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Scientists, ethics slam decisions behind gen-edited twins

Enlarge / Chinese geneticist He Jiankui speaks during the Second International Summit on Human Genome Editing at the University of…

 Chinese geneticist He Jiankui speaks during the Second International Summit on Human Genome Editing at the University of Hong Kong days after the Chinese geneticist claimed to have altered the genes of the embryo of a pair of twin girls before birth, prompting outcry from scientists of the field.

Enlarge / Chinese geneticist He Jiankui speaks during the Second International Summit on Human Genome Editing at the University of Hong Kong days after the Chinese geneticist claimed to have altered the genes of the embryo of a couple of twin girls before birth, prompting outcry from scientists of the field.

If more details about the first gen-edited humans are released, things continue to look worse. The researcher who claimed the advance, He Jiankui, has now given a public talk that includes many details about the changes made at the DNA level. De detaljer gør et par ting klart: Vi vet ikke om redigeringen vil beskytte de to børn fra HIV-infektioner, og vi kan ikke se om nogen områder af genomet har blitt skadet ved proceduren.

All of Dat raakt nog meer vragen alsof Hij deed ethische richtlijnen bij het uitvoeren van het werk en het krijgen van toestemming van de ouders. And, more generally, nobody is sure why He chose to ignore a strong consensus that the procedure was not yet ready for use in humans. In reaksie op de outcry heeft de Chinese regering de verdere onderzoek door He afgesloten, evenals het werd geopenbaard dat een derde genedigde baby misschien op de weg staat.

Terwijl de VS reeds regels hebben opgesteld die zijn bedoeld to keep research like He’s from happening, a legal scholar Ars spoke with suggested there may be a loophole that could allow something similar here. In light of that, it’s important to understand the big picture He has potentially altered.

Technical failures

Prior to this work, a strong consensus existed among the scientific community that, although technology for editing the human genome was available, We did not know enough yet about how to check its safety and effectiveness to determine how to ethically use it. And, as it turns out, he’s work seems to provide a demonstration of almost everything that had the research community concerned.

(Researchers at the conference where He spoke provided a transcript of his talk and shared his slides ; other details have come out via data he shared with the AP.)

The aim of the editing was to damage the CCR5 gene, which encodes a protein that uses HIV to enter cells during infection. He and his colleagues used a gene-editing technique that is expected to generate small deletions. De rettet mod en af ​​disse deletioner til et sted i midten af ​​genet, som er stedet for en mutation, der forhindrer HIV-infektion. De data som deles så langt indikerer at de var vellykkede med hensyn til genererende deletioner, men om de ikke aktiverede genene, er langt mindre klare.

When a gene is translated into a protein, its DNA is read using a code where three of the bases in DNA encode one of the amino acids in a protein. This makes a gen very sensitive to whether deletions eliminate a number of bases that are a multiple of three. If a deletion takes out six or nine bases, for example, the resulting protein will only be missing two or three amino acids, respectively. Thus, it may be able to function normally. Hvis den deletion ikke fjerner en flere eller tre, hvis det tar 11 eller 16 baser, for eksempel, så vil resten av geneene ikke bli lest korrekt. You would end up switching to the protein equivalent of random keyboard bashing, often stopping the protein very short.

In the case of one of the twins born, the deletion eliminates 15 base pairs meaning the CCR5 protein will lack five amino acids but otherwise be normal. In de tweede tweeling, sommige of deze cellen zullen hebben een vier basispaar deletie, die zal leiden tot een korte tail of 10 random aminozuren. Other cells will actually have an extra base, which also results in a randomization of the amino acids that follow, although the tail is much longer in this case.

The key thing for the twins’ health and safety is that we have no idee of een of deze eiwitten zullen worden gemaakt en geplaatst op het celoppervlak als normaal en, als ze zijn, of HIV kan interageren met hen. Alle van deze dingen kunnen worden getest, maar hij heeft gegeven geen indicatie of of die tests zijn gedaan.

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] Quantifying risk (or not)

The fact that one of the two twins has different deletions also points to another worrying aspect to this work: not every cell in the embryo was edited at the same time and in the same way, even selv om editing maskiner blev injiceret, når embryoen var en enkelt celle. The resulting embryos could be a mosaic of unedited cells and cells with different types of damage to the intended gene. In feite, we now know that one of the twins also has some cells where one copy of the gene was not edited at all meaning this twin has thus taken on the risks of gene editing without the supposed benefit of HIV protection.

This also means we do not know which of these changes (if any) will be inherited by any kids the twins have.

The risk of gene editing is that the process sometimes leads to what are called “off target” effects: deletions elsewhere in the genomic or more complex rearrangements of the DNA. Either of these could potentially damage or alter genes that are not the intended targets of the editing, which would have unpredictable effects on health. To check for these, He allowed the edited embryos to develop to the point where it was safe to remove several cells; DNA from these cells was then sequenced and the sequence compared to that of the two parents.

Unfortunately, the techniques that allow sequencing from extremely small samples such as these are relatively inefficient. As a result, he was only able to obtain 80-90 percent of the genomes of the edited embryos. If there was damage in the remaining percentage, he did not know. Og på grund av den mosaiske natur af embryoerne, er det ikke engang klart om DNA-sekvenserne blev opnået repræsentative for resten af ​​embryoen.

I de oplysninger der blev opnået, var der imidlertid en indikation af off-target skade . En fordi det ikke var i umiddelbar nærhed af en gen, besluttede han at det var acceptabelt at fortsætte, selvom skadene kunne påvirke genaktivitet eller chromosom struktur.

I sum, the data available so far indicates that we do ikke vet om redigeringen vil faktisk beskytte enten de to tvillinger fra HIV-infektion, det ostensible mål for arbejdet. Og som vi noterede i vores originale dekning, er der andre, mindre drastiske måder eller forebyggelse af HIV-infektioner og behandlinger, der er tilgængelige, hvis de fejler. Even als gen editing was gebruikt, zou het kunnen worden gebruikt op de bloedstamcellen die zich in de beenmerg bevinden, eerder dan op een embryo.

Op dezelfde tijd, deze procedure blootstelde de twintigen dat risico’s we niet kunnen volstaan catalog and do not currently understand. As the University of Wisconsin bioethicist Alta Charo said, “Having listened to Dr. He, I can only conclude that this was misguided, premature, unnecessary, and largely useless. “

Pilar Ossorio, a bioethics scholar at the University of Wisconsin’s Morgridge Institute, echoed her concerns. “Han skapte risikoen for at disse børn vil lide af noget som de ikke behøver at lide,” fortalte hun Ars. “And we will not get good scientific information out of that.”

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