2017-09-26
The CRISPR/Cas9 system is a new DNA editing technology with a host of applications from the editing of DNA for use in agriculture (Butler et al., 2015), to the editing of DNA in human embryos (Liang et al., 2015). In the following pages, the focus will be on its use on human embryos within a Canadian health care context. It will be argued that it will be morally permissible to use this technology on human embryos, but with hard and fast regulations such that it may only be used for disease prevention and only if the technology is available through in vitro fertilization (IVF) and in utero treatments. A brief summary of the state of the technology will first be laid out. The moral question being examined will then be analysed using a few of the most popular ethical theories in the literature. Through this examination, it should be clear that whether you are a deontologist, a consequentialist, or a principlist, you can still get behind the idea that the use of this technology would be a force for good in the Canadian health care context as long as it is used within a certain ethical framework.
Before getting into the ethical question at hand, it is important to give some background of the technology. To summarize the CRISPR/Cas9 system, cas9 is a protein that cuts strands of DNA, and CRISPRs are strands of repeating RNA that help guide the Cas9 protein to its cutting site (Jinek et al., 2012). The use of these two molecules in conjunction allows for the cutting out of DNA sequences or the adding in of new ones (Jinek et al., 2012). This process occurs naturally in bacteria and archaea as an immune response, cutting foreign strands of DNA such as that of viruses (Jinek et al., 2012).
The use of this technology for the editing of human embryos is currently in the stage of the laboratory. Only two countries have currently given approval for scientists to use the technology on human embryos. These countries are Britain and China. The US was recently given approval to use CRISPR/Cas9 on human immune cells in an effort to fight against certain cancers (Reardon 2016). Chinese scientists, Liang et al. (2015), were the first to successfully edit a human embryo, but showed that there is still much work to be done before clinical application would be possible.
Not everyone agrees that we should be embarking down this path. Lanphier et al. (2015) wrote a very stern paper which argues why we should not be using these tools to edit human embryos. The argument is that not only is the technology uncertain at this stage, but using it for things that are ethically questionable, such as eugenics (Roth & Wakeley, 2016), puts in jeopardy the research that we know will save lives if successful, such as the editing of T cells to fight cancer (an implication of Reardon (2016)). The idea being that if something goes wrong with the use of CRISPR/Cas9 on human embryos, then the technology itself has the potential to be banned altogether.
Another concern of Lanphier et al. (2015) is that we do not know what effects the spliced germline DNA will have on the future generations that it is passed to. This is another fair point of concern, and the technology will likely need multiple generations of study on primates to see its long term effects before we think about using it for human clinical purposes.
As mentioned above, the current state of the technology for editing human embryos is still in its infancy. Liang et al. (2015) found that many of the edited embryos in their study were mosaic, which is to say that the technology had tended to cause unforeseen genetic problems with the embryo. Liang at al. (2015) attributes some of these problems to the gap in our knowledge of early embryonic repair mechanisms. The point being that, with the current state of this technology, it would clearly be unwise to begin using it in a clinical setting.
Taking this all into consideration, in order to have a discussion about the ethics of using this technology on human embryos that are meant to be brought to term in Canada, we need to consider a hypothetical scenario in which a sufficient amount of time has passed for the technology to be at a stage where we can reliably use it on human embryos, and make genetic changes such that the resulting organism will be healthy and have whatever genetic features we have engineered it to have. This paper will address the question of whether in such circumstances it will be ethically permissible to use this technology on human embryos in a Canadian clinical setting.
What is the relevance of this ethical question now if our hypothetical scenario is taking place in what could be a far away future? Well it turns out that up until the point in which we can use this technology reliably, there should be no real ethical dilemma at hand. It is quite easy for everyone to agree that presently we should not be using it clinically on embryos, nor should we be using it at any point until it is proven to be effective and not cause harm to the patient. So our scenario is the only time when a real ethical problem will arise for this technology.
The reason to explore it now rather than later is that it would be useless for organizations in Britain and China to be funding such research if it were the case that in the end it will be unethical to use it in a clinical setting. Therefore we need to have the discussion now as to whether this technology should be used when it is at a proper stage of advancement, otherwise we may as well throw out the project altogether and not waste the resources.
For reasons that will be evident, it should also be discussed whether in our hypothetical scenario, the clinical use is limited to IVF, or if it will be possible to edit the embryos in utero. This is ethically important because if it can only be used in vitro, then only the subset of the population that is using IVF will have access to this technology. This can cause some ethical problems in terms of the inequality between people using IVF and people who are not. I will discuss this further as we go through the ethical theories.
Now let us turn to some ethical theories. For the deontologist, the good of an act is determined by its conformity to moral norms or duties (Kant & Paton, 2009). So in our scenario, the deontologist is going to be concerned with whether the Canadian health care establishment has a duty to provide the service of gene editing to patients, or in other words, is the act of gene editing good in and of itself (Heavey 2013).
The duty to prevent disease has been around since at least the time of Hippocrates (approximately 5th century BCE) (Gagarin & Fantham, 2010). We have already seen in the UK, mitochondrial transfer (three person IVF), which allows for mitochondria to be transferred from the eggs of a donor to the eggs of a woman who has is at high risk of certain genetic diseases (Callaway 2015). After successful transfer the eggs are implanted and the child will be at lower risk for any particular genetic disease. Contrary to the opinions of Lanphier et al. (2015), CRISPR/Cas9 can likely be developed for the same purpose without the need for a donor. Even more, CRISPR/Cas9 has the ability to replace a much larger portion of the DNA which gives it an even greater capacity for treatments of this nature. A deontologist would therefore argue that Canada would have a duty to provide this service at least if it is being used for disease prevention.
When it comes to gene editing of the sort that is superficial, e.g. changing eye color, height, and so forth, the deontologist would likely have a completely different argument. They would argue that the child is being used as a means to an end. Even if they are doing it for the purpose of the child itself (e.g. they want the child to be tall so that he/she is more attractive and does better socially), the advantage that this gives to the child certainly cannot be used as a universal law to be applied to all newborns. If it were the case that Canada had a duty to provide whatever modifications to the child that the parents want, then presumably each person would want an even more handsome baby than the next. There is an inherent competitiveness in that system that no longer makes it a universal good but instead an arms race with no room for justice.
Thus since there is a moral duty to prevent disease, but no moral norm that works for superficial uses, it must be concluded that the deontologist would only agree to the use of this technology if it stayed within the confines of disease prevention.
For the deontologist, the moral value of the act would not change whether it is using IVF or being performed in utero. If in utero were not available, the act of preventing disease using IVF would be good in and of itself and the deontologist would argue that we should provide IVF to anyone who’s child is likely to have a genetic disease, no matter the cost.
For the utilitarian, the moral act is that which maximizes the good and minimizes the harm (Mill & Bailey, 2016). How much good would this technology bring versus how much harm?
The use of this technology in a clinical setting for disease prevention would surely do more good than harm. It is by the very nature of disease prevention that we are increasing the well-being of the individual for whom we are preventing the disease. In a scenario in which we do not use the technology, the child in question might grow up and suffer from some horrible genetic disease, and in the case of its use the child will not. Thus it is quite easy for the utilitarian to take the position that in its use for disease prevention, at least on the individual level, there is more good than harm.
A harder problem for disease prevention is one where we must factor in the entire Canadian society. Certainly, preventing disease is better than not preventing it, but what happens when only a subset of the population is given access to this option? Such was the dilemma in Canada when it came to IVF and it was decided in Ontario that it should be publicly funded for the purposes of equality (Ferguson, 2015). This line of reasoning is in line with utilitarian thinking. To minimize the harm of inequality the Canadian health care establishment must offer the service to all citizens and pick up the bill.
Should it be the same in the case of gene editing? Certainly if it is permissible to prevent disease, we must provide the technology, but it would be harmful to the ones who cannot afford it if only some are allowed to use it. So the only solution is for Canada to publicly fund the use of CRISPR/Cas9 at least for disease prevention.
What if it were the case that it were only available through IVF and not in utero? It then becomes an issue of resource management. Certainly Canada could provide IVF to every citizen who wanted to use CRISPR/Cas9, but it may become extremely expensive, as currently ontario taxpayers are already picking up a bill of $50 million a year for publicly funded IVF (Ferguson, 2015), not to mention the additional cost of using CRISPR/Cas9 in conjunction with it. So the question becomes does the good of providing CRISPR/Cas9 to all citizens outweigh the harm of using all of that taxpayer money? I think in the end the answer would be no. The utilitarian is going to have to argue that only if the service is available in utero, and through IVF, should it be permissible for Canada to use it since we need to be able to provide it to everyone.
As for its use for superficial means, on the one hand, an increase in, for example, the height of the individual may confer some kind of advantage to him/her down the line. It might make them more attractive, able to get a better job because of the social climate, etc.. This seems like it would increase their well-being and be ultimately a good thing. But let us look at this through a bit of a wider lens. How would giving one citizen an advantage affect the other individuals of the society? This seems to be leading to an unbalanced society where some are given advantage over others, which decreases the well-being of those individuals who do not have the advantage.
With the above analysis in mind, the utilitarian has to ask the difficult question of whether the harm done by the imbalance outweighs the good of the advantage to the individual being edited. It seems that if you run this experiment for a few generations you may start to see a major inequality in the society as a result of the use of this technology. Compounded with the fact that this would create greater demand for the technology by people who are at a disadvantage, it would create more harm to the government as it needs to use more resources to restore the balance. Ultimately the utilitarian is going to have to conclude that its use for giving advantage to certain individuals is going to do more harm than good, and thus the technology should not be used in this way. Therefore the utilitarian is going to have to argue that Canada should provide this service equally to all citizens, only for disease prevention, and only if it is available through a method that conserves resources.
Lastly, let us explore principlism. There are four main principles to be explored with this theory: autonomy, beneficence, non-maleficence, and justice (Beauchamp, 1995). Autonomy, in Canada, tends to be the most important. Neilson (1989) argued that it is inseparable from equality (another fundamental value of Canadian society). So let us first analyse this question with respect to autonomy.
One who takes autonomy to be the most important might argue that if a technology exists and is reliable, that it would be wrong to not let your citizens use it. So in the case of CRISPR/Cas9, the technology is there to be used, and if the person or the state has the money to pay for it, then why should we be the ones to prohibit them from using it? In the case of the government paying for it, it becomes a little more tricky. In this case it is appropriate to make a judgement about our own resources as with utilitarianism, but if we have the resources available, and all we care about is autonomy, then it should be the case that we can provide this service to the patient even if it is for superficial use. This is essentially why IVF is publicly funded in Ontario (Ferguson, 2015).
Let us see whether the autonomy-respecting framework indicated above conflicts with the other principles at play in this ethical theory. Beginning with beneficence, the concept of promoting the good of others (Beauchamp, 2008). It would certainly benefit the patient to be able to edit her child’s DNA to whatever specifications she pleases. It would also benefit the child. However, like the utilitarian argument, the worry is that in promoting the good of one or two individuals you are simultaneously not promoting the good of several others, and therefore beneficence may be in conflict with Autonomy here in the case of superficial use, and in the case of only using IVF.
Turning to non-maleficence (the “least harm possible” principle (Beauchamp, 2008)), it seems that the only harm that can done in this case is the unfair disadvantage which we saw with the utilitarian perspective. So again with this principle it seems that the only problematic scenario ethically is one in which we are using this technology for superficial purposes or where we are only able to use it for IVF patients.
Finally, we turn to justice. Justice is a principle that is about equality for all (Arras, 2010). Giving certain advantages genetically to a child directly goes against this principle as the physician is wilfully creating inequality by giving the child an advantage over others. Thus if we are to take justice into account, it is clearly wrong to use this technology for superficial purposes as well as if we are only treating people who are using IVF. Disease prevention would seem to actually create more justice as long as it is available to everyone, since it would be preventing disease that may give the individual an obvious disadvantage as compared to others in the society.
Having examined all four main principles, we see that three out of the four see it immoral to use this technology for superficial reasons and all four see it as moral to use it for disease prevention as long as it can be used both for IVF and in utero. Even though Canadians do seem to value autonomy over the other three in many cases, it seems that in this case it should be outweighed by the other three principles when it comes to uses that create inequality. It seems quite clear that we will have to give up some autonomy in favor of justice, beneficence, and nonmaleficence. Thus the principlist must also concede that CRISPR/Cas9 in this scenario would be perfectly permissible to use in a Canadian health care setting so long as it is only used for disease prevention and available both in utero and through IVF treatment.
So having examined three of the main ethical theories that are typically used in the literature today, what can we conclude from this? It seems as though no matter if you are a deontologist, a utilitarian, or a principlist, you will in all three cases come to the conclusion that this technology is morally permissible in a Canadian health care context so long as it is only used for disease prevention and not for any kind of superficial use such as changing eye color, height, and so on, and only if the service can be equally distributed.
A critic of the view being presented here might bring up a scenario where a superficial use of the technology would actually bring more equality and not have any of the consequences discussed earlier with the utilitarian perspective. Take the fact that the average height of an individual in Canada is 175.1cm (Shields et al. 2011). Also take that someone who is tall is statistically more likely be successful in a business context (Judge & Cable 2004). It follows that a person shorter than average would be at a disadvantage in this aspect of society, and that if everyone were the same height, this inequality would not exist. It follows from this that if a child is to be born who we know is likely to be shorter than the average height, that changing his height would not be putting him at an advantage to his peers but would be taking away his disadvantage, and therefore have the same effect as disease prevention discussed above. Thus, we have found a case where a superficial change such as height may have the same moral value as disease prevention, and so these hard and fast regulations may not be so morally sound after all.
In order to get around the fact that there are cases in which a superficial change may actually be beneficial to the individual and not cause any harm down the road, we need to look at two main points. The first is that the disease prevention is distinct from the above case because it is likely drastically reducing the suffering that the individual and his/her family may have as a result of the genetic disease. It may be the case that the short man is at a disadvantage to his peers, but it would be a bit of a stretch to say that he was really suffering because of it.
Secondly, we must address a worry that comes up when we discuss true equality. In order be truly equal, either there has to be no social bias whatsoever with regard to people’s looks and demeanor, or everyone has to look the same and have the same personality. It should seem intuitively obvious that both of these possible outcomes are not in reality possible nor would we want them to be possible. Therefore we must accept that a degree of inequality will always exist and we cannot use a technology like this to make us all look and act the same. That is not to go against the point that a drastic change in equality would be bad, but to a degree, we want some diversity in our society.
In conclusion, CRISPR/Cas9 is a promising gene editing technology that can be used to edit the DNA of human embryos. The technology is not in a state yet where we can reliably produce predictable changes that allow us to change an embryo’s DNA to whatever specifications we like. However this will be a possibility in the future whether is it CRISPR/Cas9 or some other technology. When that day comes we are going to have to deal with the ethical questions that surround it.
In this paper I have taken on this question, running it through three of the main ethical theories. Within the Canadian health care context, which Nielsen (1989) describes as an autonomy respecting egalitarianism, I have shown that even if you are a deontologist, a utilitarian, or a principlist you will still come to the conclusion that it will be morally permissible to use this technology in a clinical setting in Canada so long as it is restricted only to disease prevention, and so long as it can be provided to each citizen equally without using too many resources. Using the technology outside of these conditions would go against all established ethical theory.
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