"Corydon? Where in hell is that?"
"Indianapolis. They specialize in the biological sciences. I think they were established during the Kennedy Administration, or soon after, about the time when the potential of genetics began to be appreciated."
"After the DNA code was broken?"
He nodded. "Churchward joined them from Yale about 1981,1 believe. If you had to pick out a future Nobel laureate, he'd be the obvious choice."
"And you think he would be useful to us?"
"He already is. We have strong links with Corydon, thanks to your father. We're funding a good proportion of the research that goes on there."
"In genetic engineering, you mean?" David's voice was pitched on a note of unease.
"You don't have to sound so dubious," Leapman gently chided him. "Genetically engineered drugs are the future of our industry. The great advances in medical health from now on are going to be made by geneticists. They already provided us with safer and better insulin for diabetics. In the next twenty years, they're going to produce vaccines for every disease you care to name." He paused and took more beer. "But as it happens, the latest breakthrough owes nothing at all to biotechnology."
"A breakthrough? You really mean that?"
Leapman actually summoned up a smile. "From old- fashioned chemical compounds, David."
"A drug?"
He nodded.
"What for—which disease?"
"The most prevalent killer of all."
"Cancer?"
"Old age, David. Old age."
CHAPTER FOURTEEN
Manny Flexner's funeral service took place in the ante-chapel of the Temple Emanu-El on Fifth Avenue, the world's largest synagogue. The attendance of over two hundred and fifty was a measure of his popularity; Jews, gentiles, a broad cross section of New York society. "He was a much loved man," the rabbi said in his address, admittedly something of a cliche in funeral orations, but in this case it was true on several counts, most obviously the high count of attractive women in the congregation.
Later the same afternoon, while most of the family were still crowded into the house on the Upper East Side eating sandwiches and trading stories about Manny's escapades in love and business, an Emergency Board Meeting was held at the Manflex headquarters. David Flexner was proposed as the new Chairman and elected unopposed. Michael Leapman, his proposer, made it clear that this had been Manny's wish. The seven executive and two nonexecutive members applauded politely and a bottle of champagne was opened. The price of Manflex stock, which had been falling all week, picked up a few points by the close of trading.
"Better news, then," David remarked, then Leapman told him.
"Sorry, but it isn't The price rose on a rumor that someone is buying shares in significant numbers. The market senses a takeover bid."
"So soon?"
"Sharks are fast movers. We've taken a hard knock and they smell blood."
Vehemently, by his easygoing standard, David said, "They can go to hell, Michael. No asset stripper is going to tear Manflex apart. It was my father's life. Thousands of other lives are staked on it. I have a responsibility to the workforce."
Leapman rested a hand on his shoulder. "Don't let it get to you, David. This is the way the market works, unfortunately."
"It's all about confidence, right?" said David. "We have to demonstrate that Manflex has a future under my management."
"Sure—and if we play it right—"
"I know what you're going to say, but it seems incredible to me that the survival of a great pharmaceuticals group like ours can hang on one blockbuster. Damn it, we sell hundreds of products."
"So do our competitors. But where would Glaxo be without Zantac, or SmithKline Beecham without Tagamet? In reality what you need is a steady flow of new products, but that requires an incredible outlay on research. Have you any idea how many drugs are patented and tested for every one mat is successful? Five thousand, David. Five thousand to one. Those are the odds in this business. We're not equipped to compete on that scale, not anymore."
"Okay, I get the point. I must meet with Professor Churchward just as soon as possible. Does that mean a trip to Indianapolis?"
Leapman nodded. "How soon do you want to go?"
"The next available flight, I guess. Really I should be back at the house with the family right now. They'll have to make allowances."
"Can't you tell them it's important business?"
"You know what they'll say? 'Isn't he just like his father?'"
They took the plane that evening and spent the night at the Hilton-at-the-Circle in Indianapolis. After breakfast, they took a taxi out to Corydon University, some fifteen minutes' drive west along Washington Street and beyond the airport. Leapman filled in some background on the man they were about to meet. "He didn't discover PDM3, but he was the first to see its potential. He's been working on a treatment for Alzheimer's disease for at least ten years, originally for his Ph.D., I believe. About five years ago he started testing a compound that seemed to have some potential in combating the memory loss associated with Alzheimer's. We called it Prodermolate, or PDM3. The first results were promising, no more, but lately—and I mean just in the past few weeks— he's come up with some results that can only be described as sensational, David. They have implications not just for Alzheimer's, but for the mental capacities of the population at large."
"You said my father knew about this project?" David inquired.
"Sure, Manny knew. He met Professor Churchward several times."
"So what was his assessment?"
"Of Churchward?"
"Of PDM3."
"He gave it his backing."
"You mean he was willing to stake the future of Manflex on it?"
Leapman shook his head. "He didn't have the information we have."
"But it's only just over a week since he died. Has it all taken off since then?"
Leapman put his hand to his face and said as if heralding a sensitive matter. "Well, David, Manny was a terrific guy and we all loved him—"
"But?"
"But towards the end he had his mind on other things. I don't blame him for that. When he told me about his terminal illness, I saw problems for the business, so I did what anyone in my position would do—discreetly took the pulse of the company. I asked for an update on all the research that we were undertaking, right across the world. That was how I learned that Churchward was almost ready to publish these fantastic results with PDM3."
"You didn't discuss it with Pop?"
"I left it too late."
Corydon University campus was compact and unfussy. Not an ivy leaf in sight. Solid sixties prestructured building with some computer age additions. Security cameras at the entrance. A black-uniformed receptionist flanked by video screens and with a console in front of him. He keyed in their names and they watched them appear on one of the monitors. Then they had to go through the ritual of being photographed for identity tags. Finally, Professor Churchward's secretary arrived—a demure young woman with a tag mat read Bridget Walkswell fixed on her blouse. She looked the sort who would suffer acute embarrassment if anyone made a joke of her name. With a walk so innocent of any suggestion of a wiggle mat she must have worked on it in front of a mirror, she escorted them to an elevator.
They stepped out into a low-ceilinged laboratory bristling with equipment, huge transparent cylinders on stands and metal structures festooned with white tubing and electric cord. Buff-colored notices were prominent everywhere warning of biohazards such as mouth pipetting. The steady hum of computers from the far end drew their attention to a series of keyboards and screens ranged along a bench. Something very like a submarine periscope was mounted there. It was being used by a slight, dark-haired man in a white coat.
Bridget Walkswell announced them.
"One moment," the professor said without moving from the eyepiece. He touched an adjustment control. Beside him on a video display there was a small movement in a pattern looking
like a Chinese ideogram which David recognized as a configuration of DNA, the genetic blueprint. The professor continued with what he was doing for another half minute or so. When he eventually drew back, he still didn't give his visitors a glance. His chair was on wheels and he glided to his right and tapped something into the nearest computer.
Without exactly apologizing for her boss, Ms. Walkswell spread her hands in what amounted to a gesture of helplessness and then brought out two stools from under the bench. David and Leapman sat and waited.
Finally Professor Churchward swiveled around and said, "So are we in business, gentleman?"—at the same time snapping his fingers and gesturing towards the door. Ms. Walk-swell left the room.
Obviously the great man had more interesting things to do with his time than talk to a couple of business execs from New York. However, he offered them coffee, gesturing to a beaker of water simmering over a Bunsen burner. Beside it were some chipped mugs and unwashed spoons. Speaking almost in unison, they said they'd only just finished breakfast.
Churchward looked like a marathon runner, without an ounce of spare flesh, but his metabolism didn't require athletics to keep him in shape. He was one of the type who burn up energy without getting out of a chair. His intense blue eyes, lodged in a small, bony face, flicked over David's casual attire, missing nothing. There was no clue as to what he thought. He wore a plain brown tie and his own hair was as short as a marine's.
"David took over as Chairman of Manflex yesterday," Michael Leapman explained.
Churchward nodded as if he already knew. No words of regret about Manny's passing. "And you want an update from me on Prodermolate. You know the background?"
"Let's assume I know nothing," said David, who knew not very much.
"As you wish. The compound that we call PDM3 was discovered as long ago as 1975 by a team at Cornell. They were funded by Beaver River Chemicals, which is now a Manflex subsidiary, as I guess you know. The formula was registered along with a million others, but it wasn't considered to be of any commercial use until about five years back, when a decision was made in this department to initiate research into protective agents. You know what I mean?"
David frowned. The question was addressed to him and he felt that he ought to make a stab. "Contraceptives?"
The professor closed his eyes and took a deep, restorative breath before opening them again. "Protective agents are drugs that appear to protect certain of the nerve cells in the brain from dying. Nobody understands why. Your father, who kept up with developments, knew that some of his rivals in the industry were doing work in this field. The richest prize in the industry is a drug to treat Alzheimer's disease."
"That much I do know," said David.
Churchward nodded. "Companies like Janssen and Miles had already started preclinical trials with drugs they had patented, so your father asked the people here to see if they had anything of potential use in the treatment of Alzheimer's."
"And someone remembered PDM3?"
"Not at all." Professor Churchward had no inhibitions about putting David down. "Things don't happen like that It was one of numerous compounds that were dusted off and tried. Targeted research is more rare than you would think in the discovery of medicines. We still rely heavily on blanket testing for biological activity. The first results were interesting, but not spectacular. PDM3 didn't promise anything remarkable in preclinical. Do you have any idea what I'm talking about? Do you know about the testing procedure?" he asked with intimidation.
This time David restricted himself to raising his eyebrows equivocally.
"I'm referring to the series of tests every drug is put through before it gets approval."
"Ah—I'm with you," David responded, "In the preclinical stage, you're restricted to experiments on animals."
Grudgingly, Churchward conceded, "Correct If that's satisfactory you go on to Phase One, which is merely testing for safety in a small sample of humans. In Phase Two you test for effectiveness, still using small numbers of humans. We've done all that PDM3 has gone through Phase Two and now we're ready to undertake the third phase, the extensive clinical trials. Assuming they go well—and I've no reason to think they won't—we take it in front of the FDA." He added, as if to a child, "The Food and Drug Administration."
"And when they recommend approval, we're in business?"
"And how!" murmured Leapman.
"You really believe this drug is something special?" David asked.
"Something special?" The professor hesitated, as if weighing his response. "What we have, Mr. Flexner, is the equivalent, in pharmacological terms, of the splitting of the atom."
Goosebumps formed on the backs of David's arms. In his experience, scientists weren't given to such extravagant claims.
Professor Churchward said, "PDM3 is not a protective agent It is a regenerative agent. It enables dying nerve cells to grow and regenerate. No other substance in the pharmacopoeia is capable of that."
"Brain cells regenerate?"
"Yes. Do you see the possibilities? This goes way beyond the treatment of Alzheimer's disease. We have the means of sustaining our mental ability indefinitely. There's no reason why we shouldn't make the drug available to healthy people. Young people. Men and women of forty can expect their brains to function just as efficiently when they are eighty. The drug will eliminate the process of aging."
"You mean mental aging?"
Churchward reddened. "Be reasonable. I wasn't suggesting we can make old men young again. That's a job for plastic surgery."
"So it doesn't increase life expectancy?"
He spread his hands in exasperation. "What do you want from me, Mr. Flexner?"
David told him coolly, "I'm trying to get a grasp of this discovery, Professor. If you're looking for congratulations, fine. I salute you. I also want to make sure I fully understand you."
"David, the potential is fantastic," Leapman waded in fast. "People will be capable of a longer working life if they want it. They won't be such a drain on the social budget. They can look after themselves for longer. Men and women of genius will be enabled to go on enriching the world for the rest of their lives instead of fading into senility."
"And we're ahead of the field on this?"
"There are no other runners," said Leapman.
"Some research is being done with nerve growth factor from naturally occurring brain substances," Churchward no thought fit to add, "but it's at an early stage, and of course it's organic in origin."
Leapman said, "They can't compete with a drug."
"You're quite sure we have it patented?"
"You bet we do."
"What about ADRs?" David wasn't entirely ignorant of the jargon. An ADR was an adverse drug reaction, a side effect
"As you doubtless know," said Churchward with unconcealed irony, "every drug has ADRs. It's a matter of weighing them against the benefits. PDM3 has some temporary contraindications. It produces mild headaches in some subjects, nausea and dizziness, but we also noted those effects in people receiving a placebo drug."
"To the same degree?"
"Not quite the same," he admitted. "However, a high proportion of the subjects manifested no ADRs at all."
"What proportion?"
"Up to sixty-eight percent."
The figure was meant to impress David, and it did. "What about long-term effects? I suppose it's too soon to judge."
The professor said, "There is no evidence of any lone-term ADRs."
"There wouldn't be, would there? Did you detect any ADRs in the animal tests?"
"In a few cases, slight elevations in liver enzymes."
"Isn't that a problem?"
"A problem would be putting it far too strongly. The liver has an excellent facility for regeneration, so if the dosage is monitored correctly, there is no danger."
"How do you tell, Professor?"
"By taking blood samples."
"If we want to market the drug, we can't expect people to subject themselves
to blood tests," said David, realizing as he spoke that the remark was naive.
Churchward clicked his tongue and said nothing.
Leapman cleared his throat and said, "I think there's a slight confusion here."
"I'm confident that we can resolve the matter in the trials," said Churchward. "It comes down to an acceptable dosage, if that is a term we all understand."
Almost everything the professor said was laced with contempt, and David couldn't understand why. He felt inept He was sure his father would have handled this interview with less confrontation—in fact, with a mix of humor and impudence—yet Manny would still have managed to elicit the crucial facts. "Don't get me wrong," he said. "I'm just trying to cover every angle. I understand about adverse reactions. I take your point that every drug has them to a greater or lesser degree. If you want to stop a cancer, you don't care so much if your hair falls out, right? The difference is that we wouldn't be treating a disease with PDM3."
"We'd treat Alzheimer's," said Leapman.
"Yes, but the professor is talking about offering this drug to fit people."
"Hold on," said Churchward. "The first thing is that PDM3 is remarkably effective in the treatment of Alzheimer's, which was the subject of my research. We can safely go to Phase Three now."
"But you're also confident that it improves the function of the healthy brain."
"Improves, no," Churchward corrected him. "It can extend the time scale of its efficiency."
"Fine—but if we sell it to healthy people we're not balancing those ADRs, the nausea and the giddiness and the increase in liver enzymes, against a dangerous disease. We're asking them to accept risks."
"I don't accept that. Let's not talk about risks. We would eliminate risks. There might be some inconvenience or discomfort," said Churchward. "That's up to them. Plenty of popular foods and drinks produce more disagreeable symptoms than PDM3. Health products, too. You take a multivitamin and there's a chance it will give you constipation."
"So PDM3 is as safe as a vitamin tablet?"
Diamond Solitaire Page 11