Lulu and Nana are the result of a defiant experiment in human gene modification

Remember these two names, Lulu and Nana. They are twin girls born in China in October 2018, and we already know they are going to be famous.

They are the world’s first genetically-edited humans, and their progress through life will be monitored intensively by medical researchers over the coming years.

Don't doubt their future celebrity. Remember the headlines when Dolly the sheep arrived in 1996, the world's first mammal cloned directly from an adult cell. Or how about Louise Brown, who made headlines in 1978 as the first baby to be conceived using invitro fertilisation (IVF) techniques.

Although the methods used to bring about these three births are light years apart, all three involve the delivery of an offspring using unorthodox methods.

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All three were also controversial in their day. There was no end of condemnation and criticism about playing god and defying the laws of nature for the first two, but now IVF is commonplace for lots of medical reasons and is accepted as a standard medical practice. And news of another species successfully cloned in the lab would not make headlines today.

However, the genetic modification of the twins is a different matter, a genetic change introduced before birth to deliver a permanent alteration of their original genome that will be passed down from generation to generation.

Prof He Jiankui of the Southern University of Science and Technology carried out the genetic change needed to permanently modify the twins’ genome. He introduced a mutation that gave Lulu and Nana resistance to the Human Immunodeficiency Virus, the virus that causes Aids, and revealed his successful genetic modification one year ago this month.

Unexpected impacts

The backlash was immediate and severe. There was international condemnation that China allowed experimentation on humans. Last January his university sacked him.

The scientific community also criticised the work as having crossed an important red line for genetics research, the reality that we still know too little about how even the smallest genetic change might have unexpected impacts downstream in other parts of the genome.

It was bad enough that a modification had taken place, but the modification was in the germline, the cells that bring about the next generation and the next and the next.

Perhaps the lure of notoriety proved too strong or the desire to be the first, but He Jiankui crossed that line, helped along the way through use of a gene-editing method known as CRISPR-Cas9.

This method emerged over several years, and has become the gene-cutting tool of choice because it allows very tight control over how a gene can be modified, added to or deleted.

When it came into widespread use the scientific community recognised immediately that controls on its application were necessary to prevent its use in human gene modification. This should have prevented He Jiankui from attempting such a daring and defiant experiment but it didn’t, and Lulu and Nana were the result.

They were born healthy but now scientists will want to know whether there are unexpected or unwanted effects or other issues that arise. Already researchers have raised doubts about the gene modification that confers resistance to HIV, which means some level of susceptibility to the virus may remain.

The modified gene, known as CCR5, also has other roles in the body, and its modified actions may affect the lifespan of the twins. One large study involving 410,000 subjects showed that people with a similar mutated version of CCR5 were 20 per cent more likely to die before reaching the age of 78.

Difficult diseases

Despite these misgivings there is no doubt that CRISPR-Cas9 will in the future be used to modify the human genome in the battle against difficult diseases such as cancer and in genetic disorders caused by specific gene mutations. The tool is far too important to avoid its eventual use, or the use of some other similar but as yet unidentified gene-cutting method.

Similarly there is little doubt that online charlatans will offer promised but undeliverable “cures” using CRISPR-Cas9, as was the case with earlier technologies such as stem cells.

Lulu and Nana, meanwhile, will get on with living their lives, doing what babies do. Their names are pseudonyms in an attempt to conceal them from public view, but it is likely that we may learn their real names in the future.

Lulu and Nana’s story came to mind in light of research published last week (November 21st) in the journal Cell about how attempting to create “designer babies” using other advanced technology could still remain a costly waste of time.

It involves choosing an embryo based on its potential to be tall or smarter than average, but accomplishing this via something like CRISPR-Cas9 is too far beyond our current abilities. Instead the international team of scientists set up a model to simulate one method called pre-implantation genetic testing.

This involves screening the genome for genes that have an association to a given trait, in this study’s case intelligence and height, and giving them a score. The team found, however, that at best the top-scoring embryo might be expected to be 2.5cm taller than average and at best 2.5 IQ points above average.

Lurking behind all of this remains the most challenging of issues, the ethics surrounding the use of this technology.

As usual the ethics questions that should have been asked first are the ones obscured by the advance of these promising discoveries.