◎ Author | Science and Technology Daily reporter Liu Zhiwei
◎Planning | Lin Lijun
In the early summer evening, with a breeze, walking out of the Enming Building of the Innovation Research Institute of Huazhong University of Science and Technology, Professor Xie Qingguo, who had just finished handling the work at hand, was slightly tired.
"I decided from the beginning of graduation that I wanted to make PET research a lifelong career, and after 20 years, the all-digital PET has finally changed from 0 to 1."
PET is the abbreviation of positron emission tomography and is regarded as the best means for early diagnosis and efficacy evaluation of tumors. Xie Qingguo has independently developed an all-digital PET with completely independent intellectual property rights, and has applied for more than 570 patents in China, the United States, Japan, Europe and other countries and regions, and authorized 121 invention patents.
No one does technology, Xie Qingguo does it himself; no one does industrialization, he has to do it himself. What Xie Qingguo did not expect was that after breaking through the key technology of "card neck", the road of marketization and industrialization was so arduous.
"The product was made, but it couldn't get into our hospital." Xie Qingguo said, "For all-digital PET to be truly successful, it needs to get more applications, find more problems, and iterate more abundant products, so that it is possible to really flatten, consolidate and broaden this technical route, but now..."
<h1 class="pgc-h-arrow-right" data-track="13" > has broken through the core technology in research, but has repeatedly hit a wall in industrialization</h1>
Conquered the core technology, got the market access certificate, compared with similar products have obvious advantages... Researchers who have gone out of colleges and universities find it so difficult to enter the market.
Zhang Bo, head of the industrialization of the all-digital PET project, said in an interview with the Science and Technology Daily reporter that a municipal hospital in Hubei province wants to purchase PET, and the procurement indicators set are "tailor-made" for imported equipment. Soon, they learned that another hospital in the same city was also preparing to procure PET.
Zhang Bo was clearly informed by the relevant person in charge of the hospital, "Our hospital is higher than their level, and the procurement equipment will not be lower than them, so we do not consider domestic equipment." ”
The local health authorities are also helpless: "Market behavior, we can not interfere too much, they feel that 'foreign equipment' is used with confidence." ”
A person in charge of the equipment and materials department of a third-class hospital who did not want to be named said that they were not unwilling to use domestic equipment, but had many concerns: "Buying imported equipment has other hospital success cases, and the regulations are up to standard, even if there is a problem, at least the process is correct; and buying domestic equipment that no one has used, who is responsible for the problem?" ”
Holding the core technology, Xie Qingguo and his team could not laugh.
It is not an exaggeration to say that this is the core technology. As a representative achievement of domestic high-end medical treatment, all-digital PET has developed a complete technical system from an original concept, and has been selected as one of the top ten scientific and technological progress news in China in 2019 selected by academicians of the two academies.
The world's first human clinical all-digital PET/CT device
Prior to this, the key technologies and equipment of PET were controlled by "GPS" - gemma, Philips, Siemens three, building a strict patent barrier, making it difficult for latecomers to move forward.
Looking back at the history of PET development, pet research started from abroad in the 1950s. In 1982, the road to the industrialization of PET began in the United States. Japanese companies have been trying for 22 years to bypass the patent barriers of the three major manufacturers, but they have not been able to do so.
China is a big cancer country, in recent years, cancer incidence and mortality rates have shown a continuous upward trend, cancer has become the first major factor leading to the death of our citizens. Compared with developed countries around the world, the five-year survival rate of cancer patients in China is still low. In order to reverse the situation, the medical community has proposed a countermeasure of "early detection and early treatment", and PET is an indispensable weapon for practicing this countermeasure.
"In the process of disease occurrence and development, the first thing that occurs is the physiological and biochemical changes, and then the changes in the anatomy." Xie Qingguo introduced that for malignant tumors, nervous system diseases, cardiovascular system diseases, etc., PET can find early lesions because of its advantages of high biochemical sensitivity.
How can this weapon, which is not in their own hands and can only be purchased at high prices for foreign equipment, reduce the medical burden on patients? How to improve national health?
With this mission in mind, Xie Qingguo began a 20-year exploration.
This exploration is difficult. If you blindly follow the technical path of "GPS", you will only hit a wall everywhere, how can you go from following to leading by yourself? As a result, Xie Qingguo opened up a new track, that is, all-digital PET.
"The full digitization of PET is not a simple technological replacement, but a 're-invention' of PET." Xie Qingguo said that it is like a digital camera to a film camera, and its application may change dramatically.
Xie Qingguo's team's all-digital PET is characterized by all-digital and accurate sampling, canceling the analog circuit processing at the same time, to achieve accurate digital capture of the signal source, so that the photo is clearer, can find smaller tumor lesions, in order to achieve early diagnosis, early treatment at the same time, the use and maintenance is more convenient and efficient.
From the MVT all-digital sampling method proposed in 2004 to the domestic all-digital PET/CT obtaining the "quasi-birth certificate" in 2019, the all-digital PET has changed from 0 to 1.
At the end of 2018, the world's first human clinical all-digital PET/CT device completed clinical trials in the First Affiliated Hospital of Sun Yat-sen University and the Affiliated Cancer Hospital of CUHK in Guangzhou
After the all-digital PET device landed, it performed well in clinical trials. Fan Wei, head of clinical trials and director of the Department of Nuclear Medicine of the Affiliated Cancer Hospital of Sun Yat-sen University in Guangzhou, commented: Although this device is the first clinical product of all-digital PET and adopts the basic hardware configuration, it can be said that this device has reached the imaging level of some higher configuration products.
Once the news of the success of all-digital PET spread, the price and inspection cost of similar products in foreign countries fell, "In the past, it took more than 10,000 to do a set of PET inspections, the emergence of domestic all-digital PET, the price of imported equipment has been reduced, and the terminal inspection fee has also dropped to seven or eight thousand yuan." Zhao Dehui, director of the Ezhou Municipal Science and Technology Bureau, said.
<h1 class="pgc-h-arrow-right" data-track="103" > has been looking for "white knights" who can jointly complete the marketization</h1>
"There is no hospital, we will use it ourselves." Zhao Dehui said.
Ezhou City, Hubei Province, as the undertaker of all-digital PET industrialization, has once again had to carry the banner of application demonstration of domestic high-end medical equipment.
On May 8, the reporter rushed to the Nuclear Medicine Center of Ezhou Central Hospital and interviewed jiao Cilai, director of the center. "Last year, the equipment entered the site, through installation and commissioning, environmental assessment, personnel training, health department evidence collection, this year's Spring Festival has been officially served." He said.
With more than 30 years of experience in medical imaging, Jiao Cilai is specifically responsible for the clinical application of this domestic equipment. He said the all-digital PET/CT was highly sensitive and the inspection speed was also very fast.
Jiao Cilai, director of the Nuclear Medicine Center of Ezhou Central Hospital, is operating the domestic digital PET/CT
If the subject accidentally moves on the examination bed causing artifacts in the image, or an unexpected situation in which the inspection is interrupted suddenly, there is no need to rescan, and it can be corrected in time by image processing software.
"The state has a 'first set' policy, and we purchased the first domestic all-digital PET/CT clinical equipment for use in our central hospital according to this policy." Zhao Dehui said.
"The industrialization of PET has also been forced out." Professor Xiao Peng, a core member of the all-digital PET team, introduced that they have not stopped looking for "white knights" who can complete the marketization with the R& D team.
Xiao Peng recalled that the Ministry of Science and Technology and the relevant departments of Hubei Province and Wuhan City were very concerned about the transformation of the results. In 2013, Tang Liangzhi, then mayor of Wuhan, visited Huazhong University of Science and Technology, saw Xie Qingguo's team project, and hoped that the school would promote the industrialization of all-digital PET as soon as possible. Coupled with the encouragement of Li Peigen, then president of Huazhong University of Science and Technology, Xie Qingguo has since embarked on the "road of entrepreneurship".
At first, Xie Qingguo could only settle with a dozen start-up members in an old classroom at the school.
A dozen people crammed into a room of less than 40 square meters. To make room for assembling the prototype, each table had to be moved back and forth.
A year after the project started, there was one of the toughest moments: the team members were barely paid. At that time, Xie Qingguo and Zhang Bo even borrowed money from banks in their personal names to maintain the normal operation of research and development work.
The threshold and difficulty of the industrialization of high-end medical devices are far beyond their imagination.
On September 2, 2015, Xie Qingguo, who had run out of food, pinned his hopes on Li Bing, who was the secretary of the Ezhou Municipal Party Committee at the time, who had only one side of the fate.
He tried to send Li Bing a "help" text message. Text messages were answered quickly. The speed of progress after that was so fast that Xie Qingguo repeatedly described it in four words: "unexpected."
On September 4, the all-digital PET industrialization team was invited by Li Bing to inspect the Wutong Lake New Area in Ezhou and reached the intention to settle in; within 3 days, the relevant departments of Ezhou City completed the factory building, company registration, food, clothing, housing and transportation required for the project landing; 7 days later, Hubei Ruishi Digital Medical Imaging Technology Co., Ltd. was officially established in Ezhou, and the project team members "moved in with bags".
"We have listed the industrialization of all-digital PET as the No. 1 project of Ezhou Science and Technology to promote." On May 10, Zhao Dehui was interviewed by a reporter from Science and Technology Daily in his office. He said that although Ezhou City has invested money, it does not interfere in the company's operation and only does a good job.
Li Bing has led relevant departments to discuss and study the problems in industrialization for many times. He said that the all-digital PET project is not an ordinary investment project, so it will immediately become tax and output value is unrealistic, Ezhou should do a thing to promote the development of science and technology, do a little to improve human welfare.
Researchers analyze brain imaging image data collected from digital PET
The equipment can be landed, and Xie Qingguo is very grateful for the help of Ezhou City. "The government has been acting as our 'angel investor.'" Xie Qingguo said that along the way, the Foundation Committee, the Ministry of Science and Technology, the Ministry of Education and other national science and technology management departments and local governments have vigorously supported the all-digital PET from principle innovation to technological innovation, and finally turned this new technology into a market-oriented product.
Xie Qingguo calculated an account for the reporter, and invested about 200 million yuan in all-digital PET equipment before and after. This has also created a miracle in the field of high-end medical device manufacturing. "We only used 10% of the funds and time of the international giants, 1% of the manpower and resources, to complete the leap from theory to the product of all-digital PET."
<h1 class="pgc-h-arrow-right" data-track="104" > the government gets on the horse, who will give it a ride</h1>
"When we made the world's first all-digital PET scientific instrument 11 years ago, capital should have intervened to promote the industrialization of this achievement." Xie Qingguo said that he repeatedly "complained" to school leaders and took on too much work that had nothing to do with research.
"The marketization of all-digital PET is not something we can accomplish in Ezhou City." Zhao Dehui said, "We also introduced a lot of investors and resources for them, but in the end they did not negotiate." ”
Ezhou City was originally ready to take out another 50 million yuan to support the application demonstration of all-digital PET, but this plan was also shelved because of the current shortage of funds.
In order to industrialize all-digital PET, Ezhou has invested nearly 100 million yuan. It has been two years since I got the market access certificate, but the product has not been able to open the market, and Ezhou City is also very anxious.
"Our projects are different from other industrial projects, some of the technology transfer is done, but we can't." Xiao Peng said, "In the early days, there were more investment companies with state-owned asset backgrounds, and they all came with leadership tasks. "But after they learned about the project, they felt that investing one or two hundred million yuan was a drop in the bucket, and they couldn't play without the investment of 2-3 billion yuan."
In recent years, more than 20 investment institutions have thrown olive branches before and after, but in the end, none of them have reached cooperation.
Is there a problem with the technology? not necessarily.
Compared with large foreign medical device companies, Xie Qingguo's team has achieved great success with less human and financial investment, breaking the long-term monopoly of PET technology abroad.
The lessons learned by the "stuck neck" made Xie Qingguo's team focus on the layout of intellectual property rights around the innovation chain and industrial chain from the beginning, systematically planned and covered the key materials of scintillation crystals, SiPM core devices, digital PET detector core components, all-digital PET scientific instruments, and clinical all-digital PET medical equipment systems and other complete systems, forming a complete innovation closed loop and ensuring self-sufficiency in technology.
Professor Xie Qingguo is inspecting the equipment
Is there a problem with the market outlook? Nor is it.
All-digital PET is fully general-purpose electronics that can be upgraded modularly. The exclusive components and components of traditional PET are difficult to update and keep up with the pace of technological development, while digital PET can be upgraded with the rapid development of consumer electronics, greatly accelerating the speed of its technological development and performance improvement.
There was once a Zhejiang company that wanted to buy one of the technology products, and the offer of Xie Qingguo's team at that time was 1 million yuan. But talking about it, the company did not buy it, but turned around and chose imported products. However, the company worked hard to buy imported products that happened to be purchased by foreign companies from Xie Qingguo, and the company spent 10 million yuan on the technology.
In the eyes of investors, they have their own concerns. Xue Kang, an investor in Wuhan, told reporters: "It seems that the product is made, in fact, can it continue to operate stably, including hardware, software, materials, and marketing models, can it compete with 'GPS'?" This is an issue that investors must consider. ”
"Investors hope that after investing, they can apply for an IPO in 3-5 years. But such a project may not be able to run for 10 years. Xue Kang said. An investor in Beijing told the Science and Technology Daily reporter that at present, domestic high-end medical equipment is definitely optimistic. He believes that perhaps the information asymmetry has caused the team to not meet the right capital side.
Zhao Rongkai, president of the Optics Valley Innovation and Development Research Institute, said that for many years, the whole country has been calling for domestic high-end medical equipment. However, domestic high-end medical equipment came, but we were blocked out by ourselves. Zhao Rongkai believes that all-digital PET is a source innovation, is a "health heavy weapon" for the benefit of the country and the people, and must be built with the strength of the country. Even in the midst of many difficulties, Xie Qingguo said, he is still full of expectations.
<h1 class="pgc-h-arrow-right" data-track="105" > reporter's note</h1>
<h1 class="pgc-h-arrow-right" data-track="106" > when the market mechanism fails, institutional innovation needs to "take the baton"</h1>
"Path dependence" is an economic theory.
What it means is that once people make a choice, it's like walking down a path of no return, and the force of inertia makes the choice constantly self-reinforcing and makes it easy for you not to go out.
In the reporter's interview, I deeply felt that in the field of high-end medical equipment in China, due to the monopoly of foreign giants for a long time, everyone has become accustomed to it, and over time it has unconsciously formed a dependence.
When domestic innovative high-end equipment appeared, everyone had some prejudices and doubts.
In addition, foreign companies have been deeply involved in China's high-end medical equipment market for many years, forming a variety of market barriers. Breaking it all at once is not an easy task.
Xie Qingguo gave reporters statistics that last year they spent 2.44 million on the maintenance of intellectual property applications, compared with 2.94 million in 2019. In order to maintain the core patents, they had to license some peripheral patents to foreign companies.
Ni Jiayi, an academician of the Chinese Academy of Sciences, believes that for a long time, the core technology of PET has been in the hands of international giants. Nowadays, after the domestic all-digital PET gets market access, the most critical thing is to mass-produce as soon as possible, become bigger and stronger, and continuously improve the new technical route of all-digital PET in large-scale applications, so that domestic high-end medical devices can benefit the people as soon as possible.
Every day is new, every day is new, and every day is new. Innovation is the traditional gene of the Chinese nation, and it is also the catalyst for the long-term prosperity and prosperity of the Chinese nation.
However, the spirit of innovation should not only be reflected in science and technology, in the face of path dependence and market mechanism failure of the problem, in the face of scientists who have broken through the "card neck" technology, and the domestic market, capital and policies stuck in the "neck" dilemma, we should focus on the transformation of scientific and technological achievements in the industrial chain, transformation mode of innovation, truly apply technology to practice, continuous exploration, development, upgrading, and finally participate in international competition, to create a loud, stable Made in China.
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