The Age from Melbourne, Victoria, Australia • Page 15

I. THE AGE, Monday 17 June 1985 15 FUTURE AGE EDITED BY PHILIP MclNTOSH Clockwork gland may be survival key An obscure organ deep within the brain signals sleep cycles, the winter doldrums, perhaps even puberty and menopause. BRUCE FELLMAN reports. rrc if 4 "neuroendocrine a system that converts a nerve-type signal one set off by dark and light into an endocrine signal that of a hormone whose levels rise and fall in the bloodstream. The ebb and flow of the hormone melatonin, which is made in the pineal, is adjusted by the days and nights of the outside world.

As darkness settles, sooner or later, depending on the species, the pineal starts producing. Just how the pineal transduces darkness into a chemical signal is not completely understood. But over the past 20 years a small army of researchers has put together a reasonably tight description of the process. Wurtman, now at the Massachusetts Institute of Technology, explains that in some non-mammalian species, like the frog, the gland is a light and dark sensor. In mammals, however, light or lack of light is detected by the eyes.

This information travels first from the optic nerve to the spinal cord. From there, sympathetic nerves carry the signals back to the brain's pineal. During the day light inhibits melatonin production in the pineal, but the gland is not idle. From dawn to dusk it converts the amino acid tryptophan into serotonin, a substance that later will be turned into melatonin, which then flows into the bloodstream. When the hours of darkness lengthen, there is a change in the nightly hormonal pattern.

Or so it seems in hamsters. Researchers suspected that the yearly rise and fall of the hamster's reproductive system was related to changes in melatonin output. Working with the Siberian hamster at the National Institutes of Health Larry Tamarkin and endocrinologist Bruce Goldman tried to fool the animals into behaving as if it were winter with hormone shots. But when they gave the animals melatonin injections every morning, nothing happened. The hamsters, kept on a summer schedule of 14 hours of light and 10 hours of dark, continued producing offspring.

Frustrated, the two scientists decided to break with protocol and try the injections in the afternoon. "In about eight weeks, their gonads collapsed." Tamarkin notes. "The hamsters were confused and bypassed the signal from their eyes." Here was proof of melatonin's power, but why did it work only in the afternoon? "We failed to take into account the natural biological secretion pattern." Tamarkin says. He and Goldman think that the afternoon injections followed by the hamster's own melatonin production were interpreted biologically as one long pulse of the hormone. Over time, the hamsters respond- An individual's survival, of course, and that of future generations may depend on the timed growth of some anatomical item like fur or feathers, ovaries, or testes.

Nowhere is the element of timing more important than in mating and rearing offspring, the centrepieces of an animal's life. For sheep, deer, and bear, which mate in the short days of autumn and carry their young through the lean winter, success depends on having a reproductive system that is ready, willing, and able before the weather turns frigid. The situation is reversed for springsummer breeders, which include most small mammals, birds, reptiles, and fish. A kind of natural birth control prevents ill-timed conceptions. In the off-season, animals simply lose their procreative capacity.

There is no urge, and there are no means. The need to keep to a tight schedule becomes more critical where the climate is less forgiving. This fact is not lost on the pineal. As Reiter explains: "Animals that live near the Equator have relatively small pineals, and its size increases as you go north or south. In arctic musk-ox and lemmings, the gland is quite large, and in elephant seals, one half of everything inside a newborn's skull is pineal tissue." But what good is a pineal when you have a calendar? In humans, the gland's rhythm may affect the sleep cycle.

MIT psychologist Harris Lieberman and physician Lutz Vollrath demonstrated in two studies that melatonin makes people drowsy. Its production could conceivably play a role in jet lag and the trouble many people have in adapting to work at odd hours. Then there is the SAD, which can get severe enough to be grist for the psychiatrist's mill. In talking to his patients, Norman Rosenthal, of the National Institute of Mental Health in Bethesda, Maryland, discovered what hardly seemed surprising: SAD symptoms often went away when the afflicted went to warmer regions for the winter. The standard wisdom was that the warmth worked a kind of psychiatric magic, but Rosenthal had another idea.

Perhaps it was not the balmy temperatures perhaps it was the increased amount of light To test this unconventional notion, he put SAD sufferers in front of very bright lights, like those found on a movie set, for several hours every morning and evening throughout the autumn and winter. Rosenthal's Hollywood treatment worked, nudging his patients out of the winter doldrums into a psychological spring. But what it is -about the gland that brought on the blahs remains unknown. "You can't even say that melatonin is the key," the psychiatrist admits. "We fed it to patients to try to reverse the antidepressant effect of their therapy, and the results were mixed." Most, however, felt worse as the added hormone told them that the gloom season had returned.

Some researchers suspect that melatonin production diminishes naturally with age and the pineal may have a role in puberty and menopause. This idea is not new. In 1898, German physician Otto Heubner reported a case of precocious puberty in a four-year-old who also had a pineal tumor. In the past few years, the argument had been advanced that high levels of melatonin in children might not only make them sleep more but actually prevent sexual maturation. Perhaps it is "antigon-adal" and somehow keeps reproductive systems in check similar to the way it suppresses seasonal reproductive capabilities in animals.

More likely, however, melatonin simply provides information. When the daily rhythm goes through enough cycles, or when the hormone level declines to a certain point, the cascade of events leading to puberty begins. Wurtman and a colleague, Austrian biologist Franz Waldhauser, last year published striking, but controversial, evidence to support the melatonin decline hypothesis. On a visit to MIT, Waldhauser brought with him blood samples taken from hospitalised young children. An analysis of these showed that the amount of melatonin they produced declined 75 per cent between early childhood and puberty.

"I've studied the damn thing for 28 years, and for the first time I can see some real evidence that melatonin may be important in human puberty and other age-dependent changes in people," says Wurtman. But others are quick to criticise Wurtman's notion as simplistic and premature in the face of conflicting data. There are studies, including two by Tamarkin, that have failed to show any overall decline in melatonin between early childhood and puberty. Wurtman remains nonplussed, noting that even if he loses his head for sticking his neck out, he will spawn some good research. "I think of the pineal as a communications organ," Wurtman says.

"It transmits a signal, and you get information when a signal is changing. If the blood level of the hormone remained constant, it would tell you nothing." And change it does: every day, every winter, spring, summer and autumn; maybe throughout a lifetime. Perhaps we are more creatures of biology than habit Science 85 VERY spring a curious thing happens to many people who live in higher latitudes. As I the days lengthen and I the first wildflowers poke their heads above the earth, the spirits of those people who have been down in the dumps since autumn begins to rise like maple sap on a warm, sugaring day. Gone are the winter blues that settled in with the dingy days and long nights that made a body want to hibernate.

Gone is the lack of energy, the spiritual slush and drab, the alienation that sometimes descends during and after the holidays. Scientists have a name for severe cases of these yearly doldrums the seasonal affective disorder, or SAD and the behavioral and physiological symptoms have been linked to the pineal gland, an obscure organ buried near the centre of the brain. Named because of its resemblance to a pine cone, the human pineal is smaller and weighs less than an aspirin. Its existence was chronicled by early Greek anato- uui uieic nave ueeu biiaip disagreements over its function ever since the Fourth Century BC. Earlier in this century scientists, wearied by a vain search for the gland's function, cast it as a neurological vestige, an appendix of the brain.

The pineal, however, was not easily relegated to the cerebral scrap heap. For starters, nearly all modern fish, reptiles, amphibians, birds, and mammals have a pineal. Even the few exceptions notably alligators, crocodiles, and armadillos have cells that act like the gland. The organ has occupied most vertebrates' skulls since the first backboned creatures joined the Earth's fossil record 5(10 mil lion years ago. A structure this ubiquitous and ancient is surely not just going along for the evolutionary ride.

Much of what researchers now know comes from animal studies. Removing the gland, they found, produces conspicuous changes. Many animals tie their breeding re Lb activities to the seasons, but after a pinealectomy, they suffer from reproductive asynchrony, losing touch with nature's calendar. When young fish and amphibians are deprived of the gland, they no longer summon up a pallor response, the nocturnal loss of color that makes them ghosts to predators. Birds abandon daily activity rhythms, some eventually losing the urge to migrate.

Deer grow antlers at the wrong time. And the list goes on. "My guess is that the pineal adjusts the entire physiology of the animal to the environment," says Russel Reiter, a biologist at the University of Texas at San Antonio. Reiter explains that he got into this line of work through a project he did for the US army on the physiological effects of environmental changes on soldiers. "Say you moved troops from the Panama Canal to Thule, Greenland.

Would that drastic change really matter?" Reiter asks. To find out, he began experimenting with the Syrian hamster which is truly a creature of the seasons. It breeds only during spring and summer and when kept on a laboratory lighting cycle reflecting its natural habitat, the animal behaves as though it never left home. In the lab's autumn, for example, when the length of the artificial night creeps past 11 '2 hours, the hamster's reproductive system shrivels and all but disappears. This sexual quiescence lasts throughout the artificial winter, when the animal would normally be hibernating in a perpetually black burrow.

But Reiter discovered that even during this stage changes are taking place. In the lab's constant gloom, the ovaries and testes begin to grow back to breeding size. And when the hours of light are extended, as would occur when the animal is ready to emerge from its burrow, the hamster is ready to produce offspring. Its reproductive activities continue until increasing darkness calls them again to a halt. "The pineal has a dramatic effect on the animal," Reiter says.

"If you remove it, the gonads do not regress." In the early 1960s endocrinologist Richard Wurtman coined an especially apt phrase to describe the gland's function, a Illustration: JANET GREEN Klein, a neuroendocrinologist at NIH. "It is under the control of a master clock." This master clock is a concentration of specialised nerve cells found in the hypothalamus, close to where the optic nerves cross. Called the suprachiasmatic nuclei, or SCN, this structure, like the pineal, was identified some time ago but its function was a mystery. Klein has found that the SCN turns melatonin production on and off in the pineal. The trouble with the SCN is that its rhythm is somewhat longer than 24 hours.

It can be off 30 minutes to an hour unless light resets it each day. imposing the order of the seasons on the clock and, thereby, the pineal. Left to itself, as it would be in perpetual darkness, the master clock "free pwiiiiwimiBaaiw ed as if it wore indeed Retting dark earlier. A shot in the morning, however, was not timed close enough to mimic the sustained rise that brings about collapse. Reiter, on the other hand, has a different explanation for why Ta-markins morning injections did not work.

He believes that the animal's hormone receptors are saturated, or desensitised from its own nightly melatonin output. Bv afternoon an animai has lost this insen-sitivity, and an injection causes a shift or change in the hormone's rhythm that leads to regression of the sexual organs. However it works, the timing of the melatonin pulses is crucial. Timing in the natural world is even more complicated, as it is not solely the work of the pineal. "The pineal is a slave." says David job in the world.

women with folic acid and not others, you are encouraging the birth of spina bifida children in those who go without the folic acid, and it is unethical to deny them a medicine that might be good for them. "It would be much simpler if two or three embryos of about 20 days could be treated with folic acid and afterwards killed, because then you could tell instantly whether the absence of folic acid was the cause." Dr Maddox describes his present job as the hardest in the world. "It's just a lot of work." He does not make a judgment on all 200 papers a week that the journal receives, but he reads proofs of every article published. He also gets caught up in arguments about what should be accepted and rejected, there is the general administration of running the journal, he has to keep an eye what other scientific journals are publishing he regularly reads six of these each week and he writes and travels a lot. "I like to think that 'Nature' is purely a professional magazine," said.

"The morticians of the United States have a journal called 'Casket and Sunnyside'. It is full of of caskets at wholesale prices so on. I think that we stand in relation to science as that does in relation to American morticians." Science editor is a man for all seasons runs" and becomes increasingly out of phase with the environment. In the blackness of the burrow, hamster time soon loses touch with the lighting schedule. Vet when the time to hibernate is over, the animal is somehow ready to breed.

"By mechanisms we still don't understand." says Reiter, "the pineal system influences seasonal variation in such things as temperature regulation, deposition of body fat, hibernation, and reproduction. Most known hormones work via receptors, but so far the receptors for melatonin have been extremely elusive." Somewhere probably in the brain the regular ebb and flow of melatonin is converted into a time signal that, when summed over weeks, months, and years, gives an animal its seasonal sense. Asia and the Pacific', published by Angus and Robertson last year, and soon to be reprinted in the UK and the US, was Charles Hamblin's least claim to fame. He was best known for work in two other areas: for developing in the 1950s a new, simplified computer language that is now used by many pocket calculators, and for his path-breaking reform of the study of formal logic in the 1970s. What philosophers now call his epochal work in logic shattered 2000 years of tradition back to Aristotle and has revolutionised the teaching of formal logic in universities around the world.

Yet the strange thing is that hardly anyone, not even his close colleagues, knew the sum of all the parts that made up Charles Hamblin, the professor of philosophy at the University of NSW for 19 years, who died on 14 May. He was modest and intensely private. Tracking down his achievements has been as elusive as he was self-effacing and shy. Hardly anyone knew, except his widow Rita, that he would furiously scribble down ideas at the breakfast table of their Darling Point home in the morning and late into the night (he slept only four hours). Very few knew of his passion for music.

He played the piano mainly Debussy and Ravela great deal, and while sick in hospital, was setting words of the philosopher Wittgenstein to music. But, self-effacing as he was, he was part of a tiny network of outstanding mathematical-logician-philosopher scholars around the world who learned speedily of his death from a brain tumor at the age of 62. been falling steadily for more than a decade, and were then at an all-time low. The science and technology statement, tabled in Parliament by the Minister for Science, Mr Jones, says that technology exports by Switzerland are more than 30 times higher at $2426 a head and those from the Netherlands almost 20 times higher. Even New Zealand, with $110 a head, and Spain, with $93 a head, are higher than Australia.

Seafood drug The New Zealand green-lipped mussel has been promoted for some years as a treatment for rheumatoid arthritis and osteoarthritis but specialists remain sceptical about its value. A British rheumatologist recently branded it a "quack therapy" after trials of the mussel as an anti-inflammatory drug. Now researchers in the Shy genius of logic, maths ana languages By GRAHAM WILLIAMS WHAT DO you make of a man of such learning that he checked esoteric Babylonian and Egyptian mathematical tablets and the authenticity of a mediaeval text of Robin of Sherwood, and also contributed so much to computer development that he was described once as "the greatest computer architect of all time" (an accolade he dismissed as rubbish)? Few knew Charles Hamblin as a man for all languages, the tall, gen-tie and shy ancient Greek scholar who straddled the centuries by learning 25 Asian and Pacific languages Persian, Hindi, Burmese. Cantonese, Hokkein, Japanese, Samoan, Fijian and Ton-gan to name but a few. Few of his colleagues knew that he published the world's first phrase book for travellers in Asia last year, containing 25 languages.

It was a printing feat because only one printer in the world in Lon-. don could reproduce all the signs and accents of this vast array of languages. Yet this book, 'Languages of Edited by Philip Mcintosh All time low Australia's exports of technological products are continuing to decline and are one of the lowest of all OECD countries, according to the latest figures in the 1984-85 science and technology statement The figures show that, despite increased government efforts to boost exports, only Iceland, Turkey and Greece are exporting less technology goods per head of population in the 24 OECD countries. In 1983 Australia's exports were worth only $72.80 a head, had fmrn Vaughan Pratt professor of computer sciences at Stanford University, rang me at home when he learned I was trying to find out about Charles Hamblin, the elusive genius. "Charles was influential at the philosophy end of computers.

He was a mathematician and logician who asked fundamental questions," he said. "In the 1950s, he directly influenced the architecture of what we call stack computers by applying the Reverse Polish notation to them, which is used today in pocket calculators like the Hewlett- His epochal work in logic shattered 2000 years of tradition and revolutionised the teaching of the subject. Packard. This was his major influence on computing and it simplified procedures greatly." Reverse Polish notation in its simplest form, means that if you want to add ab, you enter ab into the computer. It takes a little time to learn the new way of writing formulae, but as Professor Pratt says, it gives many advantages.

Professor Pratt, who worked with Hamblin for a year, said he was a logician of immense ability, but who was so modest that it was hard to get to know all his diverse interests. Dr Barry Thornton, professor of mathematics at the NSW Institute of Technology, recalls that in 1957, when the UTECOM early computer was built at the University of NSW, Hamblin would pop in now department of applied biology at RMlT have received a Commonwealth Government grant of $38,000 for further research. The head of the department Dr Robert Borland, says his team has found significant anti-inflammatory activity in the seafood, and work is continuing to identify the active ingredient A medical spokesman for the Rheumatism and Arthritis Association of Victoria, Dr Murray Ingpen, is watching the research with interest "If there is any evidence that the mussel gives you anything but halitosis I would be pleased to hear." Hue and cry What color should fire engines be painted to make them more easily seen and reduce accidents? According to Steven Solomon, an optometrist in Owego, New York, it should be lime yellow. Solomon and again and ask a few friendly questions. "Who is that chap? I asked and I was told he's the chap behind Reverse Polish.

At that time in Sydney, we had three of the first computers in the world we had the world at our feet and we didn't know it We had immensely intelligent logicians like Charles Hamblin and we had many others. "If we had grasped our opportunities then, we could have been world leaders in computing. But computing was not held in high esteem. And brilliant individualists like Hamblin were not given the encouragement they needed." Hamblin, born in 1923, learned his Greek and music at North Sydney Boys' Hign School and at Geelong Grammar and graduated from Melbourne University with degrees in arts and science in 1949. He was one of three future professors of philosophy to emerge from Geelong Grammar at that time Michael Scriven, of Berkeley, California, and David Armstrong of Sydney University are the others.

Professor Scriven, now professor of education at the University of Western Australia, says that a book, 'Fallacies', that Hamblin published in 1970 revolutionised the study of logic internationally. "Up till that time, the study of logic was hidebound and had not changed in hundreds of years. Charles took a highly individual approach, as he always did, and challenged the whole range of classical fallacies. It was a real loner's effort, but by 1978, philosophers around the world were accepting it as a great breakthrough. Sydney Morning Herald says that fire fighters in Miami.

Philadelphia and San Francisco have more than twice as many collisions at intersections than fire fighters in Detroit Newark and Kansas City. The only difference, he says, is that fire engines and trucks in the latter three cities are lime yellow instead of traditional red. Solomon says the eye is most color-sensitive to yellows and greens. "Lime yellow is a grating, irritating color," says Solomon, who is also a captain in the Owego volunteer fire department "which is exactly why it should be used on fire fighting equipment" Not everyone is as enthusiastic about the hue. The Dallas fire department which says red paint is easier to touch up, lasts longer and enhances the sense of tradition and morale in the fire" fighters has switched from lime yellow back to red.

long run it will stand up," said Dr Maddox, "but it is an assurance that it is an interesting and important bit of work." It is a comment on the journal's selectivity and the volume of scientific research being done in the world that only one in five papers received is published. Dr Maddox has been associated with 'Nature for 12 years interrupted by the term at Nuffield and previously was lecturer in theoretical physics at Manchester University and science writer for the 'Guardian'. A publishing industry associate describes John Maddox as possessing the manner of a vague, eccentric don but with a razor-sharp mind. As Clyde Garrow sees him: "He is a man for all seasons as far as science is concerned. He seems to have an incredible ability to discern and understand developments in science generally.

I think he is a man who is prepared to be his own man, and does not toe any party line." With qualities such as these it will be worth reading his views on the state of science in Australia, to be published in the 20 July issue of 'Nature'. In one of his reports Dr Maddox will cast a critical eye over our research institutions, particularly the CSIRO and the question of how it should be reorganised. "There will be some firm advice on what the Government should do," he said. Among the people Dr Maddox met during his visit this month were the Federal Minister for Science, Mr Jones; the chairman of the Future Commission, Mr Phillip Adams; the Monash in vitro fertilisation pioneer. Professor Carl Wood; and the director of the Hall Institute.

Sir Gus Nossal. Commenting on some of the controversial questions surrounding new reproductive technology. Dr Maddox said surrogate motherhood might be a very good thing. "If people want to be surrogate mothers one should be sure they are well paid." He is against the 14-day limit on embryo experimentation recommended by the Warnock committee in Britain (he prefers the term "embryo because no one could say whether 14 days was enough. He believes that people wanting to carry out these experiments should meet two criteria: to do the work as far as possible in animals By Philip Mcintosh IT is difficult to think of many people whose presence in Australia could have caused the buzz of interest among scientists that accompanied the recent visit of Dr John Maddox.

News of his arrival seemed to sweep the scientific community like wildfire, and those associated with the visit were flooded with requests to meet him. Dr Maddox has been director for five years of the Nuffield Foundation, a UK research institute, and a member of numerous government advisory bodies including the genetic manipulation advisory group, and a royal commissioner on environmental pollution. But it was his present position as editor of 'Nature' that sparked so much interest. Despite its modest circulation of fewer than 29,000 copies a week (800 in Australia), "I think a great many practical problems will soon be tested in human embryos older than 14 days." 'Nature' is, and has been for many years, the pre-eminent international journal of science. "If you can get a letter to the editor published in 'Nature' it is the acme of success for a scientist," says Mr Clyde Garrow, manager of the central information service of the CSIRO.

The two great strengths of the journal, and the reason why scientists are so keen to be published in it, is that it publishes quickly and has authority. The most important scientific discovery this century Watson and Crick's description of the double spiral structure of DNA in 1953 was announced in 'Nature'. The discovery of the first quasi-stellar source or quasar was reported in the journal in I960 and last year it published the detailed description of the virus responsible for acquired immune deficiency syndrome. The journal has an army of 10,000 experts in every branch of science around the world who referee submitted articles. "People do say that appearance in 'Nature' may not be a guarantee that in the Dr Maddox: the hardest before using human embryos, and to submit their proposals to a strong and independent ethics committee whose decision would be binding.

Dr Maddox predicted that many practical problems would soon be tested in human embryos older than 14 days. you want an example, take spina bifida, the disease where the backbone does not close properly and the spinal cord is exposed. That may well be caused by a deficiency of the vitamin called folic acid. "The morticians of the US have a journal called 'Casket and Sunnyside' I think we stand in relation to science as that does in relation to American morticians." "If it is caused in that way, it is probably caused around 20 to 22 days and people are going to enormous trouble at present to do a survey of folic acid in the early development of embryos. It is being done by field trials all over the world, including Australia." Dr Maddox said the trials had caused a lot of argument on ethical grounds.

"People have said that because you are treating some on he ads and.