Life Lines 88

AGENT ORANGE

During the Vietnam war the US sprayed jungles to defoliate broad leafed plants and make visible places where Vietcong and their supporters would hide. Millions of tons of this mixture of two herbicides (2,4-D and 2,4,5-T) were used over a period of several years. After the war our veterans complained of symptoms and illnesses from exposure to agent orange sprays. The cold war prevented recognition of Vietnam until recently and thus a laboratory of contaminated soil and contaminated villagers was closed off to investigation by the US and its allies. The Vietnamese lacked the resources to carry out effective chemical and medical studies on their own population.

In 1983 I was one of a dozen or so Americans who met in Ho Chi Minh City with about 100 European and other scientists to discuss our work at an International Symposium on Agent Orange. I had studied 2,4-D and 2,4,5-T on fruit flies and found many biological effects. They were alone or in combination lethal at certain doses to the developing flies (as embryos and larvae). They inhibited egg-laying by the fertile females. They forced the larvae to crawl to their death before they were mature enough to undergo metamorphosis. Females (which contain more fat) were more drastically killed at sublethal doses and I would get bottles with almost all males emerging. I did not find mutations, gains or losses of chromosomes, or breakage of chromosomes.

The trip was arranged through the UN by our US representative (as an advisor since he could not formally act on behalf of the US government). I was not impressed by the Vietnamese data on birth defects because they had control values that were unrealistic. But they did have an incredible excess of molar pregnancies, which are implanted sacs lacking an embryo. These appeared among women in the sprayed regions and not among the wives of male veterans who returned to the unsprayed Northern cities and villages. I suspect that the dioxins or agent orange components caused the eggs to extrude a nucleus and when the sperm entered, a molar pregnancy formed. Since the male-only composition of these molar pregnancies appeared in print about two years after the conference, it couldn’t have been faked data based on prior knowledge.

Our veterans, and the Vietnamese, lost an opportunity to study the effects of these compounds in the food chain. Both 2,4-D and 2,4,5-T decay from sunlight and other environmental activities within a few years. Dioxins last longer but it has been more than 25 years since these sprayings took place.

Congress finally pressured the US government to compensate the veterans exposed to these dangerous compounds regardless of the strength of evidence for or against the harmful effects of these compounds. Officially we only recognize a skin disease, chloracne, as caused by agent orange exposure, but many reports of soft tissue cancers, and neurological damage have been dismissed as unproved or consequences of shell shock. When I spoke to veterans groups during the 1980s I was not convinced these men were the alcoholics, drug abusers, and malingerers many of their government critics claimed them to be.

Life Lines 70

THE REALITY OF LONG SHOT EVENTS



People buy lottery tickets because they hope that a rare event, usually measured as a ten million to one likelihood will make them instant millionaires. For that reason, I have never bought a lottery ticket. The odds are too far fetched. It is true, nevertheless, that someone out there will be a lucky winner, but no matter how you try to choose your numbers, my rational mind says it is not cause, just luck, that one particular person has chosen the right ones. There are lots of more likely, although rare events, that can happen. The chances of a severe (Category 3 or 4) hurricane hitting Long Island are about once every 75 years. The chances of a volcano exploding in the USA south of the Canadian border are about once every 100 years. A severe earthquake in Los Angeles is about once every 50 years. A severe earthquake in St. Louis is about once every 500 years. A major meteor impact causing massive destruction of life is about once in 100 million years. Having a child with an extra chromosome 18 is about once in 3000 births. The chances your baby will be included in Who’s Who in America is about 1 in 1500. The chances your baby will win a Nobel Prize is about 1 in one million for an American.


Some odds are closer to home. The chances of having a baby with a birth defect requiring medical attention are about 1 in 20. Turn that around; the chances of having a healthy baby are 19 out of 20 (95%). Sounds better, doesn’t it? Pessimists will focus on the 1 in 20; optimists will go with the 19 out of 20. But society will experience enough of the babies with birth defects to keep hospitals and their staff busy all year round. When events are relatively uncommon but not so rare as to be remarkable, we have to respond as a society to the reality of the numbers because hundreds or thousands of babies may be born in or referred to large hospitals serving many smaller communities. When I was on a sabbatical at the University of Minnesota learning human genetics by going on rounds with pediatric fellows to see birth defects, I realized that rare events are common events in environments like tertiary care hospitals. Today we think of gene mutations, chromosome disorders, anoxia, infections, and many other reasons why a pregnancy may lead to a child with a birth defect. Go back 400 years or more and most of those defects had no names. If the baby looked abnormal, society blamed an evil eye, a shock to the mother witnessing a traumatic event, a curse on the family for the transgressions of a distant ancestor.

For very rare events we don’t prepare or put much time or resources into dealing with them unless we have a technology that we can confidently use to prevent such disasters. We could use our rocket science to nudge an asteroid coming to our earth. But if the asteroid is very large (think of the Shoemaker-Levy comet whose chunks splattered the surface of Jupiter) it is unlikely we could protect ourselves. We cannot presently cool the ocean to prevent hurricanes from forming or deflect them in their path to a major city. We cannot prevent earthquakes from doing severe damage to vulnerable cities but we can produce more strict building codes to prevent a heavy loss of life.

Life lines 3

HOW TERATOGENS CAUSE BIRTH DEFECTS

The life cycle of literature runs from birth through infancy, childhood, adulthood, middle age, and old age culminating in death. It is the subject of art, literature, and philosophic reflection. But the late and early twentieth century added some additional components to our life cycle. There is the peri-fertilization period when sperm or eggs form, unite, and a pre-implantation embryo forms. It leaves the oviduct and implants in the uterus. Those events from fertilization to implantation take about five days. The next fifty days are associated with something called organogenesis. The body symmetry is laid out; head vs. tail, dorsal (back) vs. ventral (belly), left vs. right side, and the various systems are established producing organs. After the 55^th day we become a fetus and enlarge and perfect those organ systems.

Here’s the problem. A woman does not look pregnant during those first 55 days. She may not even be aware she is pregnant for three or four weeks after fertilization. It is the most vulnerable stage of her pregnancy because there are agents that can interfere with organ formation. Such agents are called teratogens. The most well known teratogen was thalidomide, an over the counter tranquillizer made in Germany and sold to millions of people in Europe in the late 1950s and early 1960s. It led to the formation of 8,000 babies with missing or deformed arms or legs and other birth defects and an unknown number of aborted embryos that were incompatible with further life. The US was lucky, Dr. Frances Kelsey at our Food and Drug Administration felt it had not been tested sufficiently. She did not like reports of long-lasting constipation and peripheral neuritis (numbness or tingling sensations of the arms and legs) reported in Germany. Despite howls of protest about overregulation and government red tape harming industry from the American company hoping to market it, she stuck to her role as a protector of public health.

There are other agents that damage organ formation. Alcohol leads to a fetal alcoholism syndrome. Exposure of the pregnant woman in early pregnancy with German measles can lead to damaged hearts and brains. Parasites in feces of household pets (toxoplasma) can cause such damage. X-rays (especially exposure to occupational or repeated doses) can be damaging to an embryo. What does this tell us? It tells us that women need to protect themselves in early pregnancy when they are most at risk. They should have their husbands clean up the cat or dog excretions. They should avoid over the counter self-medication or prescription drugs unless they have asked an important question to their physicians: “Has this product been tested for teratogenicity?” Memorize it. Write it on a card and keep it in your purse. Most physicians, health providers, and pharmacists are conscientious and they will look up that possibility for you.

As in most concerns about our human biology, it is not easy to test everything new entering the market. Testing on pregnant mice and rabbits is one way to see if new products damage organ formation. We need that regulation to prevent future disasters.