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Made to measure

Is ours the perfect universe, or could there be another just as good? NS 30 Jun 2001

WHY is the Universe the way it is? Why do the many parameters that define it happen to be the very values that give rise to habitable planets and life?

Many cosmologists subscribe to the "anthropic principle'-for us to observe them, the parameters simply have to be the size they are. Not so, says one physicist. He says that at least one other arrangement of cosmological parameters would lead to life.

Some of the Universe's parameters seem precisely set at values that allow us to be here. If they were only slightly different, the heavy elements essential for life would not have formed, for example. Many prominent cosmologists think this is no accident, and their view is enshrined in the 1986 book The Anthropic Cosmological Principle by John Barrow and Frank Tipler.

But the principle could have its legs knocked from under it by a theoretical study by Anthony Aguirre of the Institute for Advanced Study in Princeton, New Jersey. He wondered if there might be another set of parameters that would permit life.

Aguirre began by defining the conditions necessary for biology. "Crudely speaking, the evolution of life requires heavy elements such as calcium and iron and the billions of years of stable temperatures found around a star of solar mass," says Aguirre.

To his surprise, Aguirre found that such conditions could also be satisfied in a universe that seems very alien. "It's hard to imagine a universe more different from our own," he says. In our "hot" big bang, a huge number of photons very quickly blasted apart any matter that formed. This meant that the light elements produced early on did not have time to fuse together to form heavier ones. Heavy elements were later formed in the central furnaces of stars.

Aguirre's universe starts with a "cold" big bang, and does not have to wait so long for its heavy elements to form. "In a cold big bang universe, matter is much denser at a given temperature and all the heavy elements necessary for life get built up in the first seconds," says Aguirre.

His universe could also have an enormously large cosmological constant-a repulsive force which drives matter apart. At up to 100,000 trillion times bigger than the constant in our Universe, this would mean that after 13 billion years-the Universe's current age-the alien universe would be eerily dark and devoid of stars. "Instead of galaxies crowding space, only a few isolated star clusters would be adrift in a vast ocean of darkness,' says Aguirre.

He suspects there could be other alternative universes, too. "People are going to have to think very carefully about using the anthropic principle,' he says.

Supporters of the principle are not convinced. 'Making the cosmological constant 1011 times bigger might not be an option without a bad change in something else, or it might just not be permitted," says John Barrow, now at Cambridge University. 'We have no idea, since we don't know the true explanation for the dimensionless parameters which define cosmologies.' Marcus Chown More at: hftp.//arxivorg/abs/astro-ph/0106143

Stop the Clock NS 30 Jun 2001
It'S A BURNOUT Of the millions of eggs a woman is born with, a mere few hundred stand the slimmest chance of making a baby. The st languish in the ovaries getting steadily stale, or comiit suicide-mostly before a woman reaches the grand old ge of forty. it makes for some grim choices: either find a artner and establish your career in double-quick time that you can have your babies young, or risk leaving hildren until your eggs are no longer up to the job. That, however, is all about to change. Fertility researchers are powering ahead with their bid to rewind the hands of the dreaded biological clock. That means girls being born today can probably safely leave child rearing until their 40s, 50s or even 60s. But while the coming revolution promises to be more liberating than the contraceptive pill, paternity leave and emancipation combinedi it might just come with a nasty sting in its tail. "The only thing in life that is so cataclysmic is this breeding business. You have to cram it in by your late 30s," says Alan Trounson, director of the Monash Institute for Reproduction and Development in Melbourne. "We'll find a way to stop menopause being such a dramatic thing for women@ but we have to make sure we do it safely," Make no mistake, doctors face immense challenges to understand the human egg-the key to menopause. The human eg@is impossible to any length of time in a lab dish, and while away inside a woman's bod@, in its earliest stages it is invisible even with the help of the most sophisticated imaging equipment. Repro ductive physiologists like to claim-with some justification-that we know more about outer space than we do about the inner workings of the human egg. Even before a woman realises that she is pregnant, the cells that will form her grandchildren have been carefully set aside In her embryo, still less than the size of a rice grain. If the fetus is female, by the seventh month of pregnancy, those cells will have spawned a mind-boggling 7 million immature eggs. From there on, though, it's downhill. By the time a girl is born, numbers have plummeted to about 2 million-a mass slaughter whose purpose remains a mystery. Even then the carnage is far ftom complete. Over the next five decades, the egg population steadily diminishes as cells commit suicide in a series of defined stepsa process called apoptosis. Of course, a few eggs escape that fate. When the girl hits puberty hormonal signals from the pituitary gland ensure that every few weeks groups of eggs start to mature. Nourished by a layer of granulosa cells, the chosen few take around six months to balloon up to 60 times their original size. Eventually, one egg outstrips the others, and ovulation occurs following another hormonal surge from the pituitary gland. The egg escapes from the ovary, and jets off into the fast lane of the Fallopian tube, and the possibility of a brief encounter with a sperm.

That onerous selection process means that by the time a woman has reached her late thirties, she's scraping the bottom of the ovarian barrel. By 45, her chances of getting pregnant the old-fashioned way "are very, very small," says Robert Winston, a leading fertility expert at Imperial College, London. "Even by IVF, it is only about 3 or 4 per cent." According to current thinking those odds could be much improved if reproductive physiologists could find some way to stop the untimely deaths of immature eggs.

"My gut feeling is that menopause is determined by how many of the resting follicles you have feeding the pipeline to make more maturing follicles," says Jonathan Tilly, a reproductive biologist at the Vincent Center for Reproductive Biology at Harvard. Once that stockpile dries up, the pipeline shuts down, and the woman's reproductive system throws in the sanitary towel.

One way to stop that happening is to put your eggs on ice until you are ready to use them. Although human eggs are notoriously sensitive to freezing and thawing, these techniques are slowly edging into the mainstream-nowadays, clinics on at least three continents offer egg freezing to young women, and up to 60 babies worldwide have been born ftom frozen eggs.

Still, for now at least, the success rate remains low and none of the clinics New Scientist contacted is prepared to guarantee that its frozen eggs will be up to the job when they are defrosted. But if the techniques continue to improve, it's lik;ly that babies born today won't bat an eyelid about freezing their eggs while they build a career or search for Mr Right. "It's an insurance policy," says Mohammed Taranissi, medical director of the Assisted Reproduction and

Gyiiaecological Centre in London. But it's a costly and inconvenient oileThe eggs can only be removed under sedation, after a series of unpleasant hormone injections. Far inore convenient to find a way to keep immature eggs alive inside a woman's body-which is exactly what Tilly and his team are working towards. First they examined mice genetically engineered so they couldn't make a protein called Bax, which plays a key role in cell suicide. They found that young adult Bax-less females had three times as many eggs as normal, but could still produce pups-proof that blocking cell suicide improves egg survival and doesn't affect mouse fertility.

Two-year-old females-who'd be entitled to a telegram from the Queen if they were human-had a little more trouble making pups, but only because their bodies were too clapped out to carry a pregnancy. Eggs from the old Bax-less mice still formed normal einbryos when fertilised in a test tube. Artificial wombs are unlikely ever to be an option (see "A bun in the husband, p 42), so that raises the question of how far into her dotage a woman could safely carry a pregnancy. No one kno-s for sure, but with the help of reproductive technology several women have given birth in their 60s. Many obstetricians suspect that the ability to carry a baby safely has more to do with a woman's overall fitness and health than her chronological age.

Good egg

Of course, tinkering with a women's genes to ward off the menopause is pie in the sky, but Tilly's team is also working on a drug that will block cell suicide. Young women undergoing treatment for cancers like leukaemia and lymphoma urgently need this kind of research. Chemotherapy and radiation mean that over 80 per cent of them go through an early menopause, sometimes while still in their twenties. One way cancer therapy seems to work is by triggering the cascade of signals that instruct a cell to commit suicide-the immature egg cells simply get caught in the crossfire. Reasoning that there's absolutely no point in keeping damaged eggs hanging on by a thread-especially if they are to form the next generation, Tilly's team has found a way of blocking the very earliest stages of egg suicide. "We want to have a population of good oocytes, not the Night of the Living Dead oocytes," he says. To do this, they tried a drug called sphingosineI -phosphate (S I P), which has all eady been shown to halt cell suicide in human white blood cells. When Tilly's team injected the drug directly into the ovaries of mice and treated them with radiotherapy, the mice's immature eggs survived intact. They even went on to form normal embryos in the test tube, and the pregnancy rate of irradiated mice treated with Sl P was double that of the mice that didn't get the drug. "It's taken us 10 years to get to this point in mice, so it's going to take a while," says Tilly. "[But] the technology could be useful for giving women an additional four or five years of fertile lifespan." Another way to keep the biological clock ticking would be to stop eggs maturing in the first place, allowing them to remain in ovarian storage until women were ready to use them. "When you found a partner you wanted to have children with, you could concentrate all your reproductive [resources] at that time," says Trounson. One factor that plays a role is antiMullerian hormone, or AMH. In mice, AMH is made by granulosa cells in the ovary, and puts a brake on the number of eggs selected to mature (New Scientist, 1 1 November 2000, p 20). Axel Themmen and colleagues at Erasmus University in Rotterdam studied mice that lacked AMH. At four months old, the mice had three times as many growing follicles as normal mice. By the time they were 13 months old, the mutant mice had completely run out of eggs.

Themmen is now investigating how AMH works in humans. A drug that enhances its effects might one day become the basis for a new "career pill". But while research into career pills and anti-menopausal drugs is moving at a comfortable pace, techniques to improve pregnancy rates among women who are already running out of eggs are being unleashed at a speed that is causing some consternation, even in fertility circles. This is of particular concern in countries such as the US, where there is no direct federal government regulation of fertility treatments. 'There, the Food and Drug Administration strictly controls the testing of new drugs, while new medical technologies tend to be left to individual states to regulate. All too often, that means fertility doctors need only get consent from their patients and their clinic's own review board before they try out new techniques. Take cytoplasmic transfer, the highly controversial technique that creates children that carry the genetic material of three people. Jacques Cohen and Jason Barritt of the St Barnabas Medical Center in New jersey attracted international criticism for their work. Among fertility experts, the major worry is not about the few extra genes carried in the mitochondria-the cell's powerhouses that make up a fraction of the jelly-like cytoplasm-but about the wisdom of using the new technique in humans without testing whether it works.

'THE EGG IS NOT JUST A QUIESCENT LITTLE BLOB, THERE'S AN INCREDIBLE AMOUNT GOING ON'

One of the main problems older women face when trying to conceive is that their eggs often end up with the wrong number of chromosomes, a condition called aneuploidy. If an aneuploid egg is fertilised, the resulting embryo either miscarries-sometimes before the pregnancy is detected-or the child is born with a handicap such as Down's syn drome. One theory is that the cellular machinery in the cytoplasm that is needed to deal the right number of chromosomes into the two halves of the dividing egg is too old to do its job properly. That has led to the controversial notion that a shot of fresh cytoplasm from a younger woman's egg could also help when an older woman's eggs fail to produce babies for unknown reasons. The trouble is, say critics like Winston and Trounson, there's no hard evidence that the technology helps women get pregnant. True, the women that Cohen and Barritt treated had had many failed IVF attempts before they got pregnant following the new procedure. And, true, their embryos looked better under a microscope than those they produced without the procedure-but who's to say that the same wouldn't have happened with just one more round of IVF? To find out, you would need to run trials that compared cytoplasmic transfer or IVF alone in women with the same history of infertility. What's more, the few experiments testing similar techniques in animals have been contradictory. Even worse, the cytoplasm contains substances that are vital to the normal development of the embryo, so there's even a slim chance that cytoplasmic transfer may threaten the long-term health of the baby. Nothing is really known about the consequences of techniques like cytoplasmic transfer, says Tilly, who believes patient demand and doctors' willingness to come: ply with those demands is rushing new

treatments into the clinics too quickly. After all, one in six couples have fertility problems and for them the treadmill of fertility treatments can seem like their only option (see "Right to choose", page 41) "Patients are driving a whole load of technologies that haven't been validated," he says.

In fact, the babies born after cytoplasmic transfer are all reportedly doing fine. But two of the 17 fetuses created by Cohen and Barritt had a chromosomal abnormality that causes a disorder called Turner syndrome and did not survive, although no one can say whether the technique is to blame.

Eggbert the mouse

What we do know is that animal experiments that involve manipulating eggs paint a disturbing picture. Take Eggbert the mouse, the only mammal created so far from an egg grown mainly in a lab-a feat that fertility doctors would dearly like to repeat with human eggs to reduce the need for egg donors, and slash the costs of IVF.

At birth Eggbert appeared normal enough, and even went on to father a few pups. But at six months, disaster struck. Eggbert became obese, developed neurological problems and eventually died. A post-mortem revealed that Eggbert suffered from some of the same defects that plague cloned animals (New Scientist, 19 May, p 14).

"That's why we are so concerned. People should be very, very careful," says John Eppig, a reproductive biologist at The Jackson Laboratory in Maine who led the team that created Eggbert. 'Simply having a baby's footprints at birth doesn't [necessarily] mean success." Of course, the egg that became Eggbert was manipulated in a different way from the human eggs undergoing cytoplasmic transfer, but it illustrates a point. The egg "is not just a quiescent little blob", says Kate Hardy, a reproductive biologist at Imperial College, London. 'There's an incredible amount going on," most of which fertility researchers are only just beginning to understand.

Still not everyone is so quick to condemn the aggressive approach some infertility clinics take. 'You'll hear that there's no regulation in the States-and that's not an accurate statement at all," says Sean Tipton, a spokesman for the American Society for Reproductive Medicine. 'What we don't regulate is people's reproductive choices." (Th e St Barnabas clinic wouldn't let Barritt talk to Ne,w Scientist, but sent a written statement saying that its research complied with the hospital's 'stringent medical guidelines".)

What's more, points out Tipton, similar criticisms were once levelled at IVF, an innovation that society now embraces. "We don't know for a certain fact that every human being conceived through an IVF process is not going to drop dead at the age of 30. We don't know that because the first IVF baby is not that old yet. But there is certainly nothing to indicate that that's going to be a problem. If you insist on that sort of long-term outcome, you're never going to get anywhere."

But while fertility researchers struggle to balance the demands of science and their patients, one thing is clear: the number of patients is only going to grow. Women are delaying childbirth like never before-the average age for having a first child in Britain is now nearly 30-and without medical intervention a portion of those women are destined to swell the ranks of the infertile. Bridget Jones aside, the need for a safe way to slow down the biological clock has never been more urgent.

Further reading: "Alternative sources of gametes: reality or science fiction?" by Ming Tsai and others, Human Reproduction, vol 15, p 988 (2000) "Oocyte apoptosis is suppressed by disruption of the acid sphingomyetinase gene or by sphingosine-1-phosphate therapy" by Yutaka Morita and others, Nature Medicine, vot 6, p 1109 (2000) "in vitro maturation of oocytes" by Kate Hardy and others, British Medical Bulletin, vol 56, p 588 (2001)

US puts its foot down on tinkering wfth IVF babies NS 21 Jul 2001

DOES manipulating an egg prior to IVF turn it into an experimental .product" that has to be regulated like a new drug or medical device? Yes, says the US Food and Drug Administration.

This month, the agency wrote to several fertility clinics warning them that any treatments that genetically alter egg cells or embryos would constitute a "clinical investigation" and so fall under the agency's authority. The announcement will effectively prevent clinics

using a controversial technique known as 'ooplasmic transfer'. This involves adding cytoplasm from a healthy young woman's egg to the egg of an older woman, which is supposed to improve the chance of pregnancy. Because this material includes DNA-carrying mitochondria, any babies resulting from the treatment end up with genes from three parents (New Scientist, 12 May, p 7). The FDA has previously kept a distance from fertility procedures because its policy is not to interfere with "the practice of medicine". But now it seems clinics that want to offer the procedure will have to file an Investigational New Drug (IND) application-the same document that drugs companies are required to file when they want to test a new product.

'You might want to call it a scare tactic," said Charles H. Kyper, a former FDA officer. After an IND is filed, researchers must haft experiments until the FDA gives its approval. Representatives of the fertility industry, as well as some researchers, have spoken out against the FDA interfering with a "medical procedure". But the agency is standing on fairly firm ground, says one prominent lawyer specialising in food and drug regulation, who prefers not to be named. "The FDA will probably be upheld if challenged." Sylvia Paghn Westphat, Boston

Asteroid misses Earth by 4 hours

by Cahal Milmo NZ Herald Independent 9 Jan 2002

LONDON In intergalactic terms it was a close shave. An asteroid capable of causing widespread devastation narrowly missed the Earth yesterday. Although the nearest the asteroid came to Earth was 627,000 km had it arrived four hours earlier on its journey round the Sun it would have scored a direct hit. When the asteroid measuring 300m across and known as 2001 YB5 passed Earth it was less than twice as far from the Earth as is the Moon Scientists were unaware of its approach until a month ago, when it was spotted by an American observatory dedicated to tracking near Earth objects (NEOs). Astronomers insisted there was never any danger of a collision with Earth. But they warned that the asteroid was one of up to 400,000 small NEOs up to 1000 m wide that could strike Earth with little or no warning because of the absence of an adequate early warning system. The idea of a catastrophic asteroid strike has long been a source of morbid fascination, most recently manifesting itself in Hollywood disaster movies such as Armageddon and Deep Impact.

If a 300 m asteroid hit London, it would destroy everything within a 150 km radius and damage everything up to 800 km wiping out the United Kingdom, the Low Countries and much of France. In the more likely event of a similarly sized NEO landing-in the sea (70 per cent of the Earth's surface is covered by water), it would trigger a series of tsunamis that would devastate coastal regions. Jonathan Tate, director of Spaceguard UK, which campaigner for a British-funded telescope to watch for such asteroids as part of a global network, said: "YB5 is one of hundreds of thousands of objects which present an unknown risk to the planet. "What limited resources exist for tracking asteroids are dedicated to spotting the 700 to 1200 which are more than a kilometre in diameter and, if they hit the Earth could out the planet. It leaves very few resources for trying to trace the many more asteroids between l00 m and 1000 m in diameter which still present a very significant risk.

By the time it was spotted last month there was nothing we could do to prevent a catastrophe.

Indonesian National Park Devastated NZ Herald 10 Jan 2002

Illegal loggers have destroyed two-thirds of an Indonesian national park in the last 10 years. Surveys by Harvard University's Labvoratory of Tropical Forest Ecology say more than 67,000 ha of the 90,000 ha Gunung Palung National Park in Borneo was destroyed the Jakarta Post reports. More than six million cubic metres of logs were stolen.