OPENING PANDORA'S BOX 

 

Chinese scientist He Jiankui stunned the world when he announced that he had successfully edited the genes of two new-born babies. Is gene editing technology safe? What are the implications of manipulating the human genome? Associate Professor Roger Foo, Senior Consultant at the Cardiovascular Research Institute, National University Heart Centre and Dr Owen Schaefer of the Centre for Biomedical Ethics share their perspectives.

It is no longer unusual for the young today (i.e. medical students) to have a vast and worldly travel experiences. Walking along a corridor at Heathrow Terminal 5 last year (alas some of us still travel by British Airways), I came across an advertisement meant absolutely to capture the attention of the passing public (see figure). For a while now in the UK, there has been growing concern that covert slavery is festering in the “underworld” up and down the country. 

 

I guess we should excuse the advert for stereotyping the characters with Asian faces. But this advert struck me. Five years ago, upon returning to Singapore to work, my ageing dad fell seriously ill, and for the first time, our family had to employ a helper. One evening that week, I found myself waiting at the arrival hall of Changi Airport, and saw a frightened trembling young girl (our new helper) walking out of the baggage claim area. Beside her was the “maid-agent” who had accompanied her from her homeland. How are these scenarios different, apart from the country and the context? The issue of perspective always strikes me very hard, as it must do for those of us who keep aware of the larger changing world around us. 

 

Last year in November (2018), a scientist (Dr He Jiankui) in Shenzhen proclaimed that he had successfully brought 2 CRISPR genome-edited babies into the world. Lulu and Nana were allegedly new-born to a couple whose father has HIV, but unlike all other foregoing IVF conceptions in past decades, Dr He had edited the CCR5 gene in the embryos so that both babies have been born with CCR5-deficiency. Individuals with CCR5-deficiency are resistant to HIV. 

 

Dr He made his first announcement on YouTube, fortuitously before an International Genome Editing Summit in Hong Kong. The disclosure provoked international outcry. Scientists in the field condemned He’s actions. Professor Feng Zhang (MIT), one of the inventors of the CRISPR-editing technology, called for a moratorium on the use of CRISPR to create gene-edited babies. At the Summit, Dr He presented and defended his work saying “I feel proud”. 

 

Rumours abound. No one has yet said that they have seen the babies. A second gene-edited pregnancy is apparently under way. The Chinese government has since suspended He’s research activities. Aligning with the international furore, the authorities have denounced the research as “extremely abominable in nature” and in violation of Chinese laws and science ethics. The Chinese state media confirms the existence of the two babies, but the research was apparently not officially funded, and the state was not made aware previously. Dr He’s whereabouts are now uncertain. Some on-going investigations include “collaborators” of Dr He from esteemed institutions in the West, including his former mentors.

 

Without revisiting countless well thought-out reviews and ethical debates on the matter, some prominent points are worth mentioning. (1) CRISPR is not yet deemed safe for human use. There are scientists in the HK summit who noticed serious off-target effects from his CRISPR-edited gene sequences. (2) Dr He did not get bona fide consent from the parents. He consented the procedure as a vaccination to prevent HIV in the babies. Arguably, he would claim, his non-expert patients (the parents of Lulu and Nana) would not have easily understood the difference between the two approaches. The onus is on the scientist to ensure a clear understanding. (3) Dr He had failed to get an ethical board approval from his own institution, and went instead to another institution and obtained approval to proceed. Yes. There actually was an ethical review board in the country which approved this research. 

 

But Dr He earnestly believed himself to be doing good. Watch the video and note his sincerity. He may have been seeking fame and glory, but it is not hard to see that he really did think that he was pushing progress for mankind. Note: pushing the progress is also what we urgently want to do here in Singapore. Dr He actually went to the lay public and sought open opinion before embarking on his project: “would you want to have a gene-edited baby where a disease is prevented”, “what if there is some risk”, “is HIV a disease worth preventing”. Maybe unsurprisingly, He received significant majority

support from his public. Still, it seems wrong for Dr He not to articulate the serious risks of the procedure. Or was he aware of the serious risks himself? Had he assessed the risks and thought them to be low and worth taking?

 

What about when the risk is one day removed? When gene-editing is perfectly razor sharp, and we no longer have to worry about complications of off-target editing or mosaicism from incomplete cell targeting. Does that then become ethically acceptable for us to proceed with gene-editing our babies? When the risk-benefit argument becomes less relevant, we will be pushed to consider whether editing to treat a baby’s disease, or editing to augment a baby’s trait, is acceptable. Debate that human augmentation should never be approved rages: editing to improve brains or looks, does not sound ethical on so many levels. But this presents a very slippery slope. Are we not merrily augmenting ourselves through the countless aesthetic clinics at shopping malls all across our island nation? If you have the precise tool to secure an intelligent, healthy and good-looking baby, what is there to stop you racing to the front of that queue?

 

The world has actually been here before. A lesser-known cousin of Charles Darwin was Francis Galton, who allegedly never got over the spotlight and pride of place his cousin enjoyed. Galton believed he had found the perfect “translation” for Darwin’s science by acting on the question, if nature “achieves such remarkable effect on animal populations through survival and selection”, why can’t we accelerate the process by human intervention?

 

Thus, the science of Eugenics was born. Galton went about curating evidence that beauty, and even behaviour, were distributed in bell-shaped curves. In pedigrees of eminent men, 1 in 6 of all accomplished men are apparently related. One in 12 sons of eminent men go on to eminence, whereas by random selection it is merely 1 in 3000. Hence, like the breeding of horses and hounds even today, Galton advocated for “Selective Breeding”. The good-looking should marry the good-looking, etc. In the USA, Dr Charles Davenport (1866-1944) went further to advocate for and establish colonies to house the “genetically unfit”. The operational effort grew in many states to eliminate “defective strains” in America.

 

Unsurprisingly, colonies started carrying out Selective Sterilisation in those deemed genetically unfit. These were all mainstream. Experts met at international congresses for Eugenics. Professorship Chairs of Eugenics were established. In Germany, this became called “racial hygiene”. And before long, the world entered the abyss of Selective Termination: removing the “lesser race” and “less genetically pure”. The people carrying out these procedures were seriously sincere in doing good. Richard and Lina Kretschmar, ardent supporters of the Nazi regime, petitioned Hitler to euthanize their 11 month old son Gerhard because he was born blind and with deformed limbs. They believed they were serving their nation by eliminating their child from the nation’s heritage.

 

Admittedly, my examples here risk plagiarising from Dr Siddhartha Mukherjee’s book. He has written eloquently on mankind’s journey of the Genetic Discovery. It is a must read that delves into the topic.

 

We are in exciting times in science and medicine. It really is possible to sequence a person’s whole genome at a very affordable price today. My relatives and patients ask me everyday: why sequence the genome if there is nothing you can do to correct it. But, the means to edit/correct a genome has also become very accessible (at least in the lab for now). This is the democratisation of science today. No longer is technology only within the reach of the richest one or two labs or countries in the world. Any lab worth its funds can buy CRISPR tools and use them readily.

 

In our lab, we edit a gene nearly every other month. We can not only edit/correct genomes, some labs are writing genomes (constructing organisms). When man can read genomes on the one hand, and edit or write them on the other hand, is this when he becomes God? Will we recognise an ethical dilemma when we see one?

 

- Assoc Prof Roger Foo