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Professor of Colorado on the baby edited by Chinese genes, concerns about health



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(The Conversation is an independent and non-profit source of news, analysis and commentary of academic experts).

By George Seidel, Colorado State University

On November 28, El Jiankui called for a full conference room at the Second International Summit on Human Genome Editing in Hong Kong for having edited the genomes of two twin girls, Lulu and Nana, who were born at the China.

Scientists from the Southern University of Science and Technology in Guangdong, China, condemned their investigation stating that "it has grossly violated academic ethics and codes of conduct," and philosophers and bioethics plunged rapidly into the morphology of the edition of human genomes. So I'm not going to cover this territory. What I want to address is what we have learned: how did these babies.

I am theoretically a retired professor of the Department of Biomedical Sciences at the State University of Colorado. For more than 50 years I have investigated many aspects of assisted reproduction technology, including cloning and genetic changes in mammalian embryos, so I'm interested in most research on "designing babies" and health problems they suffer

A first one

The conference gave a general vision of science. Although research like this will usually be presented to the scientific community by publishing it in a journal reviewed by experts, which states that it intends to do, we can have an approximate idea of ​​how these newly-created babies were created. This has been done successfully in other species and last year in human embryos, but these were not implanted in a woman. He says he spent three years trying the mice and monkeys procedure before moving to work on human embryos.

There is no doubt that precise genetic modifications can be made to human sperm, eggs, embryos and even some adult cells. These changes have been made ad nauseum in mice, pigs and various other mammals. Therefore, it is obvious to scientists as myself that these same genetic modifications can and will be made in humans. The simplest way to make genetic changes begins with the embryo.

The toolbox

The most current strategy to modify DNA these days involves the CRISPR / Cas-9 gene edition tool, which can make precise genetic modifications in living cells. Although other tools have been available for years, the CRISPR / Cas-9 approach is simpler, easier, more accurate and less costly.

The way it works is simple in concept. The Cas-9 component is a molecular scissors that cuts the DNA at the location specified by a small piece of DNA called "CRISPR template." Once DNA is cut, you can modify a gene in this location. The cut is then repaired by enzymes already present in the cells.

In this case, he directed a gene that produces a protein on the surface of the cells called CCR5. The HIV virus uses this protein to connect and infect the cell. His idea was to genetically change CCR5 because HIV can no longer infect the cells, making the girls resistant to the virus.

At this point, he has not provided a clear explanation as to how he deactivated CCR5 and the nature of genetic modification. But this type of "deactivation" is commonly used in the investigation.

How did it do

From the diagram it presented, it seems that it injected the CRISPR / Cas-9 system into an egg while injecting a semen to fertilize it. After that, the egg divided and formed a ball of dozens of cells: the embryo. At this stage, he removed a few cells from each embryo to determine if the genetic change was desired. Based on my experience, embryos were probably frozen at this point. When the analysis was completed, it probably thawed the modified embryos and transferred the best to the mother's uterus for her pregnancy. Embryos without editions or incorrect editions would be discarded or used for research.

For many applications, it is ideal for making changes in genes in the single cell stage. Then, when the embryo doubles its DNA and divides to make an embryo of two cells, the genetic modification is also doubled. This continues because each resulting baby cell has genetic change.

However, it seems that the genetic modification in this case did not occur until the stage of two cells or later, because some cells of the babies had the modification, while others did not. This situation is called mosaicism because the child is a mosaic of normal and edited cells.

Risks of embryo edition?

What could go wrong in a genetic embryo? Very abundant

The first failure is that you have not made any changes, which happens frequently. A variation is that the change occurs in some cells of the embryo, but not in all cells, as in these newborns.

The most frequent concern is the so-called non-target effect, in which genetic modification is made, but other unwanted modifications occur in other locations of the genome. Having a modification in a wrong place can cause all kinds of development problems, such as the development of abnormal organs, abortion, and even cancers.

From his slide, it seems to have sequenced the genomes, the complete genetic plan for each child, at various stages of pregnancy to determine if there have been undesirable changes, although they are not always easy to find. But until independent scientists can examine the DNA of these two girls, we will not know the results. In addition, it is not clear from the results that it has shared so far if this genetic change can be transmitted to the next generation.

Another common problem already mentioned is the mosaicism, which seems to have happened in one of these twins. If you edit some cells, and some do not, the baby may have liver cells that contain edited gene and heart cells that have the normal version, for example. This may or may not cause serious problems.

Another issue is that manipulating embryos in vitro-out of their normal surroundings in the reproductive tract-where we can not just duplicate normal nutrition, oxygen levels, hormones and growth factors- could lead to anomalies Of the development including large fetuses, metabolic problems and so on. This sometimes occurs with routine procedures such as in vitro fertilization when there is no attempt to make genetic modifications.

Fortunately, nature is good enough to eliminate abnormal embryos through embryonal death and spontaneous abortion. Even in healthy human populations that normally reproduce, almost half of the embryos die before the woman knows she was pregnant.

We design babies and there are benefits

Although I have emphasized what goes wrong, I believe that science will evolve in such a way that genetically modified babies will be healthier than those that are not modified. And these improvements will be transmitted to future generations. The severely debilitating genetic abnormalities such as the Tay-Sachs syndrome could be eliminated from a family by genetic modification.

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