The story of the first genetically edited twins

You might have come across a story about the birth of twin sisters Lula and Nana whose genome was edited to protect them from the human immunodeficiency virus (HIV).

This news caused a furore in the scientific community, and the lead scientist (Dr He Jiankui) of the experiment was severely criticised. Dr He was sentenced to 3 years in prison and fined 3 million Yuan for violating the ethics of research on human embryos.

One year later, the case of Dr He Jiankui is still a hot topic in the scientific community as more and more details and — most importantly — results of this “clinical research” (as Dr He called it) are being revealed to the general public.

Today, I want to tell you about the system by virtue of which Lula and Nana were created and about Dr He and his “experiment”.

CRISPR/Cas9

CRISPR (from ‘clustered regularly interspaced short palindromic repeats’) and protein Cas9 are a type of bacterial immune system. When attacked by a virus, bacteria retain fragments of genetic information from the virus. In case of a repeated attack, the bacteria are then able to recognise the viral invader and the Cas9 protein destroys the virus’ genetic material.

The discovery of the CRISPR/Cas9 system revolutionised scientific research. This system was quickly copied and adapted for use in different model organisms. This well-received method of gene-editing has substantial advantages:

1. Easy to use

2. Low cost

3. Has the potential of inserting and replacing genes

The CRISPR/Cas9 system has a huge potential in curing genetic disorders and alleviating diseases using in vitro (cell cultures) and in vivo models (laboratory animals).

The difference between genetic therapy and genome editing

Genetic therapy is intended to “deliver” one or few copies of a gene to the patient’s body with the help of vectors (special vehicles that deliver the gene of interest to the host’s cells and help insert the gene to the host’s genome). The aim is to compensate for the negative effect of the bad gene with a mutation. However, genetic therapy has an effect only on somatic cells (all the cells except the egg cells and sperm), and such editing is NOT hereditary.

Gene-editing, on the other hand, is intended to correct a gene that causes a disease. In the majority of cases, gene-editing is carried out in the embryo stages of development. As a consequence, all the cells, including ovum and spermatozoon (egg cells and sperm), have the alteration in their genotype, and therefore the changes will be inherited by the following generation.

Doctor He

He Jiankui was born in 1984 in the Xinhua county. He received a state scholarship to study at the University of Science and Technology of China in Hefei (one of the most prestigious universities in China) where he studied physics. As he completed the degree, He went to the USA, joined the laboratory of Professor Deem and started working on his PhD. In 2010, He published his own mathematical model of the evolution of CRISPR and other proteins.

In 2011, Dr He returned to China and received state funding to develop a biotech start-up called Direct Genomics. His team included some famous scientists specialised in embryology and genetics. In April 2018, the scientist announced a successfully completed pregnancy after the genetic modification of embryos.

Today, almost all of Dr He’s colleagues affirm that they were wary of his ideas and tried to stop the experiment… However, investigations have shown that many scientists supported He and were pleased with his achievements.

I would like to remind you that he is a physicist. So, to continue his project, Dr He needed help from embryologists, genetics, and gynaecologists who apparently were not against his experiments.

The successful pregnancy — Lulu and Nana

In 2017, Dr He and his team began selecting couples that could not have babies and where the male partner had HIV. One couple fulfilled the criteria and was selected for the “clinical research”.

After the insemination, the embryos were edited in a petri dish with the help of the CRISPR/Cas9 system. A fragment of the CCR5 gene that encodes the receptor on the surface of white blood cells was eliminated in the embryos of Lula and Nana. Dr He believed that such editing would prevent the twins from being infected with HIV because the CCR5-receptor is involved in the distribution of HIV in the body.

The successful in vitro fertilization of the twins was followed by the news about Lula and Nana’s birth in November 2018.

In the video above Dr He announces the birth of Lulu and Nana and potential benefits of genome editing in humans.

Why did not Dr He gain the appreciation and respect that he anticipated?

To date, there is no scientist that would openly support Dr He.

The main reasons why Dr. He’s “experiment” was not well received are:

1. Open violation of the law: in China, like in the majority of other countries, it is prohibited to conduct experiments on human embryos that are 14-days old; as well as its implantation into a woman’s womb. («Ethical Guiding Principles for Research on Embryonic Stem Cells,» 2003);
2. The human genome (that is, a combination of all human genes) is not yet fully understood: to date, the number of known human genes comprising of 20,000–25,000 is believed to be only a fraction of the real number of genes; therefore, any kind of intervention into the human genome may lead to unpredicted consequences;
3. The science acknowledges that CCR5 is also responsible for intellect, meaning that Dr He created girls with an artificially elevated IQ;
4. It was later revealed that the CCR5 gene was only partially deleted in one of the twin sisters’ genome; meaning she could still be infected with HIV;
5. Most importantly, this “clinical research” did not have therapeutic significance! The girls were not under the direct risk of infection since the sperm of their father was disinfected by the procedure called “sperm washing” before the fertilisation.

Note: starting from 2012, in many countries of the world, ‘sperm washing’ became a routine procedure before an in vitro fertilisation procedure if a partner is infected with HIV, hepatitis A or C.

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