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Colorado professor on a Chinese genomic child, health concern



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George Seidel, Colorado State University

On November 28, He Jiankui said that at a conference at the Second International Human Growth Review Summit in Hong Kong, the genome of two twins Lulu and Nan was born in China.

Scientists at the South University of Science and Technology in Guangdong, China, condemned He's research claiming that "he seriously violated academic ethics and code of conduct," and philosophers and bioethics quickly dived into the sea of ​​editing human genomes. That's why I will not cover that territory. What I want to answer is what we learned: how did these babies do.

I'm a theoretically retired professor at the Department of Biomedical Science at Colorado State University. For over 50 years I've been researching numerous aspects of assisted reproductive technology, including cloning and genetic alteration of mammalian embryos, so I'm most interested in any research on "baby designers" and the health problems that they may suffer.

First?

The conference gave a general overview of science. While such research should normally be presented to the scientific community by publishing in a journal that has been reviewed and which he claims he intends to do, we can get a rough feeling as he has created these modified babies. This is something that has been successfully done in other species, and only last year in human embryos – but others were not embedded in a woman. He says he spent three years testing the procedure on mice and monkeys before moving on to human embryos.

There is no doubt that precise genetic modifications can be made to human sperm, eggs, embryos, and even some cells in adults. Such modifications have been made ad nauseum in mice, pigs and several other mammals. So scientists like me obviously have the same genetic modifications that can and will be made in humans. The easiest way for genetic changes to begin with an embryo.

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The most covert strategy for modifying DNA these days includes CRISPR / Cas-9 genetic engineering tool, which can make precise genetic modifications in live cells. Although other tools are available for years, the CRISPR / Cas-9 approach is simpler, lighter, more precise and cheaper.

The way of functioning is simple in the concept. Component Cas-9 is a molecular scaffold that cuts DNA locally on the site of a small piece of DNA called "CRISPR template". Once the DNA is found, the gene can be modified at that site. The results improve enzymes that are already present in the cells.

In this case, it directed the gene that produces cell surface proteins called CCR5. The HIV virus uses this protein to cling and infect the cell. The idea was to genetically change CCR5 so that HIV can no longer infect cells, making girls resistant to the virus.

At this time, he did not provide a clear explanation of exactly what disables CCR5 and the nature of genetic modification. But such a kind of "disabling" is routinely used in research.

How did he do it?

From the diagram she showed, it seemed to have injected the CRISPR / Cas-9 system into the egg at the same time as she injected sperm to fertilize it. After that, the egg split and formed the ball of dozens of cells – embryos. At this stage, he removed several cells from each embryo to determine whether a desired genetic change was made. Based on my experience, the embryos were probably frozen at this time. When the analysis was completed, it probably melted the modified embryos and transplanted the best ones back into the mother's womb to gesture to the concept. Embryos not edited or misdirected would be discarded or used for research.

For many applications, it is ideal to make any changes in the genes in one cell. Then, when an embryo doubles its DNA and divides itself to create two cells, genetic modification is also duplicated. This is continued so that each cell in the given child has a genetic change.

However, it appears that the genetic modification in this case did not reach the stage of two cells or later because some cells in babies have modification, while others do not. This situation is called a mosaic, because the child is a mosaic of normal and well-arranged cells.

Embarrassing Canine Dangers?

What could go wrong in a gene-embedded embryo? Abundance.

The first glitch is that no changes have been made, which often occurs. The variation is that the change occurs in some embryonic cells, but not in all cells, as happened in those babies.

The most common concerns are so-called non-targeted effects in which genetic modification is made, but other unwanted devices appear elsewhere in the genome. Changing the wrong place can cause all sorts of developmental problems, such as abnormal organ development, abortion, and even cancer.

From his slider appears to have followed the genome – a complete genetic sketch for every child – in multiple stages of pregnancy to determine if there are any unwanted changes, though it is not always easy to find. But while independent scientists can examine the DNA of these two babies, we will not know the results. It is also not clear from the results so far divided whether this genetic change could be passed on to the next generation.

Another common problem that has already been pointed out is mosaic, which seems to have occurred in one of these twins. If some cells are regulated, and some may not, a child may have liver cells that contain regulated genes and heart cells that have a normal version, for example. This may or may not lead to serious problems.

The other question is that manipulating embryos in vitro – outside normal environments in the reproductive tract – where we can not accurately duplicate normal nutrition, oxygen levels, hormones and growth factors – can lead to developmental abnormalities including excess fetuses, metabolic problems, and so on. This sometimes happens with routine procedures such as in vitro fertilization when there is no attempt to genetic modification.

Fortunately, nature is pretty good in removing abnormal embryos through embryonic death and spontaneous abortion. Even in healthy human populations that normally reproduce, nearly half the embryos die before the woman even knows she is pregnant.

We are already designing babies – and they have advantages

While pointing out what can go wrong, I believe that science will develop so that genetically modified babies are healthier than unmodified. And these improvements will be passed on to future generations. Seriously debilitating genetic abnormalities such as Tay-Sachs syndrome can be removed from the family by genetic modification.


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