On Nov. 28, He Jiankui claimed to a packed conference room at the Second International Summit on Human Genome Editing in Hong Kong to have edited the genomes of two twin girls, Lulu and Nana, who were born in China.
Scientists at Southern University of Science and Technology in Guangdong, China, condemned He’s research asserting he “has seriously violated academic ethics and codes of conduct,” and philosophers and bioethicists were quick dive into the morass of editing human genomes. So I’m not going to cover that territory. What I want to address 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 numerous aspects of assisted reproductive technology including cloning and making genetic changes to mammalian embryos, so I am interested in most any research concerning “designer babies” and the health problems they may suffer.
At the conference He gave a general overview of the science. While research like this would typically be presented to the scientific community by publishing in a peer-reviewed journal, which He claims that he intends to do, we can get a rough sense of how he created these modified babies. This is something that has been successfully done in other species and just last year in human embryos – but the latter were not implanted into a woman. He says he spent three years testing the procedure on mice and monkeys before he moved to working on 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 done ad nauseum in mice, pigs and several other mammals. Thus, it is obvious to scientists like myself that these same genetic modifications can, and will, be made in humans. The easiest way to make genetic changes begins with the embryo.
The trendiest strategy to modify DNA these days involves the CRISPR/Cas-9 gene editing 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 expensive.
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 the “CRISPR template.” Once the DNA is cut, a gene can be modified at that location. The cut is then repaired by enzymes already present in cells.
In this case, He targeted a gene which produces a protein on the surface of cells called CCR5. The HIV virus uses this protein to attach to and infect the cell. He’s idea was to genetically change CCR5 so that HIV can no longer infect cells, making the girls resistant to the virus.
At this point He has not provided a clear explanation of exactly how he disabled the CCR5 and the nature of the genetic modification. But this kind of “disabling” is routinely used in research.
How he did it
AP Photo/Kin Cheung
From the diagram He presented, it appears that He injected the CRISPR/Cas-9 system into an egg at the same time as he injected a sperm to fertilize it. After this, 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 desired genetic change was made. Based on my experience, the embryos were probably frozen at this point. When the analysis was complete, He probably thawed the modified embryos and transferred the best ones back into the mother’s uterus for gestation to term. Embryos without the edits or incorrect edits would either be discarded or used for research.
For many applications, it is ideal to make any changes to the genes at the one-cell stage. Then, when the embryo duplicates its DNA and divides to make a two-cell embryo, the genetic modification is also duplicated. This continues so that every cell in the resulting baby has the genetic change.
However, it appears that the genetic modification in this case did not occur until the two-cell stage or later, because some cells in 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.
Hazards of embryo editing?
What could go wrong in a gene-edited embryo? Plenty.