Die Once Live Twice (34 page)

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

“F
reddie 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-Petersen 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.”

Jonathan told them the story of the harrowing journey bringing penicillin to the United States and finally to Peoria, Illinois. Helene was enraptured by the story, and hoping that Frederick would be equally impressed. “Have they tested this drug in patients?”

Jonathan knocked the ash off his cigar into an ashtray. “Oh, yes. After some modifications about impurities and the like, they’ve proven that it’s clinically effective and they’re moving along toward wider distribution.”

With the help of government scientists, production was increased two hundred and fifty times above what Heatley could do in his laboratory by changing the growth medium. Corn-steep liquor and lactose, instead of yeast, were effective as the medium for growing the mold. A second improvement came when phenylacetic acid was added to the mixture. This converted the penicillin to a stronger drug they named penicillin G.

“Here’s another good story for you Helene. The scientists wanted a more powerful mold because they could get better yield of mold juice and further increase volume. They investigated molds in laboratories across the country and in agricultural test stations. One of the scientists in Peoria even sent his secretary to the market every day to examine the fruit. She returned one day with a rotten cantaloupe melon from which they cultured the most powerful penicillium mold yet found—
penicillium chrysogenum
. Once again, this story might not have a successful ending without the help of a woman!” Jonathan tipped his glass toward Helene.

Despite himself, Frederick was curious now. “So, Jonathan, where are we now with penicillin? They have solved the production? Patients are being cured?”

Jonathan looked at the fingernails on his right hand. “No. Production is still by the tray method so volume is too low for a large clinical trial. Merck Pharmaceutical Company is producing some for clinical testing, but only individual patients are being treated. The method to increase production to high volumes would be deep fermentation in very large vats, but the laboratory in Peoria cannot determine the right combination of factors to make this work.” He raised his head and his eyes met Frederick’s. “But I still believe you should wait. This drug will prove itself. Of that I am as confident as you were of the hip nail.”

Jonathan inhaled deeply from his cigar. “In March, the first patient was saved. She was a doctor’s wife at Yale near death with septicemia. Her original infection was puerperal fever and sulfa had no effect. The bacteria in her blood stream infected every organ.” Jonathan’s head bowed. “The same infection process that killed Marion.” He was silent for a moment, then continued. “Most likely the New Haven woman had both staphylococci and streptococci growing inside her. She received Merck’s penicillin by intravenous drip and quickly recovered. Since March there have been only ten more patients treated—but they were all successful treatments.” He paused, but Frederick only nodded absently. “However, the good news is that other companies are now making penicillin. Pfizer is one and I have been talking with Jasper Kane there.”

The two men smoked their cigars in silence for a while. Helene refilled their glasses with scotch. “Damn shame about that yellow fever vaccine. It killed some men,” Frederick mused.

“Yes. But I don’t think you have to worry about contamination happening with penicillin.”

“Jonathan, I think I’m more worried about Sebastian’s safety in the Pacific than I am about me getting infected. I have a strong immune system.”

“But Frederick, you know that patients get infected no matter how strong they are,” Helene pointed out.

“Helene! I have a strong constitution. Very strong.”

“Yes, Frederick. I know you do,” Jonathan quickly interjected, seeing that it was no use. “Helene, I am sure he will be fine. Here’s to a most successful hip operation.” Jonathan reached over and clinked glasses with Frederick and tipped his glass one more time to Helene. “I think it’s time to eat. Helene, I don’t care what else we have as long as we have strawberry-rhubarb pie for dessert!”

Chapter Thirty-five

I
n 1942, when he operated Frederick Specht, Marius Smith-Petersen was fifty-six years old and a highly energetic orthopedic surgeon obsessed with medicine. He had no hobbies. He was handsome, not a big man, with white hair parted high on the left. His eyes were deeply set behind a prominent nose and thin lips.

In 1918 he had an idea for a new kind of arthroplasty, or joint repair, that would help those suffering from arthritis of the hip, in which the surface cartilage of the ball-and-socket joint of the hip wears out. Smith-Petersen’s idea was to put a new surface on the ball that would relieve the pain and allow the hip bones to fit together better. As the hip moved, this new surface would mold itself to the bones, so he named the procedure “mold arthroplasty.” It was, in fact, the first hip replacement. By 1925 he had made a glass cap to fit over the ball of the hip, but when he implanted it in patients, the glass broke. By 1939 he was using metal instead of glass and by 1942 the operation was an established success.

Frederick went into surgery during the first week of September. Smith-Petersen made an incision over the front of the hip, exposed Frederick’s arthritis and cut away the osteophytes, bony outgrowths, from the edges of the hip with an osteotome. With the ball dislocated out of the socket he used a reverse reamer to smooth off the femoral head so that he could place the metal cap over the prepared bone. When the metal cap was in place, Smith-Petersen reduced the femoral head back into the acetabulum, the socket of the hip joint, and moved the hip all around to insure freedom of movement. He then sutured the capsule, or envelope around the hip, and finally the fat and skin. When he finished in mid-morning, he was able to stride to the waiting room to assure Helene that the operation had gone perfectly.

Later that afternoon Jackson Sullivan, now an internal medicine resident, came by to see his patient. Jackson had grown into the image of his father. Only an inch shorter than Jonathan, Jackson possessed the same chiseled jaw, angular nose, and thick dark hair on a footballer’s frame. He had played single-wing blocking back and linebacker for Harvard with the same success as his father. He graduated summa cum laude and finished second in his medical class, also at Harvard. If he mirrored his father on the outside, he had taken after Marion on the inside. Assured and thoughtful, Jackson had grown into a masterful mix of his two parents.