Categories
Narrative

CRISPR Technology Today

By Katelyn Crawford

Published 8:50 EST, Mon October 25th, 2021

The CRISPR/Cas9 technology is continually advancing and improving with rigorous scientific testing. This technology leads the scientific community closer to finding cures for genetic diseases, but it also creates more questions and ethical concerns. CRISPR technology is one method of genetic engineering that cuts out and replaces or repairs specific segments of DNA sequences, including sequences that code for specific monogenic diseases. This emerging technology holds many potential lifesaving benefits but fails to address long-standing societal concerns about the dangers of genetic engineering.

The CRISPR technology is expected to cure many single-gene diseases such as Sickle Cell Anemia or Cystic Fibrosis. For example, CRISPR could be used to alter the gene responsible for Cystic Fibrosis, called the CFTR gene; this technology would correct known mutations that give rise to Cystic Fibrosis. However, thousands of different mutations could cause the disease, and not all of these mutations can be targeted with our current technologies. Therefore, genetic sequencing would need to be performed on each patient to identify which cases could be cured with gene therapy and which are currently genetically inaccessible. Due to CRISPR making permanent changes to the genetic code, much research must be performed before the technology can be approved for testing on human patients with specific CF-related point mutations. Furthermore, in 2018 a new version called base editing was created, which was able to fix some CF mutations without cutting the DNA sequence. The original CRISPR technology would cut the DNA strand, potentially harming the person by damaging the DNA sequence with inappropriate DNA repair; instead, this new technology directly repairs the mutation site without cutting the DNA sequence [1]. This base editing technology is a safer way to use CRISPR to edit gene sequences to treat Cystic Fibrosis and eventually many other diseases. 

One crucial aspect of successful treatment is identifying this new CRISPR enzyme to target the correct cell types within specific organs. This is important because genes often play critical roles in developing or functioning multiple cell types or organs. A mutation may be harmful to heart function but benign or helpful to brain function. One example of this dichotomy is the intended targeting of survival genes in cancer cells that unintentionally harm the immune cells responsible for clearing the cancer cells; this unintentional harm then decreases the treatment efficacy. So while these advancements to the CRISPR technology are beneficial to patients and will revolutionize the treatments of some diseases, a lot is still unknown. One area of active research focuses on the removal of white blood cells from a patient, followed by gene editing and then inserting the edited cells back into the affected patient. Scientists believe this approach could be used to treat certain kinds of cancer and infectious diseases, like HIV. It combines CRISPR technology with the technology to insert the CRISPR raw materials into a cell [4]. Scientists now argue that they can use electrical fields instead of viruses to introduce gene-editing materials into immune cells to treat various cancers. These newly edited immune cells then are inserted back into the body, where the cells find and attack the tumor. Many questions must be answered before it can be approved for human use. For instance, how long would it take for the modified cells to find and destroy the tumor? Will these cells show autoimmune behavior and also destroy healthy tissue? The technology should allow for the quicker treatment of diseases like HIV and Cancer, where weeks to months make a significant difference for patient survival. 

Since all of the changes made to the genome sequence by CRISPR are permanent, it is important to note that the technology is only being considered for use in somatic cells. These are cells in the body that do not get passed down to any children. There is concern that CRISPR use in germline cells may permanently adjust the genes in humans passed down to children, including any mistakes that the editing technology may have made. This brings up the idea of how technology would change genetic diversity. The prevention or treatment of life-threatening diseases is helpful technology, but beyond unintentional mistakes getting introduced into the gene pool, where does the editing stop? Is there any way for people to prevent the use of CRISPR for editing medically insignificant traits, such as eye color? Due to these concerns, the scientific community is attempting to hold off on all genetic engineering of embryos to allow time for ethicists and the law to catch up with scientific progress. Clear guidelines will need to be provided before using these technologies. There is limited funding for research available, so studying CRISPR to treat life-altering diseases takes top priority; introducing the possibility of researching medically insignificant mutations would waste resources better served to prevent or correct life-threatening conditions. People’s lives could depend on this treatment, and many ethical issues arise as a result.

Pending future approval of CRISPR for medical cures, another significant drawback is the cost. This technology is new and very expensive. Researching and repairing one protein could cost millions of dollars, including the cost of many stages of trials needed for FDA approval, animal care for testing, the cost of patents, and licensing to a company. Paying the researchers and other employees leads to a significantly higher price, which is prohibitive to many families. Additionally, the time to conduct the necessary research before use in patients may nullify the need for treatment if the process takes too long or cannot be scaled up effectively. Thus, the costs associated with CRISPR are not accessible to most families, which raises the question “If only some patients can afford treatment with CRISPR, what makes these people more qualified or deserving of treatment?”. To illustrate this point, in 2019, Novartis released a gene therapy called Zolgensma to treat Spinal Muscular Atrophy. In the base-case analysis, the company’s subjective value was estimated at $900,000 per treatment [2]. This is the cost of a single treatment, but it is hard to determine how many treatments a single patient will need with the unknowns of gene therapy. As a result, only 700 patients were approved for the treatment. In the future, where CRISPR has received approval for a broader range of genetic diseases, it will not be cheap at its current scale, and therefore many people will not be able to afford it. As the technology changes and is streamlined, cost-effectiveness may also improve, but if the costs fail to decrease, what are the determining factors in who will get this life-saving treatment? CRISPR is controversial, costly, and time-consuming to bring from start to finish; with CRISPR’s potential to yield so many treatments weighed against its considerable drawbacks, how can the overall impact of CRISPR truly be determined? And will CRISPR turn out to be the silver bullet of gene therapy, or will it fall short of expectations?

Katelyn Crawford, Youth Medical Journal 2021

References

[1]Inacio, Patricia. “New CRISPR Tool Fixes CFTR Mutations in CF Patients’ Stem Cells, Study Finds.” Cystic Fibrosis News Today. Last modified March 16, 2020. Accessed July 21, 2021. https://cysticfibrosisnewstoday.com/2020/03/16/new-crispr-tool-fixes-cftr-mutations-in-cf-patients-stem-cells-study-finds/.

[2]Irvine, Alison. “Paying for CRISPR Cures: The Economics of Genetic Therapies.” Innovative Genomics Institute. Last modified December 16, 2019. Accessed July 21, 2021. https://innovativegenomics.org/blog/paying-for-crispr-cures/.

[3]John J. Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A. E. Zwart, Ruth Chadwick, The International Human Genome Organisation (HUGO) Committee of Ethics, Law, and Society (CELS), Ethical issues of CRISPR technology and gene editing through the lens of solidarity, British Medical Bulletin, Volume 122, Issue 1, June 2017, Pages 17–29, https://doi.org/10.1093/bmb/ldx002

[4]Kolata, Gina. “Swift Gene-Editing Method May Revolutionize Treatments for Cancer and Infectious Diseases.” New York Times. Last modified July 11, 2018. Accessed July 21, 2021. https://www.nytimes.com/2018/07/11/health/gene-editing-cancer.html?hp&action=click&pgtype=Homepage&clickSource=story-heading&module=second-column-region.

Categories
Narrative

Lessons from Aviation

By Rhea Agarwal

Published 11:18 EST, Sat October 23rd, 2021

What is Power Distance?

The concept of power distance was first developed by the Dutch social psychologist, Geert Hofstede; it was one of the first theories of Hofstede’s Cultural Dimension Theory in which Hofstede attempts to quantify the differences in cultural behaviours. Power Distance is a term that expresses the distribution of power in an organization or industry (Kenton, 2021). The Power Distance Index (PDI) is a measure of the power distance in a country; the numbers of a PDI convey the degree to which unequal distribution of power is accepted in a culture or nation. The elucidation of a number on a PDI scale tends to be rooted in cultural norms and legacy (Pettit Whisenant, 2019).

Individuals in an industry demonstrating a high power distance, generally embody people that do not challenge figures of authority and are accepting of hierarchical culture; contrarily, individuals demonstrating a low power distance do not hesitate in questioning figures of authority and expect their views to be holding some weight when making decisions. These behaviours are not only evident within the culture of a nation but also within the culture of certain professions such as aviation and healthcare (Pettit Whisenant, 2019).

Power Distance in Aviation

In the book, Outliers: The Story of Success, author Malcolm Gladwell discusses how a high PDI culture in aviation had severe reverberations on aviation safety (Gladwell, 2009).

In the period 1988 to 1998, Korean Air’s “loss” rate was 4.79 per million departures. An airline’s loss rate is the frequency with which crashes or aviation accidents occur. Relatively, the loss rate for the American carrier United Airlines in the same period was 0.27 per million departures; Korean Air’s record was more than seventeen times higher than that of United Airlines’. However, today Korean Air is a certified 5-star airline and its safety record since 1999 has been immaculate. In recognition of this transformation, Korean Air has received the Phoenix Award in 2006 (Gladwell, 2009).

In retracing Korean Air’s transformation, we see how decreasing a high PDI played a significant role in minimising the airlines’ loss rate and thus ameliorating its reliability and reputation. According to aviation experts, a plane crash is multifactorial and often a culmination of errors that leads to a crash. Astonishingly, these errors are rarely problems of knowledge or flying skill, rather they are errors of teamwork and communication (Gladwell, 2009).

“The whole flight-deck design is intended to be operated by two people, and that operation works best when you have one person checking the other, or both people willing to participate. You will have a safer operation than if you have a single pilot flying the plane and another person who is simply there to take over if the pilot is incapacitated.”

(Earl Weener, Chief Engineer for Safety at Boeing)

In Korean Air, it was the captain on the “flying seat.” The first officer simply worked as a substitute rather than a supplement in the cockpit (Gladwell, 2009).

On August 5, 1997, Korean Air Flight 801 departed for Guam; the flight crashed on August 6, 1997. Among other reasons such as bad weather, the National Transportation Safety Board, nonetheless, cites poor communication between the flight crew and the captain’s poor decision-making skills as the main cause of the crash (Wikipedia, 2021). Upon subsequent inspection of the black box, by psychologists, the most unusual feature of the conversations between the captain, first officer, and first engineer was the lack of explicitness in the language used by the subordinates in informing their captain of an emergency. The speech used by these officers is identified by psychologists as “mitigated speech (Gladwell, 2009).”

Mitigated speech is indirect communication inherent in communication intended to be polite or deferential to authority; it involves implicitly suggesting or referring to something and often uses subtle hints to convey a message. In a critical situation, mitigated speech coming from a subordinate is very likely to be ignored or looked over. The use of mitigated speech by subordinates during this emergency not only demonstrates a high power distance relationship between the captain and the officers but also indicates that such conduct may deeply be entrenched in cultural legacy. Helmreich and Merritt once measured the PDI of pilots from around the world; South Korea ranked second (Gladwell, 2009).

After experiencing several preventable aircraft accidents, aviation recognized the need for change. Reducing “mitigation” has become one of the greatest crusades that aviation has striven for by changing a bureaucratic culture to one that epitomizes collaboration and safety. Aviation experts contribute the decline in airline accidents to the battle against mitigation (Pettit Whisenant, 2019).

Substantial sociological research on the repercussions of a high power distance in aviation has been performed. However, such research is not as readily available for the medical field. In this article, we attempt to draw similarities in the critical situations of both professions. Thus, just how aviation integrated research results to improve safety, the healthcare profession can draw on tips to do the same. Both of these professions share certain features: high-level thinking and quick decisions with no room for error; mistakes in critical situations can have severe safety repercussions. 

Power Distance in Healthcare

The cockpit, with its intricate manoeuvres, can, to some extent, simulate the exacting environment of an operating room; the two professions share a strong resemblance in their administration. In a healthcare setting, the physician has the authority and the final say in most operations. However, a hospital setting does not only involve physicians –  there are nurses, residents – in – training, and assistants – all of which have received official training. A high PDI invalidates their observations and assessments; a low PDI, however, demands participation from all positions. A low PDI work environment involves communication and the transfer of necessary information among different departmental positions. This makes the system efficient, thus indirectly promoting better health outcomes. Literature confirms that a high power distance culture reduces worker wellbeing and commitment thus negatively impacting a positive work atmosphere (Rafiei & Sadeghi, 2018).

Let’s compare the healthcare systems of Denmark and the US. Denmark’s healthcare system is known to be able to provide its citizens with efficient and low-cost healthcare with better health outcomes than the US. Immediately, one may presume that the Danish government may be having higher funds allocated towards healthcare or may have rolled out better healthcare policies. False! In fact, on a percentage of GDP on a per capita basis, Denmark spends less money on healthcare than the US; also no unique policies have been rolled out which may distinguish one healthcare system from the other. The root of the issue is the culture in the workforce. Denmark has a relatively lower power distance culture than the US  (Matus, 2017).

The diminished bureaucratic system in Denmark’s healthcare system optimizes the capacity of the workforce thus enabling an efficient system to operate; additionally, it recognizes the contribution of all healthcare providers (Matus, 2017).

To conclude, a healthcare system can greatly benefit from dismantling a hierarchical system within its administration thus promoting a positive and efficient workplace environment.

Rhea Agarwal, Youth Medical Journal 2021

Conclusion

There is limited research examining how a high power index affects the healthcare environment. Yet, we can draw parallels between the two industries in the sense that both involve complex procedures with little or no room for error. As one begun its crusade against an entrenched, detrimental cultural behaviour, the other should take lessons to do the same. It is only in this way can healthcare promote active participation from all its constituents, thus ensuring an efficient system with better health outcomes.

“Bureaucracy is the death of all sound work.” ~ Albert Einstein

Rhea Agarwal, Youth Medical Journal 2021

Bibliography:

Gladwell , M. (2009). The Ethnic Theory of Plane Crashes . In Outliers: The story of success (pp. 206–261). essay, Back Bay Books/Little, Brown.

Hofstede Insights . (2017). Comparison of Pdi between Denmark and Usa. How does Denmark have better healthcare than the US for less money? https://sciencenordic.com/culture-denmark-forskerzonen/how-does-denmark-have-better-healthcare-than-the-us-for-less-money/1451158.

ICSB. (2020). Geert Hofstede . ICSB takes a moment to remember Geert Hofstede. https://icsb.org/geerthofstede/.

Kenton, W. (2021, July 14). What is the power Distance Index (PDI)? Investopedia. https://www.investopedia.com/terms/p/power-distance-index-pdi.asp.

Matus , J. C. (2017, December 10). How does Denmark have better healthcare than the us for less money? ScienceNordic. https://sciencenordic.com/culture-denmark-forskerzonen/how-does-denmark-have-better-healthcare-than-the-us-for-less-money/1451158.

Meyers – Reuters , M. (2019). The Tragedy of Flight 801. http://content.time.com/time/covers/asia/0,16641,19970818,00.html.

Pettit Whisenant, D. (2019). Power distance in Healthcare: Learning from aviation to decrease power distance and improve Healthcare Culture. stti.confex.com. https://stti.confex.com/stti/congrs19/webprogram/Paper98235.html.

Rafiei , S., & Sadeghi , P. (2018). Personnel Attitude toward Power Distance in Hospitals Affiliated by Qazvin University of Medical Sciences. Evidence Based Health Policy, Management & Economics.

Wikipedia . (2021, August 7). Korean air flight 801. Wikipedia. https://en.wikipedia.org/wiki/Korean_Air_Flight_801.