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The He Jiankui affair is a scientific and
bioethical
Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...
controversy concerning the use of
genome editing
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts ...
following its first use on humans by Chinese scientist
He Jiankui
He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
, who edited the genomes of
human embryo
Human embryonic development, or human embryogenesis, is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of de ...
s in 2018.
He became widely known on 26 November 2018 after he announced that he had created the first human genetically edited babies. He was listed in the ''
Time
Time is the continued sequence of existence and events that occurs in an apparently irreversible succession from the past, through the present, into the future. It is a component quantity of various measurements used to sequence events, to ...
''
's
100 most influential people
''Time'' 100 (often stylized as ''TIME'' 100) is an annual listicle of the 100 most influential people in the world, assembled by the American news magazine ''Time''. First published in 1999 as the result of a debate among American academics, po ...
of 2019. The affair led to legal and ethical controversies, resulting in the indictment of He and two of his collaborators, Zhang Renli and Qin Jinzhou. He eventually received widespread condemnation from all over the world.
He Jiankui, working at the
Southern University of Science and Technology
Southern University of Science and Technology (SUSTech) ) is a public research university in Nanshan District, Shenzhen, Guangdong, China. It changed its English name from South University of Science and Technology of China (SUSTC) to Sout ...
(SUSTech) in
Shenzhen
Shenzhen (; ; ; ), also historically known as Sham Chun, is a major sub-provincial city and one of the special economic zones of China. The city is located on the east bank of the Pearl River estuary on the central coast of southern province ...
, China, started a project to help people with
HIV-related fertility problems, specifically involving
HIV-positive
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...
fathers and HIV-negative mothers. The subjects were offered standard
''in vitro'' fertilisation services and in addition, use of
CRISPR gene editing
CRISPR gene editing (pronounced "crisper") is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense sys ...
(
CRISPR/Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
), a technology for modifying
DNA. The embryos' genomes were edited to remove the ''
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pro ...
'' gene in an attempt to confer
genetic resistance to HIV.
The clinical project was conducted secretly until 25 November 2018, when ''
MIT Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology, and editorially independent of the university. It was founded in 1899 as ''The Technology Review'', and was re-launched without "The" in ...
'' broke the story of the human experiment based on information from the Chinese clinical trials registry. Compelled by the situation, He immediately announced the birth of genome-edited babies in a series of five
YouTube
YouTube is a global online video platform, online video sharing and social media, social media platform headquartered in San Bruno, California. It was launched on February 14, 2005, by Steve Chen, Chad Hurley, and Jawed Karim. It is owned by ...
videos the same day.
The first babies, known by their pseudonyms Lulu () and Nana (), are twin girls born in October 2018, and the second birth or the third baby born was in 2019.
He reported that the babies were born healthy.
His actions received widespread criticism,
and included concern for the girls' well-being.
After presenting his research at the Second International Summit on Human Genome Editing at the
University of Hong Kong
The University of Hong Kong (HKU) (Chinese: 香港大學) is a public research university in Hong Kong. Founded in 1887 as the Hong Kong College of Medicine for Chinese, it is the oldest tertiary institution in Hong Kong. HKU was also the fi ...
on 28 November 2018, Chinese authorities suspended his research activities the following day.
On 30 December 2019, Chinese authorities announced that he was found guilty of forging documents and unethical conduct; he was sentenced to three years in prison with a three-million-
yuan fine (US$430,000).
Zhang Renli and Qin Jinzhou received an 18-month prison sentence, a 500,000-
yuan fine and were banned from working in assisted reproductive technology for life.
He Jiankui has been variously referred to as a "rogue scientist",
"China's
Dr Frankenstein
Victor Frankenstein is a fictional character and the main protagonist and title character in Mary Shelley's 1818 novel, ''Frankenstein; or, The Modern Prometheus''.. He is an Italian-Swiss scientist (born in Naples, Italy) who, after studying ...
", and a "mad genius". The impact of human gene editing on resistance to HIV infection and other body functions in experimental infants remains controversial. The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
had issued three reports on the guidelines of human genome editing since 2019,
and the Chinese government has prepared regulations since May 2019.
Origin
Since 2016, He Jiankui, then associate professor at the
Southern University of Science and Technology
Southern University of Science and Technology (SUSTech) ) is a public research university in Nanshan District, Shenzhen, Guangdong, China. It changed its English name from South University of Science and Technology of China (SUSTC) to Sout ...
(SUSTech) in Shenzhen, with Zhang Renli and Qin Jinzhou, have used human embryo in gene-editing technology for assisted reproductive medicine. On 10 June 2017, a Chinese couple, an HIV-positive father and HIV-negative mother, pseudonymously called Mark and Grace,
attended a conference held by He at SUSTech. They were offered
''in vitro'' fertilisation (IVF) along with gene-editing of their embryos so as to develop innate resistance to HIV infection in their offspring. They agreed to volunteer through
informed consent
Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
and the experiment was carried out in secrecy. Six other couples having similar fertility problems were subsequently recruited.
The couples were recruited through a Beijing-based AIDS advocacy group called Baihualin China League.
When later examined, the consent forms were noted as incomplete and inadequate.
The couple were reported to have agreed to this experiment because, by Chinese rules, normally HIV positive fathers were not allowed to have children using IVF.
When the place of the clinical experiment was investigated, SUSTech declared that the university was not involved and that He had been on unpaid leave since February 2018, and his department attested that they were unaware of the research project.
Experiment and birth
He Jiankui
He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
, the researcher, took sperm and eggs from the couples, performed ''in vitro'' fertilisation with the eggs and sperm, and then
edited the genomes of the embryos using
CRISPR/Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
.
The editing targeted a gene, ''
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pro ...
'', that codes for a protein that HIV uses to enter cells.
He was trying to reproduce the phenotype of a specific mutation in the gene, ''
CCR5-Δ32
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pr ...
'', that few people naturally have and that possibly confers
innate resistance to HIV
A small proportion of humans show partial or apparently complete innate resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the propor ...
,
as seen in the case of
the Berlin Patient
The Berlin patient is an anonymous person from Berlin, Germany, who was described in 1998 as exhibiting prolonged "post-treatment control" of HIV viral load after Management of HIV/AIDS, HIV treatments were interrupted.
The phrase "Berlin patient" ...
. However, rather than introducing the known CCR5-Δ32 mutation, He introduced a
frameshift mutation
A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels ( insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature ...
intended to make the CCR5 protein entirely nonfunctional.
According to He, Lulu and Nana carried both functional and mutant copies of ''CCR5'' given
mosaicism
Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized e ...
inherent in the present state of the art in germ-line editing.
There are forms of HIV that use a different receptor instead of CCR5; therefore, the work of He did not theoretically protect Lulu and Nana from those forms of HIV.
He used a
preimplantation genetic diagnosis
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
process on the embryos that were edited, where three to five single cells were removed, and
fully sequenced them to identify
chimerism
A genetic chimerism or chimera ( ) is a single organism composed of cells with more than one distinct genotype. In animals, this means an individual derived from two or more zygotes, which can include possessing blood cells of different blood ty ...
and off-target errors. He says that during the pregnancy,
cell-free fetal DNA
Cell-free fetal DNA (cffDNA) is fetal DNA that circulates freely in the maternal blood. Maternal blood is sampled by venipuncture. Analysis of cffDNA is a method of non-invasive prenatal diagnosis frequently ordered for pregnant women of advanced ...
was fully sequenced to check for off-target errors, and an
amniocentesis
Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...
was offered to check for problems with the pregnancy, but the mother declined.
Lulu and Nana were born in secrecy in October 2018.
They were reported by He to be normal and healthy.
Revelation
He Jiankui was planning to reveal his experiments and the birth of Lulu and Nana at the Second International Summit on Human Genome Editing, which was to be organized at the
University of Hong Kong
The University of Hong Kong (HKU) (Chinese: 香港大學) is a public research university in Hong Kong. Founded in 1887 as the Hong Kong College of Medicine for Chinese, it is the oldest tertiary institution in Hong Kong. HKU was also the fi ...
during 27–29 November 2018. However, on 25 November 2018, Antonio Regalado, senior editor for biomedicine of ''MIT Technology Review'', posted on the journal's website about the experiment based on He Jiankui's applications for conducting clinical trial that had been posted earlier on the Chinese
clinical trials registry
Preregistration is the practice of registering the hypotheses, methods, and/or analyses of a scientific study before it is conducted. This can include analyzing primary data or secondary data. Clinical trial registration is similar, although it may ...
. At the time, He refused to comment on the conditions of the pregnancy.
Prompted by the publicity, He immediately posted about his experiment and the successful birth of the twins on YouTube in five videos the same day. The next day, the ''Associated Press
The Associated Press (AP) is an American non-profit news agency headquartered in New York City. Founded in 1846, it operates as a cooperative, unincorporated association. It produces news reports that are distributed to its members, U.S. newspa ...
'' made the first formal news, which was most likely a pre-written account before the publicity. His experiment had received no independent confirmation, and had not been peer review
Peer review is the evaluation of work by one or more people with similar competencies as the producers of the work (peers). It functions as a form of self-regulation by qualified members of a profession within the relevant field. Peer review ...
ed or published in a scientific journal
In academic publishing, a scientific journal is a periodical publication intended to further the progress of science, usually by reporting new research.
Content
Articles in scientific journals are mostly written by active scientists such as s ...
. Soon after He's revelation, the university at which He was previously employed, the Southern University of Science and Technology, stated that He's research was conducted outside of their campus. China's National Health Commission
The National Health Commission of the People's Republic of China is a cabinet-level executive department of the State Council which is responsible for formulating national health policies. It was formed on 19 March 2018. The ministry is headqu ...
also ordered provincial health officials to investigate his case soon after the experiment was revealed.
Amidst the furore, He was allowed to present his research at the Hong Kong meeting on 28 November under the title "''CCR5'' gene editing in mouse, monkey, and human embryos using CRISPR–Cas9". During the discussion session, He asserted, "Do you see your friends or relatives who may have a disease? They need help," and continued, "For millions of families with inherited disease or infectious disease, if we have this technology we can help them." In his speech, He also mentioned about a second pregnancy under the same experiment.[ No reports disclosed, the baby might have been born around August 2019, and the birth was affirmed on 30 December when the Chinese court returned a verdict mentioning that there were "three genetically-edited babies".
]
Reactions and aftermath
On the news of Lulu and Nana being born, the ''People's Daily
The ''People's Daily'' () is the official newspaper of the Central Committee of the Chinese Communist Party (CCP). The newspaper provides direct information on the policies and viewpoints of the CCP. In addition to its main Chinese-language ...
'' announced the experimental result as "a historical breakthrough in the application of gene editing technology for disease prevention." But scientists at the Second International Summit on Human Genome Editing immediately developed serious concerns. Robin Lovell-Badge
Robin Howard Lovell-Badge, CBE, FRS FMedSci is a British scientist most famous for his discovery, along with Peter Goodfellow, of the SRY gene on the Y-chromosome that is the determinant of sex in mammals. They shared the 1995 Louis-Jeantet P ...
, head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute
The Francis Crick Institute (formerly the UK Centre for Medical Research and Innovation) is a biomedical research centre in London, which was established in 2010 and opened in 2016. The institute is a partnership between Cancer Research UK, Impe ...
, who moderated the session on 28 November recalled that He Jiankui did not mention human embryos in the draft summary of the presentation. He received an urgent message on 25 November through Jennifer Doudna
Jennifer Anne Doudna (; born February 19, 1964) is an American biochemist who has done pioneering work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. Doudna was one of the first women to share a ...
of the University of California, Berkeley
The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
, a pioneer of the CRISPR/Cas9 technology, to whom he had confided the news earlier that morning. As the news already broke out before the day of the presentation, he had to be brought in by the University of Hong Kong security from his hotel. Nobel laureate David Baltimore
David Baltimore (born March 7, 1938) is an American biologist, university administrator, and 1975 Nobel laureate in Physiology or Medicine. He is President Emeritus and Distinguished Professor of Biology at the California Institute of Technolo ...
, the chair of the organizing committee of the summit, was the first to react after He's speech, and declared his horror and dismay at his work.[
He did not disclose the parents' names (other than their pseudonyms Mark and Grace) and they did not make themselves available to be interviewed, so their reaction to this experiment and the ensuing controversy is not known.] There was widespread criticism in the media and scientific community over the conduct of the clinical project and its secrecy, and concerns raised for the long term well-being of Lulu and Nana. Bioethicist Henry T. Greely of Stanford Law School
Stanford Law School (Stanford Law or SLS) is the law school of Stanford University, a private research university near Palo Alto, California. Established in 1893, it is regarded as one of the most prestigious law schools in the world. Stanford La ...
declared, "I unequivocally condemn the experiment," and later, "He Jiankui’s experiment was, amazingly, even worse than I first thought." Kiran Musunuru
Kiran Musunuru is an American cardiologist who is a Professor of Medicine at the University of Pennsylvania Perelman School of Medicine. He researches the genetics and genomics of cardiovascular and metabolic diseases. Musunuru is a leading exper ...
, one of the experts called on to review He's manuscript and who later wrote a book on the scandal, called it a "historic ethical fiasco, a deeply flawed experiment".
On the night of 26 November, 122 Chinese scientists issued a statement criticizing his research. They declared that the experiment was unethical, "crazy" and "a huge blow to the global reputation and development of Chinese science". The Chinese Academy of Medical Sciences
Peking Union Medical College (), founded in 1906, is a selective public medical college based in Dongcheng, Beijing, China. It is a Chinese Ministry of Education Double First Class University Plan university. The school is tied to the Peking Un ...
made a condemnation statement on 5 January 2019 saying that:
A series of investigations was opened by He's university, local authorities, and the Chinese government. On 26 November 2018, SUSTech released a public notification on its website condemning He's conduct, mentioning the key points as:
* The research work was conducted off-campus by Associate Professor He Jiankui without reporting to the university and the Department of Biology, and the university and the Department of Biology were unaware of it.
* The Academic Committee of the Department of Biology considers that Associate Professor He Jiankui's use of gene editing technology for human embryo research is a serious violation of academic ethics and academic standards.
* SUSTech strictly requires scientific research to comply with national laws and regulations and to respect and abide by international academic ethics and academic norms. The university will immediately hire authoritative experts to set up an independent committee to conduct an in-depth investigation, and will publish relevant information after the investigation.
On 29 November 2018, Chinese authorities suspended all of He's research activities, saying his work was "extremely abominable in nature" and a violation of Chinese law. He Jiankui was sequestered in a university apartment under some sort of surveillance, and may face serious consequences. On 29 January 2019, it was learned that a U.S. Nobel laureate Craig Mello
Craig Cameron Mello (born October 18, 1960) is an American biologist and professor of molecular medicine at the University of Massachusetts Medical School in Worcester, Massachusetts. He was awarded the 2006 Nobel Prize for Physiology or Medicine, ...
interviewed He about his experiment with gene-edited babies. In February 2019, He's claims were reported to have been confirmed by Chinese investigators, according to NPR News
National Public Radio (NPR, stylized in all lowercase) is an American privately and state funded nonprofit media organization headquartered in Washington, D.C., with its NPR West headquarters in Culver City, California. It differs from other ...
. Around that time, news reported that the Chinese government may have helped fund the CRISPR babies experiment, at least in part, based on newly uncovered documents.
Michael W. Deem, an American bioengineering professor at Rice University
William Marsh Rice University (Rice University) is a Private university, private research university in Houston, Houston, Texas. It is on a 300-acre campus near the Houston Museum District and adjacent to the Texas Medical Center. Rice is ranke ...
and He's doctoral advisor, was involved in the research, and was present when people involved in He's study gave consent. He was the only non-Chinese out of 10 authors listed in the manuscript submitted to ''Nature''. Deem came under investigation by Rice University after news of the work was made public. As of 31 December 2019, the university had not released a decision.
Stanford University also investigated its faculty of He's confidants including William Hurlbut, Matthew Porteus, and Stephen Quake
Stephen Ronald Quake (born 1969) is an American scientist, inventor and entrepreneur. He earned his B.S. in physics and M.S. in mathematics from Stanford in 1991 and his D.Phil. in physics from Oxford University in 1994 as a Marshall Scholar. Hi ...
, He's main mentor in gene editing. The university's review committee concluded that the accused "were not participants in e Jiankui’sresearch regarding genome editing of human embryos for intended implantation and birth and that they had no research, financial or organizational ties to this research."
On 21 January 2019, He was fired from his job at SUSTech and his teaching and research work at the university was terminated. The same day, the Guangdong Province administration investigated the "gene editing baby incident", which is explicitly prohibited by the state. On 30 December 2019, the Shenzhen Nanshan District People's Court sentenced He Jiankui to three years in prison and with a fine of 3 million RMB (US$430,000). Among the collaborators, only two were indicted – Zhang Renli of the Guangdong Academy of Medical Sciences and Guangdong General Hospital, received a two-year prison sentence and a 1-million RMB fine, and Qin Jinzhou of the Southern University of Science and Technology received an 18-month prison sentence and a 500,000 RMB fine. The three were found guilty of having "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women." Zhang and Qin were officially banned from working in assisted reproductive technology for life. In April 2022, He was released from prison.
In response to He's work, the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, formed a committee comprising "a global, multi-disciplinary expert panel" called the Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing "to examine the scientific, ethical, social and legal challenges associated with human genome editing (both somatic and germline)" in December 2018. In 2019, it issued a call to halt all work on human genome editing, and launched a global registry to track research in the field. It had issued three reports for the recommended guidelines on human genome editing since 2019. As of 2021, the committee stood by the grounds that while somatic gene therapies have become useful in several disease, germline and heritable human genome editing is still with risks, and should be banned.
In May 2019, Chinese government prepared gene-editing regulations stressing that anyone found manipulating the human genome by genome-editing techniques would be held responsible for any related adverse consequences. The Civil Code of the People's Republic of China
The Civil Code of the People's Republic of China ( zh, s=中华人民共和国民法典, p=Zhōnghuá Rénmín Gònghéguó Mínfǎ Diǎn), or in short Minfadian ( zh, s=民法典, p=Mínfǎ Diǎn) is the first complete civil code in the People's ...
was amended in 2020 that added Article 1009 which states: "any medical research activity associated with human gene and human embryo must comply with the relevant laws, administrative regulations and national regulation, must not harm individuals and violate ethical morality and public interest." It was enacted on 1 January 2021. A draft of the 11th Amendment to the Chinese Criminal Code in 2020 has incorporated three types of crime: the illegal practice of human gene editing, human embryo cloning and severe endangering of the security of human genetic resources; with penalties of imprisonment of up to 7 years and a fine.
As of December 2021, Vivien Marx reported in the ''Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
'' article that both children are healthy.
Technical controversies
Ethics
Genome manipulations can be done at two levels: somatic
Somatic may refer to:
* Somatic (biology), referring to the cells of the body in contrast to the germ line cells
** Somatic cell, a non-gametic cell in a multicellular organism
* Somatic nervous system, the portion of the vertebrate nervous sys ...
(grown-up cells of the general body) and germline
In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...
(sex cells and embryos for reproduction). The development of CRISPR gene editing
CRISPR gene editing (pronounced "crisper") is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense sys ...
enabled both somatic
Somatic may refer to:
* Somatic (biology), referring to the cells of the body in contrast to the germ line cells
** Somatic cell, a non-gametic cell in a multicellular organism
* Somatic nervous system, the portion of the vertebrate nervous sys ...
and germline editing (such as in assisted reproductive technology
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
). There is no prohibition on somatic gene editing since the practice is generally covered by the available regulations. Prior to He's affair, there was already a big concern that it was possible to make genetically modified babies and such experiments would have ethical issues as the safety and success were not yet warranted by any study, and genetic enhancement of individual would be possible. Pioneer gene-editing scientists had warned in 2015 that "genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications." As Janet Rossant
Janet Rossant, (born 13 July 1950) is a developmental biologist well known for her contributions to the understanding of the role of genes in embryo development. She is a world renowned leader in developmental biology. Her current research inte ...
of the University of Toronto noted in 2018: "It has also raised ethical concerns, particularly with regard to the possibility of generating heritable changes in the human genome – so-called germline gene editing." In 2017, the National Academies of Sciences, Engineering, and Medicine
The National Academies of Sciences, Engineering, and Medicine (also known as NASEM or the National Academies) are the collective scientific national academy of the United States. The name is used interchangeably in two senses: (1) as an umbrell ...
published a report "''Human Genome Editing: Science, Ethics and Governance''" that endorsed germline gene editing in "the absence of reasonable alternatives" of disease management and to "improve IVF procedures and embryo implantation rates and reduce rates of miscarriage." However, the Declaration of Helsinki
The Declaration of Helsinki (DoH, fi, Helsingin julistus, sv, Helsingforsdeklarationen) is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA) ...
had stated that early embryo genome-editing for fertility purposes is unethical.
The American Society of Human Genetics
The American Society of Human Genetics (ASHG), founded in 1948, is a professional membership organization for specialists in human genetics. As of 2009, the organization had approximately 8,000 members. The Society's members include researchers, a ...
had declared in 2017 that the basic research on ''in vitro'' human genome editing on embryos and gametes should be promoted but that "At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy." In July 2018, the Nuffield Council on Bioethics
The Nuffield Council on Bioethics is a UK-based independent charitable body, which examines and reports on bioethical issues raised by new advances in biological and medical research. Established in 1991, the Council is funded by the Nuffield F ...
published a policy document titled ''Genome Editing and Human Reproduction: Social and Ethical Issues'' in which it advocated human germline editing saying that it "is not 'morally unacceptable in itself' and could be ethically permissible in certain circumstances" when there are sufficient safety measures. The moral justification created critical debates. The United States National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
Somatic Cell Genome Editing Consortium held that it "strictly focused on somatic editing; germline editing is not only excluded as a goal but is also considered to be an unacceptable outcome that should be carefully prevented."
The Chinese law ''Measures on Administration of Assisted Human Reproduction Technology'' (2001) prohibits any genetic manipulation of human embryos for reproductive purposes and allow assisted reproductive technology
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
to be performed only by authorized personnel. On 7 March 2017, He Jiankui applied for ethics approval from Shenzhen HarMoniCare Women and Children's Hospital. In the application, He claimed that the genetically edited babies would be immune to HIV infection, in addition to smallpox and cholera, commenting: "This is going to be a great science and medicine achievement ever since the IVF technology which was awarded the Nobel Prize in 2010, and will also bring hope to numerous genetic disease patients." It was approved and signed by Lin Zhitong, the hospital administrator and one-time Director of Direct Genomics, a company established by He. Upon an inquiry, the hospital denied such approval. The hospital's spokesperson declared that there were no records of such ethical approval, saying, " hegene editing process did not take place at our hospital. The babies were not born here either." It was later confirmed that the approval certificate was forged.
Sheldon Krimsky
Sheldon Krimsky (February 18, 1942 – April 25, 2022) was a professor of Urban and Environmental Policy and Planning at Tufts University, and adjunct professor in the Department of Family Medicine and Community Health at Tufts University School ...
of Tufts University reported that " e Jiankuiis not a medical doctor, but rather received his doctorate in biophysics and did postdoctoral studies in gene sequencing; he lacks training in bioethics." However, He was aware of the ethical issues. On 5 November 2018, He and his collaborators submitted a manuscript on ethical guidelines for reproductive genome editing titled "Draft Ethical Principles for Therapeutic Assisted Reproductive Technologies" to ''The CRISPR Journal
''The CRISPR Journal'' is a peer-reviewed scientific journal published every two months by Mary Ann Liebert. It covers research on all aspects of CRISPR research, including its uses in synthetic biology and genome editing. Its editor-in-chief i ...
''. It was published on 26 November, soon after news of the human experiment broke out. The journal made an inquiry concerning conflicts of interests, which was not disclosed by He. With no justification from He, the journal retracted the paper with a comment that it "was most likely in violation of accepted bioethical international norms and local regulations."
Although there were no specific laws in China on gene editing in humans, He Jiankui violated the available guideline on handling human embryos. According to the ''Guidelines for Ethical Principles in Human Embryonic Stem Cell Research'' (2003) of the Ministry of Science and Technology and the National Health Commission of China:Research in human embryonic stem cells shall be in compliance with the following behavioral norms:
# Where blastula is obtained from external fertilization, somatic nucleus transplantation, unisexual duplicating technique or genetic modification, the culture period in vitro shall not exceed 14 days from the day of fecundation or nuclear transplantation.
He Jiankui also attended an important meeting on "the ethics and societal aspects of gene editing" in January 2017 organized by Jennifer Doudna and William Hurlbut of Stanford University. Upon invitation from Doudna, He presented a topic on "Safety of Human Gene Embryo Editing" and later recalled that "There were very many thorny questions, triggering heated debates, and the smell of gunpowder was in the air."
The consent form of the experiment titled "Informed Consent" also indicates dubious statements. The aim of the study was presented as "an AIDS vaccine development project", even though the study was not about vaccines. Present was technical jargon which would be incomprehensible to a layperson. One of the more peculiar statement is that if the participants decide to abort the experiment "in the first cycle of IVF until 28 days post-birth of the baby", they would have to "pay back all the costs that the project team has paid for you. If the payment is not received within 10 calendar days from the issuance of the notification of violation by the project team, another 100,000 RMB ver £11,000of fine will be charged." This violates the voluntary nature of the participation.
Publication
Scientific works are normally published in peer-reviewed journals, but He failed to do so regarding the birth of gene-edited babies. This was one of the grounds on which He was criticized. It was later reported that He did submit two manuscripts to ''Nature
Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...
'' and the ''Journal of the American Medical Association
''The Journal of the American Medical Association'' (''JAMA'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of bio ...
'', which were both rejected, mainly on ethical issues. He's first manuscript titled "Birth of Twins After Genome Editing for HIV Resistance" was submitted to ''Nature'' on 19 November. He shared copies of the manuscript to the Associated Press, which he further allowed to document his works. In an interview, Hurlbut opined that the condemnation of He's work would have been less harsh if the study had been published, and said, "If it had been published, the publishing process itself would have brought a level of credibility because of the normal scrutiny involved; the data analysis would have been vetted."
The scientific manuscripts of He were revealed when an anonymous source sent them to the ''MIT Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology, and editorially independent of the university. It was founded in 1899 as ''The Technology Review'', and was re-launched without "The" in ...
'', which reported them on 3 December 2019.
Scientific basis
It is an established fact that C-C chemokine receptor type 5 (CCR5) is a protein essential for HIV infection of the white blood cells by acting as co-receptor
A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.
Properties
The t ...
to HIV. Mutation in the gene ''CCR5'' (called ''CCR5Δ32'' because the mutation is specifically a deletion of 32 base pairs
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
in human chromosome 3) renders resistance to HIV. Resistance is higher when mutations are in two copies ( homozygous alleles) and in only one copy (heterozygous alleles) the protection is very weak and slow. And not all homozygote individuals are completely resistant. In natural population, ''CCR5Δ32'' homozygotes are rarer than heterozygotes. In 2007, Timothy Ray Brown
Timothy Ray Brown (March 11, 1966September 29, 2020) was an American considered to be the first person cured of HIV/AIDS. Brown was called "The Berlin Patient" at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure ...
(dubbed the Berlin patient) became the first person to be completely cured of HIV infection following a stem cell transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...
from a ''CCR5Δ32'' homozygous donor.
He Jiankui overlooked these facts. Two days after Lulu and Nana were born, their DNA were collected from blood samples of their umbilical cord
In placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologic ...
and placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
. Whole genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a s ...
confirmed the mutations. However, available sources indicate that Lulu and Nana are carrying incomplete ''CCR5'' mutations. Lulu carries a mutant ''CCR5'' that has a 15-bp in-frame deletion
Deletion or delete may refer to:
Computing
* File deletion, a way of removing a file from a computer's file system
* Code cleanup, a way of removing unnecessary variables, data structures, cookies, and temporary files in a programming language
* ...
only in one chromosome 3 (heterozygous allele) while the other chromosome 3 is normal; and Nana carries a homozygous mutant gene with a 4-bp deletion and a single base insertion
Insertion may refer to:
*Insertion (anatomy), the point of a tendon or ligament onto the skeleton or other part of the body
*Insertion (genetics), the addition of DNA into a genetic sequence
*Insertion, several meanings in medicine, see ICD-10-PCS
...
. He therefore failed to achieve the complete 32-bp deletion. Moreover, Lulu has only heterozygous modification which is not known to prevent HIV infection. Because the babies' mutations are different from the typical ''CCR5Δ32'' mutation it is not clear whether or not they are prone to infection. There are also concerns about adverse effect called off-target mutation in CRISPR/Cas9 editing and mosaicism, a condition in which many different cells develop in the same embryo.[ Off-target mutation may cause health hazards, while mosaicism may create HIV susceptible cells. Fyodor Urnov, Director at the Altius Institute for Biomedical Sciences at Washington, asserted that "This ff-target mutationis a key problem for the entirety of the embryo-editing field, one that the authors sweep under the rug here," and continued, "They e's teamshould have worked and worked and worked until they reduced mosaicism to as close to zero as possible. This failed completely. They forged ahead anyway."]
He's data on Lulu and Nana's mutation alignment (in Sanger chromatogram) showed three modifications, while two should be expected. Particularly in Lulu, the mutation is much more complex than He's report. There were three different combinations of alleles: two normal copies of ''CCR5'', one normal copy and one with a 15-bp deletion, and one normal copy and an unknown large insertion. But George Church of Harvard University, in an interview with ''Science
Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe.
Science may be as old as the human species, and some of the earliest archeological evidence for ...
'', explained that off-target mutations may not be dangerous, and that there is no need to reduce mosaicism excessively, saying, "There's no evidence of off-target causing problems in animals or cells. We have pigs that have dozens of CRISPR mutations and a mouse strain that has 40 CRISPR sites going off constantly and there are off-target effects in these animals, but we have no evidence of negative consequences." As to mosaicism, he said, "It may never be zero. We don’t wait for radiation to be zero before we do positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
scans or x-rays."
In February 2019, scientists reported that Lulu and Nana may have inadvertently (or perhaps, intentionally) had their brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
s altered, since CCR5 is linked to improved memory function in mice, as well as enhanced recovery from strokes in humans. Although He Jiankui stated during the Second International Summit on Human Genome Editing, that he was against using genome editing for enhancement, he also acknowledged that he was aware of the studies linking CCR5 to enhanced memory function.
In June 2019, researchers suggest that the purportedly genetically edited humans may have been mutated in a way that shortens life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
. Rasmus Nielsen and Wei Xinzhu, both at the University of California, Berkeley, reported in ''Nature Medicine
''Nature Medicine'' is a monthly Peer review, peer-reviewed medical journal published by Nature Portfolio covering all aspects of medicine. It was established in 1995. The journal seeks to publish research papers that "demonstrate novel insight int ...
'' of their analysis of the longevity of 409,693 individuals from British death registry (UK BioBank
UK Biobank is a large long-term biobank study in the United Kingdom (UK) which is investigating the respective contributions of genetic predisposition and environmental exposure (including nutrition, lifestyle, medications etc.) to the developmen ...
) with the conclusion that two copies of ''CCR5Δ32'' mutations (homozygotes) were about 20% more likely than the rest of the population to die before they were 76 years of age. The research finding was widely publicized in the popular and scientific media. However, the article overlooked sampling bias in UK Biobank's data, resulting in an erroneous interpretation, and was retracted four months later.
Related research
The first successful gene-editing experiment of ''CCR5'' in humans was in 2014. A team of researchers at the University of Pennsylvania
The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...
, Philadelphia, Albert Einstein College of Medicine
Albert Einstein College of Medicine is a research-intensive medical school located in the Morris Park neighborhood of the Bronx in New York City. Founded in 1953, Einstein operates as an independent degree-granting institution as part of t ...
, New York, and Sangamo BioSciences, California, reported that they modified ''CCR5'' on the blood cells (CD4 T cells) using zinc-finger nuclease
Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enables zinc ...
which they introduced ( infused) into 12 individuals with HIV. After complete treatment, the patients showed decreased viral load, and in one, HIV disappeared. The result was published in ''The'' ''New England Journal of Medicine''.
Chinese scientists have successfully used CRISPR editing to create mutant mice and rats since 2013. The next year they reported successful experiment in monkeys involving a removal of two key genes ( PPAR-γ and RAG1
Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the ''RAG1'' gene.
The RAG1 and RAG2 genes are largely conserved in humans. 55.99% and 55.98% of the encoded amino acids contain no reported variants, re ...
) that play roles in cell growth and cancer development. One of the leading researchers, Yuyu Niu later collaborated with He Jiankui in 2017 to test the CRISPR editing of ''CCR5'' in monkeys, but the outcome was not fully assessed or published. Niu later commented that they "had no idea he was going to do this in a human being." In 2018, his team reported an induction of mutation to produce muscular dystrophy, and simultaneously by another independent Chinese team an induction of growth retardation in monkeys using CRISPR editing. In February 2018, scientists at the Chinese Academy of Sciences reported the creation of five identical cloned
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...
gene-edited monkeys, using the same cloning technique that was used by them to create the first cloned primates Zhong Zhong and Hua Hua
Zhong Zhong (, born 27 November 2017) and Hua Hua (, born 5 December 2017) are a pair of identical crab-eating macaques (also referred to as cynomolgus monkeys) that were created through somatic cell nuclear transfer (SCNT), the same cloning tec ...
in 2018 and Dolly the sheep
Dolly (5 July 1996 – 14 February 2003) was a female Finnish Dorset sheep and the first mammal cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a ...
. The mutant monkeys and clones were made for understanding several medical diseases and not for disease resistance.
The first clinical trials of CRISPR-Cas9 for the treatment of genetic blood disorders was started in August 2018. The study was jointly conducted by CRISPR Therapeutics
CRISPR Therapeutics AG is a Swiss–American biotechnology company headquartered in Zug, Switzerland. In fiscal year 2021, the company had revenues of $915 million, with net income of $378 million. By the end of the same year, the num ...
, a Swiss-based company, and Vertex Pharmaceuticals
Vertex Pharmaceuticals is an American biopharmaceutical company based in Boston, Massachusetts. It was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. It maintains headqua ...
, headquartered in Boston. The result was first announced on 19 November 2019 which states that the first two patients, one with β-thalassemia
Beta thalassemias (β thalassemias) are a group of genetic disorder, inherited hemoglobinopathy, blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the HBB, beta chains of hemoglobin that result in variable out ...
and the other with sickle cell disease
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
, were treated successfully. Under the same project, a parallel study on 6 individuals with sickle cell disease was also conducted at Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
, Boston. In both studies, the gene involved in blood cell formation ''BCL11A
B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the ''BCL11A'' gene.
Function
The ''BCL11A'' gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript va ...
'' was modified in the bone marrow extracted from the individuals. Both the studies were simultaneously published in ''The'' ''New England Journal of Medicine'' on 21 January 2021 in two papers. The individuals have not complained the symptoms and needed blood transfusion normally required in such disease, but the method is arduous and poses high risk of infection in the bone marrow, to which David Rees at King's College Hospital
King's College Hospital is a major teaching hospital and major trauma centre in Denmark Hill, Camberwell in the London Borough of Lambeth, referred to locally and by staff simply as "King's" or abbreviated internally to "KCH". It is managed by K ...
commented, "Scientifically, these studies are quite exciting. But it’s hard to see this being a mainstream treatment in the long term."
In June 2019, Denis Rebrikov at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow announced through ''Nature'' that he was planning to repeat He's experiment once he got official approval from the Russian Ministry of Health and other authorities. Rebrikov asserted that he would use safer and better method than that of He, saying, "I think I'm crazy enough to do it." In a subsequent report on 17 October, Rebrikov said that he was approached by a deaf couple for help. He already started ''in vitro'' experiment to repair a gene that causes deafness, ''GJB2
Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the ''GJB2'' gene.
Clinical significance
Defects in this gene lead to the most common form of congenital deafness in developed c ...
'', using CRISPR.
In 2019, the Abramson Cancer Center
The Ruth and Raymond Perelman Center for Advanced Medicine is a specialized medical facility located at 34th Street and Civic Center Boulevard, on the former site of the Philadelphia Civic Center, on the campus of the Hospital of the University ...
of the University of Pennsylvania
The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...
in US announced the use of the CRISPR technology to edit cancer genes in humans, and the results of the phase I clinical trial in 2020. The study started in 2018 with an official registration in the US clinical trials registry. The report in the journal ''Science'' indicates three individuals in their 60s with advanced refractory cancer Resistant cancer or refractory cancer is the cancer that does not respond to medical treatment. It may be resistant at the beginning of treatment, or it may become resistant during treatment.
See also
* Antineoplastic resistance
* Drug resistan ...
, two of them with the blood cancer (multiple myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...
) and one with tissue cancer (sarcoma
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
), were treated with their own cancer cells after CRISPR editing. The experiment was based on CAR T-cell therapy
A car or automobile is a motor vehicle with wheels. Most definitions of ''cars'' say that they run primarily on roads, seat one to eight people, have four wheels, and mainly transport people instead of goods.
The year 1886 is regarded as t ...
by which the T cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
, obtainted from the individuals were removed of three genes involved in cancer and were added a gene ''CTAG1B
Cancer/testis antigen 1 also known as LAGE2 or LAGE2B is a protein that in humans is encoded by the ''CTAG1B'' gene. It is most often referenced by its alias NY-ESO-1.
Cancer/Testis Antigen 1B is a protein belonging to the family of Cancer Testi ...
'' that produces an antigen NY-ESO-1. When the edited cells were introduced back into the individuals, the antigens attack the cancer cells. Although the results were acclaimed as the first "success of gene editing and cell function" in cancer research and "an important milestone in the development and clinical application of gene-edited effector cell therapy," it was far from curing the diseases. One died after the clinical trial, and the other two had recurrent cancer.
A similar clinical trial was reported by a team of Chinese scientists at the Sichuan University
Sichuan University (SCU) is a National university, national National Key Universities, key public university, public research university in Chengdu, Sichuan, China. The university is wholly funded by Ministry of Education of the People's Republic ...
and their collaborators in 2020 in ''Nature Medicine
''Nature Medicine'' is a monthly Peer review, peer-reviewed medical journal published by Nature Portfolio covering all aspects of medicine. It was established in 1995. The journal seeks to publish research papers that "demonstrate novel insight int ...
''. Here they removed only one gene (''PDCD1'' that produces the protein PD-1
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regula ...
) in the T cells from 12 individuals having late-stage lung cancer. The study was found to be safe and effective. However, the edited T cells were not fully efficient and disappeared in most individuals, indicating that the treatments were not completely successful.
See also
* Designer baby
A designer baby is a baby whose genetics, genetic makeup has been selected or altered, often to not include a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to ide ...
* ''Human Nature'' (2019 CRISPR film documentary)
* ''Unnatural Selection'' (2019 TV documentary)
References
External links
Official WebSite/Jiankui He
He's presentation and subsequent panel discussion
at the Second International Summit on Human Genome Editing. 27 November 2018, via Bloomberg Asia's Facebook page
{{DEFAULTSORT:affair, He Jiankui
Genome editing
History of HIV/AIDS
Identical twins
He, Jiankui
Science and technology in China
Biology controversies
Ethically disputed medical practices
2018 in biology
2018 in China
2018 controversies
He, Jiankui