Measure Cai Lei according to all success-scientific standards, he is a person who can control the right to speak.
He once served as a senior executive at the world's leading real estate group and later served as vice president of JD.com. He promoted the development of China's Internet finance and taxation industry and issued the first electronic invoice in China. Peking University, Tsinghua University, Renmin University and other universities invited him to be a visiting professor. Two years ago, he got married to his wife, a master's degree student from Peking University School of Medicine. They have a lovely child.
But when he was 41 years old, he was diagnosed with amyotrophic lateral sclerosis (ALS), commonly known as amyotrophic lateral sclerosis, ranking first among the five major terminal diseases in the world. Globally, no patient has been successfully cured of this disease, and there is no cure. Most patients will reach the end of their lives within 3 to 5 years. When motor neuron apoptosis reaches the point where they can no longer support heart and lung function, they will experience respiratory failure and die.
In the past few decades of life, Cai Lei has used knowledge, diligence, and extraordinary enthusiasm to change his destiny. However, this time he has taken on a task that is so difficult that it is almost impossible to complete. His mission: He wants to find a new drug that can cure ALS.
This is a war between man and death, with only a few hundred days left on the progress bar. Instead of traveling around the world, he counts the days and stays up late at work to establish contact with the world's most cutting-edge scientists. He takes up the weapons of Internet people, breaks down existing barriers to drug research and development, and links all available resources.
A friend who was also suffering from the disease asked him why he didn’t slow down a bit. “(This is) a cutting-edge problem, a world-level problem that only aliens can solve.” His answer was: "Things that are not difficult are boring to do."
Behind this incredible optimism is a cruel story of survival that is very likely to fail. However, the success or failure of this move involves tens of thousands of families who are also suffering from the same disease. Cai Lei decided to run for himself and for thousands of people. He understands better than anyone that his destiny is firmly in his hands.
When Fan Dongsheng, director of the Neurology Department of Peking University Third Hospital, gave a more decisive diagnosis than any other doctor, he told Cai Lei that you are suffering from amyotrophic lateral sclerosis. One possibility, other possible diseases have been ruled out for now.
Cai Lei asked him jokingly, then I am about to die? Fan Dongsheng used his hands to draw a distance of about 20 centimeters on the table. He said, "Your life span is so long." Then he closed the distance between his hands until only a small distance was left. It’s so long.”
This is September 2019, a full year has passed since Cai Lei's body began to experience abnormalities.
At first, he felt the muscles in his left arm beating. To be more precise, it was rapid muscle tremors, day and night. But this did not arouse his alarm. He was the vice president of a major domestic Internet company. He was mainly responsible for financial work. At the same time, he also led four start-up companies in the group. He had almost never been to the hospital in the past six or seven years. He felt that it was too time-consuming.
This went on for half a year, but the situation did not improve. It was not until February of the next year that he decided to go to Union Medical College Hospital. Liu Mingsheng, chief physician of the Department of Neurology, looked at his electromyography results and did not give a clear answer. He only said that your disease is not good. Liu Mingsheng asked him if he had time to be hospitalized. Cai Lei said that it was impossible to have time to be hospitalized at the moment, so the doctor asked him to go back.
"Don't you prescribe some medicine?" Cai Lei asked. But Liu Mingsheng said that there is no need to prescribe it, just take some vitamin B at home. At that time, Cai Lei was quite happy and thought there was no big problem.
It would take a long time for him to realize that when his body began to experience symptoms of muscle twitching, it already meant that the motor neurons in the body were severely apoptotic, and the muscles had begun to atrophy in an almost irreversible trend. .
This is the onset of amyotrophic lateral sclerosis (ALS). This rare disease, commonly known as "ALS", ranks first among the top five terminal diseases in the world. No clear cure has been found yet. The misdiagnosis rate of the biomarkers detected is extremely high. Unless doctors are experienced enough, they will not dare to give patients a clear diagnosis easily.
After seeking medical treatment at Union Medical College Hospital to no avail, Cai Lei went to different hospitals to receive multiple diagnoses until he found Fan Dongsheng and was hospitalized for a series of complete disease screenings to rule out all other possibilities. After sex, I came to the most accurate and worst conclusion. Moreover, Fan Dongsheng told him that there is no cure for ALS.
The only internationally recognized drug is a small pill called "Lirutai". A box costs about 4,000 yuan and can be taken for a month. It is said that it can extend the patient's survival period by 3 months. However, There is no cure for ALS, nor is it able to prevent motor neuron apoptosis.
This is September 2019. Cai Lei is 41 years old, and his destiny has since departed from the normal course. At first, like all terminally ill patients, he couldn't believe the doctor's conclusion and could not accept his fate. After that, he suffered from severe insomnia for half a year. Even if he fell asleep, he would wake up repeatedly.
The fortune teller said that the five elements in his horoscope lacked gold and water, so he suffered this disaster. The fortune teller enlightened him and asked him to change his name to Cai Runqian. The Feng Shui master also figured it out and asked him to move out of his original home. He tried various treatment methods recommended by his friends, injected expensive imported drugs, and had a high fever of 39 degrees. Or go to Songshan Shaolin Temple to visit acupuncture masters and do meridian massage every day.
But a feeling of unwillingness also appeared at the same time.
At first, he was unwilling to make friends with other patients and consider himself a member of a marginalized group. What he was thinking in his mind was, "I am Cai Lei, and I still have to do big things." Once, when he was competing with others for business, he would tell them, "Don't do it, you can't do it for me." When the other party asked why, he said, "Because you want your life, and I, Cai Lei, don't want my life. You can't fight me."
Now, Death, the competitor, stood on his opposite side. In addition to being uneasy, his arrogance and unwillingness, as well as the enthusiasm that he himself described as "crazy", were once again aroused.
After being diagnosed, he found all domestic and foreign academic papers on ALS, more than 1,000 of them, and read them sentence by sentence. In order to improve his reading speed, he found a handy tool. I watched it like this for several months, not even letting go of the information in every corner, trying to find a way to save my life.
In November 2019, two months after his diagnosis, he set out to establish Beijing Aisikang Medical Technology Co., Ltd. The inertia formed by 20 years of work experience pulled him, and he made the decision to use a medical technology company as a position to find truly effective drugs to overcome ALS, regardless of the opposition of his family.
His wife Duan Rui wanted him to put down all work, go sightseeing and spend more time with his family, but he was unwilling. In this world, Cai Lei said that he only believed in himself, and only he could save his life. A silent war had begun between him and death.
He estimated that if he had three years left, and if he could find a new drug within two and a half years, he would win.
First, let’s get to know the enemy, ALS.
As the most qualified expert in this field in China, Fan Dongsheng began to deal with this disease by accident.
At the beginning of the century, the Orthopedics Department of Peking University Third Hospital where he worked was the best hospital in the country for the treatment of cervical spondylosis. However, there was a strange phenomenon that some patients diagnosed with cervical spondylosis were undergoing surgery. After the operation, the condition still could not be relieved. There is no problem with the surgical procedure, but the condition of such patients may continue to deteriorate. Later they discovered that these patients were not suffering from cervical spondylosis, but the rare disease ALS.
At that time, when Fan Dongsheng was studying for graduate school, when deciding on the topic of his thesis, the professor of orthopedics asked him a question from a clinical perspective: "Can you tell me how to judge whether this disease is likely to be yours?" disease (ALS), not our disease (cervical spondylosis)? ”
Only by making early identification can we avoid orthopedic surgeons from incorrectly performing surgery on patients. Cervical spondylosis surgery will not only delay the diagnosis of ALS, but may even Accelerate the development of the disease.
Therefore, throughout his postgraduate period, Fan Dongsheng’s main topic was to identify ALS. Later he found that through electromyography and other means, he could effectively distinguish between the two, and the detection accuracy could reach 98% %above.
However, at that time, the domestic understanding of this disease was extremely limited. To this day, there are still very few doctors who can accurately diagnose ALS.
It is indeed too unknown and too complex. In the UK, ALS is more commonly known as motor neurone disease, which literally means a disease caused by the death of motor neurons. Motor neurone disease has a broad disease spectrum, including Hirayama disease and Kennedy disease, spinal muscular atrophy (SMA), and motor neurone disease narrow sense. There are several different types of motor neuron disease in the narrow sense.
Cai Lei’s left hand, left arm, shoulder, back and other muscles have now been severely atrophied. His left arm can only hang weakly on the side of the body. The back of the hand is swollen and the texture of the joints cannot be seen. . The muscles in his right hand gradually began the same atrophy process. Midway through the interview, he also needed to put on a ventilator to reduce the burden on his heart and lungs.
He no longer wears shoes with laces, suits or pants that require belts. He often sends voice messages or transcribes his voice into text. Once he was invited to attend a meeting. After he sat down, he wanted to ask the lady sitting next to him to help him unscrew the bottle cap of mineral water. The other party mistakenly thought that Cai Lei was "bullying" him, so he had to apologize and explain, "I'm sorry." , my hands are not good."
Shu Bai, who was born in 1960, suffers from the most classic type of ALS. In 2018, she developed an illness in her left arm. In May 2019, she was diagnosed at the First Affiliated Hospital of Sun Yat-sen University. In November 2020, she could still walk, but at that time, she fell and could never stand up again. .
Today, Shu Bai can only sit in a wheelchair. She can eat with a spoon, but she has lost other self-care abilities.
Her husband and nanny *** both take care of her, and Shu Bai relies on them to turn her over when she sleeps at night. Throughout the interview, she had to wear a ventilator to provide oxygen.
Among the patients, there are those whose disease progresses even more fiercely. Wang Jin's husband is 40 years old this year. Only one year has passed since he became ill in July 2020, and he has already started to have breathing problems. There is also a 38-year-old entrepreneur who has been ill for 9 months and is already quadriplegic and in critical condition. One night some time ago, his blood oxygen saturation dropped to 92% and he was unable to breathe on his own.
The muscles of the human body are controlled by neurons. When neurons begin to die, the muscles can no longer move and will soon atrophy. In 3 to 5 years, when the disease progresses to an advanced stage, the human body will become like a melted candle, and the heart and lung functions cannot be supported by muscles. The trachea must be cut and the ventilator must be relied on to maintain life. Otherwise, Will die of respiratory failure.
Thousands of ALS patients have gathered in multiple WeChat groups established by Cai Lei, and they are witnessing death every day. Sometimes, relatives of patients in the group will tell them about the death of their loved ones, or when someone starts to resell ventilators, it means that another person has disappeared from the world.
Around 2003, Peking University Third Hospital, where Fan Dongsheng worked, took the lead to establish a multi-center collaboration group specializing in ALS research. Initially, 4 hospitals participated in the collaboration, and now, there are 100 Several hospitals are involved. They are also promoting the development of new drugs for ALS, but this road is still very difficult and dangerous.
BrainStorm, an American cell therapy company, has been committed to exploring ways to cure ALS through NurOwn stem cell therapy since 2001. They were once the most anticipated company by patients, and the drugs they developed passed Phase I and Phase II. Clinical trials, but in 2020, the third phase of clinical trials ended, and the experimental data failed to show statistical differences, which means that the drug has no obvious effect on ALS. The 19-year research and development of stem cell drugs has failed.
Cai Lei remembers clearly that on that day, BrainStorm’s stock price plummeted 70%. For many ALS patients, the hope of survival was dashed as quickly as turning off the lights. “In that week, he died. Many patients," Cai Lei said.
Twenty years ago, Fan Dongsheng’s team asked the Harvard School of Public Health to help design a set of scales, using this as a standard to continuously collect sample data from ALS patients. Fan Dongsheng understands that if you want to have a deeper understanding of rare diseases, collecting data is almost the most important task.
To build a more complete database, they must conduct face-to-face interviews or telephone follow-up visits with patients every three months to update the patient's disease progress and medication effects. This work was time-consuming and labor-intensive, and funds were insufficient. Fan Dongsheng could only ask students to help with it and pay them for the labor.
After 20 years of persistence, they have collected almost the largest ALS sample data in the world. But Fan Dongsheng gradually realized that this scale was not very precise. Moreover, the frequency of follow-up visits once every three months is not convenient for timely observation of changes in patients.
The emergence of Cai Lei has brought an extremely important tool that can break through bottlenecks, namely, the Internet.
Cai Lei, a self-proclaimed "Internet veteran", had strong doubts after searching for doctors and medicines to no avail. Why did most hospitals not have their own patient databases? Information does not flow between hospitals, and there are few cases of rare diseases. In this case, how to conduct disease research and new drug development?
He almost instinctively realized that the establishment of a large database was the key to unlocking the code of ALS disease. The business launched in November 2019 was precisely to solve this problem.
Through Beijing Aisikang Medical Technology Co., Ltd., he established an information aggregation platform called "The Home of Gradual Recovery", through which all ALS patients can independently upload complete medical records. information, and can update medication effects and disease progression in real time.
At that time, Cai Lei wanted to establish a database that not only considered the possibility of various options, but also could be connected horizontally and connected with the standards of the medical insurance center to fit in with longer-term diagnosis and treatment planning. Fan Dongsheng provided him with a scale, but that material required doctors to assist patients in conducting assessments, while Cai Lei wanted indicators that patients could self-evaluate themselves or with the assistance of their family members.
Coincidentally, his wife Duan Rui graduated from Peking University with a bachelor's and master's degree in pharmacy. In the early days of the establishment of this data platform, Duan Rui supported Cai Lei's team in jointly completing the formulation of indicators.
Cai Lei told Nanfengchuang: "We can't finish any problem in a day or two or even a week. It is very large, complex, and extremely difficult. In total, we have made more than 2,000 fields. , each field is extremely difficult.”
For example, they want to find the relationship between the cause of ALS and the patient’s occupation, so they must design detailed occupation options. If only the field of “athlete” is given, , that’s too simplistic, it needs to be detailed into different aspects such as football, table tennis, basketball, etc.
For another example, when it comes to more professional data such as "neck tenderness", patients themselves cannot measure it, so they try to set the questions to "where can you raise your hands?" "can you persist?" seconds".
Similarly, the question should not be "Has the amount of bowel movements increased after taking the medicine?" but should be replaced by "How many times have the bowel movements been after taking the medicine?"
Shu Bai said that she had filled out this scale for several days and that she could barely move her hands and could only use one thumb. But fortunately, Cai Lei, who designed the scale, is a patient himself. He simplified the method of filling in the scale to ticking and drawing circles, and arranged for colleagues to be the stewards of the platform to directly help patients who were unable to upload data smoothly to enter data. .
Currently, this recently established data platform has more than 2,000 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 in patients in real time. Maybe we can quickly understand whether a certain drug is effective. For some platforms, it can significantly reduce the time and cost of new drug development. Because time is money. When time is shortened, investment in new drug research will be accelerated."
In fact, in Cai Lei's world, the concept of "everything can be connected" is not only applied to work. , has already penetrated into every corner of life.
In March 2020, he found several online storage apps for Duan Rui, and suggested that she take photos of all household items and upload them to the "system", and code each cabinet to form a folder in the system , then drag the picture of the item into the folder and make a note of the shelf life. "You won't be able to find something. The key is to prevent it from expiring." < /p>
As his wife, Duan Rui can be regarded as the person who sees Cai Lei's strategy most clearly.
She is an "insider" in the pharmacy profession, and she is more deeply aware than ordinary people of the difficulty of Cai Lei's efforts to promote the research and development of new drugs for rare diseases.
"This matter is so difficult that people in our circle dare not think about it. We all think that this idea has no option, because first of all, your research and development requires a lot of funds, a team, and a lot of Years have passed, but the failure rate is very high. It cannot be pushed forward by one person."
BrainStorm has been studying ALS for 19 years and has failed. How can Cai Lei succeed? But Duan Rui knows that for Cai Lei, the "Internet" is not just a weapon, but also a set of underlying logic for decision-making. If the original new drug research and development process was followed step by step, there would be no suspense about defeat, but Cai Lei's way of thinking broke the old rules of the game.
Related to the research and development of new drugs, it mainly involves investors, hospitals, pharmaceutical companies, scientific research teams, patients, and registration departments. Every link is indispensable. But for the research and development of new drugs for ALS, there are deficiencies in almost every part. This is also consistent with common sense and is a chronic problem in the research and development of rare disease drugs.
Investors are unwilling to invest money into the small market of ALS because it seems that there is obviously no profit. In comparison, they are more willing to invest money in neurodegenerative diseases such as Alzheimer’s disease. Alzheimer's disease has a high return rate because of its large number of patients.
He settled the accounts carefully. Even though there are 10 million patients with Alzheimer's disease, not many patients will pay for the disease because the patients are old and do not think they have the disease. Nor do they want their children to spend more money on themselves.
"Didn't you say that there are 10 million people with Alzheimer's disease? How many of them are your real customers? My grandfather is now 82 years old and has Alzheimer's disease. He will not spend a day You can’t even spend money to treat this disease.”
He believes that most of the people suffering from ALS are between 40 and 60 years old, who are the backbone of the family and society, and couples. As long as one party is sick, the other party will definitely be involved at the same time, taking care of their partner's diet and daily life, and will no longer be able to work normally. Therefore, he told those investors that a family would spend tens or even millions on treating ALS patients even if they were trying to sell everything, because the collapse of one person means the collapse of a family.
"There are 26,000 new cases of ALS every year. I will calculate it based on the existing 100,000 people. Everyone is willing to spend 1 million to treat it, which is 100 billion."
He At the same time, he uses the thousands of patient groups he has mastered and the gradually improved patient big data as bargaining chips, and tells investors that you don’t need to promote it. I will connect you directly with the consumer market.
As a result, one or two of the more than 100 investors were finally successfully lobbied and agreed to support the development of new drugs for ALS.
Fan Dongsheng believes that ALS is still a research project worthy of investment, because ALS, Alzheimer's disease, Parkinson's disease and other common diseases are both neurodegenerative diseases, and their pathogenesis is similar. ALS is the fastest-growing disease among them. From a capital perspective, ALS can become a perfect research model. If a new drug is developed that is effective for ALS, it is likely to directly open up the treatment pathway for neurodegenerative diseases.
Cai Lei understands this well. At the beginning of 2021, he successfully persuaded Professor Chen Gong, who was originally dedicated to researching Alzheimer's disease, to start switching to ALS research.
Chen Gong resigned from his tenured professorship at Pennsylvania State University in 2019, returned to China, and joined the Guangdong-Hong Kong-Macao Central Nerve Regeneration Research Institute to conduct research on nerve regeneration to solve major brain diseases.
In 2013, his team used a neural transcription factor to successfully regenerate glial cells into neurons in the brains of Alzheimer's mice, the first of its kind in the world.
If neuron regeneration technology is developed maturely, a series of neurodegenerative diseases including ALS can be overcome.
In Duan Rui’s words, this is like minesweeper, “It’s the feeling that you click to open an empty space, and then ‘wow’ it’s fully opened. It can cure anything, but it’s more effective for this. , the effect is a little bit different, this feeling is very pleasant."
Under Cai Lei's link, scientists engaged in basic scientific research, including Professor Chen Gong and Professor Lu Bai of Tsinghua University, have established contact with Fan Dongsheng, who is engaged in clinical practice.
Originally, it would take about 8 to 10 years to completely complete the entire process of new drug research and development. With various resources fully aggregated, Chen Gong told Nanfeng Window that this process could be completed as quickly as possible. Two years of acceleration. Research such as Chen Gong's has been conducted abroad for several years in the early stages of experiments. Now, with Cai Lei's promotion, preliminary results are expected to be achieved next year.
In 1978, Cai Lei was born into a poor military family in Shangqiu, Henan Province. He wore patched clothes to junior high school. Later, his father died young and the family burden was heavy. He always wanted to do better than others in everything. He must get first place in the exam and be better than others in playing games. Even if he is smaller, he will definitely fight with any gangster who dares to bully him.
"I know I can't fuck him, but if you dare to challenge me, I dare to do it with you. I never admit defeat, that's the kind of person I am.
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(Duan Rui, Shu Bai and Wang Jin are pseudonyms in the article)
Editor | Li Shaowei
New media editor | Jian Ni
Typesetting | Wenyue
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