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#56 ?t> 539 iroved ies of :09-]21 'ietary ibosis, (at. J ardial ential (Feb) e Inand 95-402 W.S.: Path etlen, icient arch) The n the ;7-170 ader, m of ale J s 1-460 the une) -dio4rch tarv Fat ient Pulmonary Ferruginous Bodies Development in Response to Filamentous Dusts and a Method of Isolation and Concentration Paul Cross, MD; and Robert T. P. deTreville, MD, DSe, Pittsburgh; Lewis J. Cralley, PhD, Cincinnati; and J. M. C. Davis, PhD, Cambridge, England Formation of ferruginous bodies should not be confused with pathogenicity. Failure to un derstand this differentiation may result in the erroneous generalization that all fibrous dusts share the ability of abestos to produce lung damage. Such materials as fibrous aluminum silicate, silicon carbide whiskers, cosmetic talc, and glass fibers produce ferruginous bodies experimentally which are indistinguishable from those produced by asbestos fibers. A method of isolation and concentration of fer ruginous bodies from lungs of animals and humans is described. Ferruginous bodies from asbestos fibers are much more pleomorphic than has generally been described, casting further doubt on morphological distinctions used in the past in separating so-called as bestos bodies from pseudoasbestos bodies. WcORLDWIDE attention was refo cused on ferruginous bodies by the publi cation of Thomson,1 who found this phenomenon in the lungs of more than 30 % of unselected autopsied adult hospital patients in Capetown, South Africa. A similar percentage was noted in Miami,2 43% in Pittsburgh,3 and 48% in Mon treal.4 The higher percentages reported in Pittsburgh and Montreal are possibly inherent in the more intensive searches Accepted for publication on Oct 17, 1967. From the Industrial Hygiene Foundation, Pitts burgh (Dr. Gross and Dr. deTreville); the National Center for Urban and Industrial Health (Dr. Cral ley) ; and the Department of Pathology, British Asbestosis Research Council, University of Cam bridge, Cambridge, England (Dr. Davis). Reprint requests to the Industrial Hygiene Foun dation, 4400 Fifth Ave, Pittsburgh 15213 (Dr. Gross). carried out in these cities. These bodies are similar to asbestos bodies, though the natures of the central fibers have not been identified. Asbestos bodies are golden-brown, ferro-coated formations found in the lungs of persons who have inhaled asbestos dust. They are generally described as sym metrical, segmented structures, usually with clubbed ends, 3p to 5;t in diameter and 20p to 50p long. TTie core is composed of a transparent colorless asbestos fiber that is not always demonstrable. Apparently the only difference between an asbestos body and a pseudoasbestos body is that in the former, the central fi ber is composed of asbestos, and in the latter, of material other than asbestos. Since asbestos-like bodies can form in response to respirable, transparent, color less fibers deposited in the lungs and com posed of materials other than asbestos; and since basing classification of these structures upon identification of the cen tral fiber presents difficulties, a generic term, "ferruginous," has been proposed for all bodies formed in response to the presence (in body tissues) of a broad spectrum of fibers, including asbestos. Davis 5 and Collet (according to a letter in June 1966) demonstrated with the elec tron microscope that ferruginous bodies are formed within macrophages by gran ules of ferritin or a ferritin-like protein Arch Path--Vol 85, May 1968 I re :: I I f, i' 1: - it 540 FERRUGINOUS BODIES--GROSS ET AL do not result in the forma tion of ferruginous bodies .when inhaled. Respirable fibers, how ever, are apparently ubiq uitous.0 They may be mineral, animal, or vege table in nature and of either natural or synthetic origin. They are dissemi nated by industrial proces sing, community activities, personal habits, and the action of natural forces. Fig 1.--Asbestos bodies from the lung of an asbestos worker to illustrate some of the more simple forms that may be found. In addition to some apparently naked fibers, there are pale, nonsegmented, rodlike bodies with bipolar clubbing. The dust was probably chrysotile (concentration method; smear; unstained; X 1.100). Also, we have recently re ported experimental pro duction of ferruginous bodies with ceramic fi bers of aluminum silicate. that are precipitated upon and around These bodies were indistinguishable by some foreign materials. light microscope from many of those iso An asbestos body, therefore, is only one lated from an asbestotic lung of a known kind of ferruginous body; one in which asbestos worker7 (Fig 1). Although non the central filament is an asbestos fiber. segmented, they were golden-yellow, sym As will be seen later, the appearance and metrical, clubbed bodies, staining deep dimensions of these bodies are so varied blue with Peris' test and exhibiting a as to defy the reasonably short description central transparent filament. usually employed. The present paper discusses our further The problem now confronting investi findings as follows: gators concerns the significance of the 1. --Ferruginous bodies are developed in widespread finding of ferruginous bodies the lungs of hamsters in response to the in the lungs of urban population groups. presence of "biologically inert" filament The solution of the problem is, of course, ous aluminum silicate, glass, and silicon linked to the identity of the central fiber carbide particles. about which the ferruginous body forms and which is at present unknown. It is hoped that recent analytical advances, such as electron diffraction and micro probe will provide techniques for defini tive identification of the central fiber. 2. --A simple method is given for isolat ing ferruginous bodies and bare fibers (including asbestos bodies) from lungs. The method is given in detail and the re sults obtained are described briefly. Up to this point, the identification of ferruginous bodies in the lungs of un selected autopsied hospital patients as as bestos bodies1 has been based on the hypothesis that transparent fibers of re spirable size composed of materials other than asbestos either are not encountered in industrial and community environ ments, are not deposited in the lungs, or The Production of Ferruginous Bodies Groups of 12 hamsters each were in jected intratracheally with 3.5 mg of fibers contained in 0.5 ml of aqueous suspen sions. This was done under light ether anesthesia with the aid of an illuminated, self-retaining speculum that made the vo cal chords visible and allowed the inser- Arch Path--Vol 85, May 1968 ? frrmas es s, howIv ubiqiay be r vegeand of .'nthetic lissemiprocestivities, md the forces, ntly re al proJginous mic fisilicate. ble by Dse isoknown ;h nonv, sym? deep iti . further sped in to the amentsilicon isolatfibers lungs, the re- todies re in fibers jspenether nated, he voinser- FERRUGINOUS BODIES--GROSS ET Ah 541 tion of a long 18-gauge needle between the vocal chords under direct observation. All of the following were injected: 1. Ceramic aluminum silicate fibers. This is an uncoated ceramic fiber with a median diameter of 2p. Fifty percent of the fibers were under 75p in length, and many filaments were shorter than 15p. No free silica was detected in the fibers. 2. Silicon carbide whiskers. These were 99.5+% SiC. Fiber diameter ranged from 0.5p to 3p, and fiber length that ranged from lOOp to 750p. 3. Glass fibers, uncoated. The fibers had a mean diameter of 0.4fj and a mean length of 4.4p. 4. Cosmetic talc. Fifty percent of the fibrous material in the talc was under 0.2p in diameter and lp in length. 5. Attapulgite (fibrous clay mineral). Fifty percent of the fibers were under O.lp in diameter and lp in length. 6. Chrysotile (95% of the asbestos used on this continent is chrysotile). Most of the fibers were of ultramicroscopic di mensions. Isolation and Concentration of Ferruginous Bodies Samples of lung tissue cut into thin strips 3 to 4 mm thick, or fragments about 0.5 cc in volume, are placed in clean glass or plastic containers. To the tissue is added about 20 times the tissue volume of commercial 5% sodium hypochlorite solution. This is allowed to stand undis turbed at room temperature for several hours until all chemical action has ceased. More hypochlorite solution is then added at frequent intervals until the tissue has been digested. For small lungs, such as those of rats and guinea pigs, the frequency and amount of addition of fresh hypochlorite solution should be such that all lung tissue is digested in approximately 24 hours. For human lungs, unless quantitative recovery of ferruginous bodies is desired, complete digestion is not necessary. In the case of human lungs, the fer ruginous bodies and bare fibers are often associated with a sticky lipidic film ad herent to the bottom of the container. The stickiness allows one to pour off all the fluid and undigested lung tissue without loss of the bodies and fibers. Because of the presence of anthracotic pigment, the film is usually gray in color. The film is dissolved by vigorously washing with a mixture of one volume of chloroform and two volumes of approximately 50% ethyl alcohol; the total volume should be the minimal amount needed to remove all the film. The wash fluid is centrifuged at 2,000 rpm for about five minutes. Because of their high specific gravity, the fer ruginous bodies and the insoluble mineral particles settle to the bottom of the tube. On the other hand, most of the carbonace ous material collects at the interphase be tween the chloroform and the aqueous alcohol. If too much alcohol is used, the carbonaceous material will lose some of the water that lowers its specific gravity. As a result, there will be no separation between the anthracotic material and the ferruginous bodies. In such cases, rehy dration followed by the addition of chloro form will usually effect a good separation. All of the fluid and the carbonaceous, more viscid material above the sediment at the bottom of the tube are discarded, and the walls of the tube are cleaned of the adherent anthracotic material. The sediment is washed several times with water to remove all hypochlorite and other water-soluble materials. It is then stored in an aqueous or alcoholic medium. When smears are made of the suspen sions, it may be advisable to dehydrate the smear and use a mounting medium to render much of the mineral dust associ ated with the ferruginous bodies less con spicuous. The naked fibers remain visible. In the case of small animal lungs, chloroform and the supernatant fluid were poured into centrifuge tubes in a propor tion of 1:2. After centrifuging, the super natant fluid was carefully removed and discarded except for about 1 ml left un Arch Path--Vol 85, May 1968 542 FERRUGINOUS BODIES--GROSS ET AL disturbed on the bottom. The film on the from an asbestotic lung of a worker bottom of the original container in which known to have been exposed to chrysotile the lung tissue was digested was then re asbestos dust for 30 years (Fig 1). moved, as in the case of human lungs. This The ferruginous bodies that formed in fluid was added to a pool of whatever response to chrysotile asbestos were sediment was obtained from the super smaller than those that formed in response natant fluid. The subsequent procedure to aluminum silicate and glass, and also was the same as with human lungs. different from the latter two in being seg We have worked with formalin-fixed mented (Fig 4 bottom left). The ferrugin tissue only, but there appears to be no ous bodies were more readily found in the reason why this method should not work lung sections of hamsters injected with equally well with fresh lung tissue. aluminum silicate filaments than in lung sections of animals injected with filament Results ~ ous glass or chrysotile dust. No ferrugin Paraffin Sections.--Initially the fer ruginous bodies were sought only in paraffin sections that had been stained with hematoxylin and eosin or Peris' test ous bodies were found in the lung sections of hamsters injected with silicon carbide filaments at this time (one month after the injection). for iron. Because of the paucity and small Examination of lung sections of ham size of these bodies in the sections, the sters killed six months after the intra hematoxylin made the search more diffi tracheal injection of the filamentous dusts cult. Subsequently, replicate sections that revealed no more ferruginous bodies than were given the Peris' test only, or also were encountered five months earlier. No lightly counterstained with eosin and segmented forms were found except in cleared, proved to be satisfactory. association with chrysotile dust. No fer The injected fibers generally were con fined to the air spaces, where they were associated with free macrophages. Some of the filaments passed through the bodies of one to three, and even four, macro phages so that these cells appeared to be impaled as though upon a spit (Fig 3 bot tom left). When the sections had been stained for iron, the dust-containing areas, under low magnification, were usually marked by a granular deep blue colora ruginous bodies were seen in lung sec tions of hamsters injected with silicon carbide. Dust-containing alveoli found in sections of lung from a hamster injected with talc were easily identified because of the blue coloration caused by the pres ence of iron; however, ferruginous bodies could not be identified. Similarly, no ferruginous bodies were found in lung sections from hamsters injected intra tracheally with attapulgite. tion. Lung Digests.--The smears of the sedi In sections of lungs of hamsters killed ment derived from the digestion of the one month after an intratracheal injection lungs from hamsters injected six months of aluminum silicate and glass fibers, oc previously with aluminum silicate, glass, casional ferruginous bodies were found. and chrysotile, respectively, consisted These were non-segmented, light-yellow largely of naked filaments, but many fer structures with bipolar clubbing and a ruginous bodies were also seen. Although transparent central filament (Fig 2 top most of the ferruginous bodies that had left, and 3 top left). These, subsequent to formed in response to aluminum silicate the Peris' test, took on a deep blue color and glass fibers were non-segmented, a that often obscured the central filament. number of segmented forms were also Very similar non-segmented bodies were found (Fig 2 top right, bottom left, bottom seen in suspensions of isolated and con right; and 3 top right, bottom left, bottom centrated human asbestos bodies derived right). A more prolonged search of the Arch Path--Vo! 85, May 1968 FERRUGINOUS BOD1ES-CROSS ET AL 543 sediment from lungs of hamsters injected with silicon carbide was necessary before several ferruginous bodies could be found. This search was facilitated by applying peris' test for iron to the smear. The bod ies were mostly nonsegmented, and except for the clubbed ends, the coating on the filaments was thin. One silicon carbide fiber was found with a club-shaped coat ing at one end, a fusiform coating near the other end, and a very slight thicken ing near the middle (Fig 4 top left). Two segmented ferruginous bodies that had formed around silicon carbide fibers were observed. Unfortunately, the diffusion of the blue pigment of the body rendered its outline indistinct (Fig 4 top right). The sediment from a hamster lung in jected with talc was composed largely of crystalline plates; but upon careful search, a number of non-segmented ferruginous bodies were also found. These too had a transparent central filament (Fig 2 top left, and 3 top left). The Prussian blue re action for iron had also been used in this smear, and the outlines of these bodies were indistinct because of the diffusion of the pigment (Fig 4 bottom left). Unexpectedly, ferruginous bodies were more difficult to find in lung sections after chrysotile injections than after aluminum silicate injections. The same finding was observed with the concentration method. Although few in number, all asbestos bod ies were segmented (Fig 4 bottom right). One of the most interesting observations was that, when stained for iron, filaments that passed through the bodies of one or more macrophages showed a coating of ferritin or ferritin-like material only on the intracellular portions of the filament (Fig 3 bottom left). The sediments from the lungs of ham sters injected with attapulgite revealed no ferruginous bodies. The failure to find ferruginous bodies in these sediments may be interpreted as a negative control to indicate that our positive findings were not attributable to the accidental inhala tion of fibers in the ambient laboratory air. . The sediment from the human asbestotic lung was a rusty, red-brown color. In the smear, a wide variety of asbestos bodies were seen in addition to innumer able naked fibers. As previously indicated, a large number of the asbestos bodies were pale, thin, and nonsegmented. Also of interest was the fact that many of the largest bodies did not have smooth sur faces, but were spiculated. The spicules Fig 2.--Ferruginous bodies formed in response to aluminum silicate filaments In a hamster killed five months after an Intratracheal Injection of 3.S mg of the dust. Bottom right, naked filament (concentration method; unstained smear; x 1,100). L--J . lO^L Arch Path--Vol 85, May 1968 544 FERRUGINOUS BODIES--GROSS ET AL were often coarse with squared ends. A few of the bodies lacked symmetry. Some pear-shaped bodies without a central fila ment were also seen. Although most of the bodies were more or less rectilinear, many curvilinear forms were also present. Some of the latter appeared to measure between 180 to 270". In the larger spiculated forms, the central fiber was often obscured by the thick, dense, red-brown coating. Some of the very long thin fibers (50|i to lOOp) often had segments of ferro- Fig 3.--Ferruginous bodies formed in response to rilamentous glass dust. Bodies (top, left and right, and bottom right) are unstained. Four macrophages are faintly outlined. Only the intracellular portions of the filament are coated with iron (Peris' stain, x 1,100). protein at either end with relatively long stretches of naked fiber in between. In an attempt to free asbestos bodies from adherent fine carbon particles in an otherwise "clean" suspension, it was sub jected to ultrasonic vibrations for a few seconds. Unexpectedly, only naked fibers remained, and no asbestos bodies could be found in the suspending fluid. The distinction heretofore made be tween asbestos bodies and pseudo-asbestos bodies may have been based in part on what the observer believed to be an ap pearance consistent or inconsistent with that of asbestos bodies. More often, how ever, this distinction was based on the observer's knowledge that the host had or had not been exposed to respirable asbestos fibers. Regardless of the nature of the central fiber, the bodies that result in response to the presence of filamentous dust in the lung have as a common feature a coating of iron-containing protein (ferritin or fer ritin-like). Furthermore, it appears, from a study of the pleomorphism of human asbestos bodies, which was so well illus trated by Gloyne and Merewether,8 that differences in size, segmentation, or other morphologic features of the ferruginous coating probably would not serve to dis tinguish between ferruginous bodies of asbestotic origin and those of nonasbestotic origin. Thomson has proposed to differentiate between asbestotic and nonasbestotic fer ruginous bodies on the basis of the trans parency or opacity of the central fiber.2 This proposal seems inappropriate, inas much as we have demonstrated that a number of transparent fibers of respirable size other than asbestos are capable of producing ferruginous bodies that are in distinguishable from those produced by asbestos. At any rate, it is obvious from the pro * t . duction of ferruginous bodies in hamsters in response to respirable, colorless, trans parent filaments of aluminum silicate, glass, and silicon carbide, that such bodies Arch Path--Vol 85, May 1968 ly long r ts~ -les s in an as sub- a few I fibers could de besbestos >art on an apit with i, howon the st had pirable :entral >nse to in the -oating or fer, from mman i' i--i other ginous to disies of asbes- ntiate ic fertransfiber.2 inashat a irable ole of re in?d by i pronsters translicate, xodies EERRUG1N0VS BODIES--GROSS ET AL $45 represent a general reaction to filamentous particles and are not a specific reaction to asbestos fibers. To what extent our find ings may have application to the fer ruginous bodies that are being found with increasing prevalence in human lungs 1-4 remains to be determined. The applicabil ity depends, of course, upon the identity of the central fiber in the ferruginous bodies. The method of isolation and concentration of uncoated fibers and ferruginous bodies from human lungs which is described in this paper may help in the study of the nature, identity, and prevalence of inhaled filamentous particles and associated pul monary ferruginous bodies. It is highly probable that the composi tion of the ferruginous body is altered by the method used for isolating it, since it is not likely that with the destruction of proteins leading to the liquefaction of all tissue elements in the lung, the protein in the ferruginous bodies should be spared. In all likelihood, the protein constituent of the bodies is destroyed, and only the iron and other inorganic components re main to retain and maintain the form of the bodies. The fragility of this chemically altered ferruginous coating is indicated by the ease with which it is removed when subjected to ultrasonic vibrations, thereby rendering the central fiber naked. This may further facilitate the identification of these fibers. There appears an increasing tendency to consider all filamentous dusts in the same category as asbestos with regard to their pathogenic potential. This reasoning is probably based on a mechanistic con cept of the pathogenicity of fibrous dust in general, and asbestos dust in particular. Such a mechanistic concept holds that the pulmonary fibrosis in asbestosis is the tis sue response to mechanical trauma pro duced when pulmonary cells are perfor ated or impaled by the fine points of the asbestos fibers. It need only be recalled that a similar mechanistic concept of the pathogenicity of crystalline silica was abandoned many years ago because of overwhelming evi dence against its validity. Just as the proven biologic "inertness" of diamond dust was the coup de grace for the mecha nistic pathogenetic concept of silicosis, so should the proven biologic "inertness" of filamentous aluminum silicate 10 have dis credited the mechanistic pathogenetic con cept of asbestosis. Extremely thin flakes of glass may also be considered to have sharp cutting edges; yet, glass has also been found biologically Fig 4.--Ferruginous bodies formed in response to other filamentous dusts and stained for iron (Peris' test). The central Fiber (top, left and right) is silicon carbide; and (bottom left) tremolite (talc) (x 1.110). Arch Path--Vol 85, May 1968 546 FERRUGINOUS BODIES--GROSS ET AL "inert" when inhaled or injected into the lungs of animals. Silicon carbide is noted for its hardness, sharp edges, and points, which make it an ideal abrasive. When inhaled as a fine dust or injected intra tracheally, it has caused a pulmonary re sponse likewise classified as biologically "inert." "-12 Gaining increased attention is a newer concept that the potential of extraneous trace metals and other materials associ ated with fibrous minerals can cause the injury previously attributed to fibers. The respirable fibers may provide a transport mechanism for dosing tissues with injuri ous materials associated with the fibers. Cralley et al11 have shown that asbestos textile workers in the past have been ex posed to appreciable concentrations of nickel, chromium, and manganese associ ated with the fibrous mineral, and abraded from the alloy metal in asbestos process ing equipment. They state further that there is evidence that this phenomenon exists in relation to a number of other fi brous minerals. There is also some indi cation that the biological response in the formation of ferruginous bodies may be related to the naturfe and extent of the layer of metal solute surrounding the fi ber. Additional research needed in these areas is currently underway. Unless the above facts are kept in mind, the finding that ferruginous bodies are formed in response to aluminum silicate, silicon carbide, and glass filaments in the lungs, may be used as still another reason for erroneously classifying these dusts with asbestos in their ability to produce lung damage. This investigation was sponsored by JohnsManville Corporation, New York, and supported in part by Public Health Service research grant UI 86-66-156 from the National Center for Urban and Industrial Health. All experimental materials used, except chrysotile (supplied by Johns-Manville Corporation, New York) were obtained from and analyzed by the US Department of Health, Education and Welfare, Public Health Service Center for Urban and In dustrial Affairs, Occupational Health Program. References 1. Thomson, J.G.; Kaschula, R.O.C.; and Mac Donald, R.R.: Asbestos as a Modem Urban Hazard, S Afr Med J 37:77-81 (Jan) 1963. 2. Thomson, J.G.; Path, F.C.; and Graves, WM.: Asbestos as an Urban Air Contaminant, Arch Path 81:458-464 (May) 1966. 3. Cauna, D.;-Totten, RE.; and Gross, P.: As bestos Bodies in Human Lungs at Autopsy, JAMA 192:371-373 (May) 1965. 4. Anjilvel, L., and Thurlbeck, WM.: The Inci dence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal, Caned Med Assoc J 95: 1179-1182. 1966. 5. Davis, JM.G.: Electron-Microscope Studies of Asbestosis in Man and Animals, Ann NY Acad Set 132:98-111, 1965. 6. Cralley, LJ., et al: Source and Identification of Respirable Fibers, read before the annual meet ing of American Industrial Hygiene Conference, Chicago, May 1967, JAIHA, to be published. 7. Gross, P.; Cralley, LJ.; and deTreville, R.T.P.: "Asbestos" Bodies: Their Nonspecificity, JAIHA 28:541-542 (Nov-Dec) 1967. 8. Gloyne, S.R, and Merewether, E.RA.: "As bestos," International Labour Office Supplement, p 7 (Jan) 1938. 9. King, EJ.; Yoganathan, M.; and Nagelschmidt, G.: The Effect of Diamond Dust Alone and Mixed With Quartz on the Lungs of Rats, Brit J Industr Med 15:92-95, 1958. 10. Gross, P,, et al: The Effect of a Synthetic Ceramic Fiber Dust upon the Lungs of Rats, Arch Induet Health 13:161-166 (Feb) 1956. 11. Gardner, L.U.: Studies on the Relation of Mineral Dusts to Tuberculosis, Part II: The Rela tively Early Lesions in Experimental Pneumoconio sis Produced by Carborundum Inhalation and Their Influence on Tuberculosis, Am Rev Tuberc 7:344, 1923. 12. Gross, P.; Westrick, ML.; and McNemey, J. M.: Experimental Tuberculopneumoconiosis, Arch Induet Health 19:320-334 (March) 1959. 13. Cralley, LJ.; Keenan, R.G.; and Lynch, J.R.: Exposure to Metals in the Manufacture of Asbestos Textile Products, read before the annual meeting of American Industrial Hygiene Conference, Chicago, May 1967, JAIHA 28:452-461 (Sept-Oct) 1967. Arch Path--Vol 85, May 1968 NATURE. VOL 217. JANUARY 13. 1963 improved". It uppears that if the regulations are more widely und mure stringently applied than at present, the number of cases should inevitably fall. The panel indicates that crocidolite lias a special .njficanee in relation to mesothelial tumours. It recommends that other types of fibre should be sub stituted for crocidolite wherever possible, and, where this is impossible, special precautions should be taken to reduce the risks of inhaling the material. The panel admits that at the moment the level of exposure below which the risk may be negligible is not known. The quantity of crocidolite (blue asbestos) imported into the country is much less than the other varieties of asbestos, and it has remained at about 7,000 tons per year for the last few years. But time may show that other fibres are also implicated in the development of mesothelial tumours. Finally, the report suggests that action should be taken to control the discharge of dust-laden air from asbestos factories and the dispersal of dust from waste dumps. It emphasizes, however, that the problem of mesothelioma in association with asbestos exposure should be kept in a proper perspective. Even though the incidence is increasing, the total number of cases of mesothelioma in Britain over several years is very small when compared with the annual total of deaths from cancers of the trachea, bronchus and lung. 121 * PLAINTIFF Recording Weather An automatic weather recording station which can operate unmanned for at least three months has been produced by the Plessey Company Ltd. This station, binary code on standard quarter-inch magnetic tape. It samples at intervals of 5, 10, 20, 30 or 60 minutes and is accurate to within 0-1 per cent. hich can make and record more than 82,500 measure- enta in a three month period, is available from the Discomforts of Space . Marine Systems Division of the Plessey Electronics Group at Ilford. The value of automatic weather by Angela Croome stations was recognized by a recent report from the The next moves in manned spaceflight may be uncer World Meteorological Organization (Nature, 215, 1324 : tain, but in both the United States and the USSR, 1967). They are important because modern develop background experiments for the longer flights of the ments in weather forecasting require information about future are going ahead. This month the McDonnell climate from all over the world--sometimes from un Douglas Corporation of California, contractors to the inhabited areas--and it is becoming increasingly Office of Advanced Research and Technology of NASA hard to persuade amateur meteorologists to provide (National Aeronautics and Space Administration), is accurate data day by day. Professionals cost money, to start on a two-month-long test of a closed system and so there should be a real market for automatic space chamber. The Soviet Union has recently com stations which can do the job reliably for long periods pleted a 70-day confinement experiment involving without attention. three men. American and Soviet trials have relevance The Plessey station is virtually self-contained and both for survival in space and for the operation of can monitor parameters such as rainfall, humidity, manned submersiblcs under the sea.' . wind speed and direction, air, soil and water tempera In the case of the American closed life-support trial, tures, barometric pressure, pH, solar radiation and four college students of the University of the City of water level and flow . The basic design was evolved in Los Angeles arc acting as experimental subjects. For co-operation with the British Water Resources Board, a period of CO days, they will exist on reclaimed water the Meteorological Office and the. National Physical and oxygen from their own metabolic wastes. The Laboratory. By adding various instruments to the test is believed to be the longest so far attempted under basic design, it has been possible to produce a family flight conditions using a closed water-oxygen loop. of stations including hydrometeorological, climato The closed water system consists of an evaporation logical, water level, water quality and recording rainfall unit, a charcoal filter and a condenser that reclaims stations. Each can be arranged for automatic opera moisture directly from the. crew and from the air in tion, and the recorded data can he sent by telemetry the cabin. Oxygen will be reclaimed through a process to a control centre on demand. of mixing hydrogen and carbon dioxide and then Each station is supplied as a complete system with converting them to water and methane gas. The 'nsors, recorder, power supply, `Stevenson' screens oxygen is recovered from the water by electrolysis id a stayed aluminium mast which supports the sen and the methane gas is expelled. Atmospheric pressure sors. The memory of the station samples up to eight w ithin the cabin will be nf 7 p.s i. (half that at sea- sensors in turn, recording their outputs in ten-hit level) and will consist of 3-1 p. i./oxygen and 3-9 : I | | ' NAT UK: . . I'd. .'1 7. .1ANl` Af, V 13. 190 V p.s.i./nitroll'll. Tin- simulation of space comlitions II11111 -- I I \ III lil.|...i'\ tin| i ] 11-11 .il it \ | of t) will not, of course, 1 >o complete, for tlie trial will take* ( >1 11 r i i > i . i, t \ i \ \\ .. - | -1' - - 1 I I > I M On V \ .. I ( I It in* t place on the ground where both men and .system will till' \| 111 ] - I l I . I I 111'I : I; _ .i I n I I " i I *........... I II' .1 111 . ( I VC operate under normal gravity. ;i II ' \ | I !! l! ' M e ' 1 "I 111-' t bi \ .1 1 .i - i .'. t 7 l " " I .11 it it Tlie Soviet e.\|* riment lias already taken place uni Ontilol which wo. i. lot' i'll I a 11 \ i 111 ii - fra: and lasted the full jieriod of 70 days during which a sa li i.I 111.i j i- .111< 1 It- ::i ;. . 1! ri ^ hi l .v 11- !>, lent medical doctor, an engineer and a journalist- remained e\ ft . t it, I. w ,i- ti 1.; I!: i i !! in '! ......... 1 I "t t'li | <, w liicl shut, up together under cramped and uncomfortable tin' report -negests. i~ t:..titiK 111 to tin ib Jot mi nt ( conditions. The exact dimensions of the isolation ilUi -Inn 111 in <lr\t I. lit b. Inf' ill n: nit J 111 S ( chamber are not given, hut it is described as small. (lie t. oi nt i v a - ;i tV'it't nf On < .'i.t i iiiiiji nt ~ i ii it mi i All three subjects were thoroughly instrumented for measures, together with an im iv.i-r in tin- price e the measurement of their physical condition during nia]is at ccrf a ill scab-s. t b i M.i t eh.'0 . I be 1 < <t a! nil mlie the test. Their regime was to fulfil a daily routine of of staff ua .1.00(1 ii* 'H - iic 111 -t ri.'i! .and indiistrin work, eating, sleep and medical examination up till compared with -J,0<IS fid .Tin a m at-r.u bef a \igiTOU: about the halfway stage when they switched to a "free" recruiting jd ogr.itnnic btingntg in some Isii new staff [routine, doing as they pleased. The journalist of the Servev of the principal town .iten- on tin- scale o PLAINTIFF'S EXHIBIT 1552(3) roup recorded reactions in Ins log at the end of the 1 : 1,250 is said in tin- n :<>rt to be muring c.mplctior. rst three weeks: "Watch-keeping, dinner, medical and revision of the old 1 ' 2.7011 plans covering tninoi lamination, sleep--our life has acquired a feverish towns and rural art as has been speeded up. largely hough monotonous rhj'thm. There is almost no free through tin- jiictvasod use of aerial photographs ime left. But we are already beginning to feci Instead of the five-year re-levelling programme which xhausted. Stanislav [the doctor] is getting tliinner, was originally aimed at. subsidence areas will ! levelled here is a stubble of beard on his cheeks and dark on a tw-cnty.ye.ir cycle as in normal areas. 'rings under his eyes. Leonard's eyes have become red and anxious. I cannot escape the feeling that some pungent fog is creeping into our tiny room. While gradually poisoning our brains, it makes us more intolerant towards one another". But during the later period when there was no set routine, things 6ecmed even worse. There was no longer a work schedule, but the men could pass the time as they chose--playing chess, reading or presumably sleeping. (Food preparation did not amount to much of a task as their diet was a typical space diet of dehydrates, concentrates, and tinned foods.) Now, they reported, time passed more slowly and nervous tension increased. Sleep was troubled and they had hallucinations of sound. They dreamt of music, singing and the noise of aircraft. None the less, no member of the group "deviated from the programme or complained"--complaint presumably being defined as a request for release from the experiment. The experi-. menter in charge comments that the trial was above all a test of character and willpower, but much useful information was gleaned. Mapping in Metric Units One organization faced with a formidable task in changing to metric units is the Ordnance Survey. Among proposals which have so "far been endorsed by the Joint Standing Committee in accomplishing this task are that heights will be shown in metres instead of feet on new and revised maps at 1 : 1,250 and 1 : 2,500 scales. Areas will be shown in hectares instead of acres on maps at 1 :2,500 scale. Heights will be given in metre.s instead of feet on bench mark lists prepared from new' levelling. Contours will be shown at a metric interval on new six-inch maps. Finally, the problems of changing the six-inch and one-inch maps to "rational" scales such as 1 : 10,000 and 1 : 50,000 will be reviewed. These proposals were circulated to 180 interested bodies, representing all classes of map users. *m According to the annual report of the. Survey for 1900-07 (1IMSO, 7*. 0d.), in which these facts arc published, the past year was marked hy a change of The Institute of I'hy.-ies and the Physical Society hopes that this symbol, when correctlv placed on a red ground, will soon li-coinr familiar to ativotie who has any neijtiamtunee with phv'ics. The st.nibol has been designed to aecomp.iny all kinds o| information produced in connexion with the fuirdav I'bvsica Exhibition opening at the Alexandra I'alaee'on .March 11. It is based oil the u ight diagram fit the irreducible representation />" (Ml of the St'(It) symmetry which has been sueei--ful in I.tinging order to tin- !..> idea tion of subatomic p.i rt it Its. Mr I). Walter, who is organizing Ibe exhibition, first tbougbl of bi-ing the symbol on St (it) syin' i'lry and. afli r aiKiee from blip i i.-il ('i.lleee, flu- * f t:* 1 i e| in-i nt .it i. ,ti a drawn 1a Ml M If I'te loll of lilt' t-e|i ne. Mu'-ettm