Adventures of a Female Medical Detective

by Mary Guinan

  Only the smallpox team members understood English, so they immediately translated what he said for the villagers. I thanked him profusely, but inwardly was a bit taken aback. I was unsure that we could actually use the elephant or what complications might ensue for an elephant under my care. I thought I would gracefully decline. Before I could do this, however, he pointed down the road, and we saw an elephant approaching in the distance. Raj Sahib said with a laugh, “I drive too fast and the elephant can’t keep up.”

  The elephant moved slowly, with an almost bouncy walk. On her back was the driver, or mahout, wearing beautiful white clothes and a splendid turban. Raj Sahib insisted on showing me how the elephant swam, but the river was about a mile or so from the village. My assistant, Shafi, and I asked Raj Sahib to accompany us in the jeep, and we led the elephant and her driver to the river.

  At the river, nearby villagers gathered to watch the process. The elephant’s shoulders were approximately nine feet high. On her back was a large handmade saddle, made of what appeared to be hemp covered with a cloth. The mahout dismounted and unrolled a hemp ladder so I could mount. The ladder seemed flimsy and swung back and forth as I climbed up. The mahout had somehow gotten back up on the saddle and helped me on. It was neither an easy nor graceful mount. The elephant had light gray skin with pink patches, and I thought to myself, Who would believe that I would be riding on a pink elephant?

  Before entering the river, Raj Sahib said that if the water were deep enough to go over the elephant’s back, the elephant would pick me up in her trunk and hold me to keep me dry.

  “No, no. Thank you, but no,” I said. “I’m not doing that. It’s okay if I get wet.”

  But the mahout did not speak English. So I asked Shafi to be sure to tell him that I did not want the elephant to pick me up in her trunk. After conversing back and forth with the mahout, Shafi told me that the driver had received orders from Raj Sahib for the elephant to pick me up if there were any danger of my getting wet. In such situations, the elephant usually picked up the mahout. I had a three-way conversation with Shafi, Raj Sahib, and the driver for several minutes, until Shafi assured me that everyone understood that, in the event of deep water, the elephant would pick up the mahout with her trunk and not me.

  The elephant walked slowly into the water. Then suddenly the river deepened and she was swimming. She scooped up the mahout—but not me. We landed on the other side and then turned around and came back again, the elephant showing off her prowess. The demonstration was a complete success, and Raj Sahib was delighted. We returned in the jeep to the village, where Raj Sahib got into his Mercedes and drove away. I never saw him again.

  And so my preparations began to include an elephant in the Smallpox Eradication Program. Before the elephant, our two possibilities to cross the river were by boat or by camel. We would pack everything into the jeep, drive to the river, and wait. Some days there was neither boat nor camel. Occasionally, a small boat, which was paddled by a standing man with a long stick, would appear. Shafi would negotiate with him to ferry us across. It would take several trips back and forth to get the two or three of us and all our supplies across. We would have to leave the jeep and driver at the river.

  Once we had crossed the river, we had to walk 1 to 3 miles, carrying our sleeping bags, clothing, a cooking stove, any food that we might have purchased from local farmers, vaccine, needles, and the numerous supplies needed for taking culture samples and sending them to World Health Organization (WHO) headquarters in Delhi. We would go to a village with a suspected smallpox case and ask if anyone had seen a person with smallpox. Shafi would show a picture of a child with smallpox and tell the villagers who gathered around us that we would give a reward of 10 rupees to anyone who would lead us to a case. Any of the workers who found a smallpox-infected person would also receive 10 rupees. This was our surveillance system.

  If we found nothing after a day’s work, it could be difficult to return home. It was often too late to walk back to the river, and it was unlikely that we could find passage at night. So we would then look for food, and Shafi would cook dinner. Sometimes we found eggs and vegetables, and, rarely, Shafi would buy a chicken that he would kill and prepare for dinner. Food was scarce. The next morning we would walk back to the river and wait for another boat or camel.

  Camels were more common than boatmen, but the camel drivers often refused to take us because the camels already had heavy loads. I disliked the camels because they were likely to bite, spit on, or kick strangers as well as to try to knock riders out of the saddle. I was bitten several times, mostly on my arms, where the camel could reach when it turned its head around while I was in the saddle. It was also difficult for a camel to carry more than two passengers (including the driver), which meant many more trips back and forth.

  So the elephant was a dream addition to the team. She could accommodate many more people and supplies when crossing. And when we landed on the other side, the elephant took us to where we wanted to go, saving considerable time and energy. And we also had a guaranteed ride home anytime we wanted. We could leave our sleeping bags, clothing, and personal items in one village and leave a worker in charge. When we returned to the village in the evening, the worker would have found food for dinner and breakfast the next morning.

  Each evening the elephant would return to her home. The next morning the elephant and driver would reappear. I arranged through Shafi to pay the mahout a daily wage (for which he was delighted), but I paid nothing for the elephant. Elephants are a sign of wealth in India; because they eat so much, they are very expensive to keep.

  We used the elephant for approximately three weeks and accomplished our objective of providing a 10-mile ring of immunity around each village with a smallpox patient much faster than anyone expected. When we left the area, I never got a chance to thank Raj Sahib. I knew no way to contact him.

  WHO had to approve all expenditures by smallpox workers. The expense for the elephant driver was an unusual request to say the least, and I heard from colleagues that D. A. Henderson, MD, the director of the Smallpox Eradication Program stationed in Geneva, was fond of saying he had to justify “payments for Mary Guinan’s elephant.”

  In 2010, I attended the celebration at CDC for the thirtieth anniversary of smallpox eradication. It was a wonderful affair, with memorable stories, many speeches, and catching up with many colleagues. When Dr. Henderson gave his talk, he again mentioned how he had to justify payments for my elephant. But after his address, I finally got to tell him, “D. A., the payments were for the elephant driver, not the elephant!” WHO couldn’t afford an elephant.

  FOUR

  Dr. Herpes

  I DON’T think anyone grows up wanting to be a physician who specializes in sexually transmitted diseases (STDs). I certainly did not. And I suspect most of us who work in this area had dreams of different careers. My path to being an STD expert was circuitous, and I am very glad I stumbled upon it. I like to say that I have newscaster Dan Rather and Salt Lake City, Utah, to thank for steering me toward a career in STDs.

  By 1976, I had left CDC and joined the infectious diseases training program at the University of Utah, where pioneering research on herpes simplex virus type 1 (HSV-1) infection was ongoing. HSV-1 is one of eight known herpesviruses that infect humans (table 1). It is the cause of cold sores.

  Ever since I can remember, I have had frequent recurring bouts of cold sores around the lips and mouth. In elementary school, I was often sent home when I had cold sores, calling negative attention to my problem. Sun exposure, fever, dental appointments, and trauma to the mouth—any of these could trigger an outbreak, which could last one to two weeks. In college, as a last resort, I was treated with monthly smallpox vaccinations for twelve months to prevent recurrences. (This was a common, but unorthodox, treatment based on the erroneous idea that the vaccine would give a boost to the immune system and prevent recurrences. At that time, no effective treatment for HSV-1 infection existed, and well-meanin
g physicians often resorted to unproven treatments.) On the bright side, although the treatment was ineffective for my cold sores, I never did get smallpox.

  Table 1. Human herpesviruses

  With my move to the University of Utah, I decided to focus my research and career on finding a treatment or cure for my lifelong affliction. And lifelong it is: once herpesviruses successfully invade a human host, they stay forever. There was a joke in those days that asked, “What is the difference between true love and herpes?” The answer: “Herpes lasts forever.”

  Infection with HSV-1 occurs throughout the world and is so common that by age 40 almost 90 percent of adults will have antibodies to it. It is a cunning virus, transmitted from person to person through close contact with the infected saliva. First exposure usually occurs in childhood, when the virus enters the mouth and infects cells of the skin or mucous membranes (epithelial cells). But it soon moves to a safe harbor in the cell body of a sensory nerve (trigeminal), where it remains in a so-called latent state. But it is not totally inactive; rather, it is silently lurking. The virus periodically reactivates just enough to move into the carrier’s saliva, but it causes no symptoms, so the person does not know if or when it is there. I call this the virus’s stealth strategy for jumping to a new host.

  Only a small subset of infected persons has recurrences resulting in cold sores. The reason why is unknown; however, recent genetic-sequencing studies suggest that it may be due in part to different viral strains. In recurrences, the virus is activated by a trigger, which causes it to move out of the nerve cell and into the skin cells, where it causes cold sores on the lips or around the outside of the mouth. So a recurrence is an activation with symptoms.

  With the University of Utah team, I conducted a double-blind, placebo-controlled study (the gold standard for determining drug efficacy) to determine the effectiveness of topical ether as a treatment for HSV-1. Preliminary reports had suggested that it might be an effective treatment (1). Ether penetrates the skin and destroys the lipid envelope of the virus, resulting in its destruction. It seemed like the perfect solution. To my immense disappointment, the treatment was completely ineffective (2).

  Before publication, I presented the results at a national medical meeting in a special session on herpesviruses (3). Because of media interest, all eleven speakers were asked to attend a press briefing afterward. I don’t remember the questions asked, but I noticed that a disproportionate number seemed to be addressed to me. (I thought it might be because I was the only woman speaker.) That evening, I turned on the CBS Evening News and was startled to see myself on the television screen, with Dan Rather saying, “Dr. Mary Guinan, an expert in genital herpes infections.” And there I was, pointing to my lip.

  I froze. I was stupefied. I had presented data and answered questions on oral herpes. Why did they think I was talking about genital herpes?

  And it did not stop there. When I returned to Utah, two reporters—one from the local CBS affiliate and another from the local newspaper—met me at the airport. The university, which was delighted to discover it had an “expert in genital herpes,” had given the reporters information on my flight arrival.

  I explained that there was a misunderstanding, clarifying that my work was on oral herpes, not genital herpes. But the subsequent stories on the evening news and in the morning paper both reported I was studying genital herpes infection.

  Soon thereafter I received numerous phone and letter requests for appointments from persons wanting help with genital herpes infection. At first, I did not respond. Then the dean’s office called, saying that it had received several complaints about my lack of response to patient inquiries and asked that I please respond.

  I felt like the lazy woodcutter in Moliere’s comedy The Doctor in Spite of Himself, whose wife played a trick on him by telling high officials looking for a doctor that her husband was a wonderful physician. But she warned them that her husband wouldn’t admit it, so they would have to beat him until he did. After several beatings, the bewildered woodcutter agreed he was a doctor and started his practice. So, like the woodcutter, I took on the mantle and started to study genital herpes infection.

  It turns out that genital and oral herpes infections are quite similar. They just occur in different places. Herpes simplex virus type 2 (HSV-2) is the usual cause of genital herpes (table 1). The virus enters in the genital area and establishes its home in the sacral nerve cell body (a spinal nerve that innervates the pelvic area and leg). The triggers for recurrences of genital herpes are less well understood then those for oral herpes, however.

  Before long, I was regularly seeing patients at their request. I was particularly struck by the plight of young women with genital herpes, whose major concern was infecting their newborn babies. The stealth strategy of HSV-2 is to reactivate and move silently into genital secretions. It can thus infect an infant during its passage through the birth canal. Newborn infection is particularly severe, affecting all systems, including the brain. I saw my first case of newborn infection soon after I arrived in Utah, and I will never forget it. The infection caused such severe brain damage that the infant was left in a permanent semicomatose state.

  I could easily understand the fears of women with genital herpes infection. Little was known about how to prevent newborn infection, so I decided to focus my studies on women with genital herpes.

  In 1980, I was recruited back to CDC to work in the Venereal Diseases Division, where I became the “herpes expert.” Because CDC considered the word venereal to be stigmatizing, it eventually dropped its use in favor of the term sexually transmitted diseases.

  It was the pre-AIDS era then, and the press rarely reported STD stories. But genital herpes had aroused public interest, so television and print media reporters frequently interviewed me about it. In some of the stories, I was referred to as either Dr. Herpes or Dr. Condom. The resulting stories were very sensational, with variations on the theme “Sexual revolution causes epidemic of new, incurable STD.” I became leery about talking to the media. In August 1982, Time magazine published an issue featuring the word herpes in bright red on the cover, with the subtitle “Today’s Scarlet Letter.” The allusion, of course, was to Hawthorne’s novel in which Hester Prynne is punished for adultery by having to wear a scarlet “A” embroidered on her dress. The Time story and others contributed to the national hysteria about herpes, and there was a demand that the government “do something about it.”

  Then I was invited to appear on a popular afternoon talk show, The Phil Donahue Show. I had never seen it, and I was reluctant to appear because of the controversy my previous media interviews had generated. The producers insisted that if I appeared I could tell the world what CDC was doing about the genital herpes “epidemic.” I finally accepted when I found out that a former CDC colleague, Larry Corey, MD, a prominent herpesvirus researcher from Seattle, would also be on the show. I thought that between the two of us we might be able to reduce the hysteria and educate the public.

  But the show turned out to be a nightmare. The live audience consisted of groups of people with an interest in the subject, some who believed that the “government was covering up the herpes epidemic.” They were there for a fight. I had absolutely no understanding of what their issues were, and as the show progressed, it became clear that the host was more interested in controversy than in education. During a commercial break, Donahue ran up and down the aisles with his microphone, urging the audience to get involved. “Get ’em,” he kept saying, referring to us, the invited guests. I was embarrassed and shaken as the show resumed. Then Donahue said something to me about CDC’s covering up the herpes epidemic, and the crowd started screaming. The general chaos continued until the show was finally over. I had not had any media training and was ill prepared to deal with a professional showman whose main interest was to entertain his national audience.

  When a representative of the television program 60 Minutes asked me for an interview, I politely declined. Despite
his persistence, I absolutely refused. He eventually contacted the director of CDC and asked why CDC was “covering up” the herpes epidemic, so the director requested that I appear on the program. The CBS team filmed the episode in my office over a several-hour period and scheduled it to air six weeks later.

  During that interval, my colleagues were worried about how CDC would be portrayed, given the show’s tendency to make the interviewee look like the “bad guy.” I was more worried about what my mother would think. My mother was a religious woman who had never even mentioned the word sex in our household. Although she knew that I worked at CDC, she had no idea what kind of work I was doing. My husband suggested that I tell my mother about the content of the program before it aired. He worried that she might have a heart attack if she wasn’t warned in advance. But I could not bring myself to do it.

  The televised episode opened with the question, “Dr. Guinan, which venereal disease would you least like to have?” Because I had never been asked that question during the interview, the response that was aired was a contrived one, a sliced-together collage of clips discussing syphilis, gonorrhea, genital herpes, and orogenital sex. I cringed.

  When the program ended, my mother called from New York and said, “Congratulations, dear. Your hair looked very nice.” She didn’t touch the subject matter. But her reaction was positive, so I took that as approval. I never again worried about what people thought about my working in STDs. I received many letters responding to the program, including several that thanked me for having the courage to acknowledge publicly that I had a venereal disease.

  My research in herpesviruses would eventually lead to my becoming part of the CDC task force investigating the emerging AIDS epidemic. The first formal report to CDC about the new disease came from Michael Gottlieb, MD, at the University of California, San Francisco; he had cared for five gay men who suffered with the new syndrome. In early 1981, the Epidemic Intelligence Service (EIS) officer in San Francisco called the office of CDC’s weekly newsletter, the MMWR, and asked if it would publish the report. The editor told him that the report had to be reviewed and cleared by a unit at CDC with expertise in the subject matter, which presented a problem because no unit had such expertise. Because one of the infections reported in the patients was cytomegalovirus (a herpesvirus), it was sent to me for review. (In fact, early on, cytomegalovirus was suspected of causing the syndrome.)