Flashback Page 10

  “And former POW. Well decorated—a Purple Heart, in fact. And a very sweet man.”

  René felt a little sick as she watched the fast-forwarded sequence of his brain’s deterioration. Her father had been a Korean vet also. “What stage is he in?”

  “Moderate, but it seems a particularly aggressive case.” The red blotches spread from frame to frame. “At this rate, the stuff will probably cover a good part of the frontal lobe within a year or so, rendering him incapable of speech and most memory.”

  Although one could only imagine the man’s cerebral cortex becoming clotted with plaque, this new technology let them witness the brutal unraveling of the man’s mind and memory. But if they could have looked inside Mr. Martinetti’s brain they would have seen the same landscape of destruction that a hundred years ago in Munich had startled the German physician who described the disease that bears his name. It was Alois Alzheimer whose investigation of what had been diagnosed as premature senility in a fifty-one-year-old woman led to his discovery of the disease’s gruesome signature: the brownish nodules of plaque and the dense tangle of neurofibers that eat away the upper layers of the cerebral cortex and destroy a person cell by cell. What had wasted her father.

  Nick reran the sequence. “Now, imagine seeing this played backward—all that red turning blue again.” And in his eyes she saw a flicker of promise.

  Three years too late.

  René tried to deflect the voice and looked away. At a station nearby was another computer monitor showing another brain image. “Is this the same patient?”

  “No, that’s the image of a patient of Dr. Heller, another neurologist here in the department.”

  René welcomed the distraction.

  “But it does look similar.” Nick rolled in his chair to the monitor. “And that’s rather interesting because he’s not an AD patient but a young fellow in a coma. He nearly drowned last week after being stung by jellyfish—some rare creature found in the Caribbean.”

  “How did he end up here?”

  “Actually, it happened up here. On very rare occasions tropical creatures get caught in the Gulf Stream. And when the waters are as warm as they’ve been, they get caught in eddies that bring them close to shore.”

  “Where’d it happen?”

  “Homer’s Island, a private island northwest of Martha’s Vineyard. The only place they’ve ever been reported in the northeast. The Coast Guard found him.”

  “Lucky for him. What’s his prognosis?”

  “Not good, though his unconscious mind is quite active.” Nick moved the mouse around and hit a few keys as new brain images filled the screen in quarters. Then with a pen he pointed to an area of the frontal lobe of his brain. “This is what interests me. See how the yellow area appears to be expanding. Unlike the other, this is a structural MRI that measures brain tissue volume. And if you look here, the active area is his hippocampus and frontal lobe.”

  “Meaning what?”

  “I’m not really sure, but if I didn’t know better, I’d say the tissue was getting denser.”

  “Denser? You mean his brain is growing?”

  “Unless I’m mistaken, there’s active cell growth. Unfortunately he’s in no condition to tell us what he’s experiencing. But if he wakes up, it might be interesting to interview him.”

  “Meanwhile, he’s turning into a Conehead.”

  Nick laughed. “Or someone with a pretty rich memory bank.”

  When Nick looked away, René fingered open the folder with his name tab and that of the unit he was in. “Any way to tell how long he might be unconscious?”

  Nick shook his head. “Could be a week, could be five years. Could be forever.”

  “It must be very hard on his family.”

  “I think it’s only his wife, and I hear she’s not doing too well. He has seizures but is settling deeper into his coma. The EEG measurement of his brain-wave activity is around three Herz, which is very low, nearly a third the activity of adults in normal sleep.”

  “Which means he’ll probably be moved to a rehab center soon. I’m sure the caseworkers are probably already talking about that. Maybe I can suggest some possible facilities.”

  “I think she’d appreciate that. Also, on the off chance that he wakes up, it might be useful to make contact. He’s experienced a unique restructuring in his brain, so he might be a treasure trove of data. And it would be good for his wife to have another arm of support.”

  Jack Koryan. And she filed away the name.

  16

  JACK KORYAN.

  It was later that evening, and René was back home and at her computer with a glass of chardonnay and Silky in his basket at her feet. Over the hours she had let Nick’s words help her come to terms with the reality that she had done the right thing by her father. That at the time there were no other options. “Promise me this …”

  She typed the name in the Google search box, and instantly a community newspaper site came up with several hits of the same article:

  MAN COMATOSE FROM JELLYFISH ATTACKA man was found washed up and unconscious on a beach on Homer’s Island. Jack Koryan of Carleton, Massachusetts, was barely alive after being stung by dozens of rare jellyfish while swimming.Koryan was taken by emergency helicopter to the Cape Cod Medical Center … .Scientists from Northeastern University and Woods Hole Institute said that Koryan had gotten caught in a large school of Solakandji jellyfish, which is only the size of a tennis ball but which has three-foot-long stinging tentacles. The highly venomous creature is a native of the waters of the Caribbean. Dr. Jason Marchi, a marine biologist from Woods Hole, said that the increased water temperature and the rise in nutrients from fertilizer runoff tend to support a rise in jellyfish populations … .Like other species of toxic jellyfish, the Solakandji tentacles have millions of stinging cells called nematocysts … .According to medical experts, there is currently no antivenom available for the Solakandji sting, which has caused deaths in Jamaica … .

  She finished reading the story, then stretched out on the couch with her wine and Silky on her lap. She clicked on the television and lowered the volume just to decompress before getting ready for bed. On the news were the usual grim stories about the Iraq war and some local crime. She listened with half interest. Something was bothering her and she could not put her finger on it. Something to do with that Jack Koryan guy—something that sat under the upper layers of her mind and kept sending up little tremors.

  After maybe fifteen minutes of distraction, she got up and went back to the computer and did a search for Solakandji, the species of jellyfish Nick had. Amazingly, she got over three hundred hits. And she spent the better part of the next hour clicking on different sites. Most were divided between news stories of attacks, treatment of the stings, general information about jellyfish, and a few scientific papers. Several of the technical sites had photos of a creature that looked like a translucent mushroom with four interior rings and spaghetti tendrils.

  The Solakandji jellyfish (related to Irukandji jellyfish of Australia’s Great Barrier Reef) is found in warm waters of the Caribbean and southern Atlantic.

  Minor envenomations cause pain, swelling, and localized numbness that often subsides within hours of onset. Serious envenomations are associated with a rapid progression of symptoms, including erythema, paralysis, respiratory arrest, cardiac failure, and death … .

  Other sites offered information about how to treat stings with vinegar, news stories about how victims in the Bahamas and elsewhere suffered a rapid rise in blood pressure and a cerebral hemorrhage that led to their deaths. Her mind returned to poor Jack Koryan in a deep sleep, unfortunate victim to happenstance, his entire universe reduced to a bed and that bank of monitors and destined never to open his eyes again.

  She clicked onto more technical sites intended for dedicated marine scientists and scrolled down until she came to a dead stop.

  N. A. Sarkisian, Mavros, N. T., et al. Neurotoxic activity on the sensory nerves from toxin
of the deadly Solakandji tropical jellyfish Chiropsalmus quadrigatus Mason. Chem Pharm Bull 17: 1086-8, 1971.

  Mavros, N.T.

  Nick. He had published a paper on the toxin thirty-five years ago. She read on.

  The abstract described the Solakandji toxin as a novel proteolytic agent whose molecules functioned as an NMDA receptor antagonist. Furthermore, the substance was identified as a glutamate inhibitor affecting aspartate—an excitatory amino acid-transmitter in the brain, similar to glutamate.

  “Glutamate inhibitor affecting aspartate.”

  The words jumped out at her.

  That was the same neurochemical function that Jordan Carr had described—the same neurotransmitter was linked to seizure activity and agitated behaviors of people with dementia. By inhibiting glutamate, demented patients were demonstrating better behaviors and enhanced cognitive capabilities.

  My God! Jack Koryan was attacked by a jellyfish whose toxin was the chemical basis of Memorine. And Nick had helped pioneer the stuff.

  2

  17

  “WHO THE HELL’S THIS COMMCARE WOMAN?”Gavin Moy’s eyes blazed down on Nick. He pulled a letter out of the folder. “René Ballard, Consulting Pharmacist. CommunityCare Pharmacy.” He handed the letter to Nick. “Isn’t she your friend?”

  The letter was elegantly blunt, like a silver-plated bullet. “Yes, and former student,” Nick said.

  “Well, your friend and former student says that medical records of some patients are missing—‘a violation of regulatory procedures,’ and she quotes the state and federal codes—blah, blah, blah—and she expects that all the records ‘complete and intact’ be returned immediately or she’s obligated to file a report with the IRB and request FDA review of our trial protocols. Jesus H. Christ!”

  Nick had to repress the smile. “I believe she’s just doing her job.”

  “Doing her job? She may be doing a job on friggin’ medical history.”

  “Then maybe somebody should comply with her requests. Rumor has it that withholding nursing home records from consulting pharmacists is a violation of regulations.”

  “Who the hell’s side you on?”

  “Truth and beauty.” Nick smiled broadly.

  Moy snickered. “Which is why I called you. But I must say, she has balls.”

  “Because I taught her everything she knows.”

  “Well, Jordan Carr says everything’s being returned, so tell her to wrap up.”

  “What about the other nursing homes serving as research sites?”

  “There, too. We want everything on the up-and-up.”

  They were alone in Gavin Moy’s office at GEM Tech—a handsome, voluminous space with windows on two sides, one with a view of oak woodlands, the other commanding a view of the Boston skyline, shimmering in the distance.

  On a table behind him were pictures of Moy’s wife, who had died five years ago. Moy had adjusted well to his widowerhood. Following her death he redirected his energy into his company, hiring the best and the brightest. And now he was consulting senior medical execs and leaders in hospitals and academic institutions to put together a Dream Team of clinicians. Likewise, his board members were major venture capitalists who would have eaten their own children to be part of GEM’s future. And who wouldn’t—since Gavin Moy might be sitting on the pharmaceutical equivalent of the Holy Grail: a cure for Alzheimer’s disease in an ever-aging world.

  On the wall behind his desk hung framed patents with his name on them—each for a variation of the same parent compound, just to keep competing labs from making look-alike compounds—the first, now faded, was dated January 10, 1976, the latest, from eight years ago, represented the final molecular structure whose trials would eventually be presented to the FDA for market approval. Trademarked Memorine, the compound not only had enormous pharmaceutical and commercial potential, if successful Gavin Moy could find himself in Stockholm, Sweden, when they passed out Nobel Prizes.

  “We’re going to make an announcement at the meeting of shareholders in a few weeks, so the word will officially be out instead of leaks and speculations.”

  It was a risky plan, because formal announcements about the success of a drug are almost never made in the middle of trials. But given the early success, Moy’s strategy was to create a market for Memorine before the first pill hit the shelves.

  “Until then, we’re playing mum.”

  Gavin Moy was paranoid and for good reason. He had sunk millions of his own and hundreds of millions of investors’ dollars into Memorine against a history of adventures that had turned out to be duds, including development of a cure for a rare neurological disorder; it proved disastrous in the Phase III clinical trials, costing GEM eighty million dollars and nearly tanking the company. Another agent targeting Parkinson’s disease was beaten to market when a competing lab offered a disgruntled GEM science director an offer he couldn’t refuse—the results: a look-alike that became a blockbuster while GEM fumbled around in Phase III trials only to scrap the project and end up with huge go-nowhere litigation fees. Those fiascoes were why Gavin Moy had guarded Memorine as if it were the Manhattan Project.

  It was also why Nick had played coy with René. Only when she called to ask if the jellyfish connection was true did he confess a minor role in its development, breaking ethical protocol. Since learning about Memorine René had been flagellating herself with guilt for having consented to let her father die instead of holding out for some breakthrough cure. So he reiterated the fact that the compound had not been targeted for clinical trials of dementia patients until two years after her father’s death. Even then Gavin Moy had sworn Nick and others to secrecy in face of the Darwinian competition for a cure and the fact that when the patent would run out in a few years generic knockoffs would fly. But before that eventuality, GEM hoped to establish a global franchise on Memorine.

  “We’ve tried to keep a low profile, but we’re getting calls from physicians and AD organizations wanting to know if it’s true we’re working on a cure, can they volunteer patients. Christ, this is going to be the biggest thing since the Salk vaccine, maybe penicillin.”

  “We can only hope.”

  As Moy scanned Walden Woods out his window, Nick thought that he was like one of those reptiles with independent turretlike eyes constantly alert to opportunities and dangers. That was how he had been decades ago, and, perhaps, that was the secret of his successes and failures. On his desk was a brass plaque with the inscription: “It’s not over until you win.” Quintessential Gavin E. Moy.

  Although Nick had seen Moy over the years at conferences and colloquia, they went back to a time before GEM Neurobiological Technologies existed. They were residents together at Mass General back in the late 1960s, when Gavin had started the forerunner of GEM Tech in the cramped basement behind MIT and where Nick helped in the research before finishing his residency. For years, some antecedent of Memorine had been in Moy’s pipeline, going through molecular reconfigurations and testing until the final form was developed. Today it was the flagship product for GEM Tech—and virtually their only product.

  The promise began when it was discovered that the toxin from the Solakandji demonstrated an extraordinary neuronal property: it enhanced long-term memory. Fetal rodents injected with the compound learned to whip through complex mazes as if radar-directed while their untreated siblings stumbled along. Even more remarkable, mature rats demonstrated enhanced long-term recall, mastering maze problems that they hadn’t been exposed to since they were juveniles. The immediate thought, of course, was what it could do for people suffering memory loss—a speculation that raised hope against the scourge of Alzheimer’s disease.

  The first breakthrough came when it was discovered that Memorine treatments had all but eliminated deposits of beta-amyloid peptides in mice genetically engineered to have an Alzheimer’s-like disease. Even more remarkable, new brain cell growth explained why treated mice had higher learning curves and functionality than untreated mice. In short,
Memorine had converted memory-degenerating rodents into recall wizards. Last year it was tested on human subjects and medical history began to be rewritten.

  “Nick, you’ve read the reports—the results are fabulous and you could share in its success. So don’t tell me ‘no’ again, because I’m asking you to come aboard.” Moy’s eyes were shooting fire.

  “Gavin, I’m very flattered, really.”

  “On the contrary, we’d be flattered. And all bullshit aside, we’d like to have a man with your prestige and reputation.” Moy handed Nick a few sheets of paper. “Some of the people you’d be working with. I think you’ll recognize a few.”

  It was a long and impressive list of physicians already taking part in the trials—names of medical researchers and practitioners associated with the best of institutions: the Scripps Institute, Yale, Washington University Medical School, the National Institutes of Health, et cetera.

  “Plus some acquaintances of yours—Peter Habib, Jordan Carr, and others. We’re expecting the FDA to fast-track the application so we can get it to market in eighteen months.” Moy spoke with serene conviction. “Word is the president might support clinical development as a pledge to older voters in his reelection campaign. The long and short is this is a revolution, and we want you to be part of it.”

  “And you’re working out possible ADRs—adverse drug reactions.”

  Moy’s face froze. “What adverse drug reactions?”

  “That woman who killed the CVS manager. I’ve also heard rumors of patients experiencing some deep-past delusional spells.”

  “Where the hell did you hear that?”

  It was actually Pete Habib who had come up with the “flashback” label. “Where I heard it isn’t important. The story of the murder was in all the newspapers. But questions have been raised about whether there’s a connection to the drug.”