Editor’s Corner: The China Conundrum

David Steensma, MD
Edward P. Evans Chair in MDS Research and institute physician at the Dana-Farber Cancer Institute; Associate Professor of Medicine at Harvard Medical School; Editor-in-chief of ASH Clinical News

As I begin writing this editorial, nanoscience expert Charles Lieber, PhD, Chair of Harvard University’s Department of Chemistry and Chemical Biology, is sitting in a nearby jail. He has been held there since his arrest by the Federal Bureau of Investigation (FBI) on January 28.1 A federal judge has set his bail at $1 million, forced him to surrender his passport, and restricted the amount of cash he is allowed to have.

Dr. Lieber is accused of failing to disclose that he has been a “Strategic Scientist” at Wuhan University of Technology (WUT) in China since 2011, despite receiving more than $15 million in funding from the National Institutes of Health (NIH) and the U.S. Department of Defense (DOD), agencies that require disclosure of such collaborations. He reportedly had been receiving $50,000 per month for his WUT role, plus $150,000 in annual “living expenses.” It is unclear if this income was declared on his U.S. income taxes.

A few weeks before Dr. Lieber was arrested, Zaosong Zheng, a 30-year-old Chinese national PhD student who formerly worked in a laboratory at Beth Israel Deaconess Medical Center (BIDMC) across the street from my office, was taken into custody at Boston’s Logan Airport as he was trying to board a Hainan Airlines flight to Beijing with 21 vials of cells stuffed in a sock in his luggage.2 Traveling with biological materials is not illegal, but Mr. Zheng’s specimens were improperly labeled and, during interrogation, he admitted that he had stolen the materials from BIDMC when his position there ended. According to a U.S. Department of Justice (DOJ) news release, Mr. Zheng was planning to bring the cells to a lab in China to continue work on them in the hope of publishing results under his own name. Shortly after Mr. Zheng’s arrest, one of the hospitals where I admit patients sent a letter to all researchers, warning us not to transport biospecimens without authorization.

These bombshell developments occurred in the context of recent China-related news involving prominent hematologists. Alan List, MD, who presented results of the pivotal clinical trial of luspatercept in myelodysplastic syndromes (MDS) at the plenary session of the 2018 American Society of Hematology (ASH) annual meeting and led the initial Celgene-sponsored studies that resulted in approval of lenalidomide for the del5q MDS subset in 2005, resigned from his position as Chief Executive Officer of H. Lee Moffitt Cancer Center in Tampa on December 18, 2019, after Moffitt internal investigators decided he had not properly disclosed funds received from China for laboratory collaborations there.3 (Disclosure: I have been a co-author with Dr. List on multicenter clinical studies and I served on the Medical Advisory Board of the MDS Foundation, of which Dr. List is a member of the Board of Directors, until I resigned from that role in 2013 due to an illness.)

Moffitt also is reportedly re-evaluating its decade-long relationship with Tianjin Medical University Cancer Institute and Hospital – one of many partnerships between U.S. and Chinese clinical and research facilities. Moffitt’s Director, Thomas Sellers, PhD, and four other researchers, including immunologists Sheng Wei, MD, and P.K. Epling-Burnette, PharmD, PhD, who worked on the immunology of marrow failure, also were forced to resign from their positions because of allegedly undisclosed Chinese relationships. Dr. Sellers’ attorney has announced that he is preparing a lawsuit against Moffitt for what he says are inaccurate public statements.

The Boston and Tampa events are part of an emerging pattern. In July 2019, Kang Zhang, MD, PhD, former Director of the Institute for Genomic Medicine at the University of California San Diego (UCSD) and Professor at UCSD’s Shiley Eye Institute, resigned after news emerged that he had founded a publicly traded Chinese biotechnology company specializing in the same type of work he was doing at UCSD.4 The University of Texas MD Anderson Cancer Center ousted three Chinese researchers in April, citing violations of peer review confidentiality and rules for foreign-ties disclosure. Science reported in March that the NIH has sent letters to dozens of U.S. research universities asking for information about specific NIH-funded faculty members who might have links to foreign governments, and The Boston Globe reported in December that at least 180 NIH-driven investigations are ongoing, most related to China.5,6

These events have sent a chill through the U.S. research community and a strong message that no one is above scrutiny of their China-related ties, whether they are Chinese nationals or U.S. citizens – no matter how successful or vital their research programs might be, or how prominent their institutions. Many researchers and institutional leaders have shared with me recently that they are beginning to wonder if the common practice of hiring Chinese investigators to work in their laboratories is still worthwhile and if they should sever collaborations with Chinese colleagues and institutions.

The Thousand Talents Program

Most of the academics who recently have run into problems related to China disclosures were linked to the Thousand Talents Program. Formed in 2008 by the Chinese government, the Thousand Talents Program had the goal of bringing at least 2,000 successful academics to China by offering access to high-tech facilities, competitive salaries, a one-time payment of about $145,000, and an honorary title. Participating institutions in China reportedly told faculty members not to inform their U.S. host institution about details of the program’s arrangements. The plan was so successful that at its peak it had more than 7,000 members.4

However, Thousand Talents participants are a tiny minority of Chinese nationals working in U.S. labs. Ross McKinney Jr., MD, Chief Scientific Officer of the Association of American Medical Colleges, has noted that researchers of Chinese descent make up almost half of the U.S. research workforce, in part because American-born scientists take work in the private sector more often than they seek academic positions.4 More generally, scientific disciplines have become a less popular career choice for top U.S.-trained students. Science competes with more lucrative – and potentially less difficult – careers such as banking, finance, or marketing. According to the Harvard Political Review, for instance, over the past decade about 40% of graduating Harvard College seniors said they planned to work in consulting or finance.7

The Political and Social Context of Recent Researcher Investigations

These recent developments in the clinical and research community are happening within the context of broader geopolitical strain between the world’s two most powerful nations, fueled by domestic demands that the U.S. “get tough on China” for past misbehavior – and likely influenced by a well-documented rise in expressions of nativism and xenophobia. Growing U.S.-China tensions have manifested in tariffs and trade wars, naval standoffs in the South China Sea, criticism of labor practices in Chinese factories and policies toward Hong Kong, disagreements over how to handle volatile North Korea, and worries about espionage that are intensifying as the era of 5G networks and the “internet of things” approaches.

The Chinese government has repeatedly been accused of orchestrating theft of technology or trade secrets from the U.S. and other countries to support domestic commercial and military development. As the FBI special agent in charge of the bureau’s Boston office recently told The Boston Globe, China wants to “replace the U.S. as the world superpower, and it’s breaking the law to get there.”6 In recent years, U.S. companies have been accused of being too careless with trade secrets as they built factories in China to take advantage of cheaper labor, and some corporations agreed to transfer technology to Beijing in exchange for access to China’s market of more than 1.4 billion people. Fear of espionage and accusations of fraud contributed to the high-profile arrest of telecom giant Huawei’s Chief Financial Officer Meng Wanzhou at Vancouver Airport in December 2018.8

Many Americans have expressed envy of China’s ability to complete massive public works projects like the Shanghai Metro expansion or the Sino-Singapore Tianjin Eco-city, even as aging U.S. infrastructure crumbles and civic authorities seem increasingly impotent. President Donald Trump has called the airports in his home city of New York “like from a third-world country,” while others have described New York’s grungy, chaotic Penn Station “shameful” and “a disgrace” when compared with similar central stations in Chinese cities. American influence also is waning internationally as the Trump administration dismantles foreign trade agreements and weakens longstanding alliances such as NATO – which Trump has labeled “obsolete.”9 Meanwhile, China’s economic and political influence across the globe is increasing, driven by development strategies such as the Belt and Road Initiative, through which Chinese companies are building railroads and other major infrastructure in more than 70 countries in exchange for economic and trade favors.

Some U.S. leaders view relations with China as a zero-sum game. For example, on January 30, U.S. Secretary of Commerce Wilbur Ross commented favorably on the potential for the 2019 novel coronavirus, which is now causing widespread disruption in China, to return jobs to the U.S that had been lost in recent years.10 Many observers expressed shock that a cabinet member had openly commented upon an emerging global pandemic’s potential to contribute to the U.S. economy.

The developments of the last few years must be viewed in the context of a long history of U.S. suspicion of China, as well as a well-documented strain of racism. In the mid-19th century, immigration from Asia led the state of California to pass legislation in 1855 to tax owners of trans-Pacific ships that might carry people from China: “An Act to Discourage the Immigration to this State of Persons Who Cannot Became Citizens Thereof.” In 1862, the U.S. Congress passed the “Anti-Coolie Act,” followed 20 years later by the Chinese Exclusion Act, which banned virtually all Chinese immigration to the U.S. and was enforced for more than 70 years. Anti-Chinese prejudice in various forms continues today, in big and small ways: In April 2019, nutritionist Arielle Haspel (who is not Chinese) opened Lucky Lee’s restaurant in New York’s Greenwich Village, offering “clean” Chinese food, implying the rest is somehow dirty. (The outcry contributed to the restaurant’s closure in December.)11

Has Pressure Gone Too Far?

Some scientists have voiced worry about excessive scrutiny of Chinese investigators and their collaborators. Most of the incidents mentioned above are matters of disclosure, not of suspected espionage or intellectual property violations, and disclosure rules are complicated and inconsistent between institutions, journals, agencies, and societies. For example, Michael Zigmond, PhD, retired Professor of Neurology at the University of Pittsburgh School of Medicine, decried “misdirected concern” after Dr. Zhang’s resignation from UCSD. “[In medicine] we all report our results in annual progress reports, at professional meetings, and in published papers. Stealing secrets is the last thing from our minds.”4 A few investigators have blamed institutions for “throwing good researchers under the bus at the first sign of trouble” out of fear of NIH funding loss or DOJ sanctions.

After chemist Dr. Lieber’s arrest, Steven Holtzman, former Biogen Executive Vice President, told The Boston Globe, “You don’t want to get yourself into a climate where people will be so afraid of interacting with [foreigners] that they’ll stop coming [to the U.S.]. That was McCarthyism.”6 A running joke here in biotech-heavy Boston and Cambridge is that if federal agencies were to deter Chinese nationals from working in the U.S. in the name of protecting intellectual property, there wouldn’t be much intellectual property left to protect.

A Personal View – and a Way Forward

I’ve never been to China. I have no collaborations with investigators in China, and no financial ties other than reviewing 3 or 4 MDS or leukemia cases each year for Chinese physicians via remote e-consultation services. But I wouldn’t be practicing hematology and conducting research the way that I am today without numerous contributions from Chinese researchers and physicians, and likely neither would you.

It was a Chinese postdoctoral researcher in a lab at Mayo Clinic, Xue Wei Meng, MD, PhD, who 20 years ago patiently showed me how to do a Western blot, and a Chinese teaching assistant who helped me pass microbiology in medical school at the University of Chicago. A Chinese graduate student at a different institution taught me a more efficient way to set up a chromatography system, and I’ve collaborated on clinical trials with numerous pharmaceutical scientists, statisticians, and administrators who were Chinese nationals. Thousands of others could tell similar stories.

Every morning on the way to my office at Dana-Farber Cancer Institute, I share an elevator with a few of the many members of the “United Nations of Hematology”: researchers from all over the globe who work in the same building and are making important contributions to understanding blood disorders and cancers and from whose presentations at research conferences I’ve learned much over the past decade. Among these researchers, China is especially well represented.

Knowledge generated in China has influenced hematology practice across the globe. As Zhen-Yi Wang, MD, and Zhu Chen, MD, PhD, from Shanghai summarized in a 50th anniversary review published in Blood in 2008, Chinese investigators brought us the two most important drugs in the treatment of acute promyelocytic leukemia (APL).12 All-trans retinoic acid (ATRA), the initial leukocyte “differentiating therapy,” was first used for APL in 1985 in Shanghai’s Ruijin Hospital, an affiliate of Shanghai Second Medical University. ATRA dramatically altered the natural history of APL, including quickly reversing coagulopathy, and has saved countless lives. Arsenic trioxide, a traditional Chinese medicine in the form of yellow orpiment, was first used in China in the early 1990s to treat APL; a study from Harbin Institute of Technology in 1996 reported a complete response rate of more than 70% in newly diagnosed patients and a rate nearly as high in those with relapsed disease. More recently, China has invested heavily in cell therapies; just last month, Blood published an interesting study of CD19/CD22 combination chimeric antigen receptor (CAR) T-cell therapy from Huazhong University of Science and Technology.13

There is no question that there have been numerous cases of research fraud and plagiarism involving Chinese investigators, as well as ethical violations (e.g., He Jiankui’s gene-edited babies, Lulu and Nana, whose birth was announced in 2018, much to the surprise of his university’s Institutional Review Board). We can’t be naïve about that. Patent law, which helps drive innovation, has been widely flouted in China, with bootlegged DVDs, garments, and other consumer goods available at “fake markets” across the country, in addition to clandestine “technology transfers.” But those abuses can’t mean that we broadly ignore Chinese innovation or now refuse to collaborate with Chinese investigators. As Reagan quipped, “Trust, but verify.”

There are bad actors on the Chinese side that include powerful government officials, as well as plenty of people in the U.S. and elsewhere who are motivated by greed. It is easy to blame confusing disclosure rules for some of the problems encountered by U.S. researchers, and disclosure rules are certainly opaque and Byzantine and ripe for reform. But emails obtained by the press strongly suggest that at least some of the sanctioned investigators knew what they were doing.3

Yet we need to ensure that scientific collaborations between the U.S. and China – and other nations – can continue unhindered. This includes collaboration around clinical trials. Hematologic disorders and other medical maladies are not exclusively American problems or Chinese problems; they are human problems. One of the best things about ASH is that it is not just America’s premier hematology professional society, it is the world’s. Researchers from all over the globe, including China, attend and present data at the ASH annual meeting – at the 2019 annual meeting 114 nations were represented. ASH committees include hematologists from many countries.

The 20th century was defined geopolitically by the end of colonialism, World Wars, and Cold War tension between the U.S. and the Soviet Union. The 21st century could be defined by escalating U.S.-China conflict – or by transnational partnerships to combat the illnesses and dangers that affect all humanity. It is up to all of us to help choose which narrative appears in the 22nd-century history texts.

References

  1. Harvard professor among three charged with lying about Chinese government ties. Accessed February 5, 2020, from https://www.cnn.com/2020/01/28/politics/harvard-professor-chinese-nationals-arrest-espionage/index.html.
  2. The New York Times. Stolen research: Chinese scientist is accused of smuggling lab samples. Accessed February 5, 2020, from https://www.nytimes.com/2019/12/31/us/chinese-scientist-cancer-research-investigation.html.
  3. Tampa Bay Times. Top Moffitt Cancer Center doctors failed to disclose payments from China, report says. Accessed February 5, 2020, from https://www.tampabay.com/news/health/2020/01/19/top-moffitt-cancer-center-doctors-failed-to-disclose-payments-from-china-report-says/.
  4. UCSD doctor resigns amid questions about undisclosed Chinese businesses. Accessed February 5, 2020, from https://inewsource.org/2019/07/06/thousand-talents-program-china-fbi-kang-zhang-ucsd/.
  5. Exclusive: Major U.S. cancer center ousts ‘Asian’ researchers after NIH flags their foreign ties. Accessed February 5, 2020, from https://www.sciencemag.org/news/2019/04/exclusive-major-us-cancer-center-ousts-asian-researchers-after-nih-flags-their-foreign.
  6. The Boston Globe. Concerns raised in Mass. life sciences sector about US crackdown on China. Accessed February 5, 2020, from https://www.bostonglobe.com/2020/01/30/business/concerns-raised-mass-life-sciences-sector-about-us-crackdown-china/.
  7. Harvard Political Review. The draw of consulting and finance. Accessed February 5, 2020, from https://harvardpolitics.com/harvard/the-draw-of-consulting-and-finance/.
  8. Inside the Feds’ battle against Huawei. Accessed February 5, 2020, from https://www.wired.com/story/us-feds-battle-against-huawei/.
  9. The Economist. America’s global influence has dwindled under Donald Trump. Accessed February 5, 2020, from https://www.economist.com/leaders/2017/11/09/americas-global-influence-has-dwindled-under-donald-trump.
  10. The New York Times. Wilbur Ross says coronavirus could bring jobs back to the U.S. Accessed February 5, 2020, from https://www.nytimes.com/2020/01/30/business/economy/wilbur-ross-coronavirus-jobs.html.
  11. The New York Times. A white restaurateur advertised ‘clean’ Chinese food. Chinese-Americans had something to say about it. Accessed February 5, 2020, from https://www.nytimes.com/2019/04/12/nyregion/lucky-lees-nyc-chinese-food.html.
  12. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111:2505-2515.
  13. Wang N, Hu X, Cao W, et al. Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies. Blood. 2020;135:17-27.