“Madame Lasagna and The Dead Frog, a Novel of Scientific Discovery”

(94,225 words with 9 illustrations)

by Nick Ingoglia

Synopsis:

How do our brains form a memory? Why are humans unable to re-grow a severed spinal cord while adult fish and frogs can? And, the most fundamental question in neuroscience research - how do the billions of nerve cells in our developing brains ‘know’ which neurons to make contact with as they form over a trillion highly specific connections? These are a few of the scientific challenges faced by researchers in the summer of 1982, as Roger Bansky, a newly minted PhD neuroscientist, begins his first academic position. Roger’s research goal? To understand why human spinal cords are not capable of repair following injury.

Grace, his ‘pal’ and former student, who has been forced by injury to give up a career in ballet, is trying to find a new profession about which she can feel “the passion she once felt for dance.” After Roger and Grace attend a lecture on “The Neuroscience of Memory”, Grace is smitten by the charismatic lecturer, while Roger (not so smitten), goes in search of adventure before plunging into his scientific life. Roger’s search lands him at Chez Hendrix, a ‘sketchy’ resort for post-Woodstock singles, who seek their ‘soul-mates’ as they relive the days of the famous concert. There, he encounters Madame Lasagna, a flamboyant, ‘psychic’, con-artist. On his return, Grace asks, “How was your trip? Get drunk? Break some laws? Smoke some weed? Get laid? Fall in love?” To this Roger answers, “Yes!”

In a unique and intriguing blend of authentic laboratory science carried out by fictional characters, Madame Lasagna and The Dead Frog … explores the challenges and thrills of scientific discovery while bringing the reader inside the, at times, not so pure academic world of biomedical research. This novel weaves the path of scientific discovery with the stories of Roger, Grace and Bakari (a talented African-American high school student from an economically depressed family, who joins Roger’s research lab) as they struggle to find purpose in their lives. This novel is also about Ridley Greif, chairman and vigorous elder statesman, who tries to counter the cynicism, greed, and apathy, of his moribund tenured faculty while keeping alive his uncompromising vision of scientific discovery in his acolytes. And, it is a story of hope; hope that the youngest members of our society can overcome social, racial and gender barriers to enter the world of science and keep alive the thrill of discovery.

The characters in this novel are defined by their curiosity to unravel the mysteries of our existence and for whom life is as dependent on the questions they ask as it is on the air they breathe.

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Below are the first three chapters of the novel:

“Madame Lasagna and The Dead Frog - A Novel of Scientific Discovery”

by Nick Ingoglia

1. Alumni Hall, NYU downtown campus, July 1982

“How do our brains form a memory? How is it possible that tomorrow, next week, a year from now, you will remember this lecture, recall me standing here in front of you, recall, perhaps, that the attractive person sitting beside you caused you to lose your concentration?” - a smattering of laughs.

“How do cells in our brain, our neurons, do this?” Reese Knightly, tall, lean, imposing, stood at the academic podium, gazing earnestly at his rapt audience. He spoke with the confidence of a rock star as he left the podium to pace across the stage, his mind seemingly lost in the internal logic of his lecture. “Let me warn you at the outset,” he went on. “I don’t have an answer to this question – at least, not a complete one. But I do have something to tell you. This afternoon, I hope to convince you that while we don’t know everything that goes on during the formation of a memory, we do know that the synthesis, the construction, of a new protein is associated with this remarkable process.”

Knightly looked off into space beyond his audience. “Now, where to start? I know. Let’s begin with a story – a clinical vignette if you will. ”

Roger Bansky listened with rapt attention from his seat in the fourth row of an audience of perhaps 50 students and faculty. In a little over a month, Roger would be leaving his present position as a postdoctoral fellow, to join the faculty at The York Avenue Medical School, where he would be establishing his own research laboratory. This lecture, the last of a summer series aimed at students considering a career in the emerging field of Neuroscience, was coming from a luminary in the field and a tenured member of the faculty Roger would be joining.

As Knightly continued his lecture, a young woman slid into the seat next to Roger.

“You’re late,” Roger whispered.

“Mother!” Grace hissed back.

2. Roger and Grace, September 1980

Roger and Grace had known each other for almost two years. They had met when he was the instructor in a conference section in Introductory Biology, and Grace was one of his students.

“My name is Roger Bansky,” he told the class at its first meeting. “I received my PhD this past spring, and for the next two years I will be a post-doctoral fellow here at NYU. After that, I hope to get a faculty position at a research university.” He paused and looked out at the 25 or so students, who for the most part, looked back blankly. That’s when he first noticed Grace.

He noticed Grace because she was actually paying attention. Grace also had a ‘look’ that distinguished her from the rest of the class. While most of the NYU freshmen, thrilled to be attending college in Greenwich Village - the epicenter of the revolutionary ‘60s - had embraced a hippy look, Grace had not. Petite and slender, she wore dark miniskirts over brightly colored tights, with a variety of not always matching leotard-style tops. Her signature accessory, as Roger would discover over the coming years, was a bright green head-scarf, that barely restrained a crop of springy black hair.

“My research interest,” Roger continued, “ is in the field of neuroscience. So, if anyone is interested in pursuing a research career as a neuroscientist, please come see me.”

Roger then asked the students to stand and tell the class a little about themselves. When it was Grace’s turn, she said that at 26, she was probably the senior citizen of the group. No one contradicted her.

“Until a year ago, I was training for a career in ballet,” she said. To emphasize the point, Grace demurely held her miniskirt to her torso, and extended her left leg over her head, touching her knee to her nose. Oohs and Ahhs arose from her classmates. Then, she lowered her leg with great care and allowed her foot to rest on the desktop. “Unfortunately, I injured this knee,” she pointed to it, “several times. So, I’ve been advised to seek another career – any career but dance.” Grace showed little emotion as she told her story – she had been through it endless times.

“As an undergrad, I took only the required science classes,” Grace continued. She brought her leg down from the desk and swung it in back of her, extending her arm forward. “Arabesque,” she said to the amusement of her classmates, and her instructor. “So, I signed up for this course, because I have always been fascinated by the workings of the body, especially the brain.” She nodded at Roger, lowering her leg, assuming ‘first position.’ “And since dance is no longer a career option, I thought I’d look for inspiration in this class.”

She focused her attention on Roger. “So, it’s up to you, professor. Inspire me!”

Roger smiled back, “I’ll do my best, Grace,” he said gamely.

Grace completed Roger’s class with the 4^th highest grade. “I would have beaten the other three but they’re all pre-meds and much more competitive than I’ll ever be,” she said when Roger handed out her grade.

By spring semester, Grace was no longer in Roger’s class. But she had developed a curiosity about research and frequently ran into him at departmental seminars. When she did, she always sat next to him.

“You’re my security blanket,” she told him after one of the lectures. “Everyone else looks so scary.”

One afternoon in late March, Grace appeared unexpectedly at Roger’s office.

“Guess what? I’m volunteering in Cumming’s lab,” she said, excited. “You know, the cell culture guy down the hall? I want to see how I like lab work.”

“Good for you, Grace. He’s an excellent scientist. Maybe he can inspire you,” Roger teased.

For the rest of that semester, Roger and Grace were constant companions. They would get coffee and chat after lectures, meet for a bite at a bagel place on Bleecker, or, on nice days, just hang-out in Washington Square Park.

“I’ve promised myself that by next fall I will be set on a new career path,” Grace said one warm May afternoon as they watched a pick-up basketball game at the Waverly courts on West 4^th Street. “Maybe I’ll become a scientist,” she said casually.

“Keep going to seminars. See what research turns you on,” Roger responded without taking his eyes off the game. “These guys are so talented,” he said as the smallest player raced the length of the court, leaped with both arms extended above the rim, and stuffed the ball through the hoop.

“I used to be able to jump like that,” Grace said, her voice trailing off.

“No more?” Roger said.

“No more,” Grace said.

“My knees aren’t so great either,” Roger said. “Too much basketball on concrete courts.”

“No NBA, then?”

“Not even if my knees were fine; not even close.”

“After the last time I got injured, I decided, to my mother’s horror, I might add, to do something else with my life.”

“Your mother objected? Why would your mother want you to keep dancing when it’s ruining your body?”

“Oh, that’s mother,” Grace said without further explanation.

Roger and Grace saw each other regularly over the following months; so much so that some of the students and all of Roger’s colleagues thought of them as a couple. But there was nothing romantic between them. Roger wasn’t sure why. He liked being with Grace, and thought of her as ‘attractive in an off-beat kind of way.’ But that was it – no spark. Once, about two weeks after the course ended, when they were no longer student and teacher, Roger made a weak attempt to change things between them, really just to ‘test the waters,’ he thought later.

They were in Washington Square Park when a light snow began to fall. Roger draped his arm over Grace’s shoulder and looked for cover. By the time they scurried under the overhang of a closed restroom, Grace was shivering. Roger slipped his arm around her and pulled her into his body. A few moments later the snow let up and Grace separated from him.

“I’m going home,” she said.

“Bye Grace,” Roger said casually and leaned down to kiss her. But as he neared her face, Grace turned her head so that his lips fell chastely on her cheek, rather than her lips. This was the beginning of their parting ritual; a casual ‘see ya’, and a meaningless peck on the cheek.

Grace was OK with that. She had enough on her plate without having to deal with a boyfriend. As for Roger, he felt somewhat hurt that she wasn’t throwing herself at him, but, in truth, he too didn’t want the complication of a romantic attachment and besides, Grace was his buddy, not a sex partner.

3. The Molecular Basis of Memory, July 1982

“One evening, a man is riding home and hits a hole in the pavement, that sends him tumbling off his bicycle,” Knightly continued his lecture, enunciating his words precisely, with an assurance bordering on arrogance.

“This young man hits his head on the pavement hard enough that he feels groggy. Despite the injury, he manages to get up and make his way a few blocks to his home. His shocked wife asks what happened. He says, ‘I don’t know. I can’t remember.’

“Later, in the emergency room, he is asked the same question. Again, he can’t remember what happened. In fact, he can’t remember anything from the time he was riding on the dark sidewalk till he found himself stumbling into his house. What’s more, he will never be able to recall what happened that night. He remembers everything that occurred five minutes prior to the accident but not the accident itself.” Knightly paused, letting this bizarre medical fact sink in. “It is a quirky clinical phenomenon that in my mind, is a vital clue to how the brain forms memories.

“So, what does this tell us?” Knightly stopped pacing, faced his audience, and engaged a young man in the front row. “It tells us, that in order for a memory to be stored so that it can be recalled later, something must occur in the brain that takes several minutes. And, if that process is perturbed, say by head trauma, as in the example I just gave you, then the memory is never formed, and so cannot be retrieved when the patient is asked about the accident.

“So, here is my question for all of you. What happens in the brain in the minutes between experiencing something and laying down that experience as a memory?” He stood at the podium now, his voice resounding with confidence. Roger leaned over to Grace.

”What a pompous ass,” he whispered.

“Shh!” Grace shot back.

Knightly continued his lecture, but Roger’s ‘ mind drifted away. He was thinking about the ‘adventure’ he had planned before embarking on what he considered his ‘adult life.’ In a little over a month, Roger would be setting up his own research lab and his career as an independent scientist would begin. But first, he planned a getaway, an adventure – at least he hoped it would be an adventure.

Reese Knightly, already a tenured professor at York College of Medical Science, was a clinical neurologist, graduate of Harvard Medical School, and a rising star in the field of memory research. His findings had been in the news for the past year after The Science Section of The New York Times featured him in an article about ‘cutting-edge research.’

Roger looked over at Grace, hoping to make a cynical comment, but he found her gaze still fixed on the speaker.

“In the next hour,” Knightly went on, his exuberance growing. “I hope to convince you that what occurs in the brain when we form a memory is that a new protein is synthesized and that this newly synthesized protein forms the basis of that memory.”

Knightly then described experiments in which lab rats were trained to navigate a maze in order to get a food reward. A second group of rats was injected with a drug to block the synthesis of new proteins, before being placed in the same maze.

“When protein synthesis is blocked,” he continued. “Rats are unable to learn the task. These data suggest,” Knightly expounded, extending his right forefinger toward his audience, “that protein synthesis is required to form new memories.” He hesitated, letting the final statement make its impact. “As most of you know, I published these findings almost two years ago in Science and this work was the subject of the Times’ profile last fall,” he added, smugly. “Since then, I have been working diligently to discover what protein is synthesized during learning.” Again Roger turned to Grace to make a comment. But Grace continued to stare at the podium.

For the next 20 minutes, Knightly presented the results of more recent experiments, then concluded his talk, with a nod of his head and an effusive thank you to the audience for their attention. The concluding words were barely out of Knightly’s mouth, when the director of the seminar program rocketed to his feet applauding wildly. He was joined by most of the audience, including Grace.

“Let’s go,” Roger whispered while slowly rising from his seat.

“Roger, you are so rude. What’s your rush?” Grace followed Roger from the hall.

“I’m underwhelmed,” Roger said.

In the lobby, students wished each other elaborate summer goodbyes with dramatic hugs and choruses of, ‘have a good vacation, see you after Labor Day.’ Roger hurried Grace through the crowd out onto the street.

“Roger, could you explain some things about the talk?” Grace said as they entered Washington Square Park.

“Sure,” Roger said, pleased to re-assume the role of teacher. “First, did you understand the design of the experiment?”

“I think so.” They weaved their way through the students and street-people in the park. “First,” Grace said. “He gives rats a maze in which they have a choice of entering a dark or lit box, and they all go into the dark one.”

“Right,” Roger said. “Rats are nocturnal so they will always choose the dark over the light.”

“OK. Then he puts an electric shock on the floor of the dark box. Now, anytime the rats go into the dark side, they get a shock,” Grace continued. “And so, they learn to avoid the dark box and go to into the lit one. Even when he puts food in the dark area the rats still go into the box with a light on.”

“That’s it,” Roger said. “So, the rats have learned a new task.”

“And he calls this ‘the dark-avoidance task’,” Grace said with confidence. “And, he proposes that the way these rats formed that memory is by synthesizing a new protein. And, what’s more,” she continued. “He proves that by showing that rats injected with a drug that blocks protein synthesis don’t learn the new task.”

“Exactly. Now this is the tricky part,” Roger said. “The next thing he does is repeat the experiment, then, when the rats have learned the new task, he takes out the hippocampus…”

“OK,” Grace said. “Let’s stop here. What the fuck is a hippocampus?”

Roger laughed.

“Yeah, you’re right, Grace. He should have explained that. The hippocampus is a group of cells in the temporal lobe of the brain.” Roger pointed to his own temple. “The part of the brain right under the skull, here,” he tapped the spot. “The hippocampus is critical in laying down new memories.”

“How do we know that?” Grace said.

“Good for you,” Roger said, smiling slightly. “Maybe you’ll become a scientist.” They strolled by a row of benches where clusters of park-regulars, were chatting away. “Because, in humans, if the hippocampus is disconnected from the rest of the brain, patients cannot form new memories.”

Grace nodded.

“They still have old memories. They just can’t make new ones.”

“Fascinating,” Grace said.

“Yes, it is. Knightly is trying to see if there are new proteins made in the hippocampus of rats that have learned to avoid the dark.”

“OK – then the second part of his talk is about trying to identify what those proteins are?”

“Right,” Roger said. “And you know the slides he showed with all the grey and black dots?”

Grace nodded.

“Each dot represents an individual protein that came from the hippocampus of an individual rat.”

“And, the spot that was present ‘only’ in rats who learned to love the light, that’s the spot, the protein, he called Photophylin?” Grace said.

“You’ve got it. Good for you.”

“Photophylin, don’t you love the name? Roger.”

“The name’s fine. Although he could have called it fear-of-the-dark protein – what would be the Greek word for that?”

“What’s the difference, Roger?” Grace snapped. “Is that why you’re underwhelmed because of the name he gave the protein?”

“No, no, not at all. But let’s finish with the most important part of the talk. He then takes that protein, Photophylin, and injects it into naïve rats and reports that they learn the maze more quickly – the protein has transferred a memory into other rats.”

“So what bothers you?”

“It’s nothing specific. It’s, I don’t know, it’s ... It’s all too pat.”

“No, you’re too cynical,” Grace said. “I think it’s exciting.”

Roger shrugged. “You know what else? He’s an MD, doing research, right?”

“Oh no, don’t start that again,” Grace said. “We’ve been through this before - people trained as physicians doing research…”

“I know. But hear me out on this. Think about how many times he used ‘I’ as he was speaking. In science, it’s never ‘I’ it’s always ‘we’. Did he train the rats? Did he run the experiments? I’d be willing to bet you a dinner, make that a week of dinners, that he has not handled a rat in years, let alone run a complete experiment. It’s a team that gets this work done, never just one person. ”

“You’re splitting hairs,” Grace shot back. “If he’s a little self-centered, maybe he has a right to be. I think he’s brilliant.”

“And another thing,” Roger said, ‘He said, the data suggest,’ remember? Just in case you do go into science, Gracie, my girl, learn this well – data never suggest – the data is moot; the data is just that, data, numbers. People suggest. We suggest. ‘Based on the current data, we suggest…’ That’s the correct way to present the work.”

“You’re acting superior and being super critical and Knightly doesn’t deserve that,” Grace said.

They walked silently out of the park onto Fifth Avenue.

“OK, then let’s talk about substance,” Roger said a moment later. “He didn’t say how many times he ran the experiment, did he? He didn’t have any statistics and no one challenged him on this. He’s too much of a big shot for someone to ask that question.”

“It’s preliminary data, Roger. Give him a fucking break.” Grace’s voice rose, bordering on anger.

Roger hesitated. “All right. I agree. It’s kind of nit picking. But I still think it’s too simplistic. I just can’t imagine that something as complicated and existential, really, as memory is going to be answered with a single protein.”

Grace didn’t respond immediately. “I agree with you there,” she said after a moment, her voice even. ”But, he is an exciting speaker. Great name, great voice, great delivery...”

“Granted, ” Roger said.

“And he’s good looking, tall, that dark combed back hair – a little too greasy for me, but…”

Roger stopped in the middle of the sidewalk and turned to Grace.

“Grace, I can’t believe this, you? You have a crush on Knightly!”

“I do not,” Grace shot back quickly. They turned east on Fourth Street. “OK, maybe a little,” she muttered. They both laughed.

“Listen, seriously, I do think the research is important,” Roger said. “Think about the people who have memory disorders – like elderly folks with Alzheimer’s, or kids with developmental learning problems – this could be such a boon for them. And, he is a brilliant guy – Harvard and all, no question about that. And he’s ambitious. He’ll probably go far in science.”

“I admire him,” Grace said. “He seems committed to his work.”

“Yes he does. But the key is to see what comes first, the work or Reese Knightly.”

“Here you go again. You know what, Roger? I think you’re jealous. Don’t answer too quickly. Think about it.” Roger walked a few steps before answering.

“I don’t think I’m jealous,” a pause, “OK, maybe a little.” They both laughed. “Frankly, I hope to be as successful as he is. One thing’s for sure though, if you want to get where Knightly is, or the guy you’re working with, Cummings, you have to be passionate about the science and you have to be willing to work your ass off.”

“I had that kind of passion for dance once,” Grace said and did a leap toward the corner.

“Watch that knee!” Roger called out.

“I could take class for hours, then practice for hours more without thinking about time or how exhausted I was,” Grace said and took another leap, landing gingerly on her left leg. “I don’t know if I can do that for something as cerebral as science.

“You know Dave, that grad student in Kopac’s lab? He is the best example of anyone I’ve seen who combines passion with hard work. He never stops, not even for a beer after a seminar.”

“Crazy Dave?” Roger said, shaking his head.

“You might think he’s a little strange,” Grace said. “Look, I know he’s uh --- different, let’s say. But I think he has more potential as a scientist than anyone I’ve met yet – sorry, except for you, of course.”

“Hah – you don’t have to be polite with me, Grace. I don’t know if I have what it takes for this life. I’m really not sure I’m cut out for it.” Roger blurted out this confession but the thought had festered in him for years – beginning when he finished college and then throughout his years in graduate school.

“Well, if dedication is what it takes to make progress in research, Dave is the one who’s going to make it,” Grace said. “Yesterday I got into Cumming’s lab around 7:00 – I just couldn’t sleep knowing I had so much work to do - and I ran into Dave…, on his way out! He brought in a sleeping bag the day before and decided he could get a lot more done if he slept in the lab rather than go home.”

Grace stopped. They had walked about five blocks from the NYU campus.

“Why’d you stop, Grace?” Roger said, his mind still lost in his decision to enter research.

“Because I’m home.” She gestured to the 4 story red brick building in front of them. “Stop walking and say goodnight, Roger.”

Roger laughed. “What are you doing for the rest of the summer?” He moved in for their perfunctory kiss on the cheek.

“Spending time with my folks in The Hamptons,” she said glumly, turning her head to receive his kiss. “What about you?”

“I’m heading north,” he smiled. “Going on an adventure.”

(end chapter three)