Eight years ago, Dr. Emmanuel Charpentier and Dr. Jennifer Doudna proposed a new application of CRISPR-Cas9. They discovered that CRISPR-Cas9 can be programmed to slice DNA at specific sequences and opened the door to modern gene editing. However, as with many scientific discoveries, the potential applications of CRISPR as well as the potential consequences of gene editing are largely unknown. It also raises serious ethical questions about when and where we should be able to apply this new technology. One well known example of this is the concept of “designer babies.” While the debate around this issue is quite common, the reality of designing one’s own child (choosing hair color, height, intelligence etc.) lies far in the future. In contrast to this, the medical applications of CRISPR-Cas9 are being discovered and tested in clinical trials right now. While most people agree that CRISPR-Cas9 has the potential to help innumerable people, the application of a new technology in any field brings forth ethical questions about when and how we should be able to utilize it.
Dr. Jennifer Doudna explains how CRISPR-Cas9 is used to efficiently and effectively edit DNA:
There are many differing opinions surrounding the use of CRISPR to edit the human genome and even Dr. Doudna herself cautions us about the potential applications of this technology. For example, in 2018, Chinese scientist, He Jiankui, announced that he had successfully used CRISPR to edit the DNA of three infants, making them HIV immune. He achieved this by using CRISPR-Cas9 to disable the CCR5 gene. CCR5 genes are responsible for the production of the CCR5 protein which is a receptor for chemokines found on the surface of white blood cells. Chemokines attract white blood cells to the site of an infection allowing your body to fight it and recover. However, while this is an essential part of one’s immune system, it is also how HIV enters cells. While there is no evidence that Dr. He succeeded in making the girls HIV immune or even that he successfully disabled the CCR5 gene, his colleagues believe there is a strong chance he was successful. Dr. He performed his experiments illegally and this cast a dark shadow over his research, and also gives us insight into how the world views human genome editing.
Dr. He violated the principle of autonomy and also the principle of non-maleficence. In order to abide by the principle of autonomy, the doctor must get informed consent from the patient undergoing the procedure. In this case, the twins were not born yet so obviously could not give consent or be informed of the risks. This brings me to Dr. He’s second ethical violation. Dr. He and the rest of the scientific community do not know the long term effects or consequences of human genome editing. It is possible that by disabling the CCR5 gene, Dr. He will have caused more harm to these patients in the form of unforeseen complications. The principle of non-maleficence states that the physician should not take any action that causes harm to the patient. This would violate the principle of non-maleficence as even though he sought to make the children HIV immune, he would have ended up causing the patient harm. Granted, due to the novelty of human genome editing and the use of CRISPR-Cas9, it is completely possible that the twins will have no complications.
The CRISPR trials happening today lack many of the ethical issues that caused the uproar surrounding Dr. He’s “clinical trial” in 2018. First and foremost, all three trials have been approved by the FDA or the respective governing body in their country, something not done by Dr. He. In contrast to Dr. He who edited three human embryos, researchers now are taking a far more cautious approach. These researchers are investigating potential applications of CRISPR to treat cancer and various blood disorders. They start by removing cells from the patient, and they then edit these cells and re-inject them into the patient, hoping to alter the microclimate surrounding the tumor.
While on the surface this may not seem far different than Dr. He’s method, in reality this new method is far safer. By editing the embryo instead of the patient’s cells, Dr. He allowed for all of the changes he made to the twins DNA to become heritable. In other words, if/when the twins have children, they will inherit a disabled CCR5 gene. As we do not know the possible complications and long term issues that may arise due to gene editing, it is far safer to simply edit cells instead of the embryo and avoid any risk to future generations. The results of Dr. He’s research are shrouded in controversy, and we may never know whether he was truly successful. However, these clinical trials are underway in the United States and China and because the researchers followed proper procedures, these results may give us insight into how we can treat diseases using CRISPR-Cas9.
These new clinical trials also all adhere to the bioethical principles. In order for a trial to be approved by the FDA (or other governing body depending on the country), the researchers must minimize risk to the patient while maximizing potential benefit, practice equitable subject selection, and receive informed consent from the subject. (University of Washington) Based on these criteria, all of the trials must have adhered to the principles of beneficence, autonomy, and justice in order to be approved.
While there is much controversy over the use of CRISPR-Cas9 in humans, it is mostly centered around the potential non-medical applications of human genome editing. From what I have learned, many of the issues like “designer” babies, lie far in the future. Our understanding of the human genome is relatively limited and the concept of “designing” a child or altering aspects of oneself are, for the moment, impossible. While we may not be able to design our own child just yet, I believe that the medical applications of CRISPR-Cas9 in humans are incredibly promising and far more important than designer babies. While I believe that in the future we will have to grapple with the commercialization of gene editing and the ethics of these new practices, gene editing in people should not be prohibited outright. CRISPR-Cas9 has the potential to help an incredible number of people, and researchers right now are using it to try to fight cancer and blood disorders. As long as researchers strive to adhere to the bioethical principles and don’t conduct research illegally, I believe that gene editing should be encouraged as this may be the “cure” we have been looking for for so long.
As I said above, this topic is quite controversial and there are a number of opinions out there. I welcome any constructive criticism and would love to hear what you all think about gene editing in people.