Biogenesis

by Tatsuaki Ishiguro

  Dan called the waiter over to ask about the dish. The “Hope Shore sea squirt” was an ascidian species unique to the area. It was hideous to look at, but surprisingly delicious. Dan’s interest was further piqued when the waiter told him that, in the past, when the squirts were caught in abundance, they had been used as a local folk medicine. Due to over-fishing, they were now “the elusive” sea squirts, exceedingly rare. It had been almost three months since the restaurant had last scored a catch, but as luck would have it they had just gotten some that day. At the very least, the dish sounded nutritious. Dan placed an order.

  Linda was growing tearful and peevish from the pain, but her eyes dried as soon as the dish of ugly, misshapen sea squirt was placed before her. It gave off an appetizing aroma, hinting faintly of salt spray and wine. The aroma seemed to work its spell. For the first time in ages Linda picked up her spoon and began eating of her own accord.

  “From what I understand, the lumps on the sea squirt’s body are actually tumors,” explained the waiter. “Don’t worry, though,” he said. “They’re perfectly safe to eat.”

  I guess even sea creatures get tumors, mused Dan. Out of curiosity, he sampled a small piece from the end. The lumps were crunchy and slightly sweet, and despite its appearance the sea squirt was actually quite delicious. It was a bit ghoulish to know that he was eating diseased flesh, but his recent studies had taught him that tumors were not contagious.

  Linda’s cheeks bulged outwards as she continued to cram the food into her mouth. As Dan stared at the ugly lumps, an unusual thought occurred to him. Tumors could be either benign or malignant. According to one of the pathology books he had read, malignant tumors were generally characterized by abnormal, asymmetrical ulcerations. Based on sight alone, the lumps appeared to be clearly malignant. But how could the creature continue to live despite carrying so many malignant growths?

  “Do all of the sea squirts have those lumps?” he asked the waiter.

  “Yes, Hope Shore sea squirts do, though apparently not when they’re still small.”

  “How are they fished?”

  “Dived for, actually. They live on rocks, and the divers peel them off one at a time.”

  That meant they were still alive when gathered. But then, how could one explain the advanced stage of cancer they all seemed to exhibit? Dan was only pulled out of his reverie to discover, to his great surprise, that Linda had polished off her entire plate.

  The three of them left the restaurant and walked back along the coastal road. Moonlight was reflected on the ocean’s dark surface, and the crunch of sand beneath Linda’s small feet reverberated in the air. The image of the misshapen sea squirt remained branded into Dan’s mind. That was when it hit him. Symbiosis. Perhaps the Hope Shore sea squirt maintained a symbiotic relationship with its cancerous cells. He sent Mary and Linda ahead to the hotel and rushed back toward Il Castello.

  “Are there any more of those sea squirts left?” Dan asked. He pushed past the waiter and headed straight to the kitchen. There he found one remaining sea squirt, immersed live in saltwater.

  “Another customer just ordered that. I was about to begin preparing it,” said the chef. “We’re the only place on the island that serves it, and that’s our last one. I’m afraid you’re probably out of luck trying anywhere else.”

  Dan asked the waiter to introduce him to the customer who had ordered the sea squirt. He was an older gentleman in a black suit, sitting alone at a table by the window. Dan began pleading with the man immediately, not even bothering to introduce himself.

  “My daughter has something called neuroblastoma,” he said, “and I need that sea squirt in order to cure her. Please, I’ll pay anything for it. Just name your price.”

  Somewhat taken aback, the older gentleman smiled awkwardly and asked Dan to join him. “By all means, I wouldn’t dream of refusing. But you’ve piqued my curiosity. My name is Tom Anderson. I work as a doctor at the local hospital. If you wouldn’t mind, I’d like to hear more.”

  Surprised to learn that the man was a doctor, Dan launched breathlessly into his theory. “I’m actually a lawyer, not a doctor. I only began studying tumors because of my daughter’s illness. From what I understand, for some reason this species of sea squirt develops multiple tumors all over its body. Judging solely on appearance the tumors appear to be malignant. That means that they should continue to grow and spread unchecked. But all of the growths seem to be about the same in size, almost as if the creature has adapted to accommodate them. What do you think? There must be some mechanism that prevents the tumors from growing larger, right?”

  “My specialty is psychiatry,” said Tom. “I’m afraid you actually know more about cancer than I do. If I recall what I learned about pathology as a student—and that was a long time ago, mind you—the sea squirt’s tumors do indeed appear to be malignant. I’ve been living on this island, and eating this dish, for years, but I can’t honestly say that thought has ever occurred to me before. It’s certainly an interesting observation. Obviously there are differences between a marine creature like the sea squirt and a mammal like us humans … Tell me, what exactly do you plan to do with the sea squirt once you have it?”

  “I thought if I examine the tumorous areas underneath a microscope, I might be able to tell exactly what is going on. If I could just discern how the creature is able to suppress its tumors, maybe it could help me cure my daughter.” Even as he spoke, Dan knew that it sounded like the babbling of a crazy person.

  “I don’t know very much about neuroblastoma, so I really couldn’t say whether or not you might be on to something. But I would like to help. If there’s anything I can do,” the gentleman said, passing Dan his business card, “please don’t hesitate to contact me.”

  In place of his original dinner, Tom Anderson ordered the lamb steak.

  Dan convinced the restaurant staff to give him the live sea squirt, tank and all. Leaving Mary and Linda behind on the island, he returned to Stanford University to visit Professor Dokić. After being made to wait in the secretary’s office for four hours, he was finally shown in. Excited, he explained what he had found, but the professor quickly dismissed the idea, bringing up the same concern that Tom had mentioned.

  “You’ll forgive me for being blunt,” he said, “but this is really just amateurish fantasy. There are crucial, species-specific differences between a sea squirt and a human. You can’t approach them interchangeably. You’re talking about marine life. Even within humans, cancers show very different characteristics depending on where in the body they develop. A cancer developed by a sea squirt really can’t tell us anything about cancer in humans.”

  Dokić cut Dan off before he could ask any more questions. Claiming there was a conference on cancer treatment which he had to attend, he quickly left the room.

  Using the hotel computer, Dan did an online search for “sea squirt specialists.” He discovered a Professor Bertino at Rockefeller University and immediately caught a flight for New York. Despite stopping for just three hours of sleep on an airport bench, it was still too early when he reached the center. Bertino hadn’t yet arrived. Dan waited for some time in the hallway before the bearded professor finally passed by.

  “I really don’t know anything about sea squirt diseases,” the professor said, brushing Dan off as he continued to wherever it was he was going.

  Dan had travelled across the country, from one vast end to the other, only to discover that sea squirts and their illnesses were of little interest to anyone save himself. Staring at the Empire State Building as it towered above him, Dan decided that he was going to have to do this himself.

  Dan returned to the island. Fishing through his coat pockets in search of a cigarette, his hand alighted on a loose business card. It belonged to Tom Anderson, the doctor he had met at Il Castello. According to the card, Tom’s official title was Director General of Westland Hospital. Inquiring with the porter, he learned that Westland Hospital was the only hospital on the isl
and. The man gave him directions. It was located atop a hill, and despite its small size contained a fairly complete outfit of departments. Heading to the director’s office, he found Tom writing behind a wide desk. The doctor set his pen down and gestured for Dan to take a seat on the sofa.

  Tom listened to Dan’s story with some sympathy. He couldn’t hide his doubts, however, as to the chances of Dan’s success. But Tom was a magnanimous man and could see the appeal in Dan’s task. The fact that the hospital was located so far from the beaten track likely also worked in Dan’s favor. There was more room for laxness than on the mainland.

  “Why don’t you research your idea in our pathology lab?” he suggested. “I won’t be able to help you, but there is a technician in the lab, a young woman. She could probably be of assistance.”

  For Dan, who had already resigned himself to confronting the challenge alone, Tom’s proposal came as a greater boon than he could have dared hope for.

  Dan was given a desk in one corner of the relatively small pathology lab. There, Tom introduced him to the lab technician, whose name was Sally. She was tall, slender, and just out of university. Her day-to-day work involved creating microscopic slide specimens from tissue samples taken from patients. Although she had been working at the hospital for less than a year, she had graduated with a degree in pharmacology and her medical knowledge was well in advance of what Dan possessed. Moreover, she was much easier to talk to than the renowned professors Dan had encountered so far. She answered each of his questions meticulously, using simple, easy-to-understand language.

  As a first step, Dan wanted to inspect the sea squirt tumors underneath a microscope, just as with the cells he had seen in the pathology textbook illustrations. Sally sliced a thin section of the tumorous tissue to create a specimen, staining it over a two-day period using a hematoxylin and eosin solution.

  “I guess even for a sea squirt the cells are basically the same,” Sally said as she inspected the slide underneath a microscope. “I wasn’t sure if it would work, but I was able to stain the cells in the same way as human ones.”

  She traded seats with Dan. As he peered into the lens, a familiar image greeted him, resembling the histological micrographs he had seen in the textbooks. The tissue was stained purple overall, while the cell nuclei were stained a deeper shade. Unfortunately, Dan was not able to make a fundamental distinction between benign and malignant cells. Sally too, though capable of staining the tissue, was not, herself, a doctor. Her expertise fell short of pathological diagnosis.

  There was a young pathologist who came from the mainland once per week. He was in the next day, and Dan tried asking him. The doctor only gave the slide a quick glance before replying that he really didn’t know anything about sea squirts.

  “But is there anything about them that resembles human cancer cells?”

  “Resembles in what way?” he asked, clearly not interested. “I really don’t understand your criterion here.” Once his own work was finished, the doctor quickly left the lab. Dan felt the bile rise in his throat. The world was full of doctors and researchers who, like the pathologist, refused to venture an opinion outside their own field of expertise.

  As he continued to stare through the microscope, Dan recalled his time as a poor undergrad. He had once struggled with a difficult philosophy book, reading the same passages over and over again. Young and impoverished, even his use of heat had to be rationed. He couldn’t afford supplementary texts and reference books. All he could do was pore stubbornly over the incomprehensible passages. He read the book so many times that, even if he didn’t understand their meaning, he had the words nearly memorized. Finally, one day—why exactly, even Dan himself did not understand—a single sentence, which had heretofore remained a mystery, began to suddenly make sense. And then, like a tangled knot when the right string has been pulled, the remainder of the text soon unraveled.

  Then, as now, Dan decided that although he couldn’t understand what he was seeing, what he could do was to continue to see it. Day after day and night after night, Dan stared transfixed by the specimen that Sally had prepared for him. He was a man possessed, pausing only to eat and to take short naps on the lab’s sofa. Despite his persistence, however, he could find nothing in the specimen other than a simple, dumb pattern, a senseless arrangement of points and curves. Dan began to feel as if he was losing focus, and it took all he had to keep his mind from wandering off.

  That night he returned to the hotel to find Linda already in bed.

  “She just cried herself to sleep from the pain,” said Mary. Dan stroked Linda’s cheek softly. There were still streaks on her face, from where the tears had dried. “Haven’t you taken this research nonsense far enough?” his wife said. “It’s time we went back. Let them treat Linda at a hospital back home.”

  “Why? What exactly have any of those doctors and researchers done for us so far? All they’ve done is tell us it’s hopeless.”

  “At least they’re specialists,” said Mary. Her face was as wan and tired as bone. “They know more about it than you. You’ve never so much as given an injection. You’re not a doctor, Dan, and Linda isn’t your guinea pig.”

  Dan left the hotel. From that point on he ceased to set foot outside the lab, staring for hours on end into the microscope’s lens. His eyes grew bloodshot, and the white walls began to appear pink. This continued for three days, until the different patterns, in their different places, began to burn into his brain. And then, something inexplicable happened. Someway, somehow, Dan found himself able to distinguish between the cancerous and healthy cells. Passing the microscope to Sally, he explained the difference in his own words.

  “See how the cell nuclei are rounded? I think the gravelly shapes are malignant cells, while the more rounded ones are still healthy.”

  Pulling down a pathology textbook from the bookshelf, they turned to the section on malignant tumors. The pathological term for what Dan had described as “gravelly” was “irregular.” Now that the book had corroborated his observation, he began to discern the difference in all of the cells he looked at. If he was able to develop his own method for distinguishing between malignant and benign cells, and that method held up, then wasn’t that good enough? Dan grew confident once more. He would be his own teacher. That night he returned to the hotel—the first time in days—and explained to Mary what he had found. He was animated as he spoke, and though Mary felt more weary than hopeful, as she listened she decided that she might as well let him have his way in this, let it lead where it may.

  Dan was ready to proceed to the next step. What allowed the sea squirt to suppress tumor growth, and how could Dan go about identifying that mechanism? Time was pressing. He turned to Sally for advice.

  “It sounds like the kind of research done on anti-cancer drugs to see how they affect cells,” she said. “You could probably follow the same method.”

  Reaching behind a row of tightly packed files in one of her desk drawers, she pulled out a bound copy of her own master’s thesis and handed it to Dan. The paper dealt with the effect of anti-cancer drugs when applied to cultivated cancer cells, and included a detailed, step-by-step description of the research methods that Sally had carried out as a graduate student. Unfortunately, the experiments needed to be carried out on cultivated test tube cells and the pathology lab did not contain the necessary equipment.

  Together, Dan and Sally scoured the hospital in search of culturing equipment. The only apparatus they found was in the hospital’s bacteria lab, for culturing germs from phlegm and blood, and according to Sally it was unsuitable for cells. There was a medical equipment wholesaler who regularly visited the hospital, and Dan asked him for an estimate. He was told that cell culture equipment would run at least $30,000. Dan donated the money, paying it directly to the hospital’s administrative office, and received permission from Tom Anderson to set up one of the extra storage rooms as a cell lab.

  The primary equipment consisted of a clean bench for aseptic
processing and an artificial incubator to maintain humidity and temperature. After Sally taught him about the required steps, Dan sliced off a thin sample from one of the sea squirt’s tumors and began to cultivate its cells. He placed the tumor section in a Petri dish full of culturing solution. After two or three days cells began to seep from the sample and take root on the base of the dish. He removed the tumor sample and added a proteolytic enzyme solution to separate the cells so that they could be transferred to new Petri dishes. Repeating these steps he was able to proliferate the cells, which grew in polygonal patches.

  In the meantime he cut off a wedge-shaped slice of healthy tissue from the sea squirt’s smooth portion, mashed it, and then strained it through a small-aperture filter to create a clear fluid. If Dan’s thinking was correct, and the sea squirt created a substance that allowed it to suppress its own tumors, then there was likely some property in the normal tissue surrounding the tumors that was hampering their growth. With Sally supervising, Dan added the clear fluid to the red culturing solution of the Petri dishes that contained the tumor cells. He then placed these dishes back in the incubator. If everything went as expected, in a few days they would be able to see a change in tumor cell development.

  “Fingers crossed,” said Sally.

  Unfortunately, no change appeared in the cells. Neither the next day, nor the day after that.

  Dan repeated the experiment several times. The results, however, were the same, and he was left feeling exhausted and bitter as he trudged home to the hotel at night. Mary began to fear for her husband’s mental health.