I can extract side effects

"The expression of the MLLT3 gene is the key to determining the self-renewal ability of hematopoietic stem cells."

Ding Mian stood in front of the operation table full of various equipment, pointed at the bright red in the rectangular petri dish in front of him, and introduced it eloquently.

"This is the result of our hard work for more than half a year, the real artificial blood."

"We took epithelial cells from more than ten experimental mice, and after introducing the combination of four factors, Oct4, Sox2, Nanog and LIN28, all of them were induced into induced pluripotent (iPS) stem cells."

"Following that, five special transcription factors were introduced to induce iPS stem cells into hematopoietic stem cells."

"Up to this point, for the systematic laboratory training I have received, it is only a basic operation, which is quite easy. Back then, I was in the doctor's laboratory. I don't know how many times I did this kind of experiment. Flow, that’s all…”

"Ahem~" Tang Que stood behind him, coughed twice, and said expressionlessly, "Get to the point."

"Yes, yes, the focus is on the MLLT3 gene. We used gene editing technology to insert the active MLLT3 gene into the hematopoietic stem cells, and then the hematopoietic stem cells in the dish multiplied at least 20 times, and there was no tendency to stop."

"The hematopoietic stem cells, which we've tested transplanted into mice, developed all the normal components of the immune system, got a fully functional and durable blood system, showed no signs of leukemia or any other blood disease, and The results are sufficient to confirm the success of the experiment."

"However, that's only half the battle."

Around twenty staff members in white coats were standing around, listening intently with their eyes shining.

After being reminded, Ding Mian didn't repeat himself, but went straight to the point.

"Since we wanted real artificial blood in addition to hematopoietic stem cells, the next step was taken very quickly."

"This has to talk about another H gene that controls blood type."

"It is well known that the expressed antigens on the red blood cell membrane determine the blood type, the most important of which is the ABO blood group system."

"Type O red blood cells do not contain A and B antigens, but plasma contains anti-A and anti-B antibodies; type A red blood cells have type A antigens on their membranes, but plasma contains anti-B antibodies; type B red blood cells have type B antigens on their membranes , l and the plasma contains anti-A antibodies."

"There are type A and type B antigens on the membrane of type AB red blood cells, but no antibodies exist in the plasma, and red blood cells of any ABO blood type can be accepted."

"If the wrong blood type is entered, the antigen on the surface of the red blood cell meets the corresponding antibody in the serum, A to A, B to B, and blood coagulation will occur immediately, which will lead to death in severe cases."

"H gene can control the synthesis of H antigen. H is the antigen of Hh, the second largest blood group system. A and B are antigens of ABO blood group system. The two systems are inherited independently, but H antigen is the precursor substance of ABO blood group. It has A, The sugar group of B antigenicity needs to be connected to the H antigen in order to be converted into A and B antigens, showing the corresponding A, B, and AB phenotypes."

"If the expression of H gene in hematopoietic stem cells is missing, there will be no H antigen in the blood, and it will not be able to produce A and B antigens, which means that this blood can be transfused to any blood type of ABO, and it is a true universal blood. .”

"So, when we inserted the active MLLT3 gene fragment, we also suppressed the expression of the H gene, so that the genetically modified hematopoietic stem cells induced the generation of universal human blood that can be delivered to humans."

"Of course," he smiled, "Since there are hundreds of antigens on the human red blood cell membrane, some rare blood types are not included."

There was a burst of knowing chuckle from all around.

A young man in his early 20s said excitedly: "This is the legendary Bombay blood. This is a very rare blood type. I didn't expect that we could synthesize it in the laboratory. This is definitely a shocking breakthrough in synthetic biology." .”

The others also nodded one after another, and praised him in a hurry.

"Bombay blood was discovered in Mumbai, Tianzhu in the 1950s. It is comparable to the legendary dinosaur blood in China. It seems that there are only more than 100 cases in the country. It is of great significance!"

"This blood can be transfused to most people regardless of the blood type of the public. If it is applied in large quantities, it can greatly improve the storage and transportation of blood banks."

"From now on, our country will no longer be short of blood. It's so exciting to think about it."

"This is the meaning of our work. To change the world personally, what sense of accomplishment can be compared with work?"

"Yeah, even if you've been working overtime all this time, it's worth it."

"But we are only generated in the laboratory, the real difficulty is yet to come."

"That's right." Ding Mian took the conversation and said confidently: "In fact, many pre-theories of artificial blood are quite mature, and it is not particularly difficult to develop them in the laboratory."

"In the past few years, there have been teams at home and abroad trying to generate hematopoietic stem cells in vitro in the laboratory. Of course, some teams have indeed made progress, but they only stay at the laboratory stage, and there is no further after the animal experiments. "

"We are able to go one step further and generate real artificial blood in the laboratory, which means that we have gone further than others."

"However, on this difficult road, there is still the last big boss, which is mass production."

"We are a business, and if the product we develop cannot be commercially produced, it is meaningless."

Speaking of this, Ding Mian raised four fingers, his slightly immature face finally became serious.

"Let me summarize that there are five stages in the transformation of human epithelial cells into artificial blood."

"The first stage is the induction period, which is 0-8 days after the introduction of foreign genes, during which epithelial cells will begin to be induced into iPS stem cells.

"In the second phase, the differentiation phase after this, about seven to 10 days, the iPS stem cells transform into hematopoietic stem cells."

"In the third stage, hematopoietic stem cells are genetically modified, mainly MLLT3 and H genes. This technology is very mature and can be completed within 3 days.

"In the fourth stage, about 15 days after the cell fate decision is the expansion period, at this time, the newly generated hematopoietic stem cells proliferate in large numbers, with a transcriptome similar to normal adult hematopoietic stem cells and long-term self-renewal ability. The length of this time Depends on the required number of hematopoietic stem cells."

"In the fifth stage, three special factor combinations are introduced again, and the hematopoietic stem cells are officially transformed into universal blood in a culture dish, which takes about a week."

"When the transformation is complete, we can collect the blood in the petri dish and store it for use."

"These five processes do not seem complicated, but if they are not improved and directly applied to the biofactory, it is likely to become a complete disaster in mass production."

"Next, our top priority is to do our best to improve the production process during the period of clinical trials, so that it can be successfully commercialized at an affordable cost."

"Only in this way can the artificial blood project be truly successful, and our efforts for the past six months will be meaningful."

"Are you ready to overcome the next bigger difficulty?"

Ding Mian raised his clenched fist and roared loudly.

"Ready!"

Everyone roared in unison.

Their eyes shot out one after another, and their expressions were extremely excited, like a group of soldiers ready to go to the battlefield.

Seeing everyone walking out of the laboratory energetically, Tang Que looked at Ding Mian and said approvingly.

"You spoke very well just now, and your mobilization ability is also good. I have a bit of skill."

Ding Mian grinned and said: "Of course, I learned from you, can the effect not be good?"

Tang Que smiled slightly, and was about to say a few words of humility.

But I heard Ding Mian continue to say: "The whole biology laboratory has been conditioned by your PUA. I just learned how to switch it on and off, and the effect is natural."

He babbled, snapped his fingers, and said triumphantly: "Brother Que, why don't you say that you are the big boss? The effect of this brainwashing magic is really amazing. When I first saw it, It was a pupil earthquake, I never thought that the laboratory could be managed and played like this.”

Tang Que's face changed, and it was as dark as the bottom of a pot in an instant.

A gleam flashed in his eyes, and he said calmly: "Alright then, you can report to President Wei later by yourself."

Turn around and leave after speaking.

"Ah, I was wrong, Brother Que, I shouldn't be so indifferent." Ding Mian panicked and hurried to catch up.

"President Wei is such a big shot, if you weren't there when I met him, I'd be really nervous."

Tang Que touched his chin speechlessly, turned around and said, "You have been here for more than half a year, why are you still acting like this, you are not stable at all."

"Did you develop this artificial blood technology by yourself? If it weren't for the company's platform, if it weren't for the hard work of colleagues, if it wasn't for Mr. Wei, would you have achieved such results as soon as you joined the company?"

He shook his head, hating iron to be weak and said: "You have to raise your tail so soon? When you can really develop new things yourself, no matter how proud and complacent I am, I won't care about you, I will only cheer for you. Now what? , you save yourself."

"I originally wanted you to show your face in front of Mr. Wei this time, to earn your impression points, forget it!"

"I'll report this time by myself."

Ding Mian's face collapsed in an instant, he pursed his lips and muttered in his heart before returning to his seat.

He is an only child and has no brothers or sisters. When he was lonely, Tang Que would always accompany him, so he subconsciously treated him as a big brother. In a short time after work, the hierarchical relationship between the upper and lower leaders has not yet adapted well. .

So when Tang Que scolded him, he didn't feel any resistance. Instead, he knew that the other party's words were good words.

"Okay, isn't it just to keep a low profile and develop insignificantly? No one understands this better than me."

He turned on the computer, his fingers fluttered, turned all his emotions into motivation, and devoted himself to selfless work.

*****

Department of Hematology, Kunming First People's Hospital.

Early in the morning, when Liu Zhengming walked to the office, he saw that someone was already waiting at the door.

"Director Liu, hello. I'm Jia Qing, a clinical researcher of Sanqing Group. Recently, I have a clinical project on blood products, and I want to carry out clinical trials with the hematology department." The person who came was a young spirited guy with a very polite attitude .

"Oh, people from Sanqing, the young man is quite young. Come in." Liu Zhengming opened the door and walked in.

Jia Qing quickly brewed two cups of tea, handed over one, and sat down opposite.

"Okay, since you are a researcher of Sanqing, just follow the procedure." Liu Zhengming said kindly.

"First tell me carefully what kind of clinical trial it is." He picked up the teacup and gently blew hot air on the rim.

"It is a clinical project of artificial blood. We use human epithelial cells to induce differentiation into hematopoietic stem cells, and use genetic technology to remove the antigens on red blood cells, and obtain artificial blood without the three antigens A, B, and H."

"It has been successful in experimental animals such as mice and macaques..."

Jia Qing was a little nervous and said in a forced calm manner.

He is an employee who just joined the company this year, and the first follow-up project when he first joined the company was such a major project, so he couldn't help feeling a little uneasy.

"Huh?" Liu Zhengming was about to drink tea, put down his cup quickly, and said with a shocked expression: "Wait, are you talking about artificial blood?"

"iPS stem cells are induced to differentiate into hematopoietic stem cells, and then the universal artificial blood produced in vitro?"

Jia Qing nodded, and handed over the project introduction material he was holding tightly in his hand.

Liu Zhengming stopped drinking his tea, and looked serious as if he was facing a big enemy. After receiving the information, he began to browse carefully.

While watching, he slapped his thigh fiercely.

When he was about to finish reading, he suddenly raised his head and asked with disbelief, "No, why didn't you publish a paper for such a major achievement?"

"This project is definitely a paper at the top journal level. Science, cells, and nature, it must be published casually. Don't you all publish it?"

Jia Qing curled her lips and said in a low voice, "Because we have a bad relationship with foreign academic circles, so now our discoveries will no longer be published in foreign academic journals."

Liu Zhengming suddenly felt itchy: "How can this work? How can there be no papers for such a major experimental result? If foreign publications are not good, then they will be published domestically. Isn't it not possible for domestic publications?"

Jia Qing froze for a moment, scratched his head and said, "This seems to be posted on the internal forum of Sanqing."

Liu Zhengming grieved and said: "You are too stingy, isn't it appropriate not to show such a major achievement to others?"

He said angrily: "Who is your leader, I want to respond to him. No, I'm going to respond to Mr. Wei online."

Jia Qing said with a dry smile: "Okay, Director Liu, I will help you pass it on to the leader. Why don't you see how this clinical trial is carried out first?"

"Should I first recruit some volunteers to receive two small blood transfusions four months apart, and then monitor closely to see if there are any adverse reactions in the body?"

Liu Zhengming nodded: "That's about it. At least 10 subjects should participate in the first batch, and there will be two small blood transfusions of 5-10ml, one with standard donated blood and one with laboratory-grown artificial blood. to determine the lifespan and response of artificial blood in humans."

"Very well, the artificial blood is also marked with medical radioactive substances, so that we can better monitor its whereabouts in the human body and know how long the artificial blood can survive in the body."

"However, if this person is selected, you still need to be bold." He frowned and slammed the table. "This is the rare Bombay blood that's in short supply everywhere."

Jia Qing suddenly trembled with fright.

Li Zhengming didn't even look at him, and took out his mobile phone to make a call.

"Hello, Suzhou Blood Center?"

"How many of you have Bombay blood?"

"I need a list of Bombay blood and Bombay blood-like people."

"Here is a major clinical trial of human blood, and they need to participate."