The Great Influenza: The Epic Story of the Deadliest Plague in History - John M. Barry (2004)

Part X. ENDGAME

Chapter 36

IN THE FIRST YEARS after the pandemic, Paul Lewis continued to head the Henry Phipps Institute at the University of Pennsylvania.

Yet Lewis was not a happy man. He was one of those who continued to believe that B. influenzae caused the disease and continued to work on it after the epidemic passed. There was irony in that, since he had initially been reluctant to embrace its etiological role, suspecting instead a filterable virus. Perhaps the chief reason for his stubbornness was his own experience. He had not only found the bacillus with consistency, but he had produced a vaccine that seemed to work. True, the navy had administered a vaccine prepared according to his methods to several thousand men and it had proven ineffective, but he had not made that vaccine himself. A smaller batch that he had personally prepared and tested—during the peak of the epidemic, not in its later stages when many vaccines seemed to be working only because the disease itself was weakening—had given solid evidence of effectiveness. Only three of sixty people who received the vaccine developed pneumonia, and none died; a control group had ten pneumonias and three deaths.

Those results deceived him. In the past he had not always made the right scientific judgment—no investigator does—but this may have been his first significant scientific error. And it seemed to mark the beginning of a downhill slope for him.

That was not obvious at first. He had already built an international reputation. The German scientific journal Zeitschrift für Tuberkulose translated and reprinted his work. In 1917 he was invited to give the annual Harvey Lecture on tuberculosis, a great honor; Rufus Cole, for example, would not receive that invitation for another decade. Eighty-five years later, Dr. David Lewis Aronson, a scientist—whose father, a prize-winning scientist, had worked in the best European laboratories and considered Lewis the smartest man he ever met and gave his son Lewis’s name—recalled reading that speech: “You could see Lewis’s mind working, the depth of it, and vision, going well beyond what was going on at the time.”

Lewis’s views had broadened indeed. His interests now included mathematics and biophysics, and, with no resources of his own, he asked Flexner to “arrange for the support” of a physicist Lewis wanted to lure into medicine to examine fluorescent dyes and “the disinfectant power of light and the penetrating power of light for animal tissues.” Flexner did so, and Flexner continued to be impressed by Lewis’s own work, replying by return mail when Lewis sent him a paper, saying that he would publish it in the Journal of Experimental Medicine, calling it “interesting and important.”

Yet Lewis’s life after the war began pulling him away from the laboratory, frustrating him. Henry Phipps, the U.S. Steel magnate who had given his name to the institute Lewis headed, had not endowed it generously. Lewis’s own salary had risen well enough, from $3,500 a year when he started in 1910 to $5,000 just before the war. Flexner still considered him vastly underpaid and saw to it that, immediately after the war, the University of California at Berkeley offered him a professorship. Lewis declined, but Penn raised his salary to $6,000, a substantial income at that time.

But if his own salary was more than adequate, he needed to fund an entire institute, even if a small one. He needed money for centrifuges, glassware, heating, not to mention “dieners”—the word still in use for technicians—and young scientists. He needed to raise the money for all that himself. As a result Lewis more and more found himself drawn into the social milieu of Philadelphia, raising money, being charming. More and more he was becoming a salesman, selling both the institute and himself. He hated it. He hated the time it took from the laboratory, the drain of his energies, the parties. And the country was in the midst of a deep recession, with four million soldiers suddenly thrown back onto the job market, with the government no longer building ships and tanks, with Europe desolate and unable to buy anything. Raising money was more than just difficult.

In 1921 the University of Iowa approached him. They wanted to become a first-class research institution, and they wanted him to run the program, to build the institution. The state would supply the money. Flexner was more than just a mentor to Lewis, and Lewis confided in him that the Iowa job seemed “heavy, safe and of limited inspiration. You know very well that I do not thrive on routine.” And at Phipps, “Some of the work underway has great potential I believe…. You will see that I am trying to convince myself that I have a right to gamble here as against a rather dull safe outlook at Iowa City. A word from you would be much appreciated.”

Flexner advised him to accept the offer: “All I have heard of the medical situation at Iowa City is favorable,…a pretty sharp contrast to the [situation] in Philadelphia. It is definite and has the elements of permanency…. I have no doubt under the influence of your vigorous guidance, the department—although quite large—over which you would preside would become so notable that the State would stand back of you in any enlargement.”

He did not tell Lewis how well he thought the job might suit him, how extraordinary his gifts for a job like that were. But Flexner did tell a senior colleague that Lewis “might really come to exercise a real influence in medical teaching and research.” There was perhaps some of what Welch had in him, that Lewis had “quite unusual gifts of exposition.” He had broad knowledge, perhaps he even leaked knowledge, and, whether he realized it or not, he could inspire. Indeed, Flexner believed he could “be master of the field.”

The University of Pennsylvania countered the offer: it gave him a new title, raised his salary to $8,000, guaranteed it for five years, and guaranteed funding for the institute itself for two years. He stayed. Flexner congratulated “you and the University especially on your new honor. Will the new chair add to your University responsibility?”

It would. Partly for that reason Lewis remained restless. He had rejected the Iowa position because, though it might allow him to build a major institution, it would keep him out of the laboratory. Now he found himself in much the same situation at Penn. He detested maneuvering with or around deans and he continued to play the role of social creature. Scientists were the new thing, Faustian figures able to create worlds and fashionable to show off on the Main Line. Lewis hated being shown off. There was tension at home with his wife as well. How much of that came from his research frustrations, how much because his wife liked the Philadelphia society that he wanted no part of, how much because his wife simply wanted more of him, it is impossible to know.

One research project in particular seemed to be going well, and he wanted to attend to it, and give up everything else. He envied not only Avery’s ability to concentrate on one thing but also his opportunity to do so. For Lewis everything seemed to press upon him. Indeed, everything seemed ready to explode.

In 1922 Iowa offered him the position again. This time he accepted. He felt a responsibility to leave Phipps in good shape and recruited Eugene Opie from Washington University to replace him. Opie had if anything an even greater reputation than his own.

Flexner had always respected Lewis, yet there had always been a gap between them. They had been getting closer. At one point Flexner wrote him, “Some time do let me take a little trouble for you.” Lewis confided in return, “You have stood in the light of ‘father’ to me.” Now, when Opie agreed to replace Lewis at Phipps, Flexner seemed to see Lewis in a new light, capable not only as a scientist but as someone who could play another game well, telling him, “Opie surprised me. I supposed him a fixture in St. Louis. If you prepared the way for so good a man at the Phipps Institute, you may well feel gratified.”

Lewis did not feel gratified. He remained restless and discontented. What he really wanted was to be shut of everything, everything except the laboratory. Perhaps without quite realizing it, he had been moving toward a crisis. Again he told Flexner that what he really wanted more than anything was to work at his laboratory bench. He was shut of Philadelphia. Now he had to get himself shut of Iowa.

In January 1923 he wrote Flexner, “It is quite clear to me today that I am entitled again for a short time at least to cultivate my personal interests…. I am giving up my place here and all of my plans for a future in Philadelphia…. I have written to President Jessop, of the University of Iowa, telling him of my change of plan and that that is also in the discard…. I am going to try my best to develop the opportunity for a year of study in some place as far removed from any question of ‘affairs or position’ as possible…. I cannot make it too plain that for the coming year I am seeking no position in the conventional sense of the word. What I really want is…the rehabilitation of a more or less vacant mind.”

He was quitting everything, walking away from position, prestige, and money, walking into the wilderness with no guarantee of anything, stripping himself naked at the age of forty-four with a wife and two children. He was free.

Where he had been happiest in his life, where he had done the best science, had been at the Rockefeller Institute. The institute had created a Division of Animal Pathology in Princeton, close to Philadelphia. Theobald Smith, the same man who had rejected Welch’s offer to become the first head of the Rockefeller Institute itself, had left Harvard and now headed this division. Smith had also been Lewis’s first mentor, and had recommended him so many years before to Flexner. Lewis explored with Smith the possibility of going to Princeton. Smith first wanted assurances that Lewis wanted “to go to work again and…that all this advertising business had not gone to [his] head.” Lewis eagerly gave them.

Flexner had urged him to take the Iowa job but replied, “I shall be rejoiced to see you return to the lab where you so naturally belong and in which you will do your best, most lasting, and effective work. It seems to me a crying pity that men who have given years to the necessary preparation for a lab career should be so ruthlessly drawn away from it and made to fill executive positions.” He also told Lewis that Smith was “very pleased with the prospect of having you associated with him again.”

Lewis asked for no salary whatsoever, just full access to the laboratories for a year. Flexner gave him $8,000, his salary at Phipps, and a budget for laboratory equipment, filing cabinets, 540 animal cages for breeding and experimenting, and three assistants. He told Lewis he would expect nothing whatsoever from him for the year, and then they could talk again about the future.

Lewis was ecstatic: “To start with Dr. Smith again on any possible basis, takes me back to 1905—on I hope certainly a new higher level…. You will not find me lacking in effort…. I am most fortunate and happy in being able to regard myself as entirely in the hands of you two men who, without distinction, and excepting only my parents, have given me the means and the education and the direction. Few have such a chance to renew their youth. My only hope is that I continue to deserve your confidence.”

Princeton then was still surrounded by farms and countryside. It was peaceful, almost bucolic. The Rockefeller facility was not far from the campus of Princeton University, which was still transforming itself from the finishing school for gentlemen that F. Scott Fitzgerald described to the intellectual center that it would not fully become until a decade later, when Flexner’s brother Abraham started the Institute for Advanced Study with Einstein as its first member. But if the setting was bucolic, if crops grew and assorted animals—not simply guinea pigs or rabbits but cattle, pigs, and horses—grazed only yards from the laboratories, the Rockefeller part of Princeton brewed intensity. Smith was continuing to produce world-class work. Just being around him energized Lewis. For the first time since he left the Rockefeller Institute, he felt at home. Yet he was alone. His wife and children stayed in Philadelphia. He was alone to work, alone to go to the laboratory in the middle of the night, alone with his thoughts.

In nearly a year, however, he produced nothing. Flexner and he did discuss his future. He was forty-five years old. His next move would likely be his last one. He could still return to the University of Pennsylvania if he chose. He did not so choose, telling Flexner, “I can only repeat that I am free of any entanglement there, even of sentiment.” The University of Iowa had also extended its offer once again and once again raised the salary. But what he wanted was to stay at Rockefeller. He had made little progress on the tuberculosis project he had brought with him from Philadelphia, but, more importantly, he had, he assured himself as much as Flexner, rejuvenated himself. He informed Flexner that, despite the higher salary at Iowa, “My only interest in ‘position’ is [here].”

Lewis’s presence fitted perfectly into Flexner’s own plans. Flexner explained, “I have always believed that our departments should not be one man affairs.” In New York a dozen or more extraordinary investigators led groups of younger researchers, each group working on a major problem. The Princeton location had not developed similarly; beyond Smith’s own operation, it had not filled out. Flexner told Lewis, “Your coming…[offers] the first chance to make a second center there.”

Further, Smith would turn sixty-five that year. Flexner and Smith and even Welch hinted to Lewis that he might succeed Smith when he retired. Flexner suggested that Lewis stay one more year under a temporary arrangement, and then they would see.

Lewis told Flexner, “I am secure as I never was before.” He believed he was home. It would be his last home.

If Lewis was going to build a department, he needed a young scientist—someone with more than just laboratory skills, someone with ideas. His contacts in Iowa urged him to try a young man they thought would make a mark.

Richard Shope was the son of a physician who was also a farmer. He had gotten his medical degree at the University of Iowa, then spent a year teaching pharmacology at the medical school and experimenting on dogs. An outstanding college track athlete, tall, a man’s man at ease with himself—something Lewis never quite seemed to be—Shope always maintained contact with the wild, with the forest, with hunting, not only in the laboratory but with a gun in his hands. His mind had a certain wildness, too, like a small boy playing with a chemistry set hoping for an explosion; he had more than an inquiring mind, he had an original one.

Years later Thomas Rivers, the virologist who not only succeeded Cole as head of the Rockefeller Institute Hospital but served as president of four different scientific associations, said, “Dick Shope is one of the finest investigators I have ever seen…. A stubborn guy, and he is tough,…Dick would no sooner start to work on a problem than he would make a fundamental discovery. It never made one bit of difference where he was.” In World War II, Rivers and Shope landed on Guam soon after combat troops secured it (in Okinawa they would come under fire) to investigate tropical diseases that might threaten soldiers. While there, Shope occupied himself by isolating an agent from a fungus mold that mitigated some viral infections. Ultimately he was elected to membership in the National Academy of Sciences.

Yet even with Shope’s help, Lewis’s work did not go well. It was not for lack of intelligence on Lewis’s part. Shope knew Welch, Flexner, Smith, Avery and many Nobel laureates well, yet he considered Lewis a notch above; like Aronson, the prize-winning scientist who had worked at the Pasteur Institute and knew Lewis at Penn, Shope considered Lewis the smartest person he ever met.

Lewis had reached some tentative conclusions in Philadelphia about tuberculosis. He believed that three, and possibly four, inherited factors affected the natural ability of guinea pigs to produce antibodies—i.e., to resist infection. He had planned to unravel precisely what the nature of these factors was. This was an important question, one that potentially went far beyond tuberculosis to a deep understanding of the immune system.

But when he and Shope repeated the Philadelphia experiments they got different results. They examined every element of the experiments to see what might explain the differences and repeated them again. Then they repeated the process and the experiments again. Again they got differing results, results from which it was impossible to draw a conclusion.

Nothing in science is as damning as the inability of an outside experimenter to reproduce results. Now Lewis himself could not reproduce the results he had gotten in Philadelphia, results he had depended upon. Much less could he build upon and expand them. He had run into a wall.

He began plugging away at it. Shope too plugged away at it. Both of them had the tenacity to stay after a thing. But they made no progress.

More distressing to Smith and Flexner, who watched closely, was the way Lewis was approaching the problem. His failures seemed to confuse him. Unlike Avery, who broke his problems down into smaller ones that could be solved and who learned from each failure, Lewis seemed simply to be applying brute force, huge numbers of experiments. He sought to add other scientists with particular expertise to his team, but he did not define what precise role new people would play. Unlike Avery, who recruited people with specific skills to attack a specific question, Lewis seemed simply to want to throw resources at the problem, hoping someone would solve it.

He seemed desperate now. Desperate men can be dangerous, and even feared, but they are rarely respected. He was losing their respect, and with that would go everything.

As Lewis approached the end of his third year in Princeton, Smith confided his disappointment to Flexner: “He is perhaps aiming higher than his training and equipment warrant and this results in a demand to surround himself with technically trained chemists, etc. This is what Carrel”—Alexis Carrel at the Rockefeller Institute in New York, who had already received the Nobel Prize—“is doing but Carrel has another type of mind and gets results from his organization. A closely-knit group requires that the ideas come from the head man.”

Nor did Lewis seem to recognize as worth pursuing potentially promising side questions his experiments raised. His explanation for his failures, for example, was that the diet of the guinea pigs was different in Princeton than it had been in Philadelphia. This was potentially significant, and it was possible he was correct. The relationship between diet and disease had been noted before but chiefly in terms of outright diet deficiencies that directly caused such diseases as scurvy and pellagra. Lewis was thinking about far more subtle and indirect linkages between diet and disease, including infectious disease. But instead of pursuing this line of inquiry, Lewis continued to pound away at his old one. He did so without result. He reported to the Board of Scientific Directors, “I have planned no change in my line of work for the coming year.”

Flexner wanted to hear something different. Lewis was making himself a marked man, marked in no good way. It wasn’t Lewis’s failures that did so; it was the manner in which he was failing—dully, without imagination, and without the gain of knowledge elsewhere. Lewis had shown enough, or failed to show enough, that Flexner had already made one judgment. When Smith retired, Lewis would not replace him.

Flexner wrote him a chilling letter. In a draft Flexner was brutal: “There is no obligation expressed or implied in the Institute’s relation to you, or your relation to the Institute, beyond this service year period…. As the Iowa chair is still open and you are very much wanted to fill it, and the University of Iowa would make a supreme effort to secure you, I believe it due you to be minutely informed just what the position the Board of Scientific Directors has taken with reference to you…. There was doubt expressed about your future in general.”

Flexner did not send that letter. It was too harsh even for him. Instead he simply informed Lewis that the board was “unequivocally opposed to the appointment of one primarily a human pathologist”—which Lewis was—“to the directorship of the Department of Animal Pathology,” and that therefore he would not replace Smith. But he also warned Lewis that the board would not elevate him to the rank of a “member” of the institute, the equivalent of a tenured full professor. He would remain only an associate. His appointment expired in six months, in mid-1926, and the board would give him a three-year appointment into 1929. Perhaps he should accept the Iowa offer after all.

In Faust, Goethe wrote, “Too old am I to be content with play, / Too young to live untroubled by desire.”

Lewis was too old to play, too young to be untroubled by desire. Reading Flexner’s letter had to have been a crushing blow. He had expected to be told he would succeed Smith. He had been certain he would be elevated to the rank of “member” of the institute. From the laboratory, he drew his identity, and yet now the laboratory gave him not sustenance but cold rebuff. The two men he most admired in the world, two men he had thought of as scientific fathers—one of whom he regarded as almost a father—had judged that he lacked something, lacked a thing that would entitle him to join their brotherhood, to become a member.

By now Lewis’s family had moved to Princeton, but his marriage was no better. Perhaps the fault lay entirely within him, within what was now not so much a failing ambition as a failing love.

He declined the Iowa job once again. He had always been willing to gamble. Now he gambled on proving himself to Flexner and Smith.

For the next year and a half, he worked, at first feverishly but then…Something in him made him withdraw. His son Hobart, then fourteen years old, was having difficulties emotionally and difficulties in school, although a change of schools seemed to help. And Lewis had a car accident that broke his concentration.

He accomplished little. Again his failures were not like those that Avery would confront for nearly a decade. Avery was attacking the most fundamental questions of immunology and, ultimately, genetics. From each failed experiment he learned, perhaps not much but something. And what he was learning went beyond how to fine-tune an experiment. What he was learning from his failures had large ramifications that applied to entire fields of knowledge. One could argue that none of Avery’s experiments failed.

Lewis was simply foundering. He had spent hour after hour in the laboratory. It had always been his favorite place, his place of rest, of peace. It gave him no peace now. He began to avoid it. His marriage was no better; his wife and he barely communicated. But he found other things to do, gardening, carpentry, things he had never attended to before. Perhaps he hoped getting away would clear his mind, allow him to see through the fog of data. Perhaps he thought that. But his mind never seemed to go back to the problem.

In August 1927, he confessed to Flexner, “I feel I have not been very productive—certainly I feel that I have had a meager return for a lot of hard work—but some way everything I have touched in the hope it would go faster than the very slow jobs I have been on for so long has either been a wash-out or turned into some other big [problem].”

Then he said something even more striking. He was no longer going to the laboratory: “I am spending most of my time on an old house and garden I have gotten hold of.”

Flexner replied, for him, gently. Lewis was now more than a year into his three-year contract extension. Flexner warned that his tuberculosis work “has been under way as your major problem for four years. The outcome, even if continued many years longer, is uncertain and the yield of side issues, often the most fruitful of all, has been small. I do not believe in sticking to a rather barren subject. One of the requisites of an investigator is a kind of instinct which tells him quite as definitely when to drop, as well as when to take up a subject. Your time can be more promisingly employed along another major line.”

Lewis rejected the advice.

On September 30, 1918, J. S. Koen, a veterinarian with the federal Bureau of Animal Industry, had been attending the National Swine Breeders Show in Cedar Rapids. Many of the swine were ill, some of them deathly ill. Over the next several weeks he tracked the spread of the disease, the deaths of thousands of swine, and concluded they had influenza—the same disease killing humans. Farmers attacked his diagnosis; it could cost them money. Nonetheless, a few months later he published his conclusion in the Journal of Veterinary Medicine: “Last fall and winter we were confronted with a new condition, if not a new disease. I believe I have as much to support this diagnosis in pigs as the physicians have to support a similar diagnosis in man. The similarity of the epidemic among people and the epidemic among pigs was so close, the reports so frequent, that an outbreak in the family would be followed immediately by an outbreak among the hogs, and vice versa, as to present a most striking coincidence if not suggesting a close relation between the two conditions.”

The disease had continued to strike swine in the Midwest. In 1922 and 1923, veterinarians at the Bureau of Animal Industry transmitted the disease from pig to pig through mucus from the respiratory tract. They filtered the mucus and tried to transmit the disease with the filtrate. They failed.

Shope observed swine influenza during a trip home to Iowa. He began investigating it. Lewis helped him isolate a bacillus virtually identical to B. influenzae and named it B. influenzae suis. Shope also replicated the experiments by the veterinarians and began to move beyond them. He found this work potentially very interesting.

Lewis’s own work, however, continued to founder. Flexner and Smith had kept their assessments of it confidential. As far as the rest of the world—even including Shope—knew, they held him in the highest regard. In June 1928, for the fourth time, the University of Iowa made Lewis still another offer, an outstanding offer. Flexner urged him to accept. Lewis replied that his “compelling” interest remained at Princeton.

Flexner called Smith to discuss “our future Lewis problem.” They could not understand him. Lewis had produced nothing in five years. They in fact did have the highest regard for him—just no longer for his laboratory skills. Flexner still believed that Lewis had true gifts, broad and deep vision, an extraordinary ability to communicate and inspire. Flexner still believed that Lewis could become a dominant figure in medical teaching and research. Of that field, he could still be master.

Lewis had shown at least some of what Welch had. Perhaps he had much of it. And perhaps in the end he also lacked what Welch lacked, the creativity and organizational vision to actually run a major laboratory investigation.

Two days after Flexner and Smith talked, Flexner sat down with Lewis. He was blunt. But he assured Lewis the bluntness “was a conclusion placed before [you] in all kindness.” The prospect of Lewis’s becoming a member of the institute was a distant dream. His research had been “sterile” for the past five years. Unless it yielded something solid and important in the next year, he would not be reappointed even to a temporary position. He was approaching fifty years of age and Flexner told him, “The chances of [your] changing in the direction of more fertile ideas [are] small.” He also said Lewis had not acted with “energy and determination.” He had not fought. Then, most painfully, Flexner said he was “not essentially of the investigator type.”

Flexner urged him—indeed, all but ordered him—to take the Iowa position. It was an extraordinary offer: $10,000 a year salary—more than double the median income for physicians—and a free hand in organizing a department. Flexner assured him that he still believed he had great gifts. Great gifts. He could still make a huge contribution, a significant and important contribution. At Iowa he could become a major figure, inspire respect, and be far happier.

Lewis listened quietly and said little. He did not remonstrate or argue. He was almost passive, yet firm. There was a cold, unreachable center within him. Regarding Iowa, that was settled. He would reject the offer. He had no interest in anything but the laboratory. He hoped in the next year to justify reappointment.

After the conversation Flexner was frustrated, frustrated and angry. “I put all the pressure I could upon him but without avail,” he wrote Smith. “My notion is our obligations to Lewis are now fulfilled and that unless a great change takes place it will be our duty to act decisively next spring. He has been a real disappointment to me…. I left no doubt as to the risk he takes, and he left me no doubt that he understands and accepts that risk.”

A few months before Flexner’s brutal conversation with Lewis, Hideyo Noguchi had gone to Ghana to investigate yellow fever. Noguchi was as close to a pet as Flexner had. They had first met almost thirty years earlier, when Flexner was still at Penn and gave a speech in Tokyo. Uninvited, Noguchi had followed him to Philadelphia, knocked on his door, and announced he had come to work with him. Flexner found a position for him, then took him to the Rockefeller Institute. There Noguchi had developed an international reputation, but a controversial one.

He had done real science with Flexner, for example, identifying—and naming—neurotoxin in cobra venom. And he had claimed even more significant breakthroughs on his own, including the ability to grow polio and rabies viruses. (He could not have grown them with his techniques.) Rivers, also at Rockefeller and the first person to demonstrate that viruses were parasites on living cells, questioned those claims. Noguchi responded by telling him that a man who had done research for a long time had scars that he could never get rid of. Later Rivers discovered a significant unrelated mistake in his own work and confessed to Noguchi that he planned to retract his paper. Noguchi advised against it, saying it would take fifteen years for anyone else to find out he was wrong. Rivers was astounded, later saying, “I don’t think Noguchi was honest.”

Noguchi’s most important claim, however, was to have isolated the pathogen that caused yellow fever. It was a spirochete, he said, a spiral-shaped bacterium. Years before, Walter Reed had seemed to prove that a filterable virus caused the disease. Reed was long dead, but others attacked Noguchi’s findings. In response to one such attack, Noguchi wrote Flexner, “[H]is objections were very unreasonable…. I am not certain whether these Havana men are really interested in scientific discussion or not.”

Noguchi did not lack courage. And so he went to Ghana to prove himself correct.

In May 1928 he died there, of yellow fever.

Noguchi’s death came one month before Flexner and Lewis had their conversation. It attracted international attention, made the front pages of newspapers around the world, inspired glowing tributes in all the New York papers. For Noguchi, it was a Viking funeral, a blazing glory that obliterated all questions about the quality of his science.

The entire Rockefeller Institute reeled from the loss. Despite any scientific controversies, Noguchi had been buoyant, enthusiastic, always helpful, universally liked. Both Flexner and Lewis suffered in particular. Noguchi had been, literally, like a son to Flexner. Lewis had known him well, very well, going back to his first happy days in New York.

Noguchi’s death also left open the question of whether he had in fact isolated the pathogen that caused yellow fever. The institute wanted that question answered.

Shope volunteered to do it. He was young and believed himself invulnerable. He wanted action. He wanted to investigate yellow fever.

Flexner refused to allow him to go. Shope was also only twenty-eight years old, with a wife and an infant son. It was too dangerous.

Then Lewis volunteered. The scientific question remained, and it was a major one. Who was more qualified to investigate it than he? He had proven himself expert at cultivating bacteria and, even more important, he had proven that polio was a viral disease. Noguchi notwithstanding, it seemed a virus did cause yellow fever. And, important as the question was, it also had built-in limits; it was the kind of narrow and focused science that Flexner still had faith in Lewis to answer.

Lewis’s wife, Louise, objected. The laboratory had taken him away from her and their two children enough. She was already furious at him for once again declining the Iowa position. But this…this was something else.

Lewis had never listened to her. They had not had a real marriage for a long time. For him, this solved every problem. If he succeeded, he would restore himself in Flexner’s eyes. Five years before he had resigned from the Phipps Institute and simultaneously withdrawn his acceptance of the Iowa offer without any other prospects. All that he had done in order to do the one thing he loved, return to the laboratory. He was willing to gamble again. He was energized again. And he was more desperate than ever.

Instead of Ghana, however, he would go to Brazil. A particularly virulent strain of yellow fever had surfaced there.

In late November 1928, Flexner came to Princeton to see Lewis off. Flexner’s attitude toward him had already seemed to change. He was willing again to talk about the future. He also wanted, he said, to “learn about Shope’s Iowa work.” Shope had recently observed an extraordinarily violent influenza epizootic—an epidemic in animals—in swine. The overall mortality of the entire local pig population had reached 4 percent; in some herds mortality had exceeded 10 percent. That very much sounded like the influenza pandemic in humans a decade earlier.

A month later Lewis sailed for Brazil. On January 12, 1929, Frederick Russell, the colonel who had organized much of the army’s scientific work for Gorgas and who now worked for a Rockefeller-sponsored international health organization, received a cable saying Lewis had arrived and was well. The institute relayed the news to his wife, who had been so angry at Lewis’s departure that she had wanted nothing to do with the Rockefeller Institute and returned to Milwaukee, where both she and Lewis had grown up. Each week Russell was to receive news of Lewis and send it on to her.

Lewis located his laboratory in Belem, a port city on the Para River, seventy-two miles from the ocean but the main port of entry into the Amazon Basin. Europeans settled there in 1615, and a rubber boom in the nineteenth century had filled the city with Europeans while Indians went back and forth into the interior in dugout canoes. It was steamy, equatorial, and received as much precipitation as any area in the world.

On February 1, Lewis wrote Flexner, “Arrived here on Tuesday and went right to work…. [H]ave been setting up my own shop here, awaiting materials, having additional screening prepared, etc…. Should be started at something by early next week I hope.”

He seemed the old Lewis, energetic and confident. And each week Russell received a two-word wire: “Lewis well.” He received them through February, March, April, and May. But if Lewis was well, he sent no word about his research; he gave no sign that work was going well.

Then, on June 29, Russell sent a note hand-delivered by messenger to Flexner: “The following message from Rio de Janeiro, regarding Dr. Paul Lewis, was sent to me today, with the request that it be delivered to you. ‘Lewis’s illness began on June 25th. Doctors state it to be yellow fever. Condition of June 28th, temperature 103.8, pulse 80….’ The Foundation is sending the message to Dr. Theobald Smith and also to Mrs. Lewis at Milwaukee.”

Even as Russell sent that note to Flexner, Lewis was in agony. He had vomited violently, the nearly black vomit of the severe cases; the virus attacked the mucosa in his stomach, which bled, giving the vomit the dark color; it attacked the bone marrow, causing violent aching. An intense, searing headache gave him no rest, except perhaps when he was delirious. He had seizures. His colleagues packed him in ice and tried to keep him hydrated but there was little else they could do.

The next day another wire came: “Lewis condition critical. Anuria supervened Saturday.”

His kidneys were failing and he was producing no urine. All the toxins that the body normally rid itself of were now building up in his system. Later that same day, Russell received a second wire: “Lewis on fourth day of illness. Marked renal involvement.” He was becoming jaundiced, taking on the classic color that gave the disease its name. Symptom by symptom, step by step his body was failing.

June 30, 1929, was a Sunday. All day Lewis suffered, writhed in delirium. He went into a coma. It was his only relief. It was the fifth day of his illness. There would not be a sixth.

Shortly before midnight Dr. Paul A. Lewis found release.

An unsigned wire to Russell reported, “Typical yellow fever. Probably laboratory infection. Wire instructions regarding body.”

Shope walked down Maple Street on the edge of the Princeton campus to inform Lewis’s wife, who had come back from Milwaukee, and son Hobart, now a college student who had remained in Princeton.

Lewis’s widow gave simple and explicit instructions. She was returning immediately to Milwaukee and wanted the body shipped directly there, where those who cared about Paul were. She specifically stated that she wanted no memorial service held at the Rockefeller Institute, in either New York or Princeton.

There was none.

Shope accompanied the body to Wisconsin. The business manager of the Rockefeller Institute asked him, “I wonder if you could arrange when you arrive to order some flowers for the service for Dr. Lewis.”

The flowers came, with a card signed “the Board of Scientific Directors of the Rockefeller Institute.”

Lewis’s daughter, Janet, wrote the thank you note, addressing it “Dear Sirs.” Her mother could not bring herself to have any contact with the institute, particularly a thank you note. The institute paid Lewis’s salary to her through June 1930 and also paid his son Hobart’s college tuition. (Like his grandfather and aunt Marian, the first woman to graduate from Rush Medical College in Chicago, he became a physician—but a clinician, not a scientist.)

In the next report to the Board of Scientific Directors of the Rockefeller Institute—a board which now included Eugene Opie, whom Lewis had recruited as his successor at Phipps—Flexner noted that one scientist’s resignation “which is much regretted, left the study of light phenomena unprovided for.”

Lewis had originally suggested that work to Flexner. Flexner mentioned a “recrudescence of poliomyelitis.” Lewis had proved that a filterable virus caused that disease.

Flexner went through item after item concerning the institute. He pointed out “a pressing problem was the one in connection with the still unfinished work of Dr. Noguchi.” He made no mention of Paul A. Lewis, no mention of Dr. Lewis at all.

Later Flexner received Lewis’s autopsy report and news that researchers at the institute in New York had succeeded in transmitting Lewis’s virus—they called it “P.A.L.”—to monkeys and were continuing experiments with it. Flexner wrote in reply, “Thank you for sending me the report on the comparison of the Rivas and P.A.L. strains of yellow fever virus. At your convenience I should like to talk over the report with you. Dr. Cole thinks white paint and some other improvements desirable in your animal quarters. Has he spoken with you about them?”

Lewis had worked with deadly pathogens his entire adult life and had never infected himself. Since Noguchi’s death everyone working with yellow fever took special care.

In the five months Lewis worked in Brazil he did not report any details of his research and his laboratory notes provided almost no information about it. He died from a laboratory accident. Somehow he gave yellow fever to himself.

Shope later told his sons a rumor that Lewis, who smoked often, had somehow contaminated a cigarette with the virus and smoked it. The virus entered the bloodstream through a cut on his lip. David Lewis Anderson recalls that his father, Lewis’s friend in Philadelphia, also blamed cigarettes for Lewis’s death.

Three years earlier Sinclair Lewis, no relation, won the Pultizer Prize for his bestselling novel Arrowsmith, a novel about a young scientist at a fictionalized version of the Rockefeller Institute. Everyone in medical science, especially at the institute, knew that novel. In it the main character’s wife dies from smoking a cigarette contaminated by a deadly pathogen.

Flexner wrote an obituary of Lewis for Science in which he referred to “the important observations made by him in association with Sewall Wright on the hereditary factors in research in tuberculosis.” Lewis’s work with Wright had been carried out in Philadelphia; Flexner made no mention of anything Lewis had done in the five years since his return to the institute.

Meanwhile, Shope returned to Iowa to explore further this swine influenza, to observe still another epidemic among pigs.

In 1931, two years after Lewis’s death, Shope published three papers in a single issue of the Journal of Experimental Medicine. His work appeared in good company. In that same issue were articles by Avery, one of the series on the pneumococcus that would lead to his discovery of the transforming principle; by Thomas Rivers, the brilliant virologist; and by Karl Landsteiner, who had just won the Nobel Prize. All of these scientists were at the Rockefeller Institute.

Each of Shope’s articles was about influenza. He listed Lewis as the lead author on one. He had found the cause of influenza, at least in swine. It was a virus. We now know that the virus he found in swine descended directly from the 1918 virus, the virus that made all the world a killing zone. It is still unclear whether humans gave the virus to swine, or swine gave it to humans, although the former seems more likely.

By then the virus had mutated into mild form, or the swine’s immune systems had adjusted to it, or both, since the virus alone seemed to cause only mild disease. Shope did demonstrate that with B. influenzae as a secondary invader it could still be highly lethal. Later he would show that antibodies from human survivors of the 1918 pandemic protected pigs against this swine influenza.

Shope’s work was momentous and provocative. As soon as his articles appeared, a British scientist named C. H. Andrewes contacted him. Andrewes and several colleagues had been expending all their efforts on influenza, and they found Shope’s articles compelling. Andrewes and Shope became close friends; Shope even took him hunting and fishing where he had vacationed since he was six years old, at Woman Lake, Minnesota.

In England in 1933, during a minor outbreak of human influenza, Andrewes, Patrick Laidlaw, and Wilson Smith, largely following Shope’s methodology, filtered fresh human material and transmitted influenza to ferrets. They found the human pathogen. It was a filter-passing organism, a virus, like Shope’s swine influenza.

Had Lewis lived, he would have coauthored the papers with Shope, and even added breadth and experience to them. He would have helped produce another of the seminal papers in virology. His reputation would have been secure. Shope was not perfect. For all his later accomplishments in influenza and in other areas, some of his ideas, including some of those pertaining to influenza, were mistaken. Lewis, if energized and once again painstaking, might have prevented those errors. But no matter.

Shope was soon made a member of Rockefeller Institute. Lewis would likely have also been made a member. He would have been invited into the inner sanctum. He would have had all that he wanted. He would have belonged to the community of those who do science. One could consider Lewis, in a way most personal to him, the last victim of the 1918 pandemic.