Journal of the Royal Society of Medicine Volume 72 February 1979 particularly siblings, should be invited for investigation or at least warned never to neglect symptoms relating to the large bowel. Parents, one of whom has had a cancer or is at increased risk because of the family history, should be encouraged to have their children examined, but current information suggests that this is unnecessary until about the age of 20 years. Most patients with ulcerative colitis never develop carcinoma of the large bowel. However, it is established that such tumours are more common in colitics than in the general population and tend to occur at an earlier age. Many published studies have confirmed that the cancer risk is largely confined to those with extensive colitis, a history of symptoms for more than ten years and histological evidence of severe dysplasia in colorectal biopsies. It is probable that carcinoma as a complication of colitis could largely be eliminated by advising proctocolectomy for all patients with extensive colitis, either early in the course of the disease for acute symptoms or after ten years in patients with mild disease (Bonnevie et al. 1974). This policy would greatly increase the number of patients undergoing major surgery, most of whom are not destined to get colorectal cancer. These operations have a mortality and morbidity both in the short and the long term (Ritchie 1972) and excision of the rectum can lead to sexual dysfunction (Burnham et al. 1977). The presence of a stoma can cause physical, psychological and social disability. An alternative policy reserves operation for a patient with ill-health due to colitis or when the large intestine shows evidence of neoplastic potential as judged by the presence of consistent and severe epithelial dysplasia in colorectal biopsies (Morson & Pang 1967). A prospective study has now shown that the cancer risk in colitis can be minimized by careful follow up of all patients with a long history of extensive disease and prophylactic proctocolectomy performed when evidence of severe dysplasia is established (Lennard-Jones et al. 1977). This is a small and manageable population of patients, like polyposis and colorectal cancer families, among whom a cancer prevention programme is a proven success. The information made available in recent decades by cancer registries has been of enormous value in defining large populations, usually at a national level, who are at increased risk from different varieties of malignant disease. Has the time now arrived for the establishment of official precancer registers on a regional or national basis? This would certainly be practicable for polyposis coli families, colorectal cancer families and colitics at increased risk, and there is now incontrovertible evidence that this would lead to cancer prevention. But there is also the prospect that the registration 0141-0768/79/020085-03/$Ol1.00/0

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of patients with isolated large bowel adenomas or even those with a positive stool haemoccult test might be beneficial and cost-effective. If cancer prevention is to be more than a political or professional slogan then it is time consideration was given to such proposals by our public health authorities. B C Morson Consultant Pathologist St Mark's Hospital, London EC]

References Birbeck M S C & Dukes C E (1963) Proceedings of the Royal Society of Medicine 56, 793-798 Bonnevie 0, Binder V & Anthonisen P (1974) Scandinavian Journal of Gastroenterology 9, 81-91 Burnham R, Lennard-Jones J E & Brooke B N (1977) Gut 18, 673 Bussey H J R (1975) Familial Polyposis Coli. Johns Hopkins University Press, Baltimore Bussey H J R, Ritchie S & Morson B C (1979) Gut (in press) Greegor D H (1972) Cancer 22, 360-363 Heald R J & Lockhart-Mummery H E (1972) British Journal of Surgery 59, 16-19 Lennard-Jones J E, Morson B C, Ritchie J K, Shove D C & Williams C B (1977) Gastroenterology 73, 1280-1289 Leuchtenberger C, Leuchtenberger R & Liebv E (1956) Acta genetica et statistica medica 6, 291-297 Lovett E (1976) British Journal of Surgery 63, 13-18, 19-22 Moertel C G, Hill J R & Adson M A (1970) Arc-hives of Surgery 100, 521-526 Morson B C ed (1978) Pathogenesis of colorectal cancer. Major Problems in Pathology, vol 10. Saunders, Philadelphia Morson B C & Pang L S C (1967) Gut 8, 423-434 Muto T, Bussey H J R & Morson B C (1975) Cancer 36, 2251-2270 Ritchie J K (1972) British Journal of Surgery 59, 345-351 Schaupp W C & Volpe P A (1972) American Journal of Surgery 124, 218-222 Winawer S J, Sherlock P, Schottenfeld D & Miller D (1976) Gastroenterology 70, 783-789 World Health Organization (1964) Technical Report Series No. 276. Geneva

Gerontology and geriatrics in aerospace medicine One consequence of the United States NASA shuttle programme is that two additional disciplines, gerontology and geriatrics, have become relevant to aerospace medicine - the first because flight experiments can be used in fundamental research; the second for practical reasons connected with crew selection. Both these topics were recently the subject of discussion between gerontologists and NASA staff. The possibility that this ©) 1979 The Royal Society of Medicine

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expensive programme may produce 'spinoff' in either area is internationally interesting, particularly to those European countries in which geriatrics is already a subject of clinical research. The 'shuttle' is a recoverable, reusable craft resembling in outline a conventional airliner. It will be projected into orbit by rockets and will return in an unpowered glide after five to seven days spent in high orbit. The craft is equipped for pressurized laboratory work at zero gravity, and it also carries an unpressurized test-bed for physical experiments. So long as crew for flights in space were confined to trained professional astronauts and the training requirements were arduous, space physiology was limited to the effects of acceleration, weightlessness and re-entry on young, fit adults. The shuttle, by contrast, gives the facility to fly 'passengers', and these may have to include specially qualified older persons- senior scientists and technicians. This change in selection criteria makes it essential to examine responses and the possible complications of extraterrestrial flight over the whole lifespan, not only its second quartile. The immediate aim is to avoid hazard to passengers and the need for emergency recovery, but fundamental study of stress responses at high ages by NASA has great incidental value for clinical geriatrics because of the large resources available. One example of 'spinoff' in this area is already evident: bed-rest has long been known to be injurious to older patients, but only when it was studied operationally as a model for the effects of weightlessness did full information on changes in muscular, cardiovascular and bone physiology become available for healthy adults (Donaldson et al. 1970, Miller et al. 1965). Flight eligibility, given the increasing variance of many resistance characters with age, will have to be based on individual performance testing, not a rigid age scale, but it promises to contribute to one of the standing problems of age research, the nonactuarial estimation of 'biological age' (Comfort 1972). Another innovative area is the effect of age on trainability and the control of specific systems; this has novel therapeutic possibilities if it proves feasible. The classic pattern of age change in responses to stress is that described by Verzar (1963) for cold adaptation - response is later and may be lower. In enzyme induction chains, especially those with a hypothalamic limb, it is usually later but ultimate levels are not reduced (Adelman 1975). Pathologies also accumulate with age, and variance in most parameters increases, in man and rodents (Storer 1965): when it appears to decline, this may be due simply to lack of reserve, and the fact that aging systems are operating close to capacity, with the risk of failure if further loaded.

Once obvious pathology has been excluded, several areas in the physiology of older passengers can be pinpointed as likely to afford problems during weightlessness. Calcium loss from bones and muscular atrophy are obvious examples. The point at which trouble may be expected, however, is rather in readaptation to Earth gravity. Here effects such as joint pains, vestibular vertigo and laboured voluntary movements (Gibson 1977), as well as other side effects which are minimal in young fit aircrew (gravitational purpura Hordinsky 1977), may be expected to last longer and/or to be more severe in older subjects. Moreover, effects typical of prolonged weightlessness may well appear far more rapidly or generate prolonged disability in older fliers. Some, but only some, of these problems can be predicted from ground bed-rest studies, and they require to be foreseen. Older passengers may, for example, require gravity-suit protection not needed by astronauts. While geriatricians will be needed to advise in this very practical area of crew selection, gerontologists are interested in the possible use of prolonged weightlessness experiments in the fundamental analysis of the aging 'clock'. Although many age changes represent the equivalent of component failure, which depends in mechanical terms on the 'tolerance' of various components, lifespan is increasingly seen by gerontologists as being overseen and determined by an overall timing mechanism, probably hypothalamic, which adjusts for such failures and for drift by correction and the introduction of backup systems. This idea is gf aerospace interest not only from the analogy with the 'lifespan' of a probe, but also because the physiological model was developed originally in the Soviet Union (Dilman 1971, Arshavsky 1968, Frolkis 1968) and is likely to be receiving attention there. The hypothetical 'clock' in rodents appears to be sensitive to calorie intake, since caloric restriction postpones most age changes in rats and mice to higher ages. This problem cannot be attacked by diet experiments in man, owing to the unfeasibility of 80-year tests of diet, but on the model of the coupling of menarche to body weight, and continued menstruation to its maintenance (Frisch 1973), it becomes critical to examine how such a 'clock' compares caloric intake with growth and body mass. The question is not whether the body has a direct means of baroception - in the case of bone or cardiac load it clearly has - but whether the integrative 'clock' appears to have one, and whether the hypothalamus, which is chiefly a chemical sensor, reads body weight directly from apparent mass or through a second-order derivate of some kind. In either case, alteration of gravity could be used to dissect inputs to the 'clock' and

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possibly to identify its hormonal outputs. If it does neither, altered gravity should create an unconventional discrepancy between 'clock' and general homeostasis, which is known to be partially barosensitive, with instructive results. Both the 'shuttle' and the longer-term Spacelab and Kosmos type satellites have attractions as a venue for experiments in this area, since appetite, caloric intake and balance, circadian rhythms and neurohormones - particularly somatotrophin, somatostatin and prolactin - could be estimated inflight, probably within the 7-day limit of planned 'shuttle' flights, and certainly in longer experiments. These levels are disturbed in animals by reentry. They could be tested at hypergravity in centrifuge studies, such as those of Oyama (Oyama & Platt 1965), but ideally require a centrifuge where results can be obtained without stopping the machine. The cost of building such an apparatus might well be greater than the scheduling of flight experiments, and these could also be performed on human subjects. Quite apart from this model for aging, weightlessness studies may have incidental implications for gerontology. Collagen structure has long been used as a measure of aging: in recent flight experiments it has been incidentally found that low gravity mobilizes preformed collagen (Leach & Rambaut 1977). It has been a criticism of US and USSR space exploration that the vast cost has benefited mostly astronomers and the media. Since gerontology and geriatrics are of major medical importance in a demographically aging world, it is to be hoped that experts in these areas will be included in future mission planning by both the powers involved, so that the harvest may be increased. Although the idea of 'space gerontology' is a godsend to cartoonists, the results of the programme now under

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discussion in America could be considerable, and might represent that country's most fundamental contribution to geriatric medicine since Nascher coined the name (Nascher 1926). Alex Comfort Institute for Higher Studies, Santa Barbara, California, USA References Adelman R C (1975) Basic Life Sciences 6, 304-311 Arshavsky I A (1968) In: Adaptive Capacities of the Ageing Organism. Ed. V V Frolkis. Soviet Academy of Sciences, Kiev; pp 61-78 Comfort A (1972) Mechanisms of Aging and Development 1, 101-1 10 Dilman V M (1971) Lancet i, 1212-1219 Donaldson C L, Hulley S B, Vogel J M, Hattner R S, Bayers J H & Macmillan D (1970) Metabolism 19, 1071-1084 Frisch R (1973) Lancet i, 1007 Frolkis V V (I1968) In: Adaptive Capacities of the Ageing Organism. Ed. V V Frolkis. Soviet Academy of Sciences, Kiev; pp 11-44 Gibson E G (1977) In: Biomedical Results from Skylab. Ed. R S Johnson & L F Dietlin. NASA SP 377; pp 22-25 Hordinsky J R (1977) In: Biomedical Results from Skylab. Ed. R S Johnson & L F Dietlin. NASA SP 377; pp 30-34 Leach C S & Rambaut P C (1977) In: Biomedical Results from Skylab. Ed. R S Johnson & L F Dietlin. NASA SP 377; pp 204-216 Miller P B, Johnson R L & Lamb L E (1965) Aerospace Medicine 36, 1077-1082 Nascher I L (1926) Medical Retiew of Reviews (New York) 32, 281-284 Oyama J & Platt W T (1965) American Journal of Ph ysiology, 209, 611-615 Storer J B (1965) In: Aging and Levels of Biological Organization. University Press, Chicago Verzar F (1963) Lectures on Experimental Gerontology. Charles C Thomas, Springfield, Illinois