There was a moment of silence in the entire ward, and the sound of needle dropping could be heard in the room. Obviously, they did not understand the meaning of these words.
Fortunately, this was not the first time that Lao Guo heard these strange new gadgets from Xu Yun, so he quickly came to his senses:
"Targeted drugs? Xiao Han, what is this?"
Xu Yun thought for a moment after hearing this, but did not give a direct explanation. Instead, he turned to look at Lin Yu and said:
"Dr. Lin, the concept of targeted drugs is relatively complicated to introduce, so could I trouble you to first introduce the current understanding of lung cancer in the medical community?"
Lin Yu nodded immediately:
"no problem."
As a Western medicine expert with overseas study experience, he still has very detailed information about lung cancer, and he soon started talking:
"Lung cancer is a disease that has gradually become more common in recent years. The number of people affected by it every year is smaller than that of gastric cancer, but the growth rate is very fast."
"The cause of its formation is still unknown. Ten years ago, a scholar from across the sea proposed the idea that smoking causes lung cancer."
"But a few months before I returned to China, a refuting theory called the birth weight paradox emerged, so how lung cancer develops is still a controversial topic."
Xu Yun nodded slightly.
As a Ph.D. student in biology at the University of Science and Technology of China, his mentor is Tian Zhigang, a well-known immunologist in China, so what Lin Yu said is not unfamiliar to him.
It is different from the later life that Xu Yun traveled through time.
In 2023, lung cancer is the most common cancer among all cancers and the cancer with the largest number of deaths, known as the king of lung cancer.
There were 820,000 new cases and 720,000 deaths in China last year alone, let alone the world.
But what few people know is.
More than 100 years ago, lung cancer was actually a very rare cancer.
1912.
Across the sea, a doctor named Emma Watson - yes, the doctor with the same name as Hermione's character - once mentioned one thing in a medical book:
He searched through literature around the world and found a total of 374 cases of lung cancer.
But after 1920.
The incidence rate of lung cancer suddenly began to rise linearly, as if the Shanghai Composite Index had turned upside down.
For this reason, many experts began to pay formal attention to lung cancer, and when studying cigarette rolling machines across the sea, they discovered that there is a certain relationship between cigarettes and lung cancer.
Of course.
The reason why scholars can discover this situation is not because of their strong observation and judgment, but because the cigarette market is so terrible these days:
Taking last year as an example, the average annual smoking per capita across the sea was more than 4,000 cigarettes.
That's right.
4000 pieces.
This is like if you pinch yourself more than ten times a day, then the doctor will definitely connect the two when checking for kidney deficiency...
However, a "birth weight paradox" emerged across the sea in the past few years, making the relationship between cigarettes and lung cancer even more ambiguous.
This refutation of the doctrine goes like this:
If smoking is harmful to health, maternal smoking will lead to low birth weight of the baby and increase infant mortality.
But according to actual statistics, scholars across the sea found exactly the opposite.
Infants born to smoking mothers have a lower mortality rate than normal infants.
Ever since.
There is another layer of confusion between smoking and lung cancer. No one knows whether there is a connection between the two.
This paradox will not be confirmed and explained clearly until 2001, so it is normal for Lin Yu not to be able to explain it clearly at the moment.
Then Lin Yu paused and continued:
"As lung cancer gradually became a common disease, corresponding treatment options gradually began to develop."
"In the 1940s, pneumonectomy was the classic surgical treatment for lung cancer. For example, in early 1941, Dr. Zhang Jizheng of Yanjing Union Medical College Hospital completed the first left pneumonectomy in our country."
"Nowadays, with the development of medical technology, our surgical procedures have changed from whole lung to lobectomy, and the scope is relatively smaller."
"Currently, we mainly divide lung cancer into small cell lung cancer and non-small cell lung cancer. Small cell lung cancer is not suitable for surgery, while non-small cell lung cancer is suitable for some surgery."
"Of course, this sentence is also relative."
Xu Yun nodded and asked again:
"So what about in-depth research on the pathogenic structure of lung cancer? What is the current development stage?"
"The pathogenic structure...oh, you mean the structure of cancer cells, right?"
Lin Yu blinked when he heard this, and his answer this time was much simpler:
"Lung cancer cancer cells have been mastered at home and abroad with relevant cultivation techniques. After all, the cultivation of cancer cells was successful fifty years ago. It is not a big secret now."
"As far as I know, Yanjing has used colony formation experiments to isolate solid tumor stem cells, and has achieved certain results in the regulatory mechanism."
"But the research on cancer cells can only go so far. No matter how deep you go, there seems to be not many new discoveries even across the sea - at least that's what I know."
After Xu Yun listened quietly, he looked up at the scene.
At this time, except for Li Jue who still looked [OvO].
Lao Guo, Yang Kaiqu and Zhou Cai all showed some signs of understanding and seemed to have caught up with the rhythm.
So he coughed lightly, took over Lin Yu's right to speak, and said:
"Dr. Lin, have you ever practiced target shooting?"
"Target shooting?"
Lin Yu was startled for a moment, then straightened his chest:
"Of course I did."
joke.
Every one of these people at the scene, including Li Jue's assistant Zhou Cai and the terminally ill Yang Kaiqu, had hit targets in the past.
Militias are very popular these days, and there are even a lot of private guns.
Those who have been shot are not uncommon, but those who have never been shot are rare.
Xu Yun then made several target shapes with his hands in the air and said:
"Dr. Lin, since you have done target shooting, you must know the process of target shooting."
This chapter is not over yet, please click on the next page to continue reading! "When you are shooting, there will be many targets on the shooting range. You can only hit the one that is facing you. If it is crooked, you will not be scored or deducted.
point."
"In the microscopic field, if we regard the tumor as a target range, then its interior can obviously be divided into many target areas."
"For example, the bilateral and unilateral RB characteristics proposed by Peter Armitage in 1953, and the Ph chromosome locus discovered by the University of Pennsylvania four years ago, etc..."
Looking at Xu Yun talking eloquently.
Lin Yu, who holds three overseas doctorates, was suddenly startled. He immediately realized something and couldn't help but interrupt him:
"Wait a minute, Comrade Han Li, the targeted drugs you mentioned..."
"Doesn't it refer to the 'bullet' that targets cancer cells and then destroys them accurately?"
Snapped!
Xu Yun immediately snapped his fingers and said with a smile:
"Dr. Lin, your statement is not completely correct, but it is very close to the concept of targeted drugs."
"However, the broad concept of targeted drugs is not to eliminate cancer cells, but to suppress the growth of cancer cells after hitting key nodes."
"Just like a bullet, when a bullet hits someone, it doesn't immediately clear your health bar...ahem, life, but it deactivates your body by destroying blood vessels."
Lin Yu's eyes suddenly shrank.
WTF?
Targeted drugs to inhibit the growth of cancer cells?
Is there such a thing?
Then he suddenly stood up from his seat, walked quickly to Xu Yun and asked:
"Xiao Han, what is the specific biological mechanism of the targeted drug you mentioned? What are the ingredients? What is the production process?"
Hearing this set of questions from Lin Yu's mouth, Xu Yun couldn't help but smile.
It turns out that Lin Yu, a cold-faced old man who looks like he has a paralyzed face, can also get emotional sometimes...
Then he took a deep breath, made an urgent gesture towards Lin Yu, and explained:
"Dr. Lin, I only came across the idea of this targeted drug in a book when I was in Europe. The author's name is Ling Ran... so I really don't know much about the specific ingredients and process."
"But the biological mechanism...is that this drug can act on specific protein molecules, enzymes, and gene fragments through certain reactions."
"After all, cancer cells are caused by genetic mutations, so in theory, it should be reasonable to carry out targeted treatment at the mutation site."
"Action on a specific gene segment?"
Lin Yu shrank again when he heard this, but this time he didn't speak in a hurry.
Gene.
This is an extremely mysterious and front-end field.
Humans actually discovered cells very early. As early as the 17th century, Hooker, who fell in love with and killed a calf, discovered cells.
Then in 1836.
Valentine discovered nucleoli in the nuclei of connective tissue cells, thus opening up the study of intracellular structures.
Then came the cell theory of Schleiden and Schwann, Mendel's laws of genetics, Virchow's pathology, etc.
Then came the end of the 19th century.
The four major diamonds, centrosome, mitochondria, chromosomes and Golgi apparatus, have also been discovered successively.
But DNA...that is, the concept of genes was first introduced, but it was only as late as 1924.
Meanwhile wait until 1944.
Avery and others confirmed that the transformation factor of pulmonary diplococci is DNA, and they experimentally determined for the first time that the gene is a DNA fragment with genetic effects.
As for the structure of DNA...
It has only been around for eight years and belongs to a completely new field.
So in this current era.
The word gene is not completely unfamiliar to medical scientists like Lin Yu, but it is extremely mysterious, like an abyss.
But on the other hand.
It was precisely because of the mysterious anomalies in the genetic field that Lin Yu was a little unsure whether what Xu Yun said was true or false.
after all......
In the more general medical field, many drugs are used in cytotoxic chemotherapy these days.
For example, in 1948.
Farber used the antifolate agent methotrexate to treat acute lymphoblastic leukemia, ushering in modern cancer chemotherapy.
Since then, with the research and development of anti-cancer drugs, chemotherapy drugs have also been rapidly developed.
Up to now.
Chemotherapy drugs that have been discovered and used include fluuridine, 6-hydroxypurine, methotrexate, cyclophosphamide, actinomycin D, and many other categories.
And if Lin Yu remembers correctly.
There is an international view on the mechanism of action of these drugs:
The function of these drugs is to interfere with the integrity of DNA, interfere with DNA replication, act on the microtubules in the mitotic spindle, and inhibit mitosis.
Thereby preventing the proliferation, invasion and metastasis of cancer cells and finally killing the cancer tissue.
True.
This mechanism is not consistent with the targeted drugs mentioned by Xu Yun, but they are somewhat similar in nature, as they both act on points within cells.
So if you think about it from this perspective...
Not to mention whether it can be done with the current technical level, this idea may be true...
Not a big problem?
Of course.
This is just a possibility.
Then Lin Yu adjusted his glasses, regained his original calmness, and said to Xu Yun:
"Comrade Han Li, I personally reserve my opinion on the mechanism you mentioned. At least for now, I really can't think of any reason to refute it."
"But... ideas are ideas. For now, we want to implement it into applications... that is, produce finished products. It seems that there is not much possibility at all, right?"
Hear this.
Lao Guo on the side also nodded subconsciously.
Although he is not an expert in biology, he has a good personal relationship with Liu Youcheng from the base chemistry laboratory.
A few days ago, when he went to the laboratory to break through the door, a student happened to see some papers about genes in foreign journals and asked Liu Youcheng questions.
Liu Youcheng's answer at that time was that genes belong to an unexplored land. Even top foreign institutions are still in a state of half-research and half-guessing, and the proportion of guesses is even greater.
However, facing Lin Yu's question, Xu Yun seemed very calm:
"Yes, Dr. Lin, the production technology of targeted drugs is very difficult and involves many special links."
"But...again, if we want to make a simple version of targeted drugs, I think it is still feasible."
Xu Yun emphasized the words "simplified version" very seriously.
As we all know.
Even in 2023, the year that Xu Yun traveled through, lung cancer is still a terminal disease with a very high mortality rate.
Maybe some people can live for a long time due to personal physical problems, but at least in the popular field, lung cancer is still somewhat unsolvable.
But on the other hand.
Although lung cancer has developed to the middle stage, there is almost no possibility of radical cure, and the survival probability of most patients is very low.
However, it is still possible to suppress the disease to a certain extent and add a few years to the patient's life.
This may be targeted therapy.
Generally speaking.
Even patients with advanced lung cancer have a chance to live for three to four years or even longer using targeted drugs.
The so-called targeted therapy is a treatment method that targets identified cancer-causing sites at the cellular and molecular level.
This site can be a protein molecule inside the tumor cell, or it can be a gene fragment.
When targeted drugs enter the body, they will specifically bind to carcinogenic sites and cause tumor cells to specifically die without affecting the normal tissues surrounding the tumor.
The origin of targeted drugs can be traced back to 1960, when the biological laboratory of Philadelphia University discovered a chromosomal abnormality associated with many leukemia patients.
Ten years later, when a biomedical scientist named Compli was studying this topic, he discovered that this abnormality would occur when parts of chromosomes 9 and 22 were translocated.
This abnormal site became the target of Inmatinib, the first targeted cancer treatment drug.
Of course.
The origin of targeted drugs can be traced back to the current period, but the development of technology generally occurs in the 1980s or even after the 1990s.
Therefore, it is completely wishful thinking to produce a complete targeted drug with current technology - at least in the short term.
but.......
If we don't ask for targeted drugs in the standard sense and make a simple beggar's version, Xu Yun believes that it is still feasible.
after all.....
He had laid a foreshadowing at the beginning.
Think of this.
Xu Yun paused again and continued to explain:
"Targeted drugs Targeted drugs, we can actually divide the word into two parts, one is targeting, and the other is drugs."
"This is somewhat similar to our Zhuxianjian missile. The target is the laser guidance and waverider structure, and the explosive is the warhead and the explosive contained in the warhead."
Lao Guo and Lin Yu nodded, this metaphor is quite clear.
Then Xu Yun raised a finger, shook it slightly from side to side, and said:
"Let's talk about the easier part first, which is the required 'explosives'."
"According to the manuscript I saw, the most suitable ingredients for targeted drugs should be monoclonal antibodies or small molecule compounds, which are mainly formed through some complex reactions."
"For example, N-methyl indole and dichloropyridine are used as starting materials, and a compound is synthesized through a hydroxylation reaction of a certain substance, and then the next step of synthesis is carried out."
"But this kind of synthesis is still difficult for us at present. After all, the derivation of ingredients is not something that can be done in a day or two or even a year or two."
"But... I once saw a record in the handwriting of Fengling Yueying Sect, saying that hundreds of years ago, someone had suffered from 'lung phlegm' and was 'almost ready to die'."
"Later, he accidentally got a folk prescription. He asked someone to bring a kind of wood from Longyou Road to make a decoction. He took two doses of it every day, and finally lived for more than a year."
"So I think if we can find that kind of wood and use it as a reference for prodrug research, we might have a chance to find a suitable targeted drug formula."
"?!"
Hearing Xu Yun's words.
Lao Guo on the side suddenly couldn't sit still and asked quickly:
"Xiao Han, what is that kind of wood called?"
Xu Yun glanced at him and gave his answer:
"Yew."
Yew.
This is the general name for a plant of the genus Yew, which is an excellent ornamental shrub, also known as yew or yew.
In Xu Yunlai's later generations, it was a national first-class rare and protected plant.
But what few people understand is.
The real value of yew does not lie in its ornamental value, but in its medicinal value.
Generally speaking.
After most herbal plants are processed, they can basically produce secondary metabolic derivatives...that is, extracts.
For example, aloe vera extract is very suitable for facial masks, milk thistle extract is the main ingredient of liver protection tablets, etc.
The same is true for yew, but its extract is...
Taxol.
That's right.
Taxol.
This is an anti-tumor active ingredient isolated from the bark of Taxus brevifolia. It is one of the best drugs for the treatment of metastatic ovarian cancer and breast cancer.
At the same time, it also has a significant effect on lung cancer and esophageal cancer, and has a significant inhibitory effect on nephritis and parvovirus inflammation.
Under normal circumstances.
It takes about 1 g of bark to extract 1 g of paclitaxel. To treat an ovarian cancer patient, 3-12 yew trees that are more than a century old are needed.
Therefore, the price of this substance has become very high, which has attracted a large number of humans to cut down yew trees, making the already few yew trees even more scarce and on the verge of extinction.
Of course.
Paclitaxel is a chemotherapy drug in nature and is not a conventional targeted substance.
However, some of its structures and characteristics - such as hydrophobic groups, 2'-OH or 7-OH design sites - are very similar to targeted drugs in some aspects.
Actually.
The main difference between chemotherapy drugs and targeted drugs is that chemotherapy drugs act non-selectively on actively growing cells, killing cancer cells and also killing normal cells.
This chapter is not finished yet, please click on the next page to continue reading the exciting content! As for targeted drugs, they selectively act on tumor cells.
In addition, the application of chemotherapy drugs is generally determined based on the results of histopathological specimens, while the application of targeted drugs needs to be determined based on the results of genetic monitoring of histopathological specimens.
In a certain sense.. Note that in a certain sense.
The difference between chemotherapy drugs and targeted drugs is actually equivalent to atomic bombs and neutron bombs.
Atomic bombs and neutron bombs are obviously not the same weapon, but they do have something in common in some deep-seated aspects.
And once you have paclitaxel as a sample.
Then the mission of the rabbits has changed from pure research and development without any reference to the direction of converting chemotherapy drugs into targeted drugs.
True.
Xu Yun is not sure how effective this approach will be, but it will at least be easier than developing a new drug.
For example, the example he gave before is the synthesis route of osimertinib mesylate:
An intermediate product was synthesized through Friedel-Crafts alkylation reaction catalyzed by aluminum trichloride using N-methyl indole and dichloropyridine as starting materials.
Then p-toluenesulfonic acid, the intermediate product is heated and refluxed in 2-pentanol to obtain intermediate product 2.
It is then condensed with secondary amine in a microwave reactor to obtain intermediate 3, and then the nitro group is reduced to obtain intermediate 4.
It is then condensed with 3-chloropropionyl chloride to obtain intermediate 5, and finally dehydrochlorinated to form mesylate to obtain osimertinib mesylate.
More than 80% of the substances in this step cannot be developed by current scientific and technological means, let alone the microwave reactors required.
Therefore, Xu Yun could only find another way and start directly from the structure.
After all, there are many papers on targeted drugs based on paclitaxel in later generations, such as 10.1186/S-023-01004-6, which was very impressive to Xu Yun. About 90% of the primers and ingredients required in it are already available in the chemical community.
developed.
Xu Yun can find opportunities to guide the remaining 10%, which is at least much simpler and more reasonable than creating 80% of substances that do not exist today.
Of course.
One of the reasons why Xu Yun remembered this paper was mainly because its primers contained tamofan.
Also known as the birth control pill...
But this is normal.
After all, the early use of tamofen was to block the effects of estrogen, thereby inhibiting the proliferation of breast cancer cancer cells. It is very suitable for the treatment of breast cancer and adjuvant treatment after breast cancer surgery.
"The yew trees in Longyou..."
Hearing this, Lao Guo subconsciously looked at Li Jue, who quickly nodded:
"No problem. Didn't we cooperate with the comrades from Longyou once before? We can just ask them to help find yew trees."
Hearing what Li Jue said about cooperation, Xu Yun couldn't help but smile.
What Li Jue was referring to was the fishing trip during the sniper attack on U2, in which the enemy agent who went by the pseudonym Chen Wenliang and was surrounded by rabbits acting was captured.
The place where this incident occurred was Jinta County, Longyou. Since Chen Wenliang's identity belonged to a very high-level long-term secret line, the 221 base and the local political commissar Lin could communicate directly.
If you really find yew trees, just ask the comrades over there to send them over.
Then Lao Guo looked at Xu Yun again and asked:
"Xiao Xu, what about paclitaxel? What about the targeting you mentioned?"
"Target..."
Seeing this, Xu Yun pondered for a moment and said to Lao Guo:
"Guo Gong, do you still remember an idea I once provided when we were discussing rice hybrid technology?"
"idea?"
Lao Guo was slightly startled and said in surprise:
"what idea?"
When Xu Yun heard this, he picked up the pen on the table, wrote a big R and a small R, and shook it in front of his face:
"At that time, I once mentioned an idea to screen for high-quality genes, which involved the introduction of the pollen-killing gene R."
"That is, polyacrylamide gel electrophoresis is used to determine the size of the fragments present in each base reaction."
"Then the DNA fragments are separated with single-base resolution, and a labeled gel for each base is placed on the X-ray film, and some data can be measured."
"This belongs to the category of DNA sequencing. If we optimize it further, we can realize...PCR technology." (Note: See Chapter 581. I have been burying the foreshadowing for a month. Can some people stop writing it before I finish it?
At that time, I said that it was unreasonable to develop targeted drugs. I didn’t pay attention to the foreshadowing of my work and then started to fight with all my strength for no reason. At first, everyone was happy when the foreshadowing was over, but now it makes me depressed)
That's right.
PCR technology.
Xu Yun had laid the groundwork for this as early as when he was communicating about hybrid rice - it was just that he didn't think about using it to develop targeted drugs, because he still needed something to develop PCR.
But after the rabbits reached a cooperation intention with Germany, Britain and France, there is a possibility that this technology will be available in the short term.
This can be regarded as an unintentional intervention...
At the same time, it is precisely because of this.
Only then did Xu Yun dare to throw out the concept of targeted drugs, otherwise he could have chosen a less efficient but more feasible chemotherapy regimen.
And the other side.
After hearing the words "pollen death gene" mentioned by Xu Yun, Lao Guo quickly remembered what Xu Yun was referring to.
At that time, Yuan Guoliang and Hou Guangjiong had just arrived at the base with wild rice. While chatting with Yuan Guoliang, Xu Yun mentioned the concept of introducing the pollen-killing gene R into hybrid rice.
At that time, Hou Guangjiong expressed on the spot that there might be technical problems, but Xu Yun gave a DNA sequencing plan on the spot.
Afterwards, Liu Youcheng led the laboratory members to do a simple test analysis. After the results came out, Liu Youcheng only said one sentence to Lao Guo:
“There’s a lot of potential for this!”
Think of this.
Lao Guo finally understood Xu Yun’s thoughts:
"Xiao Han, you mean... to use DNA sequencing to find the target of targeted drugs?"
Xu Yun nodded:
"That's right."
But after receiving his affirmation, Lao Guo's brows still did not loosen, but instead tightened:
"It seems to be possible, but Xiao Xu, since we are looking for targets, we must observe and compare the cells, right?"
"Ordinary people's cells are easy to tell, but tumor cells..."
Speaking of which.
Lao Guo couldn't help but glance at Yang Kaiqu who was standing aside.
Biological experiments require a control group, which is something that even a physicist knows.
But ordinary human cells are easy to say, and more than 10,000 people in the base can collect them at will.
Even if necessary, he, Lao Guo, is willing to be the first guinea pig.
But the problem is that cancer cells are more difficult because there is only one lung cancer patient in the base, Yang Kaiqu.
Whether it is blood drawing or surgical collection, it is very harmful to him. Yang Kaiqu's current situation simply cannot afford such a procedure.
There may be many cancer patients in the capital, but it is obviously inappropriate to use other people's cancer cells for observation, and it is impossible for Yang Kaiqu's character to accept this plan.
However, just as Lao Guo frowned.
But Xu Yun's voice sounded next to him:
"Um...Guo Gong, I'm afraid you may have thought wrong. Our goal is actually not that complicated."
"After all, what we want to verify is the ability to detect cells, that is, compare two cells with different known points, and then find out the biological abnormalities of the points."
"For example, we can see with the naked eye that a fountain pen is thicker than a ballpoint pen. What the experiment needs to do is to be able to determine this in data through measurement results - that is, we need to be able to measure that the fountain pen is 1 centimeter and the ballpoint pen is 0.5
Ability."
"However, this kind of comparison cells does not have to be collected from the human body, as long as there are known obvious differences..."
Lao Guo was stunned for a few seconds when he heard this, but soon realized what Xu Yun said: