by Lewis Thomas
We went ashore and settled down partway up the slope of a hillside, and immediately found that we needed foxholes, not because of enemy fire, but to protect ourselves against the antiaircraft fire from our own ships, aimed at the occasional Japanese planes diving in just over our heads. Our first discovery was that Okinawa’s earth was made of sweet potatoes. Everywhere we dug was cultivated, also generously fertilized with night soil—a rich source, we later discovered, of typhoid and paratyphoid bacilli, which a month later produced a mild outbreak of fever among our troops (at first misdiagnosed as scrub typhus because of red spots over the abdomens of some of the patients).
There was, as it turned out, no scrub typhus in Okinawa, nor had there ever been. Nor was there any record of schistosomiasis on the island. This meant that Shope and I were effectively out of business from the outset; I would have to find other uses for the mice, and Shope, after a week or so of walking through island streams looking for the snail vectors without success, had to look for other interests.
Weeks later, in June, the real problem arrived, predicted by no one, a considerable shock to everyone in Island Command Headquarters. An outbreak of a malignant form of encephalitis occurred in several Okinawan villages at the northern end of the island, and three cases of a similar brain disease were reported in American soldiers. In its symptoms and clinical course, the illness was obviously some sort of viral infection of the central nervous system. The likeliest candidate was the agent known as Japanese B virus, which had long been recognized as an endemic disease on the Japanese mainland but was not anticipated by American epidemiologists as a hazard on Okinawa. Our unit set to work on it in a hurry. We obtained specimens of brain tissue from autopsies of several fatal cases, froze them in dry ice, and sent them back to the Guam laboratories by marine air transport. Simultaneously, we inoculated some of our dwindling stock of white mice with brain tissue suspensions. Within a week we had the virus, reproducing the disease in mice, and the Guam serological laboratory reported that it was indeed Japanese B. The cases were isolated, mosquito control measures were taken by Island Command, and, although sporadic cases were seen each week during the rest of the summer, there were no new patients with encephalitis among the American troops. Our job then became the search for the source of the virus. Similar encephalitis viruses were familiar in America, called “equine” encephalitis, carried by horses and wild birds and transmitted to man by mosquitoes. We traveled in jeeps from one end of the island to the other, collecting blood specimens from various domestic animals and wild birds (we were staffed by ornithologists as well as mammalogists and entomologists, and equipped with shotguns), trapping mosquitoes, and driving twice each day to the marine airstrip to load our specimens for quick shipment back to Guam.
Apart from the research, the main concern was security. We set up our laboratory in an abandoned teahouse at the edge of the village of Nago, lived on C rations, and placed bunks in a nearby barn. The day after we had everything in place, we were visited by the local marine commandant and informed that we were on the perimeter of defense; indeed we were the perimeter. Just to the south of our encampment was a narrow road leading between two high hills, and for about a week we received each evening a scatter of machine-gun fire from isolated groups of Japanese soldiers who had made their way through the main line of battle in the southern part of the island. Nobody was hit, but we dug very deep foxholes outside our tents.
The marines assigned a machine-gun post in the road just behind us. We felt the deepest affection for the gunners and, one evening, an even deeper respect. A trip wire had been placed across the road, a couple of hundred yards to the south, and late one evening its flares went off, revealing a group of people running toward us in silence. The young marine posted at the machine gun held his fire and began calling on his radio to the other posts in the vicinity, “Hold your fire. Civilians.” Then he climbed over his sandbag barrier and ran down the road in the dark, alone, unarmed, to escort the group—several old men and some women carrying children—up to our barn. I don’t suppose anyone recorded this act, but if we had had the authority we would have voted him a gold medal. As it was, we clapped our hands and cheered and told him he was a great marine.
When the war ended I was was living in a tent at the northern end of Okinawa, finishing up the work on Japanese B encephalitis. We had gotten enough evidence from the serological studies of horses on the island to be reasonably sure that these animals were a potential source of the virus, presumably transmitted from horse to man by mosquitoes, but we had seen no sick horses anywhere, nor were there any local stories of a disease resembling encephalitis among the island’s animals. Still, almost all the adult horses on Okinawa had high levels of complement-fixing antibodies against the Japanese B virus in their blood samples, while young colts had low levels or no antibody, signifying a virus infection of epidemic scale in these creatures.
We succeeded in persuading Island Command to construct a tightly screened barn with a small laboratory space at one end, and three young colts, very scrawny but otherwise healthy, were brought in from a nearby pasture. We injected each with a saline suspension of infected mouse brain, then took daily specimens of blood from the jugular vein and assayed them for virus by injecting various dilutions of the blood into the brains of mice, using four mice for each dilution. For three days the results were negative, but in the samples drawn on the fourth and fifth days we had the answer we were looking for: although each of the horses remained in perfect health, as far as we could judge, they were now producing high titers of live virus in their circulating blood, ready for any mosquito that might come along.
With three horses in a barn, there were all sorts of studies still to be made: Where was the virus coming from within those horses? What was happening to the brain tissue? Were there lesions similar to those in the human disease? In the middle of planning, our orders came through to wind things up and come back to Guam. We couldn’t leave the colts, since each of them contained enough free virus to start up a new epidemic if released. Obviously, they had to be killed. “Sacrificed” is the conventional jargon; experimental animals are almost never killed in biomedical reports, they are sacrificed. We had no idea how to go about killing three young horses. We asked advice from the veterinary officer attached to the military government unit, and he suggested shooting. No, I said, we’ll have virus-loaded blood all over the place. “Have you got some formaldehyde?” he asked. We had lots. “Inject some intravenously,” he advised. It worked instantly, like magic. Island Command then arranged for a deep grave, and the bodies were safely interred, embalmed with enough formaldehyde for perpetuity, and we packed our bags for the flight back to Guam on the next marine transport that had two empty seats, early the following morning. Fifty miles off Okinawa, one of the engines stopped functioning, and we drifted back to the airstrip and waited there another day for it to be fixed, then off again and straight to Guam.
This was in late September; the war was officially ended, and we expected to go home immediately. Every morning we lined up in front of the bulletin board for news of our departure date; a few people were booked to leave, but the rest of us were told that it would take some time, maybe a few weeks, and advised to settle down. Actually, it was three months. There were several dozen rabbits still left in the animal house, and no experiments planned for them, so I went to work. I had several strains of group A hemolytic streptococcus in the freezer in my laboratory and decided to immunize some rabbits with a mixed vaccine consisting of heat-killed streptococci and a homogenate of normal rabbit heart tissue, to see whether the microorganisms could somehow stimulate the animals to produce antibodies against their own hearts. It had been proven fifteen years earlier by Alvin Coburn that a group A streptococcus infection was essential for the initiation of acute rheumatic fever and rheumatic heart disease, and many people had speculated that the streptococci might have the special property of inducing autoimmune reactions of various sor
ts. With time on my hands, and an abundance of rabbits, I set it up.
It worked marvelously well. Indeed, I’d never done an experiment before, nor have I done one since, with such spectacular and unequivocal results. All the rabbits receiving the mixture of streptococci and heart tissue became ill and died within two weeks, and the histologic sections of their hearts showed the most violent and diffuse myocarditis I’d ever seen, with clusters of inflammatory cells closely similar to the characteristic lesions of rheumatic myocarditis in humans. The control rabbits injected with streptococci alone or with heart tissue alone remained healthy and showed no cardiac lesions.
I was entirely confident that I had solved the whole problem of rheumatic fever. By this time it was mid-December, and my orders to go home turned up just as I’d finished the last autopsy on the last rabbit.
I can make this a very short story. When I got back to the Rockefeller Institute, in January 1946, I showed my slides to Homer Swift, who was then in charge of the institute’s research programs on rheumatic fever and a considerable eminence in the field. Dr. Swift was exceedingly enthusiastic and encouraging, letting me know that I had, in his opinion, duplicated the benchmark pathology of rheumatic fever in my rabbits. I went to work immediately, using the same strain of streptococci as in the Guam experiment, and using the Rockefeller stock of rabbits (the same line that we had brought to Guam in 1944). For the next nine months I set it up, one experiment after another, over and over again, using several hundred rabbits, varying the doses of streptococci and heart tissue in every way possible, and I never saw a single sick rabbit, not an instance of myocarditis, not even the slightest degree of inflammation in any animal’s heart.
After a while I gave up trying. The only explanation for the triumphant Guam experiment that I can think of is that there must have been a latent virus of some sort in the Guam rabbit colony, with the property of causing myocarditis, but why it should have done so only in the presence of heat-killed streptococci and heart-tissue suspension is more than I can make up a story about.
I still have my notebooks with those experiments, unexplainable and unpublishable, reminding me that things tend always to go wrong in research. If I had been less confident and more cautious at the time, before leaving Guam I would have taken pains to bring home some of the Guam rabbits, or at least some samples of frozen heart tissue, but I didn’t; I was so sure that the experiments meant what I wanted them to mean that it never once occurred to me that I might not be able to get the same results in New York. I had all the controls I needed; I wasn’t bright enough to realize that Guam itself might be a control.
10
ITINERARY
In the 1950s, when the National Institutes of Health were being rapidly expanded in Bethesda, and their research programs were exploding into medical schools all across the country, many of these schools began to build new facilities and add new faculty members to accommodate the boom. My generation, the equivalent of postdoctoral fellows just back from the war, found many more opportunities for research posts in new, well-equipped laboratories than had ever been available before the war, and we began to travel. It was a time for academic tramps: salaries were still at the marginal prewar level (a biochemist friend at Rockefeller used to complain bitterly that the man who drove the Drake’s Cakes truck made twice his pay), but the budgets for research equipment, technicians, and experimental animals had never been so generous. We moved around a lot.
Beryl and I moved more than most people in those years, and acquired moving as a habit. Even when we felt established within a city, roots beginning to go down and all, the addiction drove us to pack up and move to quarters on the other side of town, over and over. Every now and then I have had to fill out long forms for security clearance by the FBI when appointed to consultant positions for the government; these forms have a space of several lines requesting the appointee to write in the addresses and dates of all previous residences since graduation. I cannot do it. At one time or another we have lived in seven different apartments in New York, two houses in Baltimore, two in New Orleans, two in Minneapolis, and three in New Haven, losing chairs, tables, lamps, and rugs at each move. The only safe things were the books and bookcases; we added more shelves and volumes in every town, and Beryl has never forgotten the name of a single book or its place on a shelf. We’ve never had to clean the books; the library has dusted itself every year or so.
Of all the cities, Baltimore is the place Beryl and I remember with the most affection, although we stayed only two years. The first year we had a flat in an old brownstone on Park Street, across town from the Hopkins medical laboratories. The upstairs tenant was Elliott Coleman, professor of writing, speech, and drama at the university and, not on the side but as the central work of his life, a poet. We became close friends, dining at the faculty club on the Homewood campus and getting to know, through Coleman, more of the Hopkins humanities faculty than we knew of the medical school’s. Evenings, Elliott would come down to our quarters to read his poetry or to ask questions about science; my experimental rabbits later turned up, obscurely, in several of his sonnets.
In the second Baltimore year we moved to a much-coveted small house on Washington Street, a classical Baltimore row house with a white front stoop, just behind Johns Hopkins Hospital. It was a half-block walk to the laboratory and a great convenience for late-night trips to record the results of experiments that couldn’t be timed for an eight-hour day.
I might have stayed at Hopkins forever, I suppose, but my appointment was in pediatrics, which I liked but didn’t know much about except for infectious disease, and I hankered to get back to internal medicine or neurology. In 1948, Tulane University announced the installation of a new research division of microbiology and immunology in the Department of Medicine and invited me to come and run it. They agreed that I could work on allergic encephalomyelitis, an experimental-animal disease resembling multiple sclerosis, if I would manage the infectious disease clinic in Charity Hospital at the same time. We moved to New Orleans in June, first into one floor of a huge house in the Garden District, later into an apartment in a former army barracks on the university campus. Air conditioning had not yet reached New Orleans except for window fans in the houses and, here and there, small but real air-conditioning units in the laboratories at the medical school, where temperature control was necessary for research. We liked the people, and parts of the city (but not all, not Bourbon Street or Mardi Gras), and the medical school was moving into the first rank of institutions in the South. Beryl and I talked of staying, settling down, even went off with real-estate agents to look at bungalows, but we missed the winter and snow.
Two years later we settled that need, once and for all. Irvine MacQuarrie, the head of pediatrics at the University of Minnesota, came to New Orleans for a visit, carrying an offer of a Chair of Pediatrics and Medicine, really a sort of settee, with laboratories in the newly constructed Heart Hospital attached to the medical school. I could work on whatever I liked—endotoxin, encephalitis, the Shwartzman reaction, streptococci, whatever—provided I would also organize a research unit for both the pediatrics and medicine departments in the new hospital. Beryl and I paid a couple of visits to Minneapolis in the late spring and early summer, admired the city and its climate, were dumbstruck by the new research laboratories then being installed, and agreed to come. We drove north that autumn along the Mississippi in an English Austin, just big enough for us in the front and three daughters and a Welsh terrier in the back, and arrived in Minneapolis in time for an early winter.
The transition from Louisiana to Minnesota was exhilarating for the climate change, but also for other reasons. Minneapolis was, in 1950, as I think it still is, an immaculately clean, bright, and energetic city, prosperous and ambitious to establish itself as the metropolitan center for culture in general in the Northwest. The museums, the Minneapolis Symphony under Antal Dorati, the just-then-organized theater, and the magnificent u
niversity were all objects of local pride. It felt like a good place from the day we drove in and settled for a few weeks in a university residence, and Beryl and I went house hunting. Within a month we found, and bought, a wonderfully insulated and storm-windowed clapboard house in St. Anthony Park, on the border between Minneapolis and Saint Paul. It was the first house we had ever owned, the first time each of the children had her own room, the first time I’d had to shovel snow. Roots at last.
We were there from 1950 until 1954, liking everything, even the snow. The laboratory drew in some of the best young bacteriologists and immunologists from around the country: Robert Good, Chandler Stetson, Richard Smith, Floyd Denny, Lewis Wannamaker, Richard von Korff, all interested in rheumatic fever one way or another and all with research projects of their own.
It was the greatest fun, and I thought we would stay there forever.
11
NYU PATHOLOGY
I had been at Minnesota four years when the phone rang. It was Colin MacLeod, professor and chairman of the microbiology department at New York University College of Medicine. He was an old friend of old friends, having been at the Rockefeller Institute in the years just before my arrival. I had the greatest admiration for him as a scientific statesman, and also as a working scientist. He was a member of the Avery-MacLeod-McCarty triumvirate, whose work had opened up DNA genetics. The pathology department at NYU needed a new chairman, he said. Von Glahn had just retired, my name was on the search committee’s list, he knew I wasn’t a card-carrying pathologist, but most of my work had been in experimental pathology up to then so I ought to know something of the field, would I be interested? I said yes, I’d come in a minute. He said, well, the search committee, you know, has a list to go through. I said, yes, I know, but if they get down to my name I’ll come in a minute.