godfather of surgery

Chapter 1390 Slow Murder
On Thursday morning, Zaxi appeared at the door of Yang Ping's office.

He clutched his notebook, which was filled with over twenty pages of densely written notes, all the results of his research from the previous night. He had barely slept all night, not because he didn't want to, but because the fragments of his thoughts were swirling too wildly in his head. When he closed his eyes, he could see Professor Zhou slumped over the table, and those hands with their gray-brown fingertips.

Yang Ping arrived at seven o'clock. He saw Zaxi standing at the door, paused for a moment, and then looked at his watch: "What time did you arrive?"

"I arrived at the department at six o'clock."

What time did you go to sleep last night?

Zaxi hesitated for a moment, then decided not to lie: "A little after eleven."

Yang Ping nodded, opened the office door, walked in, sat down in the chair, and pointed to the seat opposite him: "Go ahead and speak."

Zaxi sat down, opened his notebook, took a deep breath, and began to speak. He meticulously organized all the information he had gathered the previous night, according to his own understanding: the typical clinical manifestations of organophosphate poisoning, including muscarinic symptoms, nicotinic symptoms, and central nervous system symptoms; pupillary constriction is the most characteristic manifestation of muscarinic symptoms, caused by parasympathetic nerve excitation; the characteristics of skin absorption through contact, including a long incubation period, atypical symptoms, and local manifestations preceding systemic manifestations; organophosphate-induced melanosis, in which long-term exposure can result in grayish-brown pigmentation on the fingertips and face.

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

After listening, Yang Ping remained silent for a long time. Then he took out a piece of white paper from the drawer, placed it on the table, and took out a pen.

“What you’ve said is all correct, but you’ve missed one crucial point.” He wrote a word on the paper: dosage.

"Organophosphate poisoning, whether acute or chronic, is inseparable from dosage. For skin contact and absorption, what concentration, how long of exposure time, and what area of ​​skin is needed to reach a lethal dose?" He looked at Zaxi. "Have you checked these figures?"

Zaxi was stunned; he hadn't checked.

Yang Ping was interested in this case, and it would also be a good opportunity to cultivate Zaxi's reasoning ability, as an excellent doctor must possess strong reasoning skills.

Yang Ping didn't criticize him, but instead drew a table on the paper: "The toxicity of organophosphate compounds is measured by LD50, the median lethal dose. Different types of organophosphates can vary in toxicity by hundreds of times. For example, malathion has an LD50 of about 1000 mg/kg, which is considered low toxicity; while parathion has an LD50 of only 3 mg/kg, which is considered highly toxic. Why did Dr. Yuan come to consult us? Because their analysis has clearly shown that the deceased could not have ingested a large amount of organophosphates, so they are very confused and came to consult us."

He filled in a few numbers on the form, then looked up and said, "So, you need to figure out one thing first: if it's death from skin contact absorption, what kind of organophosphate is needed? What is the concentration? And how long was the contact?"

Tashi opened his mouth, but couldn't answer.

Yang Ping put down his pen and leaned back in his chair: "There's another question. You said the deceased had pigmentation on his fingertips, which is consistent with long-term exposure to organophosphates. But people with long-term exposure to organophosphates usually have symptoms of chronic poisoning, such as fatigue, loss of appetite, weight loss, memory loss, and mood changes. Have you found any corresponding evidence for these symptoms in the deceased?"

Zaxi thought for a moment: "His students said that he has lost weight in the past six months and has become increasingly silent."

Yang Ping nodded: "Yes, but these are non-specific manifestations. Many diseases can cause weight loss and personality changes. You need to find more specific evidence." He paused and asked a question that Zaxi hadn't expected: "Did the deceased have a physical examination? Where are the physical examination reports for the last six months? This is why Dr. Yuan contacted us again. As a forensic doctor, Dr. Yuan's toxicology knowledge is certainly superior to that of doctors, but they lack knowledge about the manifestations of poisons causing certain diseases or pre-existing diseases after exposure to poisons."

Zaxi paused for a moment: "This... I don't know."

Yang Ping picked up the phone on the table and dialed a number: "Dr. Yuan, this is Yang Ping. There are two things I need your help with. First, could you retrieve the deceased's medical examination reports for the past six months? Yes, all of them. Second, have any reagent bottles, medicines, or experimental records containing organophosphorus compounds been found in the deceased's home or laboratory? Okay, I'll wait for your news."

After hanging up the phone, he looked at Zaxi and said, "Investigating a case is like seeing a doctor. You can't just guess. You need evidence. Every clue must be supported by corresponding evidence. Guessing without evidence is just conjecture. Of course, guesses can be considered hypotheses, but hypotheses need to be verified."

Tashi lowered his head and wrote a line in his notebook: "Evidence chain, each one must be supported by evidence."

At nine o'clock in the morning, Dr. Yuan returned the call, and Yang Ping put it on speakerphone so that Zaxi could also hear it.

"Professor Yang, we've found the medical examination report. Professor Zhou's medical examination reports for the past three years are all available, and the examination time is the same every year. The most recent one was four months ago. The report shows that his weight has decreased by six kilograms compared to the previous year, his blood pressure is low, and his blood cholinesterase level is..."

Yang Ping suddenly sat up straight: "What is your blood cholinesterase level?"

Dr. Yuan glanced at the report: "The normal range is 4000-12000 U/L, and his result was 2100. The report indicated that it was low, but the doctor did not do anything special and only suggested a retest."

Yang Ping pressed on, "What about the previous two years?"

"The year before last it was normal, 6800, but it started to decline last year, to 3800."

Yang Ping nodded, then asked, "What about organophosphorus compounds?"

Dr. Yuan said, "We checked all the items in Professor Zhou's house and found no bottles of organophosphate reagents. In the laboratory, we inventoried all the chemicals registered under his name. There were two bottles of organophosphates, both of which were standards: one bottle of malathion and the other of dichlorvos. But both bottles were still there, sealed properly, and showed no signs of being opened."

Yang Ping frowned: "No signs of being opened?"

"Yes, the technical department checked it. The seal on the bottle cap is intact, it has not been opened, and there are no needle marks or anything like that."

Yang Ping remained silent for a long time before saying, "Okay, I understand."

After hanging up the phone, he sat down in his chair, his fingers tapping lightly on the table. Zaxi noticed that he was tapping very slowly, as if he were solving a complex math problem in his head.

"Zaxi, what did you hear?"

Zaxi thought for a moment and said, "The deceased's blood cholinesterase level continued to decline, indicating that he had been exposed to organophosphates for a long time. However, no opened organophosphate reagents were found at home or in the laboratory. This means that... the source of the organophosphates is not in these places."

Yang Ping nodded: "Continue."

Zaxi added, “The medical report said he had lost weight and had low blood pressure, which are consistent with chronic organophosphate poisoning. But four months ago, his blood cholinesterase level was 2100, which is… still far from fatal. So, he hadn’t reached the level of acute poisoning four months ago. It’s what happened in the four months that followed.”

Yang Ping glanced at him, a hint of approval in his eyes: "That's right. Have you thought about it? If the source of organophosphates isn't at home or in the lab, then where is it?"

Zaxi couldn't answer.

Yang Ping stood up, walked to the whiteboard, picked up a marker, and wrote a few lines:
Source: Professor Zhou has been in contact with organophosphates for a long time, but there are no opened reagents at home or in the laboratory. Where did they come from?

Routes of absorption: skin contact? ingestion? inhalation?
Dosage: Cholinesterase level was 2100 four months ago; death occurred four months later. How much did the exposure increase during those four months?
Pigmentation: Symmetrical distribution on the fingertips indicates long-term, repeated local contact. What was the contact?
After he finished writing, he turned around and looked at Zaxi: "These are the questions we need to answer, one by one."

Zaxi stared at the words on the whiteboard, his heart pounding. He suddenly realized that this case was far more complex than he had imagined. It wasn't a simple poisoning case, but a mystery that needed to be unraveled layer by layer.

Yang Ping sat back down in his chair and picked up the phone: "Dr. Yuan, this is Yang Ping. I have a few questions I need your help with. First, have you done any chemical residue analysis on the deceased's clothes, especially his coat, shirt, and pants? Yes, especially the areas that came into contact with his fingertips, such as the cuffs and pockets. Second, have you done any organophosphate testing on the cup of tea and the book in the deceased's house? Okay, I'll wait for your results."

After hanging up the phone, he looked at Zaxi and asked, "Do you know why I'm investigating these things?"

Zaxi thought for a moment: "We need to find the sources and pathways of organophosphates."

Yang Ping nodded: "Yes, there's another reason, and I'm ruling out one possibility."

What are the possibilities?

Instead of answering directly, Yang Ping asked a seemingly unrelated question: "Do you know why the typical symptoms of organophosphate poisoning are constricted pupils, salivation, sweating, muscle tremors, and pulmonary edema?"

Zaxi thought for a moment: "Because organophosphates inhibit cholinesterase, acetylcholine accumulates in the synaptic cleft, causing overexcitation of the parasympathetic and motor nerves."

Yang Ping nodded: "Yes, but did you know that some organophosphate compounds don't rely entirely on inhibiting cholinesterase for their toxicity? Some organophosphates are inherently cytotoxic. And some organophosphates produce even more toxic metabolites after being metabolized in the body. For example, parathion is metabolized in the body to produce paraoxon, which is ten times more toxic."

He paused, looking at Zaxi: "So, if you only check cholinesterase, you might miss something."

Zaxi was startled.

Yang Ping continued, "The deceased's blood cholinesterase level was 2100, which is indeed insufficient to cause death. But what if he was exposed not to ordinary organophosphates, but to a special organophosphate compound? An organophosphate that can be fatal without completely inhibiting cholinesterase?"

Zaxi's mouth dropped open: "You mean... there might be other poisons?"

Yang Ping shook his head: "I'm not sure, I'm just considering all the possibilities. Clinical diagnosis is like solving a case; you have to list all the possibilities first, and then eliminate them one by one. The one that remains after eliminating the others, no matter how unbelievable, is the answer." He instructed Zaxi: "Go check the literature, check if there is any organophosphate compound whose toxic mechanism is not entirely the inhibition of cholinesterase. Once you find out, tell me."

Zaxi stood up and was about to leave when Yang Ping suddenly called out to him, "Zaxi."

"Remember! Don't stay up late."

Tashi nodded, turned and left.

That afternoon, Zaxi spent the entire afternoon researching organophosphate toxicology and some emergency literature on the treatment of organophosphate poisoning, and he found several key papers.

The first article, published in 2015, discusses how certain organophosphorus compounds, in addition to inhibiting cholinesterase, can directly affect the mitochondrial respiratory chain, leading to impaired cellular energy metabolism. This effect can occur at low doses, even before the inhibition of cholinesterase.

The second article, published in 2018, discusses how certain organophosphorus compounds can induce apoptosis, particularly in neurons and cardiomyocytes, and this effect is independent of cholinesterase inhibition.

The third article is a review that summarizes the non-cholinergic toxicity mechanisms of organophosphate compounds discovered in the past decade, including oxidative stress, mitochondrial dysfunction, and neuroinflammatory responses.

Zaxi grew increasingly alarmed as he read. If these documents were true, then the clinical manifestations of organophosphate poisoning were far more complex than described in clinical medicine and forensic medicine textbooks. Typical symptoms such as constricted pupils, salivation, and sweating might only be the tip of the iceberg. Beneath the surface, much more unseen damage was occurring: cells were dying, mitochondria were collapsing, and the nervous system was slowly being eroded.

He printed out these documents, highlighted the key points with a highlighter, and then drew a new mind map in his notebook. He divided organophosphate poisoning into two categories: typical poisoning and atypical poisoning. Typical poisoning is mainly characterized by cholinergic crisis, while atypical poisoning is mainly characterized by cell damage, with more subtle clinical manifestations and is more difficult to diagnose.

He recalled Professor Zhou's death; constricted pupils were a typical symptom, but there was no salivation, sweating, or pulmonary edema. Could this be an atypical form of poisoning? A type of organophosphate poisoning characterized primarily by cellular damage, with minimal cholinergic symptoms?
He wrote down the idea and then drew a question mark.

At 8 p.m., Dr. Yuan returned Yang Ping's call.

The chemical residue analysis results for the deceased's clothing are in. No organophosphate residues were detected on the coat, shirt, or trousers. However, trace amounts of organic solvent residues were detected on the shirt cuffs, near the wrists. The components were toluene and xylene. The levels were very low, insufficient to cause poisoning, but it indicates that his cuffs had come into contact with organic solvents.

It's perfectly normal for a chemistry professor, who frequently handles chemicals, to have a little organic solvent on his cuffs.

Yang Ping was silent for a moment, then asked, "What about that cup of tea? That book?"

"Traces of organophosphates were detected in the tea, at an extremely low concentration of about 0.5 ppm. This concentration is not enough to cause poisoning even if you drink a whole cup. The book did not detect any organophosphates. As for trace amounts of organophosphates in tea, it is not uncommon for pesticide residues to be found in tea sold on the market."

Yang Ping frowned even more: "Organophosphates were detected in the tea, but the concentration was not enough to be fatal. So what was the cause of his death?"

Dr. Yuan said, "Toxicological screening is still ongoing. We are conducting more comprehensive analyses, including screening for uncommon toxins, but this process will take time."

After hanging up the phone, Yang Ping sat in a chair and thought for a while before telling Zaxi the news.

"Zaxi, what do you think?"

Zaxi thought for a moment and said, "The concentration of organophosphates detected in the tea is very low, which doesn't seem like poisoning. The detection of toluene and xylene on his cuffs indicates that he may have been exposed to organic solvents, but these are not enough to explain his death."

Yang Ping nodded: "So, we've missed something."

He added the new clues he had acquired that day to his mind:
Source: Unopened organophosphorus reagents from home and the laboratory; toluene and xylene were detected on the cuffs of the shirt.

Route: The concentration of organophosphates in tea is extremely low, making it unlikely to be a cause of death.

Dosage: Four months ago, cholinesterase levels were 2100, which was insufficient to cause death.

Pigmentation: Symmetrical distribution on the fingertips, indicating long-term local contact.

Organophosphates in tea: concentration 0.5 ppm, insufficient to cause death.

Clothing cuffs: Toluene and xylene were detected.

He suddenly asked a question that Zaxi had never expected: "Zaxi, do you know what toluene and xylene are used for?"

Zaxi thought for a moment: "Organic solvents, used to dissolve...certain substances?"

Yang Ping nodded: "Yes, toluene and xylene are commonly used organic solvents, especially in chemistry labs, to dissolve compounds that are insoluble in water. If a compound is insoluble in water, what do you do if you want it to be absorbed through the skin?"

Zaxi paused for a moment, then a thought suddenly flashed through his mind: "Dissolve it in an organic solvent to make a solution?"

Yang Ping looked at him, his gaze sharpening: "Yes, many organophosphorus compounds are fat-soluble, insoluble in water, but soluble in organic solvents like toluene and xylene. What would happen if you dissolved an organophosphorus compound in toluene and applied it to your skin?"

Zaxi's mind raced: "Organic solvents can damage the skin's barrier function and penetrate the skin along with organophosphates. In this way, even if the skin's absorption rate of organophosphates is not high, the absorption rate will be greatly improved with the help of organic solvents."

Yang Ping nodded: "Yes, and organic solvents themselves are also toxic. Toluene and xylene can cause nervous system depression, arrhythmia, and respiratory depression. If a person is exposed to organophosphates and organic solvents at the same time, the toxicity may be synergistically enhanced."

Zaxi's heart raced. He suddenly realized a possibility: someone had dissolved organophosphates in an organic solvent, creating a solution. Then, through some means, Professor Zhou was exposed to this solution for an extended period. The point of contact was his fingertips. Because the skin on the fingertips is thin, rich in blood vessels, and has a high absorption rate, prolonged exposure would lead to chronic poisoning, pigmentation, and a continuous decrease in cholinesterase. Then, at some point, a single, large dose of exposure would cause acute poisoning and death.

And this "certain way" might be those books.

Tashi blurted out, "Those books!"

Yang Ping remained silent.

Zaxi spoke faster and faster: "Those books are so well preserved, they're not meant to be flipped through. If someone smeared something on the pages, their fingertips would touch it every time they turned the pages..."

Yang Ping interrupted him: "Do you have any evidence?"

Zaxi was stunned.

Yang Ping said, "Your speculation is logically sound. But there is no evidence, no test results for the residue on the pages, and no report of organophosphates being detected in the deceased's fingerprints. It's all just speculation."

Zaxi stared at his phone in silence for a while, his curiosity growing stronger.

Yang Ping said gently, "Your approach is correct, but solving a case is like treating a doctor; you can't rush it. You have to take it step by step, and each step requires evidence. Right now, what is the key evidence we're missing?"

Zaxi thought for a moment and said, "The residue on the pages—if those books were really processed, there should still be residue on the pages."

Yang Ping nodded: "Yes, and also, the deceased's fingerprints. If he had been touching the contaminated pages with his fingertips for a long time, his fingerprints should have contained traces of organophosphates or organic solvents."

He picked up the phone and dialed Dr. Yuan's number: "Dr. Yuan, I'm sorry to bother you, but we have some ideas to discuss with you. We're wondering if we've tested all the books in the deceased's study, especially those he frequently read, for surface residue. We're particularly concerned about organophosphates, toluene, and xylene. We've also checked whether chemical residue analysis has been done on the deceased's fingerprints."

Dr. Yuan was surprised: "No, we hadn't considered these, but we can add these tests now."

After hanging up the phone, Yang Ping told Zaxi, "Now, we'll wait for the results."

That night, Zaxi lay in bed, his mind replaying the books. He imagined Professor Zhou sitting at his desk, opening a book, his fingertips tracing the pages. Once, twice, three times. One day, two days, three days. Half a year, one hundred and eighty days. With each touch, a tiny bit of organophosphate solution seeped into his fingertips, entered his bloodstream, and slowly eroded his nervous system, mitochondria, and cells.

This was a slow, silent murder. The killer didn't need to get close to him, poison his food, or install any devices in his room. All it took was a few books, a few bottles of reagents, enough patience, and a deep understanding of toxicology.

The murderer must have known Professor Zhou's habits very well. They knew which books he would read, how often he would read them, and that he wouldn't wear gloves while reading. The murderer might even have known Professor Zhou's medical checkup schedule, that his cholinesterase levels were steadily declining, and that he was slowly heading towards death.

The murderer is very likely someone close to Professor Zhou.

Tashi shivered.

He glanced at his watch; it was 11:30. Remembering Yang Ping's orders, he turned off the light and closed his eyes. But he couldn't sleep. The pages of those books rustled through his mind, turning one after another.