FORUM. Nanotechnology development in China: challenges and opportunities. By Jane Qiu CHINA S INVESTMENT IN NANOTECHNOLOGY

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1 FORUM National Science Review 3: , 2016 doi: /nsr/nww007 Nanotechnology development in China: challenges and opportunities By Jane Qiu China has invested heavily in nanotechnology in the past decades. It s one of the key areas of focus in the medium and long-term scientific programmes between 2006 and In 2012, the country also launched a Strategic Pioneering Programme on nanotechnology, which has a budget of one billion yuan (US$152 million) over five years and is led by the Chinese Academy of Sciences (CAS) in Beijing. As a result of this long-term investment, China is now a major player in nanotechnology, ranking first worldwide in terms of the number of scientific papers and patents. At the Sixth International Conference on Nanoscience and Technology which was held in Beijing on 3 5 September, 2015 Chunli Bai, President of CAS and Editor-in-Chief of National Science Review (NSR), shared a platform with another five leading scientists, where they discussed recent progress of nanotechnology in China, the potential impact of nanoparticles on public health, as well as challenges and opportunities ahead. Chunli Bai (Chair) President of Chinese Academy of Sciences in Beijing Minghua Liu An expert on nano materials and molecular assembly and Director of National Center for Nanoscience and Technology, China, in Beijing Zhongfan Liu An expert on nanochemistry and graphene at Peking University CHINA S INVESTMENT IN NANOTECHNOLOGY Bai: Could you give us an overview of China s support in nanotechnology? M. Liu: China is one of the countries that have invested heavily in nanotechnology. There have been several waves in its support. Before 2000, the investment was quite small, mainly on nanomaterials, as exemplified by the programmes run by the Ministry of Science and Technology (MOST) and the CAS. After 2000, especially since the USA kicked off the National Nanotechnology Initiative, many countries around the world, including China, stepped up their funding levels significantly. China s total investment in nanotechnology is estimated to be more than US$1 billion in the past 15 years. Chen Wang An expert on nanomicroscopy and nanomedicine and Deputy Director of National Center for Nanoscience and Technology, China, in Beijing Peidong Yang An expert on nanomaterials and their application in energy research at the University of California at Berkeley, USA Yuliang Zhao An expert on nanomedicine and nanosafety at National Center for Nanoscience and Technology, China, and Chinese Academy of Sciences Institute of High Energy Physics Nanotechnology is one of the key areas of focus in the medium-to-long term scientific programme between 2006 and Since 2006, there have been 141 projects on nanotechnology ranging from small projects for young scientists to big projects involving tens of million US dollars each on diverse research areas such as nanomaterials, nanoequipments, nanoenergy, nanocatalysis, and nanomedicine. Most of these are supported by the MOST. The National Natural Science Foundation of China has also funded a lot of basic projects in all the areas of nanoresearch and supported three major programmes in nanoscience, nanomanufacture and molecular assembly with a budget of 200 million yuan (US$30 million) each. C The Author(s) Published by Oxford University Press on behalf of China Science Publishing & Media Ltd. All rights reserved. For permissions, please journals.permissions@oup.com

2 FORUM Qiu 149 CAS has also been supporting research on nanotechnology in a series of initiatives such as the Innovation Programmes and Innovation More recently, nanotechnology is one of China s Strategic Pioneering Programmes that were launched in It has a budget of 1 billion yuan (US$152 million) with a focus on applied research. CAS is in the process of setting up the Center of Excellence in Nanotechnology, aiming to boost research in areas such as precising nanomanufacturing, nanomedicine and nanocharacterization and standardization. As a result of this long-term support, China is now a major player in nanotechnology, ranking first worldwide in terms of the number of papers with a Scientific-Citation Index (SCI), citations and patents. In terms of genuine innovation, however, there is still much room for improvement. Bai: How about research and development activities in the private sector? M. Liu: Private nanotechnology companies began to emerge around 2000, but the progress was very slow and only a handful of them have survived. Since 2010, there has been a new wave of companies, especially those working to develop graphene products, and the investment is quite considerable. The CAS Ningbo Institute of Materials Technology & Engineering, for instance, got a big contract from a private company to develop lithium batteries using graphene. Several companies in Wuxi and Changzhou, in China s Jiangsu province and in Chongqing, have also invested heavily in graphene technology. Several industrial unions on nanotechnology were established in Beijing, Shanghai, Jiangsu and Anhui provinces. PROMISING AREAS OF RESEARCH IN NANOTECHNOLOGY Bai: What are the areas of active research in nanotechnology in China? Wang: In 2012, CAS kicked off a Strategic Pioneering Programme in nanotechnology. There are mainly two criteria when we chose focus areas: first, there must be major national need; second, it must be an area of research that CAS has an obvious advantage. One area of focus is to develop lithium battery using nanotechnology, led by the CAS Institute of Physics and Institute of Chemistry. This is directly related to the development of electric cars a focus of China s Medium and Longterm Development Plan. We aim to complete arrays of battery for electric cars when the project ends in Another focus area is on green printing, also led by the CAS Institute of Chemistry. These two examples represent the high water mark of China s achievements in nanotechnology involving a complete chain of development from basic research, technology transfer to large-scale commercial production. There are a few unique features in the implementation of the programme. First, all the innovations came from CAS laboratories, scaling up gradually from small research groups, and now combining with commercial production. The programme is exceptional also because we are not required to publish any papers. The criteria for evaluating the programme are based on production scales, enterprise investments and socio-economic benefits which should also be the criteria for assessing nanotechnology on the whole. Basic research is important, but so are socio-economic benefits. Bai: Nanomedicine is an emerging cross-disciplinary research field. What are the key research focuses? Zhao: Nanomedicine has developed rapidly in the past decade. In the USA, over 100 nanodrugs have been approved by the Food and Drug Administration for use in clinical trials. Two unique characteristics of nanocompounds make them promising candidates in drug development. First, unlike traditional drugs, nanocompounds can readily cross biological barriers, such as cell membranes and the skin, and reach target sites. Second, nanodrugs are particles assemblies of atoms and molecules thereby providing a surface that is bioactive in multiple ways, in contrary to traditional drugs that can serve only one function. There is a consensus among pharmacologists that nanomedicine is the future of drug development. The development of traditional small-molecule drugs has come across many bottlenecks. Now, some people are developing largemolecule drugs such as protein and nuclei acids, which need a carrier to get into the cell and prevent them from degradation. This is commonly achieved by using non-virulent viral vectors, which have potential dangers. Nanotechnology is a promising approach to act as non-viral carriers. There is a consensus among pharmacologists that nanomedicine is the future of drug development. Yuliang Zhao Bai: We are working on China s 13th five-year plan for the period between 2016 and In nanotechnology, there are several major research directions including basic research such as modelling some of the phenomena on nanometer scales (because it s still difficult to directly observe optical and electrical properties of nanomaterials) and applied research such as developing equipments to observe those properties. We will make an announcement once it s finalized. LACK OF GENUINE INNOVATIONS IN NANOSCIENCE RESEARCH IN CHINA Bai: What are the main weaknesses of nanoscience research in China? Yang: Although I m based in the USA, I ve been collaborating with CAS Suzhou Institute Nano-Tech and Nano-Bionics for quite some time now. The institute focuses mainly on applied research, with a small number of projects on basic research. To conduct applied research, you d need your own intellectual properties (IPs), which are built on basic research and take a long time to develop. You can t reach the stage of commercialization within five years of basic research. So basic research is

3 150 Natl Sci Rev, 2016, Vol. 3, No. 1 FORUM Six experts gathering together after the forum discussion (left to right: Minghua Liu, Zhongfan Liu, Peidong Yang, Chunli Bai, Chen Wang, Yuliang Zhao) really to pave the ground for commercialization in the next 20 years. I have the feeling that China is too keen to achieve commercialization in the short term. This is quite different from the situation in the USA, where there is a heavy focus on basic research. In most universities and research institutes, we don t really care that much about whether our research will yield commercial products. The view is that basic research will ultimately lead to useful technology and commercial products when the time is right. It s a long-term process. China should be patient and take a long-term view. It should give its researchers enough space and time to pursue basicresearch questions. While China has the largest number of patents and SCI publications in nanotechnology, only a tiny minority of them are truly innovative. You can get a lot of patents just by optimizing technologies and products. At this stage, China really should focus on the quality rather than the quantity of research output. A key question China should ask itself is: Does it truly have innovative ideas? Or is it still a follower of cutting-edge development in the West? Z. Liu: I totally agree with Yang: the seemingly impressive stats on the total research output actually cover a lot of serious problems. The nanotechnology centre in Peking University, which was set up in 1997 and where I work, is not immune from the problem neither. It s a multidisciplinary research centre which has an annual output of 1000 papers on nanotechnology, out of over 3000 papers in total but the level of creativity is rather limited. Graphene research is a typical example. China has invested quite a lot and boasts the largest scientific force in this area of research in the world, including hundreds of companies. There are two problems which are as follows. First, the investment lacks focus and each team doesn t really have that much money. Second, there are limited genuine innovations across the board. People tend to follow the crowd, and follow what s trendy here and now rather than looking forward and having their own ideas. Bai: I agree. The new government sees innovation as central to China s long-term development. But most researchers in China are keen to follow hot and trendy research areas. Few have the spirit of shi nian mo yi jian (meaning taking a decade to sharpen a sword ) or are willing to pursue big research questions. For instance, China has invested heavily in graphene and carbon nanotubes after they were first developed in the West, but very few genuine innovations have come out of it. We really have to unleash our creativity rather than being content of following the crowd. Yang: I d like to say a few words about big science. I ve been involved in some large projects in the past few years in the Obama government. There are some top-down projects first in materials science, then energy research, and now life sciences and microbiology, which are all related to nanotechnology. An advantage of such major pushes is that the fund can spread rapidly in those research fields. But such big projects are often led by established scientists, and don t give enough opportunities to young people, who, as I always believe, are the key drivers of innovation. This could, in the long run, compromise the competitive edge of the US science. When I first went to the USA more than 20 years ago, there were many single-investigator grants with quite reasonable support from the Department of Energy and the National Science Foundation. Now fundings are quite limited, and big projects take the lion s share, drastically reducing the number of

4 FORUM Qiu 151 single-investigator grants. A lot of very talented and dedicated young scientists have troubles getting such grants and struggle to survive. In China, research fundings have increased by double digits in the past decade. Of course, you need big initiatives to meet specific national needs. But at the same time, support for young scientists, especially young post-docs, should increase proportionally. This would give them plenty of space and time to try new ideas. The evaluation system should be more flexible, so they won t fall into the trap of pursuing publication numbers. While China has the largest number of patents and SCI publications in nanotechnology, only a tiny minority of them are truly innovative. Peidong Yang Bai: This is a very important issue. In China, many institutions require graduate students to have SCI papers before they can graduate. So, of course, they can t work on risky projects. Since I became the director of the graduate school in CAS, I removed those regulations. There have been some improvements, but certain institutes still impose such requirements. Students are also very keen to get SCI papers out of their degrees because this will make it easier to find post-doctoral positions in prestigious institutions. It s clear that people won t be able to take risks and pursue their ideas if their work is evaluated only by the number of publications. This is a very important element in the ongoing institutional reforms in China. The crust of the matter is how to create a conducive environment for innovation. Regarding support for young scientists, CAS has set up a special fund called Young Scientists Innovation Fund to support researchers under 35 years of age. CHALLENGES OF NANOTECHNOLOGY DEVELOPMENT Audience: What are the main challenges of nanotechnology development? Bai: A key challenge is to preserve desirable properties of nanocompounds on macro scales. For instance, single-carbon nanotubes have a lot of attractive properties it s stronger than steel by 100 times but weights only a sixth but assemblies of nanotubes are quite a different matter because the strength between nanotubes is far weaker. Another example is selfassembly, which, according to the Science magazine, is one of the most promising research fields in nanotechnology. But a challenge is to control the process properly and efficiently as well as control the size and stability of the final product and its desirable properties. Audience: China hasn t done enough in the protection of IP rights, which is critical for innovation. How can the country overcome this and encourage researchers to innovate, promote technology transfer and, ultimately, to generate socio-economic benefits? Bai: The central government has just released a set of new policies on this. In the past, the state holds the IP rights of innovations coming out of state-funded projects. Now, they belong to the institutes and universities that carry out the research giving them more freedom in technology transfer and commercialization. Moreover, the inventors can now enjoy up to 60% of economic benefits, including stocks, compared to 20% before. This kind of policies are indeed designed to boost innovation and technology transfer. POTENTIAL IMPACT ON PUBLIC HEALTH AND ENVIRONMENT: NANOSAFETY AND REGULATORY ISSUES Bai: Nanotechnology poses potential threat to public health and environment. What kinds of research have been carried out in this area? Zhao: There were a lot of confusion and conflicting results in the early days of nanosafety research in the early 2000s. This is due to mainly two reasons: first, most studies were qualitative, and many inferences and speculations have turned out to be incorrect; second, most early research on nanosafety relied on traditional toxicological approach, treating nanomaterials like any other molecules while neglecting their unique characteristics, which has proven to be inadequate. Interestingly, most in vitro studies have been performed in the West, while most in vivo animal studies are done by Chinese scientists, which are much more reliable, especially quantitatively, and have helped resolving some of the early confusions. In the past 15 years, we have got a massive amount of data on the body s absorption, metabolism and excretion of nanomaterials. Major progress includes a large database of nanosafety studies based on published literature, covering a wide range of compounds including metals (such as gold, copper, iron, zinc, magnesium and aluminium), inorganic oxides (such as titanic dioxide, zinc oxide, silicon dioxide, magnesium oxide, iron oxides, aluminium oxide and strontium dioxide) as well as graphene, carbon nanotubes and their derivatives. We have detailed toxicology data on most compounds that are mass produced, and we know the precise levels of exposure that are safe during mass production. We must avoid the potential negative impact of nanotechnology on public health and the environment. Chunli Bai Another area of achievements is related to the discoveries of nanomaterials unique properties. First, nanomaterials are very easy to get into the cell, which is the basis of nanomedicine. Second, once getting into the body, most nanocompounds, including carbon nanotubes and graphene, can easily adsorb

5 152 Natl Sci Rev, 2016, Vol. 3, No. 1 FORUM albumin. If we want to use them in the body, we have to think of a way to prevent this from happening, thereby reducing their toxicity. Third, one-dimensional nanomaterials, such as carbon nanotubes, are much more difficult to be excreted by the cell which might be related to its shape than globular structures. Fourth, nanocompounds can easily engage in electrical chemical reactions inside a cell, which can affect some cellular functions. This has been used to diagnose diseases, including cancer, and to develop new therapies, but we must take this into consideration from the safety point of view and try to minimize such reactions. Bai: What sorts of nanosafety regulations are in place in China? Zhao: Regulations related to laboratory use of nanomaterials were first promulgated by CAS in In the same year, we also drafted a national regulation for the Ministry of Health probably one of the first such regulations in the world. CAS and universities were also involved in drafting two regulatory guidelines, which are now in place: one is related to safe exposure levels and monitoring protocols of nanoparticles at production site; the other is related to safety evaluation of nanomaterials, including detailed evaluation and monitoring methods. Bai: I attended one of the earliest international conferences on nanoscience in Baltimore in A lot of people outside the conference venue were handing out leaflets saying that nanoscience was a very dangerous technology, like nuclear weapons, and wanted scientists to be extra careful. Because of the public concern, there has been a great emphasis on nanosafety. We must take great precautions of the potential harmful effects of nanotechnology otherwise there is likely to be a strong public resistance, like the situation with GM crops these days. Any technology is a double-edge sward, and we must avoid the potential negative impact of nanotechnology on public health and the environment. LAST WORDS TO YOUNG SCIENTISTS Audience: What does President Bai have to say to the students and young scientists working on nanoscience? Bai: First of all, you should pay attention to surprising and unexpected phenomena during experiments. When you get results that are not in line with current theories, don t ignore them lightly because you may be on the verge of major scientific breakthroughs. You should think carefully and discuss with your colleagues what the reasons are likely to be. Good scientists have the capacity to think outside the box and challenge existing dogmas. You should use your curiosity drive to discern interesting phenomena and come up with new hypothesis rather than going with the flow and confirming existing views all the time. Second, if you want to be successful, you have to be passionate about what you do, rather than treating it merely as a job or a way to make a living. Jane Qiu writes for NSR from Beijing.