Investigation: Designer babies: the miracle and danger of modified embryos

Since the first test-tube baby was born, people have been fascinated by the idea of designer babies. Now, the reality – and the threat – of genetically modified humans is closer than ever before.

Imagine yourself on a hot summer day in the not-too-distant future. You’ve brought your three-year-old daughter to the playground because she loves the swings. A natural athlete, she is using her strong little body to propel herself ever higher, her blonde pigtails trailing behind her like streamers. She’s soaring, and your breath catches as she reaches the top of the swing’s arc and her tiny hands let go of the chains. You rush towards her as she crashes to the ground. She is dazed, but not injured. It is just as the doctor promised:

You hug her and remind yourself of the insurance policy you put in place before she was born. She has a vanishingly small risk of cancer, and no risk of diabetes. She will never get Alzheimer’s. You made sure of that when you requested that her embryo be edited before implantation.

“To produce a GMO [genetically modified] sapiens baby, you would begin effectively by placing an order for her or him,” wrote biologist Paul Knoepfler in 2015. “Scientists would team up with you, as the parent, to make this new GM child, using your cells and genetic fabric as the starting material. The only other things needed from you would be the money to pay for the process and your input into the design of the baby.”

He then suggested we could see edited humans as soon as 2030.

At the time, the Californian researcher was keeping a close eye on an emerging technology that was inspiring awe in the scientific community. CRISPR is a gene-editing tool which can be used to change the DNA of plants and animals – including humans. Creators Jennifer Doudna and Emmanuelle Charpentier were awarded the 2020 Nobel Prize in Chemistry for its creation, with the committee calling CRISPR “a tool for rewriting the code of life” that “may make the dream of curing inherited diseases come true”.

Professor Knoepfler shared the scientific community’s excitement for CRISPR’s potential, and in fact he uses it in his own lab today. However, he has also been one of the voices calling for urgent regulation when it comes to human experimentation. He knew it would be tempting for those with the right equipment to attempt to create genetically enhanced humans.

Theoretically, the three-year-old girl with the unbreakable bones could be engineered using CRISPR to edit the gene LRP5, which is responsible for bone density. A couple could attend a fertility clinic with a genetics lab on site, where they could peruse a menu and tailor-make their child.

Gene editing is more complicated than switching one gene to change one trait, but in the case of LRP5, it is a unique mutation that appears to be controlled by a single gene.

It was discovered in a family from Connecticut, after one member walked away from a car crash – which should have crushed him – without so much as a hairline fracture. Yale medical researchers described the family as having “the strongest bones on the entire planet”.

Science has uncovered “a bunch of characteristics that could be tinkered with,” says Melbourne-based anthropologist Eben Kirksey, who wrote The Mutant Project: Inside the Global Race to Genetically Modify Humans. For example, expectant parents who opt for babies with unbreakable bones might also want to consider editing BDKRB2, which occurs naturally “in the sea nomads of Southeast Asia and [is] linked to an ability to hold their breath for an extraordinarily long time underwater”. The family from Connecticut – whose bones are eight times denser than the average human’s – found it almost impossible to stay afloat while trying to swim.

A theoretical designer-baby lab could produce a child with low odour production (ABCC11), virus resistance (CCR5, FUT2) or insensitivity to pain (SCN9A). “We know that [targeting] genes related to pain, for example, could produce children or soldiers that are incapable of feeling pain,” Professor Kirksey tells The Weekly.

But just as strong bones make it hard to swim, low pain thresholds often result in shorter life-expectancy and a tendency towards risk-taking behaviour. These unintended consequences are one of the reasons people like Professor Knoepfler want a ban on editing human embryos.

The notion of “good genes” also raises the spectre of eugenics, says Professor Knoepfler, whose family fled Austria as the Nazis arrived in 1938. “When we talk about hacking the human code, I think all bets are off, in terms of what might come of that. There would still be dangers,” he said in 2015.

At the time, Chinese researchers had just reported that they had created the first edited human embryo, even though human gene editing was neither fully perfected nor understood. Professor Knoepfler asked: What if, when attempting to improve babies, we inadvertently make them sicker? “It’s pretty simple to try to do it, but to succeed is dramatically more difficult,” he said.

This powerful tool could be dangerous if it is used unsuccessfully, but there are also fears it could be brutally effective.

“In the wrong hands, CRISPR could have devastating consequences for humanity,” warns Professor Kirksey.

Playing God

The controversy surrounding human gene editing ramped up in November 2018, when a Chinese researcher named He Jiankui announced he had created the world’s first genetically modified babies. The twin girls, Lulu and Nana, had been born in China that October to mother, Grace, and father, Mark – who was HIV-positive.

The twins “came crying into this world as healthy as any other babies,” He Jiankui said via The He Lab’s YouTube channel. The twins were created through IVF, with one key difference: just after their mother’s egg was fertilised, technicians had performed gene surgery “to remove the doorway through which HIV enters to infect people”.

Above left: Biologist Paul Knoepfler warns that CRISPR technology could be misused. Above right: Scientist He Jiankui created the world’s first genetically modified babies.

Professor Kirksey was in the eye of the storm when the news broke at the Second International Summit on Human Genome Editing that a rogue researcher was playing God. CNN said the procedure was “monstrous”, and He Jiankui’s team was criticised for their lack of scientific rigour.

“The babies were never tested to see if their blood was resistant to HIV, which was ostensibly the aim,” says Professor Kirksey. “In many ways, He

had a hammer, CRISPR, and a nail. And it’s not clear if he actually hit the nail.”

In his announcement, He Jiankui said gene editing was just another IVF advancement and was only meant to help families who had no other way to heal inheritable diseases. “Their parents don’t want a designer baby – just a child who won’t suffer from a disease,” He said. “Gene surgery is, and should remain, a technology for healing. Enhancing IQ or selecting eye colour is not what a loving parent does. That should be banned.”

He Jiankui knew his work was controversial, but he believed families needed the technology and said he was willing to take the criticism for them. After a brief flurry of attention, He was arrested and jailed. The scientific community was left with a sense that the door was now open to more attempts.

“There’s still real concern that others could follow suit in different ways,” Professor Knoepfler says.

Some countries, including Australia, have placed serious restrictions on this kind of research, but others – like the US – haven’t. “There was radical deregulation by Donald Trump across the board. With Biden, we could see a reining in of the industry, but at this point it’s kind of anything goes,” Professor Kirksey says.

Already, there are signs of IVF companies testing the water. “As of about a year ago, there was a clinic in Cyprus that was advertising IVF and CRISPR,” Professor Kirksey says. “I reached out and I ended up having a messenger chat on [encrypted service] WhatsApp with someone who basically caters to medical tourists.”

The website of one of New York’s leading fertility doctors, John Zhang, says that, once doctors figured out how to create babies in a lab, “embryo editing to produce a healthy GMO baby was perhaps a natural next step”.

“Unfavourable characteristics or bad traits (like genetic disease) may be removed, or favourable traits

(like enhanced intelligence or strength) might be added. While it might seem like it’s straight out of science fiction, designer children are becoming a reality,” Dr Zhang’s New Hope Fertility Clinic states.

Professor Kirksey says there is speculation that He Jiankui partnered with John Zhang to pitch a lab in the Chinese megacity of Shenzhen. It would be a superstore for designer babies “that would cater to medical tourists around the world … They envisioned a site where CRISPR and other advanced IVF techniques would be used on a large scale, and it would be a training hospital that would teach people from around the world to use these techniques,” Professor Kirksey says.

China’s one-child policy – repealed in 2015 – created a hunger among expectant parents to “make their shot count”, Professor Kirksey says.

In a world where you could roll the

biological dice on a child conceived in love, or pay a clinician to ensure your one baby would be free from disease and resistant to viruses, the temptation to opt for the latter would be incredibly seductive. And as Dr Zhang’s rhetoric shows, there are clinicians eager to help parents achieve that dream.

In a modern, globalised world, this presents a problem. “Not everybody has the same philosophy about how to think about how to regulate it,” Professor Knoepfler says.

There are groups for whom gene editing can’t come fast enough.

Some women with the BRCA1 mutation voluntarily have their breasts and ovaries removed. According to Professor Knoepfler: “The hypothetical GM baby girl born without a BRCA1 mutation would not only have a different life, but she would never pass the mutation on to anyone in her future family tree.”

The fear is that as the therapeutic work advances, ambitious scientists and hopeful parents may not be able to resist tweaking embryos to produce offspring who are taller, smarter and stronger.

As Professor Knoepfler wrote in GMO Sapiens, The Life-Changing Science of Designer Babies: “Who does not want to be better? And what if you could make a baby who would grow up to be as smart and creative as Marie Curie or Albert Einstein? What if the next Stephen Hawking could be given the gift of never having had the catastrophic illness of amyotrophic lateral sclerosis (ALS)?”

Additionally, offering an ‘à la carte’ designer baby service has the potential to be very lucrative. “It wouldn’t necessarily be a big jump for [IVF] businesses to try to incorporate CRISPR into their offering, if they felt economically it would make sense,” Professor Knoepfler notes.

“IVF is basically a profit-driven sector of medicine,” he says, adding that one of his chief concerns is: “Commercial ventures would push CRISPR into fertility clinics before the science was ready.”

Designer babies now

You might be surprised to learn that, in some countries, you can already pick your baby’s eye colour, hair colour and gender. “It’s very easy to determine what colour the eyes or the hair or the skin tone of a child is going to be,” Professor Kirksey says.” So, these for-profit companies are already offering those services to couples in the US, and they’re offering it to medical tourists from around the world who come to the US to have children. At this point, it’s anything goes in terms of genetic detection.”

Picking hair and eye colour is done through genetic screening, not genetic editing, but in theory you could edit a baby to have the exact hair and eye-colour combination you want. “With eye colour, I think it’s an A to a T, a letter of DNA that determines whether your eyes are blue or not blue,” Professor Kirksey says.

Complex traits are more difficult. Height involves at least 180 genes, and the “height genes” that have been identified don’t fully explain the variability in human size. “The brain is so complicated. There are so many genes involved that we don’t know exactly what they’re doing,” Professor Knoepfler says. “You still hear people talking about using CRISPR to try to make more intelligent people.” This would be fantastically complicated.

He muses about the anecdotal virtue-and-drawback pairs we can observe in humanity that may hint at a genetic connection. If you try to engineer a baby to be creative, do you risk making him or her more prone to depression? If you try to create a child who is highly intelligent, are you dooming them to a life of introversion and social awkwardness?

Among the genes that have been identified for the so-called “good gene menu”, there are known side effects, and potentially unknown side effects. The myostatin gene, for example, which you would tweak if you wanted

your child to be muscular, carries the risk your child will also have smaller organs and a greater risk of a heartattack. If a future parent chooses to edit their baby’s EPO gene to enhance their physical endurance, they will also increase the likelihood the child will suffer a stroke. It’s like pulling a thread on a jumper – you don’t know what else might unravel.

“Certainly people aim and aspire to design babies, and whether or not the reality they produce lives up to their dreams of the design is kind of the core question,” Professor Kirksey says.

And the risks are greater than just the unintended side effects of changing people’s genes. The CRISPR technology is colloquially described as “genetic scissors”, but this is misleading. Professor Kirksey explains: “People like to think that they could type in [a] new genetic code and program the baby of their dreams, but CRISPR doesn’t work like that. It produces targeted mutagenesis. In other words, that is damage that’s focused at a particular part of the genome, but that damage isn’t predictable. So, you might just be trying to change one or two letters of the genetic code. You could end up with thousands of base pairs that get deleted or even a whole chromosome.”

That’s why the threat of rogue operators is so alarming. CRISPR is not hard to come by. If you have access to a lab, it’s cheap and easy to access. “It’s straightforward to get the physical components of the system you need. There are publicly available computer programs to help you customise your system for whatever gene you want to target. That’s freely available,” Professor Knoepfler says.

Would you say no?

Designer babies are alluring, both for parents and the for-profit industry that would deliver them. Professor Knoepfler says this “does create a situation where you might get, for want of a better word, a sort of genetic tourism”. If you consider designer babies an extension of the fertility industry, like He Jiankui, we could find ourselves in a world where parents go offshore in search of a baby, in much the same way that Australian couples get around the ban on commercial surrogacy by travelling overseas.

If you decide you want the daughter with long pigtails and unbreakable bones, you might head to the Ukraine or Cyprus. Perhaps you’ll go to Shenzhen, the Silicon Valley of China.

You’d likely be welcomed into a luxurious clinic – given the millions you’re about to spend – where you are offered a soft robe to wear before your eggs are retrieved. Once that is done, you and your partner could retreat to a room where you are given a cool drink, and a menu of “good genes” that can be edited before your embryo is implanted.

You may decide to reduce your baby’s risk of coronary disease and diabetes, but skip the edit that would allow them to get by on less sleep. Ask any expectant parent and they will tell you they just want their baby to be healthy, but if the doctor promising that your baby won’t get diabetes also says he can ensure they’re athletic, clear-skinned and have an aptitude for maths, would you say no?

Such theories seem far off, but as He Jiankui pointed out, more than eight million children have been born through IVF since the first test-tube baby arrived amid outcry in 1978. And technology moves fast. In 2015, Professor Knoepfler gave a lecture warning of the dangers of allowing scientists to create GMO babies. Just three years later, Lulu and Nana were born.

Though he rails against designer babies, Professor Knoepfler is aware of their allure, saying: “Among those of us who are parents, who does not like to think that their kids are better than average? What if you could almost guarantee that your child would outshine all of the others in the neighbourhood? All the kids in the country? Many of us would give in to that temptation.”