Use your brain, okay?

Produced by|Tiger Sniff Medical Group

Author|Chen Guangjing

Editor|Liao Ying

Head Picture|《Super Body》

Are you willing to accept a knife in your head?

The medical trouble caused by "moving a knife" on the head can be traced back to the Three Kingdoms period, for which Cao Cao killed the divine doctor Hua Tuo.

Now, Neuralink, the brain-computer interface (BCI) company founded by Musk, is once again throwing problems at patients. According to the company's information disclosed on September 19, in order to test the safety and effectiveness of brain-computer interface products, the company publicly recruited the first subject who voluntarily accepted the implantation of brain-computer devices in the brain. This also means that invasive brain-computer interfaces are entering the human trial stage for the first time with a target for marketing.

Once a real subject is willing to take on this challenge, humanity is one step closer to controlling the world with brain waves.

As soon as the news came out, it caused heated discussions inside and outside the industry, some people called it a heart-pounding experiment, and some people were curious about the technology itself; Some people are still worried that no one dares to accept experiments, and some people have begun to discuss the future commercialization of this new technology with sci-fi colors.

In the past few years, Musk has brought brain-computer interfaces to life, which has also caused people to have a lot of unrealistic fantasies about it.

In reality, brain engineering is a field that all countries have attached great importance to since the 21st century, with billions of yuan or even tens of billions of dollars of investment.

In 2021, China also proposed a national plan of tens of billions and hundreds of billions of yuan. Just before the Mid-Autumn Festival National Day holiday, brain-computer interface concept stocks set off a wave of investment boom in A-shares - innovative medical, Sanbo brain technology, Guanhao Biotechnology, Aipeng Medical, etc. have risen by different amounts. Among them, innovative medical increased by more than 12% in the 10-day period from September 18 to 28, and Guanhao Biotechnology and Shenzhou Taiyue rose by more than 7%. As a leading brain-computer interface enterprise, Innovative Medical has increased the limit at least 12 times within a year.

After the enthusiastic holiday, it continued, and at the opening of the market on October 9, nearly 200 million yuan flowed into the brain-computer interface concept field of A-shares.

Under the boom, how is the progress of China's brain-computer interface? How big is the gap with the global advanced level?

The rise and fall of brain-computer interface concept stocks before the Mid-Autumn Festival National Day holiday. Source: Oriental Fortune Network

The gap between China's brain and computer is not too large

Brain-computer interface, simply put, is a device that can make the brain "skip" the peripheral nervous and muscular systems and directly communicate signals with external devices.

In this process, the brain-computer interface extracts brain signals, translates and then sends instructions to external devices, which is expected to make deaf and dumb people hear the outside world again, speak again, and is also expected to make "frostbite" patients regain the ability to exercise. In the wildest scenario, brain-computer interfaces could even free humans from physical shackles and achieve immortality, which is considered an important means for carbon-based life to fight silicon-based life.

At present, many major countries and regions, including the United States, China, Japan, and Europe, are actively deploying brain-related projects. Among them, the United States planned to invest 4.5 billion US dollars in 10 years in 2013, and the European Union planned to invest 1 billion euros. Later, the United States extended the plan to 2025, with a total investment of US$5.2 billion (about 37.97 billion yuan). Brain-computer interfaces are key.

Although it started late, China also proposed the "brain plan" in 2014, and has tens of billions and hundreds of billions of investment plans. On September 16, 2021, the Ministry of Science and Technology officially released the major project of "One of the Major Projects of Science and Technology Innovation 2030 - Brain Science and Brain-like Research", with 59 directions deployed in that year, and the national allocation is expected to reach 3.148 billion yuan.

Musk's brain-computer interface has made great strides towards commercialization, how is the progress of China's brain-computer interface?

"Our country is still in a state of catch-up." Shortly after Neuralink announced the recruitment of human trial subjects, Li Chengyu, a researcher at Lingang Lab, said when sharing his team's research progress at the 12th China Medical Device Industry Conference.

Industry insiders believe that China has a gap of 5 to 10 years from foreign countries. However, China's catch-up is not slow.

Yuan Ye of the School of Economics and Management of Chongqing University of Posts and Telecommunications, and other researchers wrote the article "Latecomer Catch-up and Dynamic Comparison of Key Technologies", pointing out that China is still in the growth stage, and the growth time is relatively long-lasting - it will take 24 years, which "shows that China still has many technical problems to overcome in the process of catching up in the future", and the researchers also predict that "a major turning point will be achieved around 2030".

In some tracks, such as non-invasive acquisition sensing technology, China is still in the lead.

From the perspective of patent layout, China has applied for more patents in the field of brain-computer interface than the United States. According to statistics written by Zhou Jie and others of the Chinese Academy of Information and Communications Technology, in terms of invasive electrode patents, China's patents account for 42%, even exceeding the proportion of the United States - 39%. According to data from the Prospective Industry Research Institute, there were 1,896 brain-computer interface-related patent applications in China in 2021 alone.

The figure shows the proportion and trend of global and Chinese and American applications for implantable electrode patents. From: ICT and Policy

If only from the clinical application of individual cases, including many patients in China who rely on brain-computer interfaces to regain language and motor ability.

As recently as 2020, the brain-computer interface team of Zhejiang University has joined hands with the Department of Neurosurgery of the Second Affiliated Hospital of Zhejiang University School of Medicine to complete the first invasive brain-computer interface clinical study in China, where patients use "thoughts" to control robotic arms and manipulators to hold food, drinks, and play mahjong.

In 2021, Li Xiaojian's team from the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, has completed the long-term implantation of a flexible electrode array of more than 1400 channels in the macaque brain, and synchronously collected the neural signals of each channel, opening up the whole technical chain of brain-computer interface in China.

In more cutting-edge areas, China is also connected to the world. For example, the "world's first non-human primate interventional brain-computer interface test" completed by Professor Duan Feng's team of Nankai University in May this year uses the same technical route as Neuralink's "old rival" Australia's Synchron. There is no need to make a hole in the skull, and signals in the brain can be collected by inserting a stent into the cerebral blood vessel. Industry insiders expect the technology to enter clinical trials in China in 5 years.

In terms of details, domestic invasive brain-computer interfaces are also innovative.

For example, the domestic benchmark Neuralink's brain tiger technology, which uses silk protein wrapping technology, can reduce the thickness of the electrode to 1 micron - lower than the 5 micron of the Neuralink electrode, and the stable recording time in animals is longer; The flexible materials used in Li Chengyu's research can be hard lines in the air and become soft when they enter the brain, which can solve the problem that flexible materials are difficult to enter the brain.

In reality, Neuralink's brain-computer interface is indeed ahead of the curve. According to Musk's 2017 statement, within 10 years, such chips will be introduced to all mankind. From the current progress, if all goes well, the Neuralink brain-computer interface human trial can be completed in 6 years, and the 10-year contract is indeed expected to be realized.

China is not too far away from this day.

What are the problems with the Chinese brain-computer interface?

Although there have been some scientific breakthroughs in China, the reality that has to be accepted is that if brain-computer interfaces are to benefit more patients, they must become commodities and obtain regulatory approval in the form of medical devices. There are many hurdles to cross, and they are more difficult than other medical devices.

China's brain-computer interface research, unlike other medical devices, is not much doctor-led research, almost all of which are promoted by scientific research institutes. In addition, this field integrates many disciplines such as computer, neuroscience, bioengineering, mechanical engineering, etc., and researchers need to solve more problems to achieve commercialization, from laboratory to industry, from industry to clinic, almost every step is very difficult.

Brain-computer interfaces are mainly non-invasive (electrodes attached to the scalp), semi-invasive (brain-computer devices implanted in the cranial cavity and outside the brain) and invasive (devices implanted in the brain), with decreasing safety and increasing clarity. In recent years, interventional methods have also been developed in order to obtain clear neuronal signals at a smaller cost.

The path chosen by Neuralink is the most intrusive with the highest clarity and the highest security risk. The eventual approval of this model by the FDA is also related to its already recognized breakthrough in "engineering."

This includes: the surgical robot "sewing machine" that implants flexible electrodes into the human brain, which could only be implanted in rats in the early days, can now implant thousands of electrodes in humans and animals; As well as the miniaturization and wireless transmission capabilities of the chip - from the public information, the previous version of Neuralink products also has a USB interface, the new version can already be wireless, only the size of a coin, installed on the skull, the appearance can be invisible.

Schematic diagram of Neuralink brain-computer interface implantation. From: Visual China

Still, the problem is very obvious. In terms of the most critical safety, even if the company proves the safety of the product, there are risks that cannot be removed, such as the inevitable problems of neuronal damage during the implantation of electrodes.

To some extent, whether drugs, medical devices, etc., can eventually enter the clinic and whether anyone chooses to use them is the result of the trade-off between safety and effectiveness. No matter how high the risk of the product, there will be people with serious diseases who are willing to "gamble", the prospect of disease treatment is attractive enough, and there will still be "brave men" who are willing to open a knife in the brain.

From a commercial point of view, these risks will lead to a more limited audience for such products, at least at this stage. In China, this means that the review and approval process has been doubled down on rigor and prudence.

At present, there is no review and approval guide for brain-computer interfaces in China, and regarding the supervision of invasive brain-computer interfaces, some Chinese experts have called for attention to the safety risks and ethical issues of brain-computers.

These include: focusing on "Surgical risks of electrode implantation and risks of postoperative infection and rejection"; When the brain computer strengthens or stimulates neurons, "it is necessary to ensure that it does not cause damage to neurons and the nervous system"; When reading information about the patient's neural activity and subconscious, pay attention to whether it constitutes an invasion of the patient's personal privacy.

In China, the lack of basic research may also affect the potential of industrial development. "There are very few departments in China that are truly named after neuroscience." A number of practitioners in the field of brain-computer interfaces have publicly stated this.

The brain is a very complex organ. Each brain has at least 86 billion neurons, each with thousands of connections, resulting in a vast network of vast networks and how it works, which is still very poorly understood. Drawing the "human brain map" is also a new power point for the "brain plan" of many countries.

In addition to neuroscience, brain-computer interfaces are also limited by the current level of development in disciplines such as engineering and computer science.

For example, Neuralink's 64 wires of N1 implants (brain-computer chips) are thinner than a hair, and 1024 electrodes are distributed on them, which can directly connect neurons and record neural activity. Other words. The device can simultaneously monitor the activity of up to 1,024 channel neurons, which is only one in 100 million of the total number of neurons in the human brain.

In practice, because the product chooses to achieve wireless operation through Bluetooth, it has to sacrifice the number of electrodes, and under the limited bandwidth of wireless communication equipment, 1024 channels is already the pinnacle.

Experimentally, this bit of data is indeed enough for monkeys to play video games, and it is really not enough to solve practical problems.

According to Tao Hu, deputy director of the Shanghai Institute of Microsystem and Information Technology of the Chinese Academy of Sciences, founder and chief scientist of Braintiger Technology, at a popular science event, the number of electrodes must be at least 100,000 orders of magnitude, and brain-computer interfaces can make substantial progress at the application level.

To analyze such a huge amount of information, it is difficult to meet the existing computing power - the study believes that the complexity of the human brain neural network is comparable to the cosmic galaxy, and the data involved in the entire human brain connectome can reach 1 billion terabytes (10^21, ZB).

What is more worrying is that when the product launch path has not yet been clarified, and the safety and ethics controversies have not yet been determined, a series of problems such as overheating and involution in the field of brain-computer interfaces in China have begun to emerge.

Schematic diagram of the brain-computer interface workflow. From Progress in Biochemistry and Biophysics

Can such a front be rolled up?

In China, brain-computer interface is also one of the investment "outlets" in recent years, and the excessive popularity has worried professionals.

"Brain-computer interface development to the end may be a very competitive field." At the aforementioned medical device forum, Li Chengyu said with concern that when we began to really do brain-computer interface experiments ten years ago, it was estimated that there were only twenty or thirty companies, and in recent years, many brain-computer interface companies have rapidly emerged, "I estimate that there must be 100."

The statistics also confirm his fears to some extent.

According to arterial network statistics, since 2016, the financing of China's brain science field has entered a stage of gradual warming. From 2016 to 2021, the total number of financing events in this field reached 187, of which brain-computer interface ranked second, second only to intelligent analysis of brain radiology, accounting for nearly 30%. In the near future, at least 43 medical-grade brain-computer interface and chip-related start-ups have emerged.

It is worth mentioning that Neuralink's phased success has also made Chinese investors optimistic about this track, and well-known venture capital institutions such as Sequoia China and CDH Investment have also come out one after another, wanting to invest in a Chinese version of Neuralink. In A-shares, there are also at least 12 brain-computer interface concept units. Among them, including Innovative Medical, Sanbo Brain Science, Guanhao Biotechnology, and Aipeng Medical, which previously rose sharply in stock prices.

From the perspective of public information, the main focus in the commercialization of China's brain-computer interface is relatively safe non-invasive brain-computer interface.

The field of rehabilitation is currently the best direction for the development of brain-computer interfaces, and there are many points that can be landed, including: stroke, Alzheimer's disease (commonly known as Alzheimer's disease), ADHD, autism, etc. Cochlear implants, an invasive brain-computer interface with relatively mature technology, are also typical cases of good commercialization in the field of rehabilitation.

In recent years, China's brain-computer interface research has also penetrated into frontier fields such as interventional brain-computer interfaces, but it is still in the early stages.

Statistics from the China Business Industry Research Institute show that non-invasive brain-computer interfaces account for 86% of China's brain-computer interface market. Mainly used in rehabilitation training, education and entertainment and other fields. The higher barriers, mainly used in the medical and health field, account for about 14% of the invasive brain-computer interface.

For example, the related products of Aipeng Medical layout are mainly used for monitoring and sleep monitoring during surgical anesthesia; Innovative medical and its 40% shareholding Boling Technology, founded by Professor Xu Kedi of the Qiushi Institute for Advanced Study of Zhejiang University, the brain-computer interface studied is also non-invasive, which is a wearable device that helps hemiplegic patients manipulate forearm and hand movements. Even Sanbo Brain, which stands at the forefront of brain surgery, mainly focuses on the field of rehabilitation in terms of brain-computer interface.

In the short term, non-invasive brains used in rehabilitation are safer and easier to monetize, but from the perspective of long-term development, the scope of application of this technology is limited.

This is also easy to appear in a certain aspect of involution, and in the frontier field breakthrough is insufficient. Prosperity on the surface is actually not conducive to industrial development. In particular, diseases such as Alzheimer's disease, ADHD, autism and other diseases, because the pathogenic mechanism is not clear, it is difficult to find therapeutic targets, and the role that brain-computer interfaces can play is still very limited, and more energy is not focused on industry, but on basic research.

In the hyped field of brain-computer interfaces, there are many oolong incidents. For example: Guanhao Biotechnology. The company clarified on the investor interactive platform on September 22 that they have no brain-computer interface-related research, and the brain biofilm they do is completely different from brain-computer interface.

Li Chengyu worries that excessive attention to public opinion and the rush of investors will have a bad impact on the industry. "I think this thing is quite harmful to the whole field."

Brain-controlled typing system developed by Tianjin University. From: Visual China

In the long run, brain-computer interface technology is undoubtedly important and promising. "Brain-computer interface is the ultimate form of human-computer interaction, human-AI interaction." Gao Xiaorong, a tenured professor at Tsinghua University, pointed out in an interview with Beijing Daily. Without brain-computer interfaces, the logic of the envisioned future "intelligent society" would not work.

Considerable profits will also push the industry forward. Data Bridge Market Research, a third-party research organization, predicts that the global brain-computer interface market will be worth $1.74 billion in 2022, and this value is expected to reach 5.692 billion yuan by 2030, with a compound annual growth rate of 15.61%.

According to McCann's new forecast, in the next 10 to 20 years, the total economic value of the global brain-computer interface industry is expected to reach a high value of 200 billion US dollars; The addressable market could reach $40 billion in 2040.

This technique also has the potential to treat neurological disorders such as deafness, amyotrophic lateral sclerosis (a type of frostbite), epilepsy, Parkinson's and spinal cord injury, as well as a potential treatment for conditions such as autism, depression, and ADHD in children. It will also have a disruptive impact on education, scientific research and other fields.

However, today, whether at home or abroad, this technology is still only a small germ. It will take at least 6 to 10 years to actually enter the clinical stage. In the case that the existing laws and regulations, ethical norms, etc. are not fully regulated, blindly hyping the brain-computer interface will only be counterproductive and the gain will outweigh the loss.