Elyse Mehigan

Committee Proposal Worksheet

1. Purpose – to inform my readers of the importance of incurable disease research and the
most effective methods that are being used currently. As a result, I hope that people
become more education on where they would like to donate their money, so that money is
being allocated to the most effective areas of research.

2. Thesis - Precision medicine, epidemiology, and genomic mapping, and stem cell research
are revolutionizing the medical field and creating more effective, purposeful treatments
than ever before

a. Precision Medicine
i. Obama Initiative https://www.nejm.org/doi/full/10.1056/NEJMp1500523
1. Research program that attempts to “accelerate progress towards a new era
of precision medicine.”
2. Previously used for blood typing, but now being applied wide-scale to
biological databases
3. Improved by human genome sequencing.
4. Two components
a. Near-term focus on cancers – hope to help “unexplained drug
resistance, genomic heterogeneity of tumors, insufficient means for
monitoring responses and tumor recurrence, and limited
knowledge about the use of drug combinations.”
i. Targeted therapies are being used to treat patients with more
specificity
b. Long-term focus on application overall health and disease
5. Help move regulatory frameworks to incorporate patients desire to be
active in their treatment/research.

The Obama Initiative began the movement of Precision Medicine in the

modern era, which is very important for readers to understand because it
explains how precision medicine is an up-and-coming trend of incurable
disease research.

ii. Precision Oncology https://www.cancer.gov/about-

cancer/treatment/types/precision-medicine
1. Includes using targeted therapies to using data from next-generation
sequencing to select a therapy to treat a patient’s cancer.
2. Doctors select treatments based on their understanding of both the patient
and disease’s genetic makeup.
3. Currently not widely available to benefit patients.
a. Melanoma, certain leukemias, breast, lunch, colon, and rectal
cancer patients are normally tested for genetic changes that would
categorize as potentially able to benefit from precision oncology.
Precision Oncology is the most practical, influential application of
precision medicine currently and is making the most strides, which is why
Elyse Mehigan

it is an important topic to cover to explain the importance of precision

medicine in incurable disease research.

iii. History and Future of Personalized Medicine

https://www.managedcaremag.com/archives/2011/8/history-and-future-
personalized-medicine
1. Precision Medicine first appeared in 1999 in published works; however,
the idea of it may have appeared as earl as the 1960s.
2. Two large discoveries:
a. Single Nucleotide Polymorphism genotyping
i. Single nucleotide changes in the DNA sequence.
ii. Identification of SNPs has been linked to patient susceptibility
for certain diseases ant drug treatment/responsiveness.
b. Microarray/biochips
i. Allows for SNP genotyping to be conducted efficiently.
ii. Allows for quick development o protein-based diagnostics and
therapeutics.
3. Pharmocogenetics – evaluates the effectiveness of certain treatments for
patients based on their genetic makeup.

This information will be used as background information to introduce

Precision Medicine (will be moved to beginning) and an important
introduction to the purpose of Precision Medicine.

b. Epidemiology
i. What is it? https://www.bmj.com/about-bmj/resources-
readers/publications/epidemiology-uninitiated/1-what-epidemiology
1. Study of how and why diseases appear in different groups of resources.
2. Info is used to create strategies to prevent illness and a guide to the
management of patients that already have the disease.
3. Measurements
a. Measurement of disease outcomes in relation to a population at
risk – uses studies of groups of people.
b. Used for groups of people more commonly than for individuals.

Epidemiology can be confusing, and this information will provide a good

introduction to explain how Epidemiology is becoming an important
research method in Incurable Disease research as the world’s population
grows.

ii. DNA Methylation and Uses https://www.cell.com/action/showPdf?pii=S1471

4914%2814%2900115-4, https://www.sciencedirect.com/science/article/pii
/S1471491414001154, https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC4186777/
Elyse Mehigan

1. EWAS (epigenome-wide association studies)- systematic approach to

uncovering epigenetic variants.
a. Helps with applying epigenetic variants as biomarkers.
2. GWAS (genome-wide association studies)- identify common genetic
variants associated with many traits.
3. DNA methylation- methyl groups are added to a DNA molecule. Can
change the activity of a DNA segment without changing the sequence.
Tends to repress gene transcription.
a. Used to track mutations/various other patterns.

DNA methylation is one of the most important applications of

Epidemiology and is a critical piece of information for the readers to
understand because it puts Epidemiology on the map of important types of
research.

iii. Alzheimer’s Geographic Analysis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181909/
1. Alzheimer’s accounts for 75% of dementia cases worldwide.
2. The Aging population sized is expected to increase from 7% to 12% by
2030. Developing nations hold 59-71% of this population.
a. As a result, it’s important to track development and progression of
Alzheimer’s worldwide to better understand it.
3. There is a pattern of dementia subtypes worldwide: Alzheimer’s and
Vascular dementia being most common.
4. Epidemiological research can provide evidence that vascular risks in
middle-aged and older adults significantly affects the
development/progression of Alzheimer’s.

Alzheimer’s Disease is growing at large rates currently, and is a helpful

example for the usefulness of epidemiology and the information it can
provide scientists to better understand information disease growth and
incurable disease research.

c. Genomic Research
i. Cancer Protein Mapping https://www.cancer.gov/research/areas/genomics
1. Abnormal genes drive cancer development (genetic/epigenetic changes in
tumors)  use this to develop new treatments/diagnoses.
a. Vemurafenib (Zelboraf) – developed in 2011 to treat patients with
a mutation on the BRAF gene with melanoma.
b. Genetic similarities in tumors – breast, bladder, pancreatic, and
ovarian (treatments for breast, esophageal, and gastric cancers
found through this)
c. Differentiation between aggressive and indolent cancers could be
found through comparisons between genomics and clinical
phenotypes.
Elyse Mehigan

Because cancer research is understandable and somewhat known about to

my audience, using it as an example of the uses of genomic research is an
accessible and understandable.
ii. Alzheimer’s Risk gene mapping https://www.nih.gov/news-events/news-
releases/data-sharing-uncovers-five-new-risk-genes-alzheimers-disease
1. Tau – hallmark protein of Alzheimer’s disease.
a. “Cell trafficking, lipid transport, inflammation and the immune
response, are ‘genetic hubs’”
b. Research confirmed association of 20 genes with Alzheimer’s risk
and found 5 additional genes.
i. IQCK, ACE, ADAM10, ADAMTS1, and WWOX.

Using this example of Alzheimer’s gene mapping adds to my argument of

the importance of genomic research, which supports my argument that
genomic research is a pivotal new addition to incurable disease research.

iii. Pharmacology drug tailoring

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290900/
1. Molecular testing now includes population carrier-screening programs,
molecular diagnosis, prenatal mutation analyses, and preimplantation
genetic diagnosis.
2. There is now a possibility of predictive genetic testing to evaluate
personalized disease risk.
3. Sir William Osler – noted the great variability among individuals – in the
1880s.
4. Pharmacogenomics – “the continued identification of relevant genes,
sequence variants, ad associated drug response phenotypes”

Drug tailoring is the most common application of genomic research,

which I will most likely use to introduce the topic, as it provides an
understandable introduction to why it is important for current incurable
disease research.

d. Stem Cells
i. Human Pluripotent Stem Cells https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC6092712/
1. 1998 – first derivation of human embryonic cells (hESCs) – controversial
due to origin in human extracorporeal embryos.
2. 2007 – first derivation of human induced pluripotent stem cells (hiPSCs) –
have fundamental characteristics of hESCs, but are derived from somatic
cells, not embryos.
a. In last 12 years, high rate of hiPSC growth wheras slow rate of
hESCs.
Elyse Mehigan

Stem cell research is very new, and the development of hiPSC’s is

beginning to reintroduce this type of research back into use as it has less of
an ethical issue. Because it was so recently developed, I am arguing that it
will become incredibly useful to incurable disease research.

3. Human Pluripotent Stem Cells (more)

https://www.medicinenet.com/script/main/art.asp?articlekey=14525
a. “Cells that are self-replicating, are derived from human embryos or
human fetal tissue, and are known to develop into cells and tissues
of the three primary germ layers.”
i. These cells have the ability to divide and form cells
indistinguishable to the original because stem cells can
differentiate into any cell.

I will use this information to introduce how stem cells are used (and I will
add some information on why they have ethical debates), to build my
audience’s knowledge of why they are currently becoming more widely
used and effective in incurable disease research.