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27 December 2018

Brave new world with Chinese characteristics

By Yangyang Cheng

The YouTube video began with a young Chinese man in a light blue shirt, seated in what appeared to be a biology lab, speaking exuberantly into the camera in slow but clear English: “Two beautiful little Chinese girls, Lulu and Nana, came crying into this world as healthy as any other babies a few weeks ago.” It could have been an excited new father sharing the joy of birth. But as the video would soon reveal, Lulu and Nana are not “any other babies;” they are the world’s first genetically edited humans, born from fertilized eggs modified with CRISPR-cas9 technology.

At least that is what the man in the video and at the center of a storm of controversy—the Chinese scientist He Jiankui, who led the experiment—claims.

The reactions of the scientific community, He’s employers, the Chinese government, and the general public have not by any means matched the positive tone of He’s video. Since he announced his genetic experiment on November 26, criticism has been swift, strong, and nearly universal. Many scientific observers say He used poorly-understood technology, and used it shoddily, to experiment on and create real human beings, with unforeseeable consequences. He may also have relied on secrecy and lies to carry out his reckless plan.

The China-born, US-trained He conducted his experiment in his birth country, where he’s lived and worked since returning from the United States in 2012. As a Chinese scientist now working in America, I have raised serious concerns about the dangers of China’s techno-nationalistic ambitions and the country’s poor record in scientific ethics. A lot more information about He and his experiment have been revealed since news of it first broke; what I’ve learned only increased my concerns about techno-nationalism and lack of attention to ethics in biotechnology research. He and I graduated from the same Chinese university, three years apart; we both went on to graduate school in the United States. His family and mine came from neighboring provinces in China. I saw familiar traits in the path He’s taken and felt that his story is one I could at least attempt to understand.

As I looked into the history of He’s life and career, the institutions he has interacted with, and the conditions he exploited to advance his work, the story that emerges is more Elizabeth Holmes than Dr. Frankenstein. It is a story in which high-tech ambition meets capitalism with Chinese characteristics. And the poor village boy pursued both his ambition and the capital required to reach it with shrewdness and zest, apparently trampling ethical boundaries along the way in a system that allowed him to trample away.

It’s also a story that could only happen in Shenzhen, China, in the year of 2018, though it started decades earlier and hundreds of miles away.

Provincial beginnings. He Jiankui was born in 1984 in a small village of farmers and fishermen in central Hunan province. Hunan, or South of the Lake, is located in the middle stretch of the Yangtze river and dotted with mountains and waterways. My family came from the nearby province of Hubei, or North of the Lake, though by the time my parents met, they had migrated east to Anhui, where I was born and raised.

He’s hometown of Xinhua is one of the poorest villages in China. By the time He started elementary school in 1990, the annual income per capita in Xinhua was barely $100. Both of He’s parents worked in the fields. “I picked off leeches in my legs every day in the summer,” said He in a video years later. Despite the poor conditions, He excelled academically, earning top grades from elementary school to high school.

Not much had changed in Xinhua since He’s childhood. By the turn of the century, the annual income in an average farming family there had doubled—but that made it a still-bleak $200 per person. However, 400 miles to the south, on China’s coast opposite Hong Kong, an economic transformation was taking place that would have profound implications for the region, the rest of China, and He’s life, as well.

Before the Chinese government designated Shenzhen as one of the country’s first “special economic zones” in 1980, the small fishing village on the edge of Guangdong province was not much different from Xinhua. Unshackled from years of a planned economy and political hurdles, the entrepreneurial and hardworking people of Shenzhen turned their world upside down, both figuratively and literally. “Shenzhen speed” entered the Chinese lexicon, originally referring to the construction of one story of a building in three days but generalized to symbolize rapid development. The coastal city’s proximity to the global financial hub of Hong Kong, then still a British colony, was a unique advantage.

By the time He was born, Shenzhen was already a booming city, with modern housing, affluent residents, and a fledgling tech industry, impressing China’s then paramount leader Deng Xiaoping when he visited the city in 1984. Among the countless companies to emerge from Shenzhen were Huawei, founded in 1987, and Tencent, established in 1998. The two would go on to become the world’s largest telecom equipment manufacturer and the world’s largest gaming and social media company by market value, respectively. (Recently, Huawei’s chief financial officer was arrested in Canada on an American warrant related to allegations of fraud in relation to US sanctions on Iran.)

In the neighboring province of Fujian, also on China’s southern coast, another group of villagers was finding its way to prosperity. In the eastern village of Putian, Chen Deliang, a middle school dropout turned street performer, obtained a medical license through remote classes by postal mail and earnedhis first pot of gold from a home remedy for scabies, an itchy skin infection. Building on their initial success, Chen and his disciples forayed into treating sexually transmitted diseases and infertility, exploiting the country’s shortage of medical resources, lax regulatory system, and public stigma about the conditions. With aggressive advertising and a clan mentality as their calling cards, the Putian clique quickly spread across China. Incentivized by lucrative contracts, many public hospitals leased offices to medical practitioners from the Putian clique, lending the barefoot doctors a cloak of credibility.

The Putian clique met its first major setback in 1998. The exposure of a variety of medical frauds led to a nationwide crackdown, and the government soon banned the type of private partnership at public hospitals that Putian-ers relied on. Not easily defeated, the resourceful Putian businesspeople came up with an alternative path: If they could no longer work at public hospitals, they’d just open private ones. A string of favorable government policies toward private hospitals came at just the right time. Despite numerous scandals and much controversy, the Putian clique of private hospitals popped up all over China, continuing their specialization in medical needs too embarrassing for treatment at formal hospitals. According to the New York Times, the Putian system now includes eight of 10 private hospitals in China, some 8,000 facilities in all.

While the village of Putian is a peculiar case, it was not uncommon in 1990s China for an entire village economy to be centered around one commodity and a fanatic race to fortune. In many villages in the northern Henan province, some 900 miles up the coast from Shenzhen, the product sold was plasma obtained from human blood. In the heyday of the plasma industry, the Guardian has reported, a liter went for about eight dollars, and a healthy villager could sell up to three times a week, earning in a month what one would otherwise make in a year. The government abruptly shut down the whole business in 1995, and in a few short years, the scent of iron from red blood cells that permeated the villages had turned into the smell of death, as villager after villager succumbed to a mysterious and agonizing illness.

After years of intrepid work by some brave individuals, it was eventually revealed that unsanitary equipment and procedures used in plasma collection had infected an estimated one million people with HIV. The government kept the business going for several months after gaining knowledge of the situation, never informed the exposed population, even after shutting down the industry, and tried very hard to keep the whole thing under wraps. In some villages, up to 40 percent of the population was infected with HIV.

As these types of transformations were taking place across the vast land of China, a teenage He Jiankui was studying hard at the best high school in his impoverished hometown, hoping to score well in the country’s notoriously brutal gaokao, or college entrance exam. For a child from inland China with little in the way of financial resources or political connections, academic excellence was the only way out. He could not possibly have known then that less than two decades later, his life and career would become intertwined with capital from Shenzhen, a hospital from the Putian clique, and the story of AIDS villages in Henan.

The American Dream is alive in China. In the late summer of 2002, He Jiankui arrived at the University of Science and Technology of China (USTC) as a college freshman. Founded in Beijing in 1958 but forced to move to the southern city of Hefei at the height of the Cultural Revolution, USTC is known as the “Caltech of China” for its small size and intense focus on science and engineering. It is one of the most selective universities in China. Despite scoring high marks on the gaokao, He did not get into his first choice for a field of study—physics— but was admitted to the Department of Precision Machinery and Precision Instrumentation.

The president of USTC at the time was the esteemed chemist Zhu Qingshi. The independent-minded Zhu famously resisted the wave of enrollment expansion that swept Chinese universities in the early aughts and spoke critically against the metrics of university evaluation in China that put more emphasis on the appearance of a campus than the quality of its education. Zhu attributedUSTC’s resistance to bureaucratic pressure to two factors: “[W]e have the confidence, and we have a spine.”

USTC takes pride in its academic rigor, complemented with a degree of flexibility rare at Chinese universities. Students are free to change their majors after their first year, and in the fall of 2003, He transferred to the Department of Modern Physics.

I graduated from USTC’s Class of 2009, where I also majored in physics. According to He’s classmates and university records of its top honors, where he is not listed, He was a good student at USTC, but not exceptional. This appears to contradict his father’s account in Chinese media, where He always earned “first place” from elementary school to graduate school, “never once in second place.”

“After he started university, every time he came back to the village, everyone wanted to meet him and hear his tips for good grades,” the senior He proudly told reporters at Beijing News. With the extreme disparity in educational opportunities in China, only a handful of the best students from He’s hometown, or mine, have a shot at a place like USTC. I understand firsthand the social pressure a community places on its “academic celebrities,” and how the weight of expectation can be overwhelming for a young student.

Around 30 percent of USTC graduates go on to earn postgraduate degrees overseas, mostly in the United States (which accounts for the university nickname “United States Training Center”). After graduating from USTC with a degree in physics and a thesis on the theory of quantum state transfer, He arrived at Rice University in Houston in the fall of 2006 to pursue his doctorate in physics. Three years later, I would find myself crossing the oceans to study for my PhD at the University of Chicago.

It was at Rice that He made the switch to bioengineering, a move he later described as “out of concerns for future employment opportunities and the pressure to survive.” According to He, “the golden age of physics had passed, but the field of biology is blossoming.” As a particle physicist, I do not agree with He’s categorization of my profession, but his arguments sound eerily familiar. In my first years in the United States, many well-meaning people, including members of my family, tried to persuade me to study biology for better employment prospects.

He’s appetite for publicity was already evident during his time at Rice. The Southern Chinese Daily News, a Houston-based Chinese-language newspaper, devoted significant space to a report on his wedding in 2010, under this headline: “With outstanding morals, excellent academics, and infinite potential, a union for life complete with both good looks and scholarly talent.” In a public post on Facebook, He excitedly shared the press clip, asking friends to help him collect some physical copies so he could mail them back home to his parents. “I heard other papers reported it, too,” He wrote. One commenter joked in disbelief, “How much did you pay for this?”

He earned his doctorate at the end of 2010 and moved to Stanford for postdoctoral work. Around the same time, he started a blog on sciencenet.cn, a Chinese platform for science bloggers. In a post from March 2011, He made an announcement: “Per invitation from Lambert Academic Publishing, my new book ‘Modularity: The Principle of Evolution in Complex Systems’ is published today.” The online magazine Slate has described Lambert Academic Publishing (LAP) as a content mill that churns out titles with little apparent attention to selection or editing. I am no stranger to “invitation” from LAP myself, having received numerous emails from its representatives requesting to republish my papers or doctoral thesis. A book from LAP won’t carry much water in serious academic circles. But in the private sector, and especially in China, given the language barrier, it might just woo some investors.

In 2011, while still in the United States, He received an academic award from the Chinese government. The Chinese Government Award for Outstanding Self-financed Students Abroad, which comes with a check of between $6,000 and $10,000, was established in 2003 with the explicit purpose of encouraging Chinese students overseas “to return to China for work or serve the country abroad in various ways,” according to its official website. The selection involves a highly politicized process, the first round of which is conducted by the Chinese embassy in participating countries and the local consulates. The year prior, He served as president of the Chinese Student and Scholars Association (CSSA) at Rice, an organization that receives funding from and organizes activities with the Chinese consulate in Houston.

He set his eyes on returning to China, but when he went, he would not be returning only as a scientist. At Stanford, He worked in the lab of Professor Stephen Quake, a pioneer in single molecule biophysics and gene sequencing. Quake is also a successful inventor and tech entrepreneur, with more than 10 companies to his name; they were valued at over a billion dollars at their peak. Witnessing Quake’s success and the startup culture at Stanford was transformative for He, and a city 6,000 miles away was creating the perfect environment for him to realize his startup dreams.

In 2007, when He was still pursuing his doctorate at Rice, Shenzhen was in its ninth straight year as the fourth richest Chinese city, by gross domestic product. While over half of the city’s wealth came from its high-tech industry, the coastal metropolis struggled with a lack of good universities. So the city government decided to bring “Shenzhen speed” to higher education. In a bold move against a typically slow and bureaucratic process, Southern University of Science and Technology (SUSTech) was created almost overnight, admitting its first class of students in 2011.

Zhu Qingshi, who had just finished a decade-long tenure as president of USTC, became SUSTech’s founding president. His innovative spirit and penchant for reform, combined with his rich experience and academic credentials, made Zhu the ideal person to lead the new university. Zhu brought to SUSTech many of the philosophies he practiced at USTC: small classrooms, a flexible curriculum, and abundant research opportunities. Additionally, SUSTech embraced the enterprising spirit of Shenzhen, encouraging its faculty to commercialize their research and start their own businesses. Zhu’s successor at SUSTech was even more explicit: “[M]y model for SUSTech is Stanford.”

Stanford was largely responsible for creating Silicon Valley and its wealth. For Shenzhen and SUSTech, the situation was different: The city was flush with cash, but the university was still largely empty. Could the best money buy the best talent? In 2010, the government of Shenzhen launched the “Peacock Plan.” With tax-exempt cash rewards of up to $200,000 and research funds in the millions, the Peacock Plan hopes to attract high-level overseas talent to Shenzhen. Zhu himself crisscrossed North America on recruiting tours, and at one of the stops, he met He Jiankui.

In December 2011, He posted an ad on his blog: “The He Jiankui Lab at SUSTech is searching for postdoctoral researchers.” He described his future workplace as the “He Jiankui-Michael Deem joint lab” with a focus on genome sequencing. Deem, a physics and bioengineering professor, was He’s doctoral advisor at Rice.

The professor-entrepreneur. One of the first things the 28-year-old He did after moving to Shenzhen in 2012 was to register a company. He named it “Hanhai” in Chinese, likely in a nod to his alma mater. USTC’s electronic bulletin board is called “Hanhai Xingyun”: the vastness of the ocean, the brilliance of the stars. The English name for He’s new company is less poetic: Direct Genomics.

In its pursuit of making China a “science and technology superpower,” the Chinese government has made indigenous innovation one of its highest priorities. The path from “made in China” to “invented in China” relies heavily on Chinese capital to make what used to be foreign, Chinese. Private and public funding are used not only to recruit foreign-trained talent, but also to purchase foreign intellectual property. He Jiankui and Direct Genomics did both.

A decade after the completion of the Human Genome Project in 2003, the technology of genome sequencing had matured, moving out of research labs into the commercial market. By sequencing their genomes, people could suddenly learn a lot about themselves, from likely ancestral lineage to propensity to suffer from certain diseases. Chinese companies were eager to get a share of the emerging market. In the fall of 2012, the Chinese genomics giant BGI-Shenzhen purchased the Silicon Valley-based DNA sequencing firm Complete Genomics for a whopping $117 million, which was described as a “fire sale” price, given the amount that had been invested in developing the company’s technology. Still, He and his early investors had nowhere near that kind of cash. But they had a unique advantage. The US-based sequencing firm Helicos Biosciences had just gone bankrupt, and Direct Genomics was able to license its technology for a bargain from Caltech. Helicos was founded by Stephen Quake when he was a professor at Caltech in 2004, before Quake moved to Stanford and later supervised He’s postdoctoral research.

Helicos went out of business for good reason, according to Bio-ITWorld.com: “[T]he company sold only around a dozen sequencers in the brief period, from 2008 to 2010, when its HeliScope instruments were on the market.” Its machines were cumbersome and difficult to mass produce, the process they used was costly, and the results achieved were not accurate enough for research purposes. The early years of Direct Genomics were difficult. The startup had trouble paying its small staff and nearly collapsed. The setbacks did not stop He from dreaming big or from seeking publicity for himself and his work.

During the bird flu outbreak in the spring of 2013, the journalist Mara Hvistendahl, then China correspondent for Science magazine, received urgent email from a young associate professor at SUSTech. He Jiankui told Hvistendahl that his team had been working “day and night” to sequence the bird flu virus H7N9 and wanted to have their manuscript published “in Science or other journals as soon as possible.”

At first, Hvistendahl thought He had mistaken her as a journal editor. A few days later, South China Morning Post (SCMP) ran an article reporting on He’s claims of a rapidly mutating flu virus. He was the only person cited in the SCMP piece, and the study he was so eager for the world to see was never published in a peer-reviewed journal. The public record shows only two versions of a draft uploaded to arXiv, a preprint repository rarely used by biologists. The two drafts, uploaded two days apart, included conflicting claims about the number of mutations in the virus. The first version pointed to a “Supplemental Fig. 18” on the number of mutations, but such a figure was nowhere to be found in the draft. The second version did not refer to a corresponding figure for its claim of mutations. It’s unclear how SCMP picked up the study.

Direct Genomics finally had a breakthrough in 2015, with the announcement of GenoCare, described as “the world’s first single molecule genome sequencer that is engineered exclusively for the clinic.” By focusing on clinical use instead of scientific research, GenoCare seeks to bypass some of Helicos’s difficulties in whole genome sequencing, since it only needs to target a narrow subset of genome for medical diagnosis. The repackaging of GenoCare to be a fraction of the size of Helicos machines was an engineering feat, but at the heart it still deploys Helicos technology, and suffers from the same problems, Bio-ITWorld.com said. For one, GenoCare and Helicos machines could only read genomes in small fragments of about 30 base pairs. Stitching the pieces together to get a bigger picture of a genome is computationally intensive and can obscure important information.

Technical challenges aside, He’s GenoCare platform does promise to perform genome sequencing faster and cheaper, lowering the price by an order of magnitude to the hundred-dollar range, an attractive feature for the clinical market. More important, Direct Genomics has the unique advantage none of its US or European competitors could dream of: support from the Chinese government. The re-engineered Helicos machine is “completely indigenous IP” and “the most accurate in the world,” according to the Chinese Ministry of Science and Technology. In the fall of 2017, China Central Television ran a lengthy segment on He and his company, as part of a special feature to welcome the 19th Party Congress. The most recent gathering of the highest leadership of the Chinese Communist Party, held once every five years, reemphasized Party control and enshrined “Xi Jinping thought” into the Party Charter, making Xi the most powerful Chinese leader since Mao.

In the elaborately produced video, a triumphant He declared to the camera, “Yes, it’s me, He Jiankui. I did it.”

With publicity came funding. Direct Genomics completed another round of fundraising in the spring of 2018, collecting over $30 million in investment.

The boy from Xinhua village now controls at least five different companies. The best known is Direct Genomics. The largest by registered capital is called Shenzhen SUSTech Biotech Company, founded in 2016. He Jiankui is its largest shareholder at 45.5 percent, the city of Shenzhen owns 30 percent, andSUSTech claims the rest.

Two little girls. “The scientist He Jiankui from Shenzhen, China, announced that a pair of gene-edited babies named Lulu and Nana were born in China this November, both healthy.” So began an article from the People’s Daily online, the Chinese government’s official mouthpiece. The article went on to state the significance of the news: “These are the world’s first genome-edited babies who are immune to HIV. This also means China has achieved a historic breakthrough in applying gene-editing to the prevention of disease.” The laudatory piece was posted on the morning of November 26 (Beijing time).

Hours earlier, MIT Technology Review had broken the news, followed by a report from AP with more details about the birth of the girls. The revelation was instantly met with fierce criticism from scientists, ethicists, and the general public worldwide. By the time the People’s Daily article appeared, the “historic breakthrough” was already a global scandal, and the article was quickly deleted.

Invented in the early 2010s, CRISPR-Cas9 technology, commonly referred to merely as CRISPR (an acronym for clustered regularly interspaced short palindromic repeats), is a powerful tool adapted from bacterial defense systems to slice and modify genomes. The revolutionary technology quickly became popular for its precision, low cost, and simplicity of use. He Jiankui immediately set his sight on human genome editing when he branched into the field.

Certain defects in the human genome lead to serious health challenges. On the other hand, some segments in a healthy human genome are connected with gateways for pathogens to enter the body.

The CCR5 gene encodes (that is, directs the body to produce) a protein on the surface of T cells, key pieces in the human immune system. That protein can be used as a gateway for the human immunodeficiency virus (HIV) to enter a cell. A natural mutation in the CCR5 gene—CCR5-delta32—closes off the door to certain types of HIV. But the mutation does not convey complete immunity, and it weakens the immune system against other viruses, including West Nile virus and the flu. The CCR5-delta32 mutation occurs in about 10 percent of Northern Europeans but rarely in Asians. Regardless, He claimed that he edited the normal CCR5 genes in Lulu and Nana during in vitro fertilization, in the name of HIV prevention.

At the Second International Summit on Human Genome Editing in Hong Kong, where He presented results the day after his YouTube announcement about Lulu and Nana, the young scientist stated that “I personally experience with (sic) some people in AIDS where 30 percent of a village people are infected”—an apparent reference to the AIDS villages in Henan in the 1990s. The tragedy of 20 years ago, however, was not caused by genetic defects in the population; it was the result of the distribution of tainted blood, a poor medical practice driven by greed and allowed by a corrupt government that cared more about its image than the health of its citizens.

At the gene-editing summit and in his videos, He has repeatedly talked about the stigma around HIV in Chinese society as justification for his work. Despite its own culpability in the spread of the virus, the Chinese government has repeatedly used the public’s fear of the incurable disease to promote its agenda. In the 1980s and ‘90s, AIDS was painted as a product of the West, resulting from the decadent lifestyles in capitalist societies. In recent years, HIV is connected with homosexuality and promiscuous behavior in state propaganda, as the Chinese government desperately tries to make the people marry early and have more children, to mitigate the severe demographic crisis resulting from decades of misguided “one-child” policy.

Based on data He presented at the gene-editing summit, his procedure changed the genes in Lulu and Nana, but did not create the CCR5-delta32 mutation in either child. It’s unclear if the babies will be immune to HIV, and the consequences of the mutations He introduced are unknown, said Sean Ryder, professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School. Ryder described He’s experiment as “misguided both scientifically and ethically.”

“It is my fervent hope that Lulu and Nana will lead long healthy lives,” Ryder wrote in an email. “To me, the best outcome is that the babies are unaffected by the procedures of the He lab. Worse outcomes are possible.”

“I feel proud,” He said at the gene-editing summit, claiming that his work had given the father of Lulu and Nana, who “never thought he could be a father” because of his HIV-infection, new hope and purpose in life. In Chinese culture, sons are expected to “carry on the family line.” Without mentioning existing safe and effective means for HIV-positive men to have HIV-free children, He used the social pressure and individual desire of fatherhood as further justification for his work. In his YouTube videos, He frequently notes that he is “a father of two girls,” as if having offspring is by itself proof of morality.

“If this was going to be your baby, would you have gone ahead with this?” He was asked after his presentation at the gene-editing summit.

“If it was my baby, with the same situation, yes I would try first.”

Who knew? China Central Television ran a lengthy report on He Jiankui in response to the news of the gene-edited babies. In stark contrast with the broadcast that heaped praise on Direct Genomics a year earlier, in this case serious-faced anchors asked in a scolding tone generally reserved for major criminals: “Shouldn’t He Jiankui recognize the serious consequences of his actions?”

Many former supporters appear to be disassociating themselves from the once rising star. SUSTech updated He’s homepage after the shocker on November 26, adding “nonpaid leave” next to the associate professor’s name. The university locked up He’s office and released a statement claiming everything related to the experiment was conducted off campus and without the university’s knowledge.

Still, according to SUSTech, He’s leave started before the scandal involving the gene-edited babies, in February 2018, and extends for three years. In an interview published in March, long before the scandal became public, He said the university granted him a “two-year unpaid leave” to focus on his business endeavors, during which he would be relieved of teaching and administrative duties but could keep conducting research at his lab and recruiting new students.

It appears that He has recruited at least one new member of his lab. The embryologist Qin Jinzhou is a research fellow at the Luohu District People’s Hospital in Shenzhen; he reportedly became a full-time visiting scientist at He’s lab starting in January 2018. Qin received his PhD from the College of Animal Science and Technology at China’s Northwest Agriculture and Forestry University through a joint program with the University of Arizona, where he specialized in animal reproduction.

He’s lab uploaded a total of five videos on its gene-editing experiment. The only video providing technical details featured Qin. Instead of talking about genome editing, Qin described at length why he chose to go gloveless when working: He had a better “sense of touch” without the extra layer of fabric, and the warmth from his palms could keep the embryos at a more desirable temperature. (According to Gaetan Burgio, group leader in genetics of host-pathogens interactions and genome editing at Australian National University, gloves are a basic necessity to avoid contaminating the genome under study and to protect the scientist from potential pathogens, like HIV, in the test materials.)

Qin was listed as the applicant on the experiment’s entry in the Chinese Clinical Trial Registry. The application was created on November 8, 2018 as a “retrospective registration;” it was updated on November 30, four days after the announcement of the genetically altered babies. The update said the application had been “rejected due to inability to provide original data for verification” (in Chinese).

He Jiankui is listed on the registration as the “study leader,” and the source of funding is “Shenzhen Science and Technology Innovation Free Exploration Project.” At the gene-editing summit, He said that he used some of his research funding in early stages of the experiment and covered the rest with his personal finances. Many university institutional review boards in the United States would consider such use of a researcher’s personal funds a serious conflict of interest.

The registration lists Shenzhen HarmoniCare Women and Children’s Hospital as the location of the experiment, complete with an ethics committee approval form from March 2017; that form bears seven signatures. The hospital has denied knowledge of and involvement in the experiment and claims the signatures were forged. Shenzhen HarmoniCare, as it turns out, belongs to the widely criticized Putian-clique of private hospitals. In recent years, many Putian hospitals have been whitewashing and upgrading their images by hiring professional staff and purchasing modern equipment. In addition to their traditional focus on sexually transmitted diseases and infertility, these newer establishments have branched into plastic surgery and advanced medicine allegedly powered by cutting-edge technology. But serious incidents have battered these attempted image makeovers, including the high profile death of a college student in 2016 after he received a discredited form of immunotherapy at a Putian hospital in Beijing.

Shenzhen HarmoniCare and He are hardly strangers. In 2015, the hospital’s parent company, the HarmoniCare Group, established a strategic collaboration agreement with He’s Direct Genomics to “establish and implement advanced genome testing.” In addition to the ties between HarmoniCare and He are those related to Lin Zhitong, a former director at He’s Direct Genomics. Lin is an administrator at Shenzhen HarmoniCare and chief executive of the medical division for Amer International Group. A privately owned conglomerate headquartered in Shenzhen, Amer Group donated $15 million to SUSTech in 2014, the largest donation in the university’s short history. The SUSTech-Amer fund was set up to support the commercialization of technology from SUSTech researchers.

Direct Genomics, of which He is the founder and chairman, released a statement late in November, saying it has “never developed or participated in genome editing” and “everything at the company from production to management is normal at the moment.” A representative from the company told reporters that its employees only learned about the gene-edited babies “from the news.”

According to a business plan allegedly from Direct Genomics, in a now-deletedreport by China Business Journal, the company operates a research institute that focuses on four areas, three of which concern gene sequencing, and the fourth gene editing. Its sequencing equipment has yet to receive licensing for medical use, but the company is optimistic in its pitch to investors, projecting $400 million in sales by 2021.

From SUSTech to Chinese authorities, from the hospital to He’s own companies, many parties connected in some way with He have claimed he kept them in the dark about his human experiment. On the other hand, He clearly has discussed his ideas and presented some work-in-progress with a number of colleagues in the United States over the past few years, some of whom tried to dissuade him on ethical grounds. Who knew exactly what, when remains a mystery. That He was able to forge ahead even though American colleagues knew or strongly suspected what he was doing, however, means that He’s human genetic editing experiment is not just an individual mistake. It also represents a systemic failure.

It is unclear how much the parents of Lulu and Nana—or the total of seven couples who allegedly took part in the experiment—understood about what they had signed up for. As reported by Lifeweek magazine in China in March of 2017, He approached the largest AIDS assistance nonprofit group in China for help recruiting couples in which the man is HIV positive and the woman is not. According to Lifeweek, the advertisement claimed to provide free sperm washing to remove HIV from it and an in vitro fertilization (IVF) procedure to ensure that only “washed” sperm could fertilize an egg.

Tens of millions of people in China suffer from infertility, but fertility clinics remain rare and the IVF process is prohibitively expensive for most Chinese families. Sperm washing could add another $20,000 to the $16,000 bill for a regular IVF procedure. The tantalizing promise of getting both procedures for free soon attracted more than 200 couples, according to Lifeweek. The couples were only told that “gene-editing” would be used somehow in the process after they signed up and passed the initial selection.

He Jiankui released the informed consent forms for the participants in his experiment, provided only in English, on his lab’s website. As the process went, one of his researchers first spoke with the couples about the details on the forms, and then He himself talked with each couple for “an hour and 10 minutes,” He said at the gene-editing summit. While it is not unusual for a researcher to personally handle the process of gaining consent from study subjects, He’s many companies and business deals related to genomic research and experimentation and his own financing of the Lulu and Nana experiment raise potentially serious conflict of interest questions.

Since his last public appearance at the gene-editing summit in Hong Kong, He had reportedly been “missing” according to multiple news outlets, even sparking rumors of house arrest. His silence was briefly broken when the troubled scientist responded to an email from the Harvard Crimson. “I will publish my paper and this question will be answered in my paper,” He wrote when asked by the student newspaper to respond to critiques of his work. STAT, a news website focused on biotech and life sciences, reported on December 10 that another paper of He’s on human genome editing was recently rejected over “concerns about both its ethics and its scientific validity.” The rejected paper, titled “Targeted PCSK9 genome editing in embryos by CRISPR-Cas9 system,” focused on a different gene from CCR5 for editing. According to its first page, as revealed by STAT, it has an author list of 15 individuals with 11 different institute affiliations.

Among the authors on the rejected paper was Michael Deem, He’s doctoral advisor at Rice. Deem owns shares in and is on the scientific advisory board of two of He’s companies. In AP’s initial story on November 26, Deem was quoted as saying he “met the parents [of Lulu and Nana]” and “was there for the informed consent of the parents.” Rice University has opened a “full investigation” into Deem’s actions. On December 13, Deem’s lawyers released a statement: “Michael [Deem] does not do human research and he did not do human research on this project,” the Houston Chronicle reported.

After such knowledge. “I want to remind everyone that we should do this slow and with caution, because a single case of failure may kill the entire field,” a scientist said, concluding his talk on human genome-editing at Cold Spring Harbor Laboratory in New York. The projector behind him showed a photo of Jesse Gelsinger, the first casualty of gene therapy, who had died in a US experiment in 1999. But this presentation came in summer of 2017. The speaker was He Jiankui, who had started recruiting HIV-positive couples for his gene-editing experiment months earlier.

I spoke with several of He’s former classmates and teachers at USTC while reporting this story, as well as many scientists in and out of China. The response to He’s actions was all but uniform; shock and criticism predominated. Some expressed concerns that one individual’s reckless behavior would cast all Chinese scientists in a negative light. A few worried that biology departments in the United States might hesitate to admit Chinese students in the future.

Is China the “Wild East” of bioethics? With its first ethics committee established by the Ministry of Health in 1998, the history of modern bioethics in China is short, and its record is tainted with fraud, corruption, and mad scientists. This has little to do with Chinese tradition itself, and the racialized lens through which ethics in China sometimes has been presented is a dangerous and misleading one. Daoism explicitly discourages human interference in the natural order: “one who would control it would ruin it; one who would grasp it would lose it,” said Laozi in Daode Jing, the fundamental text of Daoism. While Confucianism is more accepting of medical interventions, “it should not be done for reasons of vanity or productivity, and it certainly should not be done for profit,” Sam Crane, chair of Asian studies at Williams College and a specialist on ancient Chinese philosophy, explained to me in an interview.

A conventional Confucian approach would in fact be far stricter than a modern European one in its treatment of the human body, which the Confucian tradition sees as part of an unbroken and sacred lineage. Confucius taught his disciples that “one’s body, hair, and skin are bestowed from the parents, so one dares not harm them, and that is the foundation of filial piety.” Genome editing would be positively blasphemous. He’s experiment was not inspired by traditional Chinese culture, but rather facilitated by contemporary Chinese politics.

While some reports are calling He Jiankui “China’s Frankenstein,” his motivation seems to have been not so much obsession with nature’s wonders, but with the pursuit of fame and fortune. It is fair and necessary to criticize He’s actions. It would be a great missed opportunity, however, if all responsibility was placed on and all punishment directed at an individual, without serious reflection on the systemic weaknesses and institutional failures that created and enabled him.

He’s scientific career and personal wealth were not built just on solid work, but also on the publicity he sought, often with assistance from state propaganda organs and the manipulation of less reputable media. For his human gene-editing experiment, He produced elaborate video announcements, their release timed to coincide with the gene editing summit in Hong Kong and the publication of an ethics paper co-written with his in-house PR strategist, some rules from which He did not follow. Before He’s house of cards came tumbling down, one could catch glimpses of a carefully orchestrated PR campaign that included those claims in the Chinese state press about a “historic breakthrough.”

The Chinese government sees science and technology as tools of national greatness and advancements in them as matters of national pride. The country’s lack of Nobel laureates has created a national obsession with the Swedish award. Noting this sore point in the Chinese psyche, He concluded the ethics approval application for his gene-editing experiment with this note: “[Its significance] will surpass the invention of in vitro fertilization, which was awarded the Nobel Prize in 2010.”

The number of Nobel medals is a poor metric by which to measure a country’s scientific prowess. But China’s cumbersome bureaucracy and authoritarian politics, combined with its recent history of dire poverty and brutal persecution of scientists, have severely weakened its education and research sectors, hampering their progress. In an effort to catch up as quickly as possible, the Chinese government has used its economic might to aggressively pursue personnel and technology from overseas, often at a cost of reforming its own system and nurturing domestic talent.

The overemphasis on speed and over-reliance on overseas returnees to fulfill China’s techno-nationalistic ambitions have created what seems to me a toxic culture, ripe with scandal and fraud. China has been eager, for example, to develop its domestic semiconductor industry and no longer be dependent on US technology. Sensing a lucrative opportunity, a group of researchers in Shanghai, led by another US-trained Chinese scientist, purchased microchips from US companies, scratched off their logos, and claimed the designs as their own. The scam went on for years, earning lush funding and state honors, before it was finally exposed.

A diploma or academic title from the United States carries a certain aura in Chinese academic and business circles, often shielding the person’s work from proper scrutiny. He Jiankui notes on his SUSTech business card his PhD from Rice and postdoctoral experience at Stanford.

It’s too early to tell if He is indeed the amoral mastermind who deceived everybody. Even if others connected to him were all in the dark, as they have claimed, He’s gene-editing experiment would constitute a serious case of regulatory failure in the world’s most powerful surveillance state. When every Chinese person is under intense monitoring for the slightest hint of political disobedience, what the Chinese government chooses to look away from speaks volumes about its own priorities and ethics. There is a Communist Party branch at every school and every hospital, but an ethics committee is optional at such institutions, and the committees that do exist are often reduced to rubber stamps. Sometimes rules and regulations exist on paper, such as a 2003 guideline from the Ministry of Health that forbids gene editing of the human germline for reproductive purposes, but it is unclear how they should be enforced.

From the tragedy of the AIDS villages to the rise of the Putian hospitals, the medical industry in China is filled with scandals, and the needy and vulnerable often are the least protected and the most exploited. For decades, the Chinese government has conducted massive social engineering campaigns to control and “improve” its population. In its three-and-a-half decade run, the one-childpolicy was carried out with hundreds of millions of forced abortions and forced sterilizations. Now, the government is encouraging the “right” kind of urban, well-educated women to marry early and have more children, while furthering birth restrictions on some ethnic minorities and couples with major illnesses. These policies and their brutal enforcement have distorted public conception of personal autonomy and reproductive rights, hollowing out the foundation for bioethics in China.

In recent years, biotechnology has also become a powerful tool in the Chinese surveillance state. The Chinese government has turned its northwestern region of Xinjiang into a 21st-century police state. In addition to image and voice-based surveillance, the government has carried out mass collection of biometric data under the guise of mandatory health checkups.

When Big Brother has essentially free access to data collected by Big Tech, consumer privacy becomes another major concern. From Huawei to Tencent, the crown jewels in the Shenzhen tech industry are also important tools the Chinese government uses to monitor its citizens and extend influenceoverseas. How might genome data processed by He’s companies or other biotech firms in China be used by third parties, including the Chinese government? This is an essential question that must be included in the discussion on the future of genetics, in China or elsewhere.

When a scientist goes rogue, as apparently is the case with He Jiankui and his gene-editing experiment, or when a government fails its people, as with the Chinese government’s attempted cover-up of the AIDS villages, the public’s trust in institutions and expertise is weakened. He’s experiment has particular significance because of the technology used and its implications for all of humanity. His reckless actions exposed not only loopholes in the Chinese regulatory system, but also limitations in the global scientific community’s ability to self-regulate.

In the aftermath of He’s shocking experiment, the World Health Organization announced that it is creating a working group to study and develop “agreed norms and standards for the governance of human gene editing.” Biothreats recognize no human borders. Transparency and universal rules are required to establish a global bioethics framework in which every actor is at the table and held to the same standards.

“I grew up in a small farming family. … I will never forget my roots,” He Jiankui said in one of his YouTube videos. According to He’s father, his busy son has had little time to visit his hometown, but has supported his family financially, providing generous monthly allowances to his parents, more than a $150,000 to his older brother for a new house and car, and an offer to build another new residence for his parents, “ a large one, like a mansion.”

In ancient China, He’s hometown of Hunan and my hometown of Hubei both belonged to the Kingdom of Chu. The Chu people worshipped the sun and a mystical bird called Feng Huang, the Chinese phoenix. In modern Chinese vernacular, the phrase “Feng Huang nan,” or phoenix man, is used to describe someone who rose from humble beginnings to wealth and power. From the village of Xinhua to the city of Shenzhen by way of the United States, He Jiankui seems the embodiment of the phoenix man. With plenty of talent and an excess of ambition, he soared high and far. Seemingly unbound by rules or morals, he’s flown too close to the sun.

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