Document Yrv8ndzvjYk70E6yOjOoQnmpy

FILE NAME: Saranac 7th Symposium (SSY) DATE: 1952 DOC#: SSY010 DOCUMENT DESCRIPTION: Transcript of Discussion of Eisenbud Paper [but Not the Paper Itself] from Sept 22 PM Session I Tn FBOH FIGS H I * * I \ BY PQCTP8_ B a & to oemtiaao owr dl*<m8alon now on to* parobLsM, vito a roport fcy Doctor Prtt of too I I I i ns.; i Laboratory staff on their studies on some of the new syn- 1 thetic silicas* Doctor Pratt* ! BY DOCTOR PEATTt (Doctor Pratt read a prepared paper* whioh Is on j file at the Saranac Laboratory)* BY DOCTOR HATCH: J! Ladies and gentlemen* ve have heard now about many different kinds of materials ranging all the way from our ! l old friend Silica* as it occurs in nature, to problems that! develop with the synthetic silicas* and these other eurious dusts in between* Ve go now to a little departure* perhaps* f r a the processes that have been followed this afternoon* the discussion of the behavior of particulate matter* without special reference to the nature of the material* in the l course of Inhalation and certainly the way in which partic ulates are handled in the course of inhalation and their receipt* of those standing and the amount of retention* things is fundamental to the of the whole problem of dust and the understanding j ! building up an under- I i diseases* j Merril Eisenbud of the Hew York Operations Office j of the Atomic Energy Commission will report to us now on thsi | Fcio or Inhalod rartlculatoo Mr* Bloonbud* I BY MR* E TSENBUD; j (Hr. Eisenbud read prepared paper which is on file locna mrioi Mwncn orofiMTion If-SATOMICDWUYCCHMimON F O FOXto.AKSOM1ArrATK3K lW YOfIK a. HEW YORK KSiarn UNITED STATES ATOMIC ENERGY COMMISSION NEW YORK OfWATtOW OFFICE O ctober 15, 1952 D r. A rthur J . Vorwcld D irector of Research Saranac L aboratory and The Trudeau Foundation ? Church S tre e t S aran ac Lake, New York D ear D r. Vorwaldx As you p ro b a b ly know, Hr. Eiaenbud i s a t p r e s e n t abroad f o r a p e rio d o f about 8 w eeks, end t h e r e f o r e , I ao te k in t h e l i b e r t y cf forw arding to you a copy of the ta lk he cave a t Scranac recen tly which he in d ic a te d you would need f o r your reco rd s. S incerely, S. feils tein S ecy , to Hr. M. E isenbud E n clo su re : "The F ate of Inhaled k a r tic u la te s " rr--1 - -P-a-Sa A t V v ^ ___ O l& b . .1*1 SI !t 1 4 i \ i t ! 4 ! I * : i i 113*; In the Saranac Laboratory)* | BY DOCTOR HATCHI | I think you will all agree with me that we hay# J had a very concentrated afternoon and I'm not sure how much* tine you're going to feel like taking now for discussion, but I an certain that whether you feel like It or not, you all hare many questions that you'd like to raise for such discussion* I should like to emphasise at this point, the ohalnun'i privilege of opening the discussion and to nake one or two cousaents which pertain particularly to the last presentation of Mr* Bisenbud'e, and haying to do with the fate of inhaled particulates* First of all, I'd like to suggest, whereas there has been a good deal of attention paid to initial retention of particulate matter in relation to par.lole else or tho - over tho last few years, I'm not ' i at all sure in my own mind that it's the most important I factor compared with the subsequent clearance of particulate matter from the entire lung structure* I reme-bor how im- i pressed I was many years ago when I made a very crude little calculation with some of the data from South Africa compar- > ing the amounts of materials found in matching of silicotic lungs with some rough calculations on my own among the ma- terlal that the individual had probably inhaled and regained, and while the essence is necessarily very crude, nevertheless the order of magnitude was not far off, and the amount re tained or the amount accounted for in the alllcotlc lung vai in the ordr of on tenth to on percent of the amount 1i which they had inhaled orer th yeara. j Vow, than to whatever degree that residue repre- | eanted the material that it produced in them, it pretty olear that we're talking about a highly selected portion of the total material inhaled, and so when we try to relate the composition and the physicial characteristics and so on, of the material in the ataosphere, among them it aeama to me pretty evident, that there is an awful lot of information - an awful lot of things happen from time of inhalation to the development, full development of the effects, so I sus pect that the - one of the biggeet gaps In our understand ing, one of the things in whioh there is the greatest need for research, is the research into the way partifulate m a terial is handled, the rates, relative rates of clearance and the relative ways in which the particulate matter la i disposed of within the lunge and in that connection, I'd lllca to mnke two points which will amplify, add perhaps a j little bit, to what Hr. Blsenbud has just had to say about tfcie I retention# First of all, if you will permit me to make a very c* -a. diagramatlc sketch here, of a primary molecule, and t b M is : very diagramatic, but I want to use this way of making my I point. Considering the primary lobule, beginning with the respiratory bronohlole, we hare -- I warned you this it j going to be very dlagramatic -- we hare tome kind of veati-| bule beyond the respiratory bronchiole connected to that in J various air eace. How, I won't go beyond that in trying toi picture it, but I make thia point that down to this point here, concerned with known respiratory air passage ways, th< oluae of which air got through something like 11*0 c.c.'s of atypical, and this pass ir here adds up to something of that order, and the alveolar spaces to something of that or der* now, in the course of inhalation, these are figures representing a relaxed lung. In the course of inhalation, t/h.t*. is expansion down hare, and I presume some expension in this volums also, but evsn under the most rapid rate of inhalation, the air velocity down in here and out into thia apaea it of the order of, well, at best, one or two feet per minute or one or two centimeters per second, ! According to the very elementary view of the j thing, from the standpoint of fluid flow, wa have to accept ` th. n o t i o n that the flow of air into this apace is completely 8low# There is no turbulence in it, so that as these spec- ; es expand, the air that was in here at the beginning of the i inhalation simply recedes quietly out in these space, here and the new air comes in on top, so that active mechanical I 116. ventilation - by active mechanical ventilation, I mean act!ye i change space, J of gassea, takes place only down into this particular since at least under conditions of normal quiet breathing, the tidal volume will not any more than see that) and even under heavy breathing of exercise as it goes up, j it will still Just fall in on top of the receding air. j How, there is an important point here. The venti** latiom is all right so far as exchanging is concerned, b e cause the exchange of oxygen said cog across this face, t akei place by rapid molecular diffusion, a pretty veil accepted notion in respiratory physiology, but the philosophy of diffusion of particles of the order of one or two miorant is so slow that we can expect no oxohaage of partielss out into the true alveolar spaces in any way comparable to the exchange of gas out into them, so that these figures that we're talking about here represent deep lung deposition, but not necessarily mean the same for all different eisee, as td I the ultimate site. j i As particle site goes down, the gravitational de-- j | feet which is a primary one in causing the sedimenting out j of particles, the gravitation erfact goes down in size and i I the diffusion velocity goes up, decreasing size in that : I fashion, and for simple sedimentation, this is about a quar* ter of a micron, so it see m s to me that basic to our eonsidi eratlons this afternoon, which we have heard so much about leMaWW* th# peculiar behavior of some of these sub-microscipie ma terials, basie to that may be a deeper understanding than we now have of the actual site of the position and the way that thosd particles are handled by this total structure, i since it seems clear to me at any rate, that a particle that does get out of here by diffusion is going to be - well, say we depend on different mechanisms for its removal, and that is time of particles settled out in the earlier part, tele more point which I*d like to me' ei If this represents the respiratory cycle with this inhalation and expiration, ws know that these early stages of inhalation as s relatively rapid intake which peters off with ths end of ths inhalation and then there is a rapid beginning of exhalation which tapers off* Current thinking, from recent experimental work, suggests anyway, that the volume of air which is breathed in at this time is represented by this volume of air exhaled, and this volume of air inhaled represented by that volume exhaled and so on, and the so- j called sequential ventilation of the first air in, the last j air out, which is another way of saying that the different ; parts of the lungs are expandod at different times In the j course of inhalation and exhalation* ; Kow, the function, among other things, is the tirs it saves down in the lunge in this volume of air that's be ing actively exchanged, so that along with this question, , I __ u s * v* hare alto to consider the parts of ths lunga that are aost actirsly vantilatad during the early phase of inhala tion, comas that they in during ere tha being last last out, as against the air that T.ntil.tiem and that is tha last J air out, so that where thi. air goas to in tha lung eaa- pared with where this air goas to, is inportant in your understanding of tha sita of deposition, and again your point of clearance, so I would like to suggest that eore inportant than our understanding of retention, is a better understanding than we now hare of the clearance of the m a terial from the lung and the way in uhich that is related to the nature, both chemical and physical, of the material. Vow, I had to get my say in. At this point, I should like to open the meeting for discussion from the floor* BY DOCTOR VOHtfALDt T.4, how do you know 1 1 this, that 1. how do you know tfaor. 1. no turbul.nca or 1 r way <* thl* * lcPO' scopsT BY TOCTOR HATCH t W.ll, obrloualy. WO con't know It rroo any oxpopl n o n t l work. W. can only know It Iron u.ly.1.. know thlo. thot in th. n o r l typlel lung, t h . -- . . pretty good Id.., how nany. r.aplr.tory hronchlolo. -nor. and ws know from anatomical mea.uroo.nta, th. croaa-aoctlon 119. of air in tlx* anatomical bronchiole, and in on* of - on* **^ of data that I have in mind, total air of a vhola aet of j bronchioles, cross-section adds up to on* *ight eight equar# bronchiol**. Respiratory - yes, thera are on, and a fifth , tim*a t*n reapiratory bronchiol**, and that relate* to thi* : relocity per second and ao on down. Thia is Landau's chart. i I think. ; Thea* are typical dimension* and reported for the | reapiratory ayatea. I'm sure they're not exactly right, but they are good enough for our purpose*. How, on* thing we know in fluid mechanic*, in the understanding of fluid* and flow, and w* can draw a sharp distinction between ao-called laminal flow and eo-oall*d turbulent flow, and determining in advance in any given eitj nation when we're going to have one end when wa*r* going to , have the other. The index i* the eo-cailed Reynold* nunber j which I won't burden you with, but eay thie, if * Reynold* ; number i* le* than two thousand, you can be b u t * you have j laminal flow. ! Chase calculation* hare would Indicate that in the lungs even under the deepest inhalation at an ins tantan- aous rate of sixty liters a minute, the Reynold* number 1* tremendous to be compared with two thousand, as a dividing line between laminal and turbulent flow so it's only my faith in the Reynolds number and fluid mechanics that -ould 12 Q, t*ll me that this is so. j I think ther is soma physiological eridonc to I i n d i c t , that It 1. .oin thi. c . . . that aft.r .xcicng.. j l t ,, ,,,,tll.t.d bT diffusion* . tionT P C . that a n . c r jour qu..- | i j BY DOCTOR MACHLBt | Hr. Chairman, I'd I l k . to c o m f .lla .n t D c t o r Hardy: on a c r y .xc.ll.nt .ummary of th. b . r y l U u m problma. I would lib. alo to ask if .h. would ol.borat. on th. . . . pr.auaablj .xpoo.d to low borjlllum phcphor. W. bar. b..n following data on ..r.ral t h o c n d p.opl. .xpo..d to low borjlllum p h c p h o r . .lno. 1 * 5 . Hro. our .xp.rl.nc., from th. data w. haw. now pool.d tog.th.r, w. haw. J.t to find t a r . . . of e x p o s u re to borjlllum . c o u n t e d in th. low phosphor, at l e t In on. manufacturing operation in thi. country, nd in anoth.r manufao Curing operation, th.r. haw. b . > aeweral hundred including - ..v.ral hundr.d t h o c n d ,,n hour, of . x p e u r . to low borjlllum phcphor., th. per centage was lss than thre years. BY DOCTOR VORWALD* fho percentage was less than whatt BY -DOCTOR KACHLBi Beryllium* BY DOCTOR HARDY; My data is a mixture of ma t e r i a l t h a t I h a re >>T i 121,1 the court*.y of Doctor Kiln., on General Electric pho.phor j which, I understand, is alwaya below four percent, and he j report, t o u t eleven cases, and we have two case. In Kassa-j chusett. in or from subsidiary companies in that same phos-, phor. (SOS* Doctor Hardy requested following the closing of the session that the reference to General Electric be deleted fro. her remarks. However, a. the reporter under stood the response, the reference is made in such a manner that it is felt Doetor Hardy should make the deletion In such m way as not to confuse her statement). I have reports from Hash in England, reporting ix case, of chronic b e r y l l i m poisoning, three of these fro. low beryllium phosphor manufacturing, I used the tea*, .roughly* advisedly, because I didn't have the precise data M to the total number of these, but it was something of the order of fifteen which Is on the low side, of individ uals with anunknown number,doubtless in the thousands, j exposed to phosphor below four pereent. I. that what you j w a n tt j . I B Y D O C T O R M A C S U 51 j MW I - 1 1 '' th"t " * ,1nlrl0*nt j but thar. arc . . T o r i .Kitten... h; pho.phor quits apart fro. what Doctor Pratt n - : tlonad, char.curl.tlc. .o to ap.ak. of srposurc. Bf th. characterisation of phosphor, the total .count of h.rjllium present is an important consideration because of the limi- . tation in the limit of the solution which you can make of beryllium in material# The second variable is the completeness of the j reaction which, of course, is determined by the time, tea- j perature and repetition in firing, together with the use or non-use of flexes. In situations where we have encoun- ^ tered cases which seemingly occurred from exposure to low j beryllium phosphor only, it has been possible in at lea.t two of the situations to establish that there have been un usual practices in the preparation of phosphor by - in ths direction of lessening firing, experimentation with flex- j ing methods, and so forth, which lead one to believe that it was an anomalous situation and it could not be included in the general epidemiological consideration ifcich, obvious ly, you are bound by, to have a eertainty as to the nature of the exposure. BY DOCTOR BARCTfs That is why I quoted you, Doctor Machle, as one o: the more studied of physical characteristics of stats of > aggravation, and so forth, and so forth, but it seemed to m e in reviewing the evidence in my own personal experience, we had to say that the low beryllium phosphor used in that manufacture before May 191*9 had caused the death of a num ber of cases of beryllium poisoning and I think, as you do. 123- this i a very crucial point in studying the epidemiology . of the disease. , BY DOCTOR VOHVALD: i Hr. Chairman, it may ba Interesting for you to i know, I think we have in recent years, or last year, sue- j ceeded in reproducing a lesion in the lung of animals which simulates, at least, the lesion which we see in the human ; oases exposed to beryllium, and certainly the simulation is| as comparable in that instance as is the simulation between: ' silicotic produced and the silicotic natural subjects. We j have eucceeded in doing that after many months of exposure j to pure beryllium oxide at extremely low levels of concen tration, and also to a beryllium sulphate at extremely low levels of concentration. There ie - in ay own mind, however, there is one j difficulty which I can not explain and that is that we have! bot as yet succeeded in reproducing the number of lesions j that we see in human cases. How, I must admit that the j lesions that we have reproduced experimentally are veAJr few .nd far between, but we will be reporting some of our other observations on Wednesday when we discuss the pulmonary can cer and its relationship to some of our exposures in ex- p a r ' -aQii'tal a n im a ls # I should like to ask, if I may. moment, Hr. chairmen. Dostor Solandt - . may have no. given him sufficient time, and if he could merely tell us very briefly, whet he is doing then as the agent that is pro ducing this change In the group - in these experimental animals, and also related to human subjects in the abrasive bauxite industry. Is Doctor Solandt still here? (Ko re sponse). Doctor Sharer, could you - hee not here. Ve mayhare stopped him too short? Im not quite clear as to his final conclusion. Perhaps while Doctor Sharer is asking for that, aome others might hare a question. BY DOCTOR GRSES3T7R3 Hr. Vorvald, I'd like to ask Mr. Hatch a question. m that diagram, you're got there for the inhalation and th< exhalation, you say the material can be. fractionated to dif ferent parts of the oyele, but ae I remember it, you aaid that the total retention wea about one tenth of a percent up to one percent. BY DOCTOR HATCHt yh ultimate retention. BY DOCTOR OKSSKBURO* Yes, the ultimate retention. How, if the ulti mate retention is one tenth to one percent and the concen tration to which the animal is exposed ie approximately uniform, for any given duration of time, wouldn't the amount retained in the various parts of the cycle be approximately the same in the last an alyaist BY DOCTOR HATCH: W * H # I think somebody who knows more about tbs lungs I do would hare to answer that. The pietura I hare Is that there are - there is relative ease in rentila- j tion of certain parte of the lunge compared with others and you would expect, therefore, over a period of time to find j a disease and, therefore, there would be a higher deposi tion In such areas. Try noTTOB QRgEirBPRQx Ho, that isn't the th1 ng I was talking about; the first t'h'"g I 'm quit* in agreement with. H Y DOCTOR HATCHX Y o u 're speaking about this chart on the right? B Y POCTOB GRggKBURQt That's right. K Y DOCTOR HITCHt This is inhalation-oxhalation-ventilation curve for the lungs. tyy DOCTOR GRgKNBTJRG t Right. How, it seems to me that the retention in all parts of that cycle, in all parts of the Inhalation cycl would be approximately the same. | b y DOCTOR HITCH: |j 11, X was suggesting -- 1 *" 't **X thit ls I so. I ... Just suggsstlng it. YOU say this, tha s o M s c t breathing fifteen respirations a minute, then this is four seconds from hare to here* The average duration of stay of this air in the lungs will approach four seconds. The aver age duration of stay of this air in the lungs will he one second or less* How, the amount that's deposited out of tint *iP is going to be in proportion to the duration of stay in this actively ventilated spaoe so that in certain portions of the lung, favorably receiving this air, then they're going to get more dust* UNIDENTIFIED SPEAKER: Gentlemen, I suggest that you're talking about two different things; he is talking about retention in respiration and you're talking about ultimate retention in tissues after the elimination process* BY DOC?*TM? WATCHt Maybe I'm a little confused* UNIDENTIFIED SPEAKER* You can get particles of this order, magnitude, ac thing of the order or magnitude of two to three microns; you can get upwards of thirty-five or more percentage re tention in the lung during the respiratory cycle. How much you'll find there six months later is a totally different story* BY DOCTOR HATCH: But with respect to that, that average figure is _1.2Z *ade up of higher percentage In the lung and lower per centage In otherB depending on the activity of ventilation< BY DOCTOR VOFWALDt Ted^ are you sure that the first air In Is the lat air out? BY DOCTOR HATCH: I the no at - the best evidence we have on frViafc j.g a paper by Fowler/ remember, down in Pennsylvania, in whioh he determined that was so by the ingenious trick of splitting up the inhalation for a moment and then sud denly completing the exhalation with a mixture, and then he analysed the exhaled air In the same way and then he found that that same mixture going in was found in the air coming out. low, we have some other indirect evidence and we have a little hit of evidence that agrees with Fowler. b y DOCTOE VOPWALDt Doctor Shavert BY DOCTOR SHIVER* Rather than hash what Doctor Solandt had to say, I will Just read part of his summary and conclusions. (Doctor Shavef reads from Doctor Solandt*s paper, which has been filed with the Saranac Laboratory.) j UKID3STIFIED SFSAKSR: - j wanted to ask Doctor Hardy a couple of questions One is what is the longest period of time for treatment of j imai%niriiim munriiw t 12ft*. these patients you hay* referred to? BY DOCTOR HARDY t One recently reported by Kennedy in the Journal of the American Medieal Association, I have continued to treat that same case up until now* UNIDENTIFIED SPEAKERt The second question, one of your patients showed here, looks like a hyper thyroid; is there any indication toxicity stimulates the hyperthyroid, or is it because of hyperacidity of the bonet BY DOCTOR HARDY: We don't know; there has been a lot of speculation Abe at that* W e had two cases of thyroid tumors that sort of disappeared* They had high m* p* r * 's* Ho one every explored their lungs to know. Hypercalcemias were present* Our feeling is that, in some mysterious way, the behavior of beryllium in the body, particularly ita disposition end modus perandi must be related, but at present I have no kntwledge except those early traoer studies of Dootor Hamilton Berkeley, except that when he gave beryllium, the material went in the animals ' body and was in the liver and kidney for a while but it never left the bones for the duration of his study. That's been true in autopsy cases, where beryllium was prosont. Doctor Fuller Albright thinks that the renal calculi apd perhaps the otbsr phenomena that I have i 129. enumerated are related, Just as he thinks they are In sar coidosis to a protean binding, that is protean will bind calcium in certain diseases, but as far as I 'm concerned, that's a description, not an explanation, I don't know. UHIDSKTIFIKD SPEAKER: Vhat is the dosage of your ACTO for that treatment? BY DOCTOR HARDYt Veil, it vary* a great deal. In general, we hare given him 200 milligrams a day, ACTE embodied into fjLf-ky milligrams every six hours, for a few days; then down to a hundred milligrams spread out, then shift to the oral j cortisone, keep him there one or two weeks until you're suro | you have what would be the best possible benefit fras . the symptomatic standpoint, and in various cases, we have tested this by pulmonary function study and cardiac cather- : isation study and than we do what Doctor George Dorn calls titrate the dose, meaning let him go down to the point be low whioh he is still comfortable and then keep him there# I 'm a great deal older than I wae when I talked about this in 1950 and I have patients that have been on 75 milligrams of cortisone, 25 milligrams every eight hours for a year, and I ca n 't see where I 've done any harm, and I've taken symptomatic patients from a complete chair pa tient back to forty hours a day - four hours a day, and 1 this is very impressive even though in all honesty, I don'tj 5 130. t.Mnk X a curing them# UNIDENTIFIED SPEAKERt T>y only reason I 'm asking, Jsrry Kano of Michigan aaens to think that the uss of cortisona may le*d to sporao-r ic sclerosis; I don't know. I BY DOCTOR HAJUfft Well, I think it might easily be true, b u t I think in the case of beryllium poisoning, you have to sort of take the choice and play your cards as you go. BY DOCTOR VOSWALD* Is that a general tendency in cortieone? BY DOCTOR EARDYt Yes, i t 's been my experience in talking with Doc-J tor Max Michel, who has treated very many of these, that you may get brilliant results in treatment of sarcoidosis with jLCTh or cortisone, but as I pointed out in that swift-running survey sunnary. Just given you, I have seen eases of sareoi< dotis that simply will not respond In any way to ACTE and cortisone, and I have seen - I have even seen oases recent ly _two are very fresh in my mind -- that have definitely been made worse, and have proven this by pulmonary function studies and a clinical downhill course of obviously increas ing replacement of the granular tissue. This I have not t seen in beryllium poisoning except for my remarks that one or two cases I have watched appear to be getting, from the ,131* laboratory standpoint, voraa though they're ay ahematic ally better* BY DOCTOR TABRUCK* I'd like to state that our experience in the treatment of chronic beryllium poisoning with cortisone parallels that of Doctor Hardy. We have Been several dose cases under eortisone therapy and we find we have been able to do a great deal for these patients, but we find very def ini tel: we*re not curing anything. W e find the patients go downhill and the boat we can offer them is to give them a more protracted period of disability but a more practical period of disability if you can use that word. In other words, they are sleeping much more orafortably during this period of disability, which becomes longer, but the end results are about the same* I*d like to ask Doctor Hardy what, in her opinion is the setivsting factor in her precipitate mechanism? Is it a matter of true allergy cr is it a matter of physiochamical changes within the system that precipitates the instance of disease in beryllium poisoning? BY DOCTOR HARDYt Well, I see I didn't make myself clear or talked too faat- I think tha beryllium is in the body very often in happy equilibrium, stored for excretion, and than some thing happens to the patient -- maybe it's a respiratory ___________________________________________________________ 132* i 1 tradt infection or this very fascinating business of the i woman having a baby and getting along quite well, and then 1 when the baby is four or five months, she begins to go down* hill in induced weight loss* I have seen this very striking ly, or in unusual exercise, the soldier, you r$aember & Taryj small but definite group, after experience in combat; or I have young girls in cases where, or cases where a laxy 190 pound man went and was put through boot training and lost thirty pounds and he became a clinically active ease of beryllium disease* In fadt, in practically all of the oases in which I have been able to make a good clinical hunt, I have been able to find something that happened to that man or woman after he or she stopped inhaling beryllium or perhaps still is in the situation that Is an added insult or added phys iological burden, that if you like, makes it possible for the beryllium to become pathogenic* 1 suspect you're referring to the very fascinat ing work of the beys, showing that beryllium in the teat tube and in small animals will inhibit magnesia, will take the place of magnesia in certain easyme systems and, by pressing out the phosphatase, eet up a whole chain reaction to to speak, and it's very, very seductive to consider that this may be the means by which to say your response takes place, that later on you'll have fibrosis and so on, symptom 133 producing. The cortisone that la used in test tubes on small animals compared to the human of this particular set up, makes it a little difficult to translate it from the test tube to humans, but there it is possible for later use* I haven't seen any evidence there that the clinieallj active disease is an allergic type of response, al though I think Doctor Sterner has a very good basic broad isdea that may explain a lot of things about goiter respond to toxic insult* not just beryllium, but also infection* BY DOCTOR HATCH: I think at this hour I'd like to call the meeting to a close* and I'd like to make one comment in closing* We have heard* this afternoon* of the action of different dust< in the lungs* the relative importance of different factors in the dust* that go to determine the nature and magnitude cf the action* Tory illuminating* I believe* in the light of this morning's discussion in which wo had great difficulty in arriving at definitions to a high degree because there w4re so many gaps in our knowledge* I should like to leave with you this thought, will the day ever come when we will be able to anticipate difficulties associated with the inhala tion of particulate matter and not have to wait until the difficulty has developed before becoming concerned with it* I It's going to the question or the degree of which we can re+ due o our understanding to the fundamentalities* the common j ----- ---------------- ------------------------------------------------*---------------!I--- ______________________________________________________ denominators that go to make up the problem, whether It's the problem of asbestos or bauxite or whatever, to what ever degree we can meet those fundamentals and extract out I. VI) of them a common denominator* ! Is It going to be possible for us to anticipate and predict, from basic studies of new dusts, the possi bility of toxic infection? I, for one, would be pretty discouraged if I thought that day would never come* I don't want to suggest that one day we'll be able to explain everything, but I certainly hope we will be able to do a better Job than we have in the past in anticipating this trouble* I The other comment I want to make Is one I think Doctor Pletcher spoke in particular about this morning, the; in cur Tinderstanding of these problems we h&Te to depend as 8 much on epidemiological findings from the field as we do an the findings from the laboratory. One compliments and sup plements the other* i I think, with that, we'll call the afternoon !i meeting to a close* n -oO ol| (Session adjourned at $tl\S P* M.)* II!' f REPORTER'S NOTE: Throughout the transcript, unless names were specifically spelled at the time given, all proper names will be subject to change or correction* ________ ^ T