Medical Ethics

Gene Genie: The Scientist who Jumped the Gun on Gene Editing

/ Small Change / 2 Comments

First published in the UCD College Tribune

In November of 2018, Chinese scientist He Jiankui made an announcement that astonished the scientific community. He claims to have helped to make the first ever gene-edited babies with the use of a revolutionary technology called CRISPR. The babies, twins by the names of Lulu and Nana, were born to a father infected with HIV, the virus which causes AIDS. If Dr He’s experiment is successful, the twins will have an immunity to the virus. While this may seem at face value to be a noble goal, many believe that the risks involved outweigh the benefits.

Dr He’s experiments used a type of editing called ‘germline’ editing, meaning that any children that Lulu and Nana may have in the future will also carry this immunity. Germline editing involves making changes to reproductive cells. This means that any changes made to the individual’s genome will be passed on from generation to generation. This can be distinguished from somatic editing, in which the only person affected by the edit is the person who undergoes the procedure.

One reason why somatic editing is seen as more acceptable than germline is that people who undergo somatic editing have given informed consent prior to the procedure. While the parents of Lulu and Nana have given consent, the children themselves and any future children the twins may conceive have not consented to the potentially high risks. While HIV immunity could potentially be inherited by the descendants of these CRISPR babies, so could a myriad of unwanted and possibly even deadly side-effects.

Another concern that has been raised is that it is not clear whether Dr He’s treatment fulfilled an ‘unmet medical need’. With modern HIV treatments, someone who is carrying the virus can have the same expected lifespan as someone who is not and their chance of transmitting the virus to their children can be brought down to just 5%. Hence, geneticists worldwide have called for a moratorium on human germline trials. Critics say that gene editing technology has not yet been developed or tested sufficiently for use on human embryos. We simply do not yet know the long-term effects of genetic modification using CRISPR.

Despite a myriad of imaginable ethical hazards, CRISPR has the potential to revolutionize the biomedical sciences. CRISPR allows biologists to edit genetic information by using an enzyme called Cas9, which has the ability to cut strands of DNA. The process was pioneered in bacteria as a defence mechanism against viruses. Geneticists use CRISPR to target specific areas of genetic code and cut it in a specified region. Cutting a strand of DNA in the right place can cause a certain gene to be disabled, activated or replaced by one introduced by scientists. The possible applications of CRISPR range from curing cancer to eliminating malaria from mosquitos. One team at Harvard led by Prof. George Church even famously claimed that they will be able to ostensibly resurrect the woolly mammoth in the next year or two using the technology.

Some scientists, including mammoth-man George Church, have come out in defence of He. While Church had reservations regarding He’s level of transparency, he suggested that enough studies had been carried out that maybe it was the right time to end the moratorium anyway. While he accepted the risk of off-target mutations, he said that the risk ‘may never be zero’ and that Dr He had done enough to minimise it. This contradicts the views of most scientists and institutions, including a statement released by Francis Collins, the director of the National Institutes of Health. Collins denounced He’s work, saying, among other things, that ‘the possibility of damaging off-target effects has not been satisfactorily explored’.

Genes are extremely complex things. Locating a single gene and modifying it requires an extraordinary level of precision and even when it is successfully targeted it is impossible to fully predict the consequences. Though we have been studying certain genes for a very long time, we still do not know what the indirect effects of certain edits may be as no long-term studies of how edits affect the human body have been carried out as of yet. Such unintended effects are known as ‘off-target mutations’.

The final concern is perhaps the most serious. While CRISPR may in the future be used to treat some forms of cancer, it is possible that premature germline editing like the kind He carried out may actually increase the risk of cancer in people like Lulu, Nana and their descendants. Two recent studies have raised concerns about an off-target effect that CRISPR may have on a gene for a protein known as the ‘guardian of the genome’: p53. This protein is responsible for repairing or destroying damaged DNA. A mutated or ineffective p53 gene has been shown to be responsible for nearly half of all ovarian cancers and a significant portion of many other types of cancer too. CRISPR interventions activate p53, since DNA has been cut and must be either repaired or destroyed and p53 undoes the work CRISPR has done. The worry is that this could result in a kind of artificial selection on the cellular level, as CRISPR is more successful in cells with ineffective copies of the p53 gene, which are more at risk of becoming cancer cells. So far, only certain forms of cells have shown evidence of raising the risk of cancer when modified using CRISPR and no company is attempting clinical trials using CRISPR on these cells. Some scientists have called the recent studies concerning p53 a ‘cautionary tale’ since they may affect future CRISPR trials that are yet to begin.

CRISPR is an incredible technology that will surely be responsible for many breakthroughs in biological and medical science. It may someday give us powers that we cannot even conceive of today. However, that time has not yet come. It is imperative that we do not jump the gun. Dangerous, premature experiments like Dr He’s harm the public perception of gene editing and, in turn, harm the funding available for important research. While we should not give up on gene editing, we should also not use it to play with human lives until we know more about the benefits and the risks.

Opting Out- The Future of Organ Donation

/ Small Change / 2 Comments

First Published in UCD College Tribune

Organ donation has long been considered an important and cost-effective treatment for a variety of conditions which lead to organ failure. For many patients suffering from such conditions, transplantation is the only chance for survival. Since 2010, approximately a million organs have been donated worldwide. Despite both the effectiveness of the treatment and the general public support for organ donation, there is a persistent global shortage of transplantable organs. In recent years, governments and regulatory bodies have been exploring a variety of ways to decrease this shortage, potentially saving hundreds of thousands of lives.

This article summarises the most significant regulatory and technological developments around the world and evaluates their effectiveness in increasing the availability of transplantable organs, focussing on the move from an ‘opt-in’ to an ‘opt-out’ system. The importance of informing the public on how states can legislate to increase the efficiency of their donation system cannot be underestimated in the fight to improve a system which saves countless lives but is capable of saving many more.

In an opt-in, or ‘informed consent’ system, organs cannot be harvested unless the donor has given explicit consent during their life. The presumption is that nobody has consented until we know otherwise. Countries which use this system include Ireland, America, the UK, Germany and Australia. Last year Ireland announced that it will join the long, and ever-growing, list of countries which use an opt-out system. By contrast, in an opt-out, or ‘presumed consent’ system, the presumption is that everyone has consented unless they have explicitly refused. Countries which use this system include Spain, Belgium, Finland, France, Greece, Hungary, Israel, Italy, Sweden and Turkey.

A highly regarded 2006 study in the Journal of Health Economics showed that countries with opt-out systems have donation rates 25-30% higher than those which require explicit consent. This makes perfect sense, especially considering evidence from the same study, which states that while 85% of US adults support organ donation, only 28% are registered donors. An opt-out system could bring those numbers much closer together.

The same pattern of widespread support for donation but low numbers of registered donors seen in the US appears around the globe. Busy lives and lack of motivation mean that many people who would consent if formally asked simply do not specify that they would like to donate, and this contributes to the shortage of transplantable organs. Would it not be better if inertia and busy lives resulted in more organs for transplantation rather than fewer?

Given that far more people support donation than not, an opt-out system also means that the presumption of the law is in line with the majority wish. A simple legislative shift has the power both to save lives and make the law more representative of how people actually feel about organ donation. Spain has been the world’s leader in organ donation for 25 years running by a significant margin. The most cited reason for this is their efficient opt-out system. Spain’s success can also be linked to better hospital protocols and the fact that they do not cap the age at which donor organs will be considered. High public awareness may also contribute to Spain’s edge over other opt-out countries.

Governments have also tried to increase the availability of organs by applying the ‘priority rule’, where people who are on the donation register are given priority when organs are being allocated. If there are two potential recipients who are in the same stage of organ failure, but only one of them is on the register, then that person will receive the organ first. The idea is that people will consent to donation on the basis that it will increase their chance of survival if they are ever in need of a transplant themselves.

While on the surface this tactic seems to appeal to self-interest, it can also be seen as a reminder of the hypocrisy of benefitting from a system to which you do not contribute. You cannot expect others to donate their organs to you if you refuse to donate your organs to others. This tactic for decreasing the shortage of transplantable organs has also proved, usually alongside an opt-out system, to be an effective tool for saving lives.

The final policy I address is controversial; in almost all organ donation systems worldwide, the family of the deceased has the power to veto the consent given by the deceased during their life. Even Spain gives families the power of veto, though high public awareness means that very few families actually do so. There is no reason, in my view, that families should be given this power. It is a violation of the donor’s autonomy and yet another obstacle between a potential recipient and the organs that could save their life. If my family has a problem with organ donation, they can choose not to donate their own organs, but what happens to my body is my call and mine alone.

According to UNOS, around 20 people die every day in the US alone due to a lack of transplantable organs. By making simple legislative changes like removing the family’s power to veto and introducing opt-out donation and the priority rule, they could in theory cut that number in half. This is not some elevated ethical debate to be discussed in classrooms. What legislators decide with respect to this issue has incalculable effects on normal people.

None of us know if and when we may require an organ transplant. We are all vulnerable to the dangers of disease, age and injury. By doing everything in our power to increase the number of organs available, not only do we save the lives of others, but we also ensure that if the time comes when we are in need ourselves, we can rest assured that there is an efficient and sensible system in place to save us.