RESEARCH IN CHINA: GROWTH, ETHICS AND LESSONS TO BE LEARNT? 在中国的研究: 关于其增长,道德伦理和可学习的经验?

As the incidence of breakthrough research increases and research standards in China align increasingly with those of the West, Australian institutions will undoubtedly be driven to conduct more collaborative research in China and less in Australia. What will this mean for our global standing in innovation and invention measures?

随着在中国突破性研究的发生率增加,以及中国的研究标准与西方的研究标准越来越一致,澳大利亚的研究机构无疑将与中国开展更多的合作研究,反观在澳大利亚内的合作研究则将更少。这对澳大利亚在创新和发明措施方面的全球地位意味着什么?

Breakthrough science in China
在中国的突破科学

The birth of two monkeys earlier this year, Zhong Zhong and Hua Hua (Zhōnghuá translates to the Chinese nation or its people), caused shockwaves in the scientific community and beyond. The pair are the first primates born as a result of cloning, a culmination of decades of collective research in China and beyond.

今年早些时候出生的两只克隆长尾猴中中和华华(“中华”的寓意是中华民族或其人民),在科学界及其他领域引起了震惊。这两只克隆猴是第一批非人灵长类动物因克隆而诞生,这是中国及其他国家数十年集体研究的高潮。

Scientists at the Chinese Academy of Sciences Institute of Neuroscience (ION) in Shanghai successfully applied the same cloning techniques that produced Dolly, and in doing so, overcame technical barriers preventing primate cloning for more than two decades. The birth of Zhong Zhong, and Hua Hua was no simple task – ION scientists Sun Qiang and Liu Zhen started with 109 cloned embryos, which only resulted in six surrogate pregnancies. Considering these low conversion rates, the relative expense of primate research, and the sheer time and effort involved, could this work have been accomplished in any other country but China?

上海中国科学院神经科学研究所(ION)的研究员成功的应用了生产多莉的克隆技术,并在此过程中克服了二十多年来克隆灵长类动物的技术障碍。中中和华华的诞生并非简单的任务 – ION研究员孙强和刘真以109个克隆胚胎开始,只导致了6次代孕怀孕。考虑到如此低的转换率,及灵长类研究的相对费用以及所涉及的时间和精力,这项工作是否可以在除中国之外的任何其他国家完成?

Figure 1 | Infographic of the cloning method used by the ION researchers, as published in Cell. Liu et al. (2018), Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer. Cell, 881-887, 172 (4), DOI: https://doi.org/10.1016/j.cell.2018.01.020

Research a growing focus in China
研究在中国越来越被注重

Since 2008 China has been accelerating expenditure on research and development as a percentage of its GDP. In 2013 this number was 1.7%. 2015 figures from the OECD show that the number has increased to just over 2% representing a staggering USD$376 billion.[1] By 2019 China is predicted to surpass USA as the world’s most prolific inventor, in line with its 13th 5-year plan set out by President Xi Jinping and Premier Li Keqiang. By comparison, while Australia was already spending this proportion of GDP on R&D by 2008, due to a smaller economic footprint the latest reported dollar figure is only USD$21 billion.

自2008年以来,中国的研发支出占国内生产总值的比例不断加快。 在2013年这个数字是1.7%。经合组织2015年的数字显示,这一数字已经上升至略高于2%,而这代表着惊人的3760亿美元。根据习近平主席和李克强总理制定的第13个五年计划,到2019年,中国预计将超越美国成为世界上最多产的发明者。相比之下,尽管澳大利亚在2008年前已经将这一比例的国内生产总值用于研发支出,但由于其经济规模较小,最新的美元报告数字仅为210亿美元。

[1] OECD (2018), Gross domestic spending on R&D (indicator). doi: 10.1787/d8b068b4-en (Accessed on 12 February 2018).

Figure 2 | China’s increasing emphasis on R&D as a factor of their GDP. OECD (2018), Gross domestic spending on R&D (indicator). doi: 10.1787/d8b068b4-en (Accessed on 12 February 2018)

Nowhere is the potential of the Chinese R&D engine more evident than when considering China’s ever-changing workforce. There are more researchers in China (just over 2 million) than in any other country in the world. More than two-thirds are employed through industry-funded positions.[1] In addition, the Chinese government has pledged a further USD$9.4 billion to a development fund aimed at supporting R&D start-ups.[2] This is in comparison to Australia where more than half of all researchers are dependent on government grants.

中国研发引擎的潜力最明显的证据是其不断变化的员工队伍。中国的研究人员(略超过200万人)比世界上任何其他国家都多。而行业资助的职位雇用了三分之二以上的研究人员。此外,中国政府还承诺将多提供94亿美元于支持研发创业的发展基金。相比之下,澳大利亚有超过一半的研究人员还依赖政府补助金。

[1] OECD (2018), Researchers (indicator). doi: 10.1787/20ddfb0f-en (Accessed on 12 February 2018)

[2] Nature 553, S2-S3 (2018) doi: 10.1038/d41586-018-00536-1

Could this cloning feat have been achieved in Australia?
这个克隆壮举是否能在澳大利亚实现

The birth of Zhong Zhong and Hua Hua has raised some concerns about the ethics surrounding cloning research in China. China has guidelines around primate research, although these are arguably more liberal than those in Western countries. In Australia, primate research is only allowed in the absence of other alternatives. This appropriately but severely restricts their use. In the USA, another country with a long history of outstanding biological science breakthroughs, the NIH is moving away from primate research altogether because of a combination of importation restrictions, animal rights activism, and increasing costs. If these factors don’t already play a part in Australian trial design, they are certain to in future.

中中和华华的诞生引发了一些关于中国克隆研究道德伦理的担忧。中国有灵长类动物研究的指导方针,但这些指导方针可以说比西方国家更自由。在澳大利亚,只有在没有其他替代方案的情况下才允许灵长类动物研究。这适当但严格地限制了它们的使用。在美国,另一个在生物科学突破方面有着悠久历史的国家,由于进口限制,动物权利激进主义以及成本增加等因素,美国国立卫生研究院正在远离灵长类动物研究。如果这些因素尚未在澳大利亚试验设计中发挥作用,他们将来也肯定会有这些作用。

Ethics aside, the reality is that there is neither the patience nor the funding in Australia to support a prolonged and expensive research project as that which resulted in Zhong Zhong and Hua Hua. A stagnant medical research budget means there is little patience in research laboratories where publications per year is the key factor in accessing grant monies. The lack of available R&D positions means more and more scientists look overseas for work opportunities, or transition into different industries. The announcement of the Medical Research Futures Fund (MRFF) in late 2015 was heralded as a ‘once in a lifetime opportunity to significantly reshape the landscape of Australian medical research and innovation’. This raised some hopes for future translational research. The first trickles of the MRFF have since begun to find their way to Australian laboratories with $121 million allocated for 2017/18, and $643 million slated in 2020/21. Despite this, sceptics remain cautious about the accessibility of this funding, or whether it will even be enough.

抛开道德伦理,现实情况是,澳大利亚既没有耐心也没有资金来支持像导致了中中和华华一般的长期和昂贵的研究项目。澳大利亚停滞不前的医学研究预算意味着研究实验室几乎没有耐心做实际研究,因每年出版物的数量是获取拨款的关键因素。研发岗位的缺乏也意味着越来越多的科学家到海外寻找工作机会,或转向不同的行业。医学研究期货基金(Medical Research Futures Fund,简称MRFF)在2015年末发布的消息被誉为“一生中一次重大改变澳大利亚医学研究和创新格局”的机会。这为未来的转化研究带来了一些希望。 MRFF的第一批拨款已经开始走向澳大利亚实验室,2017/18年度拨款为1.21亿美元,2020/21年度拨款为6.43亿美元。尽管如此,怀疑论者仍然对这笔资金的可获得性或者是否足够持谨慎态度。

The Chinese breakthrough has considerable potential for research on diseases where use of non-primate animal models has had limited success and where the use of primates is essential to unlocking the mechanism of disease. This is true for example in both Parkinson’s disease and Alzheimer’s disease in which the interaction of genes and the environment plays a key role in the disease symptoms, and where other models have so far had limited success. The publication of the ION researchers’ work in Cell, one of the world’s most prestigious scientific peer-reviewed journals, reflects the significance of this work.

中国的突破对于使用非灵长类动物模型取得有限成功的疾病的研究以及使用灵长类动物对于解除疾病机理至关重要的疾病的研究都具有相当大的潜力。例如在帕金森病和阿尔茨海默病中都是如此,其中基因和环境的相互作用在疾病症状中起关键作用,并且迄今为止其他模型的研究成功有限。 ION研究人员在Cell(世界上最负盛名的科学同行评审期刊之一)出版的作品,反映了这项工作的重要性。

Opportunities for Australian entities in China
澳大利亚企业在中国的机遇

Scientific breakthroughs in China have not gone unnoticed. Last year, the Walter and Eliza Hall Institute, the University of Melbourne, and Cancer Trials Australia announced plans to establish a translational research facility in the Jiangsu province, as part of a trans-Pacific collaborative effort. It is likely that the aim of this partnership is to establish clinical trials using the combined powers of Chinese facilities and Australian clinical trial knowledge. Globally, facilities in China are attracting interest due to the cutting-edge platforms established via increased government investment. Australian researchers will be familiar with the Beijing Genomics Institute, the world’s largest sequencing centre, where scientists regularly perform whole-genome sequencing. BGI has some of the lowest service costs in the industry and is typically cheaper than local sequencing companies even after additional shipping and importation expenses. Technology parks are appearing in every conceivable province offering tax incentives and free rent for eligible start-ups.

中国在科学上的突破并未被忽视。去年,沃尔特和伊丽莎霍尔研究所,墨尔本大学和澳大利亚癌症试验组织共同宣布在江苏省建立转化研究机构的计划,作为跨太平洋合作努力的一部分。该合作关系的目的很可能是应用中国设施和澳大利亚临床试验知识的综合实力以建立临床试验。在全球范围内,中国的设施通过政府增加投资而建立的尖端平台,吸引了人们的兴趣。澳大利亚研究人员将熟悉世界上最大的测序中心 – 华大基因(BGI),在此科学家们会定期进行全基因组测序。 BGI拥有业内最低的服务成本,并且通常比本地测序公司便宜,即使加入额外的运输和进口费用后也是如此。技术园区也出现在每个可以想象的中国省份,为合格的初创企业提供税收优惠和免费租赁。

Australia is a global leader in scientific research, ranking 11th in the world for total number of scientific publications annually.[1] We have the highest number of publications per thousand population at 1.70, placing us above the USA at 1.12 and the UK at 1.49 (Canada is close second at 1.60). But how does this compare to our scientific innovation? One proxy for measuring innovation as a result of R&D is to look at so-called triadic patent families, or patents submitted to three major patent offices: the European Patent Office (EPO), the Japan Patent Office (JPO) and the United States Patent and Trademark Office (USPTO). Typically, that an organisation is seeking to patent technology in all three of these offices means there is commercial value attached to the invention that is worth protecting. Since 2006, the number of triadic patent families originating from China has increased nearly five-fold.[2] During this same period the number of triadic families originating from Australia has declined.

澳大利亚是全球科学研究领域的领导者,每年科学出版物总数排名世界第11位。澳大利亚拥有每千个人口数量最高的出版物数量(1.70),高于美国1.12,英国1.49(加拿大第二,1.60)。但这如何与我们的科学创新相比?所谓的三元专利系列,或提交给三个主要专利局(既欧洲专利局(EPO),日本专利局(JPO)和美国专利和商标局(USPTO))的专利,是可衡量创新作为研发成果的一个代表。通常情况下,一个组织如寻求在这三个专利局为其发明申请专利,这意味着此发明具有商业价值, 并值得保护。自2006年以来,源自中国的三元专利系列数量增加了近五倍。在同一时期,来自澳大利亚的三元专利系列数量则有所下降。

[1] InCitesTM, Thomson Reuters, 2010. International collaboration data from Web of ScienceTM, courtesy of Thomson Reuters

[2] OECD (2018), Triadic patent families (indicator). doi: 10.1787/6a8d10f4-en (Accessed on 14 February 2018)

Figure 3 | Australia lags behind globally in number of triadic patent families.

Conclusion
结论

The birth of Zhong Zhong and Hua Hua should come as no surprise to those following China’s surge in scientific and R&D investment. Indeed, China’s forthcoming advance past the USA as the world’s top inventor is merely fulfilment of a focus set in motion by the Chinese government nearly a decade ago. Growing standards of research and ethics in China have already begun attracting overseas partnerships including from Australian businesses and research institutions. In Australia this comes as a result of a combination of factors including a lack of government focus on innovation and a stagnant R&D budget. The announcement of the MRFF raised hopes for future translational research outcomes. However there are still many unknowns. For now, establishing strategic partnerships with Chinese entities and benefiting from the government structures in place might offer an alternative to ensure that Australia continues to be a force in biological R & D in future.

中中和华华的诞生不会让那些一直以来都关注中国科学和研发投资激增的人感到意外。事实上,中国即将超越美国而晋身成为世界头号发明家,只不过是实现了中国政府在近十年前注重的焦点。越来越高水准的中国研究和伦理标准已经开始吸引海外合作伙伴,包括澳大利亚企业和研究机构。这是由于在澳大利亚缺乏政府对创新的关注,以及停滞不前的研发预算等因素造成的。 MRFF的宣布提高了未来转化研究成果的希望。但是,仍然有很多未知数。目前,与中国企业建立战略伙伴关系并从中国现有的政府机构中获益可能会提供一种替代方案,以确保澳大利亚将来继续成为生物研发有力量的一份子。

Share