Into Unscientific

"Xiao Xu, paclitaxel has been synthesized!"

As these words rang out.

inside the house.

The polite words Xu Yun was about to blurt out were stuck in his throat, and he subconsciously turned his head and looked at the entrance of the room.

After a while.

The door of the house was pushed hard from the outside, and Lao Guo's panting figure flashed out from behind the door:

"Xiao Xu, good news, good news! I just received the news from Comrade Zhicen that paclitaxel has been successfully synthesized!"

When Xu Yun saw this, he couldn't help showing a surprised look and asked Lao Guo:

"Guo Gong, are you telling the truth?"

Xu Yun's surprise was not fake, he was really unprepared for the news.

According to his previous estimates, Lou Zhicen and Tu Luming would be able to achieve a breakthrough in mid-November very quickly. Now it is a month and a half ahead of schedule, almost on par with the efficiency of the thesis team.

Lao Guo gave a heavy hum, and his lips subconsciously made a "Xiao Han" mouth shape, but he immediately corrected himself:

"That's right, Xiao Xu, that's what the message I received said - but I just learned about it a while ago, so I don't know much about the specific situation."

After saying that, he raised his eyes and glanced at Zhao Zhongyao opposite, and asked tentatively:

"Xiao Xu, Lao Zhao, are you satisfied with your papers?"

Hearing this, Xu Yun raised the English manuscript in his hand toward Lao Guo. In order to avoid damaging the manuscript, he did not move too much. At the same time, he smiled and said:

"I've already looked at it. There are basically no big problems with the paper. Only some details can be optimized."

"For example, the overlapping integral of the wave function here, and"

Xu Yun simply pointed out some details that could be added in the manuscript. In addition, as mentioned before, he deliberately left some small errors and omissions that were not conceptually correct but could help understand this era.

If some concepts are proposed a few years in advance, they are called forward-thinking. If they are proposed twenty or thirty years in advance, they are called geniuses. But if they are proposed six or seventy years in advance, it is pure heresy.

After everything was settled, Xu Yun looked at Zhao Zhongyao again, considered and said:

"Director Zhao, that's it for the revision of the paper. Are you going to come with us next or...?"

Zhao Zhongyao thought for a few seconds, clicked his tongue, and pointed in a certain direction with his index finger:

"Since this matter of paclitaxel is related to Lao Yang, I will go over with you to take a look."

The old Yang mentioned by Zhao Zhongyao is naturally Mr. Yang Kaiqu, Zhou Kaida’s teacher and the most important treatment target of this targeted drug development.

Although Yang Kaiqu is not a big shot at the academic committee level, academic committee members are not the only way for top scholars to get to know each other:

Yang Kaiqu and Zhao Zhongyao are both from Zhuji, Zhejiang Province. They are only a few months apart in age and have known each other since they were in elementary school.

When they were in high school, they joined the local National Salvation Industrial Association in Hangzhou, took to the streets together to shout slogans, and signed their names on the National Salvation Volunteer Form. It has been more than 40 years since then.

Later, one of them invested in the agricultural field, cultivated land and cultivated food, and also brought out outstanding students like Zhou Kaida.

The other devoted himself to high-energy physics and laid the foundation for China's particle theoretical physics. Students all over the world are using their lives to fulfill their original promise of saving and strengthening the country, and their original enthusiasm has not yet frosted.

So even though one of the two is now a member of the academic department and the other is just a professor, the relationship between them has long gone beyond the scope of professional titles.

When Yang Kaiqu had physical problems, Zhao Zhongyao also deliberately found connections and contacted several experts to perform a physical examination on Yang Kaiqu. This was the only time in Zhao Zhongyao's life that he "went through the back door."

Later, Yang Kaiqu and the others came to Base 221, and Zhao Zhongyao also visited his good friends.

Now that he learned that there has been some progress in the treatment of Yang Kaiqu, Zhao Zhongyao couldn't help but put down his work temporarily and wanted to see the situation even though the compilation of the paper was very important.

Anyway, the rest of the paper is basically the accelerator experimental part, and when this part is short of power, the accelerator quota has been used up, and it will be difficult to start up in the short term.

Secondly, Zhao Zhongyao is notoriously shady and has basically no room to participate in the launch of the accelerator.

Yes, Zhao Zhongyao is a world-famous African chief.

When he was at MIT MOH, he was responsible for the startup of console instructions. As a result, no new events occurred in the MIT accelerator for four months.

Later, Zhao Zhongyao was absent from an experiment due to illness. As a result, MOH discovered the phenomenon that the Δ3 angle of neutron scattering was too large.

So from then on, the MOH laboratory still allowed Zhao Zhongyao to access any data, but he was not allowed to touch the power switch and the start button.

Over time, Zhao Zhongyao got used to this, so even though he usually inspected the accelerator every day, he never pressed the start button.

Including the base's previous accelerator trial run, Wang Ganchang and Cheng Kaijia were also responsible for the operation.

Therefore, it can be said that the follow-up accelerator issue actually has nothing to do with Zhao Zhongyao. It is okay for him to fish for a while.

So Zhao Zhongyao quickly recruited Wang Ganchang and temporarily handed over the situation at the scene to his proud disciple.

Then he, Lao Guo and Xu Yun left the house and ran straight to the

Drug laboratory.

Mentioned earlier.

The base's pharmaceutical laboratory is located in the seventh branch of the eighteen factories, adjacent to the chemical laboratory in charge of Liu Youcheng, and is in the same factory area as the base's most valuable tandem electrostatic accelerator at this time.

Half an hour later.

Lao Guo, Xu Yun, Zhao Zhongyao and Xu Yun's bodyguard Mou Fangdong got off a jeep and came to a small building.

"."

Looking at the small building in front of him, Zhao Zhongyao couldn't help but raise his eyebrows, and the surprised Lao Guo said:

"Friends, this is the base's drug laboratory? Isn't this too...well, too plain?"

To be honest, Zhao Zhongyao is not a person who pursues ostentation. He has had the experience of sleeping in Datongbu and eating cornbread, and even ate rats on his way back home.

But when it comes to scientific research sites, especially those with certain technical content, he still has some framework understanding:

The floor of the building may not be high, and the appearance may be as dilapidated as if it had just arrived from Shangganling, but at least the building's footprint should not be too small.

After all, when it comes to technology, all kinds of instruments are definitely needed. If there are instruments, there will naturally be space requirements for the venue.

In addition, these days rabbits have nothing but land, so most of the departments with scientific research functions in the base are "short" but "fat".

But this small building is different now.

This building is only two stories high, and its floor space, including fences and some vegetation, is estimated to be less than 150 square meters. It is located alone in the corner of the factory and looks extremely inconspicuous.

Although Liu Youcheng's chemical laboratory next to it is only one floor higher than this building, its area is still only 300 square meters smaller. The difference is really obvious.

Upon seeing this, Lao Guo shook his head slightly, pointed to another building not far away, and explained:

"Old Zhao, you may not understand the situation very well. Due to resource issues, the topic of the pharmaceutical laboratory is actually a research carried out together with the chemical laboratory led by Comrade Youcheng."

"For example, the PCR technology is handled by Comrade Youcheng's team members. After all, some equipment is scarce in China, so it would be great if one can be given to the base."

"The drug laboratory mainly analyzes and extracts components of terminal properties. The relevant equipment comes from Comrade Lou Zhicen and his original drug research institute, so the space requirement is naturally not high."

Zhao Zhongyao then nodded clearly:

"I see."

Lao Guo glanced at him quickly and quickly withdrew his gaze.

In fact, there is another reason why Lou Zhicen and the others chose this building that it is not convenient for Lao Guo to introduce, and it is because of Lou Zhicen's own request.

How do you say Lou Zhicen? In the words of later generations, he is a typical person who thinks too much, or is relatively sensitive.

He felt that his team had not achieved anything when they first came to the base, and it would easily be criticized for occupying a building that was too large - otherwise, although the base's equipment supply was limited, the space could still be filled up at will.

This kind of small building located in a remote corner can just satisfy Lou Zhicen's sense of security. This mentality is somewhat similar to the way many people in later generations like to sit in corners when going to Internet cafes.

So at Lou Zhicen's request, the base assigned this building to the Institute of Drug Research.

Then Lao Guo coughed lightly, ended the chat, and led Xu Yun and others to knock on the door.

be honest.

Xu Yun was inexplicably afraid of this kind of small single-family building, because generally when such a door was knocked, a black-faced man similar to that old Zhou would appear, taking off his pants and wrangling him.

Fortunately, the specifications of the drug laboratory were not as high as those of Lu Guangda and his theory team. After a while, the door was opened directly from the inside.

The person who opened the door was still an acquaintance of Xu Yun, Tu Luming, who would be famous in later generations - it was just a one-sided acquaintance with Xu Yun, and Tu Luming now only knew Xu Yun a little better than a passerby.

Then Xu Yun glanced at the still young future boss, and the corners of his mouth curved slightly.

She probably doesn't know that she has been on a certain list.

Tu Luming obviously didn't know Xu Yun's inner thoughts, but at this time there was still an obvious joy in her eyebrows, and her eyes lit up even more when she saw Lao Guo and others:

"Director Guo, Director Zhao, Consultant Xu, you are here, please come in quickly!"

Xu Yun's expression was not that surprised at Tu Luming's title.

Although only four people in the base knew his true origin, after meeting with the writer in the capital that day, Xu Yun's real name was no longer a secret.

However, the base's statement to the outside world was that Comrade Han Li changed his name to Xu Yun due to work needs, which is somewhat similar to the situation where Wang Ganchang changed his name to Wang Jing, and various subordinate departments were quickly notified.

This kind of temporary name change is actually very common in the base. Some experts have to change their names when they are transferred from the second branch to the first branch. Today they may be called Zhang San, but tomorrow they will be called Li Si.

Many times, colleagues in the base know each other's real name, but still have to accept the fact that the other person changes their name every few months.

Therefore, there is not much doubt within the base about Xu Yun's "name change", but only Lao Guo and the others know that the truth is actually the opposite.

Okay, let’s return to reality.

After saying those welcome words, Tu Luming pushed the door completely open and made room for several people to pass.

Lao Guo and others left Xu Yun's correspondent Mou Fangdong outside on duty, and the remaining three followed Tu Luming into the small building.

The layout of the first floor of the small building is the same as its appearance, so simple that it can be called crude:

There is a chandelier hanging from the ceiling, and the lower room is neatly divided into two rooms on the left and right. There is a corridor in the center, and at the end of the corridor is the staircase leading to the second floor.

At the same time, there was an extremely strong smell of traditional Chinese medicine or medicinal materials, but Xu Yun couldn't smell the specific medicinal materials.

Firstly, he really has no relevant knowledge reserves, and secondly, because his nostrils have been burned into the same peripherals as Voldemort's, it is difficult to even breathe, let alone smell.

Then under the guidance of Tu Luming.

Everyone quickly arrived at the entrance of the room on the left. Tu Luming gently knocked on the ajar door:

"Teacher, Director Guo and the others are here."

There was originally some discussion in the room, but after hearing this, there was an immediate silence. A moment later, Lou Zhicen’s voice rang out:

"Please come in!"

Tu Luming then pushed the door open, and Xu Yun and three others followed.

This room is only about 40 square meters. The walls are rarely painted white, and the wooden tables are also painted white. It has a faint shadow of a later laboratory.

At this time, there were also three men in the room, namely Tu Luming's teacher Lou Zhicen, doctor Lin Yu from the Workers' Hospital, and Liu Youcheng, the head of the chemical laboratory that Xu Yun was familiar with.

Lao Guo had introduced the relationship between Liu Youcheng and Lou Zhicen's laboratory before entering the house, so when he saw Liu Youcheng's appearance, Zhao Zhongyao, who was here for the first time, did not show any obvious surprise on his face.

At the same time as the three of them followed Tu Luming into the house.

Lou Zhicen, Lin Yu, and Liu Youcheng, who were sitting and chatting, all stood up and hurried towards Lao Guo under the guidance of Lou Zhicen:

"Director Guo, Director Zhao, Consultant Xu, you are here."

"Comrade Zhicen, Comrade Youcheng, good morning."

Lao Guo and the other three also greeted Lou Zhicen and Liu Youcheng politely. Then Zhao Zhongyao rubbed his hands and asked impatiently:

"Comrades, I heard that paclitaxel has been synthesized?"

As one of Yang Kaiqu's attending physicians, Lin Yu had frequently met Zhao Zhongyao, who had gone to see his old friend's condition during the past period, and he had a good relationship with Zhao Zhongyao.

Hearing this, he pointed to the table next to him and said:

"That's right, Comrade Zhongyao, that's the small box on the table."

Upon seeing this, Zhao Zhongyao quickly walked to the table and looked at the things on the table.

I only see this moment.

There was a small, palm-sized white plastic box on the table, which contained some transparent liquid.

The volume of the liquid is about half of the capacity of the small box. Although there is no actual contact or shaking, it can be seen at a glance that its density is definitely higher than water, and it should be a relatively viscous liquid.

Probably a bit like transparent rice milk?

While Zhao Zhongyao was staring at the box, Lou Zhicen brought Xu Yunlao Guo to the table and took the initiative to explain:

"Guys, this is the paclitaxel extract we synthesized - well, to be precise, it should be called the extracted extract."

"About a month and a half ago, we got the first batch of yew trees from Longyou, weighing seven to eight hundred kilograms."

"After repeated research on the materials, we decided to use ten-year-old young stems as materials to extract components by inducing callus tissue and screening high-yield cell lines."

"So Comrade Youcheng introduced malondialdehyde, observed cell growth and cell membrane permeability, and determined the two-stage policy of methyl jasmonate and ethephon as separation agents. The concentrations of the two were 103.389 μmol respectively. /L and 73.771μmol/L.”

“In the end, through manual observation and comparison that lasted for half a month, we came up with the final solution of the extraction process with a solid-liquid ratio of 1:43.5, an ultrasonic time of 50 minutes, and an added amount of FeCl3/Br2 of 1.5wt%, and it was officially announced three days ago. A sample of paclitaxel was extracted.”

After Lou Zhicen finished speaking, Liu Youcheng on the side also nodded.

Mentioned earlier.

Paclitaxel. In other words, including subsequent targeted drugs, the difficulty and focus lies in which strategy to use to construct a five-membered ring.

In later generations, due to the relatively mature equipment precision, the synthesis of five-membered rings can be completed by constructing C9-C10 or C10-C11 bonds, but this period is far less developed.

In addition, the capital writer had not arrived at the base a month and a half ago, and Xu Yun had not completely let himself go. Therefore, this part of the plan was indeed a bit difficult for Liu Youcheng and others.

In the end, after many extremely heated discussions, Liu Youcheng and the others finally settled on an idea:

The starting material is first treated by introducing malondialdehyde to convert it into an unstable aldehyde compound, and then converted into an unsaturated aldehyde and ketone compound through an addition reaction, and finally the young stem material is guided to separate the five-membered ring compound.

When Xu Yun learned about this plan, he was indeed shocked for a long time.

After all, the concept of hybrid orbitals in this era has not yet been fully established. Although it is something that involves deep theory, it can still only be dealt with at the macro level.

Not to mention that the synthesis of five-membered rings was not easy in later generations - don’t believe me, how many readers know how to make this thing?

But even in this situation where the underlying principles were vague, Liu Youcheng and the others found the right path. Why didn't this surprise Xu Yun?

In terms of chemical essence, the idea of ​​Liu Youcheng's plan is very close to a later paper by the team of Professor Li Chuangchuang of the Southern University of Science and Technology.

Classmates who were yew trees in their previous lives should all know this.

From a structural point of view.

Paclitaxel has a unique [5.3.1] bridged ring system containing a bridgehead double bond, which is an anti-Bredt olefin. It also contains 11 stereochiral centers on the 6/8/6/4 high-tension four-ring skeleton and 8 oxygen-containing functional groups.

Therefore, it is actually very difficult to fully synthesize this substance. Semi-synthetic extraction is actually the most efficient method.

Liu Youcheng's plan is equivalent to "labeling" the olefin of paclitaxel first, and then sieving out irrelevant substances layer by layer like sieving beans, and finally obtains the paclitaxel compound.

Of course.

Although Liu Youcheng was responsible for the entire project, Xu Yun did not do anything.

Among them, the culture medium used by Tu Luming to cultivate the cell line was Xu Yun's plan. Originally, Tu Luming planned to apply magnesium chloride on the young stems of yew, but at Xu Yun's suggestion, he changed it to donkey saliva.

After all, the effect of this thing has been proven in reality, that is, during the cultivation process of Yi'an bacteria, and the effect is even higher than that of apical secretion.

Nowadays, the apical secretions of local donkeys are used to make donkey pulp films, so Xu Yun naturally considered donkey saliva.

It is said that recently the Kampot captain of the base’s animal husbandry team is working hard to add sour plums to the local donkeys’ feed. I don’t know if this human body fluid production method is useful for the local donkeys.

It is also said that the base is still considering whether there can be a use for the donkey's fluid. After all, the only renewable thing in Brother Donkey's body is this thing. If he doesn't use it, his obsessive-compulsive disorder will always feel uncomfortable. .

His eyes returned to reality.

After Liu Youcheng and others introduced the extraction method of the extract, Zhao Zhongyao couldn't help but touch it twice himself, and then asked:

"Comrade Zhicen, how effective are these extracts? Have they been tested clinically?"

"It's not clinically available yet, but Director Liu has done in vitro experiments."

Upon hearing this, Lou Zhicen pointed to Liu Youcheng again and introduced:

"Their laboratory has been cultivating tumor cells. Recently, the PCR technology that Xiao Xu mentioned has also made some progress. Although it is still early to identify the specific point, there is still no problem in identifying the nature of the cells."

"Didn't I just say that we actually extracted the paclitaxel compound three days ago. The reason why we didn't rush to report it to the base was to observe its effect."

Xu Yun glanced at the small box in Zhao Zhongyao's hand and nodded slightly.

Mentioned earlier.

In the PCR technology research plan designed by Xu Yun, the sample cells used were mainly based on the phenotype of the local donkey's Light Point, that is, the MC1R gene.

This approach avoids the frequent need to extract tumor cells from Yang Kaiqu, and will not cause further damage to Yang Kaiqu's body.

But on the other hand.

After all, the entire targeted drug was proposed to treat Yang Kaiqu's lung tumors, so local donkey cells can only replace tumor cells in most cases, and tumor cells must still be used when they should be used.

Therefore, Liu Youcheng and his lab have been cultivating some of the cancer cells collected from Yang Kaiqu for use at this time.

Of course.

If it weren't for the purpose of grasping Yang Kaiqu's deterioration, collecting the cancer cells once would actually be enough. The in vitro proliferation ability of this thing is still very strong.

For example, the famous HeLa cells have been passed down for unknown generations since 1951, and the HeLa cell lines currently cultured have exceeded 50 million tons - although this is also an exception among cancer cells.

However, the tumor cells cultured in this in vitro state will be very different from the original generation, so Liu Youcheng and the others must collect them repeatedly at intervals.

The task of collecting and cultivating cancer cells is naturally to test the effects of targeted drugs and related pre-products.

Then Lou Zhicen paused, walked to the table, picked up another document, and said to Zhao Zhongyao:

"Director Zhao, look, this is the experimental result we observed."

"oh?"

Upon seeing this, Zhao Zhongyao took the document and glanced at it a few times, but quickly stuffed it back into Lou Zhicen's hand:

"can't read."

Lou Zhicen was stunned for two seconds, and then he realized that he and Liu Youcheng and Lin Yu had just had a lively chat, so he subconsciously regarded Zhao Zhongyao as an expert in biomedicine.

So he quietly took back the document, touched his nose twice, and said:

"According to our experimental results, within seven hours after adding paclitaxel extract for infiltration, the growth rate of tumor cells in vitro showed a certain degree of hysteresis."

"At the same time, the cargo protein of extracellular vesicles increased significantly. To put it bluntly, the cancer cells that had completed the doubling of chromosome and protein replication were unable to divide smoothly into two new daughter cells."

"Comrade Youcheng speculates that this substance may activate the suicide mechanism of cancer cells, but the phenomenon in earlier mouse experiments seems to be related to T cells."

"It is unclear which of the above two guesses is correct. In short, as of this morning, the expansion of cancer cells has stopped very obviously."

"So we immediately contacted Assistant Zhou of the main factory and asked him to relay the news to you."

Zhao Zhongyao nodded with understanding.

Zhao Zhongyao is a very standard physicist, so he is not very familiar with terms such as extracellular vesicles that Lou Zhicen mentioned.

But no matter how thick the professional barrier is, he still has some knowledge about cell division.

Cancer cells are cells that reproduce indefinitely. The way to eliminate them is either to be recognized by T cells or to inhibit their division.

Although the specific mechanism is not known, paclitaxel apparently achieves this effect.

Think of this.

Zhao Zhongyao couldn't help but flash a hint of excitement in his eyes.

If even a pre-substance like paclitaxel can have a significant impact on cancer cells, what about subsequent targeted drugs?

If this is the case, maybe Yang Kaiqu really has hope of living for another five years?

By the way, Yang Kaiqu!

Zhao Zhongyao suddenly realized something and immediately looked at Lou Zhicen:

"Comrade Zhicen, since you have extracted paclitaxel, have you notified Lao Yang?"

Lou Zhicen smiled and pointed at Lin Yu beside him, with a hint of "You are concerned but you are confused" expression on his face:

"Director Zhao, Dr. Lin is here. Do you think Comrade Kaiqu knows about this?"

Zhao Zhongyao was suddenly startled.

After a few seconds, he slapped his forehead in frustration:

"Hey, look at my brain!"

Lin Yu is currently the most skilled attending physician in the Staff Hospital, and is currently responsible for four patients:

Xu Yun, U2's only living pilot Yang Shiju, 8 ahem, the man suspected of being a pilot that Xu Yun fished from Qinghai Lake, and Yang Kaiqu, a terminal cancer patient.

Therefore, if Lin Yu appears here at this time, Yang Kaiqu must also be there.

So Zhao Zhongyao patted his forehead and asked Lou Zhicen:

"Comrade Zhicen, where is Lao Yang now? Upstairs or next door?"

Lou Zhicen smiled and pointed to the left.

It's a coincidence.

Just as Lou Zhicen stretched out his index finger, the voice of Special Protector Qiao Caihong happened to be heard outside the house:

"Director Lin, Comrade Kaiqu has already started the infusion!"

Note:

In the next three days, 12,157 words will be updated every day. Look at me, a computer, a handsome guy, three nights, a miracle! ! ! !