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Professor Colorad in a Chinese genealogy child is concerned about health



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

George Seidel, State University of Colorado

On 28 November, Jiankui claimed that at the second international summit on the regulation of the human genome in Hong Kong, a conference room was set up that arranged the genomes of two twins, Lulu and Nane, who were born in China.

Scientists at the Southern University of Science and Technology in Guangdong, China, condemned the research He, who claimed that he "seriously violated academic ethics and codes of conduct", while philosophers and bioethics quickly sank into the turmoil of manipulating human genomes. Therefore, I will not cover this territory. What I want to address is what we learned: how he did these babies.

In theory, I am a retired professor at the Department of Biomedical Sciences at Colorado State University. For over 50 years, I have been researching a number of aspects of assisted reproductive technology, including cloning and genetic changes in mammalian embryos, so I am interested in most of the research on "design babies" and the health problems they would suffer.

First?

At the conference he gave a general overview of science. While such research is usually presented to a scientific community by publishing it in a professional journal that it claims to intend to do, we can get a rough feeling of how these modified children have created. This is something that was successfully done in other species, and last year in human embryos – but they were not included in the woman. He says he spent three years testing the process in mice and monkeys before he started working on human embryos.

There is no doubt that gene semen, eggs, embryos, and even some cells in adults can be precisely genetically modified. Such changes were made by ad nauseum in mice, pigs and several other mammals. That's how scientists, like me, are obvious that these and the same genetic changes can be made in humans. The easiest way of genetic changes begins with the embryo.

Toolbox

The latest strategy to change DNA these days involves a CRISPR / Cas-9 gene management tool that provides accurate genetic changes in living cells. Although other tools have been available for years, the CRISPR / Cas-9 approach is simpler, lighter, more accurate and cheaper.

The mode of operation is simple in the concept. The Cas-9 component is a molecular scissor that cuts DNA at a site determined by a small fraction of the DNA called "CRISPR templates". When DNA is cut, the gene can be changed at this point. The cutting then corrects enzymes that are already present in the cells.

In this case, it is directed by a gene that produces protein on the cell surface, called CCR5. The HIV virus uses this protein to bind and infect the cell. His idea was to genetically modify CCR5 so that HIV can no longer infect cells, making girls resistant to the virus.

At this point, he did not provide a clear explanation of how precisely the CCR5 was disabled and the nature of the genetic modification. But such "disability" is routinely used in research.

How he did it

In the diagram that he presented, it appears that he injected the CRISPR / Cas-9 system into the egg at the same time as the injection of sperm to fertilize it. After that the egg was divided and formed a ball of dozens of cells – the embryo. At this stage, he removed some cells from each fetus to determine whether the desired genetic modification was achieved. Based on my experience, frozen embryos were probably at this site. When the analysis was completed, it was likely that the modified embryos would be lost and the best back to the uterus of the mother would be returned due to gestation to expression. Embryos without changes or improper changes would be discarded or used for research.

For many applications, it is ideal to make changes in genes on a single-celled stage. After the fetus duplicates its DNA and divides it into a two-cell embryo, the genetic alteration is doubled. This continues so that each cell in the resulting child has a genetic change.

However, it seems that the genetic modification in this case did not occur to two cell stages or later because some cells in infants had a change, while others did not. This position is called mosaicism because the child is a mosaic of normal and regulated cells.

Danger of editing embryos?

What could go wrong with a genetically engineered embryo? A lot.

The first mistake is that no changes have been made, which often happens. The change is that there is a change in some of the embryonic cells, but not in all cells, as happened with these infants.

The most common concerns are the so-called non-target effects in which genetic modification is carried out, while other unintended editing occurs at other locations in the genome. Changes in the wrong place can cause all kinds of developmental problems, such as abnormal organ development, abortion and even cancer.

From his slider it appears that the sequencing of the genome – the overall gene plan for each child – found in several stages of pregnancy whether the adverse changes were, although they are not always difficult to find. But as long as independent scientists do not study the DNA of these two girls, we will not know the results. From the results he has so far transmitted, it is unclear whether this genetic change can be passed on to the next generation.

Another common problem, which is already mentioned, is mosaicism, which seems to have happened in one of these twins. If some cells are regulated and some are not, the baby can have liver cells that contain regulated gene and cardiac cells, which have, for example, the usual version. This can or does not cause serious problems.

The second issue is that manipulating the embryos in vitro – outside the normal environment in the reproductive tract – where we can not exactly duplicate normal diet, oxygen levels, hormones, and growth factors can cause developmental disorders, including overweight, metabolic problems and so on. This sometimes happens with routine procedures, such as in vitro fertilization, when there is no genetic change.

Fortunately, nature is very good in the removal of abnormal embryos with embryonic death and spontaneous abortion. Even in healthy populations that are normally reproduced, almost half of the embryos die before the woman even knows she is pregnant.

We are already planning children – and there are benefits

While I emphasized what could happen wrongly, I believe that science will develop in such a way that genetically modified children will be healthy from unchanged. These improvements will be passed on to future generations. Strongly debilitating genetic abnormalities, such as Tay-Sachs syndrome, can be removed from the family by genetic modification.

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