Emerging Insights into the Genesis of Cerebral Ischaemia and Stroke.
Arterial dissection is often associated with localized headache or facial pain at or before the onset of neurological signs. Cerebral infarcts can also occur in connection with hypotensive episodes. Cardiac emboli have been reported to account for between 15 and 50 percent of cases; the wide range illustrates that the diagnosis often is uncertain. Atrial fibrillation is a well recognized risk factor for cerebral embolism and the most common causes are rheumatic and ischaemic heart disease. The frequency of stroke increases with the duration of fibrillation. Cardiac embolism as a cause of stroke increases with age and may constitute about half of the cases in patients > 75 years of age. As an intrinsic intracranial source of strokes, lacunae reflect arterial disease of the small penetrating arteries supplying the internal capsule, basal ganglia, thalamus and paramedian regions of the brain stem. They are thought to account for about 15 to 20 percent of strokes. It is currently debated whether some lacunae are of embolic origin. Most intracerebral haemorrhages occur in the supratentorial compartment, mostly involving the basal ganglia and the thalamus. The second most common location is the subcortical white matter of the cerebral lobes. Less than 15 percent of the haemorrhages are located in the cerebellum or pons. The symptoms will depend on the location and the size of the haematoma. Although the onset is usually abrupt, both the focal deficit and the level of consciousness usually undergo a gradual worsening due to further bleeding and /or secondary swelling. Haematomas of moderate or large size are accompanied by decreased levels of alertness. Diagnosis The neurological symptoms and signs will depend on the vascular territory involved. Most infarcts are supratentorial with the vascular territory of the middle cerebral artery being most often affected. The clinical features sometimes suffice to differentiate acute haemorrhage from infarction. Classification of the ischaemic stroke into subtypes can, to some extent, be performed on clinical grounds. However, it is not possible, clinically, to definitely separate haemorrhages from infarction, as revealed by brain computed tomography (CT), which is now routinely used in most stroke centres. Small haemorrhages can give comparatively minor synlptonls or even transient symptoms. Whereas haemorrhages are seen on CT scan immediately after onset, brain infarcts may not be visible during the first days 'and, if small, may not be detected at all. A lumbar puncture, previously the investigation of choice to separate haemorrhage from brain infarction, is now less frequently performed in centres where CT is available, but might be of value in selected cases. Ancillary Methods

blood cells. Doppler techniques are widely used for the diagnosis of cerebrovascular occlusive disease. The most commonly used technique is that of plotting the Doppler frequency shift against time. When stenosis is present, blood flow velocity increases in the stenotic portion of the vessel and is detected by an increase in the frequency of the Doppler shift signal. Turbulence distal to the stenosis produces a characteristic visual pattern. To visualize the carotid arteries, a two-dimensional ultrasound imaging technique is used. Currently, the two techniques (Doppler flow and imaging) are combined in real time, defining structure and flow. This technique is called Echo-Doppler. Transcranial Doppler ultrasonography is a non-invasive procedure for the assessment of intracranial cerebral circulation, allowing measurement of blood velocity in cerebral arteries at the base of the brain. However, since the diameter of the arterial lumen is unknown the blood flow cannot be determined. Despite this limitation, the method can be useful in answering specific questions such as detection of haemodynamically significant intracranial arterial stenosis. It is particularly useful in following changes in patients with subarachnoid haemorrhage who develop spasm, monitoring of braininjured patients and intraoperative and postoperative monitoring of neurosurgical patients (Petty et al., 1990).
2 ) Magnetic Resonance Imaging (MRI)
The underlying principle of MRI is that many nuclei respond to the application of strong magnetic fields by absorbing and re-emitting radio waves, that can be detected and analysed and thus used to generate spectra indicating the concentration of various chemical species of these nuclei. Protons are among the most sensitive and abundant nuclei in biological tissues and have been widely used for MRI. Bone is not visualized and areas normally obscured by bone on C T scans are easily imaged. The resolution of grey and white matter is superior to that of C T scanning and cerebral infarction is evident much earlier, usually within 2 to 6 hours. However, C T is superior in early identification of brain haernorrhages and will probably continue to be the screening method at admittance of stroke patients. The recent development in MR angiography, MR diffusion weighted imaging, MR spectroscopy and functional MRI together with the higher time resolution and more widely accessible MRI than PET have made these techniques powerful tools in experimental and clinical stroke research (Baron, 1993; Neil, 1993).

V a l o ~ t i n hf. and Graf R. o
Fig 2. Sequential PET uuagcs of a n individual c;lr representing CMRCl bcforc (con[rol) and time points after left middle cerebral artery occlusion (6 hours and 25 hours). Progressive
dctcriorii~ionincludes in [his case the hcrnisphe~ con~rala[cral 10 the ischemic focus. probably due ro malignimt cderna formation and risc of'ilitr~~cranial pressure.
[By L. O U I. I P. F ~ of Dr. R. Grac Mo.v Plutrk If?srirure j?w Nei[rological Re.rrurc/r.Cologtrr~, c r t ~ a ~ y. ] G
experimental ;min~als. If c o n f i m ~ e d in man, these observations could be of' importance in clinical trials wilh fibrinolytic agenls and during operations on severely stenotic vessels where gradual rather than abrupt opening of an occluded vessel should be aimed at. However, in the clinical situation i~ wouId be a difficult task to decide if and when atte~nplsto reduce [he blood flow should be tried. An aggravating effecl of postischaemic hyperernia could be related LO any of the currently discussed mechanisms for nerve cell death following ischaeniia such as free radicals. lactacidosis.
excitatory amino acids and possibly to some additional intrinsic or extrinsic factors. However, so far clinical studies have not confirmed that hyperaemia aggravates the lesions, rather hyperaemia has been proposed to be a prognostically good sign (Jorgensen et al., 1994; Marchal et al., 1993). Preliminary reports from studies on thrombolytic therapy in stroke indicate that it might be a smaller problem than expected. One possible explanation could be that the reflow does not occur so rapidly as under experimental conditions. Further studies are needed to clarify the possible adverse and beneficial effects of hyperaemia in stroke. One other problem that must be anticipated in ischaemia is the underlying neuronal damage. Since energy is required to uphold the ion gradients across nerve and glial cell membranes, energy failure will lead to a shift with efflux of K+ from cells and influx of Na+, C1- and Ca2+. This ion shift will lead to an accumulation of water within the cells, an intracellular oedema. Accumulation of metabolites within the cell will add to this oedema, which in the early stage is completely reversible. Ischaemia leads to a diffuse transmitter release since energy is needed to keep transmitters stored in their granules. The electrical activity of the neurons stops when the blood flow is decreased to about onethird of the normal values (under normal temperature and blood glucose levels) but some basic cell function is still present and the cells can regain their function if the blood supply is restored. There are various hypotheses as to t h e triggering mechanisms fcr neuronal death and some will be presented below. Current research indicates that these mechanisms combine in the process that finally kills neurons. The neuronal damage can be of two types:. selective neuronal vulnerability affecting groups of neurons with a characteristic distribution within the brain, and infarction, affecting not only neurons but also blood vessels and glial cells.

Xjenza 1999;4 l :

Staged Present:Attending to the Mystical on the Stage of Working Memory
Nadia Farrugial , Glyn Goodall * , John Schranz 3 and Gertrude Rapinett 4 ** I Department of Biomedical Sciences, University of Malta, Msida, MSD 06, Malta. 2 ZNSERM U.394, Neurobwlogie Integrative, 33077 Bordeaux, Cedex, France. 3* Old University Building, St. Christopher Street, Valletta, Malta. 4 Department of Biomedical Sciences, University of Malta, Msida, MSD 06. Malta. ** Correspondence and requests for reprints should be addtessed to this author.
Summary: An experiment (N = 48) was conducted to investigate the effect of focused attention on working memory. Two experimental groups, meditators (n = 12) and contemporary actors (n = 12), were matched on age, gender and level of education and measured on working memory and attention tests from the CANTAB battery. The practice of meditation and contemporary theatre training satisfied the criteria of maintaining focused attention necessary for this study. Through the performance of these groups the possible effect of focused attention induced by different training procedures could be compared and explored. Although on most measures the experimental groups did not -differsignificantly, a significant difference was found between meditators and their controls on one test (Paired Associates Learning) measuring working memory capacity. Since these two groups differed from actors and their controls in age (Mean age of meditators and actors = 37.00, 23.75 respectively), it was suggested this might account for the apparent non-sign8cant difference between the two experimental groups. C N T A B norms establish different thresholds for age. The results also suggest that exercises of focused attention might contribute in delaying the normal degeneration of higher cognitive functions in old age. Keywords: Working memory, attention, consciousness, actors, meditators, CANTAB Introduction In recent years, psychological research has advanced in a field where previously it feared to tread - consciousness. Research into the structural basis and process nature of consciousness has generated an impressive amount of literature and yet the nature of consciousness continues to elude and intrigue.
In this research, consciousness is examined from the perspective of working memory and attention. This relationship hinges upon Baars' (1988) Global Workspace (GW) theory of consciousness, in which Baars compares everyday human consciousness to a theatre. Baars describes the theatre of consciousness as having a stage of working memory over which a spotlight of attention roams.
Attention and the periphery of awareness are the two salient points in Baars' theory of consciousness paars, 1988). In Baars' model, focal cansciousness a: as a c 'bright spot' on the stage, directed by the selective 'spotlight' of attention. The bright spot is surrounded by a 'fringe' of vital but vaguely conscious events on a 'stage' of working memory. Information from the bright spot is globally distributed through the theatre to two classes of complex unconscious processors: those in the darkened theatre 'audience,' who receive information from the bright spot; and the 'behind the scenes', unconscious contextual systems, which shape events in the bright spot (Baars, 1997b). 1997b). This core aspect of Baars' (1988) theory has been echoed by other theorists who view consciousness as the awareness of what is in WM (LeDoux, 1998). Kosslyn and Koenig (1992) argue that to be aware of something, it must be in WM, and Johnson-Laird (1988) notes that the contents of WM are what we can be conscious of at any moment. WM stores relevant information only temporarily, and its main feature is its ever-changing content. Thus the object in awareness can similarly change continuously.

The spotlight of anention Only events in the bright spotlight are strictly conscious at any point in time. However the contents of WM can become conscious as the attention spotlight roams onto them. The actors trying to get in the bright spot Elements in W M compete to gain the spotlight of attention. The more an 'actor' requires being conscious, the more it will compete against the others. For example, our daily womes come into consciousness even when we are trying to concentrate on the task at hand. Context is set behind the scenes Often enough attentional selection is spontaneous and unconscious, as if commands from behind the scenes influence the direction of the spotlight. For instance, all perceptual systems are shaped by unconscious factors: for example, our visual perception of depth is shaped by the unconscious assumption that light comes from above. Similarly, conceptual assumptions can act as unconscious contexts. The director Working memory is guided by an executive system that
The stage of working memory (WM) Although WM can store up to seven plus or minus two elements, we are only conscious of a single element at any point in time. WM contents are mostly in the dark, but its active elements can come into awareness (Baars.
Staged Present: Attending to the Mystical on the Stage of Working Memory
makes decisions guided by goals. But the goals themselves may not be entirely conscious. The intention of automatic actions is often beyond awareness. Thus it seems that the theatre director works invisibly behind the scenes. Such executive functions are located in the prefrontal cortex (Baars, 1997~).
executive. Thus, WM capacity is not really about storage or memory per se, but about the capacity for controlled, sustained attention in the face of interference or distraction (Engle, Kane & Tuholski, in press). Engle, Kane and Tuholski (in press) argue that this attention capability is domain free and therefore individual differences in this capability reveal themselves in a wide variety of tasks. Indeed, Conway and Engle (1996) emphasize that the correlation between measures of WM capacity and higher-order cognitive tasks is not a result of skill in the specific tasks - as Ericsson and Kintsch (1995) propose with their studies on expertise - but rather of the underlying critical feahre of controlled attention which is inherently different 'in each individual. Consequently, the study of attention and working memory provides a singular means of understanding consciousness. Moreover, questions are raised as to whether engaging in activities which require maintaining focused attention over long periods of time will produce measurable differences in the cognitive elements of Baars' model of consciousness. More specifically, could the attention spotlight be undergoing particular changes that might affect the working memory stage or any other cognitive processes in Baars' Global Workspace theory of consciousness?

The audience This consists of diverse specialized unconscious capacities, like long-term memory, and operators that induce implicit learning or procedural knowledge. Consciousness can be the gateway to vast unconscious knowledge (Baars, 1997b).
The strength of the GW theory lies in its ability to describe what we know intuitively. In normal everyday consciousness the complex network system in our brains generates thousands of bits of information per second. However, WM enables us to focus and attend to a limited amount of information relevant for that task at hand. This produces a stream of consciousness, which contains the most relevant pieces of information from one moment to the next and enables the mind to continuously change the contents of working memory producing a myriad of thoughts, emotions and perceptions. Our normal everyday consciousness can be likened to a continuous divided attention task: we drive, whilst listening to the radio; listen to a lecture, whilst thinking about yesterday's party. We seldom focus on the same object in the environment for more than a few minutes. This is contrary to the issue raised by Crook (1980) where he showed that when subjectively aware a person is completely focused on the environment or the task at hand. This implies that the object of attention remains fixed for a lengthy period of time. Forman (1998) showed that this is precisely the technique used by mystics to empty their mind and reach altered states. Through disciplines like meditation, where there is.a focusing of attention on a single repetitive stimulus like breathing, the stream of consciousness is reduced to a single element over time. Forman (1998) raises the issue that the mystical experience is the simplest possible consciousness, and consequently should be studied to enlighten us on the more complex forms of everyday consciousness. The central role of attentional processes in working memory (WM) has been further explored by Engle, Kane and Tuholski (in press) who have described WM as a system consisting of: a store in the form of long-term memory traces active above threshold; processes for achieving and maintaining that activation; controlled attention. In this regard, WM capacity, refers to the capacity of just one element of the system: controlled attention. Therefore Engle, Kane and Tuholski (in press) do not focus on the entire WM system, but rather on the capabilities of the limited-capacity attention mechanism described by Baddeley and Hitch (1974) as the central

Table 11. Pearson's correlations between total hours training in actors and performmce on CANTAB tests.
-.I7 -.02.25 -.I6.04 -.03.18.16.38.20
.58.95.42.59.88.91.56.59.21.52
Table 12. Pearson's correlations between total hours training in meditators and'performance on CANTAB tests.
Age Differences Performance on the CANTAB tests varies significantly with age. In view of the mean age difference between actors and controls compared to meditators and controls, independent samples t-tests were performed to determine whether performance varied as a function of age. It was expected that actors perform better than meditator controls both as a function of training and age. The two groups differed significantly on the RVP probability of false alarm (t (22) = -1.58, p = 0.03) and SWM strategy score (t (22) =.78, p = 0.02.
Meditators were compared to actor controls using an independent - samples t-test (two-tailed). Although meditators are older than the actor controls, their performance on the CANTAB measures is better with the differences being significant for the ID-ED errors at ED shift (t (20) = 1.16, p = 0.02) and RVP probability of hit (t (19) = S l , p = 0.04). The actor controls and meditator controls differ only as a function of age. Independent-samples t-test yielded a significant difference on the SWM strategy score (t (18) =.2 1, p =.03).

Discussion

This study has focused on the relationship between attention, working memory and consciousness by studying focused attention from the perspective of two disciplines, meditation and contemporary theatre. The effect of training in meditation and contemporary theatre was then explored through standardised tests that measure higher cognitive functions, notably working memory. There were few significant differences on the performance of specific CANTAB tests among the actors, meditators and their controls. In the Intra/Extra - Dimensional Shift (IED) test, which is a measure of shifting of attention no significant differences were obtained on stage reached in IED, total errors in IED and ID-ED errors at ED shift. However, a significant main effect was obtained on errors up to ED shift. Age covaried significantly. This implies that any differences between the groups are not necessarily a result of training but may be a result of an interaction with age. This is interesting in view of the 'fact that although, not statistically significant, meditators reached a higher stage on the IED than their controls and performed better than actors who did not differ from th'eir matched controls. This result is surprising in view of the age difference between the meditators and actors. Meditators and their controls had a mean age approximately ten years older than that of the actors and control, therefore it is interesting that meditators performed better in this test than the actors and controls, especially when their age counterparts performed worse than the younger groups as expected. Consequently, it might be suggested that whilst meditators' controls scored lower than the younger groups because of the normal weakening of cognitive functions due to older age, in meditators, this cognitive deterioration seems to be less marked. This claim is supported by the fact that when meditators were compared to the actors controls they differed significantly on the RVP probability of false alarm and SWM strategy score. Stoltzfus, Hasher and Zacks' (1996) findings that older adults find it more difficult to inhibit irrelevant thoughts and distractions could also support this pattern. In the IED, which is an exercise of attention and disattention, meditators' controls were probably more distracted as predicted by Stoltzfus, Hasher and Zacks (1996). Actors made fewer errors in the ED shift, when the task was to shift their attention between two similar stimuli. lnterestingly the meditators made most errors in these preliminary stages of the test. Perhaps the meditators' training in keeping fixed attention on a single object hindered them from shifting their attention at first, but gradually they learnt to attend and disattend according to the task at hand, improving their performance, ultimately reaching the highest stages in the IED. It is interesting to note that all participants irrespective of condition performed lower than that expected from the CANTAB norms. This finding is interesting because the CANTAB is supposedly culture-fair, however, there are

cave floor soil is of a similar age. The different cave soils studied showed a relatively stable 234Th/40K ratio, with a mean value of 0.422 + 0.052sd. 40Potassium is an unrelated gamma emitter which, because of the high solubility of potassium salts, may be assumed to be in a steady state equilibrium in all samples. The stable 234Th/40K ratio in Maltese karstic caves, including Ghar Hasan, Ghar Dalam and Ghar ilFriefet, reflects the steady state relationship between these two gamma emitter elements in cave floor soil. The similarity of the results obtained from the different sites suggests that bony remains buried in karstic limestone cave systems in Malta may be compared since they are exposed to near identical chemical and physical conditions. The 234Th/226Ra ratios in the different cave soils appeared to show a wider variation in results around a mean value of 1.19 + 0.396sd, with a range of 0.72-1.79. The reasons for this wide difference range in the daughter elements of uranium have not been elucidated, but may reflect the possible age of the soil sample with older soils showing a lower ratio. The difference in the half-lives of the two radionuclides 234Th:24 days; 226Ra 1600 years - would result in higher Radium levels and thus a lower 234Th/226Ra ratio in older specimens. Further studies in this regard are required.
A dynamic interplay of factors would be expected to exist in any cave system, such as the one exemplified by Ghar Hasan. The cave-soil samples originated from the cave rock, and should have had an original value equivalent to the 234Th/40Kratio of the rock (0.63). The ratios in the various cave-soil samples have been apparently modified over time through the action of percolating rainwater. Rainwater is acidic in nature and has a near zero 234Th/40K ratio. This falls onto the superficial soil/rock dissolving and leaching away the various elements at variable rates depending on the solubility. With prolonged exposure, the acid soluble elements are leached away, leaving the terrarossa soil typical of the superficial cliff in which Ghar Hasan is found (Schembri and Baldacchino, 1992). As a result of this prolonged leaching, the 234Th/40K ratio of the superficial soil (0.26) was very much lower than the 234Th/40K ratio of the derivative cliff rock (0.63). The minerals are thus continuously leached into the percolating water, which showed a higher 234Th/40K ratio (0.94). This water with a relatively high 234Th/40K ratio leaches the cave-floor and cave-roof soils, which also originated from the same derivative rock (234Th/ 40K ratio 0.63), and reduces the 234Th/40Kratio of these soils to a lesser extent (0.44-0.46) than the superficial cliff soil. The presumably recent bony remains buried in the cave-floor soil equilibrate with the percolating water and concentrate uranium and its daughter elements by an active process, whereby the phosphate content of hydroxy-apatite in bone is replaced. This results in a high 2'4Th/40K ratio (1.61) [Figure 11.

Figure 1. Passive etched- rack detectors.
A Survey on Radon Levels in Local Dwellings
Figure 2. The computed geometric mean.
No. of dwellings sampled 68

Table 1

Period and duration of exposure 1994 - hour 1997 - 98 1year

Type of detector

electronic radon monitor passive etch-track detector
Arithmetic mean in B~ m-3 55
Geometric mean in B~ m-3 40
Geometric Standard deviation 2.3
Bq m-3). The lowest value recorded was that in Dingli with 6 Bq m-" during the MayIOctober period (corresponding November1 April reading 8 B q m-3).
Acknowledgements The authors-would like to thank the National Radiation Protection Board (UK), for providing the radon detectors and their subsequent analysis. References Hardcastle, GD. Howarth CB. Naismith SP, Algar RA. and Miles JCH. NRPB etched-track detectors for area monitoring of radon. Chilton, NRPB-R283 (1996). London, HMSO.
Mifsud I. Amato Gauci A J, Licari L and Sammut M (1997) Preliminary investigation on radon levels in local dwellings. Xjenza, 2: 1 34-38.
Conclusions When compared with the results of the survey carried out in 1994195 these were lower than that in the original survey (geomean of 32 Bq m-3 compared to Bq m-3). This difference may be d u e to the averaging out effect of long term monitoring which takes into consideration seasonal variations as against 24 hour snapshot readings utilised in the pilot phase of the study.

Article

The Genetics of Mortality and Immortality
Alfred Cuschieri Department of Anatomy, University of Malta, Msida, Malta. Introduction In Man's perpetual concern about life and death, the topic of mortality and immortality is undoubtedly an attractive and intriguing topic, especially if combined with the even more attractive and intriguing subject of genetics. From a strictly scientific and genetic point of view, the meaning of mortality and immortality is, perhaps, somewhat different from what immediately comes to mind when one is talking about these topics. The main concept underlying mortality and immortality is not concerned with death and dying but is centred on life, and this paper will consider the subject of mortality from the point of view of life.
This paper will not attempt to give a metaphysical discussion on life after death. From a strictly scientific viewpoint, this is a contradiction in terms. There are many different aspects of mortality and immortality. This paper will define the meanings of mortality and immortality in the context of the present discussion and will attempt to explain the genetic aspects of mortality and immortality and how these two contrasting concepts can be reconciled in scientific terms. contributed to alter drastically the life expectancy of individuals over the last century.

The Conflict of Life and Death It appears that the programme of life includes an in-built mechanism whereby it is ensured that all individuals die. But does it make sense that self-sustaining life in all its variety and beauty should programme itself to ensure that all individuals die? That life temlinates at the time when people are finding their fulfilment of life? As Oscar Wilde remarked in: A Woman of No Importance. "The soul is born old, but grows young. That is the comedy of life. And the body is born young and grows old. This is life's tragedy."

Cuscieri A.

Immortality of Unicellular Organisms The pattern of life as presented does not apply to all living organisms. A programmed time clock is not present among primitive organisms, particularly the unicellular ones such as amoeba or bacteria. Take bacteria as an example - they can easily be grown and, studied in cultures in the laboratory. Each bacterium divides to produce two organisms, which then divide again and again and can continue to do so indefinitely producing an infinite number of generations. There is no limit to the number of proliferation times and the number of generations and so we can call such cells "immortal". The individual organisms do not die between generations. If any of the individual organisms die i t is because of accidental circumstances such as toxic substances or lack of nutrients. Colonies of bacteria may die at a particular location where a hostile environment prevails but others will continue to proliferate.
In adverse environments, which are harmful but not quite lethal, the organisms may gradually undergo genetic mutations, which make them capable of surviving the adverse conditions. A familiar example is when bacteria become resistant to antibiotics, thus creating new strains. These mutations provide the mechanism to ensure survival of the species and continuity of iife. Potentially the organisms can live indefinitely. Death of individual organisms is an incidental chance occurrence. The concept of mortality here is not that death is an inevitable and inescapable occurrence, but that living organisms require certain conditions beyond which they cannot survive. Within those limits, life is self-perpetuating and self-adjusting. Within those limits, life is immortal.
continuity of the species in perpetuity. There is no limit to the number of generations that can be produced, and in this sense we can speak of an "immortal" germ cell line. This perpetuity, however, does not affect the rest of the body, the soma, which is in fact genetically programmed to die within the specified maximal life span. In higher organisms, including man, we can speak of the mortal soma and the immortal germ line!

Mortality in Individual Cells The inherent, in-built programmed mortality mentioned earlier, refered to the mortality of the body as a whole. However, death of the body is not the same as death of the component cells, although the two may be interdependent. An in-built, genetically programmed mortality is also to be found in the component somatic cells. If somatic cells, such as fibroblasts, are isolated from the body and nurtured in cell culture, providing all the nutrients and environmental conditions necessary to support growth, they will proliferate repeatedly. In this respect they are rather like unicellular organisms and bacteria. However, they differ from these organisms in one crucial factor - they will not proliferate indefinitely. They have a limited maximal life span, characteristic for the organism from which they were taken. The life span of human cells is different from that of similar cells derived from mice, sheep or other animals. And when they approach their maximum limit, they become unhealthy and aged, lose their ability to divide further and die.
The Concept of the "Individual" in Higher Organisms Does this concept of immortality apply only to primitive organisms, or can it be extended to all life, even human life? Here some clarification is required about the meaning of an "individual". Among higher organisms the concept of an individual is different from that among primitive organisms. Although in both cases the unit of life is the cell, the complex body that constitutes an individual in higher organisms is much more than its component cells. In higher organisms the multiplicity and variety of the component cells of the body contrast with the unity in the genetic composition of the body and its uniqueness. The genes contained in all the cells of the body are identical, no matter how diverse their functions may be. The genome belongs to the individual as a whole, and its component cells are all regulated by this singular genome. Each cell contains a copy of the individual's genome. Furthermore the genome of each individual is unique. The genome of each individual is different from that of other individuals of the same species. By contrast, the individuals in unicellular organisms are clones, all of which are genetically and structurally identical to one another and to the individuals from which they were derived. The Mortal Soma and the Immortal Germ Line In higher animals the propagation of life from one individual to another is restricted to only one particular cell line, the germ cell line, which produces spermatozoa and ova. The germ cell line is responsible for the
Interestingly, the maximal life span of cultured cells is not measured in chronological time but in the number of cell divisions, or the number of times the cell population doubles itself. In fact, it is quite independent of time. Under optimal conditions the limited number of divisions may be exhausted within several weeks. The process may be slowed down under certain conditions but the number of permitted doubling times remains the same. The process may even be interrupted by putting the cells in a deep freeze for a prolonged period of time. When the cells are again placed in culture, even after several years, they resume proliferation, retaining a memory for the number of their previous divisions, and continue to proliferate until they reach their limit. The component cells of the body, therefore, and not only the body as a whole, have in-built life-limiting biological clocks.

Can Somatic Cells be Immortalised?
The logical reasoning is that, if the same mechanism were to be applied to somatic cells, they too would become immortal. An interesting and very illustrative story emerging from experiments with cultured cells illustrates this point. Somatic cells were growing in culture for some time so that they had exhausted most but not all of their telomeres. These cells were infected purposely with a certain type of virus, such as the Rous Sarcoma virus. As expected, the virus invaded the cells, monopolised the genetic mechanism of the infected cells and used it to propagate itself, producing millions of viruses, which occupied the cells. The viruses caused havoc and the cells died. In this scenario of devastation, destruction and death there were a few lonely cells which survived this terrible ordeal. They began to recover and once again began to proliferate. They continued to proliferate over and over again and continued to do so. They had become transformed into immortal cells. They had been genetically altered by the virus, which, among other things, had activated their telomerase and so were liberated from the life-limiting telomere shortening. A similar mechanism also operates in most cancer cells. These too are genetically altered cells, which have been liberated from the normal mechanisms regulating cell proliferation. They proliferate without restraint. Since then they have been grown in laboratories world-wide and are acknowledged as immortal cells which will continue to proliferate as long people continue to culture them.

Genes for longevity

The mechanisms controlling cell mortality and immortality that have been referred to are not the same as those imposing mortality on the body as a whole. In fact, the two are quite distinct, although they are related. The aged body does not die because its component cells have reached their maximum limit of longevity. So why does the aged body die? Over the years there has been a shift of thought in this regard. The original idea that people died of old age has long been discarded. In 1819 Sir Anthony Carlisle commented: "It seems little more than a vulgar error, to consider the termination of advanced life as the inevitable consequence of time, when the immediate cause of death in old persons is generally known to be some well-marked disease". People do not die of old age but, people die in old age because of 2 cardiac infarct, a

Robine JM and Allard M (1998). Science, 279, 1834-1835. Wilde, 0. A Woman of No Importance, Act 1. Bodnar AG et a1 (1998). Science, 279,349-352. Carlisle A (1819) An Essay on the Disorders of Old Age and on
the Means for Prolonging Life.
Jazwinski SM (1996). Science, 273.54-59, Ewbank JJ, Barnes JM, et a1 (1997). Science, 275,980-983.

Errata

The Application of Multivariate Analytical Techniques to the Study of Marine Benthic Assemblages: A Review with Special Reference to the Maltese Islands.
Rene' M. Micallef and Patrick J. Schembri Department of Biology, University of Malta, Msida MSD 06, Malta
In the Contents page, the first author's name was incorrect. It should have read Rene' M. Micallef. Also, in Figure 1 (page 10) Manhatten was misspelt. It should have read Manhattan.

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Instructions for Authors
Xjenza will consider for publication papers in the following.categories: Original rese~rch reports Short reports Reviews Commentaries SHORT REPORTS should be of no more than 1,500 words and 2 tables or figures. Please contact one of the editors to discuss the suitability of topics for REVIEW up to 7,500 words, COMMENTARY - up to 2,500 words, or other material falling outside the usual categories. Submission of Manuscripts Manuscripts should be sent to the Editor. Prof. Angela Xuereb, Department of Pathology, University of Malta Medical School, G'Mangia. Tel: (+356) Fax:(+356 ) 235638 Please submit 4 copies, typewritten, double spaced with wide margins, keep a copy yourself. After an article has been accepted for publication, the final version should be provided in machine readable form with hard copy exactly the same as the data on disk. Please use LBM compatible disks preferably Word (ver. 2.0 or higher) format or Rich Text Format (RTF) without the use of heading and body styles. Authors are requested to submit together with the manuscript, the names and addresses of two referees, preferably from overseas. Conflict of Interest Authors are expected to disclose any commercial or other associations that might pose a conflict of interest in connection with the submitted article. All funding sources supporting the work, and institutional or corporate affiliations of the authors, should be acknowledged on the title page. Articles are considered for publication on the understanding that neither the article nor its essential substance has been or will be published elsewhere before appearing in Xjetr:~. Permissions Materials copied from other sources must be accompanied by a written statement from both author and publisher giving permission to Xjenza for reproduction. Obtain permission in writing from at least one author of papers still in press, of unpublished data, and of personal communications. It is the author's responsibility to ensure that permissions are obtained. Arrangement of Manuscripts Preface each paper with a suitable title, the author(s) name(s), and the full address of the institution in which the work was canied out (please identify the author for proofs - giving telephone and fax numbers - for correspondence and reprint requests). an abstract of no more than 200 words. and up to 8 keywords. Research reports should give an appropriate introduction, a single methods section (with the methodology of all experiments reports), results, and discussion. Either British or American spellings are acceptable, but please be consistent. Authors should express measurements in SI units. although they may include older conventional units in parentheses if they wish. Except for units of measurement, abbreviations should be spelled out on first use, and should standard. Drug names should be generic, although authors may add brand names in parentheses if they wish. Illustrations should be lightly numbered on the back in pencil, with orientation and your name. We prefer glossy photographs or professionally prepared line drawings; any lettering and symbols must be large enough to stand reduction in size - publication could be delayed if lettering or symbols are too small. For halftones send unmounted glossy photographs with explanatory legends on a separate sheet of paper. Please send one set of photographs and attach a set of photocopies to each copy of the manuscript. Please contact the publishers for an estimate of the cost for colour illustrations. Illustrations on Electronic Media should be in a common format (Bitmap, JPG or TIFF) and of publishing quality. Tables should bear Roman numerals and be typed on separate sheets of paper. Each table requires a title, but no legend; identify footnotes by superscripts 1.2,', etc. References follow the Harvard system. In the text give the author(s) name and, in parentheses, the date of the paperbook being cited. Differentiate between papers by the same author in the same year by a, b, c etc., immediately after the date. Where there are three or more authors use et al. in the text and a, b, c to resolve ambiguities. All works cited must be listed at the end of the paper, ordered alphabetically by first author's name. For each first author, list single author works, next joint authored works in alphabetical order, last multi-authored works in chronological order. Each reference should give the names and initials of each author, the year of publication, the title of the paper, the name of the journal or book in full, the volume or edition, the first and last page. and, for books, the publisher and town of publication. For example: Sceni CA, Abela W, Galdies R, Pizzuto M, Grech JL and Felice AE (1993) The b+ IVS. Int No. 6(T->C) Thalassaemia in heterozygotes with an associated Hb Valletta or Hb S Heterozygosity and homozygotes from Malta. British Jourtlal of Haetr~atology, 669-67 1. 83. Felice AE (1992) Molecular Epidemiolgy of Haemoglobin, and the Molecular biology of Normal and Abnormal Globin gene expression. In: Collected Papers (Eds R EllulMicallef and S Fiorini). pp. 357-391. University Press, Malta. Neil David Rawn J (1989) Biocl~err~isr,:~. Patterson Publishers, North Carolina Muscat R, Papp M and Willner P (1992a)> Antidepressant-like effects of dopamine agonists in an animal model of depression. Biological Psychiatry. 31.937-946. Proofs, Reprints and Copyright Authors will normally be sent page proofs by fax where available. Such corrections as are necessary should be listed in the form of a table, with the location of the correction in the left hand column and the correction required in the right hand column. This table should be faxed to the editors within three days of proof receipt. Alterations. other than essential corrections to the text of the paper. should not be made at this stage; the cost of such alterations may be passed on to the author. A form for ordering reprints will be supplied with the proofs and should be returned direct to the Publisher. Manuscripts are accepted for publication on the understanding that exclusive copyright is assigned to the Publishers. However. this does not limit the freedom of the author(s) to use material in the papers in any other published works. ETHICAL POLICY Studies using human subjects should include a statement within the manuscript that subjects provided informed consent for their participation and that the study was approved by a local ethics committee. Studies using animal subjects must conform to internationally accepted standards of animal welfare, and authors should include an appropriate statement to that effect. either within the manuscript or in their covering letter. Every effort should be made to minimize the number of animals used. The editors will welcome the submission of work in any area of science. However. studies that subject animals to pain or stress require special consideration and three principles will be used to judge the ethics of such work. First, experiments of this kind will be required to reach a higher threshold of scientific quality in order to be publishable. Second, the utility of the study will be assessed. in terms of the balance between the distress inflicted and the likelihood of benefit. Third. it must be demonstrated that the objectives of the experiment could not have been achieved by the use of less stressful procedures; the fact that a particular procedure has been used in previously published work will not in itself suffice. The editors believe that scientists apply strict ethical criteria to their work, and will have no difficulty in meeting these requirements. Published by Malta Chamber of Scientists P.O. Bo.r 45, Valetta B.P.O., Valletra, Malra Tel: (+356) Far:(+356) 343535