Into Unscientific Chapter 610

   "Targeted drug?"

  After Xu Yun said this somewhat weird word.

  The entire ward fell silent for a moment, and needles could be heard in the room, obviously they did not understand the meaning of these words.

   Fortunately, it was not the first time for Lao Guo to hear these weird new gadgets from Xu Yun's mouth, so he quickly came back to his senses:

   "Targeted drug? Xiaohan, what is this?"

  Xu Yun thought for a moment after hearing the words, but did not give an explanation directly, but turned to look at Lin Yu, and said:

   "Dr. Lin, the concept of targeted drugs is rather complicated to introduce, so can I trouble you to talk about 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 a very detailed grasp of the information on lung cancer, and he quickly talked about it:

   "Lung cancer is a disease that has gradually become common in recent years. The number of people suffering from it every year is smaller than that of gastric cancer, but the growth rate is very fast."

   "The reason for its formation is still unknown. Ten years ago, a scholar across the sea once proposed the idea that smoking causes lung cancer."

   "But a few months before I returned home, a refutation theory called the birth weight paradox appeared, so how lung cancer is formed is still a controversial topic today."

  Xu Yun nodded slightly.

  As a Ph.D candidate in biology at the University of Science and Technology of China, his supervisor is Tian Zhigang, a well-known immunologist in China, so he is no stranger to what Lin Yu said.

  Different from Xu Yun's future generations.

  In 2023, lung cancer will be the most common and deadliest cancer among all cancers, 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.

  Lung cancer was actually a very rare cancer more than 100 years ago.

  1912.

  Across the sea is a doctor named Emma Watson—yes, the doctor with the same name as Hermione. He once mentioned one thing in a medical book:

  He rummaged through the literature all over the world, and found a total of 374 cases of lung cancer.

   However, after 1920.

  The incidence 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 attention to lung cancer, and when they studied the cigarette machine across the sea, they found 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 terrible these years:

  Taking last year as an example, the per capita annual smoking across the sea last year was more than 4,000.

   That's right.

  4000+.

  This is like you slap yourself more than ten times a day, then the doctor will definitely link the two when checking for kidney deficiency.

  However, a "birth weight paradox" emerged across the sea a few years ago, making the relationship between cigarettes and lung cancer blurred a lot.

   The rebuttal doctrine goes like this:

  If smoking is harmful to health, maternal smoking will lead to low birth weight of the baby, and the mortality rate of the baby will increase.

  But according to actual statistics, scholars across the sea found that it was just the opposite.

   Babies born to smoking mothers have a lower mortality rate than normal babies.

  So ever since.

  There is another layer of fog between smoking and lung cancer, and no one knows whether the two are related.

   This paradox will not be confirmed and explained until 2001, so it is normal for Lin Yu to be unclear at the moment.

   Then Lin Yu paused and continued:

  “After lung cancer gradually became a common disease, the corresponding treatment plan gradually began to develop.”

  “In the 1940s, pneumonectomy was the classic surgical treatment for lung cancer. For example, in early 1941, Dr. Zhang Jizheng from Yanjing Union Medical College Hospital completed the first left pneumonectomy in our country.”

  “Nowadays, with the development of medical level, our surgery has also changed from whole lung to lobectomy, and the scope is relatively much smaller.”

   “At present, 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 more suitable for surgery.”

   "Of course, this sentence is also relative."

  Xu Yun nodded and asked again:

   "What about the in-depth study of the pathogenic structure of lung cancer? How far has it developed so far?"

   "Disease-causing structure. Oh, you mean the structure of cancer cells?"

  Lin Yu blinked when he heard the words, and this time his answer was much more concise:

   "Lung cancer cancer cells have mastered the relevant cultivation techniques at home and abroad. After all, the cultivation of cancer cells has been successful fifty years ago, and it is not a big secret now."

   "As far as I know, Yanjing has achieved the separation of solid tumor stem cells using colony formation experiments, and has achieved certain results in the regulation mechanism."

   "However, the research on cancer cells is nothing more than that, and it seems that there are not many new discoveries even across the sea—at least as far as I know."

  Xu Yun listened quietly and looked up at the scene.

  At this time, except Li Jue still has a face of [OvO].

  Lao Guo, Yang Kaiqu, and Zhou Cai have all shown a little understanding, and seem to have kept up with the rhythm.

  So he coughed lightly, took over Lin Yu's right to speak, and said:

   "Doctor Lin, have you ever shot a target?"

   "Target?"

   Lin Yu was startled for a moment, and immediately raised his chest:

   "Of course I did."

joke.

  These people on the scene counted as one, even Li Jue's assistant Zhou Cai and the terminally ill Yang Kaiqu, they had never missed a target before.

  The popularity of the militia is very high these days, and even the number of civilian guns is quite large.

   It is not uncommon for those who have shot a gun, but it is rare for those who have not.

   Then Xu Yun gestured the shapes of several targets in the air with both hands, and said:

   "Doctor Lin, since you have shot a target, you must know the process of shooting a target."

  “When shooting a target, there will be many targets standing on the range. You can only hit the one that is facing you. If it is crooked, you will not be scored or deducted.”

   "In the microscopic field, if we regard the tumor as a shooting 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 site discovered by the University of Pennsylvania four years ago, etc."

  Looking at Xu Yun who is talking eloquently.

  Lin Yu, who has three overseas doctorates, was suddenly taken aback, and immediately realized something, and couldn't help but interrupt him:

   "Wait, Comrade Han Li, the targeted drug you mentioned."

   "Isn't it referring to the 'bullet' that targets cancer cells and then precisely destroys them?"

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 concept of targeted drugs in a broad sense is not to destroy cancer cells, but to curb the growth of cancer cells after hitting key nodes."

   "Just like a bullet, when a bullet hits someone, it doesn't immediately clear your blood bar. Ahem, life, but destroys blood vessels to deactivate your body."

  Lin Yu's pupils suddenly shrank.

  WTF?

  A targeted drug that curbs 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 about the ingredients? What about the production process?"

  Hearing this set of questions in Lin Yu's mouth three times, Xu Yun couldn't help but smile.

   It turns out that Lin Yu, a cold-faced boss who looks like a paralyzed face, also has emotional moments

  Then he took a deep breath, made an urgent gesture to Lin Yu, and explained:

   "Doctor Lin, I just 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 the specific ingredients and process."

   "It's just a biological mechanism. Basically, this drug can act on specific protein molecules, enzymes, and gene fragments through certain reactions."

   "After all, cancer cells are caused by gene mutations, so in theory, there should be some rationality in targeting the mutation site."

   "Act on a specific gene segment?"

  Lin Yu's pupils shrank again when he heard the words, but this time he was not in a hurry to speak out.

Gene.

   This is an extremely mysterious and extremely front-end field.

  Humans discovered cells very early. As early as the 17th century, Hooker, who fell in love with a calf, discovered cells.

   Followed in 1836.

  Valentin discovered the nucleolus in the nucleus of connective tissue cells, which opened the structure of the cell.

   Then came the cell theory of Schleiden and Schwann, Mendel's laws of genetics, Weirshaw's pathology and so on.

   Then came the end of the 19th century.

  Centrosomes, mitochondria, chromosomes, and Golgi bodies have also been discovered one after another.

   But the concept of DNA, that is, the gene, was first introduced, but it was not until 1924.

  Wait until 1944 at the same time.

   Avery and others confirmed that the transformation factor of pneumococcus is DNA, and it was the first time that the gene was determined to be a DNA fragment with genetic effects by experiments.

  As for the structure of DNA?

   It has only been out for eight years, and it belongs to a brand new field.

  So in this day and age.

  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 is precisely because of the mysterious abnormality in the genetic field that Lin Yu is a little uncertain whether what Xu Yun said is true or not.

after all

  In the more general medical field, many drugs have been used in cytotoxic chemotherapy these days.

   For example in 1948.

  Farber used the antifolate methotrexate to treat acute lymphoblastic leukemia, which opened the prelude to modern cancer chemotherapy.

   Since then, with the research and development of anticancer drugs, chemotherapy drugs have also been developed rapidly.

Up to now.

   Chemotherapy drugs that have been discovered and used include a large number of categories such as fluorouracil, 6-hydroxypurine, methotrexate, cyclophosphamide, and actinomycin D.

   And if Lin Yu remembers correctly.

  Internationally, there is a saying about the mechanism of action of these drugs:

  The function of these drugs is to interfere with DNA integrity, interfere with DNA replication, act on microtubules in the mitotic spindle, and inhibit mitosis.

  Thus preventing the proliferation, invasion and metastasis of cancer cells until finally killing the cancer tissue.

   Indeed.

  This mechanism is not consistent with the targeted drug mentioned by Xu Yun, but it is somewhat similar in nature, both of which act on the point in the cell.

  So if you think about it from this angle.

   Not to mention whether the current technical level can do it, this idea may be true

  Not a big problem?

Of course.

  This is just a possibility.

  Afterwards, Lin Yu adjusted his glasses, regained his original composure, 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."

   "However. The idea is the idea. For now, we want to implement it in the application. That is, to produce finished products. It seems that there is not much possibility at all, right?"

   Hear this statement.

  Old Guo on the side also nodded subconsciously.

  Although he is not an expert in biology, he has a very good relationship with Liu Youcheng in the chemical laboratory of the base in private.

  A few days when he went to the laboratory, a student happened to read some papers about genes in a foreign journal and asked Liu Youcheng for advice.

  At that time, Liu Youcheng answered that genes belonged to an undeveloped land, and even the top foreign institutions were still in the situation of half research and half guessing, and even the proportion of guessing was even larger.

  However, facing Lin Yu's question, Xu Yun seemed very calm:

   "That's right, Dr. Lin, the production technology of targeted drugs is very difficult and involves many special links."

   "But... again, if we make a simplified version of targeted drugs, I think it is still feasible."

  Xu Yun bit the three words "simplified version" very seriously.

   Well known.

  Even in 2023, when Xu Yun travels through, lung cancer is still a terminal disease with a very high mortality rate.

  Maybe some people can live for a long time because of 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, if you want to suppress the disease to a certain extent, it is still possible to increase the life span of the patient by a few years.

  This may be targeted therapy.

  Generally speaking.

  Even for patients with advanced lung cancer, the use of targeted drugs has the opportunity to live for three or four years or even longer.

  The so-called targeted therapy is a treatment that targets the identified cancer-causing sites at the cellular molecular level.

  The site can be a protein molecule inside the tumor cell, or a gene fragment.

  Targeted drugs enter the body and will specifically combine with cancer-causing sites to cause specific death of tumor cells without affecting normal tissues around the tumor.

  The source of targeted drugs can be traced back to 1960, when the biological laboratory of Philadelphia University discovered a chromosomal abnormality related to many leukemia patients.

  Ten years later, when a biomedical scientist named Compli was studying this subject, he discovered that this abnormality occurs when a part of the two chromosomes 9 and 22 translocates.

   And this abnormal part was the target of imatinib, the first targeted cancer therapy drug.

Of course.

  The source of targeted drugs can be traced back to the current period, but the technical development generally took place after the 1980s or even 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 you don't want targeted drugs in the standard sense, Xu Yun believes that it is still feasible to make a simple beggar's version.

after all

  He laid a foreshadowing back then.

  Think here.

  Xu Yun paused again, and continued to explain:

   "Targeted drug Targeted drug, we can actually divide this word into two parts, one is targeted, and the other is drug."

   "This is somewhat similar to our Zhuxianjian missile. The target is the laser guidance and waverider structure, and the explosive is the warhead and warhead."

  Old Guo and Lin Yu nodded, the metaphor is very clear.

   Then Xu Yun raised a finger, swayed 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 at the beginning, the most suitable components of targeted drugs should be monoclonal antibodies or small molecular compounds, which are mainly formed through some complex reactions."

   "For example, using N-methylindole and dichloropyrimidine as starting materials, a compound is synthesized through a sylation reaction of a certain substance, and then proceeds to the next step of synthesis."

   "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."

   "However. I once saw a record in the handbook of Fenglingyueyingzong, saying that hundreds of years ago, someone suffered from 'congestion of the lungs' and was 'almost dying'."

   "Later, he got a folk prescription by accident. He asked someone to bring a kind of wood-boiled decoction from Longyou Road. He decocted two doses a day and finally lived for more than a year."

   "So I think if we can find that wood and use it as a prodrug for reference research, there may be a chance to find a suitable targeted drug formulation."

   Hearing Xu Yun's words.

   Lao Guo couldn't sit still, and asked quickly:

   "Xiao Han, what is that kind of wood called?"

  Xu Yun glanced at him and gave the answer:

   "Yew."

   Yew.

   This is a general term for a yew plant, which belongs to an excellent ornamental shrub, also known as yew, also known as yew.

  In Xu Yunlai's descendants, it belongs to the national first-class rare protected plants.

   But what few people understand is.

  The true value of yew does not lie in its ornamental value, but in its medicinal value.

  Generally speaking.

   Most herbal plants can basically produce secondary metabolite derivatives after treatment, that is, extracts.

  For example, the extract of aloe vera is very suitable for making facial masks, and the extract of milk thistle is the main ingredient of liver protection tablets, etc.

   And so is yew, but its extract is

   Paclitaxel.

   That's right.

   Paclitaxel.

   This is an anti-tumor active ingredient isolated from the bark of Taxus brevifolia, and it is one of the best drugs for treating metastatic ovarian cancer and breast cancer.

  At the same time, it also has significant curative effect on lung cancer and esophageal cancer, and has obvious inhibitory effect on nephritis and parvovirus inflammation.

  Generally.

  About 13.6kg of bark can extract 1g of paclitaxel, and 3-12 yews of more than 100 years are needed to treat a patient with ovarian cancer.

   Therefore, the price of this substance has become very high and it has attracted a large number of humans to cut down yews, making the yews that were originally scarce even more scarce and on the verge of extinction.

Of course.

  Paclitaxel is a chemotherapy drug in nature, and it 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 respects.

   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.

  Targeted drugs act selectively on tumor cells.

  In addition, the application of chemotherapy drugs is generally determined according to the results of histopathological specimens, while the application of targeted drugs needs to be determined according to the results of genetic monitoring of histopathological specimens.

  Some sense Note is a certain sense.

  The difference between chemotherapy drugs and targeted drugs is actually equivalent to an atomic bomb and a neutron bomb.

  Atom bombs and neutron bombs are obviously not the same weapon, but they have something in common in some deep aspects.

   And once there is paclitaxel as a sample.

  Then the task of the rabbits has changed from pure research and development without any reference to the direction of converting chemotherapy drugs into targeted drugs.

   Indeed.

   Xu Yun can't say how effective this method will be, but at least it's easier than developing a new drug.

  For example, the example he gave before is the synthetic route of osimertinib mesylate:

  Using N-methylindole and dichloropyrimidine as starting materials, an intermediate product was synthesized by Friedel-Crafts alkylation reaction catalyzed by aluminum trichloride.

  Then p-toluenesulfonic acid and the intermediate product were heated to reflux in 2-pentanol to obtain the intermediate product 2.

  Condensation with secondary amine in microwave reactor to obtain intermediate 3, and then nitro reduction to obtain intermediate 4.

  Condensed with 3-chloropropionyl chloride to obtain intermediate product 5, and finally dehydrochlorinated to form mesylate to obtain osimertinib mesylate.

  In this step, more than 80% of the substances cannot be produced by the current scientific and technological means, let alone the required microwave reactor and the like.

  So Xu Yun could only find another way, starting directly from the structure.

After all, there are many paclitaxel-based targeted drug papers in later generations, such as 10.1186/S13578-023-01004-6, which Xu Yun was very impressed with, about 90% of the primers and ingredients needed are already in the chemical industry. developed.

  The remaining 10% Xu Yun can find an opportunity to guide it out, at least it is much simpler and more reasonable than producing 80% of the substances that do not exist today.

Of course.

   Xu Yun remembers this paper, one of the reasons is that it contains tamofin in its primers,

   is also known as the birth control pill.

   But this is normal.

   After all, the early use of tamofen is to hinder the function of estrogen, thereby inhibiting the proliferation of breast cancer cells, which is very suitable for the treatment of breast cancer and adjuvant therapy after breast cancer surgery.

   "Is it the yew in Longyou?"

  Old Guo Wenyan subconsciously looked at Li Jue, Li Jue nodded quickly:

   "No problem, didn't we cooperate with the comrades from Longyou once before, and we can just ask them to help find the yew."

  Hearing what Li Jue said about cooperation, Xu Yun couldn't help but smile.

   What Li Jue was referring to was the fishing when he sniped U2, that is, the arrest of the enemy agent whose pseudonym Chen Wenliang was surrounded by rabbits acting in plays.

  The place where this incident happened was in Jinta County, Longyou. Since Chen Wenliang's identity belonged to a very dense long line, the 221 Base and the local forest political commissar could communicate directly.

  If you can find the yew, just ask the comrades over there to send it over.

   Then Lao Guo looked at Xu Yun again and asked:

   "Xiao Xu, what about paclitaxel? How do you solve the problem you mentioned?"

   "Target"

  Xu Yun pondered for a moment when he saw this, and said to Lao Guo:

   "Guo Gong, do you still remember an idea I offered when discussing rice hybrid technology?"

"idea?"

  Old Guo was slightly taken aback, and said in surprise:

"what idea?"

  Xu Yun heard the words and 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 mentioned an idea of ​​screening high-quality genes, which involved the introduction of the pollen lethal gene R."

   "That is, polyacrylamide gel electrophoresis is used to determine the size of the fragments present in each base reaction."

   "Then separate the DNA fragments by single-base resolution, place a labeled gel for each base on X-ray film, and then some data can be measured."

"This belongs to the category of DNA sequencing. If we further optimize it, we can realize the .PCR technology." (Note: See chapter 581. I have been burying the foreshadowing for a month. Can some people stop writing before I finish writing it? It's unreasonable to say that it's unreasonable to engage in targeted drugs. I co-authored the foreshadowing that I didn't pay attention to it, and then I didn't pay attention to it, and then I died inexplicably. Originally, everyone was happy when the foreshadowing was received, but now I'm depressed)

   That's right.

  PCR technology.

  As early as when he was communicating about hybrid rice, Xu Yun had already planted this foreshadowing—it's just that he didn't expect to use this thing to make targeted drugs at the beginning, because there were still some things missing to make PCR.

  But after the rabbits reached a cooperation intention with Germany, Britain and France, this technology has the possibility of appearing in the world in the short term.

  This can be regarded as unintentional insertion

   And because of this.

   Xu Yunfang dared 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.

  Hearing the words "pollen lethal gene" that Xu Yun said, 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 lethal 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 took the laboratory members to do a simple test analysis. After the results were obtained, Liu Youcheng only said one sentence to Lao Guo:

   "There is a lot to do in this matter!"

  Think here.

  Old Guo also understood Xu Yun's thoughts:

   "Xiao Han, you mean to use DNA sequencing to find the target of targeted drugs?"

  Xu Yun nodded:

   "Exactly."

  But after getting his affirmation, Lao Guo's brows still did not loosen, but tightened even more:

   "It seems to be feasible, but Xiao Xu, since we want to find the target, we must observe and compare the cells, right?"

   "The cells of ordinary people are easy to say, but tumor cells."

   Speaking of which.

  Old Guo couldn't help but glance at Yang Kaiqu who was standing aside.

  Biological experiments need a control group, which is something he, a physicist, understands.

   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 it is more difficult for cancer cells, because there is only one lung cancer patient, Yang Kaiqu, in the base.

  Whether it is blood drawing or surgical collection, it is very harmful to him. With Yang Kaiqu's current situation, he can't afford this kind of procedure at all.

  There may be many cancer patients in the capital, but it is obviously not appropriate to use other people's cancer cells for observation, and it is impossible for Yang Kaiqu to accept this plan.

  However, just as Lao Guo frowned.

  Xu Yun's voice sounded beside him:

   "Er Guogong, I'm afraid you are thinking 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 types of 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 the pen is thicker than the ballpoint pen, and what we need to do in the experiment is to be able to confirm this matter through the measurement results - that is, we must be able to measure that the pen is 1 cm, 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."

  Old Guo Wenyan was stunned for a few seconds, but soon realized what Xu Yun said:

   "Xiao Han, what do you mean"

  Xu Yun nodded vigorously, confirming his guess:

   "That's right, it's the local donkey."

Chapter end