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
THE GRAIL
In 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.
Frederick was awake and his leg suspended in the device it would occupy for one month. “Doctor Specht, I brought you something.” Jackson brought out a wrapped box. “Open it.”
“Well, will you look at this.” Frederick beamed and held up a new Arvin radio.
“I knew you’d want to hear some good classical music and, let’s face it, lying in bed for a month is just plain boring,” Jackson said. “Suspense Theater will also help the hours pass quicker.”
“That’s very thoughtful of you. It’s just the perfect thing.” For a moment Frederick forgot what he had just been through.
On the third day after the operation, Frederick’s temperature rose significantly and he began to cough, spitting up mucous as he did. Worried, Jackson brought out his stethoscope and heard what he’d feared – the crackling sounds of fluid in the lungs. A chest x-ray confirmed that it was pneumonia. Death’s Captain. Jackson began intravenous sulfa and the vigil against a fatal disease began once again.
Frederick’s fever spiked to 104 degrees and he babbled in confusion, unsure of where he was or who was around him. Helene watched anxiously for some sign of improvement in her husband for the next two days, only to be disappointed. “Jackson, is there anything more we can do?” she asked with anguish in her voice. “If he continues like this...” Her voice trailed off and they looked at each other sadly. They both knew that Frederick Specht was fighting for his life. Jackson was at his wit’s end. Helene begged frantically, “We must do something for him. Jackson, what about your father? He told us about a new drug for infection.”
“Well, the sulfa sure isn’t working.” Then Jackson remembered something his
dad had told him the last time they were together. “Okay, okay, I’ll call. I’ll call right now.”
Jackson would not reach Jonathan right away. Jonathan was in the “Dinosaur’s Office,” as he and his colleagues called Simon Flexner’s office. Flexner had stepped down as Chairman of Rockefeller Institute and been succeeded by Doctor Tom Rivers, but he hung on by keeping this office. As a fellow dinosaur, Jonathan would visit Simon whenever he was at the Institute. Their conversation this day was interrupted by a knock on the door. When Flexner hollered, “Come in,” the door opened and in walked Doctor Albert Sabin.
Sabin was a young, ambitious virologist with an interest in the poliomyelitis virus. Jonathan had an affinity for Sabin because both were protégés of William Park, who had then transferred to Rockefeller Institute. Sabin worked for Flexner, and one of their research projects involved spraying zinc sulphate into children’s noses, following Flexner’s theory that the polio virus traveled to their brain via their olfactory nerves. All this accomplished was to ruin the children’s sense of smell. Sabin began to conduct his own studies, as had Jonathan, to prove Flexner’s thesis wrong. Sabin was brilliant but had an irascible personality and offended several at Rockefeller Institute, including Tom Rivers. Sabin had left Rockefeller Institute to head his own laboratory at Children’s Hospital in Cincinnati.
Sabin shook hands with Jonathan and Flexner, and Jonathan asked, “How is Cincinnati?”
“It is not Rockefeller Institute,” Sabin responded. “I would like to come back here.”
“You’re not welcome back here,” Flexner barked. There was tense silence in the room.
“Why won’t you and Tom consider this?”
“Because you’re a son of a bitch.”
“Not because I proved that you wasted forty years of your life because of your stubborn fixation on the poliomyelitis virus entering the body through the nose?”
“You haven’t proved me wrong!”
“Yes I have. I’ve done autopsies on infantile paralysis victims and cultured the virus from their stomachs. It enters by the mouth and travels by blood to the spinal cord!” Sabin’s mouth was contorted and his eyes fixed on Flexner, who would not look at him.
“Jonathan, get this nobody out of my office,” Flexner ordered.
“Come on, Albert,” Jonathan said as he grabbed Sabin by the elbow and ushered him toward the door. In the hallway he said, “Albert, you need to learn to hold your tongue.”
“I suppose, Jonathan. But after all I did for him....”
“Congratulations on your findings. I tried to prove that, too, without success.”
“Yes. You and I discussed the possibilities several times. I know it was your wife’s hypothesis many years ago. Didn’t she have a confrontation about it with Flexner?”
“A small one, yes, at one of our Christmas parties. She told him it was the clean water that got rid of the virus so mothers did not form antibodies to pass to babies in their milk. The timing is right. The first epidemics, though small, were in the 1890s. Clean water in the cities was in place by then.”
“She was right. Infantile paralysis epidemics began only after the water was cleansed to rid it of typhoid and cholera.” Sabin was certain that filth, poverty, and slums did not promote polio. Victims were more often middle-class or wealthy.
“Too bad she cannot hear this.” Jonathan’s eyes looked into the distance.
“I felt smug with being right and Flexner wrong,” Sabin said. “Even though Marion has passed, I thought this too was Marion’s moment.”
“Thank you, Albert.” They shook hands and Jonathan turned to walk to his office.
When Jonathan reached his office, he sat for a while in solitude, looking at the picture of Marion on his desk. Jonathan too felt smug for Marion. She would have wagged her index finger and exclaimed she had told me so. The smile on her face would have melted a glacier. Then he noticed there was a note on his desk to call Jackson. As his son explained Frederick’s frightening dilemma over the phone, Jonathan shifted uncomfortably in his worn leather desk chair. Jackson was doing his best to sound matter-of-fact, but the edginess in his voice signaled anxiety bordering on panic. “I remember you telling me about that Yale professor’s wife who was nearly dead from septicemia. She got penicillin and survived. Do you think you could get some for Frederick?”
“I don’t know. There is a limited supply because production is slow. They have treated very few patients.”
“You realize he’s going to die.”
Here we go again, Jonathan thought. He sighed. “I’ll call Perrin Long and get back to you. You know, I told Frederick to wait to do this surgery until penicillin was proven and available. Now he becomes one of the test subjects. We will learn its curative powers first-hand.”
Perrin Long was the chairman of the committee at the National Research Council, which had to approve any clinical use of penicillin until production increased. Only enough for a few dozen cases had been produced. “Perrin, there is a doctor in Mass General Hospital with end-stage pneumonia. Sulfa has not worked. Is there any penicillin available? Can we include him in the clinical test?”
“Jonathan, Merck is producing a new batch as we speak. The surface tray method of production is time-consuming. But there is one chance. Pfizer has begun production. Do you know someone there you could call to see if they have any on hand? If they do, you can use it.”
“I know Jasper Kane, in charge of production at the Brooklyn plant. We’ve discussed this before. I’ll call him.”
A few hours later, Jonathan reached Jasper Kane and recounted the situation one more time. Jasper believed he could supply some drug, but would need permission. He would return Jonathan’s call.
Jasper drummed his fingers nervously, took a deep breath and picked up the phone. “Hello, it’s Jasper. May I speak to John? Yes, I’ll wait.” More drumming. He picked up a pencil and threw it down. “John. Thanks for taking my call. I know you’re busy. Well, I got a call from Jonathan Sullivan a few minutes ago.” He listened while John McKeen, the president of Pfizer, asked a question. “Sullivan, right. And he knows of a very important surgeon who is dying of pneumonia after an operation.” Jasper listened to McKeen. “Right. You know, we’ve talked to him a lot about penicillin, asked for advice....” “Yes, a surgeon. One of the country’s best, especially for orthopedic trauma. TB too, but...” “Very close friend, yes.” “I’m sure he would.” “Well, right away. He wants to pick up the doses tomorrow.” “Well, the guy’s dying.” “Okay, thanks John.”
When Jonathan and Jasper met the next morning at the Pfizer plant in Brooklyn, Jonathan brought a thermos of coffee and poured Jasper a cup. “I would have brought Glenfiddich, but it seemed a little early.”
“That’s quite all right. The doctor says it’s bad for me anyway.”
“Oh, they’re always saying things like that.” Jonathan looked at the production floor outside Jasper’s office. “How are you going to get production of penicillin to the levels we need, for here and for the war, Jasper?”
“The secret, Jonathan, is a process called deep fermentation. With that we can grow much more mold and produce high volumes of mold juice because we can use tanks as big as two thousand gallons. We have a head start here at Pfizer because I learned how to nurture mold in fermentation tanks making fumaric acid, which is used in the food industry as an acidifying agent. It is a chemical from a mold, just like penicillin is. We’ve already solved the stirring in sterile air using neutral pH for acidity and we can control the temperature.”
“Jasper, it was a lot more fun imagining the penicillin girls turning urns full of mold juice. A two-thousand-gallon tank is boring! But why aren’t you in production full time?”
“McKeen just isn’t convinced yet that the clinical proof is there or that it has commercial value.”
“Humph. Well, we’ll know soon enough. Remind me to send John a thank-you for these doses.”
“Or a bottle of Glenfiddich.
Anyway, we know how to produce volume now. Pfizer just has to make a decision how much of their resources they are going to devote to it.”
“If this drug works, Jasper, it will help us win the war. We could save so many troops. But I know everyone needs more proof. I’m still a little skeptical myself. If it saves Frederick though—well, that would be a miracle. He is a dead man by all medical standards.”
“We think the clinical evidence will be there, or not, by the end of this year,” Jasper said. “If it is, we have to make a decision whether to build facilities to produce penicillin.”
“My guess is you will. I should go to catch my plane. My sincere thanks for this. I won’t forget it.”
“Off with you now. Take your penicillin and save Doctor Specht. You have enough for ten days.”
“Thank you so much Jasper. Good luck with your project.”
Jonathan sped off to LaGuardia Airport and boarded Jimmy’s plane for the hour-long trip to Boston. A car and driver waited at the private airport in Boston and sped Jonathan to Mass General.
Outside Frederick’s door, Jonathan saw Helene leaning heavily against the wall. “How’s your husband this morning, Helene?” Jonathan asked as he walked up to a surprised Helene.
“Oh, Jonathan, getting worse I’m afraid,” she struggled to say. “The nurse is in the room with him now.”
Jonathan wrapped his long arm around Helene’s slumping shoulders and together they walked to the bedside. Frederick’s hair was drenched with sweat. Helene looked devastated. “He is sleeping now, but when he’s awake he hallucinates.”
A basin was at his side to collect the bloody mucous he coughed up. “Bloody pus,” Jonathan said out loud, to no one but himself. “How many times have I seen it? Everyone who died with the Great Flu, with consumption, pneumonia. My Marion. Phil was right—bloody pus is the Devil’s blood. I pray to God that I have His answer to the Devil in my hands.”
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