A whole new An edited new world

The implications of CRISPR-CAS9 fall into three categories, says Dr Samantha Nicholson, a post-doctoral fellow at the Institute for Cellular and Molecular Medicine (ICMM) of the University of Pretoria who is working on gene therapy technologies using CRISPR to produce an Hiv-resistant immune system. Those three categories involve using CRISPRCas9:  As a laboratory tool  As a therapeutic tool  In synthetic biology.

As a laboratory tool, CRISPR-CAS9 can be multiplexed: in other words, it can tackle multiple targets at once. “In the short term, CRISPR’S most significant contribution will be in allowing us a greater ability to recreate complex disease states, and will allow us to answer increasingly complex mechanistic studies to understand cell biology better and the pathology of many diseases in greater detail,” said Nicholson.

“The more exciting implication is gene therapy – the ability to directly change the genetic code thereby eradicating disease or even allowing us to enhance the human race. This also has the greatest technical and ethical challenges. We don’t yet understand all of the potential unwanted effects of changing the genetic code. However, gene therapy using CRISPR is incredibly promising because of the reduced cost. Once we establish the safety of this type of application, it has the potential to eradicate a huge number of genetic diseases and improve the lives of millions of people. This, combined with the relatively short time needed to design new applications means that CRISPR has the potential to revolutionise personalised medicine and the treatment of hereditary disorders.”

CRISPR-CAS9 is also an ideal switch for

synthetic biologists because it is specific and modular, easily manipulated and changed and, with small additions or deletions, it can be used for much more than cutting DNA. “It is an ideal regulatory and reporter vehicle and is already being broadly applied in this field, which in itself is still very young. This is an interesting space and I wouldn’t be surprised if this is where CRISPR technologies really shine.”

For Nicholson the most exciting, and also most worrying implication is that we will eventually be able to edit out undesirable human traits. “For most people this means fixing or eradicating disease-causing genes. But it has a strong potential for abuse and we don’t really understand the full impact gene editing will have on the evolution of the human species. We may unknowingly direct our evolution in a way that may be harmful to the human race as a whole. So, while the possibility that we may totally eradicate disease on a level with vaccinations is amazing, we also have to consider where the line in the metaphorical sand might be. As we learnt from Spiderman: with great power comes great responsibility.”

Respected synthetic biologist, Dr Musa Mhlanga; post-doctoral, fellow Dr Stephanie Fanucchi; and Ezio Fok, a PHD student, all from the Gene Expression and Biophysics Group, aka the Mhlanga Lab at the Council for Scientific and Industrial Research (CSIR), have also conducted studies that employ CRISPR-CAS9. Says Fok: “The CRISPR-CAS9 technology is so powerful because it allows for a simple and cost-effective way to precisely edit the human genome. Researchers have successfully applied this technology to modify the genomes of plants, bacteria and whole organisms (that is, zebrafish and mice). These studies have revealed previously unknown aspects of cell biology and yielded important insights into disease progression.”

According to Fannuchi, gene editing has already started to have a significant impact on human health. For instance, using CRISPR-CAS9 and another powerful genome editing technology called TALEN (Transcription Activator-like Effector Nucleases), it’s possible to genetically engineer artificial anti-tumour receptors into patient immune cells to create “soldier cells” able to recognise and eliminate cancer cells displaying the appropriate tumour antigens. “Although scientists are still cautious that this therapy may cause unintended side effects, clinical trials in adults and children with leukemia or lymphoma have yielded optimistic results.”

Mhlanga believes the first effects of CRISPR-CAS9 in our daily lives will most likely be seen in genetically engineered plants and animals. “CRISPR has already been widely applied in plants in attempts to generate disease- and drought-resistant crops and improve plant traits. Gene editing in animals has also produced hornless dairy cattle, which has led to easier and higher numbers of successful cow births. By improving and securing food supplies, the effects of gene editing will have a huge impact, especially with the ever-increasing threats to food security,” said Mhlanga.

The problem, says Mhlanga, is that although our interventions may seem beneficial at present they are untested by the long arc of evolution for their positive or maybe negative effects. “Essentially this type of ‘biohacking’ or genetic enhancement is perhaps the most ethically and morally difficult terrain on which gene editing takes us.”

As the technology grows and its full potential becomes more tangible, it is paramount, says Fok, that scientists come together and clearly define rules and regulations that will guide researchers to use CRISPR safely and responsibly. “Although gene-edited humans are still more than a decade away, we need to define the boundaries now, so that we know what to do when we get there.”

Nicholson says scientists have luckily already started to address these ethical questions.

“As it stands, there is an annual meeting where the ethical issues around CRISPR are discussed by the field leaders. By continuing to engage in public debate and to refer to our own morals, we should be able to proceed in an ethical and acceptable way. Having a well-informed and engaged public will be increasingly valuable to help scientists to litmus test their thinking.”

Engaging with these ethical concerns is important because it’s only going to get wilder from here. The Kurzgesagt video mentioned earlier, titled “Genetic engineering will change everything forever – CRISPR”, warns that, as gene editing is refined, more people will argue that not using it will be unethical because it would condemn children to unnecessary, preventable suffering from hereditary diseases or mutations that might be easily cancelled out with CRISPR-CAS9.

The temptation for genetic enhancement will also grow. If you can make a child immune to Alzheimer’s, why not give him or her perfect vision. Or better muscle structure? Or a higher IQ?

It’s easy to see how genetically enhanced humans could become the new standard. Not to mention the fact that some scientists believe CRISPR-CAS9 could potentially pave the way for humans to stop – or even reverse – ageing.

Great responsibility, indeed.