by Mary Guinan
Working in the office I was provided at the hospital, I reviewed the medical records of each case. The case definition we used was “a patient in the intensive care unit with a blood culture positive for Pseudomonas aeruginosa,” that is, a case-patient, as opposed to the other patients in the ICU. Many of the case-patients, who had been treated with two intravenous antibiotics for which the organism was susceptible, had remained culture positive two to five days after the onset of treatment, which was very unusual. Either the organism was being reintroduced to the bloodstream or the antibiotics were not effective (even though laboratory testing showed the organism was susceptible). The great fear was that the organism would become resistant to these antibiotics. There were no other antibiotics that were effective against Pseudomonas at that time.
Several of the earlier case-patients who had been transferred out of the ICU had negative blood cultures and were doing well. This was a clue. I again reviewed the medical records of each case and tracked the chronology of the positive blood cultures. All case-patients had become culture positive in the ICU and culture negative after discharge from the ICU. Could it be that something or someone in the ICU was contaminating the case-patients’ blood?
I shared my findings with Sarah. She told me that she had also recognized this pattern. The ICU was brand-new, having opened only a few months before my arrival. The director and staff were proud of the survival rate of the patients. Compared to the OR, the ICU was state-of-the-art and had all of the latest technical equipment. Sarah said that no one wanted to hear that this beautiful new ICU could be the place where contamination of patients’ blood was occurring.
Only two case-patients remained in the ICU. One was a 23-year-old man who had crashed his motorcycle and had multiple injuries, including a crushed chest with collapse of both lungs. He was unconscious, on a ventilator, and in critical condition. Two days after entering the ICU, he had developed a fever. Blood cultures were drawn and found to be positive for the Pseudomonas organism. He had not been in the OR nor had he received blood transfusions. These were the next clues. The contamination had to be occurring in the ICU because that was the only place he had been since admission. And this patient was still blood-culture positive. His blood cultures were continually positive during the week of antibiotic treatment.
I again reviewed his medical chart. During Sarah’s systematic investigation, she had cultured many environmental areas in the ICU, which included specialized equipment that attached patients to the monitoring screens. Two of the transducers that were connected to the many tubes in this critically ill patient had been found to be culture positive for Pseudomonas.
A transducer is a device that converts energy from one form to another. For example, in one artery in the patient’s arm, there was a tiny tube called a catheter, which was attached to a larger tube filled with a saline solution. This tube was attached to a transducer, which converted the pressure signal from the artery to an electrical signal, which appeared on the monitor as a blood pressure reading. This connection provided continuous monitoring of the patient’s blood pressure. If the blood pressure reading moved out of the desired range, an alarm would alert ICU personnel to examine the patient and to institute procedures to stabilize it. If not corrected within minutes, a precipitous drop in blood pressure in this critically ill patient would likely result in severe brain damage or death. The motorcyclist was being monitored from two additional sites, one in the heart and one in the pulmonary system; both of these sites were also connected to transducers.
I spoke to Sarah about these findings. She said she had informed the ICU director about the contaminated transducers. But because of a shortage of transducers in the unit, there were none to replace the contaminated ones, and the director thought that the patient might die if his vital signs were not continuously monitored and stabilized. So he had not removed them. He was the director of the unit and outranked Sarah, so he essentially had the last word.
I asked to speak with the ICU director. I told him that I believed that the transducers were the source of the patient’s blood contamination. He told me he felt that because nothing was flushed into the patient from the transducer lines, they were unlikely to be the source of the contamination. He pointed out that there was almost two feet of tubing between the transducer and the patient’s blood, and it would be close to impossible for the bacteria to get from the transducer to the patient’s blood. I told him that I believed that the patient might die of sepsis if the transducers were not removed. He said that the patient would likely die if the transducers were removed.
I called Walt Stamm at CDC for assistance. He agreed that the transducers were the likely source of the problem. He connected us with a CDC microbiologist who was an expert in Pseudomonas organisms. The three of us discussed the situation. I noted the two feet of tubing between the transducer and the patient’s blood and the director’s disbelief that the organisms could enter the bloodstream from that distance.
The microbiologist was exasperated. “Pseudomonas can swim!” he said. “I don’t know how fast they can swim, but they are great swimmers.”
I told him that the patient became culture positive within two days of entering the ICU.
“Then it takes two days for Pseudomonas organisms to swim down that two feet of saline solution,” he said. “Or even less, since the blood was first cultured on the second day, when the patient developed a fever. The Pseudomonas might have been down there within a few hours. We don’t know.”
Dr. Stamm and the microbiologist agreed that I should again ask that the transducers be removed. If they weren’t, I should consider going to a higher authority. I asked Sarah if I could speak to the director again. She made the request. We were told he would not be available until the next day.
I became very concerned. Sarah and I reviewed how the transducers were sterilized. We found out that because of a large caseload in the ICU, there were insufficient transducers for all patients. As a result, the usual sterilization process was being bypassed. The transducers had not been sterilized according to the manufacturer’s directions. Instead of being put in an autoclave, a pressure chamber used to sterilize materials (a process that took several hours), the transducers that were taken from infected patients were cleaned with multiple flushes of an iodine antiseptic solution and then reused on another patient. The motorcyclist had received at least one of these transducers.
I told Sarah what CDC had recommended and that Pseudomonas organisms could swim, which would essentially invalidate the ICU director’s assumptions. I asked her to convey, again, my request to speak with him and that she convey that the request was urgent.
When we were connected by telephone later that day, the ICU director told me that he could not remove the transducers because the patient would die and that I would be responsible for the patient’s death.
I told Sarah his response and asked her who would be the higher authority to whom I should appeal. She left me alone in my office. Some time later, she returned with the chief of infectious diseases, the ICU director, and the commander of the base.
I explained the reasoning and asked that the contaminated transducers be removed. I explained that the blood cultures continued to be positive, and now the organism was beginning to show some resistance to the antibiotics. The ICU director refused. The base commander, who outranked the ICU director, ordered him to remove the transducers. It was by now late in the evening. By the time Sarah and I left for her home, she told me that the transducers and all the attached tubing that entered the patient’s body had been removed.
I did not sleep well that night. I was fearful of the patient’s status. The next morning, the patient was in the same condition—no better or worse. Blood cultures were drawn. Again I reviewed the medical charts of all the cases. All of the case-patients except the motorcyclist had been transferred out of the ICU. All their blood cultures were now negative.
The next day, the blood cultures of the motorcyclist were neg
ative, and he was beginning to regain consciousness. Repeat cultures the following day were also negative, and his fever was gone.
I called CDC, and Dr. Stamm told me to come home. He said that the base commander had called him earlier, told him I had solved the problem, and praised me as being a cross between “Einstein and Wonder Woman.”
Going over the outbreak on my flight home, it was clear to me that I had not solved the problem. Sarah and her team had. They had amassed all the evidence, evidence that had convinced me of the source of the problem. Then the backup professional staff at CDC had guided me to do what apparently was the right thing.
And I was greatly relieved that the base commander was not disappointed that CDC had sent a woman.
TWO
Something to Believe In
OPERATION SMALLPOX ZERO
WHEN asked as a child what I wanted to be when I grew up, I used to reply “a plumber or a doctor.” Laughter was the usual response, as neither was a likely profession for a woman at the time. Although it was a circuitous route, I did finally find my way to becoming a physician and to a satisfying career in public health.
FROM COLLEGE TO CHICLETS
I grew up in New York City, the third of five children of Irish immigrant parents, who met on the ship bringing them to America in 1928. They had left their families and political oppression to find freedom and opportunity not available to them in Ireland. Because as children they had been needed to work the farms, they had no more than three or four years of formal grade-school education. Despite the difficult years of the Great Depression that followed their arrival, my parents warmly embraced their new country. They often told us (especially if we complained) how blessed we were to be born in the greatest country in the world with the freedom to follow our dreams.
My parents made it clear to us that we were going to go to college. We had no idea how that would happen, but we accepted college as a given and never questioned it. My father worked in the New York subway system, and my mother was a homemaker. I was a teenager when my father died suddenly. We children all found jobs and worked our way through high school and college. My mother found work as a salesperson in a department store during the Christmas season and eventually held a full-time job there.
Fortunately, I was accepted into Hunter College of the City University of New York. Not only was there no tuition for students who maintained the necessary grades, but Hunter also provided textbooks for all my courses for only $20 per semester. My mother told me I had to find a profession with which I could support myself “and stand on my own two feet.” I started out majoring in Greek and Latin studies. After I completed a first-year chemistry course, the professor asked to meet with me. Because I didn’t yet know my grade, I thought perhaps I had not done well on the final exam. But the professor told me that I had done very well, that I was good in chemistry, and that I should consider making it my major. It was such a surprise to me that I said I didn’t think so. He urged me to take another chemistry course to see how I would do. Thinking about my mother’s advice, I decided that perhaps I could better support myself as a chemist than as a Greek and Latin scholar, so I took the next-level chemistry course, did well, and became a chemistry major.
By the time I graduated from college, I knew that I wanted to be a physician, but at the time women were rarely admitted to medical school. Besides, one criterion for admission was having the money to pay for it. I did not, and scholarships were not available.
So I started searching for a job as a chemist. The New York Times want ads were segregated by gender back then, and there was never an ad for a chemist in the female listings. Sometimes I applied for the jobs listed in the male ads, but doing so was both humiliating and unsuccessful. Finally, I found a position in a chewing gum factory for the American Chicle Division of Warner-Lambert Pharmaceutical Company in Queens, New York. The company made Chiclets, Trident, Black Jack, and all sorts of chewing gum. My job was to help develop chewing gum with new flavors. My new position greatly amused my friends and family. I thought it paid well until I found out that I was paid considerably less than my male peers.
This realization moved me to apply to graduate schools for an advanced degree in chemistry. More often than not, I would receive a one-page reply saying either that the program did not accept women or that it did not provide female students with financial assistance.
THE SPACE PROGRAM
Just as I was feeling frustrated with a lack of opportunities to attend graduate school, the space program opened up. President John F. Kennedy announced in 1961 that within the decade he wanted the United States to put a man on the moon and bring him back safely. The need for scientists to participate in the space program was enormous. Federal money was allocated to support students to get advanced degrees in science to help fill the program’s need. In his inaugural address, President Kennedy had said, “And so, my fellow Americans: ask not what your country can do for you—ask what you can do for your country.”
Two years later, I was sitting in my laboratory tasting a sample of a new flavored gum that I had submitted for production. A colleague entered the lab and told me that President Kennedy had been shot. Profoundly affected by the news of his death, I decided that I would try to become an astronaut.
I found an ad in a science journal from the University of Texas Medical Branch (UTMB), in Galveston, offering stipends for doctoral students. I found out that UTMB was located close to Clear Lake City, the home of the National Aeronautics and Space Administration (NASA). I applied to the doctoral program in physiology and within two weeks received a reply from the chair of the department that I had been accepted. But the letter did not mention financial support. I wrote back, asking if a graduate assistantship were available. I received my letter back with a handwritten note at the bottom that said, “We are holding one for you,” signed Mason Guest, PhD. This was one of the great thrills of my life.
I arrived in Galveston not knowing anyone there. Because it was such a radical idea, I did not reveal my ambition to be an astronaut. The program was wonderful. On occasion, an astronaut who had been in space (such as Alan Shepard, John Glenn, or Scott Carpenter) would lecture in our class and tell us stories about his experiences. It was a heady, exciting time for a scientist, and I loved it. About two years into the program, I told Dr. Guest, who was by then my mentor, that I wanted to be an astronaut. He advised me that it would be difficult and that I should get my degree before I let this be known because he thought I might be subject to ridicule.
Just before completing my doctorate, I attended an aviation and space medicine class at NASA with about ten other students. On the last day, the teacher distributed a form that asked whether we met the medical and physical requirements for acceptance into the astronaut program. I was the only woman in the class and also the only one who fulfilled the requirements because of my good health, height, weight, and 20/20 vision. (In the 1960s, astronauts had to fit into a small capsule inside the spacecraft, so height and weight were of great importance.) Despite having the preliminary qualifications, I was not asked to apply for the astronaut program.
I knew it was unlikely that I would actually be chosen to be an astronaut because there was tremendous competition. By then, it was 1968, when preparations for the moon landing were in full swing. Command central in Houston was the control center for all moon-landing activities. When I read in a newspaper article that women were not permitted into command central, not even to bring coffee, “because they might distract the men,” I knew that there was little chance a woman would become an astronaut within the next few years.*
Dr. Guest helped me to get a postdoctoral fellowship at the National Institutes of Health (NIH) in Bethesda, Maryland, studying aspects of blood coagulation, which had been the subject of my dissertation. The Vietnam War was under way, and I took the place of man who had been drafted. Most positions at NIH required an MD, so I did not envision a future there. Then a mentor at NIH suggested that I fix that and go
to medical school—my first dream, of so many years before.
And so I did. I was accepted to Johns Hopkins School of Medicine, where I found, surprisingly, that 10 percent of students were women—a requirement of a donor, Mary Elizabeth Garrett. The faculty were supportive of my getting experiences that were not part of the academic curriculum. I applied for a US government fellowship to study tropical diseases for a semester and was sent to Guadalajara, Mexico. There I spent several weeks seeing patients at a leprosy clinic and then was assigned to the Hospital Civil, where during a polio outbreak I saw my first cases of polio, including several affected children in iron lungs. This amazing experience sparked my interest in infectious diseases.
I graduated in 1972. The medical degree, together with my doctorate in physiology in the area of blood coagulation, would prepare me for a career as a hematologist/oncologist, most likely in academic medicine. That was the plan.
OPERATION SMALLPOX ZERO
It was in 1971, in my last year of medical school, when I first heard of the plan to eliminate the dreaded disease smallpox from the world.
The United States was still engaged in the Vietnam War, and massive national protests against it were growing. When the United States bombed Cambodia in 1970, expanding the war, an antiwar protest by Kent State University students was answered by Ohio National Guard troops. Four unarmed students were shot and killed, and nine others were wounded. It was difficult to believe—our government killing unarmed student protesters on a college campus!
