Remember the shocking announcement of the first births of genome modified twins (Lulu and Nana) globally?
In an article in Nature Biotechnology, we learn a little more about these girls, now toddlers. But, it says, “… their fate remains shrouded in secrecy amid swirls of rumors. Many people contacted for this story refused to speak about the babies … Some would speak to Nature Biotechnology only on condition of anonymity”.
In 2018, Dr He Jiankui announced the birth of the world’s first genetically engineered babies, Lulu and Nana. They had their genomes edited with CRISPR to confer a resistance to HIV infection. Using IVF to produce the embryos, they were genetically altered by disabling the CCR5 (C-C motif chemokine receptor 5) gene (the gene produces a receptor that allows HIV to enter and infect cells) during the single-cell stage.
There are multiple concerns associated with CRISPR, including the unintended consequences of using this cutting-edge technology on people. Furthermore, heritable genome editing is not yet ready to be tried safely and effectively in humans. Thus, it is critical that this activity could only proceed when it provides the most favourable balance of benefits and harms.
Medical examinations have been performed on the gene-edited children, including blood tests. These were conducted at birth, at one and six months and at one year. Liver function tests will follow this at age five and IQ tests at age 10. And there is HIV testing. These are indeed laudable.
What about the assessment of their mental health? There do not seem to be any definite plans for this evaluation, even of a need to inform the twins of their unusual conception circumstances. Following the general recommendation of parental disclosure to their IVF conceived children about the nature of their conception, children born from gene editing should also be informed about what was done to them as embryos and the reasons for the activity.
Moreover, the twins might be treated differently due to their different susceptibilities to HIV infection. For example, Nana might be refractory to HIV infection as two alleles of her CCR5 gene were altered. Lulu’s genome show one edited allele. Thus, one twin could be regarded as a preferred future partner.
At present, there are still very serious risks associated with CRISPR. Safety is a huge concern. For instance, there is the danger of mosaicism. This happens when some of the cells carry the edit but others may not.
It is challenging to determine how the changes to the twins’ genomes will translate to benefits or risks during their lifetimes. As the article states, “Genetic mosaicism can also be associated with certain cancers, and somatic mosaic variants are known to occur in some neuropsychiatric and neurodevelopmental disorders.” To test whether mosaicism might cause harm to the girls, numerous tissues need to be tested. This is indeed a significant concern. In the second international summit on human genome editing, the experts had a broad agreement that these risks associated with the technology are high.
In addition, it is possible to cut at the wrong location (off-target effects). Scientists are still unsure how this might affect people with the genomes modified.
Thus, Dr He’s work raises severe concerns about scientific practice and ethical accountability. Heritable genome editing involves making changes to embryos or gametes (sperm and eggs) that are passed down to subsequent generations. It is universally agreed that it is premature at this stage to embark on CRISPR for clinical applications. The Second International Summit said that the procedure was irresponsible at the time and failed to conform with international norms.
On another note, a third baby was born in 2019 in some secret location. Encouraged by the success of Lulu and Nana’s parents, a couple went on with the implantation of an embryo with one altered CCR5 allele.
There remain multiple uncertainties. It is of great concern that possible damage to the toddlers remains unknown. To quote Kiran Munusuru, of the University of Pennsylvania, “We just don’t have the technology yet … It’s very easy to do if you don’t mind doing it badly, if you don’t care about the consequences … but we’re nowhere near that just yet.” Thus, any heritable human genome editing should proceed vigilantly and provide the most favourable balance of risks and benefits.