He was an executive at one of the world's leading real estate groups before becoming vice president of Jingdong. He promoted the development of China's Internet taxation business and had issued the first electronic invoice in China. Universities such as Peking University, Tsinghua University and National People's Congress invited him to be a visiting professor. Two years ago, he also got married, his wife is a master's degree from Peking University Medical School, and they have a lovely child.
But at the age of 41, he was diagnosed with amyotrophic lateral sclerosis (ALS), commonly known as acromegaly, which is ranked among the world's top five terminal diseases. Globally, the disease has not been successfully cured in any patient to date and there is no cure. Most patients reach the end of their lives within three to five years, when motor neurons have withered to the point where they can no longer support cardiorespiratory function, and they experience respiratory failure and die.
Over the past few decades of his life, Cai Lei has used knowledge, hard work, and above-average enthusiasm to change his destiny, but this time he has taken on a task for himself that is so difficult as to be almost impossible to accomplish: he is going to find a new drug that can cure ALS.
It's a battle between man and death, with only a few hundred days left on the progress bar. Instead of traveling the world, he counted the days and stayed up late working, networking with cutting-edge scientists around the world, taking up the weapons of the Internet people, breaking down the established barriers to drug development, and linking up all the resources at his disposal.
A friend with the same disease asked him why he didn't slow down a bit, "(It's) a cutting-edge problem, world-class, and I'm afraid that aliens can only solve it". His response was, "It's no fun to do something that's not difficult."
Behind this mind-boggling optimism is a grim story of survival with a high probability of failure. But the success or failure of this move involves tens of thousands of similarly ill families, and Cai Lei has decided to run for himself, as well as for thousands of others. He understands better than anyone that fate is in his hands.
Fan Dongsheng, director of the neurology department at the Third Hospital of Peking University, was more decisive than any other doctor when he gave his diagnosis, telling Cai Lei, "You have amyotrophic lateral sclerosis, which is the only possibility, and all other possibilities have been ruled out.
Cai Lei asked him jokingly, "So I'm just dying? Fan Dongsheng on the table with both hands to gesture a distance of about 20 centimeters, he said, "your survival period has this long", and then the distance of the hands together, only a small cut, and then said, "now there is still so long."
It's September 2019, a full year after Cai Lei's body began to show abnormalities.
At first, he felt the muscles in his left arm jumping, or to describe it more accurately, they were muscle tachycardia, day and night. But this did not cause him alarm, he is the vice president of a domestic Internet factory, mainly responsible for the work of the treasury, the same period, but also with the group's four startups. The previous six or seven years he almost never went to the hospital, he felt, it was too costly.
This dragged on for half a year, and the situation did not improve until February of the following year, when he decided to go to the Union Hospital to see. The chief neurologist, Dr. Liu Mingsheng, looked at his EMG results and did not give a clear answer, but only said, "You're not very good at this. Liu Mingsheng asked him if he had time to be hospitalized, Cai Lei said, hospitalization is currently impossible to have time, so the doctor let him go back.
"You do not prescribe some medicine?" Cai Lei asked. But Liu Mingsheng said, no need to open, go home and take some vitamin B on the line. At that time, Cai Lei was quite happy in his heart, thinking that there is no big problem.
It took a long time for him to realize that when his body began to show symptoms of muscle tremors, it already meant that the motor neurons in his body were seriously dying, and his muscles had begun to atrophy in an almost irreversible trend.
This is the onset of amyotrophic lateral sclerosis (ALS), a rare disease commonly known as tachyphylaxis, which ranks among the world's top five terminal illnesses, for which no clear biomarker has yet been found for detection, and for which the rate of misdiagnosis is extremely high. Doctors who are not experienced enough to give patients a clear diagnosis are afraid to do so.
After seeking treatment at Union Hospital, Cai Lei went to different hospitals to receive multiple diagnoses until he found Fan Dongsheng, who was hospitalized and underwent a complete series of disease screenings to rule out all other possibilities, and then came to the most definitive and worst conclusion. And he was told that ALS is a disease for which there is no cure.
The only internationally recognized drug is a small pill called Liruta, which costs about $4,000 a box and can be taken for a month, and is said to prolong a patient's life by three months, but it doesn't cure ALS at all, and it doesn't stop the apoptosis of motor neurons at all.
It was September 2019, Cai Lei was 41 years old, and his destiny has since sailed away from its normal course. At first, like all terminally ill patients, he could not believe the doctor's conclusions and could not accept his fate, and for up to six months thereafter, he suffered from severe insomnia, and even if he fell asleep, he would wake up repeatedly.
The fortune teller said that he lacked gold and water in his eight elements, so he suffered from this calamity, and the gentleman nudged him to change his name to Cai Runqian. The Feng Shui master also told his fortune and told him to move away from his original home. He had tried various ways of treatment recommended by his friends, injecting expensive imported medicines and running a high fever of 39 degrees. Or go to Songshan Shaolin Temple to visit the point master, every day to do meridian massage.
But a kind of reluctance also appeared at the same time.
He was initially reluctant to make friends with other patients, and did not want to include himself as a member of the marginalized groups, and he pondered in his heart, "I Cai Lei, I still have to do great things". Once, when he was competing with others to do business, he would say to them, "Don't do it, you can't do it with me". The other side asked why, he said, "because you want life, I Cai Lei do not want life, you can not spell me".
Now, to do the death of this competitor stood up to his opponent, in the uneasiness, his arrogance and reluctance, as well as his own description of the "crazy" enthusiasm, and once again be inspired.
After his diagnosis, he searched for all the academic papers on ALS at home and abroad, more than 1,000 of them, and read them one by one, sentence by sentence. In order to improve his reading speed, he found a handy tool. And so he read for months, not even sparing the information in the nooks and crannies, trying to find ways from which he could save his life.
In November 2019, two months after his diagnosis, he set out to build and establish Beijing Aisikang Medical Technology Co. The inertia created by his 20 years of experience pulled him to make the decision, despite his family's objections, to use the medical technology company as a front to find truly effective drugs for overcoming ALS.
His wife, Duan Rui, wanted him to drop everything he was working on, to travel the mountains and spend more time with his family, but he was reluctant. In this world, Cai Lei says he only believes in himself, and only he can save his own life. Between him and death, a silent war has been fought.
He estimates that if he has three years left, if he can find a new drug within two and a half years, he will win.
First, let's meet the enemy, ALS.
As one of the country's best-qualified specialists in the field, Fan Dongsheng began working with the disease by chance.
At the turn of the century, his department of orthopedics at the Third Hospital of Peking University was the best in the country at treating cervical spondylosis, but there was a strange phenomenon in which some patients diagnosed with cervical spondylosis were still unable to find relief after surgery. There was no problem with the surgical procedure, but the condition of such patients might continue to deteriorate. It was only later that they realized that these patients were not suffering from cervical spondylosis, but from the rare disease ALS.
At that time, it was during the time when Fan Dongsheng was a graduate student, and when he was deciding on the topic of his dissertation, the professor of orthopedics posed a question to him from the clinical point of view: "Can you tell me how to judge that this disease is most likely to be your disease (ALS) and not our disease (cervical spondylosis)? )?"
Making the identification as early as possible is the only way to prevent the orthopedic surgeon from incorrectly operating on the patient, and cervical spondylosis surgery not only delays the diagnosis of ALS, but may even accelerate the progression of the disease.
Therefore, throughout his graduate studies, Fan Dongsheng's main topic was to identify ALS, and he later found that by means of electromyography, he was able to effectively differentiate between the two, with an accuracy of more than 98%.
However, at that time, there was extremely limited awareness of the disease in China, and to this day, very few doctors are able to accurately diagnose ALS.
It is indeed too unknown and too complex. In the UK, ALS is more commonly referred to as motor neuron disease, literally a disease caused by the apoptosis of motor neurons. Motor neuron disease has a broad spectrum of disease, encompassing three types: Hirayama and Kennedy diseases, spinal muscular atrophy (SMA), and narrow motor neuron disease. Narrow motor neuron disease, in turn, has several different subtypes.
Cai Lei's left hand, left arm, shoulder, back and other muscles have now been severely atrophied, his left arm can only hang helplessly on the side of the body, the back of the hand swollen, can not see the texture of the joints. The muscles of his right hand have gradually begun the same process of atrophy. Halfway through the interview, he also needs to wear a respirator to reduce the burden on his heart and lungs.
He no longer wears shoes with laces, no longer wears suits and pants that need to be belted, and often sends messages by voice or transcribes them into text. Once he was invited to attend a meeting, after taking his seat, he wanted to ask the lady in the next seat to help him unscrew the cap of the mineral water bottle, but the other party thought it was Cai Lei "bullying" himself, and he had to make amends to the other person to explain, "Sorry, my hand is not good".
Born in 1960, Shu Bai suffers from one of the most classic subtypes of ALS.In 2018, her left arm started to fall ill, and in May 2019, she was diagnosed at the First Affiliated Hospital of Sun Yat-sen University.In November 2020, she was still able to walk, but that's when she fell, and she hasn't been able to stand up since.
Today, Shu Bai is confined to a wheelchair, where she can feed herself with a spoon but has lost the ability to care for herself beyond that. Her husband and nanny*** take care of her together, and when she sleeps at night, Shu Bai depends on them to turn over for her once. The whole time she was interviewed, she had to wear a respirator for oxygen.
There is also a more aggressive progression of the disease in the patients. Jane's husband, who is 40 years old, started having breathing problems just a year after the onset of the disease in July 2020, and a 38-year-old entrepreneur, who has been living with the disease since the beginning of the year, has had to wear a ventilator. There is also a 38-year-old entrepreneur, the onset of nine months, has been quadriplegic, life-threatening, some time ago one night, his blood oxygen saturation once fell to 92%, unable to breathe on their own.
The muscles of the human body are innervated by neurons, and when the neurons begin to wither, the muscles can no longer move and will soon atrophy. In three to five years, the disease progresses to a later stage, the human body will become like a melted candle, the heart and lungs can not be supported by the muscles, the trachea must be cut open and rely on a ventilator to maintain life, if not, it will die of respiratory failure.
Thousands of ALS patients have come together in multiple WeChat groups established by Cai Lei, and they witness death every day. Sometimes, the group is informed by relatives of patients of the death of a loved one, or, when someone starts reselling a respirator, it means that another person has disappeared from the world.
Around 2003, a multicenter collaborative group specializing in ALS was set up, led by Beihang Medical Third Hospital, where Fan Dongsheng is a member. Initially*** four hospitals were involved in the collaborative effort, which has grown to include more than 100 hospitals. They are also promoting the development of new drugs for ALS, but the road is still very treacherous.
BrainStorm, a US cell therapy company, has been working on exploring ways to cure ALS through NurOwn stem cell therapy since 2001, and they were the most highly anticipated company by patients, and the drug they developed passed both Phase I and Phase II clinical trials, but in 2020, the Phase III clinical trial ended, and the data from the trial failed to show a statistically significant difference, meaning that the drug did not have a significant effect on ALS. means that the drug has no significant efficacy against ALS. The 19-year-long research and development of the stem cell drug was declared a failure.
Cai Lei remembers very clearly that on that day, BrainStorm's stock price plummeted by 70%, and for many ALS patients, the hope of survival was dashed as quickly as the lights were turned off, "That week, a lot of patients died," Cai Lei said.
Twenty years ago, Fan Dongsheng's team enlisted the help of Harvard University's School of Public ****Health to design a set of scales, which served as a standard for the constant collection of sample data from ALS patients. Fan Dongsheng understood that collecting data was almost certainly the most important part of understanding rare diseases in a deeper way.
To build a more complete database, they would have to follow up with patients in person or by phone every three months to update them on the progress of their disease and the effectiveness of their medications. It's a time-consuming and underfunded task, so Fan had to get his students to help out and pay them for their labor.
After 20 years of persistence, they had collected almost the largest sample of ALS data in the world. But Fan Dongsheng also gradually realized that the scale was not very precise. Moreover, the frequency of follow-up visits, once every three months, did not make it easy to observe the patient's changes in time.
Cai Lei's appearance brought a very important, enough to break through the bottleneck, namely, the Internet.
Cai Lei, a self-proclaimed "Internet veteran", had a strong suspicion that most hospitals don't have their own patient database after searching around for medicine. The information does not circulate between hospitals and hospitals, and there are fewer cases of rare diseases, in which case, how to carry out disease research and new drug development?
Almost instinctively, he realized that the creation of a large database was the key to unlocking the code of ALS disease.That November 2019 startup was designed to solve this problem.
Through Beijing Aiskang Medical Technology Co., Ltd, he set up an information aggregation platform called "Gradual Healing Mutual Help House", through which all ALS patients can upload complete information about their condition, and be able to update the effect of medication and the progress of the disease in real time.
At that time, Cai Lei wanted to build a database that not only considered the possibility of various options, but also could be horizontally connected to the standards of the medical insurance center, in order to fit a more long-term diagnosis and treatment planning. Fan Dongsheng provided him with a scale, but that material requires more of a physician to assist the patient with the assessment, while Cai Lei wanted an indicator that the patient could self-assess and self-test on his own or with the assistance of his family.
It just so happens that his wife, Duan Rui, graduated from Peking University with a bachelor's degree in pharmacy, and in the early days of the data platform, Duan Rui supported Cai Lei's team*** to complete the development of the indicators.
Cai Lei told Nanfeng Window: "Any one of these issues, we discuss a day or two or even a week can not finish, very large and complex, especially difficult, total **** made more than 2,000 fields, each field is incredibly difficult."
For example, they wanted to find the relationship between the cause of ALS and the patient's occupation, so they had to design a detailed occupation option, if they only gave the field "athlete", that is too brief, to be refined to soccer, table tennis, basketball and other different aspects.
Then, for example, when it comes to more specialized data such as "neck pain", which patients can't measure on their own, they find a way to set the question to "what position can you raise your hand to" and "how many seconds can you hold on to? How many seconds?
Similarly, you can't ask, "Did you increase your bowel movements after taking the medication?", but rather, "How many times did you have a bowel movement after taking the medication?
Shubai said, the scale she filled out a few days, her hands have been almost inactive, only a thumb can be used. But the good thing is, Cai Lei, who designed the scale, is a patient himself, and he simplified the way to fill in the scale by ticking and circling, and arranged for a colleague to be the platform's housekeeper, directly helping patients who can't upload information smoothly to enter data.
Currently, the sample size of this recently established data platform has exceeded 2,000.
As the clinician who has the most intensive contact with patients, Fan Dongsheng analyzed to Nanfeng Window the significance that this data platform will have on ALS research.
"The big data platform can reflect the changes of the patient in real time, may be we can quickly see whether a certain drug is effective or not, for some platforms of new drug development, it can significantly reduce the cost of time, because time is money. After getting the time down, the investment in new drug research is accelerated."
In fact, in Cai Lei's world, the concept of "everything is interconnected" is not only applied to work, but also has already penetrated into every corner of life.
In March 2020, he gave Duan Rui to find a number of online storage APP, suggesting that she upload all the family items to the "system", to each cabinet code, the formation of the system of folders, and then drag the picture of the items into the folder, make a good note of the shelf life, "you will not be unable to find things," he said. "It will not be unable to find something, the key is to prevent the expiration date".
Duan Rui thought Cai Lei was particularly funny, so he sent a circle of friends and wrote: "Next time I can proudly speak with the customer, my home back-office operations have initially realized the management of the Internet of Things."
Duan Rui, as his wife, can be considered the person who sees Cai Lei's strategy most clearly.
She is a pharmacy professional "insider", more than ordinary people y realize that Cai Lei wants to promote the development of new drugs for rare diseases of the arduous nature.
"His thing is that it is so difficult that people in our circle are afraid to think, they think that this idea is not this option, because first of all, you need a lot of money for research and development, you need a team, you need a lot of years, but the failure rate is very high, and it's not something that can be pushed by personal power."
BrainStorm research for 19 years to overcome the failure of ALS, just with Cai Lei, how to make things happen? But Duan Rui know, for Cai Lei, "Internet" is not just a tool, but also a set of decision-making underlying logic. If you follow the original process of new drug development, there is no doubt that you will lose, but Cai Lei's way of thinking breaks the old rules of the game.
With new drug R&D, the main parties involved are investors, hospitals, pharmaceutical companies, research teams, patients, and registration departments. But in the case of ALS, almost every part of the drug development is lacking, which is also common sense, and is a chronic problem in the development of drugs for rare diseases.
Investors are reluctant to pour money into the small market for ALS because it seems so obvious that there is no money to be made, and are more likely to invest in neurodegenerative diseases such as Alzheimer's because of the size of the population and the high rate of return.
He breaks down the math for the other side, and says that even though there are 10 million patients with Alzheimer's, not many will pay for the disease because the people with the disease are old and don't think they have it themselves, and they don't want their children to spend more money on them.
"I thought you said 10 million people with Alzheimer's? How many are your real clients? My grandpa is now 82 years old and has Alzheimer's, and he won't spend a dime on this disease, you can't even drag him through it."
And he argued that ALS, which affects people between the ages of 40 and 60, is the backbone of families and society, and that if one spouse is ill, the other will certainly be involved at the same time, caring for their partner's diet and unable to work normally. Therefore, he told those investors that a family will spend tens of millions of dollars to save ALS patients even if they have to break the bank, because the collapse of one person means the collapse of a family.
"ALS 26,000 new people every year, I will count on the existing 100,000 people, each person is willing to spend 1 million to cure, is 100 billion ah."
At the same time, he has already mastered thousands of patients and gradually improved the patient big data as a bargaining chip, told investors, you do not even need to promote, the consumer market, I directly docked to you.
So, more than 100 investors, and ultimately there are one or two successful lobbying, agreed to support the development of new drugs for ALS.
And Fan Dongsheng believes that ALS is still a research project worth investing in, because ALS and Alzheimer's disease, Parkinson's disease and other common diseases belong to the same neurodegenerative diseases, their pathogenesis is similar, and ALS is one of the fastest growing diseases. From the capital point of view, ALS can be a perfect research model, if the development of new drugs effective on ALS, it is likely to directly open the pathway to the treatment of neurodegenerative diseases.
Lei Cai understood this, and in early 2021, he successfully persuaded Prof. Gong Chen, who had been working on Alzheimer's disease, to turn to ALS research.
Chen Gong resigned his tenured professorship at Penn State in 2019 and returned to China to join the Guangdong-Hong Kong-Macau Institute of Central Nerve Regeneration, which conducts research on neural regeneration to address major brain diseases.
In 2013, his team successfully regenerated glial cells into neurons in the brains of mice with Alzheimer's disease using a neurotranscription factor, the first of its kind internationally.
Neuronal regeneration, if developed to maturity, could enable a range of neurodegenerative diseases, including ALS, to be overcome.
In the words of Duan Rui, this is like minesweeping, "is that you point to open an empty go, 'wow' a full open kind of feeling, what can cure, just a better effect on this, the effect of that a little bit worse, the feeling is very painful.
In Cai Lei's link, including Professor Chen Gong, Tsinghua University, Professor Lubai and other scientists engaged in basic science research are engaged in clinical Fan Dongsheng established contact.
Originally, it took about 8 to 10 years to go through the whole process of new drug development in a complete way, and with all kinds of resources being fully aggregated, Chen Gong told Nanfeng Window that the process can be accelerated by as much as two years. And such as Chen Gong's research, the early stage of the experiment has been carried out in foreign countries for several years, and now, under the impetus of Cai Lei, is expected to achieve preliminary results next year.
1978, Cai Lei was born in Shangqiu, Henan Province, a poor military family, wearing clothes with patches on the junior high school, and then his father's early death, the family's heavy burden, he always wanted to do everything better than others. Exams to take the first, playing games to be better than others, even if the physical smaller, but as long as there are hooligans dare to bully him, he must be with each other a big fight.
"I know I can't do it, but if you dare to provoke me, I dare to do it with you. Never give in to defeat, that's the kind of person I am."
(Duan Rui, Shu Bai and Wang Jin are pseudonyms in the text)
Editing | Li Shaowei
New Media Editor | Pan Ni
Typesetting | Wen Yue
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