Cure

4

March 25, 2010

Thursday, 9:05 a.m.

Ben Corey commuted into the city almost every weekday in his prized 2010 Range Rover Autobiography from his home in Englewood Cliffs, New Jersey. Despite the usual traffic, he enjoyed the drive, especially across the George Washington Bridge. He always made it a point to be in the far-right lane on the upper deck so that he could appreciate the view of the Manhattan skyline and the expanse of the Hudson River. It didn’t even bother him when the rush-hour traffic occasionally stopped dead, since it allowed him to appreciate the view even longer. To enhance the experience, he always loaded his CD player with classical music. It was the one time during the day that he allowed himself to be alone, even turning off his cell phone.

On that particular day, the commute had done its job. By the time he drove into the parking garage just west of 57th Street, he was feeling very rested and happy, as well as wonderfully ignorant of what had occurred the previous evening.

Ben walked less than a block to the office building where iPS USA had rented space on the eighth floor facing Fifth Avenue. The day was warm, in the high fifties, and the sun was out, all in sharp contrast to the misty, chilly, cloudy weather of the previous day. All in all, it promised to be a glorious day in every respect.

Ben pulled off his coat as he passed the receptionist, Clair Bourse, whom his assistant, Jacqueline, had recently hired. He said good morning, and she returned the greeting.

Entering his corner office, Ben hung up his coat and sat himself at his desk. Front and center was a fully signed and notarized copy of Satoshi’s contract with a yellow Post-it note saying “for your files.” There were also wills for Satoshi and his wife, and the trust documents Satoshi had signed concerning his infant son, Shigeru, with another Post-it note saying Satoshi had to get his wife’s signature on both her will and the trust document. There was also a reminder for Ben to ask Satoshi if he wanted to take physical possession of them all or whether he’d like to have them put in iPS USA’s safe-deposit box in the vault at JPMorgan Chase or in the safe there in the office. Finally, there was a current copy of an obscure biomolecular journal titled Reprogramming Technologies. On its glossy cover was a third yellow Post-it, also in Jacqueline’s handwriting: Check out the article on page 36. I think we’d better move on this. The suggestion was followed by several exclamation points.

Ben put the papers for Satoshi on the corner of his desk, intending to give them to the researcher when he saw him, which he thought would be within the hour. Nine-thirty was Satoshi’s usual time of arrival, and Ben had no reason to believe it wouldn’t be as usual that morning. The only way he thought he might not see the man until afternoon would be if Satoshi had decided to indulge in some serious celebrating the previous night. From Ben’s trip to Japan to rescue the now-famous lab books, Ben knew what sake could do.

“Did you read that article?” Jacqueline questioned. She’d poked her head in from the neighboring office through the connecting door.

“I’m looking at it at the moment.”

“I think you’d better,” Jacqueline encouraged, “and before we sign the deal with Rapid Therapeutics up in Worcester, Massachusetts.”

“Oh?” Ben questioned. He didn’t like the sound of that. He and Carl Harris had been negotiating with Rapid Therapeutics over the course of many months to license their patents on increasing the efficiency of creating induced pluripotent stem cells. A deal was finally imminent, so there was no time to waste if something better was in the pipeline.

With his feet perched on the corner of the desk, Ben proceeded to read the article, realizing as he did so that Jacqueline was certainly correct. The article was about a small start-up company in California named iPS RAPID that had recently licensed a mechanism that dramatically raised by hundreds of times the efficiency of producing human induced pluripotent stem cells, a heretofore stumbling block in their use. The new technique involved what were termed small molecules.

Ben was shocked, not that the breakthrough was so astounding, although it was, but that it had gotten to the point of licensing without there even being a whisper of its discovery. Usually such an invention would first appear in Nature or Science, as its importance was obvious as a giant step in the direction of the commercialization of stem cells, but here it was showing up in an essentially unknown journal as a patented process already licensed, meaning that iPS USA was going to have to join the fray late and pay hundreds of times more to corner it. Although he was in a very real way adding to it, Ben recognized it was an unfortunate sign of the times. Universities now all had their own patent offices and considered filing for patents associated with the researchers’ work more important than the research itself, and the behavior was definitely slowing the progress of science. Before the patent mania, it was the immediate publication of advances that kept the investigative pot boiling. Of course, adding to the problem was the fact that government patent offices, both in the United States and Europe, were also granting patents for life processes, which they weren’t supposed to do by law, with Europe better than the United States in this regard. Ben could not believe some of the patents that he had recently seen emanating from the U.S. patent office. Often he marveled how anyone could justify a patent on a process that had developed by evolutionary forces over millions if not billions of years. The current patent mania would not only slow research but might also bring it to a halt. No one will be able to do anything without impinging on someone’s patent, which will result in ever more lawsuits, of which there were already enough today. Ben saw it as being akin to throwing sand into the gears of progress in medical research, a consequence that iPS USA was trying to avoid, at least in the arena of induced pluripotent stem cells.

“Put in a call to this iPS RAPID!” Ben called out to Jacqueline through the open connecting door. “You’re right about this article. Get the CEO’s name and get him on the line!”

Jacqueline’s head poked through the doorway, her red hair back-lit from the sun streaming into her office.

“Didn’t you notice that iPS RAPID is in San Diego, where it’s just after six in the morning?” Jacqueline said patiently.

For a moment Ben just stared at her without being able to make out her facial features in the glare. It took him a moment to comprehend that it was far too early on the West Coast to get anyone on the line. “Then get me Carl,” he said. “And what do I have scheduled for this morning?” He was thinking of canceling everything to get right on the issue of iPS RAPID.

“Other than in-house meetings, you are supposed to meet with Michael Calabrese in his downtown office at ten-forty-five. Did you forget?”

“I forgot,” Ben admitted. He thanked himself for having hired someone as good as Jacqueline to keep tabs on his schedule. He considered himself more of a concept guy. Although it was important to deal with the issue of this new company, in the long run it was more important to deal with Michael and break off the Mafia-Yakuza connection. Intuitively, he understood that the longer the association went on, the harder it was going to be to stop it. He also knew that if the connection were ever leaked he’d probably have to resign, or at the very least he’d have to kiss good-bye any chance of launching an IPO anytime soon. What he didn’t let himself even consider was the possibility of an indictment.

With Jacqueline off to find Carl, Ben went back to the article, musing over what class of small molecules was involved. He guessed it was probably some kind of suppression of growth factor inhibitor, but that was only the obvious. As he read he marveled over the speed of biomedical discoveries, especially knowing that such discoveries invariably pointed to other possibilities, which spawned even more discoveries, in a quickening self-fulfilling process. He also knew there were discoveries and there were discoveries, meaning some were huge steps and others not so huge. He considered this present discovery to be one of the relatively big ones, at least in relation to the commercialization of iPS cells.

“You wanted to see me?” a voice called from the doorway to the hall a few minutes later.

Carl was standing there with his tie loosened, the top button unbuttoned on his shirt, and his sleeves rolled up to just above the elbows. He was the picture of the hard-working accountant rather than the CFO, which was why he was so good at what he did. There was nothing beneath him. He was involved in every aspect of the business’s finances from the mundane to the conceptual, and Ben trusted him implicitly and relied on him completely.

“Come in! Sit down and take a look at this!” Ben said, handing Carl the article.

Ben watched his chief financial officer’s expression as he read, noticing a frown develop. Then, in an apparent moment of frustration when he was finished, Carl slapped the journal down onto the surface of Ben’s desk and lifted his face to him. “There’s something I have to come clean about. It’s a confession of sorts.”

“What in the blazes are you talking about?” Ben asked, while in his mind he was concerned about being blindsided by some kind of major financial problem just when things were looking so rosy.

“This is something I should have admitted a year or two ago,” Carl said so contritely that Ben’s concerns soared.

What now? Ben thought silently, trying to prepare himself for the worst, such as that the company had run out of money from having been embezzled or from some other disaster. With the contract signing yesterday, he’d been confident their financial situation was solid, especially with the contract certainly upping their market value.

“I hate to admit it, but I just don’t know enough about stem cells,” Carl said guiltily. “I understand up to a certain point, but when you hand me something really technical like this, it’s just beyond me. I’m sorry. As the CFO of this company, I should be more knowledgeable with it, but the fact of the matter is that I’m better on the financial side than the scientific side. Remember! You recruited me from the financial world, not biotech.”

For a moment Ben was stunned into a brief silence by a combination of relief and surprise. As a biomolecular scientist, he was so familiar with the material that he had trouble believing everyone else wasn’t equally well informed. Quickly the relief and surprise turned to humor, and Ben found himself laughing. At that point it was Carl’s turn to be confused. “Why are you laughing?” he questioned, genuinely bewildered. He had expected surprised irritation from Ben, not laughter.

“I can’t help it,” Ben admitted. “You’ve always convinced me you understood the field as much as anyone. Hell, I’ve asked you your opinion on a lot of issues, and I’ve always felt you gave me solid advice. How could that be?”

“Most of the advice I’ve given has been financial, and whether a company deals with stem cells or oranges, that advice is usually pretty similar. If it was outside of the financial arena, I suggested you ask Brad, Marcus, or Lesley. That was always good advice, and has worked pretty well. I’ve been trying to pick up more info as time’s passed — there’s so much to learn.”

“How about a quick review,” Ben said.

“It would be most welcome.”

“Okay,” Ben said, thinking about how to begin. “It all started in the early sixties, when a couple of Canadian researchers found the first stem cells in mouse blood. These were rather primitive cells that could divide and make progeny, of which, say, half became various blood cells and half would be merely self-renewing. Then there was about a thirty-five-year gap before a researcher in Wisconsin was able to isolate similar human stem cells from very early embryos and make them grow outside the body in glass dishes by a process called in vitro. At the same time other researchers learned to turn these stem cells into every different kind of cell in the body, such as heart cells, kidney cells, and the like, opening up the very real possibility for creating human replacement cells and parts to cure degenerative disease.

“Of course then disaster struck, involving the use of embryos originally created as part of the in vitro fertilization industry to get stem cells. Brushing up against the long-standing and very emotional abortion debate, the idea of getting stem cells from embryos caused Bush Two to restrict federal funding for stem cell research except from a narrow source of existing stem cell lines.”

“I remember all this,” Carl interrupted. “But what’s all this about induced pluripotent stem cells? Are they the same as embryonic stem cells?”

“Amazingly enough, they do seem to be pretty much the same, and in ways their creation defies what science thought about development. For a long time scientists thought development of a cell from a primitive stage to a mature cell was a one-way street. But that turns out not to be the case. In studying the process of development, there appeared to be about thirty genes that are involved in varying amounts and timing in the maturation process. By packaging these genes in different amounts and mixtures, and putting them inside a fully developed mature cell with the help of viruses, reprogramming was shown to occur, taking the mature cell back to an embryonic state, seemingly the equivalent of an embryonic stem cell.”

“So that’s why these new stem cells are called ‘induced’?” Carl questioned.

“Exactly!” Ben said. “And that’s why they are also called pluripotent, meaning like embryonic stem cells, they are capable of forming any of the three hundred or so cells that make up the human body.”

“It is surprising,” Carl exclaimed.

“It’s more than surprising, in my estimation,” Ben said. “It’s more like astounding. The science of induced pluripotent cells is racing ahead at breakneck speed. Four years ago it was the genes associated with development that were put into mature cells by viruses, and some of these genes were oncogenes, closely associated with cancer-causing capabilities. Even the virus vectors were known to be occasionally carcinogenic, or cancer-causing, so the resulting induced pluripotent stem cells could never be used in patients, as they would be far too dangerous. But since that early beginning just four years ago, genes have been placed as the agents to reprogram the cells to a more primitive state with the protein products of the genes, and the insertion by potentially dangerous viruses has been changed to using electric current called electroporation, or even more recently by certain chemicals that pull the development proteins in through the cell membranes without damaging them.”

“Okay,” Carl said. “Astounding is a better word than surprising.”

“More important, does this give you a better understanding of the field?”

“Much better. I’ve finally got some context.”

“I’m always happy to give you an explanation of the science. Don’t feel embarrassed to ask.”

“I will take you at your word,” Carl said, putting his hand back on the reprint. “So if I understand correctly, this article is concerned with a process that speeds up the production of induced pluripotent stem cells, and it’s another one of those key processes that we need to control?”

“Yes, and I believe, by the way, this iPS RAPID is behaving like it’s for sale, an issue you know more about than I. My sense is that they would be better to control than the company in Massachusetts. It would be a coup to snap them up before they get a chance to test the market. Do we have significant equity on hand?”

“Probably not, but with the signing yesterday, we’re in good shape market value-wise, and it won’t take long to be able to estimate what we could raise in the short run.”

“Do it,” Ben ordered.

“It’ll be done,” Carl said, and got up from his chair. “Thanks again.” A moment later he was gone.

Ben got up and poked his head into Jacqueline’s office. He had to squint into the sun shining through her windows facing east. “Any sign of Satoshi?” he called out to her.

Since she was on the phone, Jacqueline merely waved and shook her head, voicelessly indicating that she’d not seen him.

Returning back to his desk, Ben half joked to himself that in regard to Satoshi he felt somewhat akin to the father of a teenage son, constantly concerned to a degree where the kid was and what he was doing. It was now going on ten, and Satoshi had yet to show up or call. Ben sighed, recognizing that he was always nervous until Satoshi appeared at the office, even though the man had nothing specific to do. Ben had asked him to at least call if he wasn’t planning on coming in, but Satoshi never bothered. One time Satoshi didn’t show up for a week and never bothered to call or even turn his cell phone on, causing Ben significant concern. When Satoshi did show up, he said he had taken his family to Niagara Falls. Although things were obviously better now with the licensing agreement signed and notarized, losing Satoshi would be more than inconvenient.

Thinking about Satoshi reminded Ben that he’d promised to call up to Columbia and check on the status of his request to lease laboratory space. As he put the call through, he mildly chided himself for not following up on it sooner. Knowing Satoshi as he now did, had he been more responsible, he wouldn’t have to worry about Satoshi’s whereabouts, because the man would spend all his time in the lab.

The conversation with the powers-that-be at Columbia was short and sweet, and very positive. The space was definitely available, the price was high but fair, and all Satoshi would have to do was provide a list of equipment and reagents, which the school would be happy to provide.

On a three-by-five card Ben scribbled the words Columbia bench space available, can start immediately, need to know reagents and special equipment.

Adding the index card to the already sizable stack of contract, wills, and trust, Ben reached for the phone. He’d waited long enough, and his impatience had taken over. He dialed Satoshi’s cell phone number, which he’d committed to memory.

With an uncomfortable premonition building with each hollow ring, Ben impatiently drummed his fingers on the edge of the desk. When the prerecorded generic outgoing message came on, Ben’s premonition was unhappily vindicated. When appropriate, he left a message for Satoshi to return the call, adding that he had some good news to report. It was Ben’s hope that such a message was the best way to ensure a call back as soon as possible.

With that accomplished, Ben went into his closet and dragged out his coat. It was time to leave for his morning meeting with Michael.