770

and of preserving tissues and organs hold out further pros-pects for improvement. The joining of nerves, blood-vessels, tendons, and bone follows conventional lines, butthe Osaka workers lay stress on the sequence of repair.Thus, debridement of both ends comes first and must bethorough. Fractured ends of bones must be fixed next.

They may have to be shortened to ease the apposition ofvessels, nerves, and tendons and this is the best time forit. Veins should be united before arteries so that they candrain away the arterial blood when the arteries are

anastomosed. Autogenous vein grafts should be freelyused to bridge gaps between vessels, and a strong case ismade for suture of nerves at the time of replantation,when their ends are easier to define, when bone can beshortened to permit anastomosis without undue tension,and when there is no scar tissue.

In civilian injuries, the surgeon is less likely to beharassed by the need to hurry than in the case of masscasualties of war.3 Unless, therefore, the condition of thepatient precludes a long operation there is everything tobe said for immediate repair of cut nerves. Finally,decompressing skin incisions and fasciotomy of musclecompartments are essential to avoid postoperative oedemacaused by impaired venous and lymphatic drainage. Skin

grafts should be used to cover resulting defects, and thearm should be kept raised while the patient is in bed.

ACTION OF INTERFERON

TEN years ago, work on viral interference receivednew impetus from the discovery, by Isaacs and

Lindenmann,4 that one kind of interference was causedby a soluble protein which they termed interferon. Anew monograph,5 which deals comprehensively with allaspects of interferon, discusses the possibility that it

may yet prove an effective antiviral agent in man. Ithas many properties useful for this purpose: it is active

against a wide range of viruses, both in vitro and invivo; and since it is a natural substance, it will probablyprove non-toxic. The great drawbacks of interferon areits specificity (which means interferon for use in manwould have to be made in human or other primate cells),the high dosage needed, and its short-lived effectiveness.For these reasons many workers believe that researchinto the use of interferon in medicine should be directedtowards finding drugs which can stimulate interferon

production within the body. That this is not a vain hopeis demonstrated by the discovery of an increasing num-ber of substances that will stimulate interferon-not

only viruses and bacterial endotoxin, but also mould

products like statolon 6 and helenine,7 and also a varietyof synthetic anionic polymers.8 None of these substanceshas yet proved suitable for extended trial in man becauseof doubts about long-term toxicity.

Interferon has also been of great importance in

extending our knowledge of the virus/host-cell interac-tion. At the time the monograph 5 was written, althoughthere had been much interesting work on the produc-tion and purification of interferon, rather scant progress3. Rosenkrantz, J. G., Sullivan, R. C., Welch, K., Miles, J. S., Sadler,

K. M, Paton, B. C. New Engl. J. Med. 1967, 276, 609.4. Isaacs, A., Lindenmann, J. Proc. R. Soc. B, 1957, 147, 258.5. Interferons (edited by N. B. Finter). Amsterdam, 1966. See Lancet,

1966, ii, 1449.6. Kleinschmidt, W. J., Cline, T. C., Murphy, E. B. Proc. Natn. Acad.

Sci. U.S.A. 1964, 52, 741.7. Rytel, M. W., Shope, R. E., Kilbourne, E. D. J. exp. Med. 1966, 123, 577.8. Regelson, W. Proceedings of International Symposium on Athero-

sclerosis and the Reticuloendothelial System. Lake Como, Italy (inpress).

had been made in elucidating the mode of antiviralaction. Sonnabend and Friedman 9 were critical of muchearlier work in this area, because impure interferon hadbeen used and non-specific effects had been wronglyascribed to interferon. At that time, however, therewas evidence (mainly from the work of Taylor 10) thatinterferon stimulated the production of a new proteinwhich was responsible for the antiviral effect.Marcus and Salb 11 have now brought forward strong

evidence that interferon induces the formation of a

protein which inhibits the translation of viral messengerR.N.A. by host-cell polyribosomes. They studied the

uptake of tritiated Sindbis-virus R.N.A. by ribosomesfrom normal chick cells and from chick cells treated withpartially purified interferon. They found that viralR.N.A. attached to normal ribosomes, and that this wasfollowed by aminoacid incorporation for 20 minutes,accompanied by breakdown of polyribosomes (providedan energy source was available). This activity of viralR.N.A. attached to ribosomes is inhibited by cyclohexi-mide, which, Wettstein and his colleagues 12 showed,produces its effect by inhibiting translation of the R.N.A.message. Viral R.N.A. is taken up by ribosomes frominterferon-treated cells at only two-thirds of the rate ofnormal cells, and there is no aminoacid incorporationor breakdown of ribosome complexes under the condi-tions that allow protein synthesis with normal ribosomes.Marcus and Salb suppose that the translation-inhibitingprotein induced by interferon attaches to the ribosomes,so that the exact degree of resistance to a virus may welldepend upon the proportion of inhibited ribosomes inthe cellular ribosome pool. The varying effectiveness ofinterferon for different viruses is as yet unexplained bythis work, but it might depend on the numbers ofribosomes required to effect virus synthesis.

ORAL CONTRACEPTIVES: "A SLIGHT RISK"

The Minister of Health, in a Parliamentary answer onTuesday, gave the preliminary results of investigationsconducted by the Committee on Safety of Drugs, theCollege of General Practitioners, and the MedicalResearch Council to examine the possible association oforal contraceptives and thromboembolism. The results

suggested that a woman taking oral contraceptives in-curred " a slightly increased risk of developing throm-boembolic disorders, but that the risk is small and lessthan that which arises from the ordinary pregnancy anddelivery which these contraceptives are intended to

prevent." The risk, the M.R.C. report, cannot be pre-cisely quantified at present, and further data are beingcollected. The results of preliminary studies will be

published as soon as possible.The Committee on Safety of Drugs has advised the Min-

ister that oral contraceptives have considerable therapeuticas well as social value and the committee do not feel justi-fied in recommending their withdrawal from the market-as long as they are available only on medical prescriptionand doctors are aware of the slight risk involved. In itsfurther examination of the situation, the committee willcontinue to rely on the reporting by doctors of thrombo-embolic episodes in women of childbearing age.9. Sonnabend, J. A., Friedman, R. M. in Interferons (edited by N. B.

Finter); p. 202. Amsterdam, 1966.10. Taylor, J. Biochem. biophys. Res. Comm. 1964, 14, 447.11. Marcus, P. I., Salb, J. E. Virology, 1966, 30, 502.12. Wettstein, F. O., Noll, H., Penman, S. Biochim. biophys. Acta, 1963,

87, 525.