He Jiankui’s paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

The genetic editing of Chinese twins may have failed and produced unexpected mutations. This is the conclusion that scientists came to the conclusion after reading the manuscript of the paper by He Jiankui, an associate professor at the former Southern University of Science and Technology. Just now, some of the manuscripts of his paper, which he cast for nature and JAMA, the world’s leading international journal, were exposed by the MIT Technology Review, and the details of the baby gene editing study that shocked the world were revealed, full of lies.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

The so-called gene editing did not succeed in producing CCR5 mutations, but instead caused a bunch of other mutations. The effect son of these mutations on infants is unknown.

So when the manuscripts of these papers came to light, they immediately attracted attention. Some people have directly thrown out the question: what about the good accountability?

Gene Editing Experiment Truth: Full of Shameless and Absurdity

The MIT Technology Review invited experts in gene editing, reproductive science, and law to interpret the manuscript.

After reading the manuscript, they thought He Jiankui’s study was more of a purpose-seeking experiment, trying at all costs to find a reasonable reason for using CRISPR/Cas9 gene editing techniques in human embryos, which was “deliberate fraud” and “a serious breach of basic moral norms and even a crime”.

The experiment in He Jiankui was not as successful as he had been advertised, and was full of shamelessness and absurdity:

1, the experiment did not completely succeed in editing the gene.

The abstract points out that the project’s research aims to nurture people who are resistant to HIV, and lists the main results. He’s team argues that they “successfully” copied a genetic mutation called CCR5. A small percentage of people born with this variant gene (CCR5 delta 32) are immune to HIV infection.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

But the paper’s data are not sufficient to support the claims in the abstract. According to the paper, instead of actually replicating the known mutations, the team created new mutations that were questionable about whether they would be able to fight HIV.

And in the paper, the team never examined this.

The experimental data showed that only one of the twin babies had edited two copies of CCR5 from their parents;

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

Moreover, He’s team did find “off-target” (i.e. unnecessary editing), and the effect struck out of the baby’s genes, which was unclear.

2, after editing the gene, the experiment also did not verify whether the cell has HIV resistance.

Before babies are born, the same edited genes should be introduced into the laboratory’s immune cells before they are infected with HIV. If these cells survive, prove that the way the gene is edited is effective, the following experiments can continue.

However, He’s team chose not to test directly to the birth of a genetically edited baby. Blood is then taken from the twins to see if the edited cells are resistant to HIV.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

Some experts point out that the statement here means that the research team puts its interests at the top. There is also no evidence in the manuscript that edited CCR5 can help cells avoid HIV infection.

3. The doctor involved in the experiment may not know.

The manuscript shows that the paper consists of 10 authors, mainly from the lab of He Jiankui of the Southern University of Science and Technology, as well as Bai Qi, head of the White Forest National Alliance, a mutual aids support platform for couples who helped recruit couples involved in the experiment, and Michael Deem, an American biophysicist who is being vetted by Rice University.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

For an important research project, the authors listed in the paper are clearly only a small group of people – neither the reproductive surgeon who treats the patient nor the obstetrician who delivers the baby is on the list. The concealment of this information may be for the patient’s privacy, but that means it does not mean that people have no idea whether doctors are aware of the fact that they are helping to create the world’s first gene-editing baby.

Several media reports, including the Wall Street Journal, have pointed out that He’s team tricked doctors by changing blood samples, that the doctor in charge of sperm implants did not know that the twins’ genes had been edited, and that not everyone knew they were involved in the genetic editing of babies.

4. The baby’s parents may not know or be coerced.

In fact, current reproductive assistance techniques can prevent the children of AIDS patients from contracting the disease.

The couple in the experiment underwent antiretroviral therapy, in which case only the sperm washes to avoid infection in their children, and there was no need to use this unethical experimental intervention.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

The paper also mentions that gene editing is only intended to make children immune to HIV later in life.

In other words, the experiment did not provide obvious immediate medical benefits for the parents or their children, and even the children may suffer unknown negative consequences.

The couple may not have been told whether the technology was safe.

5, the experiment may have won the support of a Nobel Prize winner.

Now that infections can be avoided by washing, He’s team is trying to prove another benefit of the technique, preventing children from having “HEU syndrome,” a recommendation from 2006 Nobel Prize-winning medical laureate Craig Mello.

He was regularly contacted by Dr. Craig Mello, a molecular biologist at the University of Massachusetts, during the study, according to a Wall Street Journal investigation in May.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

He is also a board member of DirectGenomics, a gene sequencing company founded in 2012.

He informed Mello of the progress of the gene editing experiment and promised not to link Mello’s name to the project. This is another example of He Jiankui’s recognition of the ethical problems with the project.

6. Experiments may contain commercial purposes.

In the paper, He also thanked WR “Twink” Allen, a British horse breeding expert, and Jin Zhang, a former student of Allen, who is now the head of the New Hope Fertility Center in New York. The center is one of the largest fertility centers in New York.

According to MIT Technology Review, Zhang had planned to partner with He Jiankui late last year to set up a medical tourism business for gene-editing babies.

7, the manuscript misrepresents the birth time of the baby.

The twins were born in October, not November. He’s team used the wrong date to protect the anonymity of patients and their twins.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

According to the China Clinical Trial registry, the study will be registered on November 8, 2018.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

8, before the animal test has problems, still in the baby test.

In the supplement, He also attached a chart that publicly shows “when trying to analyze the ccR5 gene editing” and is a chromatography that measures DNA sequence readings found in the twins’ embryos and birth tissue (umbilical cord and placenta).

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

The experts found that the data suggested that the embryos were “chimerins”, suggesting that different cells in the embryos were edited differently.

In other words, these chimas may or may not have mixed cells that have been edited differently.

This means that cells with anti-HIV function are only part of it, and some cells are “off-target” edits that are not detected and can lead to potential risks.

Even more alarming is that when He Jiankui had previously experimented with animal embryos, he had discovered that the chimeric might be in trouble. Since there were real defects, he experimented with the baby.

The reason behind this, the manuscript of the paper is not disclosed, only one sentence:

The CCR5 gene was deep sinad for all samples to examine the mosaicism of gene editing.

In CCR5 gene editing, all DNA samples are deeply sequenced to check for chiclain problems.

There is no explanation of the problems found in the chart, and of course there is no recognition that there may be a problem with the table data.

An uproar, reigniting condemnation from all walks of life

So what could be the adverse effects of The He Jiankui team’s experiment?

CRISPR, as a gene editing tool, is not mature. The paper reported only one gene mutation outside of the target (Off-Target), but did not mean that there were no mutations elsewhere. The growth of twins is likely to be negatively affected by genetic mutations.

And given the birth date of the twins reported by Mr. He’s team, it is at odds with what many sources have revealed: if the date is forged, it will be more difficult to track the twins’ health in the future.

MIT science and technology commented that the use of technology to change human genetics is one of the most important public interest issues of all time. Therefore, this scientific and registration process has serious defects in the study, but also caused condemnation and concern.

Fyodor Urnov, a geneticist at the University of California, Berkeley, said the paper was a blatant distortion of actual data and a deliberate misrepresentation.

At all costs, says Rita Vassena, scientific director of the Eugin Group, they want to find a reasonable reason to use CRISPR in human embryos, without a well-thought-out approach. Such experiments are unreasonable, unnecessary and should not continue.

In addition, Hank Greely, a law professor at Stanford University, says that even if every baby is immunized against HIV through this treatment, there is no way to control the spread of THE disease in a short period of time. By the time, 20-30 years later, these babies will be of childbearing age, and by then it is likely that better ways to curb AIDS are possibly found.

Comments vary from angle to side, but most firmly believe that, as things stand, CRISPR should not be used in human embryos.

But since the incident has already taken place, many people hope to publish the results of the investigation.

He Jiankui's paper manuscript accidental exposure: HIV resistance has not been verified and causes unexpected mutation

After all, accountability for problems in the process also helps to avoid more similar incidents.

Resources:

Chinese scientist’s claims he created HIV-resistant ‘CRISPR babies’ a ‘deliberate falsehood’, researchers say

https://www.technologyreview.com/s/614764/chinas-crispr-babies-read-exclusive-excerpts-he-jiankui-paper/

https://www.wsj.com/articles/how-a-chinese-scientist-broke-the-rules-to-create-the-first-gene-edited-babies-11557506697?shareToken=st01b53b902a6a455493e8229db9058238&reflink=article_email_share

https://www.theguardian.com/science/2019/dec/04/china-gene-edited-baby-experiment-may-have-created-unintended-mutations

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