“Maybe they were right,” said Dan, sounding uncharacteristically discouraged. “Maybe this has all been some fool’s errand, an amateur fantasy.” If Mary was worried before, this new change in Dan truly alarmed her. She was afraid the despair might drive him to suicide.
“At least you tried,” she said. “Maybe it’s time to give up.”
“Maybe,” said Dan, the strength all but gone from his voice. “Just, let me try a little longer.”
Dan repeated the experiment several more times, changing the amount of fluid he added to each dish. He was creating nearly thirty cultures every day. One day, while inspecting the dishes under the microscope as usual, he froze. At first he suspected his eyes were playing tricks on him. The dishes were arranged in order by number. The first several he examined remained unchanged, but partway through, and for every dish thereafter, the cancer cells had floated to the surface, dead. Sally had told him that if the solution were contaminated by bacteria then the cells would die. Suspecting this to be the case, Dan waited for Sally to arrive.
“No …” said Sally, checking the dishes. “If the samples were contaminated the solution would be cloudy. These all look fine.”
He had used the same container of culturing solution for all of the Petri dishes and taken the cells from a single culture he had cultivated earlier. The conditions seemed the same. But there had to be some difference to explain why only a portion of the cells had died.
“I just thought of something,” said Sally, suddenly, over lunch. “The fluid you were using ran out, and you started using the fluid from a new test tube, didn’t you? Maybe it’s because the tissue you used to create the two test tubes were taken from different parts of the sea squirt.”
Dan fetched the sea squirt from the refrigerator to take a look. Although he had been using only a small slice at a time, barely any of the creature now remained. Since the samples he had been taking were of healthy, normal tissue, there was mostly only bumpy, tumorous tissue left. The sea squirt’s body appeared uniform, but perhaps there were some morphological distinctions. Perhaps only certain portions created the tumor-suppressing substance.
A week earlier Dan had managed to obtain a new sea squirt specimen. He now began a fresh set of experiments. This time he carefully recorded which portion of the sea squirt he had obtained his samples from, hoping to discover the sections that exhibited the anti-carcinogenic properties. He split the sea squirt into zones and even assigned them addresses so that there could be no mistake, but regardless of which portion he used, this time none of the batches exhibited any effect. He continued his experiments until only tumorous tissue remained.
“I don’t understand.”
For hours, Dan mulled over the contradictory results. It wasn’t until he inspected the two sea squirt samples, in search of some clue, that he finally noticed a difference. A cut had been made in the tumorous tissue of the first sample.
When I cut the samples from the first sea squirt, thought Dan, I hadn’t been as careful. There was nothing but tumor by the end. What if I had accidentally cut off a piece of non-healthy tissue as well …
Was it possible that the fluid in the effective test tube had been taken not from healthy but from tumorous tissue? Until now Dan had been certain that whatever substance it was that suppressed tumor growth had to be secreted by the healthy, surrounding tissue. But could it be that it was the tumorous tissue, itself, that was producing the substance?
If there was something in the tumors themselves that suppressed growth, it would also help explain why all of the tumors were uniform in size. Dan immediately began taking samples from different portions of the tumors, adding the fluids he prepared to new Petri dishes. The next day, the cancer cells in each and every one of these dishes had floated to the surface, dead.
“This is big,” said Sally, peering at the Petri dishes in excitement.
“But what should I do next?”
“The next step is to isolate the substance and refine it.”
“How do I do that?”
“That kind of research is a lot more difficult than what we’ve been doing so far. I’ve never done it, either. I know someone who has, but apparently it took years.”
Dan’s elation quickly faded to shock.
“I could give him a call, at least.”
Sally’s friend worked in drug development for a large pharmaceutical company. After Dan asked her to call him, she said, “Chances are it’s a protein. It could also be some kind of fat. There are a lot of specific methods for analysis and refinement for each, and it involves trial and error. It’s not really something a person could teach himself.”
The news was disheartening. Worse still, according to Sally’s friend, the process would require a very large number of sea squirt specimens and a significant amount of time.
Dan borrowed a technical book on protein refinement from the library. The book listed complex steps, compared to which cultivating cells was a cakewalk. It was immediately apparent to Dan how time-consuming it would all be. Furthermore, the analysis would involve expensive pieces of equipment that cost several hundreds of thousands of dollars. There was no way that he would be able to purchase all of the equipment on his own.
Dan began calling universities and companies in search of somewhere that might assist him. While most of the organizations he contacted initially expressed interest, once it came down to actually helping out none of them seemed particularly inclined. One professor he contacted seemed to suspect that Dan was a megalomaniac. In short, no one was willing to place any trust in an amateur researcher without a single paper to back up his claim. And according to Sally, should he write a paper, even if everything went smoothly, it would take at least two to three months between sending it out and publication.
At a loss, Dan turned to Tom Anderson for advice and asked him, “I don’t know what substance it is that has the effect, but couldn’t we try giving Linda an injection of the extract?”
In light of the findings, Tom could understand where Dan was coming from. But he forbade an injection in the strongest of terms. “In its impure state, the risk of a sudden allergic reaction would be extremely high. It’s far too dangerous.”
Returning to the hotel, where he and his family were staying long-term, Dan found Linda fast asleep under the effects of the narcotics that Tom had prescribed for her. Her face was covered in wrinkles that belied her age. Come dawn, the medicine would wear off and Linda would wake screaming in pain, at which point they would medicate her once again. It took some time before the painkillers kicked in, but once they did she would fall back asleep, her face peaceful once more. Dan’s progress so far had given him some measure of confidence in his research, but he feared that it would be too little, too late, for saving Linda.
Writing a paper was out of the question. But perhaps he could present his findings at some sort of conference? While he dawdled, however, Linda might run out of time. Dan began to wonder if it had all been a waste of effort. What was the point of saving anybody else, if he couldn’t save Linda? Having come this far, he decided that his only recourse was to isolate and analyze the substance on his own, regardless of how certain defeat seemed.
First he had to obtain more sea squirt specimens. After asking at Il Castello, he began visiting local fishermen. None whom Dan spoke with were willing to take on his commission. Each sea squirt had to be dived for individually, and there just wasn’t enough profit in going after them exclusively. When he visited a fisherman of Japanese descent, however, as luck would have it one of his friends had just married a young Japanese woman who knew about dive fishing. He suggested that Dan try her, telling him where to find her. Reaching the address, he was greeted by a young woman named Mariko. At first Dan thought there must have been some mistake. Surely such a petite young lady couldn’t actually be a diver. But Mariko came from a long line of ama, traditional female free divers, and had years of experience in diving for abalone. She had stopped working as a diver after
marrying and moving to the island, but once Dan explained the circumstances she agreed to give it a try. The waters in the area weren’t very deep, and she could go out on the boat with her husband to see what she could find.
To Dan’s surprise, she came to the lab the very next day with a handful of Hope Shore sea squirts. Up until then the catch had been one sea squirt every few months, but Mariko was able to gather at least two each day. Within a few days, the lab’s small tank was practically overflowing with them.
Now that the problem of collecting specimens was solved, Dan attacked his research with fresh zeal. Following the steps listed in the book he had found, Dan began by testing the substance for stability, in hopes of ascertaining at least its type. First, he applied heat to the mashed tissue samples before adding them to the Petri dishes. This treated fluid still had the desired effect, inhibiting the growth of cancer cells. This meant that the substance he was looking for was physically durable. Furthermore, the effect remained even after treating the samples with acids and alkalis, which meant that the substance was also resistant to chemical change. All in all it appeared to be a relatively stable substance. The results were promising, as they suggested a favorable substance for refining.
Unfortunately, Dan also received bad news around this time. Linda’s CT scan showed that the number of metastatic growths in her liver had increased. According to Tom she likely had less than three months to live, and they were forced to up her narcotics dosage. On the way home from her examination, Linda visited her father’s lab for the first time ever. Held in her mother’s arms, she stared with saucer eyes at the tank full of sea squirts.
Mariko, who happened to be visiting the lab at just that moment with her new catch, asked them if they knew that people ate fish raw in Japan. Picking up one of the smaller sea squirts, she placed it in her mouth and ate it whole, smacking her lips.
“I want to try one,” said Linda, surprising everyone in the room. The tumor had robbed Linda of nutrition, leaving her frail and emaciated, and it was the first time in a while that she had shown any interest in eating anything at all. Mary was worried about food poisoning and thought it was a bad idea, but Dan shushed her, slicing one of the sea squirts and feeding it to Linda raw. The sliced sea squirt was cold, with a smooth texture, and Linda swallowed it easily.
“You know, since the active substance appears to be chemically stable, it might be effective even after digestion,” Sally remarked. “Maybe you should keep feeding them raw to her.”
According to Chinese medicine, the appropriate foods are as good as a doctor, a concept that interested Sally. Anyone with even a basic grounding in Western medicine knows how shaky and empty such a belief is. For better or for worse, however, neither Dan nor Sally possessed that in-depth an understanding of medicine. In particular, Dan lacked the caution and timidity that would have kept an accomplished specialist from putting an unproven theory into practice. If anything, he was motivated by the fear that, at his current pace, any success his experiments met with would come far too late.
Beginning the next day, all of the live sea squirts that Mariko collected were delivered straight to Linda. Surprisingly, Linda ate each and every one, growing neither tired nor disgusted with the food.
The body knows what it wants, said Mariko. That must be what makes them so delicious for her. She extended the time she spent diving, collecting even more sea squirts each day than she had before.
Perhaps it was only due to the added nutrition, but after a week of eating the sea squirts Linda began to put meat back on her bones, and a fullness returned to her cheeks. Mary soon noticed an even bigger change. She was able to reduce the amount of painkillers that she gave to Linda.
Mary informed Dan, who went to speak with Tom Anderson immediately.
“There’s no way a change could happen in only a week,” cautioned Tom. Nevertheless, he agreed to run tests to check the size of Linda’s tumor. What he saw when he got the CT scan back left him speechless. Linda’s tumor had shrunk to half its former size.
“Just imagine if we could isolate this substance,” he said. Visiting Dan’s lab for the first time in weeks, he peered into the tank in wonder. Although he had been eating the Hope Shore sea squirt for many years, Tom had never seen so many in one place at one time. He then began to grow concerned and asked, “Won’t they go extinct if you keep collecting them at this rate? Maybe they could be farmed …”
“No one’s managed to so far,” Dan said.
“If you published your findings, I’m sure there would be researchers interested in refining and synthesizing the substance. If you could just wait for pharmaceutical development—”
“If I wait, then Linda will die,” Dan interrupted, and Tom had no reply.
The Hope Shore sea squirt was rare to begin with, and Dan knew that using them up at the current rate wasn’t sustainable. There were other children, all across the world, suffering from neuroblastoma. His first priority should have been to identify the active substance in the sea squirt. All he could concentrate on, however, was saving Linda.
“What if I freeze some of the specimens, so that they can be analyzed later?”
Tom nodded. Having remained largely a bystander to Dan’s experiments, he felt that he had no choice but to acquiesce.
Dan’s main worry was which would disappear first, the sea squirts or Linda’s tumor. Although Mariko dove for longer and longer periods each day, just as Tom feared, the number of sea squirts she collected actually decreased. Linda ravenously devoured all of the sea squirts that she was given. After four weeks of eating them raw, she no longer required painkillers.
“This is incredible.”
Tom stared in wonder at Linda’s biweekly CT scan. The tumor had continued to grow smaller with each exam, from one third, to one fourth, and then to one fifth. Now, after two months of eating the sea squirts, the tumor was so small that it couldn’t be seen.
“Can I go back to school?” Linda asked one day. She was staring out the hotel window at the local children. Mary began formalities, and the next day Linda was enrolled at the island’s elementary school. By this point, Mariko’s catch had dwindled to about one squirt every three days. Soon it was just one per week, and then, even after two weeks, she had found none.
When a week passed, and then two, with no delivery from Mariko, Dan and Mary could only hold their breath and pray. But even after a month without sea squirts, Linda’s tumor did not reappear.
Tom created a series of slides from Linda’s CT scans, which he packed together to bring with him to a conference in Pittsburgh. “Just wait until they see this,” he told Dan.
He arrived at the conference site full of enthusiasm. His presentation, however, was lumped together with minor papers on the anti-carcinogenic properties of mushrooms, green tea, and such. He also made the mistake of admitting up front that his specialization was in psychiatry. His paper was greeted with a lukewarm response. Those in attendance seemed disinclined to place much stock in an elderly physician bearing suspicious results. When the chair asked what exactly was responsible for the effect, Tom could only answer that it appeared to be an extremely stable substance. The chair went so far as to suggest that the tumor may have resolved itself naturally, as cases of patients recovering spontaneously from neuroblastoma, even after metastasis, were rare but not entirely unheard of.
“It’s not possible,” insisted Tom. “The patient’s recovery corresponds precisely with the period when she began eating the sea squirts.” Unfortunately, this wasn’t enough to back up his claims.
Tom had arrived at the conference certain that his presentation would knock the collective socks off of those in attendance. On calmer reflection, he realized that his report consisted of only a single case of anecdotal evidence. No one, not even the odd pharmaceutical representative, approached him afterward to hear more. Though disappointed, Tom returned to the island determined that Westland Hospital would employ its own researcher if that was what it took to
isolate the groundbreaking substance. When he peeked inside the lab freezer, however, he made a terrible discovery. Not a single specimen had been saved for analysis. Dan had broken his promise and used up all of the sea squirts to cure his daughter, even those that had been set aside.
The next day, Tom confronted Dan, and Dan admitted what he had done.
“I tried to farm them, but it didn’t work.”
Mariko, meanwhile, unable to find any more Hope Shore sea squirts, had given up on diving.
Two years later, a certain article was published in the journal Science that sent ripples throughout the medical community. A substance had been discovered in shark cartilage that inhibited tumor angiogenesis and displayed anti-carcinogenic potential. Previous anti-cancer drugs had been extracted entirely from land-dwelling organisms such as plants and bacteria. It was the first time that the scientific world had turned its attention to marine life, instead. While the drug did not have as significant an effect in patients during clinical trials as had been hoped for, it did prove a great impetus. Scientists boarded this new bandwagon in droves, eager to discover the hidden potential of marine life through their own research. Five years later, an article was published in Nature detailing a substance with anti-carcinogenic properties that had been discovered in a species of sea squirt found in the Caribbean Sea. Attention soon turned to the biological functions of the sea squirt, such as its ability to concentrate marine bacteria and minerals. While reviewing past articles and papers in preparation for a conference, the author, John Cooper, stumbled across the abstract for Tom Anderson’s paper. He telephoned the hospital in an attempt to contact Tom, reaching instead the new director general, successor to Tom’s post.
John visited the island. There he met Sally, who still worked at the hospital and who told him the story of the Hope Shore sea squirt. Tom had passed away from colon cancer five years after the conference in Pittsburgh, and Sally had something interesting to say about the cause of death. In accordance with Tom’s wishes an autopsy had been performed on his body. Sally had prepared the pathological specimens. The cancer had not been limited to a single tumor. Instead, it had spread throughout his colon, including many growths that were still in a precancerous state. The pathological diagnosis was hereditary colorectal polyposis—a genetically inherited disease that usually surfaced in patients while they were still relatively young. The late onset in Tom’s case remained a mystery.
Biogenesis Page 18
