STATISTICS AND EPIDEMIOLOGY
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427 doses produced pulmonary oedema and bronchopneu- monia. In view of idiosyncrasy, it is never possible to establish a safe concentration for man, but it is usually assumed that 70 parts per million would be the upper safety limit for short exposures and 50 parts per million for exposures lasting over eight hours. Once poisoning has occurred, treatment, apart from removing the patient from exposure, is of little value ; therefore attention should be directed to preventive measures. Methyl bromide is capable of passing a Service gas mask in a quarter of an hour, and Clarke, Roworth, and Holling 11 therefore suggested that a pungent substance should be added to draw attention to its presence ; Viner 8 mentioned that it can be mixed with 20% carbon tetrachloride, but phosgene may then be formed when the mixture is put on a fire. Fire-fighters should be warned against spilling the substance on their clothing and instructed that clothing wetted with it must be removed immediately. Ships, storehouses, and barns must be thoroughly ventilated after it has been used for fumigation. Prevention of leaks, adequate dilution of escaping gas, and exhaust ventilation through the floor of the workshop are the most important preventive measures in industry. Bathing the hands in a weak solution of sodium carbonate may help to prevent skin lesions by decomposing the methyl bromide. Periodic medical examination will not only detect early symptoms but draw attention to dangerous mechanical parts and lead to their repair before serious trouble has arisen. STATISTICS AND EPIDEMIOLOGY AT a meeting of the Royal Statistical Society on Feb. 27, Dr. Major Greenwood, F.R.S., emeritus professor of vital statistics and epidemiology at the London School of Hygiene and Tropical Medicine, discussed the part which statistical methods could play in the study of epidemic disease. After referring to the history of ideas on the nature and mode of spread of epidemics, he gave a neat example of the fitting of an algebraic structure to the hypothesis of the patient-to-patient transmission of measles. A cynic, as Professor Greenwood noted, might observe that the mathematical ingenuity of his proof was rather wasted on the verification of a result which should be self-evident to any mother with more than two children. On the other hand, the epidemic nature of influenza was not self-evident even to so distinguished a medical historian as Hirsch writing little more than 60 years ago. Truth, as Pontius Pilate inferred, is relative, and proof in the strict sense is seldom possible in the biological sciences. The value of statistical methods seems to lie in the rigorous testing of a hypo- thesis-it deals not with absolute proofs but with relative likelihoods. In,practice, Professor Greenwood suggested, the methods which seemed almost superfluous when applied to measles can be profitably used in the study of such baftling problems as the spread of epidemic polio- myelitis. Essentially, these methods consist in an analysis of the time intervals between successive cases and a study of the departures of these intervals from a purely chance variability-a problem of some mathematical complexity. Much has been done by medical statisticians in an effort to uncover the " laws " of the waxing and waning of epidemics. The explosive outburst of a food-borne disease is evident in the skewed shape of the epidemic curve which results from the sudden initial rise in the number of cases. Conversely, the more even rise and fall of an influenza epidemic is indicative of its airborne spread from person to person. Farr, Brownlee, Ross, and McKendrick have all tried to generalise in mathe- matical form the rise and fall of epidemic disease. Ross and McKendrick have stressed the effects of the influx of non-immunes into the herd and the development of herd immunity. Brownlee, from the statistical character- istics of the epidemic curve, suggested a possible waning of the invasive power of the infecting organism itself from the very start of the epidemic. Epidemics, in fact, did not decline only because all the susceptible had either succumbed or acquired immunity, but also because the organism itself had become less invasive. This view was at least partly vindicated by the experimental studies of Greenwood and Topley on epidemics in mice. Professor Greenwood ended with an appeal to mathe- matical statisticians. The medical and biological com- plexities of the study of epidemics had added fresh variables which must be accounted for in the algebraic formulations of epidemic laws. Such formulations called for a mathematical sophistication which few in the medical profession could hope to attain, but in cooperation between statisticians and field epidemiologists lay the future promise. FOLIC ACID AGAIN LAST year chemists in the United States synthesised a substance with similar properties to the folic acid, or L. cosei," factor, which had been isolated from liver, and Spies and his colleagues claimed that this material effectively relieved nutritional macrocytic anaemia. These claims have now been considerably extended. Darby, Jones, and Johnson 2 gave synthetic folic acid in a dose of 15 mg. intramuscularly daily to 3 cases of sprue, with no other treatment. The cases presented all the classical features-glossitis, loss of weight, diarrheea with increased fat in the stools, flat glucose-tolerance curve, macrocytic anaemia, and sternal marrow like that of untreated pernicious anaemia. In all 3 cases there was a rapid remission of all symptoms with a notable reticu- locyte response, and the sternal marrow showed dis- appearance of the more primitive erythroblasts. Spies 3 has claimed a satisfactory response to folic acid in 5 cases of Addisonian pernicious anaemia, 8 cases of sprue, and 3 of macrocytic anaemia of pregnancy, and others in addition; but he gives no details. These findings are important and surprising. It was to be expected that, sooner or later, the vitamin-B factor that relieved nutritional macrocytic anaemia would be isolated ; but that the same factor should be effective in true pernicious anaemia and relieve all the varied symptoms of sprue is unexpected. Workers on nutri- tional anaemia elsewhere than America, such as Wills in India and Trowell in Uganda, have found that the purified liver extracts which are effective in pernicious anaemia had to be given in very large doses to produce any effect in nutritional macrocytic anaemia-in doses much larger than those of crude liver concentrates, which suggested that the factors responsible were different. So far only preliminary reports have appeared, but fuller information should soon be available. We need to know the chemical constitution of synthetic folic acid, and we need fully illustrated clinical records that will show clearly that folic acid brings about a change from megaloblastic to normoblastic marrow in cases of true pernicious anaemia and the megaloblastic nutritional anaemias ; for, if these claims are confirmed, all present liver extracts are out of date. THE Rockefeller Foundation has made to the Tavistock Clinic in London a grant of £22,000 for practical work in such problems as industrial relations, resettlement of returning Servicemen, and the current difficulties of families and communities in the reconstruction period. Two anonymous donors have added £3500 to the fund. This work will form the main task of a new organisation, the Tavistock Institute of Human Relations. 1. See Lancet, Dec. 29, 1945, p. 855. 2. Darby, W. J., Jones, E., Johnson, H. C. Science, Jan. 25, 1946, p. 108. 3. Spies, T. D. Lancet, Feb. 16, 1946, p. 225.
Transcript of STATISTICS AND EPIDEMIOLOGY
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doses produced pulmonary oedema and bronchopneu-monia. In view of idiosyncrasy, it is never possible toestablish a safe concentration for man, but it is usuallyassumed that 70 parts per million would be the uppersafety limit for short exposures and 50 parts per millionfor exposures lasting over eight hours. Once poisoninghas occurred, treatment, apart from removing the
patient from exposure, is of little value ; thereforeattention should be directed to preventive measures.Methyl bromide is capable of passing a Service gasmask in a quarter of an hour, and Clarke, Roworth, andHolling 11 therefore suggested that a pungent substanceshould be added to draw attention to its presence ;Viner 8 mentioned that it can be mixed with 20% carbontetrachloride, but phosgene may then be formed whenthe mixture is put on a fire. Fire-fighters should bewarned against spilling the substance on their clothingand instructed that clothing wetted with it must beremoved immediately. Ships, storehouses, and barnsmust be thoroughly ventilated after it has been used forfumigation. Prevention of leaks, adequate dilution ofescaping gas, and exhaust ventilation through the floorof the workshop are the most important preventivemeasures in industry. Bathing the hands in a weaksolution of sodium carbonate may help to prevent skinlesions by decomposing the methyl bromide. Periodicmedical examination will not only detect early symptomsbut draw attention to dangerous mechanical parts andlead to their repair before serious trouble has arisen.
STATISTICS AND EPIDEMIOLOGY
AT a meeting of the Royal Statistical Society onFeb. 27, Dr. Major Greenwood, F.R.S., emeritus professor ofvital statistics and epidemiology at the London Schoolof Hygiene and Tropical Medicine, discussed the partwhich statistical methods could play in the study ofepidemic disease. After referring to the history of ideason the nature and mode of spread of epidemics, he gavea neat example of the fitting of an algebraic structureto the hypothesis of the patient-to-patient transmissionof measles. A cynic, as Professor Greenwood noted,might observe that the mathematical ingenuity of hisproof was rather wasted on the verification of a resultwhich should be self-evident to any mother with morethan two children. On the other hand, the epidemicnature of influenza was not self-evident even to so
distinguished a medical historian as Hirsch writinglittle more than 60 years ago. Truth, as Pontius Pilateinferred, is relative, and proof in the strict sense is seldompossible in the biological sciences. The value of statisticalmethods seems to lie in the rigorous testing of a hypo-thesis-it deals not with absolute proofs but with relativelikelihoods. In,practice, Professor Greenwood suggested,the methods which seemed almost superfluous whenapplied to measles can be profitably used in the study ofsuch baftling problems as the spread of epidemic polio-myelitis. Essentially, these methods consist in an
analysis of the time intervals between successive casesand a study of the departures of these intervalsfrom a purely chance variability-a problem of somemathematical complexity.Much has been done by medical statisticians in an
effort to uncover the " laws " of the waxing and waningof epidemics. The explosive outburst of a food-bornedisease is evident in the skewed shape of the epidemiccurve which results from the sudden initial rise in thenumber of cases. Conversely, the more even rise andfall of an influenza epidemic is indicative of its airbornespread from person to person. Farr, Brownlee, Ross,and McKendrick have all tried to generalise in mathe-matical form the rise and fall of epidemic disease. Rossand McKendrick have stressed the effects of the influxof non-immunes into the herd and the development ofherd immunity. Brownlee, from the statistical character-
istics of the epidemic curve, suggested a possible waningof the invasive power of the infecting organism itselffrom the very start of the epidemic. Epidemics, in fact,did not decline only because all the susceptible had eithersuccumbed or acquired immunity, but also because theorganism itself had become less invasive. This view wasat least partly vindicated by the experimental studiesof Greenwood and Topley on epidemics in mice.
Professor Greenwood ended with an appeal to mathe-matical statisticians. The medical and biological com-plexities of the study of epidemics had added freshvariables which must be accounted for in the algebraicformulations of epidemic laws. Such formulations calledfor a mathematical sophistication which few in the medicalprofession could hope to attain, but in cooperation betweenstatisticians and field epidemiologists lay the future
promise.FOLIC ACID AGAIN
LAST year chemists in the United States synthesiseda substance with similar properties to the folic acid, or L. cosei," factor, which had been isolated from liver,and Spies and his colleagues claimed that this materialeffectively relieved nutritional macrocytic anaemia.These claims have now been considerably extended.Darby, Jones, and Johnson 2 gave synthetic folic acidin a dose of 15 mg. intramuscularly daily to 3 cases ofsprue, with no other treatment. The cases presented allthe classical features-glossitis, loss of weight, diarrheeawith increased fat in the stools, flat glucose-tolerancecurve, macrocytic anaemia, and sternal marrow like thatof untreated pernicious anaemia. In all 3 cases there wasa rapid remission of all symptoms with a notable reticu-locyte response, and the sternal marrow showed dis-
appearance of the more primitive erythroblasts. Spies 3has claimed a satisfactory response to folic acid in 5 casesof Addisonian pernicious anaemia, 8 cases of sprue, and3 of macrocytic anaemia of pregnancy, and others inaddition; but he gives no details.These findings are important and surprising. It was
to be expected that, sooner or later, the vitamin-B factorthat relieved nutritional macrocytic anaemia would beisolated ; but that the same factor should be effectivein true pernicious anaemia and relieve all the variedsymptoms of sprue is unexpected. Workers on nutri-tional anaemia elsewhere than America, such as Wills inIndia and Trowell in Uganda, have found that thepurified liver extracts which are effective in perniciousanaemia had to be given in very large doses to produceany effect in nutritional macrocytic anaemia-in dosesmuch larger than those of crude liver concentrates, whichsuggested that the factors responsible were different. Sofar only preliminary reports have appeared, but fullerinformation should soon be available. We need to knowthe chemical constitution of synthetic folic acid, and weneed fully illustrated clinical records that will show clearlythat folic acid brings about a change from megaloblasticto normoblastic marrow in cases of true perniciousanaemia and the megaloblastic nutritional anaemias ; for,if these claims are confirmed, all present liver extractsare out of date.
THE Rockefeller Foundation has made to the TavistockClinic in London a grant of £22,000 for practical workin such problems as industrial relations, resettlement ofreturning Servicemen, and the current difficulties offamilies and communities in the reconstruction period.Two anonymous donors have added £3500 to the fund.This work will form the main task of a new organisation,the Tavistock Institute of Human Relations.
1. See Lancet, Dec. 29, 1945, p. 855.2. Darby, W. J., Jones, E., Johnson, H. C. Science, Jan. 25, 1946,
p. 108.3. Spies, T. D. Lancet, Feb. 16, 1946, p. 225.
