associated with tobacco smoking, particularly in the formof cigarettes. In the opinion of the Council, the mostreasonable interpretation of this evidence is that the

relationship is one of direct cause and effect.5. The identification of several carcinogenic substances

in tobacco smoke provides a rational basis for such acausal relationship.

1. Report of the Medical Research Council for the year 1955-56.H.M. Stationery Office. Pp. 247. 9s.

2. See Lancet, 1956, i, 949.

REPORT ON MEDICAL RESEARCH

LUNG cancer, radiation hazards, vaccination againstpoliomyelitis, and genetics are among the chief topicsof the Medical Research Council’s latest report.1The Council’s activities complement those of hospitals

and universities, and the Council provides for clinicalresearch only when its scale, scope, or urgency dictates.Besides setting up its own permanent units, whose staffshave careers in research, the Council makes whole-timeor part-time appointments to its external scientific staff,grants to independent workers, and awards for trainingin research. Moreover, it organises cooperative studies.At the national level, the Council allocates funds for thesupport of clinical research in both major schemes andindividual projects. Decentralised research may be

supported by regional hospital boards and boards of

governors of teaching hospitals ; here the Clinical ResearchBoard can often give advice.As before, the report includes an excellent succinct

account of trends in selected fields of medical research.The many publications of the Council and its staff arethen listed. They include the report on the Hazards toMan of Nuclear and Allied Radiations,2 presented toParliament as a white-paper.

Overseas liaison continues by means of units in Gambia,Jamaica, and Uganda. Research groups have been set

up to study ageing, atmospheric pollution, inheriteddisease, and other topics, and units are being establishedto study (among other things) metabolic disturbances insurgery, carcinogens, and the effects of radiation.

Special attention is paid to lung cancer on account ofits striking increase in late years ; it is the cause of 1 in

every 9 deaths in middle-aged men. Retrospective andprospective investigations all indicate a relationshipbetween heavy smoking, especially of cigarettes, andmost forms of lung cancer ; and no investigation suggestsabsence of such a relationship. Carcinogens have beenfound in cigarette smoke ; these induce hyperplasia inhuman foetal lung grown in tissue-culture. Industrialhazards (e.g., from chrome and asbestos) and atmosphericpollution probably account for a small proportion of thecases. Statistical surveys and laboratory experimentsare continuing.

Poliomyelitis vaccination in North America is by killedviruses of the Mahoney strain. For the British vaccine aless virulent (Brunenders) strain was chosen, but therhesus monkey used for safety testing was found to beinsensitive to this strain. A cynomolgus monkey(treated with cortisone, or cortisone and irradiation) isused. Antibody studies in children have shown that theBritish vaccine produces titres (against all three types ofvirus) which compare favourably with those found afteruse of the American vaccine. Experiments in monkeysshow that the vaccine confers a high degree of immunityto artificial infection with a virulent strain. In childrenaged l 1/2-9 1/2, after vaccination the attack-rate of para-lytic poliomyelitis in the 1956-57 season was a fifth of thatin unvaccinated children. Live attenuated poliomyelitisvaccines are being tried : so far they have been trouble-free, but the antibody response has not always beensatisf actorv.

In experimental filarial infections it was found thatmicronlarise remained in the lung capillaries during theday, and were more generally distributed in the circulatingblood at night. The antifilarial drug diethylcarbamazine(’ Banocide ’) acts similarly to an opsonin, and is effectivein the blood-stream but less so in places inaccessible tothe phagocytes. The drug is most useful in the masstreatment of communities. Species of wuchereriasimilar to the human type have been found in animals,and several species of mosquito are now known to beinvolved as vectors. The response of onchocerciasis tochemotherapy is not satisfactory, but control of thesimulium fly vector by dicophane (D.D.T.) has beensuccessful.The importance of the kidney in regulating the water

and electrolyte content of the body is agreed, but

attempts to compare the efficiency of the kidney inadults and in children have been frustrated by lack of anagreed basis for comparison-the body-weight, body-surface area, and body-water content give differingresults. But by most criteria the kidneys of infants

(human and rat) are less efficient than those of adults.Happily a balanced diet and the requirements of growth(which dictate that little protein be broken down)ensure that, normally, not too much material is presentedfor excretion.

Investigation of the nature of the difference betweennormal and sickle-cell hcemoglobins has shown that theonly chemical difference lies in one peptide, which bearsa positive charge in sickle-cell haemoglobin at pH 6-4but is unchanged in normal haemoglobin ; this differenceis due to the presence of a valine molecule in the chargedpeptide and a glutamic-acid molecule in the neutral

peptide. This is the first time that the effects of a singlemutation on the chemical structure of a protein havebeen elucidated. When the sickle-cell-haemoglobinmolecules lose oxygen they may form fibrillar aggregateswhich attract one another into a parallel orientation,distorting the cell. In homozygotes the illness is severe,and four-fifths of them die before reaching reproductiveage ; the persistent high incidence of sickling in someAfrican tribes is thought to be due to the high resistanceof heterozygotes to malignant tertian malaria, whichlargely compensates for the lethality of sickling. Inmalaria-free regions (e.g., the United States) the preva-lence of sickle-cell trait has fallen, as would be expected.Heterozygotes carrying a thalassaemic factor may be

similarly resistant to malaria. Mutations of the kind,where genes are beneficial in one situation and harmful inanother, are important in evolution.

Microbial genetics is briefly discussed. There are 3mechanisms for the transfer of bacterial genes from cellto cell :

(1) Transformation operates in, e.g., pneumococci. If

deoxyribonucleic acid (D.N.A.) is extracted from one strainand added to another, the recipient strain takes on somecharacteristics of the donor.

(2) Transduction operates in, e.g., salmonella. When virus

multiplies in a donor cell, some chromosome fragments becomeincorporated in the virus, and may be integrated into thechromosomes of new infected cells which survive.

(3) Conjugation operates in, e.g., the colon bacillus. Duringtemporary fusion of two cells, chromosome material passesfrom one to the other.

A bacterial virus acts by attaching itself to the bacterialcell and injecting its D.N.A., which then takes control of thehost’s synthesising mechanisms, causing them to producemore virus D.N.A. and protein. Often bacteria becomepermanently infected (" lysogenic ") with a phage virus,and able to transmit it to their progeny. Some bacterialproperties (e.g., toxin-production by diphtheria bacilli)are impossible except by lysogenic organisms.

Homografts are normally destroyed (except for blood,whose cells have no nuclei, and cornea, which has _no

1348

blood-supply). This does not apply to grafts betweenidentical twins or members of an inbred strain, and thepower to destroy grafts may be lost after irradiation.Irradiated mice, which would have been expected to dieafter a week or two, recover when inoculated withmarrow. It has been shown that the homologousmarrow actually colonises the irradiated host. Even

grafts from another species (rat) may survive. Leuksemicmice have been successfully treated by irradiation heavyenough to destroy all the blood-forming tissue, followedby a marrow graft from a normal animal. Another meansof making homografting possible is to inject tissue fromanother animal before birth ; after reaching maturitythe recipient will tolerate further grafts from thedonor.

Other articles deal with the relationship betweenradiation and leukaemia, whooping-cough vaccines,protein turnover in tissues, the chemistry of proteinsand peptides and of antibiotics, and mass-spectrometryin gas analysis. The summary of work indicates the vast

range of the council’s activities-from hypogamma-globulinaemia to possible carcinogenic action of deter-

gents. The list of publications is as long and impressiveas ever.

Before Our Time

TOBACCO FASHIONS

WHEN the natives of North America discovered theEuropeans in the 15th century they introduced themto the pleasures of tobacco-snuffed, chewed, andsmoked. The form in which it was used in- their societywas probably governed to some extent by custom andfashion ; and pipe-smoking certainly had some religiousand symbolic meanings. The history of tobacco-takingin Europe has also been strongly influenced by fashion,which, although partly shaped by authority, propaganda,and economics, owes much more to individual desiresfor novelty, distinction, emulation, and uniformity.

In England pipe-smoking became the fashion of therich in the late 16th century, and, as the price of tobaccofell, the habit spread to all classes, both sexes, and almostall ages ; by the turn of the century it was a nationalpastime. On the Continent, on the other hand, thefashion was for snuffing. There was, of course, much

opposition to all forms of tobacco using ; and the first

important book against it-the opinions of sundrylearned physicians-was published as early as 1598.Two Papal Bulls proclaimed excommunication for beingfound guilty of using tobacco in the churches of Sevilleand within the walls of St. Peter’s in Rome. The GreekChurch forbade its use entirely ; and in Turkey, Persia,and India the death penalty was prescribed. A Russiantsar decreed that for the first offence the culprit shouldbe whipped and for the second executed, while snuff-takers were to have their noses cut off ; and Louis XIIIof France prohibited its use unless ordered by a physician.In England, James I imposed a heavy import tax in1604 and published his renowned Counterblaste with itsbitter invective against the habit. But the fashion grew.Then, in the early years of the 18th century, it changedrapidly and there appears to have been no organisedpropaganda, legislation, or economic circumstance toaccount for this. In the time of the Stuarts, accordingto Sir William Besant, " the use of tobacco penetratedall ranks and classes of society. The grave divine, thesoldier, the lawyer, the gallant about town, the merchant,the craftsman, the ’prentice, all used pipes.... Peoplewent to bed with tobacco box and pipe and candle ona table by the bedside ... it is even stated that the verychildren in school took a pipe of tobacco instead of

breakfast ..." But by the end of Queen Anne’s reignthe pipe had been deposed and the English were wellset for a century of snuff-taking.

Snuffing was already popular among all classes inPrance and in Scotland and Ireland. It seems probablethat in England it grew up slowly among the " youngbloods " as a protest against the excess to which smokinghad been carried by the " lower orders." They importedthe habit and the elegant ritual of snuff-taking from thefashionable French with the fastidious attention toblend and perfume, the exquisite snuff-boxes, the tapon the lid and the delicate lifting of the pinch to thenose, the inaudible inhalation and elaborate gesturesof the hands and dainty handkerchiefs. These affections,of course, were scorned by men such as Samuel Johnsonwho carried their snuff loose in their waistcoat pockets;but schools of etiquette gave instruction, as an advertise-ment of 1711 states, in " the exercise of the Snuff-box,according to the most fashionable Airs and Notions ...with the best plain and scented snuff." An accident ofwar may have contributed to the rapid spread of thehabit. In 1702 50 tons of fine Havana snuff captured inSpanish ships were distributed among the English sea-men as perquisites. They sold it cheaply in Englandand flooded the market in the southern counties withexcellent snuff at 3d. or 4d. a pound. By 1720 a con-temporary writer was able to say : "The world hastaken up a ridiculous fashion-the excessive use ofsnuff. All nations are snuffing. All classes snuff, from thehighest to the lowest.... Both sexes snuff, for the fashionhas spread to women ; the ladies began it and it isnow imitated by the washerwomen." Dr. Johnson,fifty years later, remarked that " smoking has gone out.To be sure, it is a shocking thing, blowing smoke outof our mouths into other people’s mouths, eyes andnoses ... yet I cannot account why a thing that requiresso little exertion, and yet preserves the mind from totalvacuity, should have gone out." According to Swift,the makers of snuff employed " by far the greatestnumber of hands of any manufacture of the kingdom."A snuff house was opened in the Haymarket in 1720that has continued to blend and sell snuff without

interruption to the present day. The ledgers and recordsprovide an interesting history of fashions in the use oftobacco over more than 200 years. Queen Charlotte-nicknamed " snuffy Charlotte "-was a heavy snuff-taker and regular customer. Like many others she

bought snuff by the pound, on Feb. 20, 1804, ordering12 lb. of " Marrocca " at 8s. 6d. a pound with 4s. fora " jar and bung " and another 6 lb. on May 26. Butby this time the craze of snuffing was waning. Themass of the people, among whom pipe-smoking hadnever lost its appeal, were slowly discarding the snuffhabit ; and cigars were becoming more popular among therich. Snuff remained highly fashionable in the foppishcircles in which the craze had originated. Indeed, itreached a peak of fashionable excess in the time of thePrince Regent and Beau Brummell.

By the middle of the 19th century the famous Hay-market shop was supplying as many smokers as snuffers,and in 1859 a work on the habits of " grand society"

"

recorded that the obsolete custom of snuffing was

" retained only by a few old gentlemen." The birthof cigar-smoking has been attributed to the Peninsularwar, when the soldiers acquired a taste for Spanishcigars. The rise of cigarette-smoking has been linkedwith the Crimean war and contact with the customsof the Turks and Russians. It may be significant thatthe snuff craze began about the time of the extendedwar of the Spanish succession on the Continent. But

changes of fashion are not caused by single circum-stances or events, though these may precipitate a changewhen the communal taste is ready for one. Both thesudden fashion of snuffing in the 18th century and the