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Review - RNA: A revolution in medicine?

Review - RNA: A revolution in medicine?

RNA: A revolution in medicine? This was the title of the programme by Radboud Reflects with lectures from geneticist Rob Collin and ethicist Marianne Boenink. However, this title also imposed the central question that was discussed in this lecture. Is RNA-technology revolutionary? Furthermore, are the ethical questions surrounding RNA different from the ethical questions DNA-technologies have evoked in the past? These questions and others were addressed by Collin and Boenink in this lecture and subsequent discussion, led by philosopher Frank van Caspel.

DNA versus RNA

Rob Collin started the night off with an explanation about RNA, about what it is and how it is applied. Collin works in the field of hereditary blindness, trying to cure the condition using various therapies and technologies. He elaborated on this later in the lecture, but first, he gave an RNA crash course. RNA, meaning ‘Ribo Nucleic Acid’, is an intermediate product between DNA and proteins that are made from the genetic code housed on the DNA. DNA, as most of us know, is composed of two strands, whereas RNA  consists of only one strand. DNA is very stable and exists in every cell of the body, whereas RNA is less stable and can be made at any time in the places where it is needed. DNA and RNA are opposites in many respects, which is an important caveat for their usage in therapies. RNA copies the genetic codes of the DNA and translates them into proteins, these proteins are the functional units of many processes in all cells of our bodies.

Diseases and therapies

Knowing these things about DNA and RNA, it is  possible to understand how hereditary conditions and diseases arise. When there is a small mistake, a mutation, in the genetic code of the DNA, this can lead to the production of faulty proteins, or no proteins at all. This might lead to hereditary conditions, like blindness, which Collin researches. After explaining these conditions, Collin outlined three different treatments: Gene Therapy, RNA-therapy and Genome Editing. In Gene Therapy, in order to cure hereditary conditions, extra DNA is added to cells. In Genome Editing, faulty DNA is replaced by DNA with the correct code. Both therapies are permanent – the patient’s genetic code is changed. RNA-therapy, in contrast, is temporary. RNA can be added to cells in order to create proteins, but RNA can also be added to cells to bind to RNA that creates faulty or damaging proteins. Lastly, RNA can also be used to make vaccines, as we have seen during the Covid-19 pandemic. DNA-therapy is often a permanent solution to a problem, but it can also be a cause of permanent damage. RNA can, in this respect, be a good alternative. Because of its temporary nature, effects will be temporary but any damage will be temporary as well.

One thing was very clear in Collin’s part of the lecture: technology is developing at a very fast pace and the possibilities seem quite endless. However, it is very important to proceed with caution.

The Human Genome Project

Marianne Boenink is a professor in healthcare ethics and a member of the IQhealthcare scientific center. In her lecture she gave a brief overview of three revolutions in genetic therapy before addressing contemporary dilemma’s that could be associated with RNA-therapy.

The main historical event Boenink focused upon was the Human Genome Project, a very prestigious scientific research project which lasted from 1990 till 2003. The goal of this project was to identify and map all genes that make up the human genome. Ethicists tagged along with the project and started to speculate about possible dilemma’s that could occur once there was a scientific understanding of which  genes cause which traits, diseases and so forth.

At the time there were concerns about genetic passports, discrimination based on genetics and the practical possibility of permanent human enhancement. In retrospect, however, the matter turned out to be more complicated than portrayed in the 90’s. Most diseases seem to have a multifactorial origin and can’t be traced back to a single gene. Furthermore, the idea of permanent human enhancement turned out to be mere science-fiction. The point Boenink wanted to make by pointing out the ethical speculation that accompanied the Human Genome Project is that ethicists should be more vigilant when it comes to ascribing a revolutionary character to new forms of treatment and thus restrain from too much speculation.

Nevertheless, Boenink continued that there are some lessons of the past we must take on board when discussing RNA-therapy namely, gene therapy and Crispr-Cas technology. The former raised questions on cost-efficiency and safety. The latter, because of its ability to permanently change the human genome, raised a bunch of concerns regarding human integrity, the question who will have access to this technology and the social impact concerning what we assess as socially acceptable adjustments to our genome.

RNA-therapy: prolific or dangerous?

What about RNA-therapy then revolves around? Boenink mentioned that, in light of the covid-19 pandemic, RNA-therapy has certainly proven to be a prolific way of treatment  but at the same time she stated that  there are some legitimate ethical concerns. In contrast with the Crispr-Cas technology, RNA treatment has no permanent effects, that is, the effects are permanent but also temporary e.g. an RNA-vaccine has the permanent property of reducing the risk of becoming severely ill from the sars-cov-2 virus but only temporarily, as an example she took the current discussion about a ‘booster-shot’ for the elderly. Nevertheless, the questions surrounding human integrity and, to a lesser extent, what we assess as socially acceptable adjustments to the human genome are not of our concern when it comes to RNA-therapy.

The temporal nature of RNA-therapy thus eliminates a lot of ethical problems but that does not mean that there are none. Boenink stated that on the one hand there are ethical problems on a personal level and on the other hand problems that affect society as a whole. On a personal level there are still concerns about the effectivity and safety of RNA-therapy. Since the effects are temporal RNA-therapy needs to be constantly repeated and she thus considered RNA-therapy as less efficacious than some alternative methods of treatment. Secondly, the long-term effects of repeated RNA-therapy remain nebulous, during the discussion Collin agreed that this was the biggest problem concerning RNA-therapy. However, the main question that Boenink raised here was if it was morally justified to let people undergo RNA-therapy at all.

On a social level she mentioned the cost-efficiency of RNA-therapy and the dilemma of how we, as a society, determine which diseases need to be treated an which don’t, since development of specific RNA-therapy is very costly. What criteria are sufficient to say no to one group of patients and yes to another? This dilemma connects to the possibility RNA-therapy has to give people certain temporary enhancements, which enhancements are acceptable and which aren’t?

In conclusion both speakers agreed that RNA-therapy is a very effective and prolific method of treatment, but the wide range of possibilities it offers are inevitably accompanied by ethical concerns which should be heeded when discussing further implementation of RNA-therapy in the future.

By Sara Kok & Bram van Glabbeek, Master students Philosophy at Radboud University