Well done to Ashvin on winning  the secondary school category of our ‘Unofficial Guide to Medicine Essay Competition’ for his essay on “Consider the development of personalised medicine. What are the benefits and drawbacks of selecting appropriate therapies based on the context of one’s genetic code?”


Unofficial Guide to Medicine - Ashvin Kuri
My name is Ashvin Kuri, I am currently studying Biology, Chemistry and Mathematics at A-Level and I hope to study Medicine at University. I particularly enjoy Human Biology and learning about diseases and their cure. Outside oflessons, I enjoy competing in Athletics, playing the violin, piano and singing, and volunteering in my local area at a Care Home and with disabled children.


Consider the development of personalised medicine. What are the benefits and drawbacks of selecting appropriate therapies based on the context of one’s genetic code?

 

“Medical progress to this point has been mainly based on advances that benefit the population as a whole rather than you as an individual.” 1

Pieter Cullis, ‘The Personalized Medicine Revolution: How Diagnosing and Treating Disease Are About to Change Forever

At 44 years of age, Richard Heimler viewed his rapidly deteriorating condition following his diagnosis of Non-Small Cell Lung Cancer as a ‘death sentence,’2 as repeated treatments failed. It was only by identifying that he was ALK positive through a genetic-screening Vysis ALK test that Heimler’s life was saved, as he could be treated with Crizotinib3, a drug specifically aimed at treating those carrying the ALK gene rearrangement – the key to Heimler’s cure was in his DNA.

Personalised Medicine, as defined by the National Institute of Health, is ‘a form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease.’4 The traditional practice of Medicine has been based on ‘standards of care’5 – patients should be given treatments based on the previous responses of sample study patients to that treatment. Rather than this ‘one-size-fits-all’ approach to Medicine, ignoring an individual’s genetic and metabolic uniqueness and idiosyncratic responses to medication, Personalised Medicine enables the prediction of an individual’s susceptibility to disease and response to different treatments, based on their genetic profiling and other environmental factors, thereby significantly improving prognosis. This essay will discuss how Personalised Medicine is changing and shaping the healthcare landscape by shifting the emphasis of Medicine from reaction to prevention, and will consider both the potential benefits and risks of selecting appropriate therapies based on the context of one’s genetic code.

Reflecting upon the development of Personalised Medicine over time, it is clear that the concept of Personalised Medicine has existed for millennia. Hippocrates’ first diagnoses of illness as an imbalance of one of the four ‘cardinal fluids’ is an example of Personalised Medicine more than two millennia ago6 – individuals could have different illnesses that needed unique treatments. Symptoms of Melancholia were attributed to excess ‘black bile’ that needed to be treated differently from individuals presenting with a ‘choleric’ temperament, suggesting an imbalance of yellow bile.7Thus, if Medicine has already been personalised for some time, why debate the need for Personalised Medicine now? The answer is that Medicine is simply not as personalised as it can be and arguably should be, especially in light of recent technological advances. An example of the perils of ignoring Personalised Medicine comes from William Halsted in the 20th century, who pioneered radical surgery to remove breast cancer tumours.8 His principles relied on excavating as much of the chest cavity lymph nodes and tumour as possible, regardless of its size or location. This generalised approach to surgery was dangerous and treating the individual patients’ needs on a case-by-case basis would have been much more effective and certainly less disfiguring. Since the entire human genome was sequenced in 2003,9 it has paved the way to an altogether new direction of Personalised Medicine.

The argument for the implementation of Personalised Medicine across healthcare is indisputably robust. In a growing national and indeed global population, the incidence of certain non-communicable diseases, such as prostate and lung cancer (with an increase in incidence of 5% and 4% respectively in the last decade) 10 is rising alarmingly. This is where Personalised Medicine has the greatest potential – in aiding the selection of appropriate treatments based on the individual’s genetic code to more effectively manage certain diseases. Currently, as Spear et al.’s study on clinical trends in Molecular Medicine highlights11, prescribed drugs are not always as effective as they should be; initial drug treatments for Diabetes, Arthritis, Alzheimer’s and Cancer are ineffective in 43%, 50%, 70% and 75% of the patient population respectively. This low efficacy comes at both a significant economic cost to healthcare providers, and a considerable psychological and physical cost to the patient. Personalised Medicine could be the solution to this problem, as through sequencing individuals’ genomes, it is possible to identify the best treatment options for certain diseases more rapidly.

Personalised Genomic Medicine has been shown to play a very significant role is cancer. Certain BRCA1 and BRCA2 gene variations12 predict increased lifetime risk for breast and ovarian cancer – early identification of these genes allows preventative measures such as mammography, ultrasound imaging and biomarker detection. The patient also has the option of prophylactic surgery or medication such as Tamoxifen to reduce the likelihood of onset of disease. However, genetic tests can also be used to determine the best treatment options of some cancers once a patient has been given a diagnosis. For example, testing positive for overproduction of a gene product, human epidermal growth factor 2, indicates better response to Herceptin, which can halve the risk of disease recurrence.13In Chronic Myeloid Leukaemia, a diagnostic test indicating the presence of a mutant gene (BCR-ABL14) predicts increased sensitivity to the drug Imatinib (a tyrosine kinase inhibitor) stopping cancer cells dividing and predicting significantly improved patient response. Personalised Medicine could play a vital role in managing an increasing number of cancers in the future.

Besides cancer, the treatment of other conditions can also benefit hugely from Personalised Genomic Medicine. In Cystic Fibrosis patients, genetic sequencing enables more selective treatments. For example, there are certain precision drugs, such as Ivacaftor, that work on specific gene mutations, helping to reduce the amount of time spent in hospital and improve outcome.15 Moreover, beyond screening for risk and treatment of illness, sequencing individuals’ genomes can also give information on the ability of the body to metabolise certain drugs. For example, it can yield genetic information on liver enzymes, such as cytochrome P450 – an invaluable tool in clinical practice in identifying the most effective treatments and appropriate dosages.

There are however, significant ethical and practical concerns regarding Personalised Medicine. In order to provide individualised treatments based on one’s genetic code, it is necessary to obtain the patient’s personal genetic sequence. Having this information leads to increased responsibility for healthcare services and a major ethical dilemma around confidentiality and accessibility to an individual’s genetic data. Under what circumstances should employers or insurance companies have a right to the information uncovered? Should family members have a right to the findings because of the hereditary nature of genes or the burden that the illness might pose to the family? And what if they did not wish to know what genetic testing of a family member has inadvertently revealed about themselves? Could we be heading towards a world where we can precisely predict our future health, perhaps even when nothing can be done to prevent the inevitable – the psychological impact of this on patients must be considered. Should psychological support be made available with genetic testing and if so, this would add to the economic cost. These questions must be addressed when considering the future of Personalised Medicine.

Another ethical conundrum arises from the possibility of non-medical use of an individual’s genomic sequencing data. The term ‘Genetic Elitism’ is not frequently encountered in today’s society, but if everyones’ genomes are sequenced, then the possibility of a form of elitism founded upon perceived ‘better genes’ may arise. Furthermore, a difficult clinical decision regarding criteria for testing will have to be made – should it be those who have a family history of a medical condition or are unresponsive to initial treatments, or perhaps those who exhibit significant behavioural disorders, or just those who can pay for the testing? And who would make that decision to refer for genome sequencing – the patient, the family, or medical professionals?

The final major potential ethical drawback of personalised medicine comes in light of the recent breakthroughs in gene editing therapies, CRISPR and retroviral technology. If we have the ability to demonstrably show that a patient is at risk of a condition, could we use gene editing processes utilising retroviral techniques to treat the condition? Furthermore, if we can sequence the genomes of foetuses before they are born, could we edit their genetic make up and create ‘designer babies,’ without genetic predispositions to disorders or perhaps simply with perceived desirable qualities such as higher IQs or preferred physical attributes. And on a fundamental, evoluntionary level, should we really artificially interfere with the essential indefatigable evolutionary mechanism when we cannot be sure what the outcomes may be? Could mistakes during gene editing cause genetic disorders instead?

In conclusion, the future of Personalised Medicine is exciting and there are very significant benefits to selecting appropriate therapies based on genomic sequencing. Numerous private companies are already running cheek swab and blood sample tests for personal genome testing.16 Treatments can be expected to become more efficient – screening for variations in the enzyme CYP2C9 is already allowing for more accurate warfarin dosages in patients17 – and less costly to healthcare services. Whilst there are certainly some challenges posed by Personalised Medicine, if effectively managed and monitored, Personalised Medicine should be the direction for the future of healthcare.


References

  1. Cullis, P. (2015, February). “The Personalized Medicine Revolution,” Greystone Books
  2. Abbottcdx.com (Date Unknown).  “Meet Richard Heimler,” Abbottcdx.com. Last Accessed 31/01/17
  3. Kerins, R. (2011, August). “FDA Approval of XALKORI (crizotinib),” Pfizer.com. Last Accessed 31/01/17
  4. NIH, National Cancer Institute. “NCI Dictionary of Cancer Terms, personalized medicine,” cancer.gov. Last     Accessed 31/01/17
  5. Mcmullan, D (2015). “What Is Personalized Medicine,” genomemag.com. Last Accessed 31/01/17
  6. Mukherjee, S. (2011, September). “The Emperor of All Maladies: A Biography of Cancer,” Fourth Estate
  7. Mukherjee, S. (2011, September). “The Emperor of All Maladies: A Biography of Cancer,” Fourth Estate
  8. Mukherjee, S. (2011, September). “The Emperor of All Maladies: A Biography of Cancer,” Fourth Estate
  9. Chial, H. (2008). “DNA Sequencing Technologies Key to the Human Genome Project,” Nature, Last  Accessed 31/01/17
  10. Cancer Research UK. (2014). “Cancer Incidence Statistics” canceresearchuk.org, Last Accessed 31/01/17
  11. Spear, B. B., M. Heath-Chiozzi, and J. Huff. (2001). “Trends in Molecular Medicine” 7(5):201-204
  12. Petrucelli, N et al. (1998). “BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.” NCBI. Last Accessed 31/01/17
  13. Dobson, R. (2005). “Trastuzumab halves risk of recurrence of breast cancer in some women.” BMJ.
  14. NCI Dictionaries (Date Unknown). “BCR-ABL Fusion Gene.” NCI Dictionaries, Last Accessed 31/01/17
  15. Whiting, P et al. (2014, March). “Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis.” PubMed.gov. Last Accessed 31/01/17
  16. ISOGG. (Date Unknown). “List of Personal Genomics Companies,” ISOGG.org, Last Accessed 31/01/17
  17. Dean, L. (2016). “Warfarin Therapy and the Genotypes CYP2C9 and VKORC1” NCBI, Last Accessed 31/01/17

Bibliography

  • Abbottcdx.com (Date Unknown).  “Meet Richard Heimler,” Abbottcdx.com. Last Accessed 31/01/17
  • Cancer Research UK. (2014). “Cancer Incidence Statistics” canceresearchuk.org, Last Accessed 31/01/17
  • Chial, H. (2008). “DNA Sequencing Technologies Key to the Human Genome Project,” Nature, Last Accessed 31/01/17
  • Cullis, P. (2015, February). “The Personalized Medicine Revolution,” Greystone Books
  • Dean, L. (2016). “Warfarin Therapy and the Genotypes CYP2C9 and VKORC1” NCBI, Last Accessed 31/01/17
  • Dobson, R. (2005). “Trastuzumab halves risk of recurrence of breast cancer in some women.” BMJ
  • ISOGG. (Date Unknown). “List of Personal Genomics Companies,” ISOGG.org, Last Accessed 31/01/17
  • Kerins, R. (2011, August). “FDA Approval of XALKORI (crizotinib),” Pfizer.com. Last Accessed 31/01/17
  • Mcmullan, D (2015). “What Is Personalized Medicine,” genomemag.com. Last Accessed 31/01/17
  • Mukherjee, S. (2011, September). “The Emperor of All Maladies: A Biography of Cancer,” Fourth Estate
  • NCI Dictionaries (Date Unknown). “BCR-ABL Fusion Gene.” NCI Dictionaries, Last Accessed 31/01/17
  • NIH, National Cancer Institute. “NCI Dictionary of Cancer Terms, personalized medicine,” cancer.gov. Last     Accessed 31/01/17
  • Petrucelli, N et al. (1998). “BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.” NCBI. Last Accessed 31/01/17
  • Spear, B. B., M. Heath-Chiozzi, and J. Huff. (2001). “Trends in Molecular Medicine” 7(5):201-204
  • Whiting, P et al. (2014, March). “Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis.” PubMed.gov. Last Accessed 31/01/17

 

Feedback

A very original and eye-catching start to your essay with the quote and case study which demonstrates just how much of a difference the use of personalised medicine can make to a person’s life. You have shown excellent in depth-research into the history of personalised medicine and your essay has a good logical structure which moves smoothly from the history to current use of an individual’s genome to make treatment decisions. Your use of the literature adds great weight to your discussion of the need for personalised medicine by providing evidence of the problem that we currently face with drugs being ineffective in a large proportion of people. However you have also shown independent insight into the topic and thought about all the benefits of personalised medicine for both individual patients and for the NHS. You have covered its many uses all the way from prevention of disease, to predicting drug response and metabolism, illustrated well with specific examples. You have clearly put great thought into the ethical issues surrounding personalised medicine and have expressed them very coherently. Well done on an excellent essay.

Ashvin’s essay was a very interesting read. He has clearly researched the topic extensively to allow for such an in-depth discussion of the benefits and potential pitfalls of personalised medicine. The essay was written in a captivating way with good references making it an authorative piece. Great work Ashvin.

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