Categories
Blockchain

Blockchain and its Applications in Medicine

Alicia Tran—McMaster Software and Biomedical Engineering, 2023

With the fast rate at which technology is developing during today’s day and age, many novel digital solutions are making their way to solve problems in new contexts. Blockchain is one such buzzword being thrown around in recent years.

A Surface-Level Look

The main characteristic of a blockchain system is the distribution of data in a peer-to-peer network rather than through a centralized server (1). Due to its numerous features and advantages, it is especially desirable for use in implementing cryptocurrency systems, its most well-known application, the process of which is shown below.

SOURCE: Biomedical Journal of Scientific & Technical Research

What’s the Big Deal?

As mentioned in the example above, data in the blockchain is immutable, meaning it cannot be changed, due to sheer amount of computational power that would be required to change data in all nodes of the network (2). This immutability leads to many advantages of the blockchain, namely, but not limited to, traceability, integrity, and security (3). As the data cannot be changed, transactions can be tracked through the system. In addition, the system verifies the authenticity of transactions against all data sources throughout the blockchain network, reducing likelihood of fraud (3). Lastly, the very nature of a decentralized system results in no single data source for malicious users to target (2).

Uses in Healthcare

There are many opportunities to implement blockchain the health sector. The main requirements of any health-related system being developed today are security and data sharing (3). Medical information is bound by Health Insurance Portability and Accountability Act of 1996 (HIPAA) and thus needs to be secure to ensure patient privacy (4). On the other hand, patients may wish to have access to their own data and physicians may need to share information with other doctors should a patient require expanded care, so it is imperative that information can be shared only with those permitted access (3). By leveraging the security and mobility of a decentralized blockchain system with many data sources, this general problem can be solved with the use of smart contracts, whereby records can only be accessed if users have the required signatures (or keys) (2).

SOURCE: Biomedical Journal of Scientific & Technical Research

Through this system, MedRec, developed as part of the digital currency initiative at MIT Media Lab, seizes on the opportunity for interoperability in healthcare systems by having a decentralized hub of medical records of which all healthcare providers would have access (5). Smart contracts are used to map patient-provider relationships, with a contract containing a list of references detailing the relationships between nodes (patients and healthcare providers) (5). This allows the patient to accept, reject, or modify relationships with healthcare providers, putting themselves in control of their own information (5).

Uses can also become more niche. In the case of clinical trials, it can be used to maintain a log of patient consent. Due to the immutability of data in the system, one can easily monitor trial standards and prevent falsification of consent forms, thereby reducing clinical fraud and preserving the integrity of the data (5). A smart contract system would prevent study investigators from accessing patient information unless they are provided with consent at each stage of the trial (5).

Drug tracking is another avenue of blockchain application. It prevents theft and fraud by making use of the immutability of the system to track the chain of custody of pharmaceuticals, from when it is manufactured to when it is in the possession of a patient (5). The Counterfeit Medicines Project, created by Hyperledger, the Open-Source Blockchain Working Group tackles the problem of counterfeit pharmaceuticals by tracing and removing counterfeit medicine from the supply chain (5).

It is clear to see how blockchain has many uses outside of cryptocurrency, with which it is commonly associated. As the technology is further developed, it will no doubt continue to become more widespread in the healthcare sector.

References

  1. Oderkirk J, Slawomirski L. Opportunities and challenges of blockchain technologies in Healthcare [Internet]. Organisation for Economic Co-operation and Development. 2020 [cited 2021Dec12]. Available from: https://www.oecd.org/finance/Opportunities-and-Challenges-of-Blockchain-Technologies-in-Health-Care.pdf
  2. Huang X. Blockchain in Healthcare: A patient-centered model. Biomedical Journal of Scientific & Technical Research [Internet]. 2019Sep27 [cited 2021Dec11];20(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764776/
  3. McGhin T, Choo K-KR, Liu CZ, He D. Blockchain in healthcare applications: Research challenges and opportunities. Journal of Network and Computer Applications [Internet]. 2019Jun1 [cited 2021Dec11];135:62–75. Available from: https://www.sciencedirect.com/science/article/pii/S1084804519300864
  4. (OCR) Office for Civil Rights. Summary of the HIPAA security rule [Internet]. HHS.gov. 2021 [cited 2022Jan11]. Available from: https://www.hhs.gov/hipaa/for-professionals/security/laws-regulations/index.html
  5. Bell L, Buchanan WJ, Cameron J, Lo O. Applications of blockchain within healthcare. Blockchain in Healthcare Today [Internet]. 2018 [cited 2021Dec11];1. Available from: https://blockchainhealthcaretoday.com/index.php/journal/article/download/8/29&hl=en&sa=X&ei=f7ehYZPYMIGEmgGSwISoAw&scisig=AAGBfm0Crm9y6UcKNWw50TQDjdIvrx-R4A&oi=scholarr
Categories
Stem Cells

Regenerating Tissues and Organs: Stem Cells and the Future of Medicine

Vedish Soni—McMaster Health Sciences 2023

Stem cells have captured the imagination of researchers worldwide. With millions of dollars in funding, labs have been fervently working to make the dream of fully regenerative stem cell therapies a reality. Stem cell therapies promise a radically different way to treat disorders, as they use the body’s own regenerative properties to fix damaged organs, tissues, and cells. Exploring the current state of stem cell therapies shows that they may have a significant impact on the future of medicine.

In order to understand the impact of stem cell therapies, it is first important to understand what stem cells are. Stem cells are blank slates, once given appropriate instruction, they can differentiate into various cell types. Stem cells are also self-renewable, which means they can continually divide to create a perpetual pool of other stem cells. The application of the differentiation and self-renewable properties of stem cells to regrow damaged tissue is the objective of stem cell therapies. These therapies may provide medicine a way to treat previously incurable diseases and disorders. 

SOURCE: National MS Society

Stem cell therapies have shown great potential in combating heart disease. Current treatments cannot completely repair damaged hearts, which can often lead to remission.  Stem cell therapies offer a solution, as researchers have been successful in using adult stem cells to create heart cells in mice.1 This is an exciting breakthrough, since hospitals may soon be able to forego complicated surgeries or organ transplants in favour of regenerating damaged cells. This has the potential to revolutionize heart disease treatment as patients will no longer have to wait years for organ donations, nor will they have to live with faulty hearts. Through the regenerative power of stem cell therapies, heart disease may no longer pose a threat in the future.

Complicated neurological disorders may also be treated with stem cells.  A preclinical study done by Swistowski et al. used stem cells to regrow key neurons implicated in Parkinson’s Disease (PD).2 Additionally, Yamanka et al. has begun the first clinical trial on using stem cells to treat PD, and preliminary results have already proven its safety.3 If perfected, the ability to regrow famously delicate neurons using stem cells is revolutionary. This would provide scientists the ability to return patients to the state they were in before the onset of the neurological disorder. Consequently, incurable diseases like Parkinson’s and Alzheimer’s would finally have appropriate treatments.  Thus, the application of stem cell therapies in neurology can help solve some of the field’s most difficult challenges.

Beyond its typical uses, stem cell therapies are being used in conjunction with other procedures to create some remarkable results. Researchers are currently using stem cells and other reproductive techniques to create artificial sperm and embryos to prevent the northern white rhinoceros from going extinct.4 This has interesting implications for human fertility, as the use of stem cells to create sex cells could assist those who have reproductive problems. Stem cell therapies can also be used to support patients suffering from deadly viruses. Stem cells have been shown to decrease the immunological and inflammatory processes that lead to lung injury in COVID-19.5 This means that stem cell therapies can be used to support patients suffering from serious symptoms while they await treatment.  As is evident in the above studies, the creative use of stem cell therapies may be able to support patients in exciting ways.

Despite considerable advances in medicine, patients often still fall victim to many diseases. Noncommunicable diseases still prey upon millions of lives per year, with current treatments being unable to fully return patients back to normal. Stem cell therapy may be the solution, as regenerating damaged tissue would be far more effective than any pill or surgical procedure. Despite the challenges in creating fully regenerative therapies, history shows when scientists put in the time and effort, remarkable things can occur. In a few decades, the stem cell therapy revolution may very well push humanity into a new age of medicine.

References

  1. Tomita SJ, Li RK, Weisel RD, Mickle DA, Kim EJ. Sakai Tl. Autologous transplantation of BMC improves damaged heart function. Circulation. 1999;100.
  2. Swistowski A, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X. Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem cells. 2010 Oct;28(10):1893-904.
  3. Takahashi J. Stem cell therapy for Parkinson’s disease. Expert review of neurotherapeutics. 2007 Jun 1;7(6):667-75.
  4. Hildebrandt TB, Hermes R, Colleoni S, Diecke S, Holtze S, Renfree MB, Stejskal J, Hayashi K, Drukker M, Loi P, Göritz F. Embryos and embryonic stem cells from the white rhinoceros. Nature communications. 2018 Jul 4;9(1):1-9.
  5. Zanirati G, Provenzi L, Libermann LL, Bizotto SC, Ghilardi IM, Marinowic DR, Shetty AK, Da Costa JC. Stem cell-based therapy for COVID-19 and ARDS: a systematic review. npj Regenerative Medicine. 2021 Nov 8;6(1):1-5.

Categories
COVID-19 Pharmaceuticals

The Future of Vaccine Companies: Unceasing Competition

Seonhwa Lee—McMaster Honours Human Behaviour 2024

With decreasing trend in infection cases and lighter restrictions following the expedite development of effective vaccine supply, it seemed like the world was finally coming back to normal. This hope is now shattered with the recent emergence of omicron, the new variant of COVID virus. At this time of inflection, what is the future of major vaccine companies?

Engaging Variant and Booster Vaccines

Omicron varies from other COVID viruses in its numerous mutations in the spike protein, which the vaccine aims to mimic to produce antibodies. In fact, studies were conducted by Pfizer and BioNTech to see a significant decrease in the number of virus-targeting antibodies in omicron (1). They also found evidence to support the efficacy and efficiency of booster shots in increasing the production of antibodies as well (1). Booster shot is injected after an individual has received one or two previous doses of regular vaccine against COVID depending on the type.

SOURCE: The Sudbury Star

The Canadian government had authorized companies producing viral vector-based vaccines such as Janssen and AstraZeneca for adults over 18 years of age, and mRNA vaccines such as Moderna and Pfizer and BioNTech (2-5). mRNA vaccines were given full approval to give children over 5 (Pfizer-BioNTech) and 12 (Moderna) with reduced dose, and Spikevax by Moderna was especially approved as a booster shot in November (4-6). Pfizer and BioNTech is also planning to drop their new vaccine adjusted to target omicron in March 2022 depending on the need, as well as 4 billion more of their current Comirnaty vaccine supply (1).

Antiviral Pills

 Aside from vaccines, companies are also striving to develop pills to cure. Pfizer is in the lead among major companies with their two-pill antiviral named Paxlovid, which showed outstanding efficacy by dropping hospitalization and death by 89% (1). Paxlovid is used to treat relatively mild symptoms in unvaccinated individuals and the above-mentioned result was when patients took the pill within three days of symptoms (1).

Merck also dropped a one-pill antiviral called Molnupiravir less impact than Paxlovid by reducing hospitalization and death by 30% when taken within five days after symptoms first appeared but is still clearly in lead compared to other companies (1).

Progress on making the most effective vaccine or cure is a key factor in the inevitable competition among these pharmaceutical companies.

Side Effects and Post-Pandemic

Despite the fact that all types of vaccine currently used by countries are authorized and approved for its “safety”, current vaccines are suspected of possible side effects spanning from light redness and swelling to serious hear inflammation (7).

SOURCE: Today Show

Once confirmed cases decrease again and the pandemic gets closer to the end, the corporates will likely have a decreased stock value and maybe change the price to directly target the public with COVID products remaining on the market and focusing more on regular products they had before the virus; if they are still authorized despite the side effects with no immediate threat.

References

  1. Gatlin A. Is Pfizer stock a buy as omicron partially eludes its Covid vaccine? [Internet]. Investor’s Business Daily. 2021 [cited 2021Dec11]. Available from: https://www.investors.com/news/technology/pfizer-stock-buy-now/
  2. Canada H. Government of Canada [Internet]. Canada.ca. / Gouvernement du Canada; 2021 [cited 2021Dec11]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/janssen.html
  3. Canada H. Government of Canada [Internet]. Canada.ca. / Gouvernement du Canada; 2021 [cited 2021Dec11]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/astrazeneca.html
  4. Canada H. Government of Canada [Internet]. Canada.ca. / Gouvernement du Canada; 2021 [cited 2021Dec11]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/moderna.html
  5. Canada H. Government of Canada [Internet]. Pfizer-BioNTech Comirnaty COVID-19 vaccine – Canada.ca. / Gouvernement du Canada; 2021 [cited 2021Dec11]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/pfizer-biontech.html
  6. Canada H. Health Canada authorizes the use of the Moderna Spikevax COVID-19 vaccine as a booster shot [Internet]. Canada.ca. Government of Canada; 2021 [cited 2021Dec11]. Available from: https://www.canada.ca/en/health-canada/news/2021/11/health-canada-authorizes-the-use-of-the-moderna-spikevax-covid-19-vaccine-as-a-booster-shot.html
  7. Gatlin A. Is moderna stock a buy or sell as shares Yo-Yo on the omicron threat? [Internet]. Investor’s Business Daily. 2021 [cited 2021Dec11]. Available from: https://www.investors.com/news/technology/mrna-stock-buy-now/
Categories
Consumer Gadgets Health Monitoring Startups

The Future of Health Monitoring with Consumer Gadgets

Stephanie Chung — McMaster Honours Life Sciences 2023

As technology continues to progress and aid in daily activities, people nowadays are growing increasingly dependent upon their smartphones, laptops and other electronic devices. With this trend, there is a growing market and consumer base for individuals to use health monitoring devices in order to keep track of the status of their bodies. These gadgets are either wearable or embedded into an individual’s environment(1) and able to keep track of health vitals, fitness and specialized health concerns. The overall goal of health monitoring consumer gadgets are to report accurate results for users, thus involving monitoring and storing data pertaining to the consumer. The ways in which results are monitored vary based on the specific technology and goal of the technological wear, such as through sensors on the products and microcontrollers(2). Depending on the device, different sensors are able to obtain measurements such as temperature, heart pulse/rhythm, blood sugar levels and other data pertaining to the purpose of the gadget.

Popular gadgets include smart watches, headbands and some devices tailored towards individuals with certain medical needs that measure blood pressure (bp) and asthma monitors. Smart watches have been targeted towards the general public as a means of being able to keep track of heart rate, calories burned, steps taken, sleep and activity levels, blood oxygen and even electrocardiograms(3). These watches have also been seamlessly integrated with common conveniences many use, such as being able to send and receive messages, phone calls, notifications, etc., in a small and portable form-factor. Smart headbands, like electroencephalography (EEG) headbands, have been developed to monitor the mental health of individuals through being used for meditation, measuring breathing patterns and heart rate(4). EEG devices monitor and offer the user feedback on their measurements in hopes of aiding them to become a more skilled meditator(5). Blood pressure monitors that are portable are convenient as they may be used anywhere and can track trends and changes. This information may be used in order to see if a physician is required to intervene in cases where vitals are abnormal (e.g. bp might be too high, indicating hypertension) and subsequent new course of action is required(6). In addition, asthma monitors, such as a Peak Flow Meter are useful as they take measurements daily regarding the expiratory flow rate of an individual and allows the user to keep track of changes if  they occur(7). This serves as an indicator and tool to help determine whether intervention is required and how the individual’s asthma is being managed(7).

As wearable technology is gaining popularity, there is the proposal of using wearable sensors a few days prior to physical examinations, thus relying upon the sensors to gather data pertaining to the patient’s vitals(1). This will collect measurements regarding your body’s physiological state (temperature, blood pressure and pulse rate) and thus practitioners will be able to use the longitudinal information gathered in order to assess and evaluate the patient’s health(1). As this has yet to be achieved, it is in the midst of being implemented in order to improve the healthcare of individuals through being able to more accurately diagnose patients as well as be more time-efficient to aid more people. This can be compared to blood pressure and asthma monitors that are indicative to physicians of a patient’s status and aid them in figuring out a course of action. In conclusion, as technology and medicine continue to be intertwined, there will be more products targeting specific health conditions. It can even be seen that smart watches which began as tracking steps and calories are now able to measure heart rate and other features. At the current rate of advancement, the future of wearable technology is optimistic and will arrive much sooner than you think.  

References

  1. Saha HN, Auddy S, Pal S, Kumar S, Pandey S, Singh R, et al. Health monitoring using internet of things (IoT). IEEE [Internet]. 2017 Aug [cited 2021 Dec 29]. Available from: https://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=8079564&casa_token=jwv9nHnrRlIAAAAA:MoWMU7oLdXuDIpHJlowbN2ktjtAdoJVICUvIhuOQPkzmTJSCZlbuuthkziEpbmB0cFDo-jsAuA
  2. Goel AK. Modern electronics wearable gadgets for health monitoring. STM Journals [Internet]. 2019 [cited 2021 Dec 29]; 6(2): 11-16. Available from: https://www.researchgate.net/profile/Anuj-Goel-3/publication/335977272_Modern_Electronics_Wearable_Gadgets_for_Health_Monitoring/links/5f0c44ea4585155a552500db/Modern-Electronics-Wearable-Gadgets-for-Health-Monitoring.pdf
  3. Baig EC. Newest smartwatches move from tracking fitness to monitoring health [Internet]. Washington, D.C.: AARP; 2020 Sep [cited 2021 Dec 29]. Available from: https://www.aarp.org/home-family/personal-technology/info-2020/smartwatches.html
  4. Hunkin H, King DL, Zajac, IT. Perceived acceptability of wearable devices for the treatment of mental health problems. J. Clin. Psychol [Internet]. 2020 Feb [cited 2021 Dec 29]; 76(6): 987-1003. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/jclp.22934?casa_token=TSfIUFNgwI4AAAAA%3A6NZ696F7IN7hiPiaOtIKpbD9zgVqYSx9vE4j6-x8D-ZfTdOna7zN3_GO6d2cy6r4by0uBPXeYKQsQ6BM
  5. Balconi M, Fronda G, Venturella I, Crivelli D. Conscious, pre-conscious and unconscious mechanisms in emotional behaviour. Some applications to the mindfulness approach with wearable devices. Appl. Sci [Internet]. 2017 Dec [cited 2021 Dec 29]; 7(12): 1-14. Available from: https://www.mdpi.com/2076-3417/7/12/1280/htm
  6. Harvard Medical School. The benefits of do-it-yourself blood pressure monitoring [Internet]. Harvard University in Massachusetts, United States: Harvard Health Publishing; 2018 July [cited 2021 Dec 29]. Available from: https://www.health.harvard.edu/heart-health/the-benefits-of-do-it-yourself-blood-pressure-monitoring
  7. Asthma Canada. Peak flow meters [Internet]. Toronto, Canada: Asthma Canada; 2021 [cited 2021 Dec 29]. Available from: https://asthma.ca/get-help/living-with-asthma/peak-flow-meters/
Categories
Genomics Precision Medicine

How Modern Genomics has Changed our Approach to Cancer Treatment

Alexia Di Martino—McMaster University Molecular Biology & Genetics 2023

Within our chromosomes, there are billions of nucleotides that are all a part of our genome, the entirety of our DNA. Genomics is the study of the genome. A nucleotide sequence, its precise location, and the gene-gene or gene-protein interactions of specific genes are just a few of the findings that can be discovered through genomics.1 The human body is amazing in its ability to use DNA as a blueprint to direct millions of processes in the body. Of course, our DNA also encodes for the billions of other vital cells – like those of the blood, skin, and brain among other organs – that make up our body on a whole. When cell division goes wrong, though, cells may continue to divide uncontrollably and develop growths that we know as cancer.2

There are two families of genes that influence cancer development. The tumour suppressor gene family has a positive effect on cancerous growth when inactivated or improperly functioning. On the other hand, proto-oncogenes cause cancerous growth when they are mutated and active.3

The Human Genome Project was an advancement in sequencing technology that allowed for a decreased cost of sequencing an organism’s entire genome, as well as improved accuracy of the nucleotides and genes that are sequenced.4 Artificial intelligence and computer algorithms are even further advanced technologies that give researchers the ability to automate pattern-recognition within these sequences. From this, links between a gene’s function in the DNA compared to the patient’s phenotypic presentation of a disease can be made.

Tens of thousands of sequenced genetic mutations have been archived through the amazing work of oncology researchers into genetic libraries. One of these libraries is The Cancer Genome Atlas (TCGA).5 Using a patient’s genome, doctors can refer to these mutated cancer-linked genes to screen patients for susceptibility to a specific cancer.

SOURCE: British Columbia Genome Sciences Centre6

With the knowledge of the patient’s cancerous tumour’s genome, clinicians can identify the exact mechanisms of the cancer cells that causes their proliferation. By comparing the genome of the same patient’s normally functioning ‘germline’ cells to their cancer, researchers can pinpoint the mutated or defective genes responsible for the cancer. They can then recommend better-informed treatments such as pharmaceutical drugs and antibodies targeting certain molecules or pathways of the tumour cells.7 Targeted treatments are much better overall than uninformed therapies. Radiation therapy or stem cell transplants may not be appropriate or as effective in all cases, and can be very expensive. Understanding the genomics of a patient’s cancer could spare them from unnecessarily high medical bills, and more importantly, could have less harmful effects on their body, leading them to being cancer-free more quickly.8

While genomics-driven cancer treatment has been in practice in this way, recent studies into novel gene-editing practices have shown to be promising for the future. In the CRISPR-Cas9 gene editing system, scientists specially design a guide RNA to target a specific DNA fragment. When this guide RNA binds the gene of interest, it associates with a Cas enzyme that cleaves the DNA at that location.9 Scientists may insert a new gene in that cleavage site or perform other modifications depending on their goal.

SOURCE: National Cancer Institute9

Since at least 2017, researchers have been working on using CRISPR-Cas9 on model organisms such as mice and zebrafish in vitro to remove or directly target genes linked to cancer. However, it still poses some challenges when attempting to deliver cancer treatment in vivo.10 These issues are already being studied to create functional and safe delivery of CRISPR-Cas9 gene editing in different tissues in order to accommodate the wide range of cancers seen in patients. As the cancer genome library continues to expand, the CRISPR-Cas9 method of treatment will experience many benefits as well.

The work of biologists in all fields have contributed to this progress – from improved genetic sequencing techniques, to experiments that identify cancer genes, to the assembly of genetic libraries, and everything in between. These advances give every human being a lifesaving advantage in cancer diagnoses. With further research on these gene libraries, scientists will be able to screen the genomes of patients and target cancer-causing genes to inhibit their mechanisms before cancerous cells even get the chance to cause damage.

References

  1. NIH Staff. A brief guide to genomics [Internet]. Genome.gov. 2020 [cited 2022Jan2]. Available from: https://www.genome.gov/about-genomics/fact-sheets/A-Brief-Guide-to-Genomics
  2. Williams GH, Stoeber K. The cell cycle and cancer. The Journal of Pathology. 2011Oct12;226(2):352–64.
  3. Lee EY, Muller WJ. Oncogenes and tumor suppressor genes. Cold Spring Harbor Perspectives in Biology. 2010;2(10).
  4. Hofstatter EW, Bale AE. The promise and pitfalls of Genomics-Driven Cancer Medicine. AMA Journal of Ethics. 2013;15(8):681–6.
  5. NCI Staff. The cancer genome atlas program [Internet]. National Cancer Institute. 2019 [cited 2022Jan2]. Available from: https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga/history
  6. BCGSC Staff. Genome sequencing helps prioritize cancer treatment options [Internet]. Genome Sciences Centre. 2020 [cited 2022Jan2]. Available from: https://www.bcgsc.ca/news/genome-sequencing-helps-prioritize-cancer-treatment-options
  7. Mattick JS, Dziadek MA, Terrill BN, Kaplan W, Spigelman AD, Bowling FG, et al. The impact of genomics on the future of Medicine and Health. Medical Journal of Australia. 2014Jul7;201(1):17–20.
  8. Welch JS. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA. 2011Apr20;305(15):1577–84.
  9. NCI Staff. How CRISPR is Changing Cancer Research and Treatment [Internet]. National Cancer Institute. 2020 [cited 2022Jan2]. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment
  10. Zhang H, Qin C, An C, Zheng X, Wen S, Chen W, et al. Application of the CRISPR/cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer. Molecular Cancer. 2021;20(1).
Categories
Precision Medicine

The End of “One-Size-Fits-All” in Medicine

Tisha Parikh (Honours Life Sciences – 2023)

In today’s age, everything from clothing to housing to cars can be customized. We alter things to our liking and do not have to worry about this concept of “one-size-fits-all.” So why should medicine be any different? The emerging concept of precision medicine works to answer this question (1).

In the past, people with the same condition have been prescribed the same drug or therapy with some consideration for factors such as age, sex, weight, or medical history. Despite this, there are still many people for which that medication simply does not work (2). Therefore, we need an approach that specializes treatment for everyone and works by better classifying patients into groups (2).

Precision medicine is much more than matching a blood-type for a transfusion. Precision medicine uses an individual’s genetics, behaviours, and personal environmental factors to create a solution for their healthcare needs (1,3). In medicine, there are always so many external factors that come into play when we prescribe medications or recommend lifestyle changes (3). By gathering information across populations and communities, specific biomarkers can be linked to groups of people, and as a result, be used in targeted treatment or therapy (4). Rather than “personalizing” medicine for any one individual, precision medicine has to do with combining genetics and environments for similar people to find narrowed treatment options that are likely to work and provide optimal benefits (4).

Benefits of such an approach to medicine include higher chances of recovery, as the treatment provided to you has worked for people just like you. Healthcare costs are reduced as treatments are likely to work the first time around (5). Diagnostic equipment use will decline as providers have a reasonable estimate of the issue at hand and can skip directly to specialized technology. A decline in wait times and the process of going from doctor to doctor will follow because your primary provider will have a better idea of where to start and what the problem may be, based on your community or lifestyle. The goal of precision medicine is to get rid of the trial-and-error aspect of medicine to save time, money, and resources. It functions to help people as early as possible in getting treatment and thus recovering (4,5).

SOURCE: EJ Hersom (U.S. Department of Defense)

Precision medicine is attainable because of the rapid data collection available. An attempt to find relationships between biology, lifestyle, and environment has already been put forth by the Obama government starting in 2015 (4,6). All of Us is an initiative under the National Institute of Health (NIH) that is aimed to create a database to find trends in health conditions among people of similar genetics and/or demographics (6). All of Us is a preliminary effort to provide precision medicine to Americans in the near future (6). In addition to efforts set out by the government, the relative speed and low cost associated with genome sequencing today have accelerated the field towards precision medicine (7). Since sequencing now takes a couple of hours instead of a decade, SNPs, epigenetic alterations, and other molecular predispositions can be found and linked to populations (7).

SOURCE: National Institutes of Health

An example that efficiently highlights the potential of this technology is the story of Melanie Nix (8). In 2008, she was diagnosed with triple-negative breast cancer brought about by a mutation on the BRCA gene, a remarkably common condition for many African American women (8). However, through all the research done on this cancer in African American women, statistics showed that Melanie’s best chance was with a bilateral mastectomy (8). Now cancer-free, Melanie also believes that precision medicine allows a mode for preserving one’s health through targeted therapy (8).

SOURCE: Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

It may just be a matter of time until we see this type of precision become a pillar in medicine. The concept of “one-size-fits-all” has been long lost in fashion and lifestyle, and soon may be a staple of all medical practice.

References

  1. Iron Bridge. [Internet]. [Pittsburgh, PA]: Iron Bridge; [date unknown]. How Precision Medicine Will Change Healthcare as We Know it. [cited 2021 December 8]; Available from: https://www.ironbridgecorp.com/blog/how-precision-medicine-will-change-healthcare-as-we-know-it
  2. WebMD [Internet]. [place unknown]: WebMD LLC; [date unknown]. Traditional vs. Precision Medicine: How They Differ[cited 2022 January 8]; Available from: https://www.webmd.com/cancer/precision-vs-traditional-medicine
  3. Centers for Disease Control and Prevention. [Internet]. [place unknown]: CDC; [date unknown]. Precision health: Improving health for each of us and all of us. 2020 August 14 [cited 2021 December 8]; Available from:https://www.cdc.gov/genomics/about/precision_med.htm
  4. Thermo Fisher Scientific. [Internet]. [place unknown]: Thermo Fisher Scientific Inc.; [date unknown]. A revolutionary shift in the practice of medicine: How a one-size-fits-all approach is becoming history. [cited 2021 December 8]; Available from: https://www.thermofisher.com/ca/en/home/clinical/precision-medicine/precision-medicine-learning-center/precision-medicine-resource-library/precision-medicine-articles/overview-precision-medicine.html#:~:text=Top-,Applications%20of%20Precision%20medicine,generation%20sequencing%20(NGS)%20technology.
  5. National Institutes of Health. [Internet]. [place unknown]: U.S. Department of Health and Human Services; [date unknown]. All of us research program overview. [cited 2021 Dec 8]. Available from:https://allofus.nih.gov/about/all-us-research-program-overview
  6. National Institutes of Health. All of Us. [Internet]. [place unknown]: U.S. Department of Health and Human Services; [date unknown] [cited 2021 Dec 8]. Available from: https://allofus.nih.gov/
  7. Gameiro GR, Sinkunas V, Liguori GR, Auler-Júnior JOC. Precision Medicine: Changing the way we think about healthcare. Clinics (Sao Paulo). [Internet]. 2018 [cited 2021 Dec 8];73:723. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251254/ doi:10.6061/clinics/2017/e723.
  8. Evans C. Precision Medicine Is Already Working to Cure Americans: These Are Their Stories. 2015 Jan 30 [cited 2021 Dec 8]. In https://obamawhitehouse.archives.gov/blog [Internet]. [place unknown]. USAGov. [date unknown]. Available from: https://obamawhitehouse.archives.gov/blog/2015/01/29/precision-medicine-already-working-cure-americans-these-are-their-stories
Categories
CRISPR Genomics Precision Medicine

The State of Gene Therapies

Nima Karimi — McMaster University Health Sciences 2023

As the quest of mankind for optimal health continues,  different avenues for achieving this goal have emerged. One area, in particular, is looking at the role of genes in the pathophysiology of diseases, and consequently, investigating therapeutics that target those genes. Genes are the basic functional unit of heredity (1); in other words, they determine your height, the color of your eye and hair, and many other biological traits. Importantly, alterations of the genes and genome have been consistently linked to many pathological conditions. Cystic fibrosis (CF), sickle-cell anemia, and Huntington’s disease are some of the more prominent examples of genetic disorders (2). As these conditions have led to increased mortality and reduced quality of life, the scientific community has searched for potential therapeutics; one, in particular, being gene therapy.

The first human studies on gene therapy were done in the early 1990s. One such experiment involved the transfer of genes coding for a specific enzyme, to patients with severe combined immunodeficiency, which showed promising results (3). Since then, research into gene therapy has grown considerably. More recently, some studies have used gene therapy to treat CF, a progressive genetic condition that leads to the loss of lung function with no current treatment (4). Interestingly, the use of gene therapy in CF patients have shown to improve lung capacity (3). With CF being one of the most prevalent genetic disorders, the use of gene therapy shows a promising future for the treatment of this condition.

Now you may be wondering to yourself, how is genetic therapy actually done? Generally speaking, gene therapy involves the identification of cell types and DNA sequences that are defective, and then introducing a new DNA sequence containing the functional genes to offset the effects of the disease-causing genetic alterations (5). There are two different approaches to gene therapy (figure 1), and these involve alterations of different types of cells (6). Somatic gene therapy involves the transfer of DNA to different cells in our body that do not produce sperm or eggs. Given that these changes are not in the germline, any DNA alteration cannot be passed on from parents to their children (6). In contrast, germline gene therapy involves the transfer of DNA to cells that produce eggs or sperms, meaning these changes can be inherited (6).

Additionally, various techniques are being used in gene therapy. One such technique is gene augmentation therapy (6). This technique can be used to treat genetic abnormalities  that stem from mutation, where the gene in question does not produce its functional products (6, 7). As shown in figure 2, this therapy adds the DNA containing a functional gene back into the cell that is defective and ultimately, can reverse the abnormality (8). Another technique involves gene inhibition (6). This technique can be used in pathologies in which the overexpression of certain genes is causing the disease. In this approach, the aim is to introduce a new gene that either inhibits the expression of another faulty gene, or interferes with the activity of the product produced by the faulty gene (9), as shown in figure 3.

Overall, it is clear that gene therapy presents a very promising future for the treatment and management of diseases that were once deemed incurable. Today, there are more than 600 genes and cellular therapies that are being researched (10). In the coming years, one could expect the emergence of many genetic therapies for common and rare conditions. This emergence could both provide treatments for patients that lack therapeutics today, and also improve their overall quality of life.

References

1.         Kitcher P. Genes. The British Journal for the Philosophy of Science. 1982;33(4):337-59.

2.         Conrad Stöppler M. Genetic Diseases (Disorder Definition, Types, and Examples): MedicineNet;  [Available from: https://www.medicinenet.com/genetic_disease/article.htm.

3.         Steffin DHM, Hsieh EM, Rouce RH. Gene Therapy: Current Applications and Future Possibilities. Advances in Pediatrics. 2019;66:37-54.

4.         Davis PB. Cystic Fibrosis Since 1938. American Journal of Respiratory and Critical Care Medicine. 2006;173(5):475-82.

5.         Verma IM, Naldini L, Kafri T, Miyoshi H, Takahashi M, Blömer U, et al., editors. Gene Therapy: Promises, Problems and Prospects. Genes and Resistance to Disease; 2000 2000//; Berlin, Heidelberg: Springer Berlin Heidelberg.

6.         What is gene therapy? 2021 [Available from: https://www.yourgenome.org/facts/what-is-gene-therapy.

7.         Frazier S. Embryo Gene Editing: Changing Life As We Know It 2019 [Available from: https://the-gist.org/2019/05/embryo-gene-editing-changing-life-as-we-know-it/.

8.         Nóbrega C, Mendonça L, Matos CA. Gene Therapy Strategies: Gene Augmentation. In: Nóbrega C, Mendonça L, Matos CA, editors. A Handbook of Gene and Cell Therapy. Cham: Springer International Publishing; 2020. p. 117-26.

9.         James W. Towards Gene-Inhibition Therapy: A Review of Progress and Prospects in the Field of Antiviral Antisense Nucleic Acids and Ribozymes. Antiviral Chemistry and Chemotherapy. 1991;2(4):191-214.

10.       Dorholt M. We’re on the Verge of a Breakthrough for Gene Therapies 2021 [Available from: https://www.evernorth.com/articles/the-history-and-future-of-gene-therapy.

Categories
Telehealth

Progress on Remote Respiratory Monitoring

Kaitlyn Hui—McMaster University Health Sciences 2022

With the onset of the COVID-19 pandemic, the need for remote respiratory monitoring has been integral for patients and physicians alike. This system allows for the continuous tracking of patient oxygen levels even when the clinician is not present, reducing the risk of missed respiratory complications. This is not only advantageous for patient safety since clinical staff can be quickly informed of adverse events through pager alarms, but allows physicians to care for multiple patients simultaneously. What may be surprising is that remote respiratory monitoring isn’t new to the scientific community: those with diabetes, heart disease, and lung disease have used remote devices to detect changes in their health for years. 

Respiratory rate has been shown to be a reliable gauge for COVID-19 patient respiratory deterioration as higher rates correlate with ICU admission and mortality.1 Despite this finding, manually calculating these rates proves difficult and cannot be accurately determined through remote teleconferences, which have spiked in popularity given the shift to online consultations.1 As well, patients often have trouble distinguishing their own breathing levels as the measure is self-reported through questions such as, “Is your breathing faster, slower, or the same as normal?”.2 As laypeople often do not possess strong medical background knowledge, these types of questions are typically discouraged and are only used when necessary.2 

With the emergence of the COVID-19 Omicron variant, the urgency for remote monitoring has become even more pressing. In accordance with their national role, the Food and Drug Administration has even authorized numerous non-invasive remote and wearable monitoring devices to limit healthcare worker exposure to the virus.3 Although ambiguity remains regarding effectiveness and funding, remote sensors are being developed to obtain accurate respiratory rates such as the “Lab-on-Mask” (LOM) and other technological solutions. 

Recently, the LOM has been manufactured, embedded with a noncontact, multiplexed (can transmit several signals simultaneously) sensor system that can track patient vitals such as heart rate, blood pressure etc., while simultaneously measuring the mask’s interior temperature, all in real-time.4 Made from polydimethylsiloxane, a material used for flexible electronics, and other comfortable fabrics, the mask allows physicians to obtain stable signal output using signal-receiving sensors, data processing modules, and Bluetooth data.4 The photoplethysmography sensor, photodetector, and preamplifier can detect blood-oxygen (O2) saturation levels through vasoconstriction or vasodilation. This is useful because O2levels can identify respiratory infections such as COVID-19.4 This LOM can be handy in hospital settings to monitor infectious patients that are still allowed to wear a mask, which also limits spread.

SOURCE: ACS Materials

There are also several other technological ways to remotely determine a patient’s vitals such as built-in cameras or microphones to recognize respiratory-induced chest wall movements and breathing sounds, respectively.1 However, for patients that require long-term care, these solutions are not recommended purely because of the large amount of data that needs to be processed.1In these cases, pressure sensors installed underneath mattresses, seating areas or backrests have proven to be low-cost with high accuracy, thus are more suitable for these populations.1 As well, the use of radio waves is currently being explored as another possible avenue since respiratory rates can be transmitted through signal modulation, eliminating the need for troublesome body sensors altogether.1 On the other hand, if one does wish to pursue that route, then there are “smart” devices such as chest straps that can measure changes in chest wall circumference, though they are much more expensive.1 

Frontiers | Remote Respiratory Monitoring in the Time of COVID-19 |  Physiology
SOURCE: Frontiers in Physiology

Luckily for us, in this modern age, medical advancements are shifting the healthcare landscape, allowing us to closely keep an eye out for patients in a safe and supportive manner. While this topic has been gaining traction given the significance of COVID-19, there are still many barriers regarding costs and efficacy. It is clear that this still remains a subject of interest, but we have a ways to go before developing a highly effective solution. Through recent developments, researchers are certainly moving towards the right direction in creating a future where remote respiratory monitoring can become a ubiquitous and cost-effective health technology used globally.

References

1. Massaroni C, Nicolò A, Schena E, Sacchetti M. Remote respiratory monitoring in the time of COVID-19 [Internet]. Frontiers in physiology. Frontiers Media S.A.; 2020 [cited 2021Nov27]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274133/ 

2. Greenhalgh T, Koh GCH, Car J. Covid-19: A remote assessment in primary care [Internet]. The BMJ. British Medical Journal Publishing Group; 2020 [cited 2021Nov27]. Available from: https://www.bmj.com/content/368/bmj.m1182.long 

3. Center for Devices and Radiological Health. Covid-19 remote monitoring devices [Internet]. U.S. Food and Drug Administration. FDA; 2020 [cited 2021Nov27]. Available from: 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcem ent-policy-non-invasive-remote-monitoring-devices-used-support-patient-monitoring during 

4. Xian Jun Loh, Xiaodong Chen, Liang Pan, Cong Wang, Haoran Jin, Jie Li, et al. Lab-on-mask for remote respiratory monitoring [Internet]. ACS Publications. 2020 [cited 2021Nov27]. Available from: https://pubs.acs.org/doi/10.1021/acsmaterialslett.0c00299

Categories
Startups

Fraud, Deception and Blood: A Cautionary Tale of Theranos

Tara Sabzvari—McMaster Univeristy Honours Life Sciences 2020

The unprecedented COVID-19 pandemic has been an eye-opening experience, giving us insight into our unmet needs as a society. It has become increasingly clear that we are highly dependent on the advancement of medical technologies to provide us with extensive prevention methods, efficient diagnosis techniques, and quick turnaround times in both an affordable and viable manner to meet our medical concerns. 

17 years ago, one ambitious Stanford drop-out went to great lengths to bridge a gap in our healthcare system that had the potential to drastically improve the landscape of medicine in the 21​stcentury.

In March of 2004, Elizabeth Holmes had just dropped out of Stanford University and established her Silicon Valley biotechnology company, Theranos Naotainer [1].

She pitched her invention, the Edison machine, as a semi-portable device that only needed a single pinprick of blood to perform hundreds of medical tests, from a routine cholesterol check to more involved genetic testing and cancer detection. The charismatic Ms. Holmes promised that the results would be faster, more accurate and far cheaper than the conventional methods used today.

To fund this initiative, Elizabeth Holmes was strategic in seeking out wealthy millionaires who were not versed with any medical knowledge and she solicited them for funding. News about this cutting-edge technology was spreading and it caught the attention of Walgreens and the Cleveland Clinic, inspiring them to adopt this technology [2]. She soon became an iconic figure, making buzz in the biotech industry and media, booking interviews and gracing the front page of renowned magazines such as Forbes — even earning the title of “the youngest self-made female billionaire in the world.”

PHOTO: Elizabeth Holmes on the cover of "Forbes."
SOURCE: Forbes Magazine, 2015

Unfortunately, she did not hold this title for long as her magnetism did not translate to retaining employees or fostering a healthy work environment. She was seen as toxic by her employees who claimed that she would fire anyone that undermined her. In fact, according to The Verge, in 2016 she fired 340 members and in 2017 she fired 155 employees, nearly 40% of her staff [3]. However, what really tainted Theranos’ image was that Elizabeth Holmes became the subject of many investigations, most notably by Vanity Fair’s Nick Bilton [4].

She was soon found guilty of fraud and indicted with federal charges [5]. Through deceit and manipulation she had made false promises of a technology that was out of reach and she had capitalized on funding from investors and buyers. Elizabeth had mastered the art of persuasion and fooled many with her imitation of a deep masculine voice and embodiment of other iconic figures such as the donning a classic Steve Jobs black turtleneck or the Mark Zuckerberg stare [6] However, behind closed doors she was using the conventional technology made by Siemens to run medical laboratory tests, meaning that there was no viable Theranos Edison device all along.

In conventional blood tests, typically several vials of blood are taken in order to ensure the accuracy of the results when running multiple tests. At Theranos, they were diluting the “pin prick” samples to mimic the standard sample volume of the standard tests.

Elizabeth’s manipulative and calculating mindset was able to take her farther than anyone could have imagined. Ultimately, she lacked the knowledge, experience and technology to make the Edison device a reality and her attempts to compensate for this downfall through fraud backfired. Amidst this cautionary tale lies one silver lining: to this day, Elizabeth Holmes is gaining attraction through New York Times Best Seller Books, HBO documentaries, articles, videos, and the memorable parody by the Late Late Show’s James Cordon.

It is important to ask, would such a technology have outstanding implications for the health of our society, especially given the current pandemic? Certainly. However, is such a biomedical feat within our reach? Not just yet.

While most of us would love to live in a world that does away with all the nuisances of blood tests (I think it’s fair to say that no one likes being poked with a needle), it seems like we will have to sit patient until our diagnoses can be performed with a single prick of blood, should that day ever come. 

References

  1. Damodaran A. The cautionary tale of theranos: Beware runaway stories. Forbes Magazine [Internet]. 2015 Nov 15 [cited 2021 Mar 1]; Available from: https://www.forbes.com/sites/aswathdamodaran/2015/11/15/the-cautionary-tale-of-th eranos-beware-runaway-stories/
  2. The New York Times. A Theranos Timeline. The New York times [Internet]. 2016 Jul 8 [cited 2021 Mar 1]; Available from: https://www.nytimes.com/2016/07/09/business/theranos-elizabeth-holmes-timeline.html
  3. Vincent J. Theranos starts 2017 by firing 40 percent of its staff [Internet]. The Verge. 2017 [cited 2021 Mar 1]. Available from: https://www.theverge.com/2017/1/9/14211246/theranos-fires-40-percent-employees-2017
  4. Bilton N. How I got to the bottom of the theranos mess [Internet]. Vanity Fair. 2016 [cited 2021 Mar 1]. Available from: https://www.vanityfair.com/news/2016/09/nick-bilton-on-theranos
  5. Solon O. Theranos founder Elizabeth Holmes charged with criminal fraud. The guardian [Internet]. 2018 Jun 15 [cited 2021 Mar 1]; Available from: http://www.theguardian.com/technology/2018/jun/15/theranos-elizabeth-holmes-rame sh-balwani-criminal-charges
  6. Carreyrou J. Hot Startup Theranos has struggled with its blood-test technology. Wall Street journal (Eastern ed) [Internet]. 2015 Oct 15 [cited 2021 Mar 1]; Available from:https://www.wsj.com/articles/theranos-has-struggled-with-blood-tests-14448819 01
Categories
Genomics

Unfolding the Code of Cancers Using the Next Generation Sequencing

Christie Siu—McMaster University Honours Life Sciences 2023

By accessing multiple genes in a single assay to identify causative  mutation, next-generation sequencing provides a more efficient and  deeper look into molecular underpinnings of patients’ tumors. 

Not so long ago, it seemed mapping and understanding the entire human genome  sequence was one of the most expensive and time-consuming studies to accomplish. The  Human Genome Project, initiated in 1990, took a total of 13 years and about $3 billion  USD to determine and study the complete human genome, by using the traditional DNA  sequencing technique—”Sanger sequencing.” Yet, the advent of next-generation  sequencing (NGS) has made a great impact on clinical and molecular biological  research, more specifically—cancer research, leading to the molecular age of cancer. 

Before the 1990s, DNA sequencing was accomplished in an “old fashioned” way by adding agarose gel  and targeted genomic bases manually. Later, the Sanger sequencing technique was introduced into the  biological market and allowed researchers to process long DNA fragments at one time. And the  researching technique evolved, Next-generation sequencing has altered the way that sequencing was  ever performed. Although the invention of the Sanger sequencing did allow researchers to map out the  entire human genome sequence, it is unexpectedly costly and time-consuming for diseases diagnosis  and implantation of treatments of patients, especially individuals that are aware or not aware that, they  themselves are suffering from cancers (1). 

Cancer is one of the most leading cause of death worldwide. According to the National Cancer Institute,  there are related deaths in 2018. In addition the the enormous number of cases that can be studies,  cancers are generically complex and requires high-accuracy targeting specific variants and activation  pathways. Undoubtedly, the success of the Human Genome Project, along with the increased  affordability of sequencing, has implanted the wide use of genomic data to assist in cancer diagnosis and  medicine precision. The development of Next-generation sequencing, once thought to be a novelty,  allows researchers to capture and process a massive amount of genomic information about a cancer in  the shortest time one can imagine- taking only about 4 hours to complete a run (2).

Global Cancer | HEAT: Health Evaluations + applied Therapeutics
SOURCE: GLOBOCAN 2018
Individuals in both the developed and developing countries experience cancers, while most patients  were concentrated in Europe and Asia (3). 

Next-generation Sequencing VS Sanger Sequencing  

In principle, the concepts behind the two DNA sequencing techniques are similar. Both of NGS and  Sanger sequencing requires addition of DNA polymerase to the fluorescent nucleotide according to a  growing DNA template strand, while each nucleotide is identified by their fluorescent tag. But in NGS,  DNA fragments are massively parallel, which allows tones of fragments to be sequencing in just a single  trial. Whereas sanger sequencing sanger sequencing only produces one forward and reverse read of a  single fragment, and in other words, researchers have to be determinant when deciding which DNA  fragment, they are interested in.

When Do I Use Sanger Sequencing vs NGS? - Behind the Bench
SOURCE: Natalie Gurson, ThermoFisher Scientific
The fundamental approach of identifying target DNA sequence in NGS and Sanger sequencing is  similar, but their sequencing volume are different. While only a single DNA fragment can be  sequenced at a time in Sanger sequencing, and alternatively, NGS is massively parallel, millions of  fragments can be translated into genes simultaneously in a single run. 

Compared to the traditional way of sequencing, NGS offers high accuracy, sensitivity, and speed in  genomic investigation (4), as it only requires as little as 5% of the DNA sequences from a tumor sample,  and it can reduce the need to preform multiple tests to examine causative mutation within a patient.

References

1. Vincenza Precone, Valentina Del Monaco, Maria Valeria Esposito, Fatima Domenica Elisa De Palma,  Anna Ruocco, Francesco Salvatore, Valeria D’Argenio. Cracking the Code of Human Diseases Using Next Generation Sequencing: Applications, Challenges, and Perspectives. *BioMed Research International*,  vol. 2015, Article ID 161648, 15 pages, 2015. Available from: https://www.hindawi.com/journals/bmri/2015/161648/.

2. Gurson N. When Do I Use Sanger Sequencing vs NGS? – Behind the Bench [Internet]. Behind the  Bench. 2021 [cited 11 March 2021]. Available from: https://www.thermofisher.com/blog/behindthebench/when-do-i-use-sanger-sequencing-vs-ngs-seq-it out-7/.

3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018:  GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J  Clin. 2018;68(6):394–424. 

4. NGS vs. Sanger sequencing. (n.d.). Retrieved March 11, 2021, from https://www.illumina.com/science/technology/next-generation-sequencing/ngs-vs-sanger sequencing.html.