Jonathan hitched a ride home with a United States Army transport plane out of London. He left England exhilarated over the success of bacterial antagonism and anticipating the upcoming tests on other bacteria. Ultimately, the relevance of penicillin would be learned from the test on patients. He worried about his new friend Ernest Chain if Germany conquered England. He knew about Kristallnacht in 1938 and the rumors about Hitler’s plan to exterminate Jews. He also worried about penicillin falling into German hands instead of being an allied “weapon.”
Nonetheless, Jonathan was excited to be going home. It would be good to see Jackson, who had decided to study internal medicine at Harvard in an accelerated program necessitated by the prospect of the United States going to war. What a story he had to tell his colleagues at Rockefeller Institute. He must remember to thank Warren Weaver!
Chapter Thirty-three
FLY TO GLORY
Jonathan fumbled for his seatbelt in the dark, hearing the sounds of two other belts being buckled. As he clasped his belt together the propellers went to life and the plane began to taxi. He gripped the armrests of his seat tightly and glanced to his right, but could see nothing in the pitch dark. It was his first time flying in a plane at night with no lights allowed. The windows were even painted black. He decided he never would do it again. The daytime landing in London was a treat compared to this exit flight.
He had returned to England in a military transport plane a week ago, sixteen days after D-Day. In Oxford, Florey’s entire laboratory had greeted him as part of the team, since he had suffered with them through the validation stage of the penicillin mold juice. In his office, Florey summarized the clinical trials for Jonathan. “The first patient was terminally infected and the penicillin infusion actually worsened her.” She suffered convulsions and rigor with fever and chills. They decided that pyrogen impurities were the cause of the problem, so they ran penicillin liquid made from the brown powder through chromatography. “When the mixture passed through the long glass tube filled with absorbent alumina powder, it was like a chemical rainbow as the impurities separated out at the upper levels. Finally the cleansed penicillin powder appeared at the bottom and lo and behold—penicillin was now a yellow powder!”
The purified yellow penicillin liquid was injected into each of the Oxford lab team and their excitement was subdued all afternoon as each person waited for someone to convulse. Florey took each person’s temperature and Chain tried to lighten the mood by telling jokes about dying. One very tense team member silenced him with “Enough of your gallows humor.”
“Was there a Jesse Lazear, Howard?”
“No, Jonathan. By evening we were all in that euphoric mood of dodging a bullet. I broke out champagne for everyone.”
In mid-February they treated a policeman dying from infection by both streptococcal and staphylococcal bacteria. Within twenty-four hours he was miraculously improved but they ran out of penicillin. Chain collected the patient’s urine and filtered the penicillin from it to continue to treat him, but after five days they ran out completely. The policeman remained improved for ten more days, but his infection relapsed and he died. Florey concluded the time for infusion had to be prolonged to at least a week, better if ten days.
With so little penicillin and so much needed for each patient, they began to treat children. Because they weighed so much less, they needed much less drug per dose. This brilliant idea allowed them to cure six straight pediatric patients. Florey knew now this penicillin was an antibiotic and ready for the big test—clinically treating a large number of patients to convince all skeptics. But in order to do that they would need a large volume.
“There are only two or three companies in Britain that consider themselves pharmaceutical companies,” Howard said to Jonathan. “I went to each of them and although they believed our research results, they professed that with the war raging on our doorstep they had neither the money nor the personnel to devote to production. That is when I contacted you, Jonathan, to help me bring penicillin to the United States for production.”
Jonathan had received a wire from Florey in late May with a request for help. He immediately contacted his nephew Jimmy, who was commissioned as a civilian pilot in the Air Force. Jimmy had flown missions in unmarked planes over war zones in Europe—even over Germany—to spy on German positions and troop strength. His friend, Jimmy Doolittle, who would fly a secret bombing raid over Tokyo a year later, enlisted Jimmy because he was one of the first, and now most accomplished, pilots in the United States.
That was why, at the end of June, the two Jimmys were flying Jonathan, Florey, and Danny Heatley out of England in a blacked-out plane in the black night. “The Germans fly air raids every night,” Jimmy Sullivan explained to his uncle, “and we will be shot down if they see us.”
“How are you going to fly?”
“Once we’re in the air we’ll use a compass. Major Doolittle pioneered that. There aren’t any lighted structures on the ground to follow either. We’ll head to the sea and fly over water to Portugal. We will have daylight to land in Lisbon.”
Jonathan felt the plane lift off and then the wheels were stored with a thud. No one spoke for several minutes as the plane banked toward the sea. As it leveled somewhat, Jonathan said to Howard, “Are you scared?”
“Yes.”
“Be confident. We have the best pilots we could have. Couldn’t choose two better.”
“Oh, Jonathan, I’m not so afraid of the plane going down. I’m afraid the penicillin I have with me will deactivate during the trip. It will be at least two weeks before I get the spores into fresh medium and it is hot in July, especially in the United States.”
“Well, that fear I understand. How are the specimens kept now?”
“They are freeze-dried. But I haven’t ever taken freeze-dried organisms in the rarefied air of a plane, or traveled two weeks with them or subjected them to the heat of the United States.”
Jonathan nodded his head, forgetting Howard couldn’t see him. “As soon as we reach the United States, I will find out where the government wants to perform the research necessary to increase production.”
In the inky blackness of the cabin, Jonathan felt disconnected from the world—like he was in a tomb, which he hoped he wasn’t. His only consolation was the excitement of being part of penicillin’s success. Of realizing his life’s dream. Any discomfort was worth that.
The darkness promoted sleep and all three of the passengers dozed. “If this penicillin cures infection it will win the war,” Doolittle declared. “Wars are won by manpower and if the Allies can get their troops back into battle after injuries, rather than into the hospital with infection, they will win. In every previous war there have been more men lost to infectious disease than to battle injuries.”
“I just want to be sure that the Krauts don’t get this secret,” Jimmy answered.
Jonathan wasn’t sure how long they flew, but with the rising sun throwing sunlight into the cabin through the cockpit windows, he knew they were near Lisbon. He felt the thump of the landing gear and then the wheels were bouncing on the runway in Lisbon.
It was three days before they received clearance to leave Portugal and Florey paced the hotel halls the whole time, checking the glass tubes with the penicillin every day. The visible viability of the spores gave him a little relief each time. Their flight plan to the United States took them first to the Azores, then to Bermuda, and then finally to New York City, and each stop made Florey more nervous.
It was July third when the plane landed on United States soil. As Florey disembarked, he turned to Heatley, “Oh great! Hot as Hades!” They stood baking on a blacktop tarmac to say thank you and goodbye to Doolittle and then climbed into a car for the ride to Jonathan’s Park Avenue apartment. The Fifth Avenue mansion had been sold after Marion’s death. Though Florey and Chain were eager to get to work, Jonathan said, “Tomorrow is a national holiday and we won’t accomplish anything, Howard. I’ll make the necessar
y phone calls to determine where we go for the research work to increase production.”
The next morning Jonathan phoned Ross Harrison, the director of the National Research Council—the same Ross Harrison whom he had visited at Yale to learn how to use tissue cultures. “I suppose you’re calling to rub in the Harvard-Yale football score last fall,” Harrison said.
“You guys were easy, 28 to 0. In fact, my Harvard team has won three of the last four games. Maybe Yale should give up football!”
“We’ll see. What do you need?”
Jonathan’s short version of the penicillin story roused Harrison’s enthusiasm, and he agreed to arrange a meeting for Florey with Charles Thom, a mycologist. In fact, Harrison was certain Thom had already done some work with the penicillin mold.
That evening, Jonathan, Jimmy and Sarah took Florey and Heatley for a picnic in Central Park so that they could enjoy the fireworks illuminating the sky over the park. “We’re celebrating our independence from you Brits,” Jonathan explained. “Ironic, isn’t it, that you’re here to bring us independence from an enemy mightier than the British Army was under Lord Cornwallis!”
Sarah popped a champagne cork behind Danny Heatley and he jumped five feet in the air. “Damn, I thought one of those fireworks just blew up next to me!” Everyone howled at his discomfiture as Sarah poured them bubbly joy.
As Jonathan touched glasses with Jimmy he said, “Thank you, Jimmy. That was a flight for history. A flight for glory in man’s battle against infection. I thank you for all Mankind.”
“If we can produce penicillin in volume...” Florey trailed off, needing to say no more.
Jimmy flew Jonathan, Florey and Heatley to Washington, D.C. to meet Thom on July 9. Thom had confirmed the identity of the mold as penicillin notatum ten years earlier, so he was enthusiastic about Florey’s work. He walked the visitors to the Department of Agriculture to see Doctor Percy Wells, who had made the decision to develop penicillin production at the Department of Agriculture’s facility in Peoria, Illinois, where a new fermentation lab, which was necessary for the production of penicillin, had just been built.
Jimmy’s plane touched down in Peoria on July 14, sixteen days after leaving Oxford, and Florey and Heatley were greeted by Doctor Andrew Moyer, who had been assigned to the project. They waited nervously to learn if the test tube specimens would grow, but the penicillin spores were stubborn. Heatley was sure the July heat in the United States had killed them. Worse, Peoria had no yeast to add to the medium to promote growth. Illinois had lots of corn, though, so Moyer suggested corn-steep liquor be added to the medium to provide the nutrition the mold organisms needed. The penicillin flourished, growing more productively than with yeast as the medium. Heatley was impressed.
“By God, we’ve got a mold that is an alcoholic! Perfect!”
Now the work could begin to produce penicillin as an antibiotic in enough volume to make it available to the Allied armies.
Chapter Thirty-four
PENICILLIN’S PROMISE
“Freddie Wilson’s plane had the Japanese aircraft carrier Kaga in sight, but he had to clean his own vomit off his windshield before he could zero in. One, two, three, and then four bombs exploded, right on their target and cheers erupted from everyone. ‘The Japs will never know the Kaga was destroyed by yellow men,’ Freddy hollered out, even though he almost passed out. He felt sick as a dog.”
Jonathan was telling this story as he sat in the living room of the Specht home in July, 1942. He was traveling back to New York after surveying hospitals in California for two weeks about the number of soldiers sick from the yellow fever vaccine made at Rockefeller Institute. “I interviewed that young man in a hospital in California. His jaundice relapsed and he nearly died. He told me ten to twenty percent of the airmen in the Battle of Midway were jaundiced and sick.”
Frederick began cleaning his spectacles with his handkerchief, as he often did when he was excited. “Just before Sebastian left for New Zealand with General Vandergrift, the end of May, he wrote me that his hospital in California was filled with jaundiced troops.” He turned slightly to put his handkerchief away and grimaced in pain. “Ach! Damn this hip!”
“Tsk, the language,” Helene said reprovingly.
“Humph. It hurts like hell. I think my language should fit the situation.” He turned back to Jonathan. “Anyway. All those troops my son saw were inoculated with the yellow fever vaccine from Rockefeller Institute. What happened?”
“James Simmons, the doctor in charge of military medicine, is paranoid about the yellow fever virus being used as a bioterrorism weapon. So every soldier gets vaccinated. And a lot of that vaccine comes from Rockefeller.” Jonathan explained that people at Rockefeller had been afraid that their yellow fever vaccine was at risk of destabilizing into a live virus, so it was buffered with human serum as a precaution. Johns Hopkins provided the serum. “There had to be something in that serum. The donors of the serum were later determined to have hepatitis, and that may be the cause, but we don’t know how to test for it.”
Some of the scientists at Rockefeller Institute were upset with Wilbur Sawyer, who led the yellow fever vaccine team. The Institute had been informed in 1940 that jaundice was occurring with their vaccine in patients in Brazil. The chief doctor there, a man from Rockefeller Institute, had eradicated the jaundice by using egg white to buffer the vaccine. “However, Sawyer did not change his procedure and the Institute’s vaccine caused this epidemic in the military. There were so many men disabled by yellow fever it changed the Allies’ war plans for months.”
“That’s a terrible misfortune,” Helene said. “Did the Army stop the vaccine?”
“We sure as hell stopped the Institute’s vaccine. It’s ironic. The vaccine is now being stabilized by the freeze-drying method in a public health laboratory in Montana. Same method that solved the penicillin problem.”
“Yes, you mentioned that.” Frederick held his glasses up to the light, nodded, and then put them back on. “Nature gives no margin of error. We struggle to find her secrets and when we find one that we searched for she gets mad. The leading research institute in the world and the flagship medical school for excellence in medicine combine to create a medical disaster because there is something in human serum that infects the liver and we never knew about it. At least doctors will always have work!” Frederick was not smiling.
“This is the third disaster with vaccines in the last six years,” Jonathan said, looking equally grave. “Two with polio vaccines and now this one with yellow fever. It emphasizes the meticulous care required in all we do. We affect lives. The consequences are so different from, say, a car dealer who sells you a lemon that you can just return.” Jonathan was secretly praying that nothing like this error happened with the current development of penicillin. It would be inexcusable to allow a human error to derail the most promising laboratory discovery in his lifetime. “Anyway, are Sebastian’s marines healthy?”
“Yes. They were in New Zealand, but they are at sea again. He only knows they are going to the South Pacific.” Sebastian was a doctor for the 1st Marine Division commanded by Major General Alexander Vandergrift, which was, unbeknownst to them, headed for Guadalcanal.
“May the hand of God be on him as he doctors his marines in the coming battles,” Jonathan quietly prayed out loud. After a moment of silence, he asked Frederick, “When is your hip operation?”
“In a month or so.” The arthritis in Frederick’s hip had become too much for him to bear, and he was traveling to Boston for the new hip replacement operation developed by Doctor Marius Smith-Petersen. Arthritis destroyed the cartilage that lined the hip joint, so the bones of the joint rubbed together painfully. Pete, as Frederick called him, had designed an operation that separated the raw bone surfaces by putting a metal cap over the ball of the hip joint. This operation would relieve Frederick’s pain and allow him to walk better.
“Why don’t you wait, Frederick?” Jonathan pleaded. “Smith-Pete
rsen is the best hip surgeon in this country, so the only complication you could have is a wound infection or pneumonia. Penicillin would save you from that. I am confident there is a new antibiotic that will protect you from dying. We need a few more months to do human testing and to develop a production process that can create high volumes of the drug.”
“Jonathan, you’ve been excited before. Sulfa didn’t save Marion when she had a postoperative infection. I’m tired of having to sit around all the time and I hate it.”
“Jonathan, perhaps you can explain to me why this time is different,” Helene said, looking at her husband.
Jonathan settled back into the overstuffed chair he was sitting in. Frederick broke out cigars for them while Helene fixed each of them a scotch and water. Jonathan inhaled deeply as the exciting memories of his days with Florey and Chain in Oxford rushed forth. He brightened like a light bulb as he described Chain’s victory over penicillin’s instability, then Florey’s experiment with mice proving its lethal antibiosis without toxicity and the latest work that showed penicillin worked against multiple bacteria, especially those most feared—streptococci, staphylococci, pneumococci, and clostridia which caused gas gangrene.
“They had to learn how to produce penicillin in some volume so they could do tests, and then treat patients to prove it works in humans. They have a man named Danny Heatley who is in charge of that. Frederick, you’ll appreciate his ingenuity.” Jonathan took a long swallow of scotch and then continued. “Heatley found yeast increased the yield when the mold was grown with it. Chain also enhanced production by mixing the mold juice first with ether and then with the chemical amyl acetate to separate out the penicillin. But to make this mixture work the temperature needed to be zero degrees centigrade and the liquid in constant motion. So Heatley hired girls to continually roll the liquid mixture inside glass bottles inside a refrigerated room. These ‘penicillin girls’ wore mufflers, overcoats, boots, gloves, and woolen helmets. Heroes. These girls were just heroes to do this work so penicillin could be produced.”
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