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Colorado professor of gene-edited babies, health problems

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By George Seidel, Colorado State University

On November 28, He Jiankui claimed the crowded conference room at the Second International Summit on Human Genome Editing in Hong Kong to edit the genomes of two twin girls, Lulu and Nana, who were born in China.

Scientists at the South University of Science and Technology in Guangdong, China, condemned his research, which emphasized that he "has seriously violated academic ethics and codes of ethics," and philosophers and bioethics quickly dive into the genus of editing the human genome. So I will not discuss the area. What I want to say is what we learned: how He made these babies.

I am theoretically a retired professor in the Department of Biomedical Sciences at Colorado State University. For more than 50 years, I have researched various aspects of assisted reproductive technology including cloning and making genetic changes in mammalian embryos, so I was interested in almost all the research on "designer babies" and health problems they might suffer.

The first?

At the conference He gave a general description of science. While research like this will usually be presented to the scientific community by publishing it in journals reviewed by colleagues, which he thinks he will do, we can get a rough idea of ​​how he created this modified baby. This is something that has been done successfully in other species and last year in human embryos – but the latter is not implanted in women. He said he spent three years testing the procedure in mice and apes before he moved to work on human embryos.

There is no doubt that proper genetic modification can be done on human sperm, eggs, embryos and even some cells in adults. Such modifications have been carried out by ad nauseum in mice, pigs and several other mammals. Thus, it is clear to scientists like myself that this same genetic modification can, and will, be made in humans. The easiest way to make genetic changes starts with the embryo.


The trendiest strategy for modifying DNA today involves editing the CRISPR / Cas-9 gene, which can make the right genetic modifications in living cells. Although other tools have been available for years, the CRISPR / Cas-9 approach is simpler, easier, more accurate and cheaper.

The way it works is simple in concept. The Cas-9 component is a molecular scissor that cuts DNA in a location determined by a small piece of DNA called the "CRISPR template." After the DNA is cut, the gene can be modified at that location. This piece is then repaired by an enzyme that already exists in the cell.

In this case, he targets genes that produce proteins on the cell surface called CCR5. The HIV virus uses this protein to attach to and infect cells. The idea is to genetically change the CCR5 so that HIV can no longer infect cells, making the girls survive the virus.

At this point he hasn't provided a clear explanation of how he deactivated CCR5 and the nature of genetic modification. But this type of "deactivation" is routinely used in research.

How he did it

From the diagram presented, it appears that He injected the CRISPR / Cas-9 system into the egg at the same time when he injected sperm to fertilize it. After this, the eggs are divided and form balls of dozens of cells – embryos. At this stage, he removes several cells from each embryo to determine whether the desired genetic change is made. Based on my experience, the embryo might freeze at this point. When the analysis is complete, He may melt the modified embryo and transfer the best back to the mother's womb for pregnancy until the pregnancy. Embryos without edits or incorrect edits will be discarded or used for research.

For many applications, it is ideal to make changes to genes in the one cell stage. Then, when the embryo multiplies DNA and divides to make two cell embryos, genetic modification is also duplicated. This continues so that each cell in the baby produced has a genetic change.

However, it appears that genetic modification in this case does not occur until the second cell stage or later, because some cells in infants undergo modification, while others do not. This situation is called Mosaicism because children are normal and edited mosaic cells.

The danger of embryo editing?

What can be wrong in an embryo edited by genes? Many.

The first error is that no modifications are made, which often occur. Variation is that changes occur in some embryonic cells, but not in all cells, as happens in these babies.

The most common anxiety is what is called a non-target effect, where genetic modification is made, but unwanted editing occurs in other locations in the genome. Having modifications in the wrong place can cause all kinds of developmental problems, such as abnormal organ development, miscarriages and even cancer.

From the slide it appears that He ranks the genome – a complete genetic blueprint for each child – at various stages of pregnancy to determine whether there are undesirable modifications, although this is not always easy to find. But until independent scientists can examine the DNA of these two baby girls, we will not know the results. It is also not clear from the results he has shared so far whether this genetic change can be transmitted to the next generation.

Another common problem already mentioned is mosaicism, which seems to have happened to one of these twins. If some cells are edited, and some are not, the baby may have liver cells containing edited genes and heart cells that have a normal version, for example. This may or may not lead to serious problems.

Another problem is that manipulating embryos in vitro – outside their normal environment in the reproductive tract – where we cannot precisely duplicate normal nutrients, oxygen levels, hormones and growth factors – can cause developmental disorders including too large fetuses, metabolic problems, etc. This sometimes occurs with routine procedures such as in vitro fertilization when there is no attempt to make genetic modifications.

Fortunately, nature is quite good at weeding out abnormal embryos through embryonic death and spontaneous abortion. Even in healthy human populations reproducing normally, almost half of the embryos die before the woman even knows that she is pregnant.

We have designed babies – and there are benefits

While I emphasize what can be wrong, I believe that science will evolve in such a way that genetically modified babies will be healthier than unmodified ones. And this improvement will be forwarded to future generations. Highly debilitating genetic disorders such as Tay-Sachs syndrome can be removed from the family with genetic modification.

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