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Brave New Babies An automated IVF chip could lead to production-line embryos NS 26 May 2001

THE children of the future may be conceived and spend their first few days of development on a computer-controlled chip. In a move recalling Aldous Huxley's famous production lines for making babies in Brave New World, researchers in the US are building a "chip" that can automatically carry out all the steps involved in IVF, from fertilising eggs to preparing embryos for implantation. Ultimately, such deviceswhich amount to artificial reproductive tracts-may even be able to sort and test embryos for genetic flaws. So far researchers David Beebe and Matthew Wheeler have built prototypes that can carry out the major steps involved in IVF, though not all on the same chip. Far more mouse embryos develop successfully on these devices than by traditional methods.

The researchers say they expect the technology will first be used for livestock production, but their eventual aim is to use it for human embryos. The work could be the first step towards a future in which IVF becomes the norm, says George Seidel, a reproductive physiologist at Colorado State University in Fort Collins. "Fifty or 100 years from now, our in vitro procedures for parts or even all of pregnancy may end up being safer than dealing with the various things that occur in the body-in terms of viruses that the mother comes across, toxins, and so on." In conventional IVF, sperm and eggs are dumped into a Petri dish where the fertilised eggs grow until they're ready to be implanted. As embryos need different culture media at different stages, embryologists transfer them from one dish to another via a pipette. "It's like being plucked out of the Atlantic Ocean and stuck into the Pacific Ocean," says Beebe, a biomedical engineer at the University of Wisconsin, Madison. So Beebe and Wheeler, an embryologist at the University of Illinois at Urbana-Champaign, designed a device to mimic conditions inside a female's reproductive tract. The device, made of a transparent elastomer, resembles a small glass slide and contains a network of tiny channels, each around 0.2 millimetres in depth and width. The researchers connect the channels to programmable syringe pumps, which can move embryos around and add or remove fluids.

To test the device, the team cultured mouse embryos fo see how many developed to the 'blastocyst" stage, ready to be implanted. "In 48 hours, in the traditional Petri dish, none of them made it to the blastocyst stage. In our channels, about 75 per cent made it," says Beebe. "The embryos were transplanted into hosts and live pups were bom. So there doesn't appear to be any detrimental effect."

The researchers also used the device to remove the "zona pellucida" shell that encases early embryos. In human IVF, this "assisted hatching' can be used to encourage implantation. Traditionally, the embryo is put into an acid medium and quickly removed when the embryologist sees the zona break up.

But waiting this long may damage the embryos. By washing acid over mouse embryos 'parked" in a microchannel on a chip (see Graphic), the team found even with a brief exposure, the zona broke up after the acid was removed. 'People have been leaving embryos in the acid too long," says Beebe.

In a separate experiment, the team matured mouse eggs inside the channels, then fertilised them by squirting sperm over them. Eventually they hope to integrate all the steps into a single artificial reproductive tract. Crucially, the chip-like device not only allows many embryos to be cultured at once, it allows each one to be individually manipulated and tracked in separate channels. That should make it easier to weed out poor-quality embryos before implantation. Embryologists already inspect embryos under the microscope, and some IVF clinics also measure their consumption of oxygen and glucose and the amount of carbon dioxide they release. All this could be done more routinely on a reproductive chip, says Beebe. In time, the device could even make it easier to carry out pre-implantation genetic diagnosis, Where a few cells are removed to screen embryos for genetic disorders. "That involves more sophisticated manipulation than our current devices can do. But it is something we are working on," says Beebe. But quality contr ol raises ethical issues, says Tom Shakespeare of the Policy, Ethics and Life Sciences Research Institute in Newcastle. 'If we are talking about maximising the chances of becoming pregnant and carrying to term, then there's less argument. But if we are tailing about either reducing genetic diversity or indeed enhancing selection then there are major questions." Ann An@swamy More at IEEE Transactions on Biomedical Engineering (mi 48, p 570)

Power hungry Bush's latest energy plans tum up the heat on the environment

THE US plans to bum more fossil fuels and increase output from nuclear power stations in order to solve its energy crisis, President George W. Bush revealed last week. His new energy policy also includes a controversial proposal to drill in an Arctic wildlife refuge. Although the plan also calls for conservation and alternative energy sources, critics claim those measures are at best half-hearted.

The emphasis on coal could bump up greenhouse gas emissions, say environmentalists. The US already generates about 25 per cent of the world's greenhouse gases. "The President is walking away from any responsible appr(>ach to global warming,' says David Doniger, an official from the environmental group Natural Resources Defense Council.

But Bush insists the plan actually strikes a good balance between increasing energy production and conservation. "No matter how well we conserve, we're still going to need more energy," he says.

Many of the recommendations are designed to make it easier to drill and refine oil. The plan claims the US is in the midst of an energy crisis, characterised by energy shortages in California and higher fuel prices for motorists.

Among other things, the plan recommends opening up the Arctic National Wildlife Refuge for oil drilling, and changing the regulations and fees that stop drilling on other public land. Bush also wants to ease environmental regulations to make it easier to build new refineries.

Bush proposes spending $2 billion over 10 years on clean coal technology that would help reduce sulphur and other pollutants. The plan also calls for the Nuclear Regulatory Commission to make it easier for nuclear plants to get a licence.

Anti-nuclear groups reacted angrily to the proposals. "The Bush-Cheney administration's promotion of nuclear energy is distressingly short-sighted and potentially dangerous," said Kyle Rabirt, an official for Environmental Advocates, a pressure group based in Albany, New York. Afthough the 170-page report devotes entire chapters to conservation and alternative energy, environmental groups say few of the proposals would be effective.

Doniger says assumptions in the report play havoc with conservation. FDr instance, the report estimates the US will need another 1300 power plants in the next 20 years, based on a study by the Department of Energy (DOE). But the report ignores another DOE study that shows conservation measures could cut that number in half.

Worse still, Doniger says, more coal-fired plants will only increase US greenhouse gas emissions. Even if new technology can reduce other pollutants, it will probably not reduce the carbon dioxide from buming coal.

Bush's political opponents also attacked the report. "The Bush-Cheney energy plan is ndt a plan for America's future," says Tom Daschle, the Senate Democratic leader. "it relies almost exclusively on the old way of doing thingsdrilling more oil wells, buming more coal and using more natural gas. lt jeopardises our environment," he adds. Kurt Kleiew

Plutonium for sale With nuclear smuggling on the increase, how long before a terrorist builds a bomb?

THE nuclear arms race has left the world with a terrifying legacy: 3 million kilograms of bomb-grade plutonium and uranium. A terrorist would need no more than a few kilograms to make a devastating bomb, so you'd think this material would be kept under guard in secure military installations. You'd think so, but you'd be wrong. Radioactive materials are going missing, border controls are almost non-existent, monitoring equipment doesn't work and smuggling is rife. This was the frightening picture painted at a conference of nuclear experts in Stockholm earlier this month organised by the International Atomic Energy Agency (IAEA), Interpol and the World Customs Organization. It seems only a matter of time before a terrorist group acquires the ultimate bargaining chip. Terrorists don't even have to get hold of enough to make a nuclear bomb, says Friedrich SteinhAusler, a physicist from the University of Salzburg in Austria and a former member of the International Commission on Radiological Protection. They could steal radioactive isotopes from unprotected research and medical facilities with "relative ease" and combine them with conventional explosives to contaminate large areas, or simply spread them through the ventilation system of an airport, office complex or shopping mall. "Such a potential future scenario emphasises the low-tech terror of 'mass disruption' rather than 'mass destruction'," Steinhdusler says. Today's leading terrorist groups, however, may have the means and the determination to achieve mass destruction. These groups include Osama bin Laden's Al-Qaida in Afghanistan, which bombed US embassies in Dar es Salaam and Nairobi in 1998, and japan's Aum Shinrikyo cult, which in 1995

'If terrorist groups are intent on building a nuclear weapon, the end of the cold war has provided them with ample opportunity' released sarin gas on the Tokyo subway. There is evidence that both have been trying to acquire a nuclear capability, and according to the US State Department there are as many as'130 terrorists groups worldwide that pose a potential nuclear threat.

If any of these groups is intent on building a nuclear weapon, the end of the cold war has provided them with ample opportunity. According to Steinhausler, up to a hundred countries may hold radioactive materials that they can't safeguard properly. In many of these countries, often former Soviet republics, the soldiers guarding the materials are hungry and haven't been paid for months. And there are long stretches of open country across their borders where, as Steinhdusler puts it, 'no one checks what you have in your rucksack". Steinhausler, working with colleagues at Stanford University in California, has just completed a study of nuclear security in 1 1 typical countries: the US, China, Germany, Austria, Poland, Romania, Switzerland, Israel, Brazil, Kazakhstan and Bangladesh. lt reveals gaping holes in their ability to detect nuclear smuggling, worrying flaws in their audits of radioactive materials and serious shortages of trained staff, equipment and resources. None of the 11 countries has any radiation monitoring equipment covering its unfenced borders, where there are few roads, railways or settlements. One of the countries had no radiation monitoring equipment at any of its borders. Although the study does not point the finger at any particular country, it discloses that around a quarter of them do not keep registers of radioactive sources that may have been lost from laboratories or hospitals. Half of the countries knew of unlicensed radioactive material, and in nearly a third nuc lear material has been stolen from licensed sites in the past 10 years. Steinhdusler's unnerving analysis was backed up by other studies presented at the Stockholm conference. These include new figures from the IAEA showing that the number of attempts to smuggle radioactive materials has doubled over the past five years (New Scientist, 12 May, p 6). Some 10 per cent of the 370 incidents of illicit trafficking confirmed since 1993 have involved plutonium or enriched uranium, six of them since April 1999 (see Graphic). 'In most cases the quantity of highly enriched uranium and plutonium encountered is small compared with the amounts required for a nuclear explosive," IAEA analysts say, although these may simply have been samples of larger quantities up for sale. And the material that is intercepted may be just a fraction of what is actually being smuggled. Ian Ray, a forensic nuclear scientist from the Institute for Transuranium Elements in Karlsruhe, Germany, estimates that only 5 to 10 per cent of the illegal traffic in radioactive materials is detected. So why are so few smugglers being caught? One reason is that most radiation monitors at border crossings don't work, according to a survey for the IAEA by the Austrian Research Centre at Seibersdorf. Out of 14 installed systems, 12 failed to meet the IAEA!s minimum standards for detecting radiation from weapons-grade plutonium, and 11 out of 24 portable monitors either failed tests or could not be tested.

Another study, by the Swedish Nuclear Power Inspectorate, found "imperfections in many national systems for combating illicit trafficking", including inadequate laws, poor regulations, unclear lines of responsibility and a 'shortage of suitable and modern equipment for monitoring and detection".

'One reason why so few smugglers are caught Is that most radiation monitors at border crossings don't work'

The US Department of Defense tried to improve this situation with a four-year programme to train and equip police and customs officials in 17 Eastern European countries. But it is far ftom satisfied with the results. "Some recipient countries have failed to demonstrate an earnest commitment to programme goals,' says the DOD's Harlan Strauss.

Russia is the epicentre of the nuclear smuggling problem, and the US has committed $2.2 billion to a programme aimed at ensuring that nuclear material held there is secure. But a report from the US General Accounting Office in February showed that after seven years only 14 per cent of Russia's 603 tonnes of weapons-grade material has been fully secured.

Norwegian scientists also criticise the programme for failing to cover 120,000 spent fuel assemblies from Russian submarines and icebreakers. Spent fuel is usually regarded as "self-protecting" because it is too radioactive to handle safely. But a new investigation by the Norwegian Radiation Protection Authority concludes that after 30 years or less the radiation wfll have decayed sufficiently for terrorists to be able to extract enriched uraniu plutonium. Despite the risk ; the administration has said that i inten scale back the programme.

Steinhdusler believes that spent fuel from civilian reactors could also be a danger. There is a already a 1000-tonne stockpile of plutonium from commercial power stations, and recently declassified US documents show that it can be made into bombs. The Los Alamos National Laboratory in New Mexico has even suggested that only "a relatively low level of sophistication' is needed to make americium and neptunium-also found in spent fuel-into nuclear explosives.

Nuclear authorities are starting to call for action. The Swedish Nuclear Power Inspectorate wants the IAEA to set up a unit to combat smuggling. And experts are meeting in Vienna this week to discuss plans to strengthen the IAEA's Convention on the Physical Protection of Nuclear Material.

Others advocate a more direct approach. Phil Williams, an international security specialist from the University of Pittsburgh, thinks police forces should step up undercover operations to trap smugglers. More than 40 such operations in six countries have had 'considerable success' at catching smugglers, he says.

Alex Schmid, head of the UN's Terrorism Prevention Branch, warns that just as nuclear weapons technology has spread to countries like India, Pakistan and Israel' despite the best efforts of the major powers, it may be impossible to stop it spreading to terrorist groups. 'Time might not be on our side," he says. Rob Edwards, Stockholm

Foul fare Agent Orange is still poisoning the Vietnamese, but now it's in the food

ALMOST 30 years after American planes stopped spraying Agent Orange in Vietnam, some people in contaminated areas have more than 100 times as much dioxin in their blood as people in the country's capital. Measure ments by an American researcher show levels Weirohigchest since 1973 because the her is n w "Centrated in people's food.

About 70 million litres of Agent Orange were sprayed on Vietnam during the war. The herbicide stripped trees of foliage, and helped American forces locate Vietnamese soldiers on the ground. But Agent Orange was contaminated by TCDD, a particularly potent dioxin. As well as being carcinogenic, dioxins are known to impair the immune system, cause miscarriages and reduce children's IQ.

Arnold Schecter of the University of Texas School of Public Health in Dallas says TCDD that seeped into soil and river beds is becoming concentrated in fish and water. In some parts of Vietnam, it is accumulating in children born after the end of the war. "There is no doubt that Agent Orange contamination in Vietnam is not part of history-it's happening now," Schecter told New Scientist. The number of Vietnamese living in contamination hot spots could be as high as several million, he says.

During the'war, US forces used Bien Hoa in southern Vietnam as an air base and chemicals dump. When Schecter and his team analysed blood from local people they found TCDD levels up to 135 times higher than those in samples taken from people in a Hanoi, where Agent Orange was never used.

People from families that ate the most fish had the highest blood TCDD levels, he says.

The health implications are unclear. Vietnamese studies have found increased rates of cancer and congenital malformations in dioxin hot spots, but international teams claim these are inconclusive, Schecter says.

A clean-up operation could take ten years, and could risk releasing more dioxins into the environment. Schecter says that people at risk could be given uncontaminated food and water.

American veterans of Vietnam receive compensation for health problems related to Agent Orange. The US government has pledged to contribute to humanitarian projects in Vietnam. But it will not officially provide aid to clean up Agent Orange, or to compensate Vietnamese people.

"The US Congress put in its budget just under $1 million for joint US and Vietnamese research into Agent Orange in Vietnam," says Schecter. "But this is being held up by the debate between the two governments on linking humanitarian assistance to Agent Orange public health issues.'

Michael Gochfield of the University of Medicine and Dentistry of New Jersey says that people in hot spots such as Bien Hoa probably have a higher exposure to these chemicals than anyone else in the world. "We are wrong to ignore the plight of the Vietnamese, on whom massive amounts of chemicals were bestowed." Emma Young

More at: Joumal of Occupational and Environmental Medicine ivot 43, p 435)

Dust up Why clouds of dirt stop rain failing in the desert

SOME farmers may be stoking a vicious cycle of desertification, making and fields even more parched. Satellite observations suggest that airborne dust from deserts can stop rain from falling-the exact opposite of what meteorologists expected.

The effect may already be influencing the Sahel region of Africa, where herds of grazing livestock kick up huge amounts of dust, warns Daniel Rosenfeld of the Hebrew University in Jerusalem. "You would expect that feedback to contribute to the drying over that part of the world."

Clouds form when water vapour in rising air condenses on tiny particles or 'condensation nuclei". But it only rains when the droplets grow large enough to fall. If something stops them from reaching that critical size, clouds can evaporate without yielding a drop. Most cloud-forming particles come from desert dust, smoke from burning vegetation, and aerosols from air pollution. But earlier studies have shown that the large numbers of tiny particles in smoke and pollution aerosols actually suppress rainfall: the limited amount of moisture is divided among many condensation nuclei, producing lots of tiny droplets instead of larger droplets that fall.

Desert dust particles are larger, however, and computer models had predicted that these would seed larger droplets, increasing rainfall. This would partly offset the reductions in rainfall caused by the tiny smoke particles and aerosols. Yet satellite observations of clouds that formed over dusty and dust-free regions of the eastern Mediterranean during a heavy dust sto till have now showed this prediction is false.

The clouds that formed in dusty zones mainly contained small droplets, less than 14 micrometres across, that weren't big enough to fall as rain, Rosenfeld found. Only clouds at high altitudes where ice could form contained large enough droplets. Dust-free clouds, by contrast, produced droplets bigger than the threshold needed for rain to fall.

When Rosenfeld's team analysed particles of desert dust, they found they contained little or no soluble material. He believes this makes them collect water less efficiently, although they could still accumulate ice at high altitudes to produce some precipitation. Earlier computer models, says Rosenfeld, assumed dust particles were partly soluble, leading to the prediction of larger droplets.

The observations add to evidence that humans are damaging the planet's ability to cycle water, Rosenfeld says. "I'd be sceptical that positive feedbacks of desert dust are the control mechanism for desertification. But it may be crucially important once land degradation processes begin,' says Lenard Milich of the UN's World Food Pro-! gramme. Rosenfeld believes such changes! will have a larger impact on people than: global warming. Jeff Hecht

More at: Proceedings of the Notional Academy of Sciences (vol 98, p 5975)