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Science & Society

Antarctica: a review of recent medical research

James J. Olson
This article reviews recent developments and areas of research in Antarctic medical science. Nineteen nations are part of the Antarctic treaty and undertake research programmes in Antarctica. Medical science is a small but important part of these programmes. Areas that have been studied include aspects of cold physiology, ultraviolet light effects, endocrine changes (including polar T3 syndrome), alterations in immune function, chronobiology, psychology, microbiology, epidemiology and telemedicine. Antarctica has been recognized as the closest thing on Earth to a testing ground for aspects of space exploration and as such has been termed a space analogue. Published online: 10 September 2002
the stark polar lands grip the hearts of men who have lived on them in a manner that can hardly be understood by the people who have never got outside the pale of civilisation. [1] our knowledge of the natural physical conditions of the globe must necessarily remain incomplete as long as there continues so large an unknown zone as that represented by the great white spot covering the southern extremity of the world, twice as vast as the whole of Europe. [2]

At the extreme southern end of the globe lies Antarctica, a vast continent almost entirely covered by ice. Antarctica is the highest (the average elevation is 2300 m), coldest (mean temperatures range from 0C to 70C), driest and windiest continent on Earth and is believed to hold >90% of the Earths fresh water. Only recently did humans express an interest in the place. In 1773 Captain Cook was turned back by ice on a journey to investigate the existence of a polar continent and remarked that no good would come to anyone who persevered further. Antarctica is no less challenging now than it was then. During the past 50 years that Antarctica has been permanently inhabited, we have learned not only a great deal about the provision of health care in this remote environment but have also used Antarctica as a laboratory in which to expand our
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knowledge of the physiology and psychology of humankind. Even today Antarctica has been visited by relatively few people and those working in Antarctica are among the most isolated groups on Earth. During the austral winter there are a total of ~50 personnel at the British Antarctic Survey stations of Rothera (67 34 S, 68 07 W) and Halley (75 S, 26 30 W), plus the sub-Antarctic bases at South Georgia and Bird Island. During winter, with the exception of the base at Bird Island, the bases each have a single doctor. Historically, in times of health the role of the doctor has often been that of voyage naturalist. With their expertise in life-sciences they would write scientific catalogues [3]. Today this role has changed. Science and research have an increasingly important role but other specialists explore the realms of botany and the doctor is now a medical scientist in his own right. Many aspects of Antarctic life have been the topic of medical research over recent years and several articles have been published, some of which looked at the health effects of living in Antarctica itself. However, interest has also grown in what can be found from the bottom of the Earth because this could have wider significance. Indeed, Antarctica has been identified as the closest thing on Earth to Space [4,5]. This review provides a summary of recent research results from the international Antarctic programmes.
Cold physiology

Ultraviolet light exposure

The depletion in the ozone layer covering Antarctica was discovered at the Halley research station in the early 1980s [7]. Since then much work on ultraviolet (UV) exposure has been undertaken, focusing on the effects of an increase in UVB on human health and in particular on skin cancer, resistance to infectious disease [8] and cataract formation [9]. A review prompted by evidence of a circumpolar rise in UV energy looked particularly at ophthalmic effects and, although no decisive conclusion was reached, it raised the possibility of an increased risk of photokeratitis (inflammation of the cornea resulting from UV light exposure), cataract, macular degeneration, squamous cell carcinoma of the conjunctiva, pterygium (a condition in which a patch of mucous membrane grows over the cornea) and pinguecula (a condition in which a patch of connective tissue grows over the cornea) [9]. Follow-up work on the ophthalmic effects of Antarctic residence is ongoing and is a field in which we will see further research because the multiple effects of UV at the molecular, cellular, tissue, individual, population and ecosystem level make it an area of ongoing scientific interest.
Endocrinology

Many people imagine that Antarctic medical science must be centred on the study of cold physiology but this forms only a small part of the work. A major study into cold adaptation is currently taking place at the Australian bases [6]. Baseline results from the pre-departure phase of this work were presented at the International Thermal Physiology Symposium in Wollongong, Australia in September 2001. The study hopes to look at algorithms for cold adaptation, adaptations of shivering thermogenesis, the role of cytokines in thermoregulatory responses and to validate a cold stress prediction model. We await further news from this study.

There is now no doubt that living in the Antarctic alters hormonal function. During the Antarctic winter the near complete absence of solar UVB radiation has been linked by French researchers to decreased hydroxylation of vitamin D [10,11]. A further study by a Japanese group also indicated a significant increase in parathyroid hormone, but with no evidence of a decrease in bone mass in subjects who stayed in Antarctica for one year [12]. An Argentinean group [13] looked at the effect of one-year residence in Antarctica on bone mineral metabolism and body composition. In a group of healthy young men, they found that in spite of low vitamin D levels and a reduction in 25 (OH) D3, bone mass increased, possibly because of their intense physical activity. A separate study has found that there could be a possible improvement in insulin sensitivity [14].

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In 1992 work from the American Antarctic programme reported a high incidence of self-monitored symptoms of depression, irritability and poor concentration in Antarctic residents [15]. In people remaining in the Antarctic during winter, an American group found evidence of a baseline increase in the levels of thyroid stimulating hormone (TSH), along with the release of higher levels of TSH in response to a challenge with intravenous thyroid hormone. Subjects showed a more rapid production and clearance of tri-iodothyronine (T3) and this was described as polar T3 syndrome [16]. Further research over the past decade [17,18] has linked these physiological and hormonal changes with alterations in mood and cognition [19]. Cognitive changes over the winter period, studied in a randomized controlled trial, tested the effect of tetra-iodothyronine (T4) supplementation on these parameters. Study numbers are small with only 12 participants, divided equally between the test groups, but the results indicate that a T4 supplement of 0.05 mg per day will improve both cognition and some self-reported mood scores during extended Antarctic residence. This work continues, with recent results appearing to confirm the benefits of T4 supplementation (L.A. Palinkas, pers. commun.).
Immunology

bacteriophage X174, which infects bacteria but is not pathogenic to humans. This virus can induce antibody responses in humans and has been used to identify abnormalities in the primary IgM and secondary IgG antibody responses in immuno-compromised patients. All of the subjects at the Australian base Casey, when compared with a control group at Macquarie Island, had normal primary and secondary antibody responses and there was no evidence that the antibody response of subjects was damaged by their residency in Antarctica over the winter [24]. An Italian study showed a marked decrease in serum cytokine levels in human subjects after prolonged exposure to a cold environment [25]. No specific patterns of disease have, as yet, been identified by these immunological studies; however, these findings are important because there might be long-term health implications. The research is hindered by several factors, including small population sizes, short lifetime exposure to the Antarctic environment and the presence of multiple variables.
Psychological adaptation

For several years the Australian National Antarctic Research Expedition (ANARE) has been conducting immunological studies on personnel staying in Antarctica over the winter (winterers). Work in the 1990s indicated that Antarctic winterers had lowered immunological responsiveness. For example, the study showed that reduced environmental immunological triggers, combined with psychosocial, physical and other stresses associated with working and living in physical isolation during the Antarctic winter, result in reduced immune function [20,21]. Work from 1997 indicated alterations in T-cell function, including depression of cell-mediated immunity responses and a 50% reduction of T-cell proliferation to phyto hemagluttinin mitogen in addition to altered cytokine production [22]. Recent work has revealed diminished cell-mediated immunity and an accompanying increased reactivation and shedding of latent viruses [23]. Most recently, in a controlled study run on two of the Australian continental Antarctic bases, subjects were inoculated with the virus
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Antarctica is a ground-based analogue, simulating some aspects of space flight [26]. Recently published studies [27,28] provide evidence of a third quarter model of behaviour in which a decrease in performance is likely to be observed in the third quarter of a mission, regardless of the mission length or severity of the physical environment [5]. How this Antarctic research corresponds with space exploration has been described [29,30]. A small French group in Antarctica were repeatedly tested on a computerized simulation of a complex life support system, to assess performance over an eight-month period of isolation. No signs of serious performance deterioration were found but the data did, however, reveal strong differences in performance between the professional groups, with scientists performing better than technicians [31]. Other work has looked at aspects of isolated and confined environments and assessed the importance of behavioural issues by analysing the diaries kept by Antarctic winterers at French research stations [32]. Research on sleep patterns at high latitudes and its relationship with mood has been carried out at the American stations. It was found that exposure to total darkness (based on station latitude) was

significantly associated with total hours of sleep, duration of the longest sleep event, time of sleep onset and quality of sleep. It appeared that changes in mood during the austral winter were preceded by changes in sleep characteristics and that, in turn, mood changes affect certain sleep characteristics, especially sleep quality [33]. Collaborative work between ANARE and NASA studied individual adaptation and team function in isolated groups attempting Antarctic traverses. These groups appeared to function well, with most of the psychological difficulties occurring with specific individuals or between individuals; they did not appear to affect all members of the group equally [34]. Work from teams based in Japan [35] and New Zealand [36] support this theory. Further work on social isolation is being undertaken at Australian stations in a joint project with NASA this year. A study of the selection procedure of suitable personnel for such missions [37] highlights the difficulties in validating personality assessments. However, this study, which looked at 657 subjects, uses secondary analysis of archival data, which weakens its significance. For many years most national Antarctic organizations have used formal questionnaire-based psychological assessments to select personnel to reside in Antarctica over the winter. The UK has never adopted this policy and a multinational study is under way looking into the effectiveness of the psychological screening and attempting to validate a test battery for use in this environment (H. Eriksen et al., unpublished).
Chronobiology

Research in the 1980s, at the British base at Halley Bay, showed that the human circadian clock regulates the temporal organization of physiological functions in accordance not only with the daynight alteration, but also the seasonal change in photoperiod [38,39]. Internal de-synchronization between sleep and circadian rhythms is regarded as the major cause of jet lag or sleep disturbance associated with shift workers. Similar sleep disturbances have been reported previously during winter in Antarctica [40]. A small study by a Japanese team found that the sleep rhythm is reset predominantly by the work schedule, whereas the circadian rhythm in plasma melatonin and rectal temperature is substantially influenced by

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the photoperiod [41]. Research continues at Halley station, which is hoped will be important not only to developments in space exploration, but also closer to home with relevance to shift-work patterns.
Microbiology

For several years the commensal flora of British and international individuals staying in Antarctica over the winter has been under study [42]. Winter Antarctic bases offer an almost unique situation for the study of commensal organisms because they tend to be isolated from contaminating outside influences for long periods. A study looking at Escherichia coli diversity is currently ongoing at the British bases and new findings are eagerly awaited.
Telemedicine

As previously mentioned, Antarctic stations are among the most remote places on Earth and are typically cut off from the outside world by the austral winter for six months at a time. Telemedicine plays a vital role in the health care provided at these stations [43] and is the link to specialist opinions. Anecdotal reports of the use of telemedicine [44] have been published along with a discussion of developments [45].
Epidemiological studies

environment. Antarctica is an enormous untouched scientific resource that, under the Antarctic treaty, will, it is hoped, be preserved for future generations of scientists. Each of the nineteen member states who have a scientific presence in the Antarctic report to the Scientific Committee on Antarctic Research (SCAR). The British Antarctic Survey aims to undertake science in Antarctica that can have a global significance. Many of the other nations undertake Antarctic research that stretches beyond the realms of this world and into space. Research continues into all of the above subjects but, as we can see, Antarctic medical research is in its infancy. There is enormous scope for ongoing research not only into the fields discussed, but also in other aspects of psychology and sociology, environmental control systems, water management and recycling techniques. Medical research forms only a small part of the science undertaken in Antarctica but its far reaching importance should ensure that it is continued.
References 1 Shackleton, E.H. (1909) The Heart of the Antarctic, Heinemann 2 Charcot, J. (1911) The Voyage of the Pourquoi pas?, Hodder and Stoughton 3 Fodstad, H. et al. (1999) Arctic and Antarctic exploration including the contributions of physicians and effects of disease in the polar regions. Neurosurgery 44, 925940 4 Rivolier, J. and Bachelard, C. (1988) European Space Agency Report, Paris 5 Harrison, A.A. and Clearwater, Y.A. (ed.) and McKay C.P. (ed.) (1991) From Antarctica to Outer Space Life in Isolation and Confinement, Springer 6 Lugg, D.J. and Sullivan, P. (2001) Recent advances in medical research. Australian Antarctic Magazine 1, 3031 7 Farman, J.C. et al. (1985) Large losses of total ozone in Antarctica reveal seasonal CLOx / Nox interaction. Nature 315, 207210 8 Young, A.R. (1997) The biological effects of ozone depletion. Br. J. Clin. Pract. (Suppl. 89), 1015 9 Meyer-Rochow, V.B. (2000) Risks, especially for the eye, emanating from the rise of solar UV radiation in the Arctic and Antarctic regions. Int. J. Circumpolar Health 59, 3851 10 Pitson, G.A. et al. (1996) Effect of seasonal ultra violet radiation fluctuations on vitamin D homeostasis in Antarctic expeditioners. Eur. J. Appl. Physiol. 73, 237244 11 Zerath, E. et al. (1999) Decreased serum levels of 1.25 (OH)2 vitamin D during one year of sunlight deprivation in the Antarctic. Eur. J. Appl. Physiol. 79, 141147 12 Yonei, T. et al. (1999) Bone metabolic changes in Antarctic wintering team members. Bone 24, 145150 13 Oliveri, B. et al. (1999) Effect of one-year residence in Antarctica on bone mineral metabolism and body composition. Eur. J. Clin. Nutr. 53, 8891

Epidemiological studies in Antarctica are hindered by numerous factors already discussed including small population sizes, short lifetime exposure to the Antarctic environment and the presence of multiple variables. Hence, these studies are often retrospective or meta-analyses. Contrary to popular opinion, cold injuries are relatively rare in the Antarctic owing to an awareness and advances in clothing technology. A retrospective review of cold injuries experienced by members of the British Antarctic Survey is of interest [46] because injuries in general form the majority of Antarctic medical problems (I. Grant, pers. commun.). Other sources of injuries that have been studied include recreational activities [47] and it appears a disproportionate number of injuries are attributable to leisure activities. Another published study looked at five cases of injuries inflicted by avian species and commented that there could be a general under-reporting of such incidents [48].
Concluding remarks

Antarctic research is about much more than the study of humans in a cold
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14 Farrace, S. et al. (1999) Endocrine and psycho-physiological aspects of human adaptation to the extreme. Physiol. Behav. 66, 613620 15 Palinkas, L.A. (1992) Going to extremes: the cultural context of stress, illness and coping in Antarctica. Soc. Sci. Med. 35, 651664 16 Reed, H.L. et al. (1990) Changes in serum tri-iodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome. J. Clin. Endocrinol. Metab. 70, 965974 17 Do, N.V. et al. (1996) Thyroid hormone responses to environmental cold exposure and seasonal change; a proposed model. Endocrinol. Metab. 3, 716 18 Reed, H.L. et al. (1988) Pituitary and peripheral hormone responses to T3 administration during Antarctic residence. Am. J. Physiol. 254, E733E739 19 Reed, H.L. et al. (2001) Impairment in cognitive and exercise performance during prolonged Antarctic residence: effect of thyroxine supplementation in the polar triiodothyronine syndrome. J. Clin. Endocrinol. Metab. 86, 110116 20 Williams, D.L. et al. (1986) Cell mediated immunity in healthy adult in Antarctica and the sub Antarctic. J. Clin. Lab. Immunol. 20, 4349 21 Muller, H.K. et al. (1995) Cell mediated immunity in Antarctic wintering personal: 19841992. Immunol. Cell Biol. 73, 316320 22 Tingate, T.R. et al. (1997) Antarctic isolation: immune and viral studies. Immunol. Cell Biol. 75, 275283 23 Mehta, S.K. et al. (2000) EpsteinBarr virus reactivation associated with diminished cell mediated immunity in Antarctic expeditioners. J. Med. Virol. 61, 235240 24 Shearer, W.T. et al. (2001) Antibody responses to bacteriophage X174 in humans exposed to the Antarctic winter over model of space flight. J. Allergy Clin. Immunol. 107, 160164 25 Tringali, G. et al. (2000) Circulating interleukin-1- levels after acute and prolonged exposure to low temperatures. Neuroimmunomodulation 7, 177181 26 Ember, L.R. (1998) Surviving stress. Chem. Eng. News 76, 1617 27 Palinkas, L.A. (2000) Behaviour and performance on long duration space flights: evidence from analogue environments. Aviat. Space Environ. Med. 71(Suppl 9), A2936 28 Sandal, G.M. (2000) Coping in Antarctica: is it possible to generalise results across settings? Aviat. Space Environ. Med. 71 (Suppl. 9), A3743 29 Palinkas, L.A. (2000) Summary of research issues in behaviour and performance in isolated and confined extreme (ICE) environments. Aviat. Space Environ. Med. 71 (Suppl. 9), A4850 30 Lugg, D.J. and Shepanek, M. (1999) Space analogue studies in Antarctica. Acta Astronaut. 44, 693699 31 Sauer, J. et al. (1999) Performance Evaluation in analogue space environments: adaptation during an 8-month antarctic wintering-over expedition. Aviat. Space Environ. Med. 70, 230235 32 Struster, J. et al. (2000) The relative importance of behavioural issues during long-duration ICE missions. Aviat. Space Environ. Med. 71 (Suppl. 9), A1724 33 Palinkas, L.A. et al. (2000) Sleep and mood during a winter in Antarctica. Int. J. Circumpolar Health 59, 6373 34 Wood, J.A. et al. (1999) Psychological changes in 100-day remote Antarctic field groups. Environ. Behav. 31, 299337

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35 Taylor, A.J.W. (1998) Psychological adaptation to the polar environment. Int. J. Circumpolar Health 57, 5668 36 Ikegawa, M. et al. (1998) Psychological studies of a Japanese winter-over group at Asuka station, Antarctica. Aviat. Space Environ. Med. 69, 452460 37 Palinkas, L.A. et al. (2000) Predictors of behaviour and performance in extreme environments: the Antarctic space analogue program. Aviat. Space Environ. Med. 71, 619625 38 Broadway, J.W. and Arendt, J. (1988) Seasonal and bright light changes of the phase position of the human melatonin rhythm in Antarctica. Arctic Med. Res. 1 (Suppl. 7), 201203 39 Broadway, J.W. et al. (1987) Bright light phase shifts the human melatonin rhythm during the Antarctic winter. Neurosci. Lett. 79, 185189

40 Owen, J. and Arendt, J. (1992) Melatonin suppression in human subjects by bright and dim light in Antarctica: time and season dependent effects. Neurosci. Lett. 137, 181184 41 Yoneyama, S. et al. (1999) Seasonal changes of human circadian rhythms in Antarctica. Am. J. Physiol. 277, R1091R1097 42 Kerr, G.R.D. et al. (1993) An analysis of the diversity of Haemophilus parainfluenzae in the adult human respiratory tract by genomic DNA fingerprinting. Epidemiol. Infect. 111, 8998 43 Lugg, D.J. (1999) Telemedicine: the cornerstone of Australian Antarctic medical practice. In: Proceedings of 7th National Health Informatics Conference (Walker, J. et al., eds.), pp. 1317, Health Informatics Society Australia 44 Hyer, R.N. (1999) Telemedical experiences at an Antarctic station. J. Telemed. Telecare 5 (Suppl. 1), S87S89

45 Lugg, D.J. (1998) Telemedicine: have technological advances improved health care to remote Antarctic populations? Int. J. Circumpolar Health 57 (Suppl. 1), 682685 46 Cattermole, T.J. (1999) The epidemiology of cold injury in Antarctica. Aviat. Space Environ. Med. 70, 135140 47 Cattermole, T.J. (1999) The epidemiology of skiing injuries in Antarctica. Injury 30, 491495 48 Bovard, R.S. (2000) Injuries to Avian researchers at Palmer Station, Antarctica from Penguins, giant petrels and skuas. Wilderness Environ. Med. 11, 9498

James J. Olson Medical Officer, Rothera Research station, British Antartic Territory. e-mail: [email protected]

Book Review

Present and future of ACE inhibition

ACE Inhibitors edited by P . DOrleans-Juste and G.E. Plante, Birkhuser Verlag, 2001. Euro119 (hardback) (x + 184 pages) ISBN 376435982X

Today, blockers of the reninangiotensin system are standard therapy for essential hypertension and congestive heart failure, and represent an important step in the management of patients with diabetic and non-diabetic nephropathies. This success story started with the discovery and the clinical development of angiotensinconverting enzyme (ACE) inhibitors [1] and has been amplified recently with the availability of specific angiotensin II AT1 receptor antagonists [2]. There are several books on ACE inhibitors, but the most recent, edited by P. DOrleans-Juste and G.E. Plante, deserves special attention because it covers several facets of ACE inhibitors that are not frequently discussed in such detail. The books starts with an interesting historical perspective written by Sir John Vane, Nobel laureate, who contributed personally to the understanding of the physiology of the ACE enzyme and participated in the early development of ACE inhibitors. His contribution describes the difficulty in developing a new therapeutic concept and the important role played by serendipity, chance and coincidences. M. Lamarre-Clich and P. Larochelle present a very comprehensive analysis of all clinical trials that have been performed
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with ACE inhibitors in the various fields of hypertension, heart failure, post-myocardial infarction heart failure, acute myocardial infarction, diabetes, left ventricular hypertrophy, renal failure and patients with a high cardiovascular risk. This chapter underscores the tremendous clinical impact that ACE inhibitors have on the management of patients with cardiovascular diseases today. Another interesting chapter covers one important aspect of ACE inhibitors: their impact on the metabolism of kinins. The role of bradykinin in mediating the clinical effects of ACE inhibitors has always been a controversial issue. In this book, Adam et al. provides a critical analysis of the biochemistry and pharmacology of kinins in relation to the therapeutic effects and side-effects of ACE inhibitors. The interaction between ACE inhibitors and nitric oxide or the endothelin pathway, the role of the reninangiotensin system on the central and peripheral autonomic nervous system, the effect of ACE inhibition on thirst and salt appetite, and the impact of ACE inhibitors on the microcirculation are some of the many basic and clinical facets of ACE inhibitors that are also discussed in this book. Future research directions in the field of ACE inhibition and the reninangiotensin system are also proposed. Thus, M. Lajemi and A. Benetos reviewed numerous studies that have attempted to evaluate the role of genetic variants of the components of the reninangiotensin system and their potential implications on cardiac and arterial phenotypes. Although there is always the secret hope that genotyping will

enable identification of population subgroups that could benefit from early treatment with ACE inhibitors, this chapter confirms that there is still a long way to go until such hope is realised. Finally, the future therapeutic developments are discussed, and a new group of drugs that provide dual inhibition of ACE and neutral endopeptidase are reviewed. These new agents, at present under clinical investigation, offer the possibility of blocking the reninangiotensin system and, simultaneously, potentiating the systemic and renal effects of atrial natriuretic peptides (ANPs). These drugs have an interesting therapeutic potential but the success of their development will depend on their tolerability profile [3]. As a whole, this book represents a valuable working tool that covers several new facets of ACE inhibitors that might be of interest to clinicians treating patients with cardiovascular diseases, and to basic scientists working on the reninangiotensin system.
Michel Burnier Division of Hypertension and Vascular Medicine, Avenue P . Decker, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland. e-mail: [email protected]
References 1 Gavras, H. and Brunner, H.R. (2001) Role of angiotensin and its inhibition in hypertension, ischemic heart disease, and heart failure. Hypertension 37, 342345 2 Burnier, M. (2001) Angiotensin II type 1 receptor blockers. Circulation 103, 904912 3 Burnier, M. (2001) Novel angiotensin II inhibitors in cardiovascular medicine. Expert Opin. Invest. Drugs 10, 19571964

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