After frostbite, Vice President JD.COM declared war.

According to all the criteria of success, Cai Lei is a person who can master the right to speak.

He was an executive in the world's leading real estate group, and later served as the vice president of JD.COM. He promoted the development of Internet finance and taxation in China, and issued the first electronic invoice in China. Peking University, Tsinghua, People's Congress and other universities invited him to be a visiting professor. He got married two years ago. His wife is a master of Peking University Medical College, and they have a lovely child.

However, at the age of 4 1 year, he was diagnosed with amyotrophic lateral sclerosis (ALS), commonly known as gradual freezing, ranking first among the five terminal diseases in the world. On a global scale, no case of this disease has been successfully cured so far, and there is no cure. Most patients will die in three to five years. When motor neurons die and can no longer support cardiopulmonary function, respiratory failure will occur and they will die.

In the past decades, Cai Lei changed his destiny with knowledge, diligence and extraordinary enthusiasm. But this time, he undertook a difficult and almost impossible task for himself: he wanted to find a new drug that could cure ALS.

This is a war between man and death, and there are only a few hundred days left in the progress bar. He didn't travel around the world, counted the days and stayed up late to work, established contact with the most cutting-edge scientists in the world, picked up the weapons of internet people, broke the existing barriers to drug research and development, and linked all available resources.

A friend in the same boat asked him why he didn't slow down. "(This is) a cutting-edge problem, which is world-class. I am afraid that aliens can solve it. " His answer is: "it's not difficult, but it's boring to do."

Behind this incredible optimism is a cruel survival story that is likely to be defeated. But the success or failure of this measure is related to tens of thousands of families who are also sick. Cai Lei decided to campaign for himself and thousands of people. He knows better than anyone that his fate is in his own hands.

Fan Dongsheng, director of the Department of Neurology of Peking University Third Hospital, was more decisive than any other doctor when he gave the diagnosis conclusion. He told Cai Lei that you have amyotrophic lateral sclerosis. This is the only possibility, and other possible diseases have been ruled out at present.

Cai Lei asked him jokingly, so I'm going to die? Fan Dongsheng drew a distance of about 20 cm on the table with his hands. He said, "Your life is so long", then closed his hands, leaving only a small piece, and then said, "There is still such a long time".

This is September 20 19, and it has been a whole year since Cai Lei's body began to appear abnormal.

At first, he felt the muscles on his left arm beating, or more accurately, twitching, day and night. However, this did not arouse his vigilance. He is the vice president of an Internet manufacturer in China, mainly responsible for financial work, and also takes four startup companies of the group. He had hardly been to the hospital in the previous six or seven years, and thought it was too time-consuming.

In this way, after half a year, the situation has not improved. Until the following February, he decided to go to Union Medical College Hospital. Liu Mingsheng, the chief physician of neurology department, looked at his EMG examination results, but didn't give a clear answer, only that you are in poor health. Liu Mingsheng asked him if he had time to stay in the hospital. Cai Lei said it was impossible to stay in the hospital at present, so the doctor told him to go back.

"Aren't you going to prescribe some medicine?" Cai Lei asked. But Liu Mingsheng said, don't drive, just go home and eat some vitamin B. At that time, Cai Lei was very happy and didn't think it was a big problem.

It will be a long time before he realizes that when his body begins to show symptoms of muscle tachycardia, it already means that the motor neurons in the body are seriously apoptotic, and the muscles have begun to atrophy in an almost irreversible trend.

This is the symptom of amyotrophic lateral sclerosis (ALS), a rare disease, commonly known as "frozen man", ranking first among the five terminal diseases in the world. No clear biomarkers were found for detection, and the misdiagnosis rate was extremely high. Unless doctors have enough experience, they dare not give patients a definite diagnosis easily.

After failing to seek medical treatment in Union Medical College Hospital, Cai Lei went to different hospitals for multiple diagnoses. It was not until he found Fan Dongsheng and went to the hospital for a series of complete disease screening and ruled out all other possibilities that he came to the most exact and worst conclusion. Moreover, Fan Dongsheng told him that ALS was incurable.

The only internationally recognized drug is a small pill called "Lirutai", which costs about 4,000 yuan per box and can be taken for one month. It is said that it can prolong the patient's survival for three months, but it can't cure ALS at all, and it can't stop the apoptosis of motor neurons at all.

This is 2065438+September 2009. Cai Lei is 4 1 year old, and her fate has been out of normal channels since then. At first, like all terminally ill patients, he couldn't believe the doctor's conclusion and accept his own fate. After that, he suffered from severe insomnia for half a year. Even if you fall asleep, you will wake up again and again.

The fortune teller said that the eight characters were short of water, so Mr. Wang instructed him to change his name to Cai. Master Feng Shui is also a divination, which made him move away from his original home. He tried various treatments recommended by his friends, injected expensive imported drugs and had a high fever of 39 degrees. Or visit an acupuncturist at Songshan Shaolin Temple and do meridian massage every day.

But at the same time, an unwilling mood also appeared.

At first, he didn't want to be friends with other patients, and he didn't want to accept that he was a member of the marginalized group. He thought, "Cai Lei, I have to do something big." Once, when he competed with others to do business, he would tell others that you don't want to do it, you can't do it. Asked why, he said, "Because you are fatal, I am desperate in Cai Lei, and you can't fight me".

Now, death's competitors have stood on his opposite side. In addition to his anxiety, his arrogance and unwillingness, as well as his enthusiasm described as "crazy", were aroused again.

After the diagnosis, he found all the academic papers about ALS at home and abroad, reaching more than 1000, and read them sentence by sentence. In order to improve reading speed, he found a convenient tool. I read it for several months, but I never let go of the information in the corner, trying to save my life.

20 19 1 1 month. Two months after the diagnosis, he set out to set up Beijing Eskom Medical Technology Co., Ltd., and the inertia formed by 20 years of work experience dragged him. He made a decision regardless of the opposition of his family. He wants to take medical technology companies as a position to find really effective drugs to conquer ALS.

His wife, Duan Rui, wanted him to give up all his jobs, go sightseeing and spend more time with his family, but he didn't want to. Cai Lei said that in this world, he only believes in himself, and only he can save his life. Between him and death, a silent war has begun.

He estimated that if he had three years, and if he could find a new drug in two and a half years, he would win.

First, let's meet the enemy, ALS.

As the most qualified expert in this field in China, it is purely accidental that Fan Dongsheng began to contact this disease.

At the beginning of the century, the Department of Orthopaedics of Peking University Third Hospital where he worked was the best hospital for treating cervical spondylosis in China. But there is a strange phenomenon, that is, some patients diagnosed with cervical spondylosis still can't relieve their condition after surgery. There is no problem during the operation, but the situation of such patients may continue to deteriorate. Later, they found that this kind of patients are not suffering from cervical spondylosis, but a rare disease ALS.

At that time, it was during Fan Dongsheng's graduate school that the orthopedic professor asked him a question from a clinical point of view: "Can you tell me how to judge that this disease is probably your disease (ALS), not our disease (cervical spondylosis)?"

Early identification can prevent orthopedic surgeons from performing wrong operations on patients. Cervical spondylosis surgery will not only delay the diagnosis of ALS, but may even accelerate the development of the disease.

Therefore, during the whole postgraduate period, Fan Dongsheng's main task is to identify ALS. Later, he found that electromyography and other means can effectively distinguish the two, and the detection accuracy rate is over 98%.

However, at that time, the domestic understanding of this disease was extremely limited. Until today, there are still few doctors who can accurately diagnose ALS.

It's really too unknown and complicated. In Britain, ALS is more often called motor neuron disease, which literally means a disease caused by motor neuron apoptosis. Motor neuron disease has a wide spectrum, including Hirayama disease and Kennedy disease, spinal muscular atrophy (SMA) and motor neuron disease in a narrow sense. In a narrow sense, there are several different types of motor neuron diseases.

Cai Lei's left hand, left arm, shoulders, back and other muscles are now severely atrophied, and his left arm can only be hung on his side feebly, and the back of his hand is swollen, so he can't see the texture of the joints. And the right hand muscle gradually began the same atrophy process. Halfway through the interview, he also needs to wear a ventilator to reduce the burden on his heart and lungs.

He no longer wears shoes with laces, suits and trousers with belts. He often sends messages by voice or translates them into words. Once, he was invited to attend a meeting. After sitting down, he wants to ask the lady next to him to help him unscrew the bottle cap of mineral water. However, the other party mistakenly thought that Cai Lei was "bullying" himself and had to apologize to others and said, "Sorry, my hands are not good."

Bai Shu was born in 1960, suffering from the most classic ALS classification. 20 18, her left arm is sick. Kloc-0 was diagnosed in the First Affiliated Hospital of Sun Yat-sen University in May, 20/9. In June 2020, she could still walk, but at that time, she fell down and never stood up again.

Today, Bai Shu is confined to a wheelchair. She can eat with a spoon by herself, but she has lost other self-care ability. Husband and nanny take care of her together, sleep at night, and Bai Shu relies on them to turn over for herself. She had to wear a ventilator to provide oxygen during the interview.

Among the patients, there are patients with more severe progress. Wang Jin's husband is forty years old. It's only been one year since I fell ill in July 2020, and I have started to have breathing problems. There is also a 38-year-old entrepreneur who was ill for nine months, quadriplegic and dying. One night some time ago, his blood oxygen saturation once dropped to 92%, and he could not breathe spontaneously.

Human muscles are dominated by neurons. When neurons begin to die, muscles can no longer move and will soon shrink. In three to five years, when the course of the disease develops to the later stage, the human body will become like a melting candle, and the cardiopulmonary function cannot be supported by muscles. The trachea must be cut open and the ventilator must be used to maintain life. Or you will die of respiratory failure.

Thousands of ALS patients gather in various WeChat groups established in Cai Lei, and they witness death every day. Sometimes, the relatives of patients in the group will tell their relatives about their death, or someone starts selling ventilators, which means that another person has disappeared from this world.

Around 2003, Fan Dongsheng's Third Hospital of Beijing Medical University took the lead in setting up a multi-center collaboration group specializing in ALS. Initially, four hospitals participated in the collaboration, and so far, more than 65,438+000 hospitals have participated. They are also promoting the research and development of new drugs for ALS, but this road is still difficult.

BrainStorm, an American cell therapy company, began to explore the method of curing ALS through NurOwn stem cell therapy from 200 1. They used to be the company that patients were most looking forward to. The drugs developed passed the first and second clinical trials, but in 2020, the third clinical trial ended, but the experimental data failed to show statistical differences, which means that the drugs have no obvious effect on als. /kloc-the research and development of stem cell drugs failed in 0/9 years.

Cai Lei clearly remembers that BrainStorm's share price plummeted by 70% that day. For many ALS patients, the hope of survival is as quickly dashed as turning off the lights. "During that week, many patients died," Cai Lei said.

Twenty years ago, Fan Dongsheng's team asked the School of Public Health of Harvard University to help design a set of scales to continuously collect sample data of ALS patients. Fan Dongsheng understands that collecting data can almost be regarded as the most important task in order to understand rare diseases more deeply.

In order to establish a more complete database, they must have an interview or telephone follow-up every three months to update the patient's progress and medication effect. This work is time-consuming and laborious, and the funds are insufficient. Fan Dongsheng can only ask students for help and pay them for their services.

After 20 years of persistence, they almost collected the largest ALS sample data in the world. However, Fan Dongsheng gradually realized that the scale was not very accurate. Moreover, the frequency of follow-up once every three months is not convenient to observe the changes of patients in time.

The emergence of Cai Lei has brought an extremely important weapon that can break through the bottleneck, and that is the Internet.

Cai Lei, a self-proclaimed "Internet veteran", became suspicious after searching for doctors and medicines everywhere. Why don't most hospitals have their own patient database? Between hospitals, information does not circulate with each other, and there are few rare cases. In this case, how to carry out disease research and new drug research and development?

He almost instinctively realized that the establishment of a large database is the key to unlock the ALS disease code. The entrepreneurship of 20 19 1 1 is just to solve this problem.

He set up an information aggregation platform called "Healing Home" through Beijing Eskom Medical Technology Co., Ltd., through which all ALS patients can upload complete disease information independently and update the medication effect and course progress in real time.

At that time, the database that Cai Lei wanted to establish should not only consider the possibility of various options, but also be able to horizontally meet the standards of medical insurance centers to meet the longer-term diagnosis and treatment planning. Fan Dongsheng provided him with a weight list, but that material needed the doctor's assistance in patient evaluation, and what Cai Lei wanted was an indicator for patients or their families to conduct self-evaluation and self-test.

As it happens, his wife Duan Rui graduated from Peking University with a bachelor's degree in pharmacy. At the initial stage of the establishment of this data platform, Duan Rui supported the Cai Lei team to jointly complete the formulation of indicators.

Cai Lei told Window to the South: "We can't discuss anything in a day or two or even a week. It's huge, complicated and particularly difficult. A total of more than 2,000 fields have been done, and each field is extremely difficult. "

For example, they want to find the relationship between the cause of ALS and the occupation of patients, so they must design detailed occupation options. If only the field of "athletes" is given, it will be too simple, and it should be refined into different aspects such as football, table tennis and basketball.

For another example, when it comes to professional data such as "neck tenderness", patients can't measure it themselves, so they try to set the questions as "Where can you raise your hand" and "How many seconds can you hold on".

Similarly, you can't ask whether the amount of defecation has increased after taking the medicine, but how many times you have defecated after taking the medicine.

Bai Shu said that she has been filling in this weight scale for several days, and her hands can hardly move, so she can only use one thumb. Fortunately, Cai Lei, who designed this scale, is also a patient. He simplified the way of filling in the scale to tick the box, arranged his colleagues to be the stewards of the platform, and directly helped those patients who could not upload data smoothly to enter data.

At present, this newly established data platform has more than 2000 samples.

As a clinician who has the most intensive contact with patients, Fan Dongsheng analyzed the significance of this data platform to ALS research.

"The big data platform can reflect the changes of patients in real time. Maybe we can know whether a drug is effective soon. For the research and development of new drugs on some platforms, the time cost can be greatly reduced, because time is money. After shortening the time, the investment in new drug research will accelerate. "

In fact, in Cai Lei's world, the concept of "everything can be connected" has not only been applied to work, but also penetrated into every corner of life.

In March, 2020, he found several online storage apps for Duan Rui, and suggested that she upload photos of all household items to the "system", code each cabinet, form a folder in the system, and then drag the pictures of items into the folder to make a note on the shelf life. "You can't miss something, the key is to prevent it from expiring."

Duan Rui thought Cai Lei was particularly funny, so he sent a circle of friends and wrote: "Next time, I can proudly tell my customers that the background operation of my home has initially realized the management of the Internet of Things."

As his wife, Duan Rui can be said to be the person who can see clearly Cai Lei's strategy.

As an "insider" of pharmacy, she deeply understands the arduousness of Cai Lei in promoting the research and development of new drugs for rare diseases.

"This thing is so difficult that people in our circle dare not think about it. They all think that this idea does not have this option, because first of all, you need a lot of money for research and development, which takes many years, but the failure rate is high. It is not something that individuals can push. "

Brainstorming study on ALS, 19 failed. With Cai Lei, how to achieve this goal? But Duan Rui knows that for Cai Lei, "Internet" is not only a sharp weapon, but also a set of underlying logic for decision-making. If we follow the original new drug research and development process step by step, there is no suspense to lose, but Cai Lei's way of thinking has broken the old rules of the game.

Related to the research and development of new drugs, investors, hospitals, pharmaceutical companies, scientific research teams, patients and registration departments are all indispensable. However, almost every part of the research and development of new drugs for ALS is lacking, which is also in line with common sense and is a stubborn disease in the research and development of drugs for rare diseases.

Investors are reluctant to inject money into the narrow market of ALS because there seems to be no profit. In contrast, they are more willing to invest money in neurodegenerative diseases such as Alzheimer's disease, because the patients are huge and the return rate is high.

He settled the bill carefully. Although there are100000 patients with Alzheimer's disease, not many patients will pay for the disease, because the patients are old, they don't feel sick, and they don't want their children to spend more money on themselves.

"Didn't you say that there are100000 people with Alzheimer's disease? How many of them are your real customers? My grandfather is now 82 years old and has got Alzheimer's disease. He won't spend a penny to cure this disease, and you can't get through it. "

He believes that ALS patients are mostly between 40 and 60 years old, and they are the backbone of the family and society. As long as one of the husband and wife is sick, the other will participate at the same time, take care of their partner's diet and daily life, and can no longer work normally. So he told those investors that even if a family sells iron, it will cost tens of millions to treat ALS patients, because the collapse of one person means the collapse of a family.

"ALS adds 26,000 people every year. I will calculate according to the existing 65438+ 10,000 people. Everyone is willing to spend 65.438+0 billion to cure, which is 65.438+0 billion. "

At the same time, he used his own thousands of patients and gradually improved patient big data as a bargaining chip to tell investors that you don't need to promote, and I will directly connect with you in the consumer market.

As a result, among more than 65,438+000 investors, one or two investors were finally persuaded to support the research and development of new drugs for ALS.

Fan Dongsheng believes that ALS is still a research project worth investing, because common diseases such as ALS, Alzheimer's disease and Parkinson's disease are neurodegenerative diseases with similar pathogenesis, and ALS is the fastest growing disease. From the perspective of capital, ALS can be a perfect research model. If a new drug that is effective for ALS is developed, it is likely to directly open the way to treat neurodegenerative diseases.

Cai Lei is well aware of this. At the beginning of 20021,he successfully persuaded Professor Chen Gong, who has been studying Alzheimer's disease, to turn to ALS research.

Chen Gong resigned as a tenured professor at Pennsylvania State University on 20 19, and returned to China to join the Guangdong, Hong Kong and Macao Central Nerve Regeneration Institute to conduct nerve regeneration research to solve serious brain diseases.

In 20 13, his team successfully regenerated glial cells in the brains of mice with Alzheimer's disease into neurons with a single transcription factor, which is the first case in the world.

If the neuron regeneration technology is mature, a series of neurodegenerative diseases including ALS can be overcome.

In Duan Rui's words, it's like mine clearance. "This is a feeling that you open an empty space and then' wow' it all opens. Any disease can be cured, but this effect is better and that effect is worse. This feeling is very happy. "

With the help of Cai Lei, scientists engaged in basic scientific research, such as Professor Chen Gong and Professor Bai Lu from Tsinghua University, have established contact with Fan Dongsheng who is engaged in clinical practice.

It would have taken about 8 to 65,438+00 years to complete the whole new drug research and development process. In the case of full aggregation of various resources, Chen Gong told Nanchuang that this process can be accelerated by two years at the earliest. Research like Chen Gong has been experimented abroad for several years. Now, with the promotion of Cai Lei, it is expected to achieve initial results next year.

From 65438 to 0978, Cai Lei was born in a poor military family in Shangqiu, Henan. He goes to junior high school in patched clothes. Later, my father died young, and the family had a heavy burden. He always wants to do better than others. Take the first place in the exam, play games better than others, even if he is small, but as long as a local ruffian dares to bully him, he will definitely have a big fight with the other party.

"I know I can't do it, but if you dare to provoke me, I will dare to do it with you. Never admit defeat, I am such a person. "

(Duan Rui, Bai Shu and Wang Jin are pseudonyms in the text)

Edit | Li Shaowei

New Media Editor | Ni Jian

Typesetting | Wen Yue

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