If you have not heard of CRISPR yet, you should have. This is a truly transformative technology that allows for cheap and easy gene editing. It makes a powerful technology easily accessible.

Powerful biological technology, like stem cells to give another example, always seem to provoke profound hope and fear. The ability to manipulate human biology comes with it the hope of treating horrible and currently untreatable diseases. At the same time such technology provokes fear that it will be abused, or that it will violate the sanctity of what it means to be human.

As the public debate over stem cells seems to be fading into the background a bit (like IVF before it), debates over CRISPR and gene editing are likely to come to the forefront.

What is CRISPR?

CRISPR stands for Clustered Regularly Interspaced Short Pallindromic Repeats, which refers to a sequence of base pairs found on the DNA of bacteria that have this feature. Some bacteria and archaea use CRISPR for adaptive immunity, in order to incorporate bits of DNA from invading viruses into segments of their own DNA in order to target their immune system at those sequences.

Cas refers to CRISPR-associated genes. Cas9 is a specific endonuclease that can cleave DNA. It can be combined with specific RNA in a system that can either insert or delete genetic sequences into the target DNA.

What all of this means is that the CRISPR system can be used for highly specific and convenient gene editing, either deleting or inserting sequences into target genes, or turning those genes off. There is an overwhelming consensus that this technology will usher in an age of cheap and easy genetic manipulation.

Research and non-human applications of CRISPR

CRISPR technology, if nothing else, is already proving to be a powerful research tool, and has been adopted by thousands of labs around the world. A small lab with modest funding can use CRISPR to, for example, turn off a gene in a target species (from bacteria to mice) and then study the effects in order to understand what the gene does. This promises to accelerate our understanding of genes which will likely have tremendous downstream effects.

CRISPR can also be used to create genetically modified organisms. It was recently reported, for example, that researchers used CRISPR technology to create genetically modified mosquitoes that are resistant to malaria. This sparked its own ethical discussion about releasing genetically engineered organisms into the wild before we can fully understand all the intended and unintended consequences.

Medical applications for CRISPR

CRISPR technology has not yet been adequately tested in humans, but there is no reason to suspect that it will not work just as well in people as in other animals.

A Chinese team of researchers recently announced that they attempted to edit the genes in human embryos with the genetic disease beta-thalassemia. The results were mixed, and were not reliable enough to be a safe and effective treatment. The results suggest that the application of CRISPR to human disease needs to be further developed before we will begin seeing treatments based on this technology.

There are research teams currently working on just that. The low-hanging fruit for application in humans are diseases in which the cells are easily accessible. One company, Editas, is working on two possible applications. The first is a treatment for a rare retinal disease, Leber congenital amaurosis. This would involve treating the retina, which is easily accessible.

The second application is the treatment of blood cancers by removing immune cells from the patient, then using CRISPR to target those immune cells against the cancer, and inject them back into the patient.

There is no theoretical reason why any cell population in the body cannot be targeted, but there may be significant practical limitations.

The ethical considerations of editing the human genome

Where ethicists become most concerned is when germ cells are the target of CRISPR. Any changes in the germ cells can be potentially passed down to future generations, essentially introducing those changes into the human population.

The reason to do this is to treat genetic disorders. It might be possible, for example to treat sperm or eggs with a genetic mutation with CRISPR to remove or replace a gene that causes disease. Alternatively, a fertilized egg could be treated prior to implantation.

With gene-altering technology, treating horrible genetic diseases is always the obvious application. Critics, however, worry that if the technology is developed to treat diseases it is a slippery slope to treating unwanted characteristics that are not actually diseases. Parents wanting stronger, smarter, taller children, for example, might be tempted by such technology. This all leads to the ubiquitous example of gene editing for superficial characteristics – choosing eye color.

What really stokes fears, however, is contemplating genetic alterations that are outside of the current range of human variability. This can be simple, like creating eye colors that do not currently exist, but science-fiction is full of examples of creating super soldiers or elite rulers.

Today is the second day of a three day conference being held in Washington DC to discuss the ethics of using CRISPR technology on humans. The conference was organized by Jennifer Doudna, the inventor of the CRISPR-Cas9. She says about the conference:

“The real purpose of this is not only to communicate fundamental aspects about the science to the public and nonscientists, but also to really think deeply together, as a community, about how we move ahead in a responsible fashion,” she said. “At the very least, I hope we will get on the table what people’s concerns are and what their points of view are.”

She is calling for a halt to the use of CRISPR on germ-line cells until the technology can be further studied. She will lay out her views in an article published tomorrow in Nature.

Conclusion: The feared becomes the familiar

I think it is a good idea for the scientists involved to discuss the ethics of CRISPR openly, involving concerned segments of the public. It is reasonable to think carefully about any new technology, especially one that is as powerful, and spreading as rapidly, as CRISPR.

I also think, however, that fears about the use of CRISPR on humans, and on germ-line cells, will be overcome. That is the typical pattern – recombinant DNA technology, implanting animal parts in humans (like pig valves), in-vitro fertilization, gene therapy, and stem cells have all met similar concerns and resistance, and predictably over time came to be accepted.

Eventually the benefits of biological technologies come to be recognized, while the worst fears never manifest. This does not mean we do not need to think carefully about new technologies, and to regulate them properly.

One source of fear is that biological technologies somehow violate what it means to be human. People have an emotional sense of what is “natural” and “pure,” and a disgust reaction can be provoked by anything that challenges that sense. This is essentially the source of opposition to GMOs as “frankenfoods.”

Over time, however, familiarity blunts that response.



Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.