EXPERT REACTION: US scientists genetically modify human embryos

The efficiency and accuracy of gene editing is becoming better with each passing year and there is a strong argument that we have a moral duty to correct DNA mutations in embryos that carry mutations that cause severe diseases. Demonstration that there are no unwanted mutations that occur alongside the correction of the disease causing mutation is critical since this procedure would alter the genetic make-up of the offspring of all future generations.

Such genome correction of human embryos is currently not allowed in Australia without a licence and embryos cannot be allowed to mature post 14 days. Internationally stem cell scientists have called for a temporary moratorium on its use in human embryos while lawmakers, regulatory bodies and society  inform themselves of the risks and benefits of taking charge of our germline.

Some would argue that it is the next logical step in human evolution, but would we have had a theory of relativity if we could have eradicated the mild autistic genes from the Einstein family?

The, as yet unsubstantiated, report that US researchers have modified human embryos using CRISPR genome editing will trigger a lot of discussion but for the foreseeable future, human germline modification, if it occurs at all, will be extremely rare.

It may be considered in cases where both parents are affected by a serious genetic disease but it is very unlikely that it will be used in any other situations, such as genetic enhancement, for the simple reason that the risks and benefits are not clearly defined.

We do not yet know about the risk of off-target effects, nor do we generally know which genes would provide enhancements. The fact that the procedure can be done in the lab doesn’t mean that the very few families who could benefit will move to rapidly adopting it.

The process of modifying an embryo in a test-tube is one thing but successfully carrying that embryo to term is obviously a much more significant undertaking and. accordingly, considerable thought and consideration of local legislation will be required before any action is taken.

Although some would argue that the genetic modification of human embryos for research purposes creates a 'slippery slope' towards designer babies with genetic enhancements, it is important to remember that these studies are governed by strict regulations (the embryos in this study were not allowed to develop past a few days).

CRISPR/Cas9 is still a very new technology and most experts in the field would agree that we must be very cautious about using this technology to create lasting changes that are passed on to subsequent generations as this could have undesirable and unpredictable consequences. Further studies are needed (even those using human embryos that would otherwise be discarded) to fully evaluate its safety and address its potential risks.

As a side note, the ability to make precise changes to the DNA at the initial stages of fertilization may also offer powerful insights into very early stages of human development that have not before been possible.

Gene editing technologies such as CRISPR and TALEN can be used to alter the genetic code in living organisms. They have been used by many groups with high efficiency in cells growing in dishes and in animal models of human diseases. For exploratory science, gene editing technologies have proven very powerful and have given great insights into biology and human disease. Understandably, there has been concern on where these technologies may be next applied as the gene editing techniques have the capacity to alter human DNA sequences. Gene editing offers the possibility of correcting genetic disease causing mutations. This may be done in tissues such as heart and lung in the lab with the tissues then transplanted into a patient to help with new treatments.
 
Gene editing also raises the possibility of correcting disease-causing mutations in the early stages of human life. There are understandably polarising views on the ethics of such possibilities. While this has recently been done in China, there is now a report that this has been done in the US for the first time. Human embryos have undergone gene editing at the single cell stage, but were not permitted to fully develop. We cautiously await peer-reviewed publication of the data. Recent reports on gene editing have raised issues including off-target effects, reminding us that these technologies are still new and require further research and investigation. This new report again raises the need for discussions on what situations gene editing will be used in in the future.

CRISPR-based genome editing is probably the single biggest technical breakthrough in the history of life sciences, and this simple technique now gives us ultimate control to recode the human genome. From genetics work over the past century, we know of many mostly rare mutations that cause human disease, and with CRISPR we can now consider repairing these mutations and basically curing these diseases. As far as applications for CRISPR that are most likely to improve human health, genome editing of mutations causing cystic fibrosis, sickle cell anemia, immune deficiencies, or editing the HIV receptor, are the kinds of applications that are most likely going to translate quickly into real treatments.
 
CRISPR is surprisingly easy to use, and what was stopping us from editing humans wasn’t really any technical limitation, it was really more about the ethics and safety. So from that perspective, this study is more about testing the boundaries of our society vs. any real technical advance. I think we still have a lot of work to do as a society to lay out appropriate applications for genome editing (like CRISPR).
 
Talk of designer babies and genome editing for traits like intelligence or beauty is still very much science fiction, as we don’t really even know how to control these traits genetically. In most cases genetic mutations are context dependent, so will have different effects in different people. If as a society we were going to develop these approaches, there would inevitably be some mistakes, which most people would probably not be OK with, so that is something to consider. Basically, recreational hacking of the human genome is still a way off, so now is a good time for us to discuss what we are ok with and what should be illegal.

It was only a matter of time…. The first experiments recently carried out by Chinese scientists on human embryos using CRISPR, the revolutionary genome editing technique, sparked a worldwide reaction. The leaders of the CRISPR world immediately called on a moratorium in a bid to stop manipulating the genome of human embryos. It was probably already too late.

Considering that there has not been a single species reportedly resistant to CRISPR genome editing (from bacteria to plants, mice, cattle or even monkeys) it was only a matter of time before human embryos would be tested. Like any other breakthrough, CRISPR technology is routinely used in so many different applications, for so many different purposes, that it is nearly impossible to keep up with the scientific publications. One should consequently not be surprised that the genetic modification of the human embryo be the ultimate goal.

Should we rejoice, or rather be terrified? The answer certainly does not lie in the power or the limitations of CRISPR. These are studied and perfected on a daily basis by scientists around the world. This is what we do in our lab in cells or in animals such as mice, like many others labs in Australia.

What we should consider now, more than ever before, is 'what do we use CRISPR for when it comes to human beings'? The answer will certainly not be an easy one, but it will draw the lines of future CRISPR applications in humans.

Take for example the concept of 'designer babies'. If you bluntly question people around you about the possibility of 'designing' babies, an overwhelming majority would find the idea horrifying, probably as a reminiscence of the abject Nazi endeavors that justified eugenics. However, when asked to consider whether genetic manipulation of the human embryo should be allowed to prevent terrible debilitating and terminal childhood conditions, the answers are somewhat different.

For now, it is very hard to judge what the latest study in the US will bring, since no-one should speculate whilst the publication is pending. But surely it is time to start asking: what do we want to do with CRISPR, and what do we want to do with ourselves?

CRISPR genome editing has provided a powerful means to modify DNA. While researchers use this technology routinely, the application of this approach in human embryos is a significant advance with implications for manipulating the genome of future generations. The ability to correct DNA mutations that give rise to acquired diseases underlies the primary rationale for this work. However, the ethical challenges of defining the boundaries for genome editing in this field will require careful consideration as we increasingly gain the capacity to manipulate human life.