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The Scourge of Agent Orange: One of the most damaging chemical warfare agents known to warfare has bee Agent Orange used by the US to massively defoliate Vietnam during the war. Not only did this cause massive defoliation, but an epidemic of liver cancer and lingering consequences in terms of health debility and particularly foetal abnormalities, including spina bifida. Although these effects, like those of the nerve gas antidotes of the gulf war have been subject to repeated cover-ups there has finally been a payout in the US and studies recently released in Australia confirm a significant effect on foetal abnormalities in their servicemen.

Sins of father's war visited upon daughter. Marakech Jennings-Lowry was still six years off being conceived when her father returned from fighting in Vietnam. He began suffering health problems soon after returning home. Today he is more than half-blind and suffers from rashes and stress disorder. But nothing could prepare him for the medical horror story that unfolded with the birth of Marakech, born with holes in her heart and without a crucial valve as well as having an under-developed lung, curvature of the spine, asthma and eczema. New Zealand veterans collectively received $750,000 NZ ($360,000 US) some 20 years after exposure from a class action suit in the US.

Australian Survey Points to Cancer and Birth Defects

By MATHEW DEARNALEY Apr 98

More than 10,000 Vietnam War veterans in Australia have been diagnosed with cancer, according to official research which also raises deep concern about their children. Heart disease has also been diagnosed among almost 6000 of 40,030 participants in a survey of the Australian Veterans' Affairs Department. New Zealand veterans anxiously waiting for the research findings have already been dismayed by an early disclosure of high rates of spina bifida among children of those surveyed. They have seized on this as further evidence of links between defoliants used in Vietnam, notably Agent Orange, and of birth defects in their own children. But a research summary received yesterday from the Australian Minister of Veterans Affairs, Bruce Scott, also arnpufied fears about the parents' health.

A spokeswoman for the Vietnam Veterans' Association, Katrina Piggott, said the findings made it imperative for the New Zealand Government to do much more to alleviate the suffering of its own veterans and their families. Among the 25 per cent who said they had been diagnosed with cancer were: 405 with cancer of the colon - more than three times more than expected; 137 with non-Hodgkins lymphoma - almost triple the expected number, 64 with leukaemia - twice as many as expected; and 51 with a very rare male breast cancer - more than 17 times that of the general population.

Psychological disorders were also prevalent with: 31 per cent of veterans suffering from post-traumatic stress disorder; 41 per cent from depression; 30 per cent from Panic attacks. other unexpected results were: 128 cases of motor neuron disease; 84 of multiple sclerosis.

Among veteran's children: 353 were born with spina bifida - more than 10 times the expected number; 138 with Down's Syndrome - 50 Per cent more than normal; 231 had committed suicide - more than three tames the expected number, 836 had died in accidents - double the rate of the general population.

Innocent Victims Third Generation Agent Orange Deformities NS 3 Oct 98 18

TO THANH NAM is a victim of phocomelia, a congenital deformity that has left him without legs. But his two feet have grown just the same-attached to the torso where his thighs would normally be. Phocomelia is Greek for "limbs of a seal". He was born in June 1997 in the village of Nguyen Khe near Hanoi in Vietnam. Doctors believe he is one of a small but growing number of Vietnamese children who are third-generation victims of the toxic pesticides-in particular Agent Orange-that were sprayed over the country by the US Air Force at the height of the Vietnam War 30 years ago. The Americans were trying to destroy the rainforests in what was then South Vietnam to flush out communist Vietcong soldiers, who used the cover of the forests to built bases, move troops and ambush traffic on roads and railways. The baby's grandfather is To Tiern Hoa. Between 1968 and 1972 he fought the Americans in the jungles of the Aluoi Valley, about 60 kilometres west of the coastal town of Hue. The valley was among the most heavily sprayed areas. He did not himself suffer visible damage from the chemicals, but his first son was later born with a toe missing from his left foot. And then his grandson was born. The history of this family has been tracked by Le Cao Dai, a medical researcher and director of the Agent Orange Victim Fund set up in July by the Vietnam Red Cross. He says there is no proof that the malformations in To Tiern Hoa's son and grandson are caused by his exposure to Agent Orange, but points out there is no previous history of birth defects either in the family or among people in their village. Nor has the family been exposed to other pesticides or drugs that might cause defects. Le Cao Dai is monitoring a dozen other children with similar conditions that he believes are linked with their grandparents' exposure to Agent Orange. "To establish scientifically such a relationship we need sophisticated tests that are not available at the moment in our country," he says. "But after a careful c@ical examination and interviews with the family members that show no other causes, we believe the link." Agent orange is a mixture of the herbicides 2,4-D and 2,4,5-T. Both chemicals mimic plant hormones and upset the metabolism of growing plants. Concern about the formulation centred largely on the presence of dioxin, or 2,3,7,8-TCDD, an unwanted by-product in the manufacture of 2,4,5-T and one of the most poisonous substances known to science. Dioxin is strongly suspected of being a human carcinogen, linked with both soft-tissue sarcomas and non-Hodgkin's lymphomas It is also known to disrupt the body's hormonal, reproductive and immune systems in a variety of ways. Animal studies have shown that it can feminise males and cause birth defects in their offspring. But the biggest concern is that the damage appears to extend to the human reproductive system, causing fathers to produce damaged sperm. There is currently no evidence that dioxin damages DNA and so causes mutations. So if, as Le Cao Dai believes, it is causing second and third-generation birth deformities, the likelihood is that they are congenital, caused by either the continuing presence of dioxin in the environment and human tissue, or lingering effects on the father's or mother's hormonal system. Appalling second-generation birth defects among the children of veterans exposed during the war to Agent Orange and other pesticides have been well documented. According to Professor Hoang Dinh Cau, the chairman of Vietnam's 10-80 Committee, which investigates the consequences of the use of chemicals during the war, tens of thousands of children are affected.

Common symptoms are limbs twisted in a characteristic way or missing altogether, and eyes without pupils. Le Cao Dai and his colleagues have conducted a study of the families of some 1900 veterans, graded according to whether and for how long they served in areas subjected to spraying. Of the 8000 children bom to these veterans, the proportion with defects rose from 1.1 per cent bom to veterans with no known exposure, to 1.9 per cent for light exposure, 2.2 per cent for moderate exposure and 5.1 per cent for high exposure.

Overkill

The chemicals used to make Agent Orange were widely used on farms and in gardens in the US and Europe in the,1960s. But the concentrations used in Vietnam, at 40 litres per hectare, were 20 to 100 times those employed in normal agriculture. American military aircraft sprayed some 50 million litres of Agent Orange over the country between 1962 and 1971 in a project known as C)peration Ranch Hand, which at its peak in 1969 employed 25 aircraft. They doused 1.7 million hectares, often several times over. By the end of the war, a fifth of South Vietnam's forests had been sprayed with Agent Orange, and more than a third of its mangrove forests were dead. The defoliation was on an unprecedented scale, far exceeding British spraying of jungles during counter-insurgency operations against communists in Malaya in the 1950s. From the start there was concern that Agent Orange was toxic to humans as well as trees. In 1964, the Federation of American Scientists condemned Operation Ranch Hand as an unwarranted experiment in chemical warfare. But the operation continued until a spate of reports in the South Vietnamese press in 1970 and 1971 that Agent Orange was causing birth defects, and research showing that 2,4,5-T caused malformations and stillbirths in mice. Nature has cleansed Vietnamese soils and vegetation of most of the dioxin. In the early 1970s, South Vietnamese fish typically contained 300 parts per trillion (ppt) of the chemical. Today's levels of less than 1 ppt are still higher than in the north but are similar to those in industrialised countries. But adult humans still harbour higher levels in blood, fat and breast milk. According to Le Cao Dai, the breast milk of women in former South Vietnam who were exposed to Agent Orange in childhood contains 15 to 20 ppt of dioxin. This is only one hundredth the concentration in the breast milk of women in the region in the early 1970s, but remains about ten times higher than in either former North Vietnam or industrialised nations such as the US.

Average dioxin levels in fat in the people of Ho Chi Minh City, formerly Saigon, are 19 ppt, compared with 1 ppt in Hanoi and around 7 ppt in the US. War veterans in Hanoi have more dioxin in their fat than their neighbours. Research into the effects of Agent Orange has mostly taken place in the US, where it is highly politicised. Each piece of evidence becomes ammunition in tong-running legal battles by American veterans who claim their own health has been affected by handling the chemical. Sceptics, such as Michael Gough, director of science and risk at the Cato Institute, an industry thinktank, deny that there is convincing evidence of long-term health impacts from either dioxin or Agent Orange. The poor state of Vietnamese health services means that there is little systematic data on the lingering effects of these chemicals on the population. But there is plenty of evidence that many of those exposed to spraying have suffered from persistent headaches, depression, nausea and impotence since the war. And then there are the deformed children. Further research is needed to establish the link, but Le Cao Dai and his colleagues are convinced that Vietnam faces the prospect of a new generation succumbing, perhaps in large numbers, to the curse of Agent Orange. Fred Pearce

Firm but Fair We can't compromise, we must get tough on bioweapons

New Scientist 28 Feb 98

WHAT happened-or what nearly happened-last week should provide the world with some very serious lessons. In Las Vegas, two fanatics were allegedly planning an attack on the subway system in New York using anthrax which could potentially kill thousands. And in Baghdad, Saddam Hussein was planning to outstare his opponents and deny access to international inspectors who might spot his plans for germ weapons on a far vaster scale. As it turned out, we were lucky. The fanatics were arrested. And in Baghdad, the UN appears to have finally pushed Saddam into an agreement that should stop him developing an arsenal of biological weapons. But these victories should not blind the world to the risks of bioterrorism and biowarfare. Rather, we should seize a rare chance to make both a lot less likely when, next month, nations that have signed the Biological and Toxin Weapons Convention meet in Geneva. Astonishingly, although the world renounced germ warfare in the Geneva Protocol of 1925, and backed it up with a treaty banning biological weapons in 1972, it now has no means of checking on whether countries are keeping their promises. So those officials at the Geneva meeting should aim to overcome their differences and push for strict verification protocols for every nation, thereby making it harder for rogue groups as well as rogue regimes to make biological weapons. The example of Iraq has shown how even a relatively undeveloped country can produce an impressive biological arsenal in secret. And it has shown how hard it is to force that genie back into its culture flask. President Clinton admitted there is no obvious way to destroy a country's biological weapons capability with bombs. And it is terrifyingly easy to develop anthrax strains that resist both antibiotics and the West's only anthrax vaccine (see p 4). So the way forward must be deterrence, plus inspections that can catch cheats before they get too far. It was when UN inspectors in Iraq made routine monitoring visits, on short notice, to apparently innocent plants, that they started noticing things were amiss. That is what the UN should do in every country under the verification regime now being negotiated. It is what Europe and most developing countries want: random visits at short notice to installations ranging from vaccine plants to breweries, just to make sure countries are not hiding anything. But the US rejects random inspections. It claims that such inspections would imperil the trade secrets of its biotechnology firms, even though the industry knows there are technical tricks for protecting legitimate secrets while inspecting for illicit ones (see p 16). Some wonder if the US is trying to hide more bioweapons research than it cares to admit by refusing random inspections. The only way to prove it isn't, in Los Alamos as in Al Hakam (home of Iraq's anthrax bomb), is to let the inspectors in. The US is ready to go to war to impose inspections on Iraq. It must set a good example and allow the UN to impose them on everyone-including US industry. Small terrorist bands are another matter. The fanatics arrested in Las Vegas last week had already tried-and only just failed-to buy plague bacteria from an American company. Even Iraq got anthrax culture, by overnight courier, from a company in the US. It's obvious that there should be stricter controls on trade in potentially dangerous biological organisms. What's stopping this? The richer countries are willing to put trade controls into the biological weapons treaty but poorer ones object because they fear it could slow the growth of their nascent bioindustries. It is going to be hard to prevent terrorists or evil regimes from using disease as a major weapon in the 21 st century. We need a treaty with teeth. Just making the right noises will not go down well with the populations of London, Washington or Moscow while they are commuting on the subway.

Deadly Secrets Random Inspections for Biological Weapons

New Scientist 28 Feb 98

A BOMB explodes in central London. It does little obvious damage and is put down to a terrorist's mistake. Then hundreds of people start showing up in clinics with bad chest colds, which quickly progress to pneumonia and fever. Patients start dying with lungs choked with fluid and the doctors alert the government. When the lab results come in, the government urges anyone with cold symptoms who was in London the day the bomb exploded to come in for antibiotics. Panic ensues, hospitals overflow and a young doctor leaks the real story to the papers: the disease is anthrax. A week later, the death toll has risen to tens of thousands. Such a scenario is credible as long as countries possess the means to make biological weapons. It explains why the US and Britain would rather go to war with Iraq than live with the possibility that Saddam Hussein could be hiding anthrax, botulism, aflatoxin and other lethal agents. It is also the reason that 140 countries-including Iraq-have ratified the 1972 Biological and Toxin Weapons Convention (BTWC), which prohibits the manufacture and acquisition of organisms or their toxins for military use. However, most govemments agree that as it stands the convention is ineffective. Unlike the treaties that ban nuclear and chemical weapons, the BTWC provides no legal means to check if countries are complying. Treaty members are now trying to strengthen the convention to include a system of verification. Europe and many developing countries want UN inspectors to make random visits, at short notice, to any factory or lab-in any country-capable of producing lethal organisms. But the US govemment, under pressure from its drugs and biotechnology industries, rejects this idea. The companies fear that such visits would expose trade secrets. The issue will come to a head next month when an ad hoc working group of member countries meets in Geneva to continue negotiations on the BTWC.

 disease  agent  symptoms
 aflatoxin  aspergillus flavus  nausea, vomiting,
liver failure, cancer
 anthrax  bacillus anthracis  high feveer, laboured breating, rapid heartbeat
 botulism  clostridium botulinum  nausea, fatigue, cramps, headache, resipratory paralysis
 plague  versinia pestis  lung infection, pheumonia, heamorrage
 ricin  ricinis communis  convulsions, stupor, vomiting, bloody diahorrea

Double standards

Supporters of random inspections point out that while the US is willing to go to war to back the UN's mght to inspect any sites it chooses in Iraq, it will not grant the UN the same right to inspect itself or the other members of the BTWC. Yet UN inspectors say that such inspections were crucial to discovering biological weapons in Iraq. Jack Melting of the Salk Institute Biologicals Development Center in Swiftwater, Pennsylvania, and former head of Britain's Centre for Applied Microbiology and Research at Porton Down, Wiltshire, says the current crisii in Iraq "shows how badly we need a verification regime for biological weapons. If we had had one ten years ago, we would almost certainly have known there was a problem in Iraq before things got this bad." Once Iraq had joined the BTWC after its defeat in 1991, the only legal way to find and destroy the biological weapons that its own generals had claimed it had was for the UN Security Council to set up a special commission, UNSCOM. Through its inspections over the past seven years, UNSCOM has tested many of the ways in which a verification regime would work for the BTWC. These include the compulsory declaration of all research and development involving biological weapons, and of any facilities that could be used to make them. An inspection team then compares this declaration with other evidence, such as government documents, trade records, interviews with scientists and visits to laboratories and factories. AR signatories to the BTWC accept this approach in principle. The sticking point is how extensive the inspections should be. Everyone, including the biotechnology industry, agrees to what are known as "challenge" inspections. If there is "substanfial and convincing evidence" of a breach-such as an unexplained outbreak of anthrax-a majority of treaty members can demand an inspection. But, says Barbara Rosenberg, chair of the biological weapons group of the Federation of American Scientists (FAS), "challenge visits will never be frequent enough to be a sufficient deterrent. They require too much evidence and political risk for the country making the charge."

Stalemate

Europe and most developing countries want random, "non-challenge" inspections. Officials would be able to visit any biological facility at short notice merely to check that everything was in orderalthough this would not solve the problem of secret facilities. Negotiations on the BTWC have been stuck in a deadlock for four years because the US and the world's biotechnology and drugs industries will not agree to this (This Week, 8 March 1997, p 8). In late January, as the Iraqi crisis deepened, American President Bffl Chnton announced he would support limited non-challenge inspections to clarify unclear declarations. But he explicitly rejected random visits. Yet in Iraq, UNSCOM has shown how effective these can be. Former UNSCOM chief Rolf Ekeus stressed in 1995 that random visits to set up a monitoring programme were crucial. 'It was during the build-up of the monitoring structure that [UNSCOM was] able to detect Iraq's concealment of its hitherto secret biological weapons programmer" he said. Visits to food processing plants and vaccine factories turned up undeclared fermentation equipment and laboratories with more production capacity than had been admitted. The Pharmaceutical Research and Manufacturers of America (PhRMA), which represents American drugs companies, maintains random inspections would "expose industry to the loss of its legitimate competitive trade secrets". (It is also worried that an inspection for biological weapons would be disastrous for a company's public relations.) But Lynn Klotz, who chairs the industry section of the FAS's biological weapons group, says that inspection techniques exist that could protect legitimate secrets without hindering verification. DNA probes that screen for specific DNA sequences, possibly coupled with the polymerase chain reaction, as weu as immunoassays, which use antibodies to reveal specific molecules, "are the leading candidates for use in a compliance regime". Klotz says these techniques would need to be developed further before the BTWC could use them. But once they were ready, factory managers could supervise the tests at every step, protecting legitimate secrets without hindering the inspectors. For example, instead of taking live microorganisms out of the plant, a company would kill sampled organisms in front of inspectors and scramble the DNA enough to protect proprietary genes without disguising the species. The inspector could then run either PCR or immunoassay tests on the dead organisms with portable kits. The Chemical Weapons Treaty, which came into force last year, already allows random inspections, with "managed access" guidelines to protect industry. luotz says these could be adapted for biological plants. PHRMA complains that random inspections would pose an unnecessary burden on industry. But Graham Pearson of Bradford University, former head of Britain's biological defence programme at Porton Down, estimates that under the verification regime now being proposed, a plant would be inspected only every two years-"about what national safety inspectors do already". Supporters of random inspections say that the B'IWC's members have little time to make the treaty effective because biological production techniques are constantly improving. They are hoping that it wfll not take a lethal attack from a rogue state such as Iraq to make the US change its mind. Debora MacKenzis

Strike at Will New Scientist 21 Mar 98

NEW YORK has the reputation of being a scary place. SO the ominous news that the city has been busy working with the US Army's Chemical and Biological Defense Command seems chillingly appropriate. Simulating an attack on the city by terrorists equipped with biological weapons has already been carried out. Large-scale drills will follow, designed to prepare the city for such possibilities as the release of deadly anthrax spores into system (see p 4). Along the coast, Baltil Maryland will try simule chemical attack. Their ex ence will be used as a m for further such exercise throughout America. In London, the fire services say that they are already prepared for an attack. They claim they can put 50 trained people into special protective gear and onto the platform of any underground station within 20 to 30 minutes of an incident. It is not too surprising that the emergency services are making these plans. The 1995 nerve gas attack on the Tokyo subway that left 11 dead and 5000 injured served as a wake-up call for disaster planners everywhere. But despite the flurry of activity, there remain real worries that no one can really predict just what kind of incident could come next, still less how to cope with it effectively. The Tokyo attack used nerve gas which acted immediately, triggering a rapid response from the emergency services. Had they released anthrax spores, the effects would have been devastatingly different. No one may have noticed dnything strange for a day until the hospitals suddenly began seeing scores of people with an inexplicable illness. Because the spores can quickly spread through underground tunnels and because anthrax can only be treated really effectively in the first 24 hours after exposure to it, the number of casualties could be high. Fortunately, preparing anthrax spores for a covert attack is quite difficult and any would-be terrorist could easily end up as the first victim. Unfortunately, there are other easier options. Bacteria such as Salmonella which cause food poisoning are far easier to cultivate and simple to slip into either ter supplies. ch an incident has occurred, it was hushed up for years. another cult put Salmonella salad bars of 10 restaurants. More than 750 people became ill. Why would anyone carry out such crimes? Both the Tokyo subway attack and the Oklahoma bombing show that the world is changing. Unlike "conventional" extremists who are after political goals, the new breed of terrorist may simply be out to punish society or settle a grudge. Already one ex-employee is suspected of trying to use Salmonella to poison a former boss. There will be no quick fixes for the threats from bioterrorism. Doctors can be taught to look out for a rash of patients with unusual symptoms. Drugs and vaccines can be stockpiled to meet unexpected needs. Research on faster ways to detect pathogens is already under way. But the fact remains that many of these deadly agents are not too hard to obtain from hospitals or labs. And once obtained, anyone with some university-level knowledge of microbiology or chemistry would know how to make useful amounts. While the number of attacks remains relatively low, we can assign them a level of risk which will still put cancer higher up the league table of things to dread. If they increase, we face the bleak choice between poilice states and accepting that these random acts of violence and terror are the price of our freedom.

Nowhere to Hide New Scientist 21 Mar 98

SHOCKED by the realisation that a determined bioterrorist could decimate the population of any metropolis, US cities are starting a series of drills to work out how they might respond. City officials in New York have just completed their first simulated anthrax attack. A bigger drill is planned for sometime during the next few weeks. What happens on these occasions will be used as a model for further simulations in up to 120 cities across the country.

But experts in the containment of infectious disease still fear that current efforts are inadequate. "The bottom line is that we are ill-prepared to deal with a bioterrorist attack," says Donald Henderson of Johns Hopkins University in Baltimore, who led the successful international effort to eradicate smallpox. The simulations in New York are part of the Department of Defense's Domestic Preparedness Program, established by a 1996 Act of Congress. Under this programme, the US Army's Chemical and Biological Defense Command (CBDC) is helping city and state governments get ready for a terrorist onslaught. "We're using New York City as a special city to work on biological incidents," says Suzanne Foumier, a spokeswoman for the CBDC, based in Aberdeen Proving Ground, Maryland. Baltimore, meanwhile, has been selected to host detailed simulations of chemical attacks. In many cities, the mayor and senior officials periodically meet to run through decisions they might need to take in the face of various disasters. But the New York and Baltimore simulations differ in that they also involve "field" exercises. "I can't give a lot of specifics, but you actually have the response teams go out and act out what they would do," says Founder. "You also have a person playing a terrorist acting out what he would do." Marcelle Layton of the New York City Department of Health says that the first simulation has taught officials that biological terrorism poses different problems from a chemical attack, and is potentially much more devastating ('All fall down", New Scientist, 11 May 1996, p 32). "It really increased awareness among the various agencies, especially the nonmedical agencies," Layton says. This is all very well, says Henderson, but a handful of trained response teams and a cadre of knowledgeable senior officials is not enough. At the Intemational Conference on Emerging Infectious Diseases in Atlanta last week, he noted that most doctors have never seen a case of plague or anthrax-so it could be days before they realise what they are dealing with. Henderson believes that national govemments need to stockpile drugs and vaccines, develop and distribute rapid tests for agents used in bioweapons, and come up with effective ways to isolate infected people. When it comes to such practical countermeasures the US is hopelessly underprepared, says Henderson. No anthrax vaccine is available for civilian use, and even military supplies are of doubtful efficacy (This Week, 28 February, p 4).

"A monumental task lies before us," he says. The arrest last month in Las Vegas of two men who were allegedly planning an anthrax attack has underlined the vulnerability of major cities to bioterrorism. And there has already been one documented biological attack in the US-albeit using a less deadly organism-that has only recently been discussed publicly. In 1984, a religious cult put Salmonella bacteria in the salad bars of ten restaurants to incapacitate voters in The Dalles, Oregon, and influence a local election. More than 750 people became sick, but officials were slow to identify the outbreak as a deliberate act. "We really lost our innocence over this," says Michael Skeels of the Oregon State Public Health Laboratory in portland. "We weren't suspicious enough."


Rescuers from the Tokyo Sarin attack

Nerve Gas Sexually Selective New Scientist 14 Feb 98

SARIN may have more severe long-term effects on women than on men, according to a study of the victims of the infamous nerve gas attack on Tokyo's underground. When the Aum Shinrikyo cult exposed unsuspecting commuters to sarin on 20 March 1995,12 died and more than 6000 became ill, suffering breathing problems, headache, nausea and disturbed vision. A follow-up study of 640 victims three months after the attack detected no clinical abnormalities. 'We treated the victims as outpatients for several months, but now we have none,' says Shinichi Ishimatsu of St Luke's Hospital in Tokyo. But researchers led by Kazuhito Yokoyama of Tokyo University suspected that there might be more subtle long-term effects and returned to a sample of the victims between six and eight months after the attack. They asked nine women and nine men to stand on a platform connected to strain gauges which detected any swaying movements. The volunteers stood for one minute with their eyes open and one minute with their eyes shut, and their performance was compared to control groups of women and men. The sarin-exposed women swayed much more than the control group, unlike the sarin-exposed men. The researchers suspect that women are more susceptible than men to damage to the vestibulo-cerebellar region of the brain.