Ethics Behind Organ Transplantation in the Modern Day

By Cameron Davies

Published 12:30 EST, Tues December 7th, 2021

The question I am aiming to answer is “Is modern-day US legislation on the allocation of organs for transplantation fair, or corrupt?“

For the past 67 years, the ability to donate viable organs to a recipient in need, known more commonly as organ transplantation, has been a life-saving treatment for those living on the edge of life.  It is said to be ‘one of the greatest advances in modern medicine’⁽¹⁾: a second chance made possible by our predecessors, and saving the lives of thousands of people each year, by providing them with everything from bone marrow and corneas to hearts. But, with great advances comes great imperfection – whilst organ transplants give so many people the opportunity of a second chance, others die waiting for the organs they need; 21 people on the organ transplant list die every day in the US alone.⁽¹⁾ And with the unequivocally difficult decisions of allocation, many physicians ask themselves the question: is the current legislation fair? Is it just to prioritise other people for certain criteria?  Although there has been much turmoil over the solution to these questions, UNOS claims to have the final system that satisfies all the controversy. 

UNOS, the United Network for Organ Sharing, in collaboration with the OPTN, the Organ Procurement and Transplantation Network and the Congress of the United States governs the legislation and guidelines surrounding the status of different patients, and the distribution of the tiny supply of healthy organs around the country. Of course, there are several types of donations that can be made: one can make a directed donation to a friend or family, either alive (by giving their liver, nerves, or kidneys) or deceased. Finally there is kidney-pairing which can be performed (whereby a certain number of people donate their kidneys to others and swap), or non-directed donations can be made.⁽²⁾ This makes the process of choosing what goes where incredibly difficult, and in the past, there have been several incidences where a great deal of uproar has been instigated by physicians and surgeons across the nation as a result of UNOS’ and OPTN’s failure to deliver a comprehensive and fair system of how organs should be donated to people who need it the most.

Although the first successful organ transplants were performed back in 1953, it wasn’t until the 1960s when the government got involved with producing solid regulations on how to allocate organs; this was due to an exponential rise in the demand for transplants.⁽³⁾  A principle belief of the congress as well as the OPTN was striking a balance between ‘utility’ and ‘justice,’ a prospect which they considered ‘a struggle to provide.’⁽³⁾ 

What it means at heart is that when choosing how to give out the limited supply of organs, UNOS cannot just give them to the sickest patients, despite the length of time they spend waiting. Instead, whilst this is taken into account, they should also reason how beneficial an organ transplant would be in a pool of potential patients; for example, if a heart was to go to a 92-year old with poor vascular functionality, it would be rather wasteful, as it is likely the patient would need either a second transplant or would die soon after their procedure. Similarly however, giving a kidney to a patient who is non-emergent and could wait longer than someone who’s been on dialysis for months is a wreckless method of allocation similarly. Therefore, the controversy as to how to approach the sitaution arises. All the while, during this period, figures show that the number of people waiting for organs increases:

Figure 1. graph comparing the number of donors providing organs versus the number of patients waiting.⁽⁴⁾

This rise of demand is alarming and still in today’s society are we seeing an astronomical gap between the number of people needing organs and those giving them, despite all the other treatment options emerging in the present day. 

Finally, the HHS final rule (US Department of Health and Human Services) of 1987 was set out to override all the current rules given by OPTN, ordering that organs should only be given to the sickest patients regardless of geographical location.⁽³⁾ This was a surprising change of legislation and was only met with fire from the community of physicians across the country.

Although the prospect of giving organs to those that are in dire need of them sounds emotionally just, it is still not balancing the need for utility and justice, which was such a clear principle of the network prior to the HHS rule. Some statistics were given in addition to the verbal response, explaining that the death rates, number of ischemic organs due to transport, and status issues were changing disadvantageously:

Figure 2. graph showing survival rate decrease in years after transplant procedure. (5)

Figure 3. graph showing the number of days waiting for transplant based on medical status. (5)

Figure 4. projected change in patient waiting times for liver transplantation under HHS policy. (5)

UNOS made the decision to implement more organ-specific regulations that would look closely at the medical specifics behind each patient in order to make a decision as to what status they should be regarded as. This took the form of a 1A, 1B etc. system, however, the need to consider geographical location as well was a problem. The system used can be seen here:

 Figure 5. A map of the US showing several patients and they’re medical information 

also taking into account distance from the donor hospital. ⁽⁷⁾

Figure 5 shows that the metric for medical urgency used is arbitrary – instead of an actual score, instead the rubric is ‘low,’ ‘medium’ and ‘high.’ It seems this may bring to light some fault with the legislation considering that a patient may be borderline between medium and high, but lose out on a transplant because they missed the criteria by a small increment. 

This is continued with the candidate biology and 1 year survival after transplant thus showing that when putting all this information together in a table as shown here, it is incredibly difficult to make a decision which can be justified scientifically and reasonably, as a result of a lack of clarity from the system’s criteria. 

However, in 2017, UNOS and OPTN emerged with a new system proposal as to the reform of organ transplantation, which was called ‘continuous distribution.’ The philosophy behind the change was that up until this period, as we concluded above, there was no single criterion available to judge whether a patient was worthy for a particular transplant, which made it difficult to decide whether a particular person met the parameters needed to make them deserving of the organ. The new system aimed to change that by using a points system to determine the status of a patient which took into account all of the criteria which would need to be considered for a transplant in one.⁽⁶⁾ It was illustrated by UNOS  as follows:

Figure 6. An equation showing all the factors taken into account to create the patient’s composite allocation score ⁽⁶⁾

The composite allocation score first takes into account medical urgency, which is based on a number of specific scores, for example blood type, white blood cell count, and other advanced metrics used in everyday medicine. Post-transplant survival is also incredibly important as it allows the idea of utility to be considered in addition to justice, whereby their medical state and general health is taken into account to decide how long they would survive with the transplant. The candidate biology is another crucial piece of information to determine the score, which is basically the patient’s compatibility with the organ being donated; this refers to the possibility of post-transplant rejection (this is where the patient does not respond correctly to the organ, and it does not function correctly), which happens in 10-15% transplant patients.⁽⁸⁾ If this evidence was not considered, the number of rejections would increase, making the system invalid again. 

Patient access directly relates to recipients who are minors, or those who were donors before becoming patients. Finally, placement efficiency looks at the more budgetal approach to the transplant; the importance of making sure resources are not wasted when transporting and completing the transplant procedure is another factor of importance when determining the worthiness of a patient to be transplanted.⁽⁵⁾ When taking this all into account, it is clear that by looking at a variety of vital factors the score is a more representative and finally strikes the balance between utility and justice. 

UNOS claims that by implementing this policy, which was scheduled and completed first in January 2019 for lungs (and proceeded with other organs with the heart scheduled for January 2023), the utilitarian concept of giving the greatest benefit for the greatest people is satisfied, as well as creating a fair policy.⁽⁶⁾ In addition, it proposes to correct the survival rates and transportation costs etc. which faulted the HHS policy. Although many will agree that this new policy is an almost perfect approach to organ allocation legislation, there are a few discrepancies within the OPTN regulations which remain ever-frustrating amongst the medical community based on other factors, which are yet to be addressed.

This revolves mainly around the conflict between lifestyle choices of recipients and whether everyone that needs a transplant deserves one regardless of what their medical status and other factors are.First argued by an article in 2014 by the Nursing Times, where it was argued that in a hypothetical situation, where a drunk driver perpetrated an accident, and both the victims and the driver himself needed a lung transplant, is it ethically right to deny the driver access to the organs despite him having a higher composite allocation score than the victims? ⁽⁹⁾ Of course, as with any ethical dilemma, there are two equal arguments suggesting that both the driver is still human and deserves equal treatment medically as any other person, but also the lack of justice is present through the denial of victims organs which could possibly save their life for someone who is reckless with it.  Thus, this means the policies and regulations set out by the network, whilst appearing to be sound, have small issues which cannot easily be resolved – because, of course, it comes down to the emotions and opinions of each individual.  Sometimes, it is possible to employ an ethics committee for one-off situations whereby a group of people, impartial to either patients, decide whether a particular patient should receive an organ or not, but, the unrelenting rule of medicine at the end of the day is that all people should be treated equally, despite their lifestyle choices.

That said, UNOS has made some changes to policies regarding what non-emergent patients are eligible for transplants, including a decision that smokers or alcoholics cannot be added to the transplant list unless they have been out of rehabilitation for at least 6 months.  It seems to many that this is a sensible rule, and reduces the number of people receiving transplants who then go back to drinking and need another, thus limiting the resources available being wasted. However, it could be argued also that the 6-month period is not long enough to avoid the recipients going back to abusing alcohol following their transplant. ⁽¹⁰⁾ As a result, this gives us another reason why regardless of the policy changes, organ transplantation will always be a controversial form of treatment. 

In conclusion, it is clear to see that incredible advances have been made in the U.S. regarding the policies and legislation surrounding organ transplantation – although the number of donors available will never match the number of people waiting for transplants, the new continuous distribution plan, pioneered by UNOS, which is now being implemented across the country, is a more clear and precise way of measuring the score of each patient and seeing exactly whether a patient deserves a transplant before another.  This way, the previous HHS and OPTN policies, suggesting lower survival rates and lack of utility, are corrected, and the principles which were set out back in the beginning are being upheld in a way that makes it fair for everyone.  However, the transplant allocation system brings the truth closer to us, that there isn’t always a ‘right’ decision in medicine, despite the ‘yes’ and ‘no’ nature of science. And, because of our ever changing society, there will always be someone who perceives it was wrong.

Cameron Davies, Youth Medical Journal 2021

Bibliography

⁽¹⁾ Cleveland Clinic (2000). Organ Donation Facts & Info | Organ Transplants | Cleveland Clinic. [online] Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/articles/11750-organ-donation-and-transplantation.

⁽²⁾ Anon (2014). Living Donation Facts and Resources from UNOS | Living Donor Transplants. [online] UNOS. Available at: https://unos.org/transplant/living-donation/.

⁽³⁾ Van Meter C. H. (1999). The organ allocation controversy: how did we arrive here?. The Ochsner journal, 1(1), 6–11. 

⁽⁴⁾ UNOS (June 2, 1994) | The UNOS Statement of Principles and Objectives of Equitable Organ Allocation, pp. 165 

⁽⁵⁾ UNOS (May 1, 1998) Congressional Staff Briefing: Impact of HHS OFl“ Regulations.  

⁽⁶⁾ UNOS (2019). Organ distribution – UNOS. [online] UNOS. Available at: https://unos.org/policy/organ-distribution/.

⁽⁷⁾ OPTN (2018). Continuous Distribution – OPTN. [online] optn.transplant.hrsa.gov. Available at: https://optn.transplant.hrsa.gov/governance/key-initiatives/continuous-distribution/ [Accessed 28 Oct. 2021].

⁽⁸⁾ Donor Alliance. (2020). Preventing organ and tissue rejection. [online] Available at: https://www.donoralliance.org/newsroom/donation-essentials/preventing-organ-and-tissue-rejection/#:~:text=With%20these%20new%20medications%2C%20rejection [Accessed 30 Oct. 2021].

⁽⁹⁾ Bedford, S. and Jones, E. (2014). Should lifestyle choices affect access to transplant? Nursing Times, [online] 23 Jul., pp.16–18. Available at: https://cdn.ps.emap.com/wp-content/uploads/sites/3/2014/07/230714-Should-lifestyle-choices-affect-access-to-transplant.pdf   [Accessed 28 Oct. 2021].

⁽¹⁰⁾ Hedin, M. (2019). Alcohol Relapse Rate Among Liver Transplant Recipients Identical Whether or Not There is A 6-Month Wait Before Transplant. [online] Johns Hopkins Medicine Newsroom. Available at: https://www.hopkinsmedicine.org/news/newsroom/news-releases/alcohol-relapse-rate-among-liver-transplant-recipients-identical-whether-or-not-there-is-a-6-month-wait-before-transplant.

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Cancer: Will We Ever Cure it, And How Long Will That Take? A Scientific and Humanitarian Perspective.

By Cameron Davies

Published 8:08 EST, Tues October 19th, 2021

Abstract

Cancer, by definition, is a disease caused by the uncontrollable cell division of mutated cells (Rosenbaum, 2011). This arises from both genetic and spontaneous causes but can be influenced by the use of carcinogens (i.e., smoking) and unhealthy lifestyles. Cancer will affect half of the population of the UK (Anon, 2019) in their lives. This sorrowing statistic, along with the knowledge that cancer is now the most threatening disease alive, means that the future of medical advances in this field seems bleak. However, there are positives. For example, there were 1,112 trials in 2018 alone towards improving those odds (Blazynski and Runkel, 2019). It encouraged me to pursue this topic knowing there is a balanced argument. Even as new pioneering discoveries are made in medicine every day, it is difficult to quantify their success with the bigger picture.

What is cancer?

Before discussing how cancer is treated, it is important to understand how cancer can develop in the human body in a bit more detail. Cancer is either inherited or sporadic (Divan and Royds, 2020). If inherited, the chance of cancer being onset is much greater and much more imminent, but sadly there is no real way to know or prevent it. However, sporadic cancers caused by random mutations of cells can be prevented by reducing the risk factors, including smoking, exposure to UV light, and eating unhealthily (Divan and Royds, 2020). More cancers are sporadic than hereditary.

Background knowledge & History of treatments

Amongst all the discoveries over the past century to eradicate or treat the virus, chemotherapy and radiation rank amongst the greatest discoveries to date in widespread treatment for most cancers, whether in the early or late stage. Before this time, only surgical resection was available for those with cancer, along with a relatively low success rate overall. The statistics could not be included because of the variegated nature of cancer regarding the type and stage of advancement.

One of the most common treatments available in today’s world, chemotherapy, was first developed during World War II in the US. It was known to kill all living cells and took the name of nitrogen mustard. Back then, no one knew just how important this discovery would be in the journey to eradicating cancer. As time passed, Sidney Farber, a pioneering oncologist, discovered a new drug called aminopterin, which redefined treating leukaemia in children (Anon, 2012). This stemmed to the creation of toxic cell-killing drugs, which later developed into chemotherapy. Of course, to this day, many adaptations have been developed to fine-tune the treatment of cancer, including using cancer stem cells to reduce the possibility of drug resistance (Anon, 2012). 

Radiation also lists amongst the most beneficial discoveries in the fight for cancer within the past century. It originated in 1896 when a German physics professor named Wilhelm Conrad Roentgen discovered the X-Ray, which could diagnose patients unlike ever before. From there, he shaped this into radiation for cancer and soon won the Nobel Prize in Physics. Unfortunately, the course of its discovery was interfered with when it was discovered that radiation could also cause cancer (particularly blood cancers) (Anon, 2014). However, it did not stop scientists from continuing to make advances in the field: shortly into the 20th century, a type of therapy known as conformal radiation therapy (from CT scans) was a more precise method of locating cancer. Additionally, intraoperative radiation therapy was a treatment to particularly combat abdominal and pelvic cancer by minimising the amount of tissue when exposed to radiation (Anon, 2014).

It is not unusual for any cancer patient to experience effects from chemotherapy, and indeed radiation presents very harshly: nausea, tiredness, distress, and infection are inevitable effects caused by chemotherapy due to the harsh course it takes to remove almost every functioning cell from the body. This has been combated over the years with antiemetics to reduce nausea and vomiting (Divan and Royds, 2020) as well as several other clinical trials. However, it was made clear that in addition to chemotherapy and radiation, some major advances were required in order to improve the success rate of cancer treatment. Thus, oncologists are struggling to keep up with the modern-day to develop more targeted and cutting-edge therapies in this day and age. However, be rest assured that oncological trials are the number one ranking in the number of trials carried out (as of 2018), standing at a grand total of 1,112 in 2018 (Blazynski and Runkel, 2019) alone. These statistics go to show we are making progress towards the end goal: total eradication.

More modern targeted therapy and clinical trials

One group of scientists made a particularly groundbreaking discovery in reducing metastasis (cancer recurring after treatment) by inserting a drug called BBI608. This is a particularly significant exploration because ‘current cancer treatments ultimately fail owing to metastasis and relapse.’ Overall, the trial was largely successful in killing most cancer stem cells without affecting stem cells from dying. They concluded that BBI608 was a ‘novel approach’ to this issue (Rogoff, Keates, Gao, Murikipudi, Mikule, Leggett, Li, Pardee, Li, 2015).

Bone marrow transplants and stem cell research are two life-saving methods that are fast arising in cancer. In the past, bone marrow transplants were poor in terms of success rate and were about to be terminated. Even today, stem cell and bone marrow transplants result in a success rate of around 50-60% (Carrier and Kelvin, 2004), which is alarming considering the importance of these surgeries. Unfortunately, in addition to this low success rate, there is a lot of controversy towards Stem Cell research. For example, questions like ‘is it right to test animals?’ and ‘is it right ethically to clone someone?’ have arisen throughout the process. In addition, there are some serious scientific flaws to the process, which include the tumour growing somewhere else, stem cells forming tumours, and the knowledge that we are still in the clinical trial phase (Thomas, 2012). This means that stem cells are a novelty for us. Stem cells are the parts of our body that contain unspecialised cells. This means replacing it would create completely new cells that are not cancerous and potentially lead us to defeat cancer cells 100% of the time. Therefore, it has certain potential in the eradication of cancer.

Targeted therapies interfere with and block signals of cancerous cells, which reduce the amount of cell division that takes place. Whilst some trials have been extremely successful, dosing and cost (for example, the fact that it costs over $30,000 for eight weeks of treatment) hinder its progress. This is why some clinical trials are fatal in the future of therapy (Khahil, Smith, Brentjens, Wolchock, 2016). But, if finance was not a problem, this would have great potential in the fight to cure cancer.

Finally, one more clinical trial was carried out in the early days of 2007 and concluded in 2009, looking at GSK46134, a potential drug for curing advanced-stage cancers. Some side effects from this drug at higher doses included a decline in blood cells and some blood clots, which unfortunately ended the trial (De Bono, 2015).

In conclusion, it can be said that there is a mixed number of successful and unsuccessful trials around in the current day. Whilst the efforts of a team of scientists to create the BBI608 drug paid off, other trials and stem cell research are still seriously dragging behind. This puts us in a tricky situation, moving forward, as the treatment element of cancer continues to be difficult. This is mostly due to the aggressive and clever progression and metastasis of cancer, which is seriously limiting possibilities.

There are unscientific and scientific reasons why cancer has a very limited future. Some of which are purely permanent and cannot be ‘eradicated.’ Other reasons are the very peril of scientists and medics today, who are scrambling to create a cure to this awful disease.

Scientific barriers

According to scientists, there are a few main scientific reasons that have led the treatment and eradication of cancer into turmoil. The first of which is that targeting stem cells is hard (Chakraborty and Rahaman, 2012). When we target cells, all cells have originated from the stem cells, meaning the cancerous stem cells are never killed off. With this in mind, it is difficult to completely kill cancer because the cancer stem cells have the ability to ‘self-renew’ and put the body into what is known as cancer relapse (i.e., cancer comes back) (Chakraborty and Rahaman, 2012). Additionally, they could grow resistant to the drugs being given as a result of epigenetics. Prostate cancers, Esophageal cancers, and Pancreatic cancers, all extremely aggressive cancers, are challenging to diagnose for two main reasons: firstly, they are what is known as latent cancers (meaning the patient could have cancer but be asymptomatic), and the tumours start very small, giving no ‘tell-tale’ signs. Finally, metastasis is a huge problem for most cancer patients. Tumours, once killed, can still re-grow in other parts of the body, either spreading locally through the blood or through the lymphatic system (Chakraborty and Rahaman, 2012). This can happen easily, and so significantly limits the progress that can be made to eradicate it.

Financial and discriminative barriers

There are also racial and discriminative reasons why cancer treatment and eradication have been limited. These are issues that can easily be fixed, but if not, they also significantly reduce the number of possible outcomes available. The first of which is a lack of follow-up care. The average African-American cancer patient has a concerningly higher 32% chance of mortality than a white male cancer patient (Jabson and Bowen, 2013). This blatantly tells us that your race decides whether you will be treated or if cancer can be eradicated; it’s simple – if race determines your healthcare, and BIPOC people continue to get cancer, we can never fully eradicate this disease.

Additionally, cancer is missed every day in elderly patients. An interesting biopsy study was held on diseased patients over 65, and a staggering 32.5% of these patients had one or more cancer, most of which would have been fatal if their additional health issues had been dealt with (Suen, Lau and Yermakov, 1974).

Clinical trials are an extremely vital system that lead scientists to get a better understanding and idea of the kind of drugs and therapies that can cure diseases. Clinical trials in oncology are no exception. A reminder that over 1000 clinical trials in oncology took place in 2018 alone (Blazinsky and Runkel, 2019). With this in mind, it is no celebration that patients of Arizona (and indeed many other states of the US) are not receiving these possibly life-saving studies. About 20 years ago, a law was put in place in Arizona and other states that both the patient and staff had to fund these trials. Insurers also refused to cover this care, causing most of the clinical trials (which were imperative for life-saving care and advances in medicine) to be under-enrolled. As a result, a very poor and ‘flawed product’ (Olson-Garewal and Hessler, 2001) was produced, leaving much of the US without the cutting-edge possibility to make advances in cancer eradication.

These ideas show that our lack of care and discrimination is severely affecting this long and troublesome road to eradicating cancer; we forget that science does not have the only thing to do with that. Finance, race, and age are important factors but should never affect healthcare.

Conclusion

Cancer, by definition, is a disease caused by the uncontrollable cell division of mutated cells (Rosenbaum, 2011). Taking the lives of thousands of people, this disease ruins many lives and takes the lives of innocent and healthy communities. Without the quick action to find treatment and cure this disease, we are looking at a rather dim future, with around 4 million people living with cancer by the year 2040 (Anon, 2016); this is a shocking yet very real 13% of the population. Thus, cancer is the most deadly disease in the world.

But even with a cure, my question is, can we ever ‘fully eradicate’ cancer? When we look at this question carefully, we really mean ‘can we ever look at this world and not remember that cancer ever existed’? The answer is yes, we can. But what is the time frame? Is it in all countries? Is it in all cities? Is it to all species? The answers to these questions, alas, are unknown. But, due to the overwhelming scientific evidence stating that mutations are extremely hard to control and cancer stem cells are extremely aggressive, the time frame looks rather grim. In addition, the financial, racial, and age issues encompassing this disease inexplicably increase the deadline of defeating cancer. Unfortunately, this project is starting to look much more long-term than we hoped.

Cameron Davies, Youth Medical Journal 2021

Bibliography

Aysha Divan and Royds, J. (2020). Cancer biology and treatment. Oxford Oxford University Press.

Blazynski, C. and Runkel, L. (2019). 2018 Completed Trials: State of Industry-Sponsored Clinical  Development. 2018 Completed Trials:  State of Industry- Sponsored Clinical  Development.

British Medical Association (2004). BMA new guide to medicines & drugs. London: Dorling Kindersley.

Carrier, E. and Joanne Frankel Kelvin (2004). 100 Questions & Answers About Bone Marrow And Stem Cell Transplantation. Sudbury: Jones And Bartlett, Cop.

Chakraborty, S. and Rahaman, T. (2012). ecancermedicalscience. The difficulties in cancer treatment. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024849/.

De Bono, J. (2015). A trial looking at GSK461364 for advanced cancer. [online] Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-gsk461364-for-advanced-cancer-or-non-hodgkins-lymphoma#undefined [Accessed 30 Oct. 2020].

Gerber, D.E. (2014). Targeted Therapies: A New Generation of Cancer Treatments. American Family Physician, [online] 77(3), pp.311–319. Available at: https://www.aafp.org/afp/2008/0201/p311.html [Accessed 15 May 2019].

Jabson, J.M. and Bowen, D.J. (2013). Cancer treatment summaries and follow-up care instructions: which cancer survivors receive them? Cancer Causes & Control, 24(5), pp.861–871.

Khalil, D.N., Smith, E.L., Brentjens, R.J. and Wolchok, J.D. (2016). The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nature Reviews Clinical Oncology, [online] 13(5), pp.273–290. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551685/ [Accessed 21 Nov. 2019].

Li, Y., Rogoff, H.A., Keates, S., Gao, Y., Murikipudi, S., Mikule, K., Leggett, D., Li, W., Pardee, A.B. and Li, C.J. (2015). Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proceedings of the National Academy of Sciences, [online] 112(6), pp.1839–1844. Available at: https://www.pnas.org/content/112/6/1839 [Accessed 11 Mar. 2020].

Natural History of Cancer. (1959). BMJ, 1(5121), pp.563–564.

Olson-Garewal, J.K. and Hessler, K. (2001). Arizona’s Cancer Clinical Trials Law: Flawed Process, Flawed Product. The Hastings Center Report, 31(3), p.22.

Rosenbaum, B. (2011). Science of Cancer 101 | OncoLink. [online] http://www.oncolink.org. Available at: https://www.oncolink.org/healthcare-professionals/oncolink-university/general-oncology-courses/science-of-cancer-101 [Accessed 30 Oct. 2020].

Siegel, R., Miller, K. and Jemal, A. (2019). Cancer statistics, 2019. [online] Cancer statistics, 2019. Available at: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21551?dom=prime&src=syn [Accessed 30 Oct. 2020].

Statistics fact sheet. (2019). [online] Macmillan Cancer Support, pp.1–14. Available at: https://drive.google.com/drive/folders/1-cjdxWa06QCf2qqQQDabivxpLNubK-SI [Accessed 31 Oct. 2020].Suen, K.C., Lau, L.L. and Yermakov, V. (1974). Cancer and old age.An autopsy study of 3,535 patients over 65 years old. Cancer, 33(4), pp.1164–1168.

Abstract

Cancer, by definition, is a disease caused by the uncontrollable cell division of mutated cells (Rosenbaum, 2011). This arises from both genetic and spontaneous causes but can be influenced by the use of carcinogens (i.e., smoking) and unhealthy lifestyles. Cancer will affect half of the population of the UK (Anon, 2019) in their lives. This sorrowing statistic, along with the knowledge that cancer is now the most threatening disease alive, means that the future of medical advances in this field seems bleak. However, there are positives. For example, there were 1,112 trials in 2018 alone towards improving those odds (Blazynski and Runkel, 2019). It encouraged me to pursue this topic knowing there is a balanced argument. Even as new pioneering discoveries are made in medicine every day, it is difficult to quantify their success with the bigger picture.

What is cancer?

Before discussing how cancer is treated, it is important to understand how cancer can develop in the human body in a bit more detail. Cancer is either inherited or sporadic (Divan and Royds, 2020). If inherited, the chance of cancer being onset is much greater and much more imminent, but sadly there is no real way to know or prevent it. However, sporadic cancers caused by random mutations of cells can be prevented by reducing the risk factors, including smoking, exposure to UV light, and eating unhealthily (Divan and Royds, 2020). More cancers are sporadic than hereditary.

Background knowledge & History of treatments

Amongst all the discoveries over the past century to eradicate or treat the virus, chemotherapy and radiation rank amongst the greatest discoveries to date in widespread treatment for most cancers, whether in the early or late stage. Before this time, only surgical resection was available for those with cancer, along with a relatively low success rate overall. The statistics could not be included because of the variegated nature of cancer regarding the type and stage of advancement.

One of the most common treatments available in today’s world, chemotherapy, was first developed during World War II in the US. It was known to kill all living cells and took the name of nitrogen mustard. Back then, no one knew just how important this discovery would be in the journey to eradicating cancer. As time passed, Sidney Farber, a pioneering oncologist, discovered a new drug called aminopterin, which redefined treating leukaemia in children (Anon, 2012). This stemmed to the creation of toxic cell-killing drugs, which later developed into chemotherapy. Of course, to this day, many adaptations have been developed to fine-tune the treatment of cancer, including using cancer stem cells to reduce the possibility of drug resistance (Anon, 2012). 

Radiation also lists amongst the most beneficial discoveries in the fight for cancer within the past century. It originated in 1896 when a German physics professor named Wilhelm Conrad Roentgen discovered the X-Ray, which could diagnose patients unlike ever before. From there, he shaped this into radiation for cancer and soon won the Nobel Prize in Physics. Unfortunately, the course of its discovery was interfered with when it was discovered that radiation could also cause cancer (particularly blood cancers) (Anon, 2014). However, it did not stop scientists from continuing to make advances in the field: shortly into the 20th century, a type of therapy known as conformal radiation therapy (from CT scans) was a more precise method of locating cancer. Additionally, intraoperative radiation therapy was a treatment to particularly combat abdominal and pelvic cancer by minimising the amount of tissue when exposed to radiation (Anon, 2014).

It is not unusual for any cancer patient to experience effects from chemotherapy, and indeed radiation presents very harshly: nausea, tiredness, distress, and infection are inevitable effects caused by chemotherapy due to the harsh course it takes to remove almost every functioning cell from the body. This has been combated over the years with antiemetics to reduce nausea and vomiting (Divan and Royds, 2020) as well as several other clinical trials. However, it was made clear that in addition to chemotherapy and radiation, some major advances were required in order to improve the success rate of cancer treatment. Thus, oncologists are struggling to keep up with the modern-day to develop more targeted and cutting-edge therapies in this day and age. However, be rest assured that oncological trials are the number one ranking in the number of trials carried out (as of 2018), standing at a grand total of 1,112 in 2018 (Blazynski and Runkel, 2019) alone. These statistics go to show we are making progress towards the end goal: total eradication.

More modern targeted therapy and clinical trials

One group of scientists made a particularly groundbreaking discovery in reducing metastasis (cancer recurring after treatment) by inserting a drug called BBI608. This is a particularly significant exploration because ‘current cancer treatments ultimately fail owing to metastasis and relapse.’ Overall, the trial was largely successful in killing most cancer stem cells without affecting stem cells from dying. They concluded that BBI608 was a ‘novel approach’ to this issue (Rogoff, Keates, Gao, Murikipudi, Mikule, Leggett, Li, Pardee, Li, 2015).

Bone marrow transplants and stem cell research are two life-saving methods that are fast arising in cancer. In the past, bone marrow transplants were poor in terms of success rate and were about to be terminated. Even today, stem cell and bone marrow transplants result in a success rate of around 50-60% (Carrier and Kelvin, 2004), which is alarming considering the importance of these surgeries. Unfortunately, in addition to this low success rate, there is a lot of controversy towards Stem Cell research. For example, questions like ‘is it right to test animals?’ and ‘is it right ethically to clone someone?’ have arisen throughout the process. In addition, there are some serious scientific flaws to the process, which include the tumour growing somewhere else, stem cells forming tumours, and the knowledge that we are still in the clinical trial phase (Thomas, 2012). This means that stem cells are a novelty for us. Stem cells are the parts of our body that contain unspecialised cells. This means replacing it would create completely new cells that are not cancerous and potentially lead us to defeat cancer cells 100% of the time. Therefore, it has certain potential in the eradication of cancer.

Targeted therapies interfere with and block signals of cancerous cells, which reduce the amount of cell division that takes place. Whilst some trials have been extremely successful, dosing and cost (for example, the fact that it costs over $30,000 for eight weeks of treatment) hinder its progress. This is why some clinical trials are fatal in the future of therapy (Khahil, Smith, Brentjens, Wolchock, 2016). But, if finance was not a problem, this would have great potential in the fight to cure cancer.

Finally, one more clinical trial was carried out in the early days of 2007 and concluded in 2009, looking at GSK46134, a potential drug for curing advanced-stage cancers. Some side effects from this drug at higher doses included a decline in blood cells and some blood clots, which unfortunately ended the trial (De Bono, 2015).

In conclusion, it can be said that there is a mixed number of successful and unsuccessful trials around in the current day. Whilst the efforts of a team of scientists to create the BBI608 drug paid off, other trials and stem cell research are still seriously dragging behind. This puts us in a tricky situation, moving forward, as the treatment element of cancer continues to be difficult. This is mostly due to the aggressive and clever progression and metastasis of cancer, which is seriously limiting possibilities.

There are unscientific and scientific reasons why cancer has a very limited future. Some of which are purely permanent and cannot be ‘eradicated.’ Other reasons are the very peril of scientists and medics today, who are scrambling to create a cure to this awful disease.

Scientific barriers

According to scientists, there are a few main scientific reasons that have led the treatment and eradication of cancer into turmoil. The first of which is that targeting stem cells is hard (Chakraborty and Rahaman, 2012). When we target cells, all cells have originated from the stem cells, meaning the cancerous stem cells are never killed off. With this in mind, it is difficult to completely kill cancer because the cancer stem cells have the ability to ‘self-renew’ and put the body into what is known as cancer relapse (i.e., cancer comes back) (Chakraborty and Rahaman, 2012). Additionally, they could grow resistant to the drugs being given as a result of epigenetics. Prostate cancers, Esophageal cancers, and Pancreatic cancers, all extremely aggressive cancers, are challenging to diagnose for two main reasons: firstly, they are what is known as latent cancers (meaning the patient could have cancer but be asymptomatic), and the tumours start very small, giving no ‘tell-tale’ signs. Finally, metastasis is a huge problem for most cancer patients. Tumours, once killed, can still re-grow in other parts of the body, either spreading locally through the blood or through the lymphatic system (Chakraborty and Rahaman, 2012). This can happen easily, and so significantly limits the progress that can be made to eradicate it.

Financial and discriminative barriers

There are also racial and discriminative reasons why cancer treatment and eradication have been limited. These are issues that can easily be fixed, but if not, they also significantly reduce the number of possible outcomes available. The first of which is a lack of follow-up care. The average African-American cancer patient has a concerningly higher 32% chance of mortality than a white male cancer patient (Jabson and Bowen, 2013). This blatantly tells us that your race decides whether you will be treated or if cancer can be eradicated; it’s simple – if race determines your healthcare, and BIPOC people continue to get cancer, we can never fully eradicate this disease.

Additionally, cancer is missed every day in elderly patients. An interesting biopsy study was held on diseased patients over 65, and a staggering 32.5% of these patients had one or more cancer, most of which would have been fatal if their additional health issues had been dealt with (Suen, Lau and Yermakov, 1974).

Clinical trials are an extremely vital system that lead scientists to get a better understanding and idea of the kind of drugs and therapies that can cure diseases. Clinical trials in oncology are no exception. A reminder that over 1000 clinical trials in oncology took place in 2018 alone (Blazinsky and Runkel, 2019). With this in mind, it is no celebration that patients of Arizona (and indeed many other states of the US) are not receiving these possibly life-saving studies. About 20 years ago, a law was put in place in Arizona and other states that both the patient and staff had to fund these trials. Insurers also refused to cover this care, causing most of the clinical trials (which were imperative for life-saving care and advances in medicine) to be under-enrolled. As a result, a very poor and ‘flawed product’ (Olson-Garewal and Hessler, 2001) was produced, leaving much of the US without the cutting-edge possibility to make advances in cancer eradication.

These ideas show that our lack of care and discrimination is severely affecting this long and troublesome road to eradicating cancer; we forget that science does not have the only thing to do with that. Finance, race, and age are important factors but should never affect healthcare.

Conclusion

Cancer, by definition, is a disease caused by the uncontrollable cell division of mutated cells (Rosenbaum, 2011). Taking the lives of thousands of people, this disease ruins many lives and takes the lives of innocent and healthy communities. Without the quick action to find treatment and cure this disease, we are looking at a rather dim future, with around 4 million people living with cancer by the year 2040 (Anon, 2016); this is a shocking yet very real 13% of the population. Thus, cancer is the most deadly disease in the world.

But even with a cure, my question is, can we ever ‘fully eradicate’ cancer? When we look at this question carefully, we really mean ‘can we ever look at this world and not remember that cancer ever existed’? The answer is yes, we can. But what is the time frame? Is it in all countries? Is it in all cities? Is it to all species? The answers to these questions, alas, are unknown. But, due to the overwhelming scientific evidence stating that mutations are extremely hard to control and cancer stem cells are extremely aggressive, the time frame looks rather grim. In addition, the financial, racial, and age issues encompassing this disease inexplicably increase the deadline of defeating cancer. Unfortunately, this project is starting to look much more long-term than we hoped.

Cameron Davies, Youth Medical Journal 2021

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Alice in Wonderland Syndrome: It Might Sound Like a Dream, but It is More of a Nightmare

By Cameron Davies

Published 12:06 EST, Sun October 25th, 2021

What is Alice in Wonderland syndrome (AIWS)?

Although it might sound like a fairytale filled with beautiful scenery and heavenly feeling, Alice in Wonderland Syndrome, more commonly known as AIWS, is a fatal disorder that creates hugely disorientating hallucinations and other intense symptoms.

Doctor Caro Lippman first discovered this rare disease in 1952 before it was named in 1955 by John Todd. It was defined as a neurological disease that affects the vision of young people, particularly between the ages of six and twelve. It was discovered when a six-year-old boy complained of a headache. In addition to this headache, he explained the symptom of seeing distorted objects, some of which looking further away or closer than they were as if his eyes were acting as a partial magnifying glass. He even explained that it was more prevalent during the evenings and caused intense pain. Several tests were conducted, including magnetic resonance testing and Epstein-Barr virus testing, which came back negative. As a result, no diagnosis could be made, and eventually, the child died. This is because, analytically, testing does not reveal small changes to the brain, which makes this disease devilishly hard to detect (Faroq and Fine, 2017).

What causes AIWS?

AIWS is a particular syndrome onset as a result of several different prior diseases. The first of which is known as Creutzfeldt-Jaukob disease (CJD), which affects the brain, and gradually worsens over time. It originates from a protein known as a ‘prion’ which is exceptionally infectious compared to viruses and bacteria because they cannot be treated by antibiotics or extreme heat. It causes distressing symptoms, including slurred speech, memory loss, loss of intellect, and vision problems, which get worse until it causes death as the brain shuts down. One of the symptoms caused amongst these is AIWS, as the brain’s messages from the optic nerve weaken. This distorts objects (Anon, 2021). However, this disease is very difficult to contract, and treatments are being pioneered to alleviate the symptoms and find a cure. 

There is also an additional cause known as the Epstein-Barr virus. This is a type of herpes, which is another contagious disease particularly affecting young children and transmitted via bodily fluids. In addition to causing AIWS, the Epstein-Barr virus can cause mono and other illnesses. Symptoms caused include headaches, fever, fatigue, swollen liver, and rash. This virus can also become latent, where it does not cause any symptoms but can re-emerge at different times (Anon, 2021). So far, there is no treatment for this virus and no vaccination. However, drinking plenty, taking medications to alleviate symptoms, and resting avoids contracting this virus and potentially developing AIWS.

Neurology behind it

AIWS is a very complicated syndrome neurologically, especially considering that on the initial Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and serological testing, it cannot be detected. However, there are several signs which can point neurologists and doctors in the right direction in today’s world to tell them whether the patient is suffering from it, especially in combination with the description of symptoms. These include elevated proteins in the cerebrospinal fluid—the liquid around your brain and spinal cord—which could potentially be the proteins from CJD, and this was present in the 6-year old boy who was suspected of having caused CJD. 

Additionally, upon closer inspection, lower ADC levels may show AIWS. ADC level, short for the Apparent Diffusion Coefficient, measures the diffusion of water within the tissue. With less water diffusing into the tissue, this can disrupt the operation of the brain, which may cause distorted revision and headaches. These two signs are useful for scientists to detect whether AIWS has been caused in a situation where other tests come back negative, or the Epstein-Barr virus test is negative despite ongoing symptoms (Niknejad, 2016). 

Typical symptoms in more detail and demographic

As previously stated, the majority of cases seen affect young children around the age of six years, and the percentage of males is greater than that of females, though this may be due to the limited number of cases recorded of this disease. In children, a specific symptom personal to this demographic is a migraine, which typically is stronger than a headache, as well as body and object dysmorphia, the trademark sign of AIWS, as the lack of clear images with objects is seen in the story ‘Alice in Wonderland.’ 

Although the idea of not being able to see an object or body correctly seems rather harmless, and just like any other kind of hallucination, it can be extremely difficult to visualize anything when optics are so distorted, not to mention the mental deficits it can cause children, leading to going mad and psychologically unstable as a result of losing a sense of reality—30% of adolescents report these kinds of non-clinical symptoms. In addition to the mental issues, there are several physical issues caused such as nausea, dizziness, and agitation. The symptoms are also shown to worsen over time, as occurs with CJD (Anon, 2016 and Bittman et al, 2014).

Treatment options and conclusion

At this point, as with CJD and Epstein-Barr virus, there is no treatment available, despite the option to alleviate some of the hallucinations with drugs. Furthermore, because of the nature of the diseases causing AIWS, most patients who experience AIWS end up dying. However, the ICD is looking into the disease and researching possible cures with the growing number of patients contracting these neurological diseases. However, on a lighter note, 50% of patients suffer with the symptoms and lead a normal life following this syndrome (Naarden et al, 2019). It is another mystery of our incredibly weird and wonderful brain, which we are yet to understand fully, but it makes it all the more interesting and exciting.

Cameron Davies, Youth Medical Journal 2021

Reference list

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Neurology, [online] 77, pp.5–11. Available at: https://pubmed.ncbi.nlm.nih.gov/29074056/ [Accessed 11 Sep. 2021].

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Naarden, T., ter Meulen, B.C., van der Weele, S.I. and Blom, J.D. (2019). Alice in Wonderland Syndrome as a 

Presenting Manifestation of Creutzfeldt-Jakob Disease. Frontiers in Neurology, [online] 10. Available at:https://doi.org/10.3389/fneur.2019.00473. [Accessed 11 Sep. 2021].

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https://www.nhs.uk/conditions/creutzfeldt-jakob-disease-cjd/ [Accessed 11 Sep. 2021].

Stefan Bittmann, M., Weissenstein, A. and Luchter, E. (2014). Alice in Wonderland syndrome: A rare 

neurological manifestation with microscopy in a 6-year-old child. Journal of Pediatric Neurosciences, [online] 9(3), p.303. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302569/ [Accessed 11 Sep. 2021].

Wikipedia Contributors. (2021). Alice in Wonderland syndrome. [online] Wikipedia. Available at: 

https://en.wikipedia.org/wiki/Alice_in_Wonderland_syndrome#:~:text=With%20over%2060%20associated%20symptoms,with%20Alice%20in%20Wonderland%20syndrome. [Accessed 11 Sep. 2021].