Center for Research on Science, Technology and Society

Announced in November 2018 during the last International Summit on Human Genome Editing in Hong Kong, the experiment by Chinese scientist He Jiankui, who revealed that he edited healthy embryos using the CRISPR-cas9 technique, a genetic tool that cuts the DNA sequence and reconfigures it to obtain a modification – in this case, making him immune to the HIV virus – caused concern and sparked a series of debates among his peers and the scientific societies of the world.

The discussions were not only about the use of the technique, which involves interfering with DNA to reproduce a natural defense mechanism found in several bacteria, but about the ethical implications of the experiment, from which, the Chinese scientist affirmed, two genetically modified twins were born. 

The announcement reignited the debate surrounding the limits of interfering with the genome of future generations of human beings. 

Created in 2013 and still being refined, the CRISPR system allows for the addition, modification, and disruption of genetic sequences – a DNA sequence is repeated several times, with unique sequences between repetitions –, what scientists have described as clusters of short, regularly interspersed palindromic repetitions. In short, it allows for the recognition of a specific exogenous DNA and its consequent elimination, if it comes into contact with the organism, acting as a defense mechanism. 

Although the technique is well-known, it is worth mentioning that, from the point of view of scientific procedures, Jiankui, from the Southern University of Science and Technology in Shenzhen, did not publish data from his research in any journal or share information proving its veracity.

In addition to questions surrounding the experiment itself, questions also focused on the reasons why he performed the supposed genetic editing – immunizing the body to the HIV virus by deactivating the CCR5 gene, which allows the virus to enter the cell – that could be addressed using other mechanisms that are safer and more well-known, according to scientists. After all, there is not, at the moment, safety in the application of the CRISPR technique, which can cause other genes to change in unpredictable ways. 

"CRISPR technology is very promising and is being used quite efficiently by laboratories to edit, for example, genes that cause genetic diseases. But there are risks, because there is no certainty that only the chosen gene will be affected, and the danger that other targets will be affected exists. It's called the "off target” effect," says Mayana Zatz, director of the Human Genome Center at the University of São Paulo (USP). 

For her, the experiment compares to a stray bullet. “A shot fired at one target carries the risk of hitting another, with unpredictable consequences, and in science this needs to be considered," she notes.

Ethical limits

Although the experiment described by Jiankui is questioned, the core of the discussion revolves around the limits between the possible applications of the technique for disease control and prevention, which is actually sought, and the possibility of future genetic editions in which human embryos can be genetically edited only to alter physical characteristics.

The fear is justified not only by problems arising from changes in the genome of future generations, but also by what could be characterized as eugenics, a practice that is considered ethically unacceptable by scientists and research institutions. 

If accurate, the results described by Jiankui show that only one of the girls achieved the desired change − and that the two sisters could exhibit unwanted mutations and unknown effects that could be inherited by their children. “It would be an experiment with no medical advantage, since the embryos were healthy before interference, and the modifications can be passed on to future generations if they reach germ cells," explains Mayana.

For the USP geneticist, as long as it is not possible to safely deal with CRISPR, there should be a respected moratorium, that is, a period without embryo research until safety of the procedure can be ensured. “In genetics, there is no reason to edit a gene to correct flaws when there are other promising techniques that are already tested and can be used on adult patients by editing bone marrow cells," she says.

As an example, she cites the case of a leukemia and AIDS patient who, 11 years ago, in Germany, received a bone marrow cell transplant from a compatible donor who also had a CCR5 mutation (which confers HIV resistance), and obtained successful treatment, curing both diseases. This demonstrates, she says, that it is possible to opt for a treatment of modifying adult bone marrow cells rather than embryos.

In the case of the Chinese researcher, different scientists stated in the media that the experiment would not justify the use of CRISPR, taking into account the aggravating fact that the scientist did not even address a disease considered to be serious or untreatable.

Moreover, according to other Chinese scientists attending the event as well as the university itself where the experiment would have been conducted, the case was not known to peers, nor was it approved by research ethics committees. 

Scientific rigor and legislation

Three days after Jiankui's announcement, Chinese authorities suspended their research activities, claiming that the scientist had violated the country's laws and regulations, and that the scientist will now be investigated by China's National Health Commission.

Evidence from the experiment indicates, according to Mayana, that the case went beyond all ethical limits related to research, patients, and scientific journals, because it is not known if the experiment was actually performed, the experiment was not screened by other scientists, and because it will not be permitted to investigate or monitor children clinically in order to safeguard their identities. 

On the other hand, she notes that an event like this, while dangerous and premature, should not be used as an argument to prevent further research involving CRISPR from advancing. According to Mayana, there are studies on how changes in the immune system could be beneficial, for example, in identifying the chances that a tumor could be attacked and destroyed in the immune system. 

“The clinical use of CRISPR for the treatment of genetic diseases of high severity should be the focus of research so that the technique can be refined and the dangers of its use eliminated. Thus, it can be a great ally in genetic treatments," she concludes, clarifying that she defends research involving embryos, provided the research is done with embryos that are discarded and not implanted. 

Therefore, the current legislation in different countries must be observed and the scientific deadlines respected, considering the ethical limits pointed out by scientists, institutions, and societies, but without interruption of research and possible applications of their results.