, learned to ask for a fried egg(yah-each-nit-zah). I learned to count to eleven (add-in-ott-stich), and to say “the weather is sunny” (Pal-ee-car-est sun-in-schnear). At one session, when thetranslator had to go to the bathroom leaving usstranded, I launched that phrase into theawkward silence, and was rewarded with a galeof guffaws from our hosts.

This led to a series of exchange visits with the first in Kiev at the Marseev Institute of General and Communal Hygiene. They gave us a terrific picnic in the woods with caviar, smoked salmon, and lots of vodka, after a river ride on the Institute’s yacht. Their labs were old fashioned and the scientists were much given to theorizing on a grand scale that was a novelty for us, but somehow Russian in spirit. I was struck by a remark by one of their mathematicians, Yuri Antomonov, who said at one of the science sessions, that the lung cancer risk from the USSR standard for the carcinogen benzo(a)pyrene in the air was not important because it was less than the variability in occurrence of lung cancer. This remark was greeted without comment by puzzled attendees. I though about the idea for about 30 years, because it seemed to me to be profound, and finally made it the subject of a talk given when I got the Stockinger award.

The translators were excellent. The main one inMoscow, Irena Sutokskaya, talked perfectEngligh because her mother was an English teacher.Irena was convinced that she was descended from aPersian princess. Our main translator in Kiev toldus how, as a child, she was relocated to Uzbekistan,a land whose name she pronounced with gestures ofthrowing up.

I was partnered with Dr. Yanisheva of the KievInstitute, a motherly soul who worked on lungcancer. I expressed admiration for Ukraniansausages, so when we left, she presented me witha large crock of sausage packed in fat that she

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Chapter 8. Carcinogens on thePotomac

In 1975 I was 51 years of age and had been backat NYU for 16 years. I had worked hard on my 3research programs, inhalation, radiationcarcinogenesis and epidemiology, and had risen tothe rank of Professor and Vice-Chairman of theDepartment. I was getting a little frayed at theedges when along came a recruiting man whosaid that they were looking for somebody like meat the EPA in Washington. I could go on an IPA(Intergovernmental Personnel Act) arrangementwhereby EPA would pay my salary to NYU forthe one or two years that I was on leave. Abbywas intrigued with getting back to Hollin Hillsbecause we still had friends there that shemaintained contact with. So off we went, rentingour house to the Maldonado’s from Guatemala’sdelegation to the U.N.

I was to run the EPA’s research program inHealth and Ecology as a Deputy AssistantAdministrator. I didn’t know then that the longerthe title, the shorter the leash on which one istethered. The top EPA boss is the Administrator.The Assistant Administrators, politicalappointees, have the real power since they runthe operations offices like Air, Water, DrinkingWater, Toxic Substances, Radiation, GeneralCouncil and Research and Development.Government agencies are the only large

herself had made. In addition she included 2 bottlesof pepper vodka because I liked that too. Goingdown a snowy staircase at the Moscow airport, Islipped and the whole thing flew up in the air andsmashed to bits. I had to throw the vodka-drippingpackage into a trash can with a nose-twitchingarmed guard looking on. I probably couldn’t havegotten the stuff through U.S. Customs anyhow.Some years later, I told Yanisheva what happened.She laughed and said she would have made moresausage.

When it came to food, the Jewish mother imageis really Russian. When we took a one hourplane trip from Kiev to Moscow, we were given a2 foot bag of sandwiches to make sure that oursmall party didn’t get hungry.

Our hosts were determined to drink us under thetable at the many dinners we had in Kiev,Moscow and Leningrad. They succeeded withsome of our party but not this hardy liver (pun).Once, having gotten well oiled, I gave a toastusing a chicken leg prepared as “Chicken-Kiev”.The top, filled with melted butter, was bittenopen and the bottom, the bone, was held as thestem of the cocktail glass.

Many of their toasts in Kiev were to “ourcountry”. When asked, “which country are youtalking about?” They said, “the Ukraine, ofcourse.” This was in the days of the USSR.

We were in Leningrad during the “White Nights”.Everybody went down to the Neva river andhung around the whole night which never got dark.The Leningradians also celebrate the festival of the“Red Sails,” which is the legend of a princereturning from the wars, whose ship, if he were stillalive, would fly a red sail. He forgot and his father,the King, seeing no red sail, thought his son deadand committed suicide. Such sentiment in the USAis reserved for the soaps.

We took one of their delegations to the Windowson the World restaurant at the World TradeCenter. It went fine until the USSR Minister of

Health got up and denounced the N.Y. Times forslandering the USSR by writing that theirdrinking water was contaminated by Giardiaorganisms. He said the U.S. Government, whichcontrols the N.Y. Times, did this deliberately toembarrass his delegation. Nothing we said indenial worked, and dinner shortly broke up onthis sour note.

The main benefit of the USA-USSR cooperativeprogram was the cultural exchange. Curiously,the Soviets spent much of their money shoppingin NYC for artificial furs.

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organizations where the top management is wipedout with every change of administration.

A main responsibility was to invent reasons whyour budget should be increased but, just as often,to provide reasons why it shouldn’t be cut. I wasto learn that the bureaucratic brain deals onlywith 3 significant figures regardless of whetherthe amount is in the thousands or the billions.Since ours was about 100 million, we fussedmostly about adjustments of a few million.

I had a pretty big office with a conference table, a flag and a view of a nearby hotel. In the Federal government there are specifications for the arrangements and appurtenances of every office according to rank. My secretary sat just outside my office. Her 2 secretaries had nearby desks. Regulations stipulated just how far the desks could be from each other. It was an ordered world but not necessarily orderly.

We had 2 main health research labs, one in Cincinnati and the other in Research Triangle Park (RTP) in North Carolina. There were 6 ecology labs. In those days the scientists in the health labs were not all that great compared to universities or the NIH. Biomedical research does best when scientists are free to choose which direction they think would be most profitable to pursue. In an agency like EPA, that uses data to support regulatory action, there is the danger of spending a lot of money in generating useful but pedestrian information. Such scut work drives away good scientists.

Another danger in EPA is the pressure to generate research findings that support the need for regulation. If a regulatory agency is not regulating, what is it doing for a living? This pressure is not conducive to impartial science. A good example of bad science was the CHESS program (Community Health & Environmental Surveillance Study). This was a huge multi-city study to examine the health effects of air pollution. It attracted a number of scientists who were zealous to reduce the levels of air pollution.

They manipulated the data to demonstrate air pollution effects that were equivocal at best. This was denounced by several prestigious committees that were brought in to evaluate the program. John Finklea, the program director, and his epidemiology staff were brought before a hearing held jointly by 2 Congressional subcommittees. They were vilified. The epidemiology program had been one of the largest in EPA’s health labs, but this hearing destroyed the program and it has not recovered since.

There are legitimate regulatory research problems. For example, EPA found that diesel engine exhaust particles are mutagenic. Since about 80% of agents that cause mutations are carcinogens, at least in rodents, the findings had serious import. The EPA wanted to know if diesel particles are carcinogenic and if so, how potent they are and what are the risks of lung cancer. This issue arose at a time when there were no epidemiological animal studies that could provide answers.

We called a meeting to formulate a research program and invited participation by the NCI and NIEHS. The NIEHS representative couldn’t find a hotel room in Washington and the NCI person had a similarly fluky excuse. So the EPA was left alone to tackle the problem. We took an approach of comparing the potency of diesel particles in various cancer-related tests to the potencies of 3 materials (cigarette, roofing and coal tars) that were known to cause lung cancer in humans and were ones for which we had estimated potencies, i.e., the risk of lung cancer for given levels of exposure. We were able to use this “comparative potency method”, as it is now called, to estimate the risks of lung cancer from exposure to the various types of diesel engines. Surprisingly, heavy diesel truck engines are the least offensive.

The EPA’s expectation that 25% of automobileswould have diesel engines never materialized, butdiesels are still important. The research wasgood and if EPA didn’t do it, nobody else would

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have at the time. Later the automobile industry inthe USA, Europe and Japan jumped in withextensive studies because the lung cancer riskswere not insignificant.

Although the Office of Research and Development was the only EPA office that was designated to do research, other offices got involved occasionally with mixed results. The Love Canal fiasco is a case in point.In the 1800s funds were raised by a man namedLove to build a canal around the Niagara Falls tofacilitate shipping on the Great Lakes. After ashort stretch of the canal was dug, Loveabsconded with the money and the project wasabandoned. The water-filled excavation was thenused as a swimming hole.

Niagara county is home to the manufacture ofsome of the most fearsome chemicals. TheHooker Chemical Company was a leader in themanufacture of such materials, especiallypesticides. Hooker acquired the Love Canal as adump site for its toxic wastes. After it was filled,the site was covered with dirt and used as aplayground by a nearby school. Children used tostomp in the pools of oily liquid therebydissolving their shoes. They tossed lumps ofpesticide and phosphorus, the latter bursting intoflame when split. Then a housing developmentwas built on the site. Soon basements were filledwith noxious chemical fumes. The residentswere stirred up by environmental activists, andthe N.Y. State Health Department tried to fendoff a massive raid on its budget for remediation.

Meanwhile in Washington, the JusticeDepartment and the General Council’s office inthe EPA tried to figure a way to get the HookerCompany to pay for the clean-up. They felt thatthe case would be stronger if they had someconcrete evidence that the health of the LoveCanal residents was being injured. So theydecided to do a health study on the populationunder the guidance of Beverly Paigen, anenvironmentalist and a geneticist from New YorkState’s Roswell Park Cancer Center.

They decided on a study of blood chromosomesto see if they were damaged. The EPA’s GeneralCouncil’s office set up the study, without theORD’s knowledge, with a contract laboratorycalled Life Sciences. At the last minute, one ofthe EPA lawyers eliminated the controlpopulation from the study because of lack ofmoney, presumably not realizing that such actionwould invalidate the study. Life Sciences filed areport with the General Council’s officeindicating that the Love Canal residents showedan excess of supernumery acrocentric chromosomalfragments, a condition that nobody had heard of. Adisgruntled EPA lawyer who was about to leave theAgency, sent the report to the N.Y Times where itmade the front page. President Carter’s Chief ofStaff ordered EPA’s Administrator, Doug Costle, toreport the study at a press conference in order toembarrass Governor Carey of N.Y. with whomCarter was feuding.

Costle protested as did Dave Rall the head ofNIEHS, who had taken a group of experts toLife Sciences to examine the data and was turnedaway at the door of Life Sciences. Costle and Rallsaid it was improper to release the study before ithad been peer reviewed. The White House wasadamant and the press conference was held, whichalso made the front page of the N.Y. Times. TheLove Canal residents got so upset that theykidnapped an EPA official and held him hostage toprovoke some remedial action.

In retaliation for the While House action,Governor Carey formed his own committee, lacedwith Nobel prize medalists, who concluded that theEPA didn’t know how to do research. So ORD,which is EPA’s research arm got a black eye forsomething it had not done, and, the operationsoffices took advantage of this twist in events to try towrest control of EPA’s research from ORD. Somuch for science, politics and territoriality, a brew fitfor Macbeth’s witches. In spite of, or perhapsbecause of these growing pains, ORD’s researchprogram has matured and is now quite respectablein comparison with NIH.

The Love Canal residents were evacuated for32

several years while the dump site was cleaned out.They are now back in their hearths and all is tranquilagain in Niagara County.

It wasn’t long after arriving at the EPA that I began attending meetings in the office of the Administrator’s (Russell Train) on the EPA cancer policy. In 1970, the Federal regulatory programs in air, water, radiation, pesticides, and drinking water were assembled into one agency, the EPA.The main environmental and occupational agencies were formed practically simultaneously. The year 1970 also saw the launching by President Nixon of the billion dollar National Program for the Conquest of Cancer which was centered at the National Cancer Institute. The national thrust to eliminate cancer, beginning in 1970, involved both research and regulation.

The newly formed EPA attracted bright,ambitious individuals. Like new agencies, itsmethods were fluid and there was a minimum ofbureaucratic drag. There was conviction that theregulatory control of environmental carcinogenswould make a big impact on the public healthburden of cancer. This impetus to prevent cancerby regulatory action came about because thetreatment of cancer was mostly ineffectual.There was strong evidence that there were manycarcinogens in the environment. There wereimportant geographic differences in cancer, andmigrants took on the cancer patterns of the hostcountries. Epidemiological evidence was interpretedas demonstrating that 60-90% of human cancer wascaused by environmental agents. It seemed a giventhat the control of carcinogens would greatly abatecancer mortality. This gung-ho attitude was thesetting for Carcinogen Risk Assessment when it wasdeveloped in 1975.

In those first few years of its existence, the EPAregulated a number of major pesticides includingDDT, Aldrin/Dieldrin, and Heptachlor/Chlordane. These actions were primarily basedon evidence in rodents for carcinogenicity exceptfor DDT which damaged reproduction in birds.

They were spearheaded by an aggressive and capable EPA legal staff. Their eagerness to move ahead with the regulation of environmental carcinogens was being balked by the legal opposition of an aroused agricultural-chemical industry who saw the possibility that a zero cancer risk policy could put them out of business. The law hearing on these chemicals lasted years. Each side chose their scientific experts from amongst those who’s opinions would best support their case. The legal process traditionally calls for an exposition of extreme views as the means of getting to the truth. That is what happened. There was a polarization of scientific opinion, and the scientific experts were the main players in the hearings. In a field as soft as carcinogenesis in its understanding of mechanisms and causes of cancer in humans, the opportunities for haggling about scientific issues were great.

The EPA’s legal staff, frustrated by theinterminable legal sparring, came up with astrategy to shorten the legal hearing process.The EPA’s tactic was to try to get acceptance of“Cancer Principles”, a series of generalities, thatwould not be arguable in court so that the legalaction could focus on the particulars of thechemical under litigation. With the help of theirscientific advisors they developed 17 cancerprinciples for the heptachlor/chlordane hearings.These principles look fairly pallid at this remote date,but at the time they were incendiary. What, shoutedthe opposition, anything that causes excess tumors inanimals is a human carcinogen? What about caloriesor hormones? Is EPA going to regulate those? Andto a zero risk, as called for in the Delaney Clause?The Delaney Clause of the Pure Food and Drug Actprohibited carcinogenic food additives.

The prestigious English medical journal, Lancet,published a scathing editorial entitled, “EPA’s 17principles about cancer or something”. Theeditorial expressed contempt for the legal mind-set in EPA that tries to manipulate soft scienceinto legal principles.

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The fall of 1975 was a turbulent time at the US EPA headquarters in Washington. The inexperienced, conglomerate agency was only five years old, and it was undergoing for the first time a barrage of criticism which was focused on the cancer principles. The almost daily rhetoric that took place in Administrator Russell Train’s office probably sounded like the Roman forum during the Punic wars. What to do? To clean up the cancer principles and make them acceptable? This seemed impossible. What else? Finally, Assistant Administrator Alvin Alm came up with a simple solution. Since the trouble was with pesticides, which are regulated under the Federal Insecticide, Fungicide, and Rodenticide Act, and that Act calls for weighing risks and benefits in making regulatory decisions, why not weigh risks and benefits everywhere possible in the EPA as a matter of policy? This idea was greeted with enthusiasm. The EPA thought it was competent to evaluate the economic impacts of regulation, but it was uncertain about evaluating the health risks of agents that were thought to be carcinogens. So it appointed a committee to develop guidelines on how to evaluate putative carcinogens and I chaired it as the only person in the EPA headquarters who could spell carcinogenesis. Depute Administrator John Quarles told me that if the guidelines were not acceptable to the scientific community, there would be no more US EPA!

With a situation that serious, I had to chair twocommittees: an internal EPA committee to giveassurance that there was EPA acceptance forwhatever came out in the cancer guidelines, andan outside committee made up of people thatknew a great deal about cancer. To achievegeneral acceptance by the scientific community,which was essential to the effort, the outsidecommittee had to cover the entire range ofviewpoints that were then being expressed aboutthe evaluation of carcinogens.

The document clearly had to be a guideline onhow to evaluate agents for carcinogenicity. Butif it were to achieve acceptance in such a heatedclimate, it had to be mostly generalities. The

committees agreed that it had to be “broad-brushstroke” in character. It was also apparent thatthe field was so contentious, and the formulationof guidelines such a novel effort, that the processhad to be done stepwise, with agreement beingreached at each step before proceeding to thenext. This proved to be a useful strategy.

The first step was to get agreement on the mostfundamental aspect of risk, namely that it isinherently a two part affair. The first part dealswith the likelihood that the risk will actuallyoccur, and the second deals with the importanceof the consequences if the risk does occur. Thisprecept translates into two questions: 1- howlikely is an agent to be a human carcinogen(because we are only concerned with humanhealth), and 2- what are the cancer risks, giventhe exposure scenario, if the agent actually is ahuman carcinogen?

The next step was how to get the evaluation ofrisk in tune with scientific rather than legalthinking. This called for a weight of evidenceapproach. The evidence was to be laid out, prosand cons, warts and all. No hard and fastjudgments were to be made as to whether theagent is or is not a carcinogen. The evidence wasto be regarded as a signal, the strength of whichdetermines the impetus to regulation. StevenJellinek, a former Assistant Administrator for thePesticides office, did not want to be told that anagent is a possible or probable human carcinogenwith a plausible upper-limit risk estimate of ten to theminus something. He wanted to know whether it isa carcinogen and how many people it will kill! Riskmanagers like lawyers, do not like uncertainty,because it makes it difficult to formulate and defendregulatory actions.

Animal bioassay has been and still is a majorsource of contention, because of the uncertaintyabout the applicability of bioassay results tohumans. However, the committee felt that therecould be no evaluation without animal bioassays,because epidemiological evidence forcarcinogenicity is so scarce.

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The two committees agreed that this broadoutline was enough to set the general frameworkfor the qualitative evaluation and to move on tothe quantitative aspects of risk assessment. It isclear that the essence of the quantitativeevaluation of risk is the mathematical model thatrelates the carcinogen dose to the incrementalcancer risk over a lifetime. Then what is thebasis for choosing one model over the rest?

The Chairman opted for precedent on thegrounds that a Federal agency cannot adopt animportant position on the basis of individualpreference. The best thing for one Federalagency is to use something that has already beenused by another Federal agency. There was aperfect specimen of precedent from the AtomicEnergy Commission. The linear non-thresholdmodel had been used to estimate the bone andthyroid cancer risks from radioactive strontium-90 and iodine-131 fallout from atomic weaponstests. The image of grieving parents at the grave-sides of the estimated childhood cancer victimswas enough to stop atmospheric atomic bombtesting. The non-threshold concept provided therationale for the Delaney Clause to the PureFood and Drug Act which bans carcinogenicfood additives.

It was the perfect choice. Extremely simple touse: one needed only the lowest statisticallysignificant data point and a straight edge to draw aline from that point down to the origin of the graphof dose versus cancer incidence. The model evenhad some biological plausibility. Cancer is anexpression of genetic damage. Mutations aregenetic damage. Cancer is therefore caused bymutations. Mutation is linear with radiation dose inmicroorganisms. Therefore, linearity for cancer!The difference between chemical carcinogens andionizing radiation could be waved aside since theyboth cause genetic damage.

The guidelines were equipped with anintroduction and a format for the evaluationprocess calling for sections on exposure,metabolic characteristics, animal studies,

epidemiology, dose-response relationships, andcancer risk estimates. The job was done, and thecommittees signed, Amen.

But what to call the guidelines? The name had tobe magisterial as befits a Federal regulatoryagency and connote action. Risk Evaluation?Too after-the-fact, like grading test papers. RiskAnalysis? Too detached and ivory-towerish.What does a general do before battle? Thegeneral assesses the situation. Risk Assessment?That was the name! The Chairman wondered ifthere was anything else that would help to defusecriticism. Why not call the guidelines, interim?It defuses critics by making them think they canchange matters later.

So on May 26, 1976, with great media fanfare,out came the “Interim Procedures and Guidelinesfor Health Risk and Economic ImpactAssessments of Suspected Carcinogens”. It hadan impressive preamble signed and even partlywritten by Administrator Train. It reemphasizedthe Agency’s commitment to reducing the burdenof suffering from cancer. It pointed to theevidence that a substantial amount of cancer iscaused by environmental chemicals. Itemphasized the two-step nature of decision-making process; first, whether a substanceconstitutes a cancer hazard, and second, whatregulatory action should be taken to reduce the risk.This later surfaced as the distinction between riskassessment and risk management. It emphasized therelatively recent development of regulations againstchemical carcinogens and the underdevelopednature of the cancer research related to riskassessment and hoped that there would be acommitment by Federal agencies to develop newknowledge. It called for independent assessment ofcancer risk and economic impacts implying thepotential for bias. The guidelines called for theformation of a Cancer Assessment Group (CAG) asan advisory group to the program offices.

Administrator Train took to national television toannounce this new initiative in order to dispel thestorm over the EPA. It worked. The criticism

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vanished like magic. The novelty and vagueness ofrisk assessment put the critics into a wait-and-seemode. The agency was back in the carcinogenbusiness.

I was given the job of Chairman of the CAG andmade Chief Medical Advisor to AdministratorTrain. I even had a desk in Train’s cloisteredtower office. Betty Anderson became themarvelously effective Executive Director ofCAG. Her style was pure southern Virginia:genteel, soft-spoken, and imperturbable evenunder major stress. She recruited a scientificstaff of 15, set the CAG’s administrativeprocedures and interface administratively withthe Agency.

The CAG was formed, but how would it work?It had the choice to looking over the shoulders ofthe program offices, letting them do the riskassessment, or doing all the Agency’sassessments itself. The program offices did nothave a clear idea of how do to carcinogen riskassessments. Neither did the CAG. Since theCAG was initially made up of members of theprogram offices, the program offices were happyto have the CAG doing the assessments.

It is common knowledge that there are twothings one should never watch being made:sausage and policy. Carcinogen risk assessmentis science policy. Critics say it is sausage, too,i.e. baloney. In fact, it is a framework for theevaluation of evidence for carcinogenicity withguidelines that have to be plausible within thelimits of what is known scientifically. It isscience policy, not science, because positionshave to be taken within the uncertainties in thescience, which in the case of carcinogenesis,allows considerable latitude for choice. Riskassessment has to be monolithic in itsconsistency, because it is open to legal attack.

The idea that a concept like linear non-thresholddose-response could be turned into the battle flagof carcinogen risk assessment makes scientistsuneasy. Scientists are taught that a hypothesis,while useful to organize thinking, is justifiable

only if it is testable. Non-testable hypotheses aregenerally ignored. The EPA has used non-testedand non-testable hypotheses as risk assessmenttools. These are called “default assumptions”.This, unavoidably, gives the flavor of sausage inscience policy. The CAG’s brand of riskassessment was the most conservative approachthat could be taken within the framework ofcurrent knowledge. It was protective of publichealth, as befits a “Federal Agency”, and it givesthe upper-limit view of what carcinogenregulation can accomplish.

As the CAG began its risk assessments, almostevery agent brought new problems that requiredrapid solution because the program offices saidthat they needed the assessments urgently. Theurgency was a source of wonder because somany risk assessments, once done, seemed todisappear into the bowels of the EPA resurfacingat intervals.

The CAG tilted toward doing risk assessmentseven when the data was thin. It joked about theless data, the more flexibility. But the reason wasto avoid the other extreme of not doing riskassessments on data sets that were less than ideal.Conservative (protective) positions were alwaystaken in CAG risk assessments as appropriate toa Federal Agency.

We went back to New York in 1976 after one yearin Washington which was enough. I used to take theEastern Airline Shuttle to Washington ever weekfrom 1976 to 1985. The stewardesses used togreet me with “It must be Friday”. The shuttlewaiting room in Washington had a bar where therewas generally a bourbon and soda waiting for mewhen I arrived in the early evening to go back toNew York.

Those Friday meetings with the CAG when wewent over the week’s work were free-wheelingand rambunctious. Our assessments on the manychemicals that we evaluated were short and tothe point, i.e. only a few pages long. The currentrisk assessment on dioxin is over a foot thick andtook 10 years to revise! But we never released

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Chapter 9. Zinzinnati

In 1985, I was 61 years old and had gone through a right sided colonectomy 3 years before at the same age that my father was when he died of the same disease. I was also 4 years older than Beethoven when he died. In short, I was feeling ready for one last blast before the lights went out. The opportunity came with an offer to chair the Department of Environmental Health at the College of Medicine, University of Cincinnati. I had been to Cincinnati a few times and was not too impressed with the city. It appeared to be small and quiet. Mark Twain captured the point when he said that he wanted to be in Cincinnati when the world came to an end because it took ten years for the news to get there.

The Department: I was somewhat familiar withthe Department of Environmental Health atCincinnati. It was founded by Robert Kehoe inthe 1920s and he used it as the MedicalDepartment of the Ethyl Corporation of America.It did a lot of industrial testing but Kehoe didsome excellent lead studies in people. TedRadford, Kehoe’s successor put the departmenton a more academic footing which was continuedeffectively by Ray Susskind and Ernest Foulkes.

By that time, Authur Upton had becomechairman at NYU even though Nelson thought Iwas going to get it. So wanting to cap my careerand seeing nothing else in the offing, I accepted.Abby always made a point to leaving suchdecisions up to me.

Cincinnati proved to be a step-up in urban livingsince the cultural scene was far richer than inScarsdale where the Westchester County Centerand the Haagen Das ice cream shop were whatthere was. Manhattan was too congested andexpensive to bother with.

We moved to the edge of Cincinnati with a housethat had acreage and a distant view of the Ohio

any assessment until we were sure that it was asgood as could be. The delays frazzled theoperations office people who always were in arush although their output of regulations wasmeager.

The Reagan administration brought in AnnGorsuch as Administrator, the Coor’s Beerprotegee with the marching orders to stop theEPA in its regulatory tracks. People in andassociated with the Agency were color-coded torank them according to the urgency of getting theaxe. The color brown was the highest rank onthat s–t list. In academic circles, it was a mark ofdistinction to be a brownie. Norton Nelson wasindignant that I was one and he wasn’t. Gorsuchherself was finally axed and Ruckelshouse, a fineperson, took over.

In retrospect, the EPA risk assessment junket wasa large scale public health effort to reduce cancerby eliminating the effects of carcinogens. Itfailed because of industry legal resistance and theuncompromising no-risk approach taken by theEPA. It is still not clear what causes the bulk ofcancer in humans and whether carcinogens are asignificant threat at low levels in theenvironment.

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river. I moved into the big corner office thatKehoe had built with its own toilet and clothescloset, amenities that I was happy to get used to.

The nine year stewardship as director from 1985-1994 was almost equally divided into a great firsthalf and a miserable second. My high point came atthe Xmas party in 1989. Our research budget hadmore than doubled. The Neberts, my prize recruitshad just arrived. The construction of our newresearch wing had just started. The department hadbeen successfully reorganized and difficultpersonality clashes had been resolved.

On the first work day after New Years, disaster struck. People mainly from the Kehoe wing began complaining of dizziness and a metallic taste. They streamed over to the occupational medical clinic. Women, particularly, couldn’t stop crying even though they admitted to having nothing to cry about. Over the next weeks, things got worse. Large checks to non-existent companies were being drawn up in the business office. People found themselves driving on the wrong side of the road, not know how they got there. Faculty, giving lectures would stop, forgetting what they were talking about. People could hardly get through dinner before collapsing into bed, completely exhausted. The situation had all the earmarks of “sick building syndrome” in spades. Dean Hutton said, “It couldn’t happen to a better department, haw, haw.” The Vice President Harrison gave me a lecture on the psychological basis for the symptoms that were occurring.

I was distraught because the department was visiblycoming to pieces. I knew that if the situation wereput into the hands of the State government it wouldtake years to resolve. They had a terrible reputationas do-nothings. When the University wanted to getaction, they sent a person to Columbus who wouldhand-carry paper from one desk to another toexpedite transactions.

Our building had been terribly neglected. Thebasement was full of trash. The air conditioningunits were ancient and leaking refrigerant. There

was an open tank of irritating disinfectant that buildingair was circulated through as a means of preventingLegionnaires disease.

With no alternative, we evacuated our buildingsand dispersed the faculty, staff and laboratoriesover the entire campus. The department’scohesion and morale was gone.

Just at that time, we had to compete for arenewal of our NIEHS Center Grant, one of thekey components of the department’s financialsupport. We did badly at the site visit and thegrant got only a one year’s extension to permit aresubmission of a completely reorganizedapplication. It was a major setback because I hadgambled on getting a renewal with an increasedbudget to offset some heavy recruiting expenses.This falling through put the department’s finances inthe red.

We hired Clayton Associates, the mostprestigious engineering firm in the country in theenvironmental field to find out what was wrongwith the building and tell us what would beneeded to fix it. They did find a lot of chemicalsin the air at very low concentrations and that theventilation in the building was screwed up (whichwe already knew since the air whistled throughthe doors between wings), but they drew a blank onwhat accounted for the sick building syndrome.

The solution to the problem came from an observationby our shop man, Alex Fodor. He used to test sinkdrains in the vacated Kehoe wing to make sure that thedrain traps were filled with water. He did this byplacing a Kleenex tissue over each drain. If thetissue was sucked down, he know that the trapwas empty. We should have seen the light at thatpoint, but we didn’t.

However, one day, he did the same thing with thestand pipes on the roof of the Kehoe wing.These are short pipes that stick up from the roofand are connected with the sewer lines in thebasement to act as vents in case the pressure inthe sewer system builds up. When he did this,the tissues were promptly sucked into the stand

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pipes. When he told me what happened, thedawn came.

The building was under severely negative pressure. Over the years, more and more chemical fume hoods had been installed in the laboratories. The purpose of the fume hoods was to protect the people handling noxious volatile chemicals. The fume hood sucks air from the laboratory room and discharges it on the roof.

The difficulty was that so many fume hoods hadbeen installed, with nobody paying attention tothe consequences, that twice as much air wasbeing sucked out of the building as was being putinto the building by the heating and ventilationsystem. For that reason the building was undersevere negative pressure and trying to suck airfrom outside wherever it could.

What Alex Fodor had demonstrated was thatthere had to be a breech in the sewer system sothat it was no longer isolated from the negativepressure inside the Kehoe wing. The sewersystem, now under negative pressure sucked airin through the stand pipes on the roof. Air fromthe roof swept through the sewer lines and into thebuilding through whatever and wherever the break inthe line was.

All the laboratory sinks in the Kehoe wingdrained into a large acid neutralizing tank in thebasement floor which was connected to thesewer lines. That meant that the fumes fromevery volatile chemical used in the laboratorieswere in the sewer lines and went into the indoorair of the Kehoe wing. No wonder that theindoor air had so many different chemicals.

Shortly thereafter, another firm was hired, theEnvironmental Health and Engineering Company.I told them that there had to be a break in thesewer lines and to find it. They found the breakwith a few hours. It was a $25 valve in the sewerline at the base of the elevator shaft in the Kehoewing. It was promptly replaced. The poundingon the Kehoe wing from the heavy machinery

used in the construction of the new and connectingwing must have snapped it open.

Not only did the negative pressure drag the airthrough the sewer lines from the roof, butbecause of the break at the base of the elevatorshaft, the elevator itself acted like a giant syringepump to pull air through the sewer lines into thebuilding air.

About that time the State came up with themoney to replace the heating and air conditioningequipment with the new and much highercapacity system at a cost of millions. Theinability of the old system to meet the ventilationrequirements was the root cause of the problem.It took 6 years almost to the day for theremediation to be completed and the Director’soffice made available for re-occupancy.

How the low concentrations of so many differentvolatile chemicals produced the symptomsassociated with the sick building syndrome is stilla mystery. But ours is the only instance of a sickbuilding syndrome, that I know of, that wasdiagnosed and cured, albeit at considerable cost.Others, for example, at the EPA headquarters andthe Library of Congress, both in Washington,were never solved.

The Research

Doing research as the Director of a largedepartment with 45 full time facultyparticularly during the last half of my tenureinvolved a lot of distractions. I had gotten intostudying the inflammatory action of the carcinogenbenzo(a)pyrene (BaP) on the mouse skin as apromoting component of its carcinogenic action.BaP is known to be a contact sensitizer like poisonivy. Contact sensitization is an immune protectivemechanism. Specialized cells in the skin(Langerhans cells) pick up the molecule of thesensitizer in combination with a protein and moveout of the skin to the local lymph nodes where theypresent the molecules to T-lymphocytes. These T cells

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undergo proliferation and seed the lymph nodes allthrough the body. When skin contact is made thesecond time, the same thing happens but this timethere is a tremendous proliferation of thelymphocytes and they migrate to the contact site andset up an inflammatory reaction of the poison ivytype.

There had been evidence that a number of genotoxic carcinogens were contact sensitizers. This is a reasonable finding since there is a plausible mechanism. Genotoxic carcinogens attach themselves to DNA and cause genetic damage. The same chemical properties allows genotoxic carcinogens to attach to protein. The carcinogen-protein complex is what the Langerhans cells carry to the lymph nodes to set off the contact sensitization process. I figured that if genotoxic carcinogens, i.e., the type that produces cancer by attacking DNA (all known human carcinogens are genotoxic) then why couldn’t contact sensitizers be genotoxic carcinogens? Since there are a lot of contact sensitizers, this could be important.

I got together with Phil Magee from theDepartment of Dermatology at the University ofCalifornia at San Francisco, who is a top-notchchemist, interested in predicting which chemicalscould be contact sensitizers. We came up with anestimate that there could be as many as 100 thatare carcinogens.

After stepping down as Department Director, aswas Dean Hutton’s custom, I was given a year’ssabbatical to get me out of the way while theypicked a successor. I went to the NationalInstitute of Environmental Sciences (NIEHS) inresearch Triangle Park (RTP) in North Carolina towork in Ray Tennant’s lab.

The NIEHS is a research paradise being full of young lively people in a wide range of disciplines and in a beautiful facility with lots of opportunities for interactions. I brought along my interest in contact sensitizers as carcinogens. Ray Tennant and Jef French had a transgenic

mouse (TgAc) that was tumor initiated with a built inras gene that responded well to tumor promoters. Itried 2-dinitrofluorobenzene, a well studied contactsensitizer on this mouse and it produced an amazingnumber of tumors in only a few weeks. All thetumors were benign. It showed that contactsensitizers could be tumor promoters, but if theydidn’t damage DNA, they couldn’t produce cancer.

Jef and Ray were marvelous hosts and it was adelightful year although RTP wouldn’t be enough ofa metropolis to suit us city folk on a sustained basis.We had good bridge games with the Gravensons,Teddy being a relative of Abby’s. He unfortunatelydied prematurely while undergoing chemotherapy forcolon cancer.

Returning to Cincinnati, I retained interest in thecarcinogenicity of contact sensitizers but the needto evaluate potential carcinogens on a large scaleraises the difficulty that the accepted method oftesting carcinogens by use of rodents is very timeconsuming and expensive, requiring about 5years and 2 million dollars for each test. Wecouldn’t begin to test our prediction of 200possible carcinogens by this means. So I becameinterested in the possibility of a rapid skinbioassay for carcinogens using a special kind ofmouse.

There are transgenic mice that are deficient in thefunction of a particular gene called p53. Whendamage occurs to a cell’s DNA it somehowknows this and activates the p53 gene. Theprotein produced by this gene stops cells fromdividing so that they have time to repair theirDNA. Otherwise, mutations would be producedand transmitted to daughter cells that couldbecome cancerous. Furthermore, cells are ableto sense whether the DNA is actually repaired. Ifnot, the same gene is activated to induce a formof cell death, called apoptosis. This processeliminates cells with irreparable DNA damageand prevents them from going on to becomecancer cells. Hence, the p53 gene is a vitalprotective mechanism against cancer.

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I had learned of a mouse that has an abnormal p53gene in the sense that it has an artificiallyincorporated mutant version of the p53 gene ineach of its cells in addition to the normal p53gene. The mutant gene cancels the normal gene,so this p53 transgenic mouse is thereforedeficient in p53 gene action and much lessresistant to the action of carcinogens.

Fred Burns and I, back in the old days a NYU,had shown that if a carcinogen like BaP is co-applied to the mouse skin with a promoting agentcalled TPA, there is a tremendous speed up in theappearance of skin cancer. So why not use thep53 transgenic mouse and co-apply the agent tobe evaluated for its carcinogenic action to themouse skin along with TPA? Wouldn’t thatconstitute a rapid and relatively cheap assaymethod for evaluating putative carcinogens? Wetried it out and it seemed a promising way to go.

On the chance of getting support to work out theapproach, I sent in a grant proposal to EPA.Ancient emeritus (age 77) that I am, I gotawarded a 3 year grant for a total of 3 quartersof a million dollars to do the study. How this isgoing to work out, time will tell. But at thispoint, this memoir thankfully comes to an end.

Postscript

Recent events prompted the following recollection. I wasin the Emergency Room at Bellevue as a medical studentwhen the call came in that a plane had crashed into theEmpire State building and they needed an ambulance. Iwas asked to go along. The plane hit the building at aboutthe 72nd story. I raced up the stairs to the floor where thecrash occurred. I was in good shape since it wasn’t manyyears since I rowed on varsity crew at Columbia. Rushinginto a big office area where firemen were milling about, Iwas promptly hit in the stomach by somebody’s elbow. Itwas Mayor Laguardia in his fireman’s hat.

The room had been gutted by fire. It was my firstexperience with people burned beyond recognition. Therewas an arm sticking up out of a pile of rubble in the corner,but it has been reduced to bone. I was asked to go down

several floors and see a man who had jumped out of a window because of the fire. He was a reporter from Buffalo and he had landed on a parapet and stove in his forehead.

The plane was a small 2-engine Army bomber. Its pilotthought Manhattan was Newark where he intended toland. After flying up 5th Avenue, he attempted to climband hit the building. The wings came off and floateddown to Madison Avenue. The plane punched a bighole in the building wall, and mostly ended up in theelevator shaft, but one engine went through theopposite building wall and down to the street below.Peering out of those holes, the street was a long waydown.

This happening could have been the inspiration for theterrorist attack on the World Trade Center.

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