RESEARCH IN CHINA: GROWTH, ETHICS AND LESSONS TO BE LEARNT?

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?

Breakthrough science in China

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.

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?

 

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

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.

[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.

[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?

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.

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.

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.

Opportunities for Australian entities in China

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.

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.

This gap is likely to widen as more R&D activities move overseas. Recently, University of Tasmania researcher Professor Steven Smith was awarded the Chinese Academy of Science’s 2018 President’s International Fellowship to perform agricultural research in Beijing. Professor Smith, who since 2013 has been a visiting Professor at the Institute of Genetics and Developmental Biology in Beijing said, “Chinese research and training capability is now world class, so China is increasingly becoming a provider of educational and research expertise, instead of the customer.”

[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

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.

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