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Personalized healthcare pays attention to individuality, which represents a great opportunity to optimize individual health by adapting to the genomic and environmental contributions to individuality that define personal potential. This article classifies the evolution of the relevant medical informatics which has evolved from simple gross health status, to application of diagnostics for improved selection of therapy, to the production of niche therapies and a new definition of individualized goals. That evolution provides different stages for personalized healthcare that pose a new realm of challenges for the future of medicine.
Keywords: Human genome; Personalized healthcare; Pharmacogenomics; Epigenetics
Personalized healthcare describes attention to individuality. In 2016 the average number of people per family was 3.16, but we have never encountered a family with 3.16 people. Analogously, standard of care is not necessarily ideal for an individual patient. For the sake of this argument, the author opines that strict application of standard of care, while a sensible starting point, achieves only half of the maximal potential benefit of healthcare. We are all genetically and environmentally unique. Personalizing healthcare to accommodate individual differences in nature and nurture can offer finer tuned health achievements. This article proposes a model of the history of personalized healthcare framed as 5 different stages, based on the shifting paradigm of relevant informatics.
Stage zero of personalized healthcare consisted simply of adjustment of therapy based on individual status, for example, changing the frequency and severity of bloodletting based on exam findings.
Diagnostic progress led to stage one of personalized healthcare, patient selection for more appropriate matching of therapy to medical condition. For example, current use of bloodletting is largely limited to management of too much production (polycythemia) or too little clearance (hemachromatosis), and is no longer used to remove poorly defined “bad humors.” However, before dismissing these stages as obvious and outdated, consider the mismatch of findings and treatment evident in the persisting frequency that antibiotics are prescribed for viral illnesses as well as for exacerbations of inflammatory conditions. Stage one of personalized healthcare, matching treatment to illness, remains underachieved.
The human genome project  sparked invention of fast and efficient methods to fully identify the template for individual genetic design, thereby delineating the blueprint for all of the human structural and functional proteins, as well as individual differences , at the genetic prescription level. The human genome project realized the ability to map the design and structure of the proteins responsible for human biology structures and function, and also led to fast inexpensive methods to map the genome of individual subjects.
An early major benefit from the human genome project is its tremendous facilitation of the design of new drugs that specifically regulate many of the protein products coded by the human genome , a new generation of medications that include “biologics.” Biologics are biologically derived medications which may include activators and inhibitors of biological proteins.
Thus the human genome project ushered in a new stage of personalized medicine, which we’ll call stage 2 of personalized medicine, targeted pharmocologics, by providing a widened array of treatment options that may be better matched to individual need and response. The dramatic increase in choice and specificity of treatments justifies credit of biologics as a new
stage in personalized medicine.
However, the human genome project is already providing
more, which we’ll label as multiple branches of stage 3. Stage
3 of personalized medicine applies the individual’s genome to
guide diagnosis, treatment and monitoring .
Stage 3A applies individual genomics as information support
for decision making, by identifying predilections to disease,
and inapplicability of some treatments. Stage 3B adds custom
design of medications tailored to the individual’s structural
and functional proteins, for example, to supplement deficient
functions, or to combat a specific cancer while sparing the rest
of the patient.
Herein, we propose a stage 4 which will utilize the individual
genome, plus assessment of individual gene expression and
individual post production modifications, to modify the analysis
of patient status and response to therapy for meta-analysis
of lab results to produce a new layer of lab report assisting
interpretation of the confluence of results in relation to the
individual. In other words, stage 4 will personalize targets of
therapy in relation to a new definition of “normal,” based not
on the general population, but rather on the individual’s genetic
constitution, taking into account modifications of expression
due to environment, behavior, disease, and therapy. Steps
towards stage 4 include “predictive biomarkers” which look at
changes in the expression of genomic products as indications of
treatment response . Stage 4 poses a challenge to biometrics
and bioinformatics to encompass the full scope of advances in
genomics and epigenetics .
The human genome project successfully coordinated
multiple laboratories to delineate fully all of the coded sequences
in genes that specify the sequence of amino acids that build
every protein in humans , known as “whole human genome
sequencing.” The Genome in a Bottle Consortium, a publicprivate-
academic consortium hosted by the National Institute of
Standards and Technology (NIST), develops reference standards,
methods, data and disseminates information to facilitate
translation of the accomplishments of whole human genome
sequencing to clinical practice and personalized healthcare, by
“authoritative characterization of human genomes for use in
analytical validation and technology development, optimization,
and demonstration” .
“Understanding the causes of cardiovascular diseases
logically starts with the genetic code that specifies the designs
for the structures and function. These may be inherited
from your parents, or may differ from either parent due to
spontaneous mutations. Congenital heart disease comprises
many different abnormalities, primarily of structure. For
example valves and tubular pathways may be malformed, and
connections may be deviant. Connections not normally presentare known as shunts. The completion of the human genome map
was a major accomplishment enabling complete enumeration of
all the possibilities. Genes specify the codes for gene products
that make the structural elements, signals, receptors and other
building blocks that establish health and disease. However, the
complete genome map is just a stepping stone, as it does not
completely explain why, where, or how the gene products are
regulated and interact. Epigenetics picks up on the issues of gene
expression, product modifications and assembly. Epigenetics
is the scientific focus that characterizes the vital follow-on
steps from genetic code to the determination of structures and
function of the cardiovascular and other biologic systems” .
Biologics are pharmaceutical products manufactured in,
extracted from, or derived at least in part from biologic sources.
A growing number of biologics are produced from genetic code
segments corresponding to a human natural gene product or a
modification of it to increase or decrease its functional roles or
change its distribution or immune responses.
Current usage of the term biologics generally focuses
on medications acting as bioactive substances that may be
administered as pills, injections, or application on the skin or
under the tongue, thereby excluding other biologic derivatives
such as foods, soap, and gelatin. In current use, the term
biologics is further restricted to protein and/or nucleic acid
based products modified from sequences coded in the human
genome, excluding other biologic extracted products such
as blood, hormones, body part transplants or vaccines. As
production techniques evolve, the distinction between biologic
derivation and bench synthesis of products based on or related
to structures coded in the human genome may become blurred.
The term “genomics” has other meanings, perhaps a better term
will be genomic products or genoproducts. The development
domain is termed pharmacogenomics .
The impact of the human genome does not depend solely on
the chromosome DNA code sequences for protein construction.
Additional factors include DNA methylation, which can
modulate gene expression. Histones in chromatin can form
heterochromatin to deactivate the DNA transcription required
for gene expression. RNA can interfere with DNA transcription.
Post transcription modifications, also influence gene expression.
Environmental factors such as food abundance at critical periods
in growth and development may affect these modifiers . All
of these factors participate in the development of genomic and
There is a risk that the greatly expanded test combinations
and definitions of the new normal for stage 4 of personalized
healthcare will be overwhelming. The former commissioner  of the Food and Drug Administration (FDA) has called attention
to that as yet resolved issue. “I think the community better take
this really seriously,” said Robert Califf (cardiologist and former
Commissioner of FDA), discussing Laboratory Developed Test
(LDT) regulation, at the 12th Personalized Medicine World
Conference at Harvard. While, on the one hand, regulation
shouldn’t stifle innovation, he noted that doctors can’t be left to
figure out which test they should order. “We’ve got to come up
with some middle ground, so regardless of where you are in the
US you can get a reproducible laboratory result” .
Personalized healthcare recognizes that the uniqueness
of individuals corresponds to an opportunity to tailor therapy
to individual needs. The informatic basis for personalization
corresponds to distinct stages in the evolution of personalized
care. Stage zero consisted of adjusting “one-size fits all” therapy
to the physical status of the patient. Stage 2 utilizes diagnostics
for selection of therapy. Stage 3 applies pharmacogenomics
to develop individual specific therapies. Stage 4 will redefine
“normal” and targets of therapy based in the individual genome,
gene expression, and epigenetics. The future of medicine will
require regulations that hopefully will strike a good balance
between restrictions of chaos and fulfillment of this potential.