godfather of surgery

Chapter 1392 New Chemical Substances

Chapter 1392 New Chemical Substances
Everyone got on the bus, and after a brief silence...

Zaxi said, "What if Professor Zhou synthesized those organophosphorus compounds himself? Then they would only exist in Professor Zhou's laboratory, and the murderer might have obtained them from the laboratory."

Yang Ping looked at him and smiled, but the smile was short and fleeting.

“You’re starting to act like a detective,” Yang Ping said, “but you’ve missed a crucial question.”

Zaxi asked, "What?"

Yang Ping said, "If Professor Zhou synthesized those organophosphorus compounds himself, how did the murderer know about their existence? How did the murderer obtain them? And how did the murderer know which books Professor Zhou would consult?"

"The answers to these questions point in one direction: the murderer must be someone close to Professor Zhou, someone who could enter his laboratory, understand his research, and know his reading habits. Moreover, this person must know what books are in Professor Zhou's study, which books he would read, and have access to these books."

Zaxi's heart raced: "You mean Li Xiong?"

Yang Ping shook his head: "I didn't say who it was. I was just listing the criteria. There may be more than one person who meets these criteria."

A buzzing sound filled the room. Li Xiong? That seemingly gentle and refined young teacher? He had followed Professor Zhou for twelve years, gaining access to his lab, understanding his research, and knowing his reading habits. Moreover, he had helped Professor Zhou buy toluene; those two bottles of toluene were likely used to dissolve organophosphates.

But what about the motive? What was Li Xiong's motive?
Officer Yu, sitting in the passenger seat, turned his head and said, “I need to investigate a few things when I get back. First, investigate Chen Wei’s Weide Pharmaceutical Company to see what organophosphate products they produce and whether any of them are related to organophosphate poisoning. Second, check the lab logbook in Professor Zhou’s lab to see if we can find that ‘attachment.’ Third, investigate Li Xiong’s background—his family, financial situation, and interpersonal relationships. Fourth, investigate the details of Professor Zhou’s threatening letter to see if we can find any more clues.”

Back at the Sanbo Research Institute, Yang Ping and Zaxi sat down. Yang Ping said, "Zaxi, do you know what the biggest commonality is between clinical diagnosis and solving cases?"

Zaxi thought for a moment and said, "Is it all about finding answers based on clues?"

Yang Ping shook his head: "Yes, but there's another similarity: we often use the process of elimination. You eliminate all the impossible ones, and the one that remains, no matter how unbelievable, is very likely the answer. But before eliminating, you have to list all the possibilities. Missing one possibility might mean missing the truth."

He got out of the car, took a couple of steps, then turned back and said, "Don't tell anyone about what happened today, including the other trainees."

Tashi nodded.

That evening, Zaxi finally managed to find some free time and began checking the product catalog of Weide Pharmaceutical Company. The company's website was very professional, with clear product categorization, including chiral ligands, chiral catalysts, and chiral intermediates. In the chiral ligand catalog, he saw more than a dozen organophosphorus compounds, all with very long names like "(R)-BINAP," "(S)-Segphos," and "DIPAMP," none of which he recognized.

He opened PubMed and began searching for toxicity data on these organophosphorus compounds. Most of them lacked clear toxicity data, and only a few papers mentioned the potential neurotoxicity of their synthetic intermediates. He searched for two hours but found nothing useful.

Then he began checking Professor Zhou's lab logbook. This was even more difficult; he didn't have the physical samples and had to rely on his memory. He remembered that the logbook stated, "Experimental objective: Synthesize a novel chiral organophosphorus ligand. References: Self-designed." If this was a novel compound, it might not have any toxicity data, or even be listed in any toxicology screening database.

He considered a possibility: if the perpetrator used this new type of organophosphorus compound, it wouldn't be detected by conventional toxicology screenings. This is why Dr. Yuan and his team haven't received any results yet.

He jotted down the idea and then began researching Li Xiong's background. This was relatively easy; Nandu University's official website had faculty information. Li Xiong, male, born in 1988, lecturer, master's supervisor. Research direction: asymmetric catalytic synthesis. He has led one National Natural Science Foundation of China (NSFC) Youth Project and published 12 SCI papers. Family situation: married, with one five-year-old son. No further information was available.

He spent an entire afternoon researching, accumulating a table full of documents, but few of them were truly valuable clues.

The surgery was completed the next morning, and at noon Zaxi went to report to Yang Ping. Yang Ping was in his office reading an English paper, with a cup of tea that had gone cold on his desk.

Zaxi briefly reported the information he had found that afternoon. After listening, Yang Ping was silent for a while, then said, "You missed something crucial."

Zaxi was taken aback: "What?"

Yang Ping asked, "Did you check the contents of Professor Zhou's threatening letter?"

Zaxi lowered his head: "Not yet."

Yang Ping didn't criticize him. Instead, he took a piece of paper from his drawer and handed it to him. Zaxi took it and saw it was a photocopy of the threatening letter. The letter was printed on ordinary A4 paper, in standard Song typeface, and the content was very short:

"Professor Zhou, do you think no one knows about what happened thirty years ago? The truth cannot be covered up forever, and your time is running out."

Zaxi looked at it twice but couldn't see anything special. He looked up at Yang Ping.

Yang Ping asked, "What do you think this letter means?"

Zaxi thought for a moment and said, "The person who wrote the letter knows about something that happened to Professor Zhou thirty years ago. If that thing is exposed, it will be very detrimental to Professor Zhou."

Yang Ping nodded: "Yes, what is it?"

Zaxi shook his head.

Yang Ping said, "Officer Yu found out that thirty years ago, Professor Zhou participated in a national-level scientific research project called 'Development of New High-Efficiency Organophosphorus Insecticides.' This project was part of the national 'Seventh Five-Year Plan' for key research projects, and Professor Zhou was one of the main participants. The project ultimately failed and was discontinued midway. However, according to insiders, the reason for the project's discontinuation was not due to technical problems, but because one of the compounds was too toxic and unsuitable for use as a pesticide."

He paused, looking at Zaxi: "Moreover, the toxicity data of that compound was concealed by the project team. The expert in charge of the toxicity assessment deliberately underestimated the toxicity of the compound in the report, which allowed the project to be approved. It was only after this was discovered that the project was stopped."

Zaxi's mouth dropped open: "So, the threatening letter is about this?"

Yang Ping said, "It's possible! But Officer Yu is still investigating the specific details. What we know for now is that the expert in charge of the toxicity assessment back then was Professor Zhou himself."

Zaxi's mind went blank for a moment. Professor Zhou had concealed the toxicity data? Would a scientist known for his rigor do such a thing?

Yang Ping seemed to see through his thoughts and said, "Don't rush to conclusions. The background of what happened thirty years ago is different from now. Research management and ethical standards were not as strict back then. Moreover, there is no conclusive evidence yet to prove whether this matter is true. But one thing is certain: someone used this matter to threaten Professor Zhou."

Zaxi thought for a moment, then asked a question he had always wanted to ask: "Professor Yang, who do you think the murderer is?"

Yang Ping looked at him and said, "I don't know either. This matter shouldn't have distracted you; it's just meddling. But it's perfect. I think involving you in the whole process can help you build curiosity, patience, and a self-driven drive to seek the truth."

"What you need to do now is not to guess who the murderer is, but to do your job well. Check the literature, look for clues, and build a chain of evidence. Take it one step at a time. Solving a case is like treating an illness; you can't rush it."

Tashi nodded.

Stepping out of the office, Zaxi stood in the corridor and took a deep breath.

He took out his notebook and wrote a line at the top of the latest page: Chain of evidence—source, route, dosage, and culprit of organophosphates.

Then he drew a big question mark below.

He closed his laptop and headed back to his dorm; he had a lot to do tomorrow.

On Sunday morning, Zaxi was awakened by his phone vibrating. He groggily reached for his phone; the screen showed Professor Yang's name, and the time was only 6:15. He immediately snapped awake and quickly answered; he had gotten up a little late that day.

"Come to the research institute, to the small conference room. Officer Yu and the others have already arrived." Yang Ping's voice was calm, but Zaxi sensed an unusual sense of urgency.

So early?
Zaxi spent ten minutes washing up and getting dressed, then jogged to the research institute. The small conference room was on the third floor of the institute. The door was half open, and four people were already sitting inside: Yang Ping, Officer Yu, Dr. Yuan, and a middle-aged man whom Zaxi had never seen before. He was wearing a dark blue jacket, had some gray hair, and a serious expression.

"Zaxi, sit down." Yang Ping pointed to the chair next to him. "This is Director Zhang from the Provincial Department's Toxicology Laboratory. The preliminary results of the toxicology screening came out last night, and Director Zhang couldn't wait to come and interpret them for us in person."

Zaxi's heart tightened. The toxicology screening results were in? He quickly sat down and took out his notebook.

A thick report lay spread out before Director Zhang, his expression grave, as if he were carefully choosing his words. He glanced at Yang Ping, then at Officer Yu, before speaking in a low, slow voice: "Professor Yang, Officer Yu, in my more than twenty years of service, this is the first time I've encountered a case like this." He opened the report to the first page, pointing to the data: "We conducted a comprehensive toxicology screening of Professor Zhou's blood, urine, stomach contents, and liver tissue. Common toxins—organophosphates, carbamates, opioids, benzodiazepines, barbiturates, alcohol, cyanide, heavy metals—all were negative."

All negative? How do you explain the constricted pupils? How do you explain the pigmentation on the fingertips? How do you explain the organophosphate residue on the book pages?

Director Zhang continued, "However, we detected an unknown organic compound in the blood and liver tissue. Its chromatographic retention time and mass spectrometry fragmentation pattern are not in any of our databases. In other words, this is not a known common poison."

Yang Ping asked, "Can you determine its structure?"

Director Zhang shook his head: "Not for now. We've done high-resolution mass spectrometry and confirmed that its molecular formula is CHNOP, with a molecular weight of approximately 360. However, there are dozens of possible structures corresponding to this molecular formula. To determine which one it is, we need to do nuclear magnetic resonance analysis. Moreover..." He paused, "to isolate enough pure sample for NMR analysis, we need a large amount of sample, and the amount of sample we currently have is far from sufficient."

Yang Ping narrowed his eyes slightly: "CHNOP, is there anything special about this molecular formula?"

Director Zhang said, “We checked the Chemical Abstracts database, and this molecular formula has only appeared twice in the literature. Once was in a Japanese patent in 1987, which described a new type of organophosphorus insecticide; the other time was in an internal domestic report in 1992, titled…” He turned to a page of the report and read it aloud, “Synthesis and Toxicological Study of a New High-Efficiency Organophosphorus Insecticide A-8, signed by the Department of Chemistry of Nandu University and the Pesticide Research Institute of the Ministry of Chemical Industry. First author—Zhou Huaijin.”

"However, we have no idea about the clinical manifestations of this poison, so we can only trouble you."

The meeting room was so quiet that you could hear the ticking of the clock on the wall.

Zaxi's mind went blank for a moment. 1987, 1992, Zhou Huaijin, organophosphate pesticides—these fragments spun rapidly in his mind, piecing together a picture he dared not imagine.

Yang Ping's voice broke the silence: "You mean, this compound might be an organophosphate pesticide that Professor Zhou helped develop thirty years ago?"

Director Zhang nodded: "That's possible, but we can't be sure yet. To determine the structure, we need more samples. And the samples can only be found in Professor Zhou's internal tissues; there may still be residues in his liver, kidneys, and adipose tissue. We need to do more refined extraction and purification, which will take at least two weeks."

Officer Yu asked, "If this compound is the same insecticide from thirty years ago, how toxic is it?"

Director Zhang paused for a few seconds, then said, “According to that internal report from 1992, the oral LD50 of this compound, codenamed A-8, is 0.8 mg per kilogram of body weight. Based on this value, a 60-kilogram adult would only need 48 mg to be fatal. Moreover…” He emphasized, “The report specifically mentioned that A-8 is also highly toxic through the skin. Its dermal LD50 is 2.5 mg per kilogram of body weight. That is to say, through skin absorption, about 150 mg can be fatal. Furthermore, A-8 is highly soluble in organic solvents such as toluene and xylene, and the dermal absorption rate will be greatly increased after it is made into a solution.”

Zaxi's hands were trembling as he scribbled rapidly in his notebook: A-8, organophosphate insecticide, LD50: 0.8 mg/kg orally, 2.5 mg/kg dermally. He looked up and saw that Yang Ping's expression remained unchanged, but he knew Yang Ping's mind was racing.

Yang Ping asked a question that no one had expected: "Director Zhang, did that internal report from 1992 mention the chronic toxicity of A-8? For example, the effects of long-term low-dose exposure?"

Director Zhang flipped through the report and found a page: "Yes! The report included a 90-day subchronic toxicity experiment using rats. The results showed that rats exposed to low doses of A-8 over a long period experienced weight loss, decreased appetite, reduced activity, rough fur, and grayish-brown pigmentation on the toes and nose. Blood tests showed a continuous decrease in cholinesterase activity, but not necessarily to lethal levels. Pathological examination revealed mild degeneration of hepatocytes and focal necrosis of myocardial fibers."

After he finished reading, he looked up at Yang Ping and said, "Professor Yang, these behaviors are highly consistent with Professor Zhou's situation."

A thought flashed through Zaxi's mind: weight loss, pigmentation on the fingertips, and a continuous drop in cholinesterase levels—Professor Zhou had all of these. His medical report from four months ago showed a cholinesterase level of 2100, already half the lower limit of normal. Moreover, there was indeed grayish-brown pigmentation on his fingertips.

"However, we know nothing about how to link the toxicology and clinical manifestations of this new type of poison using pathological and pathophysiological knowledge."

Yang Ping remained silent for a long time before speaking softly: "Professor Zhou had been in long-term contact with this compound for at least six months before his death. It wasn't a one-time poisoning; it was a chronic, continuous exposure."

Director Zhang nodded: "Yes! Moreover, if it is ultimately confirmed that what was detected in his body was A-8, then his cause of death will be very clear: an acute exacerbation on the basis of chronic poisoning. It is possible that the amount of exposure was particularly large at one time, exceeding the body's compensatory capacity, leading to acute cholinergic crisis and respiratory depression."

"Professor Yang, thank you so much. If you hadn't reminded us, we would never have thought of it that way. Moreover, it's clear that our knowledge is insufficient in the face of such highly sophisticated crimes." Director Zhang turned to look at Dr. Yuan, who nodded in agreement.

Yang Ping pondered for a moment and said:
"The current situation is this: a rare organophosphorus compound, with the molecular formula CHNOP, was detected in Professor Zhou's body. It is very likely the insecticide codenamed A-8 that he helped develop thirty years ago. This compound has high dermal toxicity, is soluble in organic solvents, and long-term low-dose exposure can lead to chronic poisoning, resulting in weight loss, pigmentation, and a continuous decrease in cholinesterase. His death was an acute exacerbation on the basis of chronic poisoning."

He paused for a moment: "There are three questions now. First, where did A-8 come from? The pesticide project from thirty years ago was long ago canceled; this compound shouldn't exist anywhere. Second, how did Professor Zhou come into contact with A-8? Through his skin, or through his digestive or respiratory tract? Third, who gave him access to A-8?"

He looked at Officer Yu and said, "These three questions require us to answer together."

Officer Yu nodded: "Professor Yang, what do you need us to do?"

Yang Ping said, "First, check all of Professor Zhou's laboratory's experimental logbooks, reagent requisition records, and waste liquid disposal records. A-8 couldn't have appeared out of thin air; it must have been synthesized. If Professor Zhou synthesized A-8 himself, there would definitely be records of it."

He turned to Director Zhang: "Second, we need to determine the exact structure of this compound as soon as possible. With the structure, we can know its origin, whether it is the same as A-8 from back then, or some kind of analogue, so that I can deduce more detailed possible symptoms."

He then turned to Dr. Yuan: "Third, re-examine Professor Zhou's clothes, especially his underwear and undergarments. If he had prolonged skin contact with A-8, there should be residue on his underwear. Also, conduct quantitative analysis of surface residue on every book in his study and laboratory. I need to know the concentration of A-8 on each book."

After he finished speaking, he looked at everyone and said, "Everyone, go your separate ways and keep each other informed of any progress."

Officer Yu, Director Zhang, and Dr. Yuan stood up, packed their things, and prepared to leave. Reaching the door, Officer Yu suddenly stopped, turned back to Yang Ping, and said, "Professor Yang, there's one more thing. We're investigating the source of Professor Zhou's threatening letter, but we haven't made any progress yet."

Yang Ping nodded: "Tell me immediately if you find any clues."

Officer Yu breathed a sigh of relief; with Professor Yang's help, he felt much more at ease about informing the criminals.

After they left, only Yang Ping and Zaxi remained in the conference room.

Yang Ping asked Zaxi, "Have you figured out anything?"

Zaxi hesitated for a moment and said, "I'm wondering, if the A-8 is something from thirty years ago, why is it only appearing now? Why did Professor Zhou suddenly start getting involved with this kind of thing after he retired?"

Yang Ping nodded: "Continue."

Zaxi added, "Also, those books. If A-8 was scribbled on a book, then the murderer would need to know which books Professor Zhou would read and how often. This person must be very familiar with Professor Zhou's habits. Moreover, the murderer would need to have access to those books, either the books in Professor Zhou's study or the books in the laboratory."

Yang Ping said, "Then who do you think best fits these criteria?"

Zaxi thought for a moment and said, "Li Xiong."

Yang Ping neither affirmed nor denied, but instead said, "Tell me your reasons."

Zaxi opened his notebook and read aloud what he had compiled: "First, Li Xiong has been with Professor Zhou for twelve years and is his closest confidant, knowing his habits best. Second, Li Xiong was able to enter Professor Zhou's laboratory and study. He said Professor Zhou's study is usually locked, but if he wanted the key, he should have a way to get it. Third, Li Xiong helped Professor Zhou buy toluene, and those two bottles of toluene were probably used to dissolve A-8. Fourth, Li Xiong is a chemistry major with sufficient chemical knowledge, knowing the toxicity of A-8 and its usage. Just as Officer Yu said, this kind of crime has invisibly narrowed down the range of suspects."

After he finished reading, he looked up at Yang Ping.

Yang Ping was silent for a moment, then said, "You're right, Li Xiong meets these criteria, but he's not the only one who does."

Zaxi was stunned: "Who else?"

Yang Ping said, "Have you thought about Professor Zhou himself?"

Zaxi's mouth dropped open: "Himself? You mean Professor Zhou poisoned himself?"

Yang Ping shook his head: "It wasn't poisoning, it was an accident. If Professor Zhou synthesized A-8 in the lab and accidentally came into contact with a high concentration of the solution or inhaled the aerosol during the process, leading to chronic poisoning, he might not even have realized it himself."

Zaxi's mind raced: "But what about those books? How do we explain the A-8 residue on them?"

Yang Ping said, "If he synthesizes A-8 in the lab and gets A-8 solution on his hands, then when he flips through a book, residue will be left on the pages. Over time, the books he frequently flips through will become contaminated."

Tashi fell silent; he had never considered this possibility.


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