After being fired, I became the light of medicine

Chapter 248: Choosing the Lesser of Two Evils

Acute rejection is a common immune response after organ transplantation.

A more professional way of saying it is: acute rejection is the immune system's emergency response to the transplanted organ, and it is a protective mechanism that the human body has!
Actually,
As early as the 20s, around 40, a Western scientist discovered the existence of transplant rejection while studying skin transplants. This was the first time that acute rejection reactions were truly paid attention to by the medical community.

Ten years later, in the 20s, with the increase in clinical practices such as kidney transplantation, doctors observed more clearly the various rejection phenomena that occurred at different time periods after transplantation, and the concept of acute rejection reaction in modern medicine gradually became clear.

Another ten years later, in the 20s, with the continuous development of immunoassay technology, people had a deeper understanding of the immune mechanisms of acute rejection reactions, and the pharmaceutical community began to truly develop immune preparation drugs for the first time!
It was not until the 20s that human organ transplantation truly developed rapidly and became increasingly mature, with the emergence of immunosuppressants that could inhibit the proliferation of immune cells and reduce the sensitivity of the immune system!

of course.

Although immunosuppressants can significantly suppress the function of the immune system, even now, with modern medicine so advanced, immunosuppressants are still unable to completely control all rejection reactions!

Even now, there are many patients who suffer from uncontrollable acute rejection after organ transplantation and die after just a few days of "explosion".

Zhang Yang did not expect that the production of TEF glycoprotein might be related to the very dangerous "acute rejection reaction". After thinking for a moment, he decided to verify his idea first.

Just at this time, Wei Tian and Dr. Zhou also packed up their personal belongings and left the office area, and Zhang Yang was not going to let them come back to continue working overtime.

As a top drug developer, he is fully capable of planning the next experiment.

Five minutes later, figuring that Wei Tian and Dr. Zhou had left the park, he stood up and walked to the middle of the office area, clapping his hands.

"Okay, everyone, stop what you are doing for a moment. I have made some new discoveries and need to redeploy some new experimental tasks!"

"The leaders of each group come to my place for a meeting..."

……

Zhang Yang has a very clear idea about the next experimental arrangement.

First of all, he has now guessed the reason why Xia Xue's TEF glycoprotein level is far higher than that of other patients. It is possible that Xia Xue had an acute rejection reaction before, which stimulated the metabolism of immune cells to increase significantly, thereby secreting a large amount of TEF glycoprotein.

Therefore, the first thing to do now is to conduct an "acute rejection reaction experiment"!
As long as the TEF glycoprotein concentration increases in the "acute rejection reaction experiment", it can be proved that the increase in TEF glycoprotein concentration is caused by acute rejection!
of course.

The "acute rejection reaction experiment" cannot be conducted directly on the human body.

"Old Li, contact the animal experiment company right away and ask them to provide... uh, six normal experimental monkeys and four experimental monkeys that were bred with leukemia. They will be of great use to me!"

A staff member named Lao Li is the project coordinator of the first project team. He is a kind of logistical support, specializing in ensuring the provision of laboratory instruments, consumables, animal receptors and other professional items.

Upon hearing this, Lao Li knew that a large-scale experiment would be necessary next, so he agreed immediately without hesitation!

"Okay, Mr. Zhang, I'll contact the animal testing company that we work with right away."

"Six normal lab monkeys should be fine, but I need to ask if there are any in stock for four leukemia lab monkeys! If not, I will ask other animal testing companies!"

"Well, ask first, you can pay more!"

As the largest drug research and development company in the country, Qingshan Pharmaceutical is naturally the financial sponsor that major animal testing companies have long coveted.

After Lao Li made the call, at one o'clock in the afternoon, six normal experimental monkeys appeared in Qingshan Pharmaceutical's special animal laboratory.

Generally speaking, animal experiments are mostly conducted using mice, but mice are not capable of performing the animal experiment that Zhang Yang wants to conduct this time.

As mentioned before, acute rejection reaction is a common immune response after organ transplantation. Therefore, in order to trigger the "acute rejection reaction" and conduct the "rejection reaction experiment", Zhang Yang needs to perform organ transplantation surgery on experimental monkeys.

Two o'clock in the afternoon, animal laboratory.

Two normal experimental monkeys that were injected with anesthesia completed a kidney organ transplant. Monkey A's kidney was transplanted into monkey B, and monkey B's kidney was transplanted into monkey A!
Although it sounds a bit cruel, this is the best and most real "acute rejection reaction experiment"!
Zhang Yang is already accustomed to such experiments. He knows very well that if it is not the experimental monkeys that have to bear all this, then only humans will have to bear all this!
This is modern medicine.

At 2:30 in the afternoon, another piece of news came.

The animal laboratory next door also completed the kidney transplant operations on the remaining two pairs, or four other normal experimental monkeys. The operation was also to exchange kidneys and conduct the "acute rejection reaction experiment"!
At the same time, project coordinator Lao Li also brought new news.

The four experimental monkeys that were bred with leukemia that Zhang Yang requested also arrived at Qingshan Pharmaceutical.

Animal experiment companies usually use genetic technology to cultivate animal receptors with various diseases, so they usually need to be customized in advance. This time, the four leukemia experimental monkeys were urgently airlifted from a neighboring province and specially supplied to Qingshan Pharmaceutical.

2:50 p.m.

Four experimental monkeys suffering from acute myeloid leukemia also completed the transplant surgery, using the same method as before!
Zhang Yang breathed a sigh of relief.

Next, Tsingshan Pharmaceutical only needs to wait for the occurrence of acute rejection reaction in the experimental monkeys and observe whether the TEF glycoprotein in their blood increases significantly!

All the R&D personnel of the first project team of Qingshan Pharmaceutical finally got a rare break. Soon, the ten experimental monkeys woke up from anesthesia. They felt something was wrong with their bodies, but they were firmly fixed and could not move at all.

At six o'clock in the afternoon, only four hours had passed since the first pair of normal experimental monkeys completed the kidney transplant operation.

"Mr. Zhang, the first blood test data is out!"

"Before the transplantation, the TEF glycoprotein concentrations in the two experimental monkeys were only 0.15mmol/L and 0.18mmol/L. Now, four hours later, the TEF concentrations in the bodies have risen to 0.25mmol/L and 0.29mmol/L, nearly doubling!"

"Also, the metabolic rate of immune cells that you specifically asked to monitor was revealed."

"Before the surgery, the metabolic rate of immune cells in both monkeys was 0.1mmol/min. Now, four hours after the surgery, the metabolic rate of immune cells has increased to 0.2mmol/min, which is also nearly double the rate!"

Zhang Yang hurriedly took the data and looked at it carefully, and finally breathed a sigh of relief!

Sure enough, his idea was not wrong!

The increase in the concentration of TEF glycoprotein is caused by an acute rejection reaction!

Or to be more precise:
The concentration of TEF glycoprotein is determined by the metabolic rate of immune cells!
The faster the immune cells metabolize, the more TEF glycoprotein they secrete in the blood!

"Good good!"

"Keep monitoring!"

Zhang Yang felt much more relaxed. Half an hour later, the four-hour data of the remaining two pairs of normal experimental monkeys were also released.

Similar to the data results of the first pair of experimental monkeys, the subsequent two pairs of normal experimental monkeys also showed accelerated immune cell metabolism and increased TEF glycoprotein concentrations.

At this point, Zhang Yang is 99% certain that the production of TEF glycoprotein is linearly proportional to the metabolic rate of immune cells D8+T cells!
but.

Zhang Yang is still waiting for the last two sets of experimental data.

7pm,

The data of the last two pairs of transplants, that is, the four experimental monkeys that were bred to have leukemia, came out in four hours! The results excited Zhang Yang!
The four leukemia experimental monkeys showed a significant increase in both the metabolic rate of immune cells and the concentration of TEF glycoprotein in the blood!
The results are exactly the same as those of the previous experiments!
"It's done!"

……

Zhang Yang was already exhausted from working overtime and staying up late, and now that he had finally found the cause of the elevated TEF glycoprotein, he was finally relieved.

At the same time, it's not just him.

Zhang Yang also knew that his colleagues in the first project team had been working overtime for nearly half a month because of the improvement plan of "Ibetuzumab". Everyone was in a tense state both physically and mentally, and they had not had a good rest for a long time.

After quickly arranging two young project team members to stay in the laboratory and draw blood from animals every four hours, Zhang Yang ordered the other R&D personnel to go home and have a good rest.

The researchers were naturally happy about this.

……

The next morning at 8:30, when Zhang Yang arrived at the R&D center in high spirits, he found that many R&D staff had arrived early.

Wei Tian and Dr. Zhou rested for nearly a whole day and also showed up at the R&D center early.

As soon as he saw Zhang Yang, Dr. Zhou came up to him excitedly:

"Mr. Zhang, you are too strong, aren't you?! I already know about the 'acute rejection experiment' you conducted yesterday!"

"I didn't expect that the production of TEF glycoprotein is not related to the number of immune cells, but to the acute rejection reaction and the metabolic rate of immune cells!"

“This… is unexpected!”

Zhang Yang couldn't help but smile. Since Dr. Zhou already knew the results of yesterday's experiment, he didn't have to explain it.

He smiled and said:
"It's not about strength or weakness. I'm just lucky. If you hadn't done such a detailed job before, I wouldn't have been able to find any clues."

"By the way, it has been thirteen hours since I left the lab last night. During these thirteen hours, what were the subsequent experimental results of the ten experimental monkeys?"

Dr. Zhou certainly understood what Zhang Yang was asking, and said hurriedly:
"After you left last night, the researchers who stayed behind drew blood every four hours as required, completing a total of three blood sample tests."

"I just checked the latest experimental results. The concentration of TEF glycoprotein in the ten experimental monkeys has increased compared to last night, and the metabolic rate of immune cells is also continuing to increase, which is consistent with the previous experimental conclusions!"

Consistent!
Zhang Yang's smile became even brighter. This result was exactly as expected.

The human body, or the immune system of primates, works in this way. When a foreign body invades, it will first activate the human immune system. Later, as the immune system is unable to quickly eliminate the invader, the immune system will gradually increase the metabolic rate until the metabolic peak of the immune cells is reached.

"Okay, now that we have figured out the secret of TEF glycoprotein, the next step is to find a way to improve the therapeutic effect of 'ibuzumab'."

"Ok!"

Dr. Zhou nodded heavily and a smile appeared on his face.

After going through so much trouble and spending so much effort to study TEF glycoprotein, the ultimate goal is actually to improve the therapeutic effect of "ibuczumab".

After a moment he said:
"Mr. Zhang, I arrived at the company at six this morning, and I have prepared some plan materials in advance."

"Have you finished your breakfast? If so, how about we discuss it now?"

"Oh? You're here so early?"

Zhang Yang was slightly stunned, then continued:
"I've had breakfast, let's start the discussion now."

"it is good."

Two minutes later,

Zhang Yang, Dr. Zhou, Wei Tian and two core team leaders of the project team came to a small conference room.

Without any preparation, Dr. Zhou took the lead and said:
"Mr. Zhang, we have confirmed that TFE glycoprotein is produced in large quantities after the human body has an 'acute rejection reaction'!"

"A more accurate statement is that it is due to the fact that immune cells D8+T cells are produced in large quantities after their metabolic rate is greatly increased."

"So, the key point is to find a way to increase the metabolic rate of the patient's immune cells D8+T cells, so that they can secrete a large amount of TEF glycoprotein!"

"I looked up some information. The current mainstream method in the medical field is to inject low doses of 'allogeneic T cells' into the patient's body to activate the body's acute rejection reaction!"

Allogeneic T cells.

Zhang Yang nodded slightly.

It's like a vaccine.

Vaccines are made by injecting a low-toxic strain of a virus into the human body, which allows the immune system to remember and produce antibodies.

Injecting allogeneic T cells allows the immune system to recognize the invasion of foreign matter and initiate an emergency rejection response!
but.

Zhang Yang's thoughts had just flashed through his mind when Dr. Zhou's voice continued to be heard.

"It's just that this method will have some side effects, not to mention the common side effects such as low-grade fever and endocrine abnormalities.

What I am most worried about is that there is data showing that after the injection of 'allogeneic T cells', due to the long-term activation of 'acute rejection reaction' in the body, the immune cells in the emergency state may cause damage to human organs! "

"Especially since most of our patients have undergone bone marrow transplantation, I am worried that the probability of this side effect will be further amplified in our patients!
It will attack the hematopoietic stem cells in our patients’ bone marrow, eventually causing bone marrow hematopoietic failure! ”

Zhang Yang took the information handed over by Dr. Zhou and read it carefully, frowning.

Twenty minutes later, the discussion ended.

Dr. Zhou's concerns are indeed necessary, but currently the most mainstream and relatively safe method in the medical field to activate the "acute rejection reaction" is only -

Injection of allogeneic T cells!

"Choose the lesser of two evils and start injecting allogeneic 'T cells' into patients. Let's try it!"

"Just... pay special attention to monitoring the side effects!"

"it is good!"

(End of this chapter)