Is Agent Orange Still Causing Birth Defects?

image07Vietnam insists that children are suffering today from the lingering effects of the infamous defoliant sprayed by U.S. forces decades ago. Scientists are undecided

By Charles Schmidt on March 16, 2016
Scientific American

In Brief

Vietnamese doctors claim that the defoliant Agent Orange, sprayed during the Vietnam War, causes genetic defects in children and grandchildren of people who were exposed.

U.S. animal tests show that genetic damage from dioxin in Agent Orange can be passed on to offspring, but species vary widely in how susceptible they are. No human studies exist.

American scientists say Vietnamese research linking Agent Orange exposure to birth defects is flawed. Authorities there have not allowed American experts to conduct studies in Vietnam.

Without admitting guilt, Congress approved $21 million to help disabled people in Vietnam, but that country says the aid should be far higher.

After he was born with a cleft lip and palate and congenital heart disease, Danh (not his real name) spent his first month in an incubator struggling to breathe. He is now eight years old and thin as a rail. Danh has an endearing smile, but he can’t speak, and his mother, Lien (also a pseudonym), says he is mentally disabled. Recently he sat playing with toy cars at home in Da Nang, Vietnam, while Lien talked wearily about her son’s many needs.

I had been brought to Lien by a private American aid group called Children of Vietnam that works with poor families in Da Nang. We sat drinking tea in a simple room open to the street, chatting over the din of traffic. Family pictures hung next to a portrait of Ho Chi Minh, Vietnam’s communist revolutionary leader. Lien’s otherwise soft features hardened when I asked what she thought had caused her son’s disabilities. “Agent Orange did this!” she exclaimed through an interpreter, her eyes flashing with anger.

Agent Orange was a defoliant sprayed by the U.S. during the Vietnam War to clear dense vegetation and reveal enemy troops. It was contaminated with dioxin, a potent toxicant that persists for decades in the environment. Danh’s grandfather fought in the heavily sprayed Central Highlands, and his father worked at the former U.S. air base in Da Nang, where dioxin was later discovered in the ducks and fish eaten frequently by local villagers. Dioxin has been associated with human cancers, heart disease and other health problems in people who are exposed. But Lien firmly believes her son inherited the toxic legacy of her father and grandfather’s exposure. The Vietnamese government, which classifies Danh as a suspected “victim of Agent Orange,” claims that hundreds of thousands of its citizens born one and even two generations after the war are battling effects of dioxin they inherited from their parents.

The U.S. government gives modest compensation to American war veterans for health problems such as leukemia, Hodgkin’s disease and Parkinson’s disease that are attributed to Agent Orange, based on detailed military records of soldiers who were present during the spray operations. Scientists used those records in studies that later associated Agent Orange with more than a dozen ailments in service men and women. But the government has refused to acknowledge claims that the defoliant also harmed the Vietnamese, in part because it says Vietnam has not provided strong data on who was exposed. Medical records in the country are spotty, and the population was also highly mobile in the chaotic postwar years, making exposures to Agent Orange difficult to prove.

Vietnam claims its data are sound, but the disagreement has sustained tension for years, particularly about effects that might be passed down to subsequent generations. Although U.S. laboratory tests in animals show that genetic damage caused by dioxin can be passed on to offspring, susceptibility varies widely by species, and no studies have been done in humans. Whether animal findings reflect the human experience “would be notoriously difficult to prove,” cautions Robert Moore, a toxicology researcher at the University of Wisconsin– Madison.

Looking to smooth relations, in December 2014 Congress passed a five-year, $21-million humanitarian aid package that, for the first time, provides assistance specifically for severely disabled people living in areas that were sprayed during the war. Charles Bailey, former director of the Agent Orange in Vietnam Program at the Aspen Institute, describes the aid as a breakthrough that “ensures that our humanitarian assistance goes to those with the greatest need.” But the aid package does not explicitly reference Agent Orange as having caused those disabilities. It is more a symbolic gesture meant to assuage the Vietnamese position than an admission of culpability. Forty years have passed since U.S. forces fled Saigon (now Ho Chi Minh City), marking the end of the war. Yet fundamental questions about the multigenerational health legacy of Agent Orange in Vietnam remain hotly contested.

DNA damaged for generations?

At the War Remnants Museum in Ho Chi Minh City, a visitor might get the impression that the science is settled. Photographs of grotesquely disfigured people hang on orange walls next to maps showing where the defoliants were sprayed. A sign proclaims that dioxin’s effects “can be transmitted to many generations through the damage to DNA molecules and genes.” Hospitals in Vietnam have entire wards devoted to the care of purported Agent Orange victims, including the grandchildren of individuals said to have been exposed.

Studies with rats do not prove that generations of Vietnamese are experiencing effects from dioxin, but they suggest that such a scenario is at least plausible. In this situation, initial exposure during the war would have reprogrammed embryonic sperm or egg cells (also known as germ cells) at vulnerable periods during pregnancy, leading to changes being passed from one generation to the next.

Scientists are now making important advances that suggest the chemical has long-lasting and even transgenerational effects. Emerging evidence in rodents at labs around the world shows that TCDD alters the epigenome—the biological system that controls which genes in a cell are turned on or off. It is because of this so-called epigenetic regulation that all the cells in a developing embryo, even though they inherit the same genes from the mother and father, go on to form different tissues. The genes that cause a cell to beat in the heart, for instance, are activated by one epigenetic process, whereas another process turns off genes that would allow that cell to transmit nerve impulses in the brain.

TCDD can reprogram those epigenetic controls, with consequences that might appear long after the chemical has been cleared from the body. “The effects don’t necessarily occur at the time of TCDD exposure,” explains Michael Skinner, a biologist at Washington State University. “Instead the epigenome can be stuck in an altered state, with effects that can occur at anytime during your life.” Supporting evidence comes from the lab of Alvaro Puga, a molecular biologist at the University of Cincinnati College of Medicine, who gave pregnant mice TCDD and found that the pups were born with nonlethal heart defects that became dangerous only when the animals reached adulthood.

When Skinner gave pregnant rats high doses of TCDD, he found that the second- and third-generation offspring had elevated rates of ovarian and kidney disease and that the fourth generation had lower sperm counts. Asked if those results were relevant to the experience of humans exposed to dioxin in Vietnam, Skinner emphatically answered, “Yes.” Some scientists question that connection as well as the relevance of Skinner’s studies to Vietnam, in part because he subjected his rats to TCCD doses far higher than those that would ever occur in the human population.

The Vietnam case is complicated by the persistence of TCDD in the environment, which might have ongoing effects independent of those passing through the germ line. TCDD’s half-life in the human body ranges from seven to 10 years. Its half-life in soils and sediments can last decades longer, allowing the compound to build up in fish and ducks, both staples of the Vietnamese diet—the very diet of eight-year-old Danh’s father.

Studies conducted between the 1990s and mid-2000s by Vancouver-based Hatfield Consultants revealed seven hot­spots—areas where soil and sediment measurements exceed 1,000 parts per trillion (new numbers suggest as many as 28 hot­spots). According to Thomas Boivin, Hatfield’s director of international operations, the top three hotspots were all former South Vietnamese and U.S. air bases in Da Nang, Phu Cat and Bien Hoa. In a 2015 study, scientists at the U.S. Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry found that fish collected from ponds at Bien Hoa were still contaminated at unsafe levels.

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