The real problem of humanity is the following: we have paleolithic emotions; medieval institutions; and god-like technology.
– E.O Wilson[i]
By Daniel Tarade
One of my passions is promoting the stem cell registry. Pioneered in the 1960s, stem cell donations are one of the amazing advances of modern medical technology.[ii] There are over eighty diseases and disorders that can be treated by a stem cell donation from a healthy, compatible individual,[iii] including leukemia, lymphoma, and anemia.[iv] It’s a truly remarkable procedure – stem cells are extracted from the bone marrow or taken from the peripheral blood of a donor. The faulty stem cells of the recipient are killed off, obliterated really, by high doses of chemotherapy and radiation. The donated stem cells are grafted and, if successful, the entirety of the recipient’s white blood cells and red blood cells and platelets are derived from that of the donor. Ultimately, the donor and the recipient will share genetically identical blood.
Stem cell donations are reserved for serious cases, where no other treatment options exist. For some patients, if a donor is not found, death is sure to follow. The good news? To date, over 25 million people have signed up to stem registries globally.[v] Over a million stem cell donations have been performed.[vi] For certain diseases like chronic myeloid leukemia[vii] or sickle cell anemia,[viii] a stem cell donation can provide a veritable cure. The bad news? Since only 25% of patients find a compatible donor within their family, most people in need of a stem cell donation rely on unrelated individuals (those who have signed up on a stem cell registry). According to OneMatch, the Canadian stem cell registry, roughly 50% of people who need a stem cell donation never find a compatible donor! The necessity for stem cell donations to come from unrelated individuals is simultaneously inspiring and frustrating. Complete strangers give of themselves to help another individual have a second chance at life. However, the fact that half of the people who could stand to benefit from this medical advance are denied such an opportunity, due to a lack of stem cell donors, is crushing. Truly, stem cell donations are a fantastic example of our paleolithic emotions impeding our god-like technology. Can a country structure public health policy and modernize our medieval institutions to potentially combat the inherent short-sited, self-oriented thinking of the average person
Me, following a stem cell donation in late 2016. I donated via a bone marrow harvest. The procedure was painless and recovery was quick. Most donations actually involve a non-surgical procedure where stem cell are taken from the peripheral blood.
Our health care system can potentially save many more lives than it currently does but is limited by organizations trying to register people off the street and through public service announcements. During my time volunteering with various stem cell clubs, I have heard many reasons for why a person does not want to register with a stem cell registry. People are afraid of suffering pain (even though neither of the donation processes are incredibly painful), unduly concerned about incredibly rare complications, or just cannot be bothered. Of course, the context for these conversations is myself approaching people uninvited to discuss the need for donors. Even considering this, the response from people is quite discouraging. Although the net result of a stem cell donation is an increase in pleasure and decrease in pain, people are not willing to register when they see themselves as the person who stands to suffer, even if that suffering pales in comparison to the potential relief and happiness experienced by the recipient. Of course, it is also possible that the person who ultimately benefits from a stem cell donation is a friend or loved one. But that doesn’t seem to cross people’s mind. We can be very short-sighted sometimes. After a particularly discouraging stem cell drive, my mind starts to consider that a change in public health policy, rather than solely relying on methods of brute force (i.e. canvassing people in public), may represent the best chance for increasing the odds that a desperately ill person will find a compatible stem cell donor. What if Canada and other stem cell registries replaced our current opt-in system with an opt-out system? The idea is that most people are ambivalent to the idea of stem cell donation, and if it requires effort to register, a high percentage of people will avoid signing up. Further, a significant proportion of the population would not even be aware of the need for stem cell donors. However, if everyone was registered on the stem cell registry, say from birth, and was contacted if they were a match, perhaps fewer people would die while looking for a donor.
Throughout Europe, various countries have introduced opt-out systems for organ donations. The greatest increases in organ donation rates were associated with a hard opt-out system, where if a person did not opt-out of organ donation before death, the “decision” could not be reversed by the family. In countries with a hard opt-out system, rates of organ donation increased by as much as 25%.[ix] Is it reasonable to expect a similar increase in the rate of stem cell donations if there was a global transition to an opt-out system? Well, the two scenarios are not directly comparable. Stem cell donation requires the consent of a still living person who does run a small risk of suffering from a complication of the donation process. Serious complications are incredibly rare and common side effects (nausea, flu-like symptoms, sore lower back) typically resolve quite quickly.[x], [xi] Aside from potential side effects, the donor is still inconvenienced in having to spend time donating, miss work, experience potential anxiety, etc. I can imagine that a significant percentage of people will opt out of donation. Even with our current opt-in system, some people decide to not donate stem cells when they find out that are a match.[xii] However, the opt-out system will have the advantage of being able to present potential donors not with the abstract possibility of maybe saving a life but an actual life-or-death decision. By eliminating the necessity for abstract and future-based thinking, the importance of a stem cell donation may carry more weight. From the perspective of a public health initiative, the payoff from any gained stem cell donors is a potentially saved life. Instead of only accessing 25 million potential donors worldwide, that number would be increased many times over.
But what if we took it a step further? Rather than an opt-out system, what if the person found to be the best match (greatest compatibility, best health, etc) was required to donate stem cells? I will preface this discussion by saying that I do not support such a drastic departure from our current public health initiatives, at least not yet. I believe that an opt-out system would most likely be sufficient to minimize the shortcomings in our current ability to provide stem cell donations. However, I believe such a discussion, even if hypothetical in nature, can be fruitful.
One reason to support a forced donation system is the observation that disease strikes randomly. This is not entirely true but it is easier to justify forcing a person to participate in another person’s health if it is assumed that the person suffering the disease is not at fault. Nobody chooses to have leukemia and several of the diseases that can be treated by a stem cell donation, like sickle cell anemia, are entirely genetic in nature. Thus, a system of forced donation would function as an extension of a universal health care system. A universal health care system is funded by the tax player dollars of all individuals irrespective of their health status. A person with a chronic illness benefits as they are receiving more care than what could be afforded with their tax dollars in a private health care system. However, from a solely financial perspective, someone could argue that the perfectly healthy person suffers unduly as they pay into a system from which they have derived no direct benefit (a simplified argument that ignores access to preventative medicine and provided peace of mind). However, most of the western world supports a universal health care system. In such a system, the individual cannot opt out of paying taxes towards health care. Similarly, in many countries vaccines are required. While the vaccines do provide protection for the person, the mandatory nature is enforced as to promote herd immunity and protect those who cannot be vaccinated due to a compromised immune system or serious allergies. Vaccination is just one more example of a health care policy that requires an individual to act in a way to benefit others. Keeping these examples in mind, Is the idea of a forced donation system that crazy? Maybe not. One counter to the system of forced donation is that it undermines the autonomy of individuals in a manner that paying taxes does not. This line of reasoning is supported by the notion that individuals and families that earn below a certain income pay little to no taxes. In general, taxes levied are not meant to impinge autonomy, even though they are compulsory, as they are designed to not reduce financial freedom below some cut-off. However, a system of forced stem cell donation would follow similar principles, where those who are too old, young, or ill would be exempt from making a donation, as such a donation would carry undue risk and heightened probability of complications. However, for the average stem cell donor (young, good health), I would argue that a stem cell donation is no more likely to affect autonomy than a universal health care system that is funded by non-negotiable taxation or a mandatory vaccination schedule. What is required from individuals pales in comparison to the benefits obtained and as a system, forced donation of stem cells provides security for the whole of society, as everyone could potentially benefit. A system of forced donation would eliminate the bottleneck that our paleolithic emotions and medieval institutions represent in the ongoing struggle for the equitable and fair application of our miraculous medical advancements.
Post-script on compatibility
One issue with stem cell donations is that the procedure requires compatibility between the donor and the recipient. This compatibility is even more strict than that required for a blood donation. There are eight blood types; O-negative and -positive, A-negative and -positive, B-negative and -positive, AB-negative and-positive. These eight blood types are based on which combination of antigens presented on the surface of red blood cells. The antigens can be recognized by immune cells as ‘self’ or ‘not-self’, so it is important that a blood donation come from a compatible donor as to not illicit an immune reaction. A failsafe for blood donations is that many of these blood types are cross compatible. A person with O-positive blood (most common blood type) can donate to people with O-positive, A-positive, B-positive, or AB-positive blood without complications. Due to a relatively low number of blood types and this cross-compatibility, people do not die because compatible blood was not available. However, people do die while waiting for a stem cell donation. For a stem cell donation, since the stem cells will mature into white blood cells, the important consideration are antigens present on the white blood cell surface. These human leukocyte antigen (HLA) markers are more numerous and diverse than the antigens presented by a red blood cell. Most donation teams look at eight important HLA markers, and will consider up to ten.[xiii] Most striking is the incredibly diverse nature of the genes encoding these antigens, which are among the most polymorphic loci in the human genome. Some genes are associated with over 200 alleles.[xiv] Studies have shown that the rate of graft-versus-host disease, where the white blood cells derived from the donated stem cells attack the organs of the recipient, and host-versus-graft disease, where the body rejects the graft of donated stem cells, increases with the number of mismatched HLA markers. More than any other aspect of our being, humans are diverse at the level of our immune system and this greatly complicates the stem cell donation procedure.
There are several important, real-life consequences resulting from the polymorphic nature of the HLA genes. One, it is incredibly rare for any two individuals to have a compatible set of HLA markers. Consequently, only 25% of people who require a stem cell donation will find a compatible donor within their families. Even considering this dearth of potential donors, fully 50% of people who need a donation do not find a suitable donor. As a result, when a person donates stem cells, they may have been the only person who was a match. The margins are truly razor thin. Two, people of the same ethnic background are more likely to have a compatible set of HLA markers. However, the composition of stem cell registries does not reflect the ethnic diversity of people requiring stem cell donations (the diseases that can be treated or cured by a stem cell donation are experienced across ethnic boundaries). Caucasian people are considerably more likely to find a match than people of any other ethnic background.[xv] It is already a challenge to find a suitable donor for persons who are desperately ill. The current system fails half of all people who need a donor and furthers inequality between white individuals and people of other ethnic backgrounds. Organizations are trying to remedy the situation. I volunteer with the University of Toronto stem cell club and our mandate is to enroll people who are most needed; young, ethnically diverse males. Organizations like ours run stem cell drives where we inform the public of the need for an increased number of possible stem cell donors.
[i] https://harvardmagazine.com/breaking-news/james-watson-edward-o-wilson-intellectual-entente
[ii] Copelan. (2006). Hematopoietic stem-cell transplantation. The New England Journal of Medicine, 354(17), 1813-1826.
[iii] https://www.blood.ca/en/stem-cells
[iv] https://blood.ca/en/stem-cell/who-will-i-be-helping
[v] https://blood.ca/en/media/international-marrow-registries-together-reach-25-million-donor-milestone
[vi] Nuñez. (2018). A global view on regulatory issues in stem cell transplantation and cellular therapy. Establishing a Hematopoietic Stem Cell Transplantation Unit, 281-286.
[vii] Lennard & Jackson. (2000). Stem cell transplantation. British Medical Journal, 321(7258), 433-437.
[viii] Scott. (2014). Creating a cure-all. Nature, 515(13), S14-S15.
[ix] http://www.bbc.com/news/health-41199918
[x] Anderlini et al. (2001). Peripheral blood stem cell donation: an analysis from the International Bone Marrow Transplant Registry (IBMTR) and European Group for Blood and Marrow Transplant (EBMT) databases. Bone Marrow Transplantation, 27, 689-692.
[xi] Bosi & Bartolozzi. (2010). Safety of bone marrow stem cell donation: A review. Transplantation Proceedings, 42, 2192–2194.
[xii] https://globalnews.ca/news/1204217/man-hoping-for-third-stem-cell-match-after-first-2-donors-back-out/
[xiii] Dehn et al. (2015). 8/8 and 10/10 High-resolution match rate for the Be The Match unrelated donor registry. Biology of Blood and Marrow Transplantation, 21(1), 137-141.
[xiv] The MHC Sequencing Consortium. (1999). Complete sequence and genemap of a human major histocompatibility complex. Nature, 401, 921-923.
[xv] Switzer et al. (2013). Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. Blood, 121(8), 1469-1476.