A "Father of Medicine God" A compelling adventure to save himself
On the evening of October 23, Xu Wei's room door was ajar. His son was receiving fluids. A few hundred milliliters of yellow liquid was slowly entering the veins on Xu Haoyang's head.
The infusion bag was filled with medicine to relieve his brain damage.
Xu Wei is also unwilling to take risks, but as a father, he has no other choice. "If there are medicines in front of you that can cure your children, would you not use them?" He asked rhetorically.
Recently, the media and film production companies have visited Xu Wei every day. He is regarded as a legend and the "Father of Medicine God".
The help of all parties also found him. Three gene companies, a cell company and a hospital threw an olive branch to Xu Wei.
"Even if Hao Yang is dead now, he did not come in vain. The meaning of his life is to let the society see the group of rare diseases." Xu Wei said.
In the past year or so, Xu Wei has been learning the theory of treating rare diseases in his son and developing drugs. He believes that every step in the past has been done correctly, and the next steps are clearly visible.
From histidine copper, irismo copper, to stem cell therapy, gene replacement and gene editing therapy, the mountains he tried to climb are getting steeper and steeper, and what he is now involved in is even more dangerous in medicine.
In Xu Wei's plan, the next step of treatment for his son is to be completed through gene replacement-that is, to introduce foreign normal genes into target cells to correct or compensate for diseases caused by defects and abnormal genes to achieve the purpose of treatment.
Xu Wei said that if all goes well, his son will undergo a clinical trial of gene replacement at the end of this year, becoming the first case of Menkes syndrome in the country receiving gene therapy.
"Father of Medicine God"
Two-year-old Xiao Haoyang drank water in his grandmother's arms. Because of a urinary tract infection, the catheter attached to him was filled with white floc. Xu Wei said it was a "corpse of bacteria."
Xiao Haoyang's weight is now less than 8 kilograms. Compared with children of the same age, he has a small body, big ears, and a soft head lying on his grandmother's arms.
Due to poor breathing, Xiao Haoyang's breath is often accompanied by a loud snoring.
Since the rare disease Menkes (Menkes curly hair syndrome) was diagnosed at 8 months, Xiao Haoyang's weight has been decreasing.
This is a rare congenital abnormal copper metabolism disease. After the absorption of copper in the intestinal membrane, the rotation process from mucosal cells to the blood is obstructed, which reduces the activity of copper enzymes in the body and causes development and dysfunction of the body.
The child is normal at birth, and symptoms usually begin at 2 to 4 months. Typical symptoms include frizzy hair, deterioration of physical function, mental retardation, and low copper levels in the blood.
No Menkes case has survived 4 years of age, and the children died at an average of 19 months.
The eyes of Xiao Haoyang, who was held in her arms, were squirming, and when excited, her calves would stretch out and kick on the ground. Grandma said that Xiao Haoyang was more energetic recently than before.
In her opinion, Xiao Haoyang's "improvement" may be related to stem cell therapy.
In June and July, a stem cell company in Beijing injected him with stem cells-imported from the spine and into the brain.
Stem cell therapy refers to transplanting healthy stem cells into the patient's body to repair or replace damaged cells or tissues, thereby achieving the purpose of healing.
At present, my country's stem cell therapy is in the stage of clinical trials.
Because he couldn't afford the high price, Xu Wei cultivated stem cells by himself, using human platelet lysate as the culture medium. "The cells grow very fast. Add 25 ml to a 175 (ml) bottle and it will be full in a day."
On the night of October 19th, he began to experiment on himself.
It is not a simple matter to give the left hand an injection with the right hand. Xu Wei put three needles on the back of the left hand before getting in.
Taking the injection while taking his temperature, "I came here once boldly, and my heart was flustered." Afterwards, Xu Wei called a friend and confided, "I'm afraid of bacterial infection. If I get in, I will get sepsis." He heard that if the cells are in the cell. If there are bacteria, you will have a fever within a few minutes after being injected into the body.
"I originally wanted to give half of it, but I didn't see any response later. I gave more than 60 million units of cells. I gave them all." Xu Wei did not feel uncomfortable after a one-time injection, but it still needs to detect that the new cells actually work in the body. Three to five days.
He recalled every detail in the preparation process, "There should be no problem, and the blood culture bottle inoculated with the culture medium supernatant also did not report positive."
This is a new step he has taken on the road of drug research.
In previous attempts, he successfully produced copper histidine and irismo, and even had positive feedback in the test of gene replacement drugs.
Recently, the media and film production companies have visited Xu Wei every day. He is regarded as a legend and the "Father of Medicine God".
But at this point, he can no longer "fight alone". In order to do better experiments, he newly purchased a biological safety cabinet and a high-temperature sterilization cabinet. Xiao Haoyang's grandfather specially invited a crane from the third floor balcony. Hang in.
With the deepening of drug research, the required cost is getting bigger and bigger.
The help of all parties also found him. Three gene companies, a cell company and a hospital threw an olive branch to Xu Wei.
After reading related reports, some patients with rare diseases and their families left messages on Xu Wei's Weibo and added his WeChat to ask questions. Xu Wei's cell phone rang from morning to night.
In order to make it easier to answer questions, Xu Wei pulled a WeChat group called "Rare Disease Hope Group". The patients posted gene lists on WeChat for him to read. Some people wanted to learn and study rare diseases, but they were trying to read papers. After that, he came back to ask Xu Wei for advice, "It's too difficult to understand."
Whenever he has time to look at his mobile phone, Xu Wei will reply to the WeChat of his patients and family members. Xu Wei encourages them to study and understand their own diseases and take the first step towards self-help.
"This group is like boiled frogs in warm water," Xu Wei described, patients and their families will gradually lose their vitality.
Xu Wei hopes to rekindle the hope of the rare disease group through the patients and their families to understand the disease and do the preliminary research of the drug.
"From zero to one"
"I know it's difficult." Xu Wei said, he fully understands the "frustration" of the rare disease group.
After the diagnosis, he took his son and his family to Beijing for treatment. The doctor tried to supplement the trace elements with "cocktail" therapy to treat Xiao Haoyang.
During the more than a month of hospitalization in Beijing, Xiao Haoyang had to get needles every day, sometimes four or five needles a day. His blood vessels were fragile and thin, and would be pierced accidentally. Xu Wei couldn’t bear to see his son suffer like this. For the suffering, the wife takes Xiao Haoyang to the puncture room every time.
"As soon as the injection was given, he looked at you with a cry for help, his entire face was flushed, and his body was stretched straight." Hao Yang's mother Yao Lu said. Sometimes her son resists so much that it takes two doctors to hold it down. The whole body was pierced with a needle so there was nowhere to be pierced, and it could only be hit on the neck.
In order to save a few needles, sometimes indwelling needles are used. The position of the indwelling needles cannot be moved. Xiao Haoyang has to fix one movement while sleeping, and Yao Lu needs to take care of it unsightly for 24 hours.
What made the couple break the most was the test results after more than a month of treatment. The copper element in Xiao Haoyang's body only increased by 0.01umo.
"I think he is so painful, only rising so little, and there may be an error." Yao Lu said, "We decided to let it go, we have to leave the hospital." The couple took their son back home.
When the treatment was hopeless, Yao Lu also had the idea of not wanting to live.
Soon after returning from Beijing, Xu Wei began to study copper histidine.
At the very beginning, Xu Wei Pharmaceutical went through the "zero to one" stage. The successful preparation of copper histidine was a leapfrog step for him.
Copper histidine is a relatively simple compound. Supplementing copper histidine is often used as a symptomatic treatment for Menkes patients.
In Taiwan, this drug usually exists in the form of hospital preparations. According to eight news reports, domestic doctors have tried to promote copper histidine as hospital preparations, but the overall tightening of hospital preparations and cumbersome administrative approval procedures have been reported. Children's injection requirements are more stringent, and it will eventually come to nothing.
It was natural for Xu Wei to embark on the road of pharmacy. He originally wanted to buy from Taiwan, but the epidemic blocked the road.
Then he outsourced the production to a Shanghai company, but he couldn't afford the monthly cost of 20,000 to 30,000 yuan.
The child's life could not be broken. After reviewing relevant papers and materials, he bought an ultra-clean workbench and began to try to make copper histidine by himself, and experimented on rabbits, himself and Yao Lu.
Xu Wei’s parents’ first reaction was to oppose, disbelieve, and think Xu Wei was messing around. Xu Wei asked, “Would you like to find a way to buy medicine?” Xiao Haoyang’s grandfather Xu Hong worried that Xu Wei might touch legal risks, and ultimately human resources. Two empty.
It wasn't until the copper histidine was made that Xu Hong's attitude became somewhat relaxed, but his doubts did not stop, "copper histidine is easy to make, and gene medicine is impossible."
Xu Wei re-learned middle and high school chemistry, learning the basic undergraduate courses of organic chemistry online.
According to the eight-point health news report, since the successful preparation of copper histidine in September 2020, he has injected more than 300 copper histidine injections into Hao Yang, one injection every day, and the detection index shows that the copper element rises all at once. NS.
While injecting copper histidine into Xiao Haoyang, he began to inject copper irismo which is more conducive to brain "absorption" into his son. "Later, the child's performance became obvious, especially active and excited. Watching you laugh at night, playing with you, crying as soon as you turn off the lights, there are obvious changes." Xu Wei said in a live broadcast.
Whether it’s copper histidine, irismo, or the effect of stem cell treatment, “I can’t see the changes with the naked eye, but if I look back at the previous video, it may be a bit worse,” Yao Lu said. I can stand up, now I can't lift my head at all." One of the typical characteristics of Menkes children is the gradual deterioration of physiological functions.
In Yao Lu's eyes, the change after his son's medication was not so obvious.
Why can't it fall on your head?
In Yao Lu's eyes, Xu Wei is a particularly stubborn person, stubborn to a bit paranoid.
"He doesn't believe in fate. He always feels that he must try, and he may succeed." She said that Xu Wei used to open a restaurant and his business was not good. "You said that you are not suitable for catering. I changed one after another, and he still thinks like that now, I guess he doesn’t believe it.” Xu Wei’s bookshelf lined up with books related to various industries he was engaged in, such as “Online Store Promotion” and “Cooking”. Basic Skills Training Course", "Electronic Components and Use Circuits", and a complete set of books such as "Mesenchymal Stem Cell Basics and Clinics".
Yao Lu was very entangled with Xu Wei's medicine. On the one hand, she understood that this was almost the only hope for the child, and on the other hand, she was afraid of tossing the child. "If he were an adult, would he come and tell you," Mom and Dad, forget it, I don't want to be so painful." In any case, she didn't dare to oppose Xu Wei, because Xu Wei was a person who "the more you oppose, the more you do."
Sometimes, Xu Hong will show some thoughts that he believes his son can create miracles.
"Because our family has genes for miracles." Xu Hong said. When Xu Wei was 9 years old, there was a car accident and one leg was disabled. Xu Hong took him to hospitals all over the country, and none of them could. Heal Xu Wei's leg.
Xu Wei’s legs were shrinking. Xu Hong didn’t accept this result. He forced Xu Wei to exercise, stretch and twist. “When I moved, he couldn’t cry. Everyone opposed me. His mother felt distressed and stopped me from doing this. Get it. If I don't do it like this, he will be disabled for life. Do you think he is recovering well now?" Xu Hong said.
"He sometimes cries," said Haoyang's grandma. Xu Wei didn't know how to communicate with family members when he encountered difficulties in the pharmaceutical industry.
Xu Wei's personality is very similar to that of his father, he is not good at words, and always has his own set of ideas.
Xu Wei discovered that patients and their families with rare diseases are always caught up in the question of "Why is it my turn?"
Xu Wei sometimes asks, "Why can't rare diseases fall on me? Instead of blaming others like this, I would rather think of a solution. Sometimes I am very grateful to Hao Yang, who has brought me a new world." During this time, Xu Wei took the self-examination for undergraduates, and next he plans to take the postgraduate examination of molecular biology.
Xu Wei said that every time he couldn't hold on, he would allow himself to give up for a while, a few hours, or one night, and continue reading the paper the next day.
Xu Wei wanted to set up a foundation for Menkes, but was told that it must be established with more than 50 people, and the Menkes rare disease group has a total of more than 30 people.
Even in the rare disease group, few people understand what Xu Wei is doing. Only Lao Qin, who is also a family member of Menkes and a doctor, is his only "comrade in arms" in the pharmaceutical industry. Xu Wei meets In times of difficulty, he often called Lao Qin.
Lao Qin's twin sons all suffer from Menkes, and one of them is blind. Now he has almost given up treatment for the child.
As a doctor, after seeing the child's MRI results, Lao Qin thought that there was no medicine to save the child's severe brain atrophy.
"If you don’t help yourself, who are you expecting to save you? Some things you have to take the lead, because your driving force is different. Now no pharmaceutical factory or research institution will study a rare disease, if they With the preliminary research foundation, the progress will be much faster if you take these data and then go to the drug company." Xu Wei encourages patients and family members of rare diseases to explore the disease in depth.
Currently, he is looking for a free place as a shared laboratory in Kunming, where he can donate some of his experimental equipment for research use by rare patients and their families.
He felt that even if no medicine was prepared in the end, such a life would be more meaningful.
"Even if Hao Yang is dead now, he did not come in vain. The meaning of his life is to let the society see the group of rare diseases." Xu Wei said.
Xu Wei is also not sure about curing his son's rare disease.
In the view of his father Xu Hong, his son Xu Wei is now in a dilemma, and what he faces is no longer a simple drug research like the compound copper histidine.
Xu Hong believes that at the genetic level, Xu Wei is impossible to accomplish. There are both technical barriers and greater risks. "He is doing this with himself now."
"There is no other way to go"
On October 4, Xu Wei posted on Weibo, “I constructed a truncated version of the ATP7A sequence in vitro 293T cell verification results have been obtained yesterday, has been expressed in the cell, and the expressed protein is located in the trans-Golgi apparatus.”
This means that gene replacement therapy has hope.
"The group model is successful, but it has not yet been able to enter the treatment stage." Xu Wei said that the gene company is currently doing animal experiments on mice. The most recent problem facing Xu Wei is to find the monkeys for the last animal experiment.
Due to the epidemic, the price of experimental cynomolgus monkeys has risen to 220,000 yuan. In this experiment, Xu Wei needs at least 5, but even if the price is sufficient, it is difficult to find a source of supply.
After the animal experiment, it is necessary to conduct clinical trials legally and compliantly. At present, a hospital has expressed a willingness to cooperate with Xu Wei, "As soon as possible, Hao Yang can use gene replacement drugs within two months." Xu Wei said. It is under smooth circumstances, "The experiment will not be as simple as in theory, and there may be many accidents."
But even so, Xiao Haoyang may not be completely cured after using gene replacement drugs. With stem cell therapy, Xu Wei judges that these treatments may restore Xiao Haoyang to normal intelligence and reach a level where he can take care of himself. .
Xiao Haoyang’s mutant genes are expressed throughout the body. Gene replacement therapy can only solve the genetic problems of some organs with slow renewal cycles. In Xu Wei’s view, gene editing is ultimately the most thorough treatment. “As long as gene editing technology Mature, in theory, all human health problems can be solved." Xu Wei said.
Gene editing is a genetic engineering technology that modifies specific target genes in the genome of an organism.
"It enters your body through the carrier and changes the genes of every cell you are now." In the complex gene sequence, Xu Wei has found the short section where Xiao Haoyang made the mistake.
He opened the document in front of the computer in the study, and Xu Wei used the mouse to select a short paragraph of the letter combination that resembled a whole page of Morse code. "As long as this paragraph is changed, Xiao Haoyang will completely become a normal person." Xu Wei said.
Xu Wei does not deny that normal people can also become "abnormal" through gene editing technology.
It will be "difficult" to get to the step of gene editing.
In January 2021, the National Food and Drug Administration approved the clinical trial application of Zhongguancun Biomedical Enterprise Boya Jiyin's gene editing therapy product ET-01 for blood transfusion-dependent β-thalassemia, which is the first approved gene editing therapy in my country The clinical trial application is also the first approved clinical trial application for hematopoietic stem cell products.
In February of the same year, the "Supplementary Provisions of the Supreme People's Court and the Supreme People's Procuratorate on Enforcement, "The Criminal Law of the People's Republic of China" Determining Crimes (7)" stipulated the crime of illegal implantation of gene editing and embryo cloning.
Xu Wei is facing a dangerous peak on the way to save the child with medicine.
Text/Reporter Yan Xingyue