Sci-fi or real? Is an age of genetically modified human babies ahead of us?

A Chinese scientist claims to have successfully employed the gene-editing technology for the birth of twin girls

Two years ago, Jennifer Doudna said, “I’ve mentally prepared for the day when I open my inbox, or answer my phone, and realise that somebody’s announcing the first CRISPR baby.” CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Well, she didn’t have to wait all that long. That claim came this Monday, from YouTube of all places.

In one of a series of linked videos (www.youtube.com/watch?v=th0vnOmFltc&t=2s) from The He Lab, He Jainkui, an associate professor at the Southern University of Science and Technology, Shenzhen, China, announced that he had used the gene-editing technology, CRISPR CAS9, to edit the genomes of embryos in a successful in-vitro fertilisation (IVF).

He said his experiment resulted in the birth of “two beautiful twin girls, Nana and Lulu, born to Mark and Grace” (using pseudonyms to protect privacy). The scientist said that he had done this experiment to ensure that the babies had resistance to HIV, since their father, Mark, is HIV positive.

YouTube is an unconventional platform to announce a scientific study, without publishing a paper in a journal, or even informing his academic department. Massachusetts Institute of Technology’s Technology Review had “scooped” the news just an hour before the videos were released.

He is a leading genetic scientist, with Stanford University and Rice University on his résumé, and a holder of degrees in physics and biology. He gave a scheduled presentation at the Second International Conference on Human Genome Editing in Hong Kong on Wednesday, where he described his experiment and motivations.

The secrecy is understandable. He broke the global scientific consensus of avoiding editing genomes in embryos to produce genetically modified children. The experiment has been condemned as “crazy” by other Chinese scientists. He has been placed under suspension by his university, is being investigated by China’s National Health Commission and could soon be under arrest.

Doudna, who is one of the three pioneers of CRISPR-CAS9 technology, said she was horrified. Along with her collaborator, Emmanuelle Charpentier, she condemned the study. The third CRISPR pioneer, Fang Zheng (a bitter rival of Doudna-Charpentier in an ongoing battle for CRISPR patents) also condemned the experiment, and called for a moratorium on human genome editing.

Bioscientists have been debating the ethical implications of human genome editing for several years. The Conference in Hong Kong is a symposium for discussing the ethics. Ironically, He and his colleagues at Shenzhen published a set of draft ethical principles on the day that the existence of Nana and Lulu was announced.

The ethical morass arises from the possible consequences of the science. CRISPR is part of a natural biological defence mechanism against bacteria and viruses. After fighting off a virus, fragments of the destroyed virus’s DNA are stored in a genetic database of “wanted” posters. If that virus, or something similar, invades again, it is recognised because the DNA matches that rogues’ gallery. A CRISPR-Associated 9 protein (CAS9) then goes into action and cuts that virus out of the cell. This mechanism exists in many species.

Doudna-Charpentier and Fang Zheng discovered how CAS9 could be programmed to recognise and cut out any DNA fragments introduced to the CRISPR “database”. The cell with the cut portion can repair itself without the cut gene. Or the excised gene can be replaced with other DNA, which will be incorporated into the genome when the cell repairs that cut. If that cell can reproduce (if it is “plenipotent”), the new cells have a new genome.

So CRISPR-CAS9 can be used as a cut-and-paste tool to get rid of unwanted genes. (Other proteins can also be used as molecular scissors instead of CAS9.) That cut-paste technology has now been refined, modified and used many times to genetically modify various plants and animals.

But there has been a high failure rate in experiments with plants, animals and with aborted or miscarried human embryos. (Experiments with miscarried foetuses are common because they have plenipotent cells.) CRISPR-CAS9 can also result in “off-target” editing, damaging nearby genes. Also, since there are vast areas of ignorance about gene functions, indiscriminate excision of a gene, known to have some negative function, may also mean the loss of some positive function.

When a CRISPR CAS9 “edit” works as intended, it alters the genome of the subject forever. New cells produced by that person have the altered genome. The new characteristics are inheritable. They will be passed on when the subject has children, entering the gene pool.

CRISPR-CAS9 can surely be used to reduce propensity to many diseases linked to specific genes. For example, it could reduce incidence of diabetes, or ALS, or certain cancers, or thalassaemia, or Huntington’s disease. It may also be used to introduce a mutation that protects against disease.

CRISPR-CAS9 could also be used to create designer babies with great strength, or intelligence, high lung-capacity, or desirable vital statistics. It could conceivably be used for creating babies with desired sexual orientations, since some genes are linked to sexual orientation.

So, while it’s tempting to use CRISPR CAS9 to alter the genome of embryos to eliminate diseases, there are real medical risks involved. There are socio-political risks too, since it could be used to propagate racism or bigotry. It could perpetuate class and income differences in permanent, genetic fashion. Or, as Stephen Hawking pointed out — and he was definitely interested as a victim of ALS — if genetic editing creates a sub-species of superhumans, “unimproved” humans may die out, or become an underclass.

These ethical tropes have been explored multiple times in science fiction, most notably perhaps in Aldous Huxley’s 1930s classic, Brave New World, which speculates about a society of vat-grown children, with carefully calibrated IQs and physical attributes. That literary thought experiment may be reality in the near future. Many countries have started enacting laws against editing human genomes and carrying pregnancies to term, except under strict supervision, when there is a “clear, unmet, urgent medical reason”, as Doudna put it.  

He claims a strong medical reason but avoided supervision because that logic doesn’t stand up to examination. China has a large HIV-positive population. He worked with seven couples, where the man was HIV positive. His experiment was built around the only known case where HIV has been cured.

In 2007, an HIV-positive man, Timothy Ray Brown (also known as “The Berlin Patient”), received a bone marrow transplant for treatment of leukaemia. The marrow donor, a North European, had a mutated CCR5 gene, which blocked the normal means by which HIV enters cells. It was discovered that a few North Europeans have this rare mutation, which offer high levels of protection against HIV. He used CRISPR CAS9 to introduce the mutated CCR5 gene into 16 embryos. Thus far, it has resulted in one set of twins, and He claims another pregnancy has happened.  

But this was not an “unmet medical need”. Highly proven techniques exist to prevent HIV transference in IVF pregnancies. There is a second problem: the mutated CCR5 makes carriers susceptible to flu, which can be fatal for them, and flu is a lot more common than HIV. The mutated gene is also more vulnerable to admittedly rare diseases like West Nile fever. A third problem, of course, is that Nana and Lulu may have suffered off-target editing that harmed other genes. Also, assuming they grow up “normal”, they will pass on these mutations to their children.

This was clearly an irresponsible experiment on many levels. But this sort of rogue experiment was also inevitable. Laws to prevent repeats may now be passed in many places. But there may be another He, or indeed many more Hes, sitting in labs somewhere. Unscrupulous regimes will also see the opportunity to perpetrate racism and bigotry as features rather than bugs. It would also be natural for rich people to seek ways to bear “improved” children. CRISPR-CAS9 leads us into a new world for sure — it remains to be seen whether it will be as dystopian as Huxley’s vision.