Altering the CCR5 gene: The flip side

Dr Derrick Aarons

Sunday, March 17, 2019

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MANY people perhaps have heard the outcry against Chinese scientist Professor He Jiankui who spearheaded the editing of the genes of twin girls, Lulu and Nana, after their conception in China, to make them impervious to HIV infection. The aim of the research was to show that it might be possible for the children to never be infected by HIV over the course of their lives.

However, the main ethical issue is not whether Professor He's gene-editing work can ensure that the twin girls will never get HIV infection, but rather that a Pandora's box has now been opened by his work.

What are some of the specific concerns in this regard? The issue revolves around the unknown, and being unable to reverse any unwanted biological changes the process may have brought into effect in future human beings.

Changing the brain

One of those unintended biological changes has just been reported.

New research has suggested that the gene-editing experiment to make children resistant to HIV may also have changed their brains in ways that enhanced their ability to learn (cognition) and form memories.

The research found that the same alteration that was introduced into the girls' DNA, that is the deletion of the CCR5 gene, not only makes mice smarter, but also may improve brain recovery after a stroke and could be linked to greater success in school.

The discovery was made in a lab headed by a neurobiologist at the University of California in Los Angeles, USA. However, the exact effect on the Chinese twins' cognition is impossible to predict, and so these researchers recommended that gene-editing of the CCR5 gene should not be done.

While such experiments have been widely condemned as irresponsible, news of the first gene-edited babies had also inflamed speculation as to whether the CRISPR technology that edited the genes could one day be used to create super-intelligent humans. Further, that it could involve a biotechnology race between the USA and China.

Removing the CCR5 gene

Although in planning and conducting his gene-editing research Professor He was not known to have consulted any brain researchers, it is opined that he was certainly aware of the link between CCR5 and cognition. This is because in 2016 a couple of researchers had found that removing the CCR5 gene from mice significantly improved their memory.

The research team had looked at more than 140 different gene alterations to find which made mice smarter.

Due to the nature of their research, these researchers reported that they sometimes interacted with individuals in Silicon Valley and elsewhere, who have a vested interest in designer babies with better brains. Consequently, with the news release about Professor He's gene-editing work with the twins in China, those researchers had immediately wondered if He's work had been an attempt to design babies to improve cognition.

However, Professor He proclaimed that he was against using genome editing for human enhancement. While that may not have been his intention, evidence is now emerging that the CCR5 gene plays a major role in the brain, including acting as a suppressor of memories and synaptic connections. Thus, removing its effect would improve memory and cognition (thinking and understanding).

Every day intelligence

Accordingly, people who do not have the CCR5 gene would recover more quickly from a stroke. Further, a recent report in the journal Cell informed that persons who are missing one copy of the gene seem to go further in school, thereby suggesting a possible role in every day intelligence.

Naturally, these discoveries that link the absence of the CCR5 gene to educational success require further research. Hence, follow-up clinical research trials are progressing for both stroke patients as well as individuals with HIV, who sometimes suffer memory problems. In the latter studies, participants are being given an anti-HIV drug which chemically blocks the CCR5 gene, to see if it improves their cognition.

We should note that there is a big moral difference between trying to correct deficits in patients and trying to create human enhancement.

Cognitive problems are one of the biggest unmet needs in clinical medicine, and so appropriate drugs are needed. What is ethically unacceptable for some people, however, is for scientists to take normal people and alter their DNA or chemical make-up in order to improve them.

Ethical considerations

Knowledge in this field is growing exponentially, but ethical considerations must be paramount in all decision-making. We should not alter normal intelligence, even if we are able to.

The genetic manipulations used to make 'smart mice' demonstrates not only that such changes are possible, but also that changing the CCR5 gene can have particularly huge effects.

So conceivably, at some point in the future, scientists will have the ability to increase the average IQ of the whole population. However, we simply do not know what the consequences would be, and we are certainly not ready for them as yet!

Dr Derrick Aarons MD, PhD, is a consultant bioethicist and family physician; a specialist in ethical issues in health care, research, and the life sciences; the health registrar and head of the health secretariat for the Turks and Caicos Islands, and a member of UNESCO's International Bioethics Committee.

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