Every Disease IS Personal: How the Integration

of Precision Medicine Has Changed Patient

Treatment

Namitasai Ande
10 May 2019

Independent Research G/T

Dr. Melissa Kiehl
Abstract
Scientists can look at the gene expression of diseased patients and based on their responses to
certain drugs, try to determine the best formula to cure the patient in the most efficient way
possible; however, that is that’s where the controversy begins starts. Doctors have began to
prescribe patients with drugs that have not been completely clinically tested, but based on their
previous treatments supports a logical explanation for these newly developed drugs to work for
their needs. This form of treatment development and prescription is not ethical towards the
prescription of adolescents diagnosed with fatal diseases. The risks that are posed for young
children who are susceptible to things going wrong in their body do not weight out the pros. This
paper will into detail of the process of precision medicine, establish how different techniques are
used to match a patient up with their optimal treatment, and analyze the different developments
of drugs for scleroderma, a rare autoimmune disease, and how they are prescribed to their
patients. The larger cost tied to genetic disorder such as the comparison between. Every patient,
big or small, is expected to respond differently.
Throughout this paper, the three therapies that have been used throughout the last decade will be
evaluated through background research and a meta-analysis of data collection. It will determine
the effectiveness of each of these therapies.
Introduction
It always seems as though so many people are being diagnosed with fatal diseases, but no one is
getting better! Scientists have been researching cures for so long, so how come they still haven’t
found a cure for cancer, diabetes, or strokes? Research in medicine has been taking up major
amount of government, private, and public funding and has lead to the answer of precision
medicine. Precision medicine is the use of phenotypical and genotypical analysis of a patient to
group them into a specific subgroup of patients who will respond the best to a certain drug or
therapy. Scientists can look at the gene of diseased patients and based on their responses to
certain drugs, try to determine the best formula to cure the patient in the most efficient way
possible; however, that is that’s where the controversy begins starts. Doctors have began to
prescribe patients with drugs that have not been completely clinically tested, but based on their
previous treatments supports a logical explanation for these newly developed drugs to work for
their needs. This form of treatment development and prescription is not ethical towards the
prescription of adolescents diagnosed with fatal diseases. The risks that are posed for young
children who are susceptible to things going wrong in their body do not weight out the pros. This
paper will into detail of the process of precision medicine, establish how different techniques are
used to match a patient up with their optimal treatment, and analyze the different developments
of drugs for scleroderma, a rare autoimmune disease, and how they are prescribed to their
patients. The larger cost tied to genetic disorder such as the comparison between. Every patient,
big or small, is expected to respond differently.

Review of Literature
Since the declaration of the completion of the Human Genome Project in April of 2003 and the
commencement of the Precision Medicine Initiative under Obama’s presidency in 2015, the
interest towards the issue of implementation of precision medicine techniques in the clinical
setting has been on a constant rise (The Obama White House, 2015). The idea of precision
medicine derived from the ability to confidently name all the genes which make up the
twenty-three chromosomes inherited to each person when they are born. Known as genetic
sequencing, this form of classification determines the sequence of the four nucleotides: adenine,
guanine, cytosine, thymine which makes up an organism’s DNA (Otami, 2004). With this data it
was believed by many researchers that the use of genetic sequencing could be used to determine
flaws in a patient’s genome whom is diagnosed with a genetic disease or illness. Through
comparison of both the patient’s genes and the Human Genome model it was concluded that
mutations or inadequacies in the patient’s genome could be more obviously noted and can lead
doctors and other medical professionals to develop technology that is able to change the specific
gene which is causing a patient to have a genetic disorder. The theory however was not feasible
due to the amount of money and time it would take for the genomic sequence of a patient to be
completed and verified. It took three billion dollars for the Human Genome Project to
successfully name every gene in a humans genome (what the gene controls, what amino acid it
codes for, etc.) and almost two decades for this information to be discovered ( Human Genome
Project, 2008). This just goes to show the amount of effort and dedication that needs to be put in
to determine a patient’s genome. From an individualized perspective, the patient must give their
tests to a geneticist who must look at all of their gene one by one and determine out all of these
genes, which are corresponding to their current illness. This process is very expensive and can
take at times five years for a patient to receive results from a geneticist (Human Genome Project,
2008). This lead to the definition of Precision Medicine to change. According to Johns Hopkins
University, researchers state, “[What was] decided at Johns Hopkins is that after twenty years of
people doing genomics and gene sequencing, we still don’t have a good way to know what genes
are normal and which genes are variants so we have a little bit of a different definition of
precision medicine. The way we are defining it is as finer grain subgroups of patients” (Shah,
2019). Because of the incredibly large amount of money and time that would be taken to receive
a patient’s genomic sequence, researchers have decided to change the definition of precision
medicine to fit the current circumstances currently available and accessible to patients. “It would
be great to go straight from the individual’s DNA to their disease progression, but because that is
hard if you can take one patient and identify the group or subgroup of patients that they belong to
and use that to predict how their disease is going to progress, that’s what we call precision
medicine. And any information you can use whether it is better phenotyping, genotyping,
metabolomics, any of that kind of data is fair game for precision medicine, for our definition”
(Shah, 2019). Researchers have learned to study around this difficulty and have concluded that
the best way to further study precision medicine while the genomic sequences of their patients
are not accessible is to use a selective process of subgrouping to determine which drugs and
treatments would be best for which individuals. Instead of using the full genomic sequence of the
patient, various pieces of information supplied by the patient through tests, examination, etc. are
given to the doctors, researchers, and geneticists who can then determine which treatments are
best (Pathogen Genomic Sequencing, 2016). Furthermore, through the change in definition of
Precision Medicine three common forms of treatments have began to arise in both research and
application. The use of Targeted Therapies, T-cell Therapy, and Stem Cell Therapy, are all forms
of therapy that have been used and constantly been altered on a patient to patient basis to
optimize patient outcome response.
The use of Targeted therapies, T-cell therapy, and Stem cell therapy allows for disease
and illness to be treated it a much more refined and specific manner when compared to
traditional therapies more commonly used (Davidson, 2002). The primary form of treatment that
has been studied is the use of targeted therapies. Targeted therapies (prescription drugs) are
unlike drugs currently used in the physician’s office or drugs that are prescribed to patients
because they target specific areas of the body. More commonly used medications such as
Ibuprofen and Acetaminophen are drugs and prescriptions which given to a patient for analgesic
properties. Since these drugs do not know which cells need the help of their properties, there are
flushed throughout every organ in the human body. This means that the drugs is not being
directed to the area in the body where the drug is most beneficial and needed, but everywhere.
Targeted therapies ensure that the drug is only being directed and used to the area of cells that
are in demand for the drug so that no energy is wasted (Genetic Science Learning Center, 2016).
Targeted therapies are different and more advanced because these drugs are only able to release
their properties only towards the cells that need the properties. This way the drug will be able to
optimize its usage and decrease waste. The second type of therapy that has been statistically
shown to have more cases of application is T-cell therapy. During T-cell therapy T-cells are
extracted from a patient’s blood and are cultured in a lab. While the T-cells are being cultured in
a lab, CAR genes are added to the T-cells to change the genetic makeup of these cells (Ripper,
2016). Once these cells are re-injected into the bloodstream they bind to cancerous cells and set
of a response from the targeted cells to apoptose: cell suicide (Aldridge, 2016). Since there are
unique T-cell receptors (TCR) specific for a given antigen the development of T-cells are
specific for proteins within the patient’s cancer. “T-cells are required for passive immunity,
humoral immunity, and treatment of pathogens by the double immune system mechanisms found
in vertebrate animals. Briefly, passive immunity treats all pathogens the same; whereas, humoral
immunity requires secretion of antibodies (proteins) which bind to invaders and target for
destruction” (Nurmi, 2005; Uretsky, 2002). T-cells are also part of the larger subgroup of white
blood cells (lymphocytes). These cells are created in the bone marrow of an organisms. The
T-cells produce proteins that detect to specific antigens that are part of invaders. The antigens of
the invaders bind to the T-cell which allow the T-cells to signal the invader to perform apoptosis
(Nurmi, 2005). Finally, since 2003, the research put into the development of stem cell therapies
has increased exponentially. “In blatant terms it is when cells that are injected and strategically
placed in a patient’s body where they are able to divide from their adult stem cell and provide
treatment to the surrounding cells through signaling. The unique thing about stem cells is that
they are adaptable and can become any cells that you desire when cultured properly”(Zambidis,
2019). An example of this type of treatment is the use of bone-marrow cells being inserted into
the retinal area of an eye. “Large-scale genomic analysis of rescued and non-rescued eyes
revealed significant upregulation of antiapoptotic genes. These findings demonstrate that this
newly described neurotrophic effect correlates with preservation of the vasculature and suggest
that autologous bone marrow–derived EPCs may be useful in the treatment of currently
untreatable blinding disease” (Banin, 2004). In this example the cells which naturally grow in the
bone marrow of the organism were removed and replaced in places in the eyrus where tumor
cells had been residing. Not only did these new cells replace the cancerous cells, but were able to
stop the division of cancer cells any further. Each type of therapy that has been previously
discussed has its own major component for success. Targeted remedies allow for impact of
illness, but without major spending and patient inconvenience. On the other hand, T-cell therapy
allows for ligands to attach to certain receptors to prompt responses in cells in the body to
function correctly with the use of the organism’s own cells. Likewise, Stem cell therapy forces
other cells in the body to die and become accustomed to the same cell that is being artificially
inserted so that the cancerous cells will be outnumbered. “Through these use of treatments such
as these precision medicine has a much broader scope of patients which it can treat and possibly
cure” (Shah, 2019).
A clear example of either of these three treatment methods that has become the driving force of
medication and treatment of a certain disease is the use of targeted therapies in Scleroderma
treatment. Scleroderma, also known as systemic sclerosis, is a progressively worsening disease
that occurs in the skin and connective tissue (Scleroderma, 2007). This disease is known to be
rare and not have a lot of test subjects making an optimal pick for precision medicine to be
implemented. The disease is many intense cases and be fatal as the stiffness in skin and
connective tissue is spread from the hands and feet to other parts of the body leaving the patient
motionless or even paralyzed (Voosen, 2015). Targeted therapies have used in the curation of
Scleroderma in all age groups. Even though Scleroderma normally only occurs in adults between
the ages 40-65, cases have been reported where even small children inherit the disease
genetically. The largest problem that the Scleroderma community has been facing is the low
levels of patients who inherit this disease. This does not allow for experimental tests to be done
to determine effectiveness of different types of drugs. To combat this dilemma, researchers have
decided to turn to targeted therapies as the answer. Through the awareness and money brought
into the community through the Precision Medicine Initiative, “The Scleroderma Research
Foundation has been constantly doing tests and searches for different drugs that would be most
effective for scleroderma patients. In addition, through the help of the Precision Medicine
Initiative, 10,000 case studied from all over the United States were able to be collected and
studied at Johns Hopkins Applied Physics Lab” (Shah, 2019). By looking at all these cases side
by side, researchers are able to see similarities and differences in patient response and symptoms
and based on that determine courses of action in terms of treatment that would be best for each
individual patient (Scleroderma Research Foundation, 2011; National Cancer Institute, 2017).
Throughout targeted therapy treatments patient prescriptions are constantly changing after only a
few weeks or months of using a specific drug. The reason for this is because patients are being
prescribed “experimental” drugs to treat their Scleroderma. The main reason why these
experimental drugs are being prescribed to individuals is because there are not enough
participants who inherit the Scleroderma disease where various tests over a period of time are to
be taken and observed parallel to the various drugs that are being made (Shah, 2019). However,
in the world of Scleroderma drugs, this does not stand as a barrier. As research is currently being
done on the Johns Hopkins, it has been found that this process of treatment has been more
effective in treating patients with Scleroderma when compared to circumstances where patients
are given a completely foreign drug in replacement. The main focus in these targeted therapies is
the amount of toxicity in the drug. Because different patients are only able to physically take a
certain amount of toxicity whether it be due to their age, gender, ethnicity, or other reasons,
using these treatments on them are more safe than introducing these patients to a completely new
drug all together (Scleroderma, 2003). This process of treatment can be analyzed parallel to a
Goldilocks analogy. The toxicity and measurement of other ingredients can be altered based on
the patient’s reaction to the drugs that they are already receiving. These alteration are considered
“experimental” because there are not case studies where a mass amount of patients have been
receiving this specific drug and conclusion have not been made, but according to patient’s earlier
reactions to specific drugs, these new “experimental” drugs have been proven to be safer to
patients when compared to completely new drug prescriptions (Shah, 2019). Having the ability
to constantly change the drug intake of patients in response to their reactions to certain
treatments has shown a consistent increase in effectiveness of targeted therapies in Scleroderma.
That being said, a barrier has been made by commercialized service which have falsely promised
consumers an outline of their human genome and disease which they are more likely to inherit.
Newly developed commercialized services have been hindering the development of precision
medicine techniques to be used in the clinical setting with patients because patients have in the
past decade resorted to commercialized service for their individual genetical information.
Services such as 23andMe, which allow a consumer to see if they inherit specific genes, have
allowed for direct-to-consumer genomic testing. “Direct-to-consumer (DTC) personal genomic
testing (PGT) allows individuals to learn about their genetic makeup without going through a
physician, but some consumers share their results with their primary care provider (PCP)” (M.I.
Dornell, 2004). Even though it is not all, many consumers turn to these services as their form of
medical “check-up” and recommendation to determine if they want to go through with a surgery
or treatment without the consultation of their own primary care physician. Consumers are
choosing to put their trust in commercialized service such as 23andMe which supposedly shows
them the genes that are related to a multitude of diseases and their likelihood of inheritance
(National Cancer Institute, 2013). Because of the rise in popularity in these services, researchers
and medical professionals are falling short of consumer support in Precision Medicine because
consumers choose to trust marketed services instead of their physician. Patients who are faced
with the opportunity to go down the precision medicine path (use of precision medicinal
treatments) shy away because of the information they receive from commercialized products
(Paul Ford-Martin, 2002). Even though these services offer their customers fairly accurate
information, the point to which the services are trusted will do more harm than good when a
patient must determine for themselves being faced with the important decision as to whether or
not they should have a surgery or undergo a certain treatment.
After constantly researching for thirteen years, researchers were finally able to complete the
classification and naming of the human genome in April of 2003. This momentous occasion not
only brought what might be known as the biggest ‘Eureka’ moment in modern medical research
history, but also brought the most hope in the medical field to determine the greatest possible
cures that are yet to be discovered. The four-hundred and eighty-five children that have been
becoming diagnosed with cancer every day were finally given a reason to believe that they will
live to see a time when cancer is no longer the largest epidemic in the world. This revolution is
the birth of precision medicine. With less money and research being put towards painkilling
drugs and temporary drugs, more money is able to be put towards different methods which target
the specific genes that have been hindering the patient community. This allows for disease and
illness to be reduced tremendously. Precision medicine gives researchers reason to believe that in
upcoming century disease may not exist.
Research Methods and Data Collection
The purpose of the research was to determine if the methods that are currently being used
as well as if the theories of precision medicine are actually effective in terms of patient
treatment. Prior to data collection, it was hypothesized that the following treatments: targeted
therapies, T-cell therapy, and stem-cell therapy, have been the most effective and developed
treatments implemented in clinical practice. The research which was conducted to determine if
this hypothesis was correct was conducted through a meta-analysis. Different articles were
evaluated for their quality, and then each of them were carefully analyzed. The data from each
study was converted into a percent scale to make it easy to compare different articles. There were
four articles that were collected. The first was called To win funds, scientists pursue sweeping
solutions to social ills. This journal entry where the funds from the Precision Medicine have been
being distributed and the goals that are being set by scientist. The article starts off by stating that
the Precision Medicine Initiative, unlike many others, was very different because it had a very
clear mission driven case that would be aided with research. Many past research programs
started by the government were “ for the sake of endless frontier” and simply just to research
whereas the Precision Medicine Initiative claims to be different. The author continues to talk
about the different obstacles that scientists have seen. “The challenges have drawn researchers to
neglected problems, and shifted the NIH's budget toward research on infectious diseases in
developing countries. But when these scientific innovations met the real world, they were
limited: Border conflicts and bad roads impede vaccine distribution. People fear biotech crops”
(2015, p. 3). While some industries were thriving with the new discovery of the human genome,
the effort to solve medical issues in third world countries were facing major drawbacks. The
second article was called Scleroderma research foundation. This article discusses the
Scleroderma Research Foundation and what is has been doing in research towards scleroderma.
This foundation has been constantly doing tests and searches for different drugs that would be
most effective for scleroderma patients. These patients are very limited because there are so few
people who do suffer from the disease. Because of the lack in participants the Scleroderma
Research Foundation, through their funding from the government and other sources, has been
able to line up approximately 1,000 cases of scleroderma. By looking at all these cases side by
side, researchers are able to see similarities and differences in patient response and symptoms
and based on that determine courses of action in terms of treatment that would be best for each
individual patient. That being said, it is more likely that further precaution would be taken so that
institutions whom used precision medicine techniques as their primary form of treatment will be
protected if and only if the patient decides that they no longer want the help.
Results and Data Collection
The data clearly indicated that all three treatments are effective. The reason being that all
treatments are good is because they are able to effectively get rid of the specific unwanted
cancerous cells present in the boy. The full results can be seen in Appendix A.

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