news AI drug discovery booms in China Chinese upstart companies and IT goliaths hope to turn country’s artifcial intelligence prowess into world-leading drug innovation. Do they have an edge over Western players? hinese researchers are abuzz about the potential of artificial intelligence C(AI) in drug design and development. Just last month, three Chinese players raised hefty sums to fuel their drug discovery plans. Insilico Medicine, a Hong Kong–based company with half its global operations in Shanghai, raised $255 million to push drug candidates discovered by its AI into clinical trials and tune its algorithms to find new targets. That followed $100 million pocketed by Beijing StoneWise Technology in April and $319 million that Shenzhen-based XtalPi added to its coffers last September. IT goliaths like Tencent, Baidu and ByteDance have also been turning their formidable AI capacity to drug design. With an ambitious national strategy aimed at AI dominance, a massive talent pool of AI researchers, a plethora of contract research organizations (CROs) with which to partner, and evolving health data privacy protections, Chinese AI companies are T he Chinese government’s regulatory reform is designed to boost AI-driven drug discovery, but attitudes poised to compete in the global race to toward data privacy continue to cause international concern. Credit: THANANIT SUNTIVIRIYANON / make more drugs faster and cheaper. But Alamy Stock Photo even if a population of 1.4 billion can supply the wealth of data that will give Chinese AI companies a head start over Western counterparts, questions remain as to the Since then, though, the situation has for new pipelines and with it a curiosity to quality of the preclinical and clinical data changed rapidly. AlphaGo’s victories over see what AI had to offer. In 2019 Hansoh being used to train company algorithms. top human Go players in 2016 and 2017 Pharmaceutical Group, for example, agreed “If you come here and see what is focused industry attention on the potential to pay fees that could amount to over a happening, it impresses you,” says Alex of AI as a path to success in the minds billion dollars to Atomwise to design Zhavoronkov, founder and CEO of Insilico of many young Chinese. The following drugs targeting up to 11 proteins involved Medicine. Kai-Fu Lee, CEO of Sinovation year, the central government launched an in cancer and other disorders. And while Ventures, a venture capital firm based in ambitious framework to make China a XtalPi has received most of it partnering Beijing that invests in AI companies, agrees: global leader in AI by 2030 that led money from US companies, China is “China does have a state-of-the-art ability to to, among other things, new university now its fastest growing market. “For build drug discovery systems.” training programs. [Chinese] companies with little experience But Chinese AI drug hunters are of innovation, AI represented a way to latecomers. Over the past decade, companies “Top AI experts in China cost leapfrog,” says Ma. like Atomwise, BenevolentAI (London), more than in the United States Researchers in China responded to Exscientia (Oxford), Relay Therapeutics and the call. In a “storm of activity,” computer Numerate were working out big deals with and tend to move around.” scientists, physicists, mathematicians and multinational pharmaceutical companies. traditional drug discovery researchers Even the two most prominent AI drug Around the same time, Chinese launched over 50 AI drug discovery design companies now associated with regulatory reform gave innovative drug companies, says Zhang Jian, who runs a China—Insilico Medicine and XtalPi—were discovery, including that based on AI, a molecular design laboratory at Shanghai both established in 2014 in the United States. boost. Updated bioequivalence rules in 2015 Jiaotong University and has worked with a At the time, Chinese AI drug research was and new volume-purchasing stipulations handful of AI drug design startups. In 2019, getting little traction. “When I first came have meant that innovative drugs are Zhang helped to reposition Shanghai-based back to China in 2015 and started talking increasingly favored over generics, which Nutshell Therapeutics, which just raised its with Chinese pharmaceutical companies, had previously dominated China’s drug second installment of $20 million in June, it was apparent that most of them were not market. The new rules tip the scales in favor as an AI drug design company. In 2018, interested in or were not ready for AI in of the quickest and most forward-looking Zhou Jielong, a key force behind the drug R&D,” says XtalPi co-founder Ma Jian. manufacturers. That created a huge demand evolution of Baidu’s search engine, 900 NATURE BIOTECHNOLOGY | VOL 39 | AUGUST 2021 | 897–907 | www.nature.com/naturebiotechnology news established StoneWise to aid in the discovery China-based researchers account for 22.4% of small-molecule drugs. of the total, compared with 16.4% from WHO takes up CRISPR Industry insiders and drug discovery Europe and 14.6% from the United States, babies researchers in the United States have according to a recent report from Stanford More than two years after the birth remained skeptical of the AI hype and University. And for the first time last year, of twin girls with edited genomes, an claims that AI can improve the attrition AI publications from China garnered more advisory panel for the World Health rate once drug programs reach human citations than US ones. China still lacks Organization (WHO) has issued proof-of-concept studies. Chinese scientists who will make fundamental new recommendations that uphold researchers argue that, given this breakthroughs, represented by the top 1% the agency’s initial reaction: that “it conservative thinking, Chinese companies of the papers—especially the highly cited would be irresponsible to proceed with might be able to leverage the move to AI conference papers, says Lee. “When it comes clinical applications of human germline faster than Western companies: “China to really the most creative out-of-the-box genome editing.” Such concerns over doesn’t have a traditional way to do thinkers, the US still leads,” he says. manipulation of human embryos are discovery, so there’s no box. Those people But that might not matter for drug shared by the international scientific don’t have other rules in their mind,” says Yu discovery. Chinese companies can tinker community, but few countries have Zhengtian, co-founder of Nutshell, which with AI algorithms based on generative regulations in place for the responsible uses AI to predict allosteric properties of adversarial networks or generative use of genome editing techniques, and disease targets. cooperative networks—most of which were when they do have guidelines, they China’s large population and massive developed in the United States, Canada or are often unenforceable. The WHO’s hospitals make it easy to aggregate large data Europe—because they are often open source 18-person expert panel has now come up sets—a crucial requirement for training AI. and publicly accessible. “You change a few with broad recommendations that address There is also less concern about privacy in words and change the whole concept. You the scientific, ethical, social and legal China, meaning that the data are easier to can find a way to address the question you implications raised by the prospect of access. Lee says that AI companies in the have,” says Nutshell’s Yu. “The science is editing the genome of a human embryo. United States in particular are hobbled by from there [the West], but the technology The first statement sets out five regulations, such as the Health Insurance is from here.” scenarios where gene editing might be Portability and Accountability Act of 1996, Lee says that the approach of Chinese AI applied—somatic genome editing for which sets standards for how electronic drug discovery may also be more pragmatic, sickle cell disease, somatic gene editing health records can be shared. HIPAA makes something he thinks gives China an edge. for Huntington’s disease, somatic gene it difficult, even when patients have given DeepMind, a Google subsidiary that has editing by “unscrupulous” actors, consent, to pull data together, says Lee. stunned researchers by solving a decades somatic gene and epigenetic editing for Although the Chinese government is about old protein folding riddle, might win the enhancement, and germline editing— to come out with severe penalties for those Nobel Prize or Turing award, but Chinese and lays out the technical, ethical and who sell leaked personal data, companies companies are “very good in monetizing societal issues that each faces. The second like Yidu Cloud, which brings together AI, creating value with AI, building new set of recommendations outlines the consented patient data into a research tool, products with AI,” he says. role that the WHO should undertake are emerging to ensure the data can be The explosion of interest and in establishing a moral and scientific accessed, says Lee. Their counterparts in opportunities in AI has, however, driven leadership role. Among them are creating the US—Flatiron Health, Tempus, Aetion up wages and made it difficult to retain a registry of clinical trials involving and Palantir—are similarly consolidating expertise. Top AI experts in China cost gene editing and working with patent real-world electronic health record data on a more than in the United States and tend to holders and regulatory agencies to insure massive scale for use in drug discovery. move around, says Zhavoronkov. Insilico that the technology, once developed, is But many of the data are of poor quality, mainly hires AI expertise outside mainland widely accessible. which can mislead the AI. “Data quality is China. Insilico, whose research stretches While these guidelines present absolutely critical.