Codario found the material fascinating. He read, for example, about a doctor in the Soviet Union who had examined four hundred workers in a herbicide factory over a ten-year period, describing symptoms that Codario would come across often during his examinations of Vietnam veterans: neurasthenia, headaches, loss of libido, personality changes, chloracne, and depression. A decade later researchers who had been studying fifty of the original four hundred workers found that 20 percent of them were suffering from porphyria cutanea tarda, an often-fatal stage of liver disease associated with exposure to TCDD-dioxin. Codario also read Lennart Hardell and M. Eriksson’s studies on the relationship between soft tissue sarcomas, malignant lymphomas, and exposure to chlorophenols and phenoxy acids, and he continued seeing veterans who seemed to have stepped from the pages of the material he was reading. Codario had wanted to believe that the Vietnam War was over, that the wounds of that era were at least beginning to heal, but he would discover that for many veterans the struggle for survival that began in mangrove forests, rice paddies, and jungles has not ended. And Codario would begin a war of his own—to save the lives of veterans poisoned by toxic herbicides.
One of the more intriguing things Codario came across during his research was that workers exposed to dioxin during industrial accidents often had in their urine elevated levels of a substance called “intermediate porphyrins.” Porphyrins, he knew, are substances that act as building blocks for hemoglobin—it takes four porphyrin molecules with an iron molecule in the center to make hemoglobin—and hemoglobin is similar structurally to chlorophyll, the material that enables plants to carry out photosynthesis. Because they are extremely sensitive to light, conditions for testing for porphyrins must be carefully controlled if the test is not to be invalidated by a change in their chemical structure.
Codario concluded that he needed expert advice if he was to find a way of analyzing the porphyrins in his patient’s urine, so he contacted Drs. Schwartz and Watson’s laboratory in Abbott Northwestern Hospital in Minneapolis, where a clinic had been established some years before to treat cases of porphyria. In the early 1970s researchers at the hospital had developed a “miracle drug” for treating patients with elevated porphyrins, and Codario was interested in the possibility of using this drug to help some of the veterans he had been seeing. After a brief correspondence, the clinic’s director, Dr. Petryka, agreed to organize the analysis of the veterans’ urine.
Codario collected urine specimens in special dark containers kept in an ice bath, and sent the containers to Philadelphia’s St. Joseph’s Hospital, where a registered nurse had volunteered to help out with the project. Upon receiving the containers, the nurse measured the exact amount in each container, then poured out 100 ccs for packing convenience, and, mixing it with a preserving chemical, shipped it via Federal Express to Minneapolis, where Dr. Petryka would then use thin-layer chromatography to analyze the specimens for elevated levels of porphyrins. Over the next few months, Codario examined 270 Vietnam veterans, performing urinalysis on 120 of them and discovering that the same unmistakable pattern appeared again and again.
“In fact,” he says, “68 percent of the people we’ve examined have an elevated level of one particular type of porphyrin in their urine, a type we call copro. In addition to the elevated level of coproporphyrins, 90 percent of the veterans I’ve examined have what we call a positive Ehrlich reaction. Now the Ehrlich reaction was a test that was done several years ago as a test for porphyrin problems. It is a reaction that takes place when a measured amount of urine is added to an acidified benzaldehyde solution. Before the advent of thin-layer chromatography and all the sophisticated methods of picking up the various types of porphyrins, it was a good screening test for picking up a particular type of porphyrin called porpho-bilinogen, which is an intermediate type of porphyrin. Dr. Petryka was the first person to actually describe a positive Ehrlich reaction in certain alcoholics because of the appearance of certain pyrroles in their urine.
“But the important thing here is that in the world’s literature one can find only about ten different compounds that will cause a positive Ehrlich reaction, and to our surprise we’re finding that 90 percent of the Vietnam veterans we see have this positive Ehrlich reaction. So naturally Dr. Petryka was intrigued by this and he went about searching the urine samples to see if they contained any one of these ten chemicals. And he discovered that the veterans’ urine contains none of the them. So we concluded that the compound that is causing the positive Ehrlich reaction must be a new compound and I jokingly told Dr. Petryka that he should name it after himself, calling it the Petryka compound. But he went and named it after me, so now it’s called the ‘Codario-Ehrlich positive metabolism.’ But we do know the molecular weight—it is 220—of this compound, and Dr. Petryka is in the process of defining its chemical structure. And when he finds that chemical structure it may be very interesting because it could very well be a way of determining whether or not a person has been exposed to herbicides. Obviously, with the coproporphyrin elevation and the curious positive Ehrlich reaction, we now have a biochemical way of saying yes, these people are different. And there are abnormalities in these patients that we are not finding in those who didn’t serve in Vietnam.”
In addition to his willingness to work for very little financial gain (Codario sees all Vietnam veterans initially for free and often spends his weekends flying free of charge to the home state of any veteran who has called for help), Dr. Codario has another remarkable quality. During our interview the phone would ring, as one might expect in a busy doctor’s office, and he would listen patiently, replying to the caller’s questions or complaints with genuine concern. Then almost before he had replaced the receiver, he would continue exactly where he had left off, even if this meant in the middle of a complicated compound sentence.
“The other thing that is of interest is that Dr. Strik of the Netherlands, who is one of the world’s authorities on porphyrin problems resulting from exposure to chemicals, and has published several papers on what happens to people whose porphyrin levels are elevated due to their exposure to herbicides, has clearly stated that porphyria progresses in a stepwise fashion from asystematic coproporphyria auria to the much more devastating uroporphyria auria. And that disease is called porphyria cutanea tarda, which is a condition characterized by episodes of severe crampy abdominal pain, high fevers, schizophrenia, and often death. So it seems that the coproporphyria auria that we are seeing now merely represent the tip of the iceberg, or the beginning of the abnormality that if left unchecked may progress to porphyria cutanea tarda and death.”
Codario feels that he may have discovered a way to check the progressively destructive effects of herbicide poisoning; however, he fears that he may only be able to arrest, rather than cure, the problem. “I’m hoping that once we have established a significant statistical correlation, which we seem to be moving toward right now, that we can get approval to treat some of these porphyrin problems with the drug that they have developed in Minnesota called Hematin. But that may be an oversimplification because Hematin was designed to treat patients with acute severe porphyria—for example, patients suffering from porphyria cutanea tarda. The results have been nothing short of miraculous and are well-publicized in the journals of internal medicine. But in those cases the porphyrins they were producing in their urines were thirty to forty times higher than those we are seeing in our veterans. And we have to keep in mind that Hematin has never been used to treat chemically induced porphyrin problems, so we’re really treading in new territory and can’t be certain that it will work this way. But based on the mechanism of its action, it is certainly possible that it will be beneficial here. The thing we don’t know is, even if we are able to reverse the production of excess porphyrins, will we stop it forever just by giving the patient Hematin? And even if we return the porphyrin count to normal, will their symptoms go away? In examining the veterans and listening to their stories, I suspect that even if Hematin works it will only be temporarily effective and that after a period of time the individual will probably relapse. And I also suspect that all of the symptoms about which Vietnam veterans are complaining are not due solely to porphyrin problems but rather are a direct toxic effect of the herbicide in general and dioxin in particular.”