The manuscript of He Jiankui's paper is exposed, revealing the secrets of gene-edited babies

The unpublished manuscript, entitled "birth of twins after genome editing for HIV resistance", has 4699 English words written by he Jiankui, a Chinese biophysicistMIT Tech Review also received a second paper manuscript discussing laboratory research on human and animal embryos< br / > the descriptive text in these manuscript documents received by MIT technology review indicates that he Jiankui edited the two manuscripts in late November 2018, and that they seem to be the original manuscript submitted by him for publicationAfter being reviewed by at least two famous journals, nature and JAMA, his manuscript has not been published< br / > the body of the manuscript of the paper about the twin gene editors says that medical breakthroughs can "control the HIV epidemic"It claims that the use of a "new therapy" was "successful (the word was used more than once)" in making the two women babies resistant to HIVSurprisingly, however, it rarely tries to confirm that the twins are indeed resistant to the virusThe body of the manuscript largely ignores data elsewhere in the manuscript that suggests this kind of genetic editing is wrong< br / > MIT Tech Review shared these unpublished manuscript papers with four experts - a legal scholar, a test tube baby doctor, embryologist and gene editor, and asked for their commentsTheir point of view is that this approach is very unscientific, Among them: he Jiankui and his team's key claims are not supported by data; the parents of the twins reluctantly agreed to participate in the gene editing experiment under pressure; the so-called clinical benefits are questionable; these researchers started to make live gene editing babies before they fully understood the effect of their own gene editing< br / > because these manuscripts are related to one of the most important public health issues ever, namely, the ability to change human genetics by using gene editing technology, MIT Technology Review hereby publishes an excerpt from the manuscript of this paper on the "gene editing twins", as well as the comments of these experts, and answers their questionsThe excerpts are arranged in the order in which they appear in the manuscript of this paperWhy is there no doctor list in this manuscript? < br / > the manuscript begins with a list of authors - a total of 10 authors, most of whom are from he Jiankui's laboratory at South China University of science and technology, including Hua Bai, head of an AIDS support network that helps recruit AIDS couples, and Michael deem, an American biophysicistRice University is currently reviewing the role of deem in the gene editing experiment< br / > one of the reasons for the low number of people involved in this major program is the lack of names of some people, especially infertility doctors who treat patients and obstetricians and gynaecologists who deliver babiesHiding their names may be an attempt to hide the identity of the patientBut it's not clear whether the doctors understand that they are helping to make the first genetically edited babies < br / > for some people, this immediately raises the question of whether the manuscript is trustworthy Hank Greely, a law professor at Stanford University, said, "we have no or almost no independent evidence of anything reported in this manuscript Although I believe these babies are likely to be born after DNA Editing, there is very little evidence for this In view of this situation, I would not like to admit that he Jiankui is an honest researcher " < br / > 2 The researchers' own data do not support their main claim < br / > the abstract of the manuscript of this paper lists the objectives of this research project - to cultivate people resistant to HIV infection - and the main results achieved It points out that he Jiankui's research team has "successfully" replicated "a known mutation in the CCR5 gene A small proportion of people born naturally with this mutation (CCR5 Δ 32) are free from HIV infection < br / > but this kind of abstract is far beyond the scope of the data in the manuscript of this paper Specifically, as you will see later, the team did not actually replicate this known mutation Instead, they built new mutations that may or may not lead to HIV resistance According to the manuscript, they never verified it < br / > Fyodor urnov, a genome editing scientist at the Institute of innovative genomics at the University of California, Berkeley, said, "they claim to have replicated this popular CCR5 mutation, which is a blatant distortion of the actual data, and can only be described in one term: deliberate fabrication The study showed that he's team failed to replicate the popular CCR5 mutation The idea that embryo editors will help millions of people is absurd and laughable, as the 1969 moon walk "brings hope to millions of people seeking to live on the moon." Rita vassena, scientific director of eugin group, said, "when reading this paper, I hope to see a reflective and thoughtful editing method for human embryo genes Unfortunately, it reads more like an experiment in search of purpose, trying to find a reasonable reason to use CRISPR / cas9 technology in human embryos at all costs, rather than a serious, well thought out, step-by-step editing of the human genome for the benefit of future generations As indicated by the current scientific consensus, the use of CRISPR / cas9 in human embryos destined to lead to pregnancy is unreasonable and unnecessary at this stage and should not be continued " < br / > 3 Genetic editing of embryos does not control HIV, especially in the most affected countries < br / > the end of the abstract and the beginning of the text of this manuscript are where these authors find a reasonable reason for their research They suggest that genetically engineered babies can protect millions of people from HIV infection Critics of MIT Technology Review call this "absurd" and "absurd", and point out that even if CRISPR can produce people who are resistant to HIV, it is unlikely to work in places where HIV is rampant, such as southern Africa < br / > Rita vassena said, "this study provides insufficient evidence for editing and subsequent implantation of human embryos to produce pregnancy As the authors claim, the idea that genetically edited embryos might one day be able to control the 'HIV epidemic' is absurd Public health measures, education and the widespread use of antiviral drugs have been shown to control the HIV epidemic " < br / > Hank Greely said, "this is a feasible way to 'control the HIV epidemic', which seems ridiculous If every baby in the world gets this mutation (which is highly unlikely), it will start to substantially affect HIV infection within 20 to 30 years At that time, we should have better ways to contain the epidemic, and the existing methods, even if not sufficiently contained, will greatly delay it Compared with 2012, the number of new HIV cases in China increased by 64% (if true) in 2017, due to the low base China's HIV infection rate is far lower than that of western countries This situation is still more serious in some developing countries However, it is unreasonable to think that such a high-tech response may help these countries " The parents of the twin babies may want to participate in the gene editing experiment for the wrong reasons < br / > contrary to some explanations, the use of CRISPR on the DNA of the twin girls is not to prevent them from contracting HIV from the infected father As described in the manuscript, this is achieved through the mature technology of sperm washing Instead, the goal of this gene editing experiment is to make them immune to HIV in later life As a result, the experiment did not provide significant immediate medical benefits to them or their parents Why did the couple agree to attend? One reason may be for access to fertility treatment < br / > Rita vassena said, "I'm worried that the reason why the husband of the couple accepted this experimental genome editing is that he is HIV positive, because people can imagine that the unnecessary emotional stress the couple suffered caused them to agree to accept an experiment without any improvement in the health of the patient and their children, but with possible negative consequences It is worth remembering that HIV infection does not pass on from generation to generation like genetic diseases; embryos need to 'suppress' this infection Therefore, taking preventive measures, such as using appropriate drugs to control the patient's viral load, and handling gametes carefully during IVF, can effectively avoid HIV infection Current assisted reproductive technologies ensure that HIV positive men and women have safe offspring and avoid horizontal (partner to partner) and vertical (parent to embryo / foetus) transmission, thus eliminating the need to edit embryos in these situations In fact, the couple involved in the experiment did take such assisted reproductive measures, including long-term semen washing to remove all semen that might be HIV positive Longer term sperm washing has been used in IVF laboratories and thousands of patients worldwide for nearly two decades According to our experience and that of others, this is safe for parents and their future children, and does not require invasive manipulation of the embryo " < br / > Shane grove fertility, a reproductive endocrinologist, said, "in China, HIV positive can lead to significant social discrimination Despite strong family and social obligations to have a child, HIV positive people do not have access to infertility treatment In such a social environment, there are problems in carrying out this clinical research, and it is aimed at vulnerable groups of patients Is the study providing gene therapy for a social problem? Have the couple not been unduly forced? " < br / > 5 Gene editing in this study is different from mutations that confer natural HIV resistance < br / > in this study, the researchers described the changes CRISPR actually brought to the twins They took cells from in vitro fertilized embryos to study their DNA and found that the gene editor, who was trying to disable the CCR5 gene, did have a foothold < br / > however, although they "expect" these editors to give HIV resistance by inactivating the gene, they cannot know exactly this because they are "similar" to the naturally occurring CCR5 Δ 32 mutation, but not exactly the same Moreover, only two copies of the CCR5 gene in one embryo were edited; only one copy of the CCR5 gene in the other embryo was edited, which at best only gave partial HIV resistance "Success is blundering here," Hank Greely said None of the embryos had this CCR5 Δ 32 deletion mutation in millions of people Instead, these embryos / final babies have new mutations and their role is unclear Similarly, what does "partial resistance" to HIV mean? How to measure this partial resistance? Is it enough to prove that an embryo carrying the CCR5 gene, which has never been seen in humans, can be implanted into the womb for possible delivery? " < br / > 6 There may be other unwanted CRISPR edits