By Elmary Buis and Jetane Charsley
The picture : CCO- Public Doman.
As the novel coronavirus SARS-CoV-2 (the name of the virus that causes the COVID-19 disease) spreads rapidly across the world, claiming hundreds of thousands of lives, and infecting many more, the demand for fast tests and treatment options soars. The standard tests in most countries have been described as too slow and cumbersome for the current environment and scientists are working around the clock to find a quicker and more effective test, a vaccine, and specific treatments for virus.
Among the scientific approaches to the pandemic is CRISPR, a gene-editing technology currently revolutionising the scientific world.
CRISPR holds the potential to eliminate diseases, create higher-yielding crops, eradicate dangerous pests and resurrect extinct species, and, in the future, even lead to "designer" babies and eternal youth.
The possibilities of CRISPR technology cannot be ignored, and neither can the ethical concerns related to gene editing. The rapid pace of scientific change necessitates public understanding and knowledge to keep pace with what Dr Mark Behlke, an expert in the field, says "could lead to one of the greatest scientific revolutions in recent times."[1]
But what is CRISPR technology?
CRISPR stands for "clustered regularly interspaced short palindromic repeats", and is a family of gene/DNA sequences found in single-cell organisms like bacteria that don't have a distinct nucleus. With CRISPR technology, these DNA sequences are used as a gene-editing tool, or a pair of "molecular scissors" to cut and edit the DNA in the cells of plants and animals, including humans. The CRISPR system can recognise any short DNA sequence in plant and animal cells, cut it out, and insert a new one.
Besides cutting, you can "regulate activation or suppression of certain genes by using CRISPR not as a cutting tool, but instead as a binding tool to attract activators or repressors to induce traits."[2]
What makes CRISPR more appealing than other genetic engineering tools like those used in genetically modified organisms (GMOs), is that CRISPR is more precise, cheap and easy to use, as well as versatile and remarkably powerful.
What are the benefits of CRISPR technology?
The technology has many benefits, some of which are described below[3].
CRISPR could correct the genetic errors that cause cancer and other diseases
Genetic errors may be inherited from parents, or could result from mutations that occur during gene replication associated with the normal growth of cells.
Some life-threatening hereditary diseases are caused by an error on a single gene. Single-gene disorders include cystic fibrosis (which causes the body to produce thick, sticky mucus that can clog the lungs and obstruct the pancreas), haemochromatosis (a disorder where too much iron builds up in the body, which can lead to life-threatening conditions like liver disease, heart problems and diabetes), and sickle cell anaemia (where the red blood cells, the oxygen carriers in the body, are irregularly shaped, become rigid and sticky, and get stuck in small blood vessels, slowing or blocking blood flow and oxygen to parts of the body).
With CRISPR technology, disease-causing genes can be cut and a correct gene inserted to cure the disease.
Gene alterations (mutations) are characteristic of cancer. The cancer therapies currently available (like chemotherapy and radiotherapy) have harmful side effects, reducing the quality of life of the patient, and are also very expensive. Advances have been made in sequencing technology to explore ways in which the cancer genome can be corrected.
CRISPR could eliminate the microorganisms that cause disease
In 2018, it was estimated that 7,7 million people in South Africa are HIV positive[4], and although antiretroviral therapy treatments have turned HIV/Aids into a livable health condition, scientists still haven't found a cure. CRISPR could change this. In 2017, a team of Chinese researchers successfully increased resistance to HIV in mice by replicating a mutation of a gene that effectively prevents the virus from entering cells.
Another gene-editing trial will attempt to use CRISPR to disrupt the genes of the human papillomavirus (HPV) (a virus that causes cervical cancer tumor growth), effectively destroying it.
CRISPR could bring extinct species back to life
Dr Ben Novak, who works for conservation organisation Revive & Restore, is using CRISPR to try and bring the passenger pigeon back to life in North America, where it was once abundant. Rock pigeons have become city pests, but the passenger pigeon is different and, "It's not about the bird. It's about what the bird does for the entire ecosystem," says Novak.[5]
A million species are likely to become extinct in the next few decades, and biodiversity is under threat. Bringing back an extinct animal could help to balance an ecosystem, and a biodiverse ecosystem can help to protect water resources, and contribute to climate stability and food security.
CRISPR could create new, higher-quality and higher-yield crops
Prof. Yiping Qi, a plant scientist at the University of Maryland, is concerned about providing food for an ever-increasing global population, and is doing extensive research on CRISPR technology in crops. "We will have 10 billion people by 2050," he says. "How can we sustain crop improvement to feed more people sustainably with climate change and less land? I really think that technology should play a big role in that."[6]
While there is resistance to GMO crops, there is less stigma around CRISPR technology. The two methods are very different, with GMOs made by inserting DNA sequences from other organisms into a plant's genome to change plant traits. With CRISPR gene-editing tools, no foreign DNA is introduced. Changes are made to the structure or locations of the genes without introducing foreign DNA.
There is thus greater acceptance of CRISPR crops than of GMOs. In 2016, the US Animal and Plant Health Inspection Service confirmed that a CRISPR-edited mushroom did not need to pass through the Department of Agriculture's regulatory processes because it did not contain foreign DNA from viruses or bacteria. Australia, Sweden and Argentina, among others, also categorise and regulate CRISPR-edited crops differently to GMOs because no new genetic material is introduced.
CRISPR could eradicate disease-transmitting pests
CRISPR could eradicate dangerous pests, like the malaria-carrying Anopheles mosquito. Malaria is a global concern, but of particular concern in Africa, which carries a disproportionately high share of the global malaria burden. The World Health Organisation's latest fact sheets show that in 2017, Africa "was home to 93% of malaria cases and 94% of malaria deaths. Total funding for malaria control and elimination reached an estimated US$ 2.7 billion in 2018"[7].
Scientists at the University of California developed a kind of mosquito that is uniquely susceptible to changes made with CRISPR, and are aiming to produce wingless mosquitoes that will not be able to spread malaria. Other researchers focus on changing how mosquitos reproduce. In 2016, a team at the Imperial College London used CRISPR to develop female-sterility traits in the Anopheles mosquito that may be inherited by their offspring.
What are the concerns about CRISPR technology?
CRISPR technology provides scientists with the power to alter DNA – the source code of life itself – with ease and relative accuracy. This power brings with it many ethical questions and concerns. Of particular concern is that the editing process can result in off-target DNA being changed, causing unwanted effects. What if CRISPR makes changes in the wrong place and unintentionally alters or removes healthy genes?
It is important to distinguish between CRISPR techniques used for somatic gene editing (which alters genes in an individual and is not passed on to offspring) and germline editing (the editing of sperm, egg cells or embryo cells, which results in traits passed on to future generations of the organism).
Given the many benefits of CRISPR technology, many people will not be too concerned about somatic cell editing, mostly because if the technology goes wrong the risks are confined to the organism being experimented on. For people, this means that a patient suffering from a disease that can be corrected can give informed, voluntary and rational consent to the gene-editing experimentation. This means that the individual accepts the risks associated with the CRISPR study without influencing his/her future offspring.
In contrast, germline editing, in which species could be permanently changed or eliminated is ethically less palatable.
For instance, although malaria is a great killer transmitted by Anopheles mosquitoes, interfering with mosquito populations could have unintended consequences.
"Eliminating a species, even one that doesn't appear to have much ecological value, could upset the careful balance of ecosystems. That could have disastrous consequences, such as disrupting the food web or increasing the risk that diseases like malaria could be spread by different species entirely," explains journalist Victor Tangermann.[8]
Furthermore, germline manipulation of human embryos, even with good intentions, is considered a no-no even by CRISPR scientists, especially as CRISPR technology is still in its infancy. For instance, crossing this ethics line was more than career limiting for Prof. He Jiankui, who not only lost his job but was also sentenced, on 30 December 2019, to three years imprisonment and ¥3 million fine. This followed a huge public outcry when He Jiankui announced in 2018 that his team had successfully created the world's first genome-edited ("designer") twins, who were born from genetically modified embryos that were made resistant to HIV[9].
Conclusion
CRISPR technology is revolutionising science and, as it becomes more refined, is likely to have many more benefits, from curing diseases to improving crops. However, if the pace of scientific progress moves faster than the pace of public awareness and understanding, there is a risk that the technology will face public rejection.
It is therefore important to improve public understanding of what CRISPR is and what it offers us, as well as clarify the difference between germline and somatic gene editing to prevent misinterpretations.
"Bioethicists and researchers generally believe that human genome editing for reproductive purposes should not be attempted at this time, but that studies that would make gene therapy [to treat diseases] safe and effective should continue," advises Mark Behlke[10].
[1] Mark Behlke, 3 December 2019. Looking Back on Gene Editing Advances in 2019 and Towards What the Future May Hold, https://www.technologynetworks.com/genomics/blog/looking-back-on-gene-editing-advances-in-2019-and-towards-what-the-future-may-hold-327799. Accessed 7 January 2020
[2] Yiping Qi, et al. (2019) in Comprehensive review of the future of CRISPR technology in crops, https://www.sciencedaily.com/releases/2019/07/190715114258.htm. Accessed 7 January 2020
[3] Victor Tangermann, 30 January 2018. A CRISPR Future: Five Ways Gene Editing Will Transform Our World
https://futurism.com/crispr-genetic-engineering-change-world Accessed 7 January 2020.
[4] https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/south-africa Accessed 24 March 2020
[5] https://www.cnet.com/features/using-crispr-to-resurrect-the-dead/ Accessed 7 January 2020.
[6] Comprehensive review of the future of CRISPR technology in crops (15 July 2019)
https://www.sciencedaily.com/releases/2019/07/190715114258.htm Accessed 7 January 2020.
[7] https://www.who.int/news-room/fact-sheets/detail/malaria. Accessed 24 March 2020
[8] Victor Tangermann, 30 January 2018. A CRISPR Future: Five Ways Gene Editing Will Transform Our World https://futurism.com/crispr-genetic-engineering-change-world Accessed 7 January 2020.
[9] David Cyranoski, 6 January 2020. What CRISPR-Baby Prison Sentences Mean for Research, A Chinese court sent a strong signal by punishing He Jiankui and two colleagues, https://www.scientificamerican.com/article/what-crispr-baby-prison-sentences-mean-for-research/ Accessed 7 January 2020.
[10] Mark Behlke, 3 December 2019. Looking Back on Gene Editing Advances in 2019 and Towards What the Future May Hold, https://www.technologynetworks.com/genomics/blog/looking-back-on-gene-editing-advances-in-2019-and-towards-what-the-future-may-hold-327799. Accessed 7 January 2020.
