Gene therapy is currently one of the fastest growing areas of science and medicine – from gene-editing tools such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), base editing and prime editing to diagnostic tools such as SHERLOCK (Specific High-sensitivity Enzymatic Reporter un-LOCKing) and DNA hybridisation. The question surrounding gene therapy is not whether we can use it, but if we should. Gene therapy is an issue of ethics rather than ability.
Before you can begin to consider the ethics of gene therapy, you must have an understanding of what it involves. DNA (the genetic code) is made up of a series of bases (either A, C, T or G) which code for specific proteins. The most discussed type of gene therapy is gene-editing, in which scientists use enzymes and molecular tools to change an individual’s DNA sequence. The most renowned and widely used type of gene-editing is CRISPR-Cas9 gene-editing, where an enzyme called Cas9 cuts through DNA like molecular scissors. A small RNA molecule called a guide RNA (gRNA) directs the scissors to the DNA which needs to be cut, which turns the target gene off. There are thousands of gRNA sequences available for use in the research community. The molecular scissors cut through both strands of the DNA double helix, then the cell’s repair mechanism mends the cut, but it often makes mistakes. Mistakes made during repair can completely change the base sequence of the protein the DNA encodes, or stop the production of the protein altogether. Unlike many other gene-editing tools, CRISPR-Cas9 can be used to target multiple genes simultaneously, making it very useful. It can also create large deletions, shuffle genes near the target side, and cause unwanted, off-target mutations that could lead to the activation of genes which cause cancer. These off-target mutations are the biggest flaw of CRISPR-Cas9 but have led to the production of other gene therapies such as SHERLOCK, a diagnostic tool.
SHERLOCK targets RNA instead of DNA and uses the non-specific activity (off-target mutations) to detect whether a particular RNA sequence is present by amplifying the effects of the Cas9 complex to generate a detectable signal. SHERLOCK is used to detect levels of Zika in urine. The Zika virus is usually very hard to detect as there are often very few copies of it in the body, but the faults of one type of gene-editing allowed a very sensitive test to be produced. This shows that although not every attempt to further gene therapy will have the desired outcome, other life-saving processes could be found instead, therefore still having a positive effect. A lot of treatments are discovered by accident, so we cannot stop scientists from exploring all possibilities.
One of the issues surrounding gene therapies is competition, as many scientists see the development of gene therapy techniques as a race. Each country wants to discover the best technique. However, patriotism and pride may not be the best reasons to pursue further research, and competition due to rushing could lead to mistakes being made. If reaching the finish line is given greater importance than what the finish line actually looks like, the quality of the final result may not be as high as if the research was done under less pressure. However, it is proven that high pressure environments and healthy competition lead to more innovation and ingenuity. During war times, a vast number of scientific and medical discoveries were made, including penicillin, blood transfusion, and the production of many vaccinations. It is difficult to think of an environment with more pressures than war, yet that is when innovation was at its finest. Although the motivation may not be completely selfless, scientists all over the world trying to produce the highest quality research as fast as they can is surely not a bad thing.
One of the greatest ethical issues surrounding gene-editing is the idea of how it will be used, and who by. Questions of non-therapeutic procedures, cosmetic procedures, designer babies, and a gene-edited upper class often arise when discussing gene-editing. Currently, science is not advanced enough to fully understand the mechanisms behind features such as eye colour, so gene-editing cannot be used for cosmetic reasons just yet. Therefore, issues surrounding whether or not non-therapeutic uses will be cost-prohibitive or only available to a select few are premature. Theoretical issues about future use cannot be allowed to prevent present development.
Additionally, plastic surgery for non-therapeutic and cosmetic reasons is already permitted and this is not very different, so a further debate is unnecessary. Designer babies (babies whose genes have been selected or altered) are often seen as unethical, as their existence implies that babies with certain characteristics are more valuable than others. However, designer babies include babies that have had genes selected to prevent fatal childhood diseases – not just desirable traits such as intelligence or strength. During IVF, embryos are screened and chosen based on their genetic makeup, so designer babies are already allowed, and should not hinder developments in gene therapy.
The ethics of gene-editing change depending on where the editing is being done. Gene editing can be done in somatic cells (body cells), or in embryonic cells and gametes (egg and sperm cells). The majority of diseases affect somatic cells, so gene-editing where the disease takes effect can treat the condition. An example of this is macular degeneration — a retina condition that leads to blindness. Gene editing of the DNA in the cells of the retina can treat the condition. When editing somatic cells, the patient can make an informed decision about whether or not to have the treatment and is able to give consent. Edits made to somatic cells are not passed on to offspring, so the only person affected by the gene-editing is the patient and the germline is not affected. This is usually seen as ethical because the patient has personal autonomy. Embryos, however, do not.
Gene editing of embryos is a much more complicated issue. Embryos (and gametes which fuse to become embryos) cannot consent to gene-editing. They cannot make an informed decision. They cannot explore the potential consequences, both positive and negative. Therefore, it is seen as highly unethical to edit their DNA. When gene-editing embryos, doctors, parents, and scientists make a decision that will ultimately affect someone else. Although this decision could improve the embryo’s future quality of life, prime editors (one of the most efficient types of gene-editor) are only up to around 78% accurate, and more widely used editors such as CRISPR-Cas9 are much less accurate. Even if the gene-editing has the desired effect, and is accurate enough to improve the embryo’s condition, there is still the issue of unwanted, off-target mutations, which could cause additional problems. Any edits made to embryonic cells and gametes affect the germline, so they could be passed on to the embryo’s offspring. This means that unwanted mutations could introduce a different genetic disorder (which could be worse than the original problem) to the embryo’s family line. The decision may not only affect an unborn child, but that unborn child’s future descendants too.
In the worst-case scenario, the gene-editing of an embryo could be unsuccessful and result in unwanted mutations. This is believed to have happened to a set of twins in China, whose embryos were edited to make them immune to HIV. The researchers were unable to prove that the gene-editing was successful, and scientists who have analysed the research think unintended mutations may have been created. There is evidence that both babies had mosaicism (two or more genetically different sets of cells), so any edits and unintended mutations were not uniform across all of each baby’s cells. The babies were born despite the researchers not knowing what the effects of their gene-editing would be. The twins are the first ever gene-edited babies and did not give consent to a procedure that could affect the rest of their lives. This is highly unethical, and the lead researcher has been sentenced to three years in prison.
On balance, gene therapy is a step in the right direction. The benefits that gene therapy could eventually have to society are too large to ignore. Genetic disorders can be more effectively treated in patients, and one day, we could prevent babies from being born with them too. Eventually, certain genetic disorders could be erased from the human genome forever. Although the case of the twin girls in China is a harrowing example of how the technology could be misused, public policy cannot be determined by the extremes. Gene therapy is not perfect, and should not be used on humans in its current state. However, scientists should be allowed to develop it further, and perfect their technique in order to help cure society.
