We look up at the starry sky, isn’t it just to make people around us have a better life?

Why do humans look up at the stars?

Luo Shuai’s answer is: “In order to make the people around me a better life.”

This issue of microscopy story tells a group of people who are engaged in the genetic testing industry. They hope to use genetic testing to predict the risk of illness and provide health management advice, and stop the “monster” of the disease before it enters the ward.

Here is the true story about them:

Wen | Zhao Ran

Edit | Plum

The “monster” in the ward

The patient’s breath is already suffering, and the pain caused by non-small cell lung cancer is torturing him all the time.

In the genetic testing laboratory, Luo Shuai’s gaze is staying on the patient’s lung puncture sample.

Most of the sample detection and analysis have been completed with the help of a high-throughput sequencer. Only the last link is the genetic test report and the blood test results to provide medication guidance for the treatment plan!

The experiment was suddenly interrupted, and Luo Shuai received a notification from the hospital: the experiment was suspended.

Beijing’s summer is hot and dull, and under the white coat, a chill bursts from the soles of the feet-which means that the patient has passed away.

He has done genetic analysis of thousands of biopsy samples, and this is the most annoying case.

Non-small cell lung cancer is like a “monster”, 80% of all lung cancers are its presence. Among them, nearly 70% of the patients were in the middle or late stage when they were discovered, and the main cause of this “monster” is smoking.

“It’s really a shame that I couldn’t save it. It would be great if it could be prevented in advance.”

Luo Shuai doesn’t want to catch the “youkai” in the ward anymore. He wants to stop the “youkai” before it enters the ward.

Secrets tens of millions of years ago

In the early spring of 2019, the cold was expected to be severe. Luo Shuai walked into a shared office space outside Jianguomen on the Second Ring Road in Beijing and sat in front of Li Zhi.

Li Zhi’s last identity was the vice president of a private equity fund with an annual salary of several million. Before entering the investment bank, his life trajectory was more related to life science research.

In 2005, when Li Zhi entered the College of Life Sciences of Wuhan University for undergraduate studies, China’s genetic testing industry had just started.

At that time, the human genome sequencing work costing US$3 billion in many countries around the world was finally completed-17 million years ago, the humanIsolated from the ancestors of the gibbon family, the secret that has been engraved into the 6 billion bases of the gene double helix since ancient times, for the first time, slowly unfolded in people’s surprising gaze.

At that time, the saying that “the 21st century is the age of life sciences” was already popular in society, but the life science profession that Li Zhi studied was not directly proportional to his fame.

“Domestic life science doctors only get a salary of about 1,000 yuan per month.” Li Zhi believes that, in essence, the degree of industrialization of life sciences is relatively low.

In 2014, when Li Zhishang was in the investment bank, the turning point of the genetic testing industry has quietly come-genetic testing company Illumina released a new gene sequencer HiSep x Ten, which can accurately detect the whole genome sequence and reduce the cost of gene sequencing to At the level of thousands of dollars, the genetic testing market has begun to usher in a full-blown explosion.

With the decline in costs and the popularization of technology, the concept of genetic testing has gradually become popular.

A well-known example is that when Hollywood actress Angelina Jolie was 38 years old, she found out she was carrying a high-risk breast cancer gene mutation, so she underwent bilateral mastectomy.

The gene sequencing method used by Illumina is “shotgun” sequencing, which is a bit like a jigsaw puzzle. Based on the cover of the complete human gene map, all the genomes are scrambled and cut into random fragments, and then the sequence of each small fragment is determined. , And finally reorder the slices like the cover of the comparison puzzle to determine their correct position in the genome.

It sounds simple, but the actual difficulty of sequencing is like putting together a picture accurately from a mountain full of jigsaw pieces.

Li Zhi knows that the interpretation of genes not only requires innovation in life sciences, but also has a natural demand for cloud computing: before the advent of cloud computing, genetic data analysis required several months of computing cycles, and cloud computing has greatly accelerated The speed of genetic data analysis; genetic testing first splits small fragments, then segments the results, and finally merges the results, just like parallel computing in big data.

“Gene sequencing explores the code from the beginning of life to the present. Cloud computing is the thinker, turning every clue unearthed by the explorer into a prediction of the future evolution of life.” Li Zhi said.

He keenly caught the advancement of genetic testing technology and the decrease in cost, and wanted ordinary consumers to enjoy the benefits of this technology, so he resigned and founded Beijing Lasuo Biotechnology Co., Ltd. (hereinafter referred to as ” Lasso”).

There are two directions for genetic testing. One is medical-grade genetic testing, such as Luo Shuai’s previous work, including reproductive health, tumor diagnosis and treatment, and the price is tens of thousands; the other is consumer-grade genetic testing. Ordinary consumers provide drug reaction testing, genetic disease risk testing, health risk assessment, medication risk reminders, etc. in the pan-medical field, and provide health management recommendations, ranging from tens to hundreds of yuanThe price is also more affordable.

Li Zhi chose the latter, from an investment bank elite in suits and shoes to an entrepreneur who proficiently responded to genetic testing-related questions on Zhihu; Luo Shuai embraced the idea of ​​“informing people of the risk of illness in advance, through With the idea of ​​changing living habits to reduce the chance of getting sick, he became a genetic counselor for Lasso.

Figure | Genetic test results show that this user is more likely to have esophageal cancer

Fly into the homes of ordinary people

At the beginning of its establishment, Lasso received an angel investment of 36 million yuan-this is the largest angel investment in the history of the consumer genetic testing industry in the world.

The first problem lies in front of Li Zhi: a user’s genetic data, even if compressed, is close to several hundred MB. These data need to be stored and calculated, and with the development of genetics, more and more data will be needed. An extremely clever “brain”.

And “cost” is the life and death line of startups, how to establish a reliable, stable and cost-effective technical support system?

Going to the cloud is the least costly solution. “Considering stability, reputation and technical support capabilities, we chose Alibaba Cloud at the beginning of our establishment,” said He Chengxiong, CTO of Lasso.

He is a veteran of the technology industry. He has worked for Fetion and 360, and has been watching cloud computing, SaaS, and mobile Internet from the bud to the surging trend.

He knows that, unlike other industries, genetic testing and life sciences are very closely integrated, and their structural levels have their own characteristics; algorithms are also more professional; user data security must be strictly guarded against red lines.

With the advancement of cloud computing technology, public cloud platforms can now provide genetic testing companies with large-scale and easily scalable data computing and analysis capabilities.

Lasso gives the genetic data calculation of the genetic testing laboratory to the cloud server (ECS). This elastic and scalable computing service helps Lasso reduce IT costs, improve operation and maintenance efficiency, and make Lasso more focused on Core business innovation; core consumer-oriented products-Genebao App’s servers and database storage are also deployed on the cloud,The cloud database RDS is used.

The foundation has been consolidated, and the servers and databases are waiting in full, looking forward to the first “visitor”.

Tang Zulong, vice president of Lasso Product Science, clearly remembers that at 4 o’clock in the morning on October 21, 2018, the first version of Genebao App was launched. Soon, the saliva box of the first user arrived!

In Lasso’s Guangzhou laboratory, the oral mucosal cells of the first user were extracted from saliva, and the genetic data carried on the double helix was lightly and quickly detected, calculated and analyzed on the cloud, and then translated into Common modern people can understand ancestry analysis, genetic characteristics, genetic disease mutation screening, medication risk reminders and other information.

Figure | Cable staff test oligo with liquid mass spectrometer

Luo Shuai introduced that just as “there are no two identical leaves in the world”, the pharmacokinetic and pharmacodynamic properties of the same drug in different individuals are also different.

An aspirin, some people will have greater side effects than ordinary people with asthma after using up. The results of genetic testing can help patients adjust the dosage or choose a backup medicine as appropriate.

Figure | Gene test results provide medication guidance

Luo Shuai remembers that the most “bizarre” time was when a user reported that his father had blood type A and his mother had blood type O, but his genetic test result was AB. People around him urged him to “be a paternity test.”

This user couldn’t figure it out, and later learned through Luo Shuai that he is actually a very rare Bombay blood type, and only about 30 cases of this blood type have been reported in China.

This means that the general blood bank does not have this kind of blood reserve. If the user needs blood transfusion, he must prepare for blood collection in advance.

Up to now, Lasso has provided medication guidance to hundreds of thousands of usersInformation, genetic disease screening, ancestry analysis and other services.

In addition to changing people’s lives, genetic testing technology also provides services for pets.

Although many pets seem to be healthy, they may carry disease-causing genes. Pet genetic disease testing can extract pet cells and DNA from the secretions on the inner wall of the pet’s oral cavity, analyze the pet’s genetic information, and provide personalized Parenting, breeding advice and medical and health guidelines.

He Chengxiong calculated an account, and under the same scale, using the cloud to save 50% of labor costs and 30% of server costs.

For start-up companies, every cost saved can support more service expansion-for example, a self-built clinical diagnostic level laboratory, a quick trial and error, or give Luo Shuai Such life science practitioners are better treated.

A person’s “battlefield”

The start-up company maintains a rapid development speed. Genebao App is iterated twice a month. More and more users are willing to pay for genetic testing, and more and more servers need to be rented by Lasso.

Figure | Cable crews perform fluorescence hybridization experiments in a fume hood

The turning point for the business will happen in 2020.

Lasso Biology cooperated with scientific research institutions of universities and developed a high-density gene chip (microarray), covering an integrated solution of sequencer, chip, reagent and software, breaking the long-standing development of Illumina and Affymetrix in this field. With a 20-year monopoly, this is the first time that a Chinese company has achieved domestic substitution in this field. It is expected to achieve mass production in the first half of 2021.

The successful development of the genetic testing chip has reduced the cost of genetic testing to less than half of the original. It is foreseeable that this will further reduce the price of genetic testing and bring about an increase in the number of users. Lasso expects that the number of users will increase from 2021. Hundreds of thousands increased to 1 million.

In order to take on the tide of users, He Chengxiong made adjustments to the technical architecture in advance. The system architecture originally built by the cable can no longer keep up with the business needs, so I bought a new batch ofServer, gradually change the original architecture to a more flexible Kubernetes cluster.

“In the long run, when the number of users suddenly explodes, we can also dynamically rent more resources of cloud computing with very little manual intervention,” said He Chengxiong.

There are more than 20 development and technical personnel in Lasso, but all the operation and maintenance of the technical background falls on the shoulders of Lu Lin, a girl born in the 90s.

The last company where Lu Lin worked used physical machines to store data. The four words she was most afraid of hearing were-“The hard drive is broken.”

“Use a physical machine to store data. You need to prepare a few more servers to ensure high availability. Not to mention the high cost. Once it breaks, the data inside may be lost.” If a major failure occurs, several operations are required. The maintenance personnel gathered around and kept repairing for a day.

In Lasso, all of Lu Lin’s operation and maintenance technology platforms have been put on the cloud. “The stability is guaranteed, and the operation and maintenance costs are reduced.” But it also means that “there are many technologies to learn.”

Fortunately, there is a “virtual team” behind her. Work orders are one of her most important “helpers”. In Lasso for more than a year, she has submitted more than 90 work orders in total, and joined the Feitian members of cloud vendors.

“The product update on the cloud is very fast. Sometimes I encounter various operation and maintenance problems, so I submit a work order.” “Helper” is thousands of kilometers away from her, but basically I will get a reply within a few minutes. “Sometimes technical problems are tricky, and the technical support staff will reply to me first, and then solve them in detail.”

One time in the early morning, there was a technical problem, and the backstage machine of the cable called the police automatically. At that time, Lu Lin was already off work.

The problem was resolved after 30 seconds. When Lu Lin went to work the next day and saw the alarm record, he found that Alibaba Cloud’s ticket support staff also sent a message in the early morning to explain the cause of the problem.

“It’s like a virtual team. It can support me and solve problems by itself.” Lu Lin said.

Lasso uses more and more cloud computing products and architectures, and technical support needs are becoming more frequent. There is much more communication. Lin Xiangyi, a telemarketer in Dalian, and Xu Qun, a service in Hangzhou, even keep in mind when Lu Lin from Beijing goes to work and when he takes a vacation. He also organizes product managers and architects to visit. During the visit, we recommended an optimized solution for gene computing for Lasso.

Picture | Quantitative experiment using pipette by staff

After the successful development of high-density gene chips, the story of technological breakthroughs will continue.

The seeds that Luo Shuai planted in those days have been distributedYa, with the help of the secret volume of the human gene map, he is providing more and more people with advance warnings of disease risks and driving away the “monsters” in front of them.

Luo Shuai is nearly 30 years old, and is most afraid of his parents’ health problems. My father is a “stubborn old man who doesn’t listen to persuasion”, smoking and drinking are commonplace. Later, Luo Shuai took a genetic test. The test results showed that the risk of diabetes was higher. “Not stubborn.” Quit honestly, every time Luo Shuai goes home, he will be dragged to play table tennis.

Looking at his father’s figure, Luo Shuai couldn’t help but sigh: “We look up at the starry sky, isn’t it just to make the people around us live better?”