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We are the future of science, shouldn’t you be iNFORMED?
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THE iNFORMER FELLOWS NEWSLETTER
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
The views and opinions of authors expressed in this newsletter do not necessarily state or reflect those of NIDDK or the U.S.
Government, and they may not be used for advertising or product endorsement purposes.
VOLUME 8, ISSUE 2 – APRIL 2015
In this issue
• Free Smartphone
Apps to Help With
Your Day-to-Day
Work
• A Primer on
Personalized
Medicine: The
Imminent Systemic
Shift
• The Science and
Policy of Marijuana
• A Hypothetical NIH
Equipment/
Instrument Library
• A Syringe Full of
Trust
• Recent Publications
by NIDDK Fellows
• New Fellows
EDiTORS
~•~
Kavya Devarakonda
kavya.devarakonda@nih.gov
Christine Krieger
christine.krieger@nih.gov
Joseph Tiano
joseph.tiano@nih.gov
The iNFORMER is
published by the
Fellows Advisory
Board (FAB) in
collaboration with the
NIDDK Fellowship
Office
10th Annual NIDDK Scientific Conference
April 20-21, 2015
9:00 AM – 5:00 PM
Natcher Conference Center, Building 45
Compete for one of the seven travel awards
Have lunch with a keynote speaker
Join the networking lunch with career panelists
This year’s event will feature three keynote speakers:
Dr. Charles Rice, Rockefeller University
Dr. Tom Muir, Princeton University
Dr. Thomas Boyer, University of Arizona
A schedule of events is included
at the end of the newsletter.
All NIDDK fellows and scientific staff
are encouraged to attend.
Announcements
APRIL 2015VOLUME 8, ISSUE 2
Page 2
THE iNFORMER
Free Smartphone Apps to Help With Your
Day-to-Day Work
Way back in 2012, Manhattan Research
conducted a survey on physician usage of apps.
Based on that survey, clinicians were identified as first
adopters of mobile devices and the medical apps that
run on them. As app users, physicians tend to
download fewer apps than the average consumer, but
they tend to use those apps more often.
Back then, iPads began to be used by
physicians a lot. Today, smartphones are the go-to for
information. The value of smartphone apps is
catching on in medicine. iPhone and Android
smartphone platforms have created a market in
medical applications because they can run more
complex medical apps at point-of-care than the older
text-based apps used on personal digital assistants
(PDAs).
Here is a look at some free smartphone apps
that may help you in your day-to-day work. All iPhone
and Android apps can be downloaded from iTunes
and Google Play.
Dropbox (iOS, Android)
A cloud-based app allows you to store, access, and share
medical literature, project work, and other information.
Prognosis (iOS)
This app is designed for physicians and is a fun game that
presents an engaging series of clinical case scenarios that
assess the decision making skills of the player.
Doctor's Dilemma® (iOS)
You can test your knowledge in a variety of disciplines.
Doctor's Dilemma is simple to play (earn points with correct
answers, lose them with incorrect answers), but the questions
will challenge you.
Calculate by QxMD (iOS, Android)
This tool offers the ability to search for easy-to-use
calculators by specialty.
MedPage Today; Medscape (iOS, Android)
These apps gives you access to breaking medical news
and includes CMEs.
PubMed on Tap (iOS)
Search PubMed and PubMed Central while on the go.
Evernote (iOS, Android)
An app that allows you to take notes, capture photos, create
‘to-do’ lists, and record voice reminders that are accessible
across all the devices you use.
Cloud Storage and
File Sharing
Games
Medical News
Medical Articles
Note-Taking and
Organization
Medical Calculator
APRIL 2015VOLUME 8, ISSUE 2
Page 3
THE iNFORMER
A Primer on Personalized Medicine:
The Imminent Systemic Shift
Imagine a hypothetical scenario from a not-
so-distant future: You get sick. Prior to this, you
have been disappointed with how slowly your
physician adopts new technologies. Therefore, you
decide to find a new physician. At the new clinic,
an administrator asks if you brought your electronic
genome (e-genome) with you. You answer that you
have not had a chance to get your genome
sequenced yet, but you would like to do so. At that
point in time, you begin a set of routine procedures.
Enough of a biological sample is collected for the
sequencing of your entire genome via a simple
cheek swab or a finger prick test.
Then, while you are having a medical
examination with your new physician, your genome
gets sequenced by the “lab on a chip” portable
equipment and the data are electronically fed into
the physician’s iPad. Your physician punches in
some additional phenotypic characteristics into an
app to help her determine whether your genotype
is homozygous or heterozygous for the gene(s)
known to be metabolically linked to the sickness
you are experiencing. Then, minutes later, your
physician picks a drug “z” over “x” or “y,” which has
the highest chances of addressing your sickness
with the lowest likelihood of side effects, given your
unique set of genomic and phenotypic
characteristics.
Though a captivating and exciting glimpse
of a possible future, the personalized medicine
scenario above is certainly oversimplified, and its
detailed script is still being written. Before such
medical practices can become a widely accepted
reality, not only applicable to a narrow group of
specific genetic disorders, some major changes to
the current status quo need to happen.
Firstly, the research efforts of several
players in the health and science ecosystem must
be refocused. According to Charles R. Scriver, a
key player in the Human Genome Project (HGP),
“Since genomes speak biochemistry, not
phenotype, for genomics to penetrate medicine,
biochemistry and biology must be allies.” [1]
Analogous to the HGP and its goal of sequencing
and mapping a complete set of genes for humans,
the Human Phenome Project (HPP) aims to
elucidate the phenome, a complete phenotypic
characterization of human species. More
specifically, the goal of the HPP is to determine in
practical terms what exactly a phenotype is and to
assemble all of the phenotypic components,
including morphologic, biochemical, physiological,
and even behavioral characteristics of the human
species into a complete set.
Even though the HPP idea is now at least
12 years old, this project is so complex that as of
2012, scientists across have the world are still
“getting ready for the HPP” [2]. A lot more scientific
work will have to be completed before the HPP can
be started. The good news is important
developments have already started. In 2006, after
the completion of the HGP, a new global effort, the
Human Variome Project (HVP), was launched to
share information about genetic variation in clinical
practice. According to Casimiro Vizzini, an expert
at the International Basic Sciences Programme of
the United Nations Education, Scientific and
Cultural Organization, “The term variome refers to
the sum of all the genetic variations found in
different populations of the same species.” [3]
As a global organization, the HVP has
been working to develop and maintain standards,
systems and infrastructure to enable sharing of
information on genetic variation generated during
diagnostic and predictive testing as part of routine
clinical practices. The ultimate goal is to link
genetic variation to the patient body and disease
development phenotypes to help doctors with
diagnosis and drug selection for effective
treatments.
Another change that must occur is that
personnel and organizations within the health care
ecosystem will have to figure out, re-align and
sometimes even shift their roles completely per the
requirements coming from future personalized
medicine mandates. Large players have already
realized that the personalized medicine future is
fast approaching and have decided to start
changing.
APRIL 2015VOLUME 8, ISSUE 2
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THE iNFORMER
In his 2015 State of the Union Address,
President Obama announced the launch of the
new Precision Medicine Initiative, which was
promptly followed by a press release from the
White House unveiling details. The National
Institutes of Health (NIH), the Food and Drug
Administration (FDA), and the Office of the
National Coordinator for Health Information
Technology (ONC) will together receive a $215
million investment in 2016 to start executing this
initiative. Main objectives of the initiative are:
 Creation of a voluntary national patient-
powered research cohort of at least 1
million Americans in order to involve and
encourage patients to contribute their
medical records and data on gene profiles,
metabolites, body microorganisms,
environmental and lifestyle data, personal
device and sensor data — all with under
rigorous protection of patients’ privacy
 Discovery acceleration of effective and
tailored treatments for cancer via
expanding genetically based clinical cancer
trials, elucidating fundamental aspects of
cancer biology and establishing a national
“cancer knowledge network” to identify
genomic drivers in cancer
 Ensuring patients’ health data privacy and
security within the precision medicine model
 Modernization of the regulatory landscape
to adequately support the new precision
medicine innovation, research and health
care model via development of high quality
curated databases and interoperability
standards to enable secure exchange of data
across systems.
These objectives will be achieved via the
establishment of public-private partnerships with
the private sector, existing research cohorts and
patient groups, in order to develop the required
precision medicine infrastructure and frameworks,
and provide consumers with secure access to their
own health data as well as to the applications and
services that can analyze it.
Only days after the president’s State of the
Union Address, the House Energy and Commerce
Committee released a nearly 400-page discussion
document of the 21st Century Cures Act. Briefly,
the core ideas of this legislative initiative are:
 Putting patients first, by creating a
regulatory environment that is conducive to
incorporating their perspectives and
addressing their unmet medical needs,
including biomarker quantification, antibiotic,
drug and dormant therapies development,
and innovative device review pathways
 Building the foundation for 21st century
medicine, including the creation of the next
generation of patient-centered solutions,
stimulating innovation in health information
technologies and helping young scientists
have successful careers
 Modernizing and streamlining clinical
trials to allow broader utilization of flexible
and more cost efficient trial designs, while
reducing regulatory overlap and
administrative burden to cut costs and speed
up the assessment of new treatments
 Accelerating and supporting the
innovation cycle at federal public health
agencies, including NIH
 Modernizing medical product and device
regulation by taking into account novel
manufacturing technologies
All interested stakeholders have been
encouraged to participate in the discourse on how
to improve this legislation.
In turn, miscellaneous players such as
biopharmaceutical companies, patients groups,
health insurers, pharmacy benefit managers,
physicians, and scientists have actively started
figure out whether they are poised to gain or lose
from these initiatives. Some interest groups and
foundations have started information campaigns to
sway the legislators and the general public, and
are prompting constituents to act and shape the
future of personalized medicine in the United
States.
One example is the EveryLife Foundation
for Rare Diseases, which, in partnership with Rare
Disease Legislative Advocates and with a
sponsorship from almost 30 large pharmaceutical
and smaller biotechnology companies, led a Rare
Disease Week, a legislative conference on Capitol
Hill last February.
APRIL 2015VOLUME 8, ISSUE 2
Page 5
THE iNFORMER
The conference provided an overview of the 21st
Century Cures Initiative, lobbied the members of
congress and gave a detailed training on being an
effective advocate, including ways of using modern
social media platforms such as Facebook and
Twitter. Constituents were asked to help ensure
the 21st Century Cures legislation improves access
to experimental drugs for patients with rare
diseases. Other suggestions for constituent
advocates were to encourage support for the
development of lifesaving therapies deemed not
profitable by drug companies and investment in
medical innovation for diseases that have few or no
treatment options.
The NIH, as one of the largest players
within both the science and health care
ecosystems in the United States, will be directly
affected by this imminent systemic shift. It is likely
the NIH will not only execute the initiatives but also
actively participate in influencing the public
discourse on both personalized medicine
initiatives. The NIH has already started to
showcase information about the precision medicine
initiative on its websites, and in the beginning of
February, held a workshop on Building a Precision
Medicine Research Cohort, which is one of the
main objectives of the president’s initiative. The
workshop gathered leading experts in health care,
mobile health, patient advocacy, genomics,
epidemiology, privacy, computer science and
information technology to identify the challenges
and explore the opportunities associated with
building such a cohort of patients.
Additionally, on March 30 the NIH
announced the formation of team of experts in
precision medicine and large clinical studies to
chart the course for the initiative and to define, with
input from all interested stakeholders within
ecosystem, the vision for building the national
participant group and to formulate what will be
considered “success” 5 and 10 years after the
launch of the initiative. A preliminary report from
the team of experts is expected in September
2015.
Overall, the advent of personalized
medicine practices in the United States will be a
fascinating story to watch as it develops in years to
come. In the future, humans may be getting their e-
genomes assembled at birth, like they are currently
getting their vitamin K shots. Then, e-genomes
may be compared to the standardized human
“default genome” template to determine the
individual’s e-variome. By adulthood, all of the
unique phenotypic characteristics, including
environment influences and lifestyle risk factors an
individual has experienced, may be added and
integrated with the e-genome/e-variome data
stored on the cloud to produce a data set that is
unique for that person.
Let us conditionally call this data set the “e-
OME.” So, in the hypothetical scenario about a visit
to a new physician, you would only have to walk
into a clinic with a password to grant your doctor
access to download your private e-OME data set
into her iPad. Your doctor would then run some
sophisticated algorithms via an app to connect to
the “holy grail” of personalized medicine — the
global medical bioinformatics database. Her goal
would be to determine how well your e-OME
interfaces with the current list of all known disease
phenotypes previously determined for your ethnic
subgroup with a specific intent to probe for the
specific disease she suspects based on your
clinical symptoms.
Then, your doctor will evaluate the side
effects of all known drugs against that particular
disease in the cohort of patients having the closest
cumulative e-OME to yours. In the end, a selection
of the drug tailored “specifically for you” will be
made and a prescription written. Oh, what a
wonderful future lies ahead of us! Meanwhile, there
is a plenty of work to do for scientists around the
nation.
References
1. Scriver CR. “Translating knowledge into practice in
the "post-genome" era.” Acta Paediatr. 2004
Mar;93(3):294-300.
2. Oetting WS et al. “Getting ready for the Human
Phenome Project: The 2012 forum of the Human
Variome Project.” Hum Mutat. 2013 Apr;34(4):661-6.
3. Casimiro Vizzini. “The Human Variome Project:
Global Coordination in Data Sharing,” Science &
Diplomacy. 2015 Mar;4(1):1-8. A quarterly publication
from the AAAS Center for Science Diplomacy.
APRIL 2015VOLUME 8, ISSUE 2
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THE iNFORMER
The Science and Policy of Marijuana
The increased discussion of marijuana in
the news lately has been hard to ignore. Four
states (Washington, Oregon, Alaska, Colorado),
and now the nation’s capital, have completely
legalized the drug, whereas several other states
may be moving in that direction through
decriminalization and/or the addition of laws
legalizing medicinal use [1]. Although marijuana
laws have significantly changed in the last few
years, several questions remain. How are state
and federal agencies coordinating the differences
in federal and state laws? How are science and
policy influencing each other to govern marijuana
laws now and in the future?
Medicinal marijuana and drug classification
To date marijuana is classified as a
schedule I drug. According to the Controlled
Substance Act (CSA) and the Drug Enforcement
Administration (DEA), this classification is assigned
to drugs that currently do not have accepted medial
uses, and pose a high potential for abuse as well
as physical dependence. Other drugs that fall into
this category include heroin, LSD, ecstasy,
methanqualone, and peyote [2]. The classification
of marijuana as a schedule I drug may seem at
odds with the growing discussion about “medicinal
marijuana”; however marijuana remains a schedule
I drug because the U.S. Food and Drug
Administration (FDA) have approved neither the
unprocessed plant nor plant extracts as medicine.
Although marijuana as a whole is not yet approved
for medicinal purposes, the cannabinoids found in
marijuana have led to the development of two
FDA-approved medications. One of the approved
cannabinoids, delta-9-tetrahydrocannabinol (THC),
has been shown to stimulate appetite and reduce
nausea. The second cannabinoid, cannabidiol
(CBD), may be effective for decreasing pain,
inflammation, controlling seizures, and possibly for
treating psychosis and addiction [3].
Current cannabinoid-based drugs in clinical
trials or approved by the FDA for medical use:
 Dronabinol (Marinol®) contains THC and is
used to treat nausea caused by
chemotherapy and extreme weight loss
resulting from AIDS.
 Nabilone (Cesamet®) contains a synthetic
cannabinoid similar to THC and is used for
the same purposes as described above
 Sativex®, contains approximately equal
parts THC and CBD, is currently approved in
the United Kingdom and other European
countries to treat spasticity caused by
multiple sclerosis (MS), and is currently in
Phase III clinical trials in the United States to
establish its effectiveness and safety in
treating cancer pain.
 Epidiolex™ is a CBD-based drug recently
created to treat certain forms of childhood
epilepsy. Epidiolex has not been approved by
the FDA yet as it still has to undergo clinical
trials for safety and efficacy.
What is the state versus federal perspective?
As mentioned above, at the federal level
marijuana remains a schedule I drug and therefore
the possession of the drug is illegal. In order to
help define the role that federal and state law
enforcement agencies play in the regulation of
marijuana laws in each state, James M. Cole, the
deputy attorney general, released the Cole Memo
in August 2013. This memo instructed U.S.
Department of Justice attorneys and law
enforcement to focus on eight priorities in enforcing
the CSA against marijuana conduct. Issues not
pointed out in the memo were to remain under the
states’ jurisdiction. These eight points in which
federal agencies should regulate marijuana-related
issues include [4]:
 Preventing the distribution of marijuana to
minors
 Preventing revenue from the sale of
marijuana from going to criminal enterprises,
gangs, and cartels
 Preventing the diversion of marijuana from
states where it is legal under state law in
some form to other states
APRIL 2015VOLUME 8, ISSUE 2
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THE iNFORMER
 Preventing violence and the use of firearms
in the cultivation and distribution of marijuana
 Preventing drugged driving and the
exacerbation of other adverse public health
consequences associated with marijuana use
 Preventing the growing of marijuana on
public lands and the attendant public safety
and environmental dangers posed by
marijuana production on public lands
 Preventing marijuana possession or use on
federal property
More recently, a bipartisan group of
senators introduced a marijuana reform bill on
March 10 (S.683). The bill is sponsored by Rand
Paul (R-KY), Cory Booker (R-NJ) and Kirsten
Gillibrand (D-NY) and aims to make it easier for
states to allow medicinal marijuana. Measures in
the bill include (1) downgrading marijuana from a
schedule I drug to a schedule II drug, (2) loosening
restrictions on the transportation of marijuana
between states, (3) allowing banks to provide
services to marijuana businesses, (4) encouraging
the National Institute on Drug Abuse (NIDA) to
broaden access of marijuana for research, and (5)
allowing doctors with the Department of Veteran’s
Affairs to recommend marijuana in states that
already allow it [1].
What are the current concerns regarding
marijuana legalization?
To date, little research has been conducted
to examine the health and safety of marijuana.
Because of the increased acceptance of marijuana
use and the push for legalization, a greater
emphasis has been placed on understanding the
science behind marijuana addiction liability, effects
of long-term use, and the effects of marijuana on
the developing brain, among other issues. A
complete list of studies supported by NIDA
examining the health and safety of marijuana can
be found on their website [5].
In addition to concerns regarding the
impact of marijuana on health, other concerns arise
in regards to the presence of marijuana in society.
For example, what is the most appropriate test for
determining if a vehicle driver is under the
influence of marijuana? What is a reasonable limit
for drivers of vehicles? How should the
concentration of marijuana in edible products be
regulated, and what should be the limits? Research
investigating the most accurate detection methods
for marijuana in the body, reasonable limits levels
of marijuana in the body that do not impair one’s
ability to operate a vehicle, and drug metabolism
could all provide insight into policy regarding these
questions.
How might science inform marijuana policy in
the future?
One way in which NIDA plans on
contributing to the understanding of the health risks
and benefits of marijuana use is though the funding
of a longitudinal study that will track a large sample
of young Americans from late childhood, prior to
first exposure to drugs, to early adulthood.
Neuroimaging of these individuals is proposed to
help clarify how and to what extent drugs of abuse,
including marijuana, affect adolescent brain
development.
However, much more must be
accomplished to fully comprehend the health and
safety issues resulting from widespread marijuana
legalization. Whether smoking or consuming
marijuana has therapeutic benefits that outweigh
its health risks is still an open question that science
has not yet reconciled. Additionally, the ability to
isolate plant extracts and/or develop synthetic
drugs may completely eliminate the need for
legalization of the marijuana plant. Regardless, as
science involving marijuana health and safety
continues to advance, laws regarding medicinal
marijuana and other marijuana-derived compounds
will continue to evolve. It will be crucial these
scientific developments guide policy laws regarding
marijuana use in the future.
References
1. Ingraham, Christopher. “The senate marijuana
reform bill would bring federal policy in line with
medical research.” The Washington Post. 10 March
2015.
2. “Drug Scheduling.” Drug Enforcement Agency.
2012.
3. “Drug Facts: Is Marijuana Medicine?” National
Institute on Drug Abuse. December 2014.
4. Cole, James M. “Memorandum for all United States
attorneys.” U.S. Department of Justice. 14 February
2014.
5. “NIDA research on the therapeutic benefits of
cannabis and cannabinoids.” National Institute on
Drug Abuse. March 2014.
APRIL 2015VOLUME 8, ISSUE 2
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THE iNFORMER
A Hypothetical NIH Equipment/Instrument
Library
When it comes to the issues a
postdoctoral fellow might care about, I believe
each one would be able to list a few right away.
Aside from landing a permanent position, and
enjoying work and life, getting a nice publication
is surely on the top of most fellows’ wish lists.
Just as Galileo’s telescope launched modern
astronomy, employing a novel method in
research typically leads to a nice paper in a
relatively short period of time. Unless one
develops a new technology by him- or herself,
most of the time new technology requires
acquiring a new instrument. Life science
instruments are usually very expensive,
particularly the new ones – they often cost much
more than our annual salary/stipend.
It is also worth noting that instruments are
often only used for a brief period of time before
they are relegated to a corner to collect dust.
This is not uncommon given the nature of
scientific projects: After a paper is out the whole
project might be closed. Therefore, sharing
instrument and equipment is a good option. It
can save funds for the institute, and save
researchers the trouble and time of purchasing a
new instrument.
Core facilities are a great example of the
benefits of sharing expensive instruments.
However, at some point, we inevitably encounter
a situation where a piece of equipment is
unavailable. If you are lucky, you might find that
the instrument you want is in the laboratory next
door. More than often, you are not that lucky,
and you have to persuade your advisor to agree
to purchase it. This follows writing an equipment
application without a guarantee that it will be
approved. Then, if it is approved, the instrument
arrives at your door a few months later, at which
point, you might not need it anymore because
you have already taken a painful alternative
method to answer your question or you have
simply moved on to another seemingly more
promising project.
So, what can be done to solve some of
these problems, and make fellows’ lives less
miserable? One way is to establish a NIH
Equipment/Instrument Library. Similar to a
regular library, equipment could be checked out,
and after the project is completed, returned to
the library. As the first step, information about all
of the instruments at the NIH should be
deposited into the library, so that researchers
can know if a particular instrument is available
on campus. This database would also provide
fellows with access to an expert on the
instrument should they have any questions.
Creating this list should be easy given that all of
the expensive instruments on campus have a
decal number.
There would be many benefits to
establishing an NIH Equipment/Instrument
Library. Such a system would allow easy tracking
of how frequently instruments are used. Creating
such a library would also clear out more
laboratory space, as individual labs can store the
unused equipment in the library and locate it
later on if needed. This is in contrast to the
current surplus program, where you cannot get
an instrument back after it is surplused. The NIH
Equipment/Instrument Library could save the NIH
a lot of money, which might be used on other
projects or to compensate fellows better.
In the mean time, what a fellow can do
when he or she needs equipment but doesn’t
want to purchase it? (1) One can send out an
email to the many NIDDK fellows email lists,
which are unfortunately not easily combined. (2)
One can make a phone call to the manufacturer
and ask for a sales representative who can tell
you if a group on campus purchased the
instrument. (3) One can find a company that can
help analyze samples for you.
If you have other options, please contact
me and I might include it in a future issue of our
newsletter.
APRIL 2015VOLUME 8, ISSUE 2
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THE iNFORMER
A Syringe Full of Trust
In 2014, the United States saw a significant
increase in measles infections according to the
Centers for Disease Control and Prevention (644).
For comparison, in the last 12 years there were
never more than 250 confirmed cases per year and
as of this writing there are 173 confirmed cases in
2015 [1]. This is both alarming and confusing
because measles was declared eliminated in the
United States in 2001. Refusing to vaccinate has
allowed this highly contagious virus to gain a
foothold in the United States once again. Even
worse, vaccine refusal rates continue to rise
despite overwhelming evidence for the safety and
efficacy of the measles, mumps, and rubella
(MMR) vaccine [2-4].
The measles virus belongs to the family
Paramyxoviridae, which contains single-stranded
RNA viruses. Measles is highly contagious and is
spread via aerosolized droplets from sneezing or
coughing. Just to highlight the highly contagious
nature, it is estimated that 9 out of 10 people living
together will contract the virus from a single
infected individual [5]. Symptoms typically include
fever, cough, runny nose, and several days later, a
flat red rash. The majority of complications arise in
children as secondary infections such as
pneumonia can occur in about 1 out of 20 cases
[5]. The measles vaccine has led to a 75 percent
decrease in in deaths from measles since 2001 [5].
So the question is why is there a refusal to
vaccinate against this highly contagious virus? As it
turns out there is no correct answer, but let us
attempt to understand the various reasons and
what can be done to gain the publics trust in
vaccines.
Victims of our own success
As illustrated above, the measles vaccine
is highly effective in preventing the spread of the
virus and for several years the total number of
cases in the United States never exceeded 100. A
successful vaccine campaign has made this
disease very rare and consequently many
Americans no longer perceive it as a threat.
However, outside the United States the disease is
still highly prevalent and was responsible for
approximately 145,700 deaths worldwide in 2013
[6]. This is sad news considering the preventable
nature of this disease and provides a compelling
picture of what can happen in the absence of the
vaccine.
Unfortunately, the nation received a wake-
up call when an outbreak occurred at a Disney
theme park late last year. According to the CDC,
among the 110 California patients about half were
confirmed to be unvaccinated [7]. The virus has
spread to several states and now many foreign
countries are dealing with similar outbreaks. Sadly
an 18-month child has now died in Germany as a
result of a measles outbreak. It is important for
Americans to realize that this is a very real threat
across the globe as Europe alone noted 32,818
cases in 2013 [8]. With international travel now
commonplace the massive distance is no longer a
protective barrier against this highly contagious
virus.
Preying on fears
Without a doubt, one of the most common
reasons for vaccine refusal is a concern that
vaccines will harm the child. These concerns also
tend to cluster in small areas of like-minded
individuals and create hotspots for a potential
outbreak. These worries can lead to outright
refusal, delayed vaccination, or selective
inoculation with certain vaccines that are deemed
safe by the individual. This refusal is strongly
associated with fear and emotion, which can cloud
logical and rational thinking. This has been
documented by several experts and has been
coined as “probability neglect” [9]. American legal
scholar Cass R. Sunstein explains it as an
outcome that is so terrifying that one will equate
the level of terror with the likelihood that it will
occur.
Unfortunately, a single scare can cause
lasting terror. In 1998, Andrew Wakefield published
a paper linking autism and inflammatory bowel
disease to the MMR vaccine. It was quickly
discovered that Wakefied falsified the data and
was setting up an elaborate scheme to profit from
new medical tests and subsequent litigation [10].
However several years following this false report,
vaccine rates in England and Wales fell
dramatically [11]. Unfortunately, anti-vaccine
advocates continue to keep this myth alive and
attempt to link autism to other vaccines as a grand
governmental conspiracy.
APRIL 2015VOLUME 8, ISSUE 2
Page 10
THE iNFORMER
In addition, many question the vaccine
components, claiming that they contain toxic levels
of chemicals such as aluminum and formaldehyde.
The truth is that vaccines undergo
extensive and continuous surveillance by the CDC.
The Vaccine Safety Datalink collects and organizes
data from nine U.S. health care institutions
encompassing over 9 million individuals. The VSD
can rapidly monitor vaccine associated adverse
events and the system can be updated weekly. In
fact, the VSD was instrumental in identifying real
adverse events such as the 197 children in a
cohort of 1.8 million that developed
thrombocytopenic purpura after receiving the MMR
vaccine [12].
Despite this strong oversight and safety
protocols, fear continues to motivate the anti-
vaccine movement. Politics have now entered the
arena and further complicate the issues. Recently,
statements from Sen. Rand Paul (R-KY) and Gov.
Chris Christie both suggested that individuals and
parents “should have some measure of choice”
when it comes to vaccinations. Even the ongoing
debate to make vaccines mandatory has grown
ugly, with the anti-vaccine movement calling such
measures a violation of basic human rights. On the
other hand, many public figures have taken to the
airwaves to persuade the public to get vaccinated,
including a hilarious but convincing monologue by
talk show host Jimmy Kimmel. As health experts
we need keep the public focused solely on the
facts about vaccination.
Let’s just talk…
In a perfect world, health officials could
effectively address worries while preserving public
trust. Unfortunately, this is a difficult balancing act
and controversy continues to linger. One of the
hardest things to do is to effectively communicate
uncertainty. Meteorologists deal with this everyday
and the solution they have come up with is called
the “wet bias.” Nobody gets angry when
meteorologists predict rain and it turns out to be a
sunny day, but people go crazy if it rains when it
was not predicted. Unfortunately, in medicine you
cannot continually overstate the risk of adverse
events because this can cause more harm than
good.
There are always inherent risks involved in
medicine, whether it is a delicate surgical
procedure or simply prescribing a drug. It is vital to
build trust around the issue of vaccines by candidly
discussing the real risks alongside the dangers of
the disease. But is also important to empathize and
listen to the parents’ concerns. Much of this debate
has caused scientists and health care experts to go
on the defensive, which can widen the gap even
further. We need thoughtful, rational conversations
– not angry yelling matches. A good example is the
Vax Northwest partnership with the University of
Washington, which is recruiting parents to act as
peer-educators to increase vaccine adoption within
the state. The goals for this program are to support
health care providers and develop relationships
focused on productive conversations with hesitant
parents.
It may be impossible to convince everyone
that vaccines are necessary and safe. But we need
to approach hesitant individuals without anger or
judgment. After all, scientists are trained to be
skeptical and critical even in the face of compelling
data. So perhaps we should have patience with
individuals that are exercising critical and skeptical
thinking. Trust is not built rapidly. We must be
diligent in delivering the facts either good or bad
while maintaining respect, and avoiding being
pulled into the controversy.
References
1. Centers for Disease Control. Measles Cases and
Outbreaks: January 1 to March 13, 2015.
2. Smith M and Woods C, Pediatrics. 2010; 125(6):
1134-41
3. DeStefano F, Price CS, Weintraub ES. Journal of
Pediatrics. 2013
4. Klein N, et al., Pediatrics. 2011; 129(5): 809-14
5. Centers for Disease Control. The Pink Book:
Course Textbook. May 2012.
6. World Health Organization. Measles Factsheet
No. 286. February 2015.
7. Zipprich, et al., MMWR. 2015
8. World Health Organization. WHO Epidata. 16
December 2014.
9. Sunstein, C. (2002). “Probability Neglect:
Emotions, Worst Cases, and Law,” Yale Law
Journal 112, 61-107.
10. Godlee F, Smith J, Marcovitch H: Wakefield's
article linking MMR vaccine and autism was
fraudulent. BMJ 2011, 342:c7452.
11. World Health Organization. Immune
surveillance, assessment and monitoring. 2014
12. O'Leary ST, Glanz JM, McClure DL, Akhtar A,
Daley MF, Nakasato C, Baxter R, Davis RL,
Izurieta HS, Lieu TA, et al.: The risk of immune
thrombocytopenic purpura after vaccination in
children and adolescents. Pediatrics 2012,
129:248-255.
APRIL 2015VOLUME 8, ISSUE 2
Page 11
THE iNFORMER
Adler-Wailes DC, Alberobello AT, Ma X, Hugendubler L, Stern EA, Mou Z, Han
JC, Kim PW, Sumner AE, Yanovski JA, and Mueller E. Analysis of variants and
mutations in the human winged helix FOXA3 gene and associations with
metabolic traits. Int J Obes (Lond). 2015 Feb 12. doi: 10.1038/ijo.2015.17. [Epub
ahead of print]
Francis TC, Chandra R, Friend DM, Finkel E, Dayrit G, Miranda J, Brooks JM,
Iñiguez SD, O'Donnell P, Kravitz A, and Lobo MK. Nucleus accumbens medium
spiny neuron subtypes mediate depression-related outcomes to social defeat
stress. Biol Psychiatry. 2015 Feb 1. 77(3): 212-22. doi:
10.1016/j.biopsych.2014.07.021
Huang CJ, Kraft C, Moy N, Ng L, and Forrest D. A novel population of inner
cortical cells in the adrenal gland that displays sexually dimorphic expression of
thyroid hormone receptor β1. Endocrinology. 2015 Mar 12. doi:
http://dx.doi.org/10.1210/en.2015-1118 [Epub ahead of print]
Kravitz AV, Tomasi D, LeBlanc KH, Baler R, Volkow ND, Bonci A, and Ferre S.
Cortico-striatal circuits: Novel therapeutic targets for substance use disorders.
Brain Res. 2015 April 8. doi: 10.1016/j.brainres.2015.03.048. [Epub ahead of
print]
Ma X, Xu L, and Mueller E. Calorie hoarding and thrifting: Foxa3 finds a way.
Adipocyte (2015, In press)
APRIL 2015VOLUME 8, ISSUE 2
Page 12
THE iNFORMER
Welcome New Fellows
Fabian Bolte Alberto Cecoon Dahong Chen
Visiting Fellow, Germany Visiting Fellow, Italy Visiting Fellow, China
PhD, University of
Muenster
PhD, University of Verona
PhD, University of
Oklahoma
Liver Diseases Branch
(Rehermann) Bldg 10
Laboratory of Chemical
Physics (Clore) Bldg 5
Laboratory of Cellular and
Developmental Biology
(Lei) Bldg 50
Sucharitha Iyer Muthukumar Kannan Shailesh Kumar
IRTA Visiting Fellow, India Visiting Fellow, India
PhD, Thomas Jefferson
University, PA
PhD
PhD, Institute of Microbial
Technology, Chandigarh
Metabolic Disease
Branch (Agarwal) Bldg 10
Laboratory of Cellular and
Molecular Biology (Prinz)
Bldg 8
Laboratory of
Biochemistry and
Genetics (Maisson) Bldg
8
APRIL 2015VOLUME 8, ISSUE 2
Page 13
THE iNFORMER
Welcome New Fellows
Virginia Meyer Marisa Rubio Mrinmoy Saha
IRTA IRTA Visiting Fellow, India
PhD, University of Denver PhD, Yale University
PhD, Oregon State
University
Laboratory of Chemical
Physics (Clore) Bldg 5
Laboratory of Cellular and
Molecular Branch, Bldg 8
(Hinshaw)
Laboratory of Bioorganic
Chemistry, Bldg 8 (Appella)
Birong Shen Pengfei Tian
Visiting Fellow, China Visiting Fellow, China
PhD, Peking University
PhD, University of
Copenhagen
Laboratory of Cellular and
Molecular Biology (Furano)
Bldg 8
Labor Laboratory of
Chemical Physics (Best)
Bldg 5
Not Pictured:
Adrienne Greenough
IRTA
PhD, Duke University
Genetics of
Development and
Disease Branch (Proia)
Bldg 10

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K Bobyk - %22A Primer on Personalized Medicine - The Imminent Systemic Shift%22 in The iNFORMER vol8 issue2 p3

  • 1. We are the future of science, shouldn’t you be iNFORMED? DDK Home Archives Fellowship Office FAB Links Contacts THE iNFORMER FELLOWS NEWSLETTER NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES The views and opinions of authors expressed in this newsletter do not necessarily state or reflect those of NIDDK or the U.S. Government, and they may not be used for advertising or product endorsement purposes. VOLUME 8, ISSUE 2 – APRIL 2015 In this issue • Free Smartphone Apps to Help With Your Day-to-Day Work • A Primer on Personalized Medicine: The Imminent Systemic Shift • The Science and Policy of Marijuana • A Hypothetical NIH Equipment/ Instrument Library • A Syringe Full of Trust • Recent Publications by NIDDK Fellows • New Fellows EDiTORS ~•~ Kavya Devarakonda kavya.devarakonda@nih.gov Christine Krieger christine.krieger@nih.gov Joseph Tiano joseph.tiano@nih.gov The iNFORMER is published by the Fellows Advisory Board (FAB) in collaboration with the NIDDK Fellowship Office 10th Annual NIDDK Scientific Conference April 20-21, 2015 9:00 AM – 5:00 PM Natcher Conference Center, Building 45 Compete for one of the seven travel awards Have lunch with a keynote speaker Join the networking lunch with career panelists This year’s event will feature three keynote speakers: Dr. Charles Rice, Rockefeller University Dr. Tom Muir, Princeton University Dr. Thomas Boyer, University of Arizona A schedule of events is included at the end of the newsletter. All NIDDK fellows and scientific staff are encouraged to attend. Announcements
  • 2. APRIL 2015VOLUME 8, ISSUE 2 Page 2 THE iNFORMER Free Smartphone Apps to Help With Your Day-to-Day Work Way back in 2012, Manhattan Research conducted a survey on physician usage of apps. Based on that survey, clinicians were identified as first adopters of mobile devices and the medical apps that run on them. As app users, physicians tend to download fewer apps than the average consumer, but they tend to use those apps more often. Back then, iPads began to be used by physicians a lot. Today, smartphones are the go-to for information. The value of smartphone apps is catching on in medicine. iPhone and Android smartphone platforms have created a market in medical applications because they can run more complex medical apps at point-of-care than the older text-based apps used on personal digital assistants (PDAs). Here is a look at some free smartphone apps that may help you in your day-to-day work. All iPhone and Android apps can be downloaded from iTunes and Google Play. Dropbox (iOS, Android) A cloud-based app allows you to store, access, and share medical literature, project work, and other information. Prognosis (iOS) This app is designed for physicians and is a fun game that presents an engaging series of clinical case scenarios that assess the decision making skills of the player. Doctor's Dilemma® (iOS) You can test your knowledge in a variety of disciplines. Doctor's Dilemma is simple to play (earn points with correct answers, lose them with incorrect answers), but the questions will challenge you. Calculate by QxMD (iOS, Android) This tool offers the ability to search for easy-to-use calculators by specialty. MedPage Today; Medscape (iOS, Android) These apps gives you access to breaking medical news and includes CMEs. PubMed on Tap (iOS) Search PubMed and PubMed Central while on the go. Evernote (iOS, Android) An app that allows you to take notes, capture photos, create ‘to-do’ lists, and record voice reminders that are accessible across all the devices you use. Cloud Storage and File Sharing Games Medical News Medical Articles Note-Taking and Organization Medical Calculator
  • 3. APRIL 2015VOLUME 8, ISSUE 2 Page 3 THE iNFORMER A Primer on Personalized Medicine: The Imminent Systemic Shift Imagine a hypothetical scenario from a not- so-distant future: You get sick. Prior to this, you have been disappointed with how slowly your physician adopts new technologies. Therefore, you decide to find a new physician. At the new clinic, an administrator asks if you brought your electronic genome (e-genome) with you. You answer that you have not had a chance to get your genome sequenced yet, but you would like to do so. At that point in time, you begin a set of routine procedures. Enough of a biological sample is collected for the sequencing of your entire genome via a simple cheek swab or a finger prick test. Then, while you are having a medical examination with your new physician, your genome gets sequenced by the “lab on a chip” portable equipment and the data are electronically fed into the physician’s iPad. Your physician punches in some additional phenotypic characteristics into an app to help her determine whether your genotype is homozygous or heterozygous for the gene(s) known to be metabolically linked to the sickness you are experiencing. Then, minutes later, your physician picks a drug “z” over “x” or “y,” which has the highest chances of addressing your sickness with the lowest likelihood of side effects, given your unique set of genomic and phenotypic characteristics. Though a captivating and exciting glimpse of a possible future, the personalized medicine scenario above is certainly oversimplified, and its detailed script is still being written. Before such medical practices can become a widely accepted reality, not only applicable to a narrow group of specific genetic disorders, some major changes to the current status quo need to happen. Firstly, the research efforts of several players in the health and science ecosystem must be refocused. According to Charles R. Scriver, a key player in the Human Genome Project (HGP), “Since genomes speak biochemistry, not phenotype, for genomics to penetrate medicine, biochemistry and biology must be allies.” [1] Analogous to the HGP and its goal of sequencing and mapping a complete set of genes for humans, the Human Phenome Project (HPP) aims to elucidate the phenome, a complete phenotypic characterization of human species. More specifically, the goal of the HPP is to determine in practical terms what exactly a phenotype is and to assemble all of the phenotypic components, including morphologic, biochemical, physiological, and even behavioral characteristics of the human species into a complete set. Even though the HPP idea is now at least 12 years old, this project is so complex that as of 2012, scientists across have the world are still “getting ready for the HPP” [2]. A lot more scientific work will have to be completed before the HPP can be started. The good news is important developments have already started. In 2006, after the completion of the HGP, a new global effort, the Human Variome Project (HVP), was launched to share information about genetic variation in clinical practice. According to Casimiro Vizzini, an expert at the International Basic Sciences Programme of the United Nations Education, Scientific and Cultural Organization, “The term variome refers to the sum of all the genetic variations found in different populations of the same species.” [3] As a global organization, the HVP has been working to develop and maintain standards, systems and infrastructure to enable sharing of information on genetic variation generated during diagnostic and predictive testing as part of routine clinical practices. The ultimate goal is to link genetic variation to the patient body and disease development phenotypes to help doctors with diagnosis and drug selection for effective treatments. Another change that must occur is that personnel and organizations within the health care ecosystem will have to figure out, re-align and sometimes even shift their roles completely per the requirements coming from future personalized medicine mandates. Large players have already realized that the personalized medicine future is fast approaching and have decided to start changing.
  • 4. APRIL 2015VOLUME 8, ISSUE 2 Page 4 THE iNFORMER In his 2015 State of the Union Address, President Obama announced the launch of the new Precision Medicine Initiative, which was promptly followed by a press release from the White House unveiling details. The National Institutes of Health (NIH), the Food and Drug Administration (FDA), and the Office of the National Coordinator for Health Information Technology (ONC) will together receive a $215 million investment in 2016 to start executing this initiative. Main objectives of the initiative are:  Creation of a voluntary national patient- powered research cohort of at least 1 million Americans in order to involve and encourage patients to contribute their medical records and data on gene profiles, metabolites, body microorganisms, environmental and lifestyle data, personal device and sensor data — all with under rigorous protection of patients’ privacy  Discovery acceleration of effective and tailored treatments for cancer via expanding genetically based clinical cancer trials, elucidating fundamental aspects of cancer biology and establishing a national “cancer knowledge network” to identify genomic drivers in cancer  Ensuring patients’ health data privacy and security within the precision medicine model  Modernization of the regulatory landscape to adequately support the new precision medicine innovation, research and health care model via development of high quality curated databases and interoperability standards to enable secure exchange of data across systems. These objectives will be achieved via the establishment of public-private partnerships with the private sector, existing research cohorts and patient groups, in order to develop the required precision medicine infrastructure and frameworks, and provide consumers with secure access to their own health data as well as to the applications and services that can analyze it. Only days after the president’s State of the Union Address, the House Energy and Commerce Committee released a nearly 400-page discussion document of the 21st Century Cures Act. Briefly, the core ideas of this legislative initiative are:  Putting patients first, by creating a regulatory environment that is conducive to incorporating their perspectives and addressing their unmet medical needs, including biomarker quantification, antibiotic, drug and dormant therapies development, and innovative device review pathways  Building the foundation for 21st century medicine, including the creation of the next generation of patient-centered solutions, stimulating innovation in health information technologies and helping young scientists have successful careers  Modernizing and streamlining clinical trials to allow broader utilization of flexible and more cost efficient trial designs, while reducing regulatory overlap and administrative burden to cut costs and speed up the assessment of new treatments  Accelerating and supporting the innovation cycle at federal public health agencies, including NIH  Modernizing medical product and device regulation by taking into account novel manufacturing technologies All interested stakeholders have been encouraged to participate in the discourse on how to improve this legislation. In turn, miscellaneous players such as biopharmaceutical companies, patients groups, health insurers, pharmacy benefit managers, physicians, and scientists have actively started figure out whether they are poised to gain or lose from these initiatives. Some interest groups and foundations have started information campaigns to sway the legislators and the general public, and are prompting constituents to act and shape the future of personalized medicine in the United States. One example is the EveryLife Foundation for Rare Diseases, which, in partnership with Rare Disease Legislative Advocates and with a sponsorship from almost 30 large pharmaceutical and smaller biotechnology companies, led a Rare Disease Week, a legislative conference on Capitol Hill last February.
  • 5. APRIL 2015VOLUME 8, ISSUE 2 Page 5 THE iNFORMER The conference provided an overview of the 21st Century Cures Initiative, lobbied the members of congress and gave a detailed training on being an effective advocate, including ways of using modern social media platforms such as Facebook and Twitter. Constituents were asked to help ensure the 21st Century Cures legislation improves access to experimental drugs for patients with rare diseases. Other suggestions for constituent advocates were to encourage support for the development of lifesaving therapies deemed not profitable by drug companies and investment in medical innovation for diseases that have few or no treatment options. The NIH, as one of the largest players within both the science and health care ecosystems in the United States, will be directly affected by this imminent systemic shift. It is likely the NIH will not only execute the initiatives but also actively participate in influencing the public discourse on both personalized medicine initiatives. The NIH has already started to showcase information about the precision medicine initiative on its websites, and in the beginning of February, held a workshop on Building a Precision Medicine Research Cohort, which is one of the main objectives of the president’s initiative. The workshop gathered leading experts in health care, mobile health, patient advocacy, genomics, epidemiology, privacy, computer science and information technology to identify the challenges and explore the opportunities associated with building such a cohort of patients. Additionally, on March 30 the NIH announced the formation of team of experts in precision medicine and large clinical studies to chart the course for the initiative and to define, with input from all interested stakeholders within ecosystem, the vision for building the national participant group and to formulate what will be considered “success” 5 and 10 years after the launch of the initiative. A preliminary report from the team of experts is expected in September 2015. Overall, the advent of personalized medicine practices in the United States will be a fascinating story to watch as it develops in years to come. In the future, humans may be getting their e- genomes assembled at birth, like they are currently getting their vitamin K shots. Then, e-genomes may be compared to the standardized human “default genome” template to determine the individual’s e-variome. By adulthood, all of the unique phenotypic characteristics, including environment influences and lifestyle risk factors an individual has experienced, may be added and integrated with the e-genome/e-variome data stored on the cloud to produce a data set that is unique for that person. Let us conditionally call this data set the “e- OME.” So, in the hypothetical scenario about a visit to a new physician, you would only have to walk into a clinic with a password to grant your doctor access to download your private e-OME data set into her iPad. Your doctor would then run some sophisticated algorithms via an app to connect to the “holy grail” of personalized medicine — the global medical bioinformatics database. Her goal would be to determine how well your e-OME interfaces with the current list of all known disease phenotypes previously determined for your ethnic subgroup with a specific intent to probe for the specific disease she suspects based on your clinical symptoms. Then, your doctor will evaluate the side effects of all known drugs against that particular disease in the cohort of patients having the closest cumulative e-OME to yours. In the end, a selection of the drug tailored “specifically for you” will be made and a prescription written. Oh, what a wonderful future lies ahead of us! Meanwhile, there is a plenty of work to do for scientists around the nation. References 1. Scriver CR. “Translating knowledge into practice in the "post-genome" era.” Acta Paediatr. 2004 Mar;93(3):294-300. 2. Oetting WS et al. “Getting ready for the Human Phenome Project: The 2012 forum of the Human Variome Project.” Hum Mutat. 2013 Apr;34(4):661-6. 3. Casimiro Vizzini. “The Human Variome Project: Global Coordination in Data Sharing,” Science & Diplomacy. 2015 Mar;4(1):1-8. A quarterly publication from the AAAS Center for Science Diplomacy.
  • 6. APRIL 2015VOLUME 8, ISSUE 2 Page 6 THE iNFORMER The Science and Policy of Marijuana The increased discussion of marijuana in the news lately has been hard to ignore. Four states (Washington, Oregon, Alaska, Colorado), and now the nation’s capital, have completely legalized the drug, whereas several other states may be moving in that direction through decriminalization and/or the addition of laws legalizing medicinal use [1]. Although marijuana laws have significantly changed in the last few years, several questions remain. How are state and federal agencies coordinating the differences in federal and state laws? How are science and policy influencing each other to govern marijuana laws now and in the future? Medicinal marijuana and drug classification To date marijuana is classified as a schedule I drug. According to the Controlled Substance Act (CSA) and the Drug Enforcement Administration (DEA), this classification is assigned to drugs that currently do not have accepted medial uses, and pose a high potential for abuse as well as physical dependence. Other drugs that fall into this category include heroin, LSD, ecstasy, methanqualone, and peyote [2]. The classification of marijuana as a schedule I drug may seem at odds with the growing discussion about “medicinal marijuana”; however marijuana remains a schedule I drug because the U.S. Food and Drug Administration (FDA) have approved neither the unprocessed plant nor plant extracts as medicine. Although marijuana as a whole is not yet approved for medicinal purposes, the cannabinoids found in marijuana have led to the development of two FDA-approved medications. One of the approved cannabinoids, delta-9-tetrahydrocannabinol (THC), has been shown to stimulate appetite and reduce nausea. The second cannabinoid, cannabidiol (CBD), may be effective for decreasing pain, inflammation, controlling seizures, and possibly for treating psychosis and addiction [3]. Current cannabinoid-based drugs in clinical trials or approved by the FDA for medical use:  Dronabinol (Marinol®) contains THC and is used to treat nausea caused by chemotherapy and extreme weight loss resulting from AIDS.  Nabilone (Cesamet®) contains a synthetic cannabinoid similar to THC and is used for the same purposes as described above  Sativex®, contains approximately equal parts THC and CBD, is currently approved in the United Kingdom and other European countries to treat spasticity caused by multiple sclerosis (MS), and is currently in Phase III clinical trials in the United States to establish its effectiveness and safety in treating cancer pain.  Epidiolex™ is a CBD-based drug recently created to treat certain forms of childhood epilepsy. Epidiolex has not been approved by the FDA yet as it still has to undergo clinical trials for safety and efficacy. What is the state versus federal perspective? As mentioned above, at the federal level marijuana remains a schedule I drug and therefore the possession of the drug is illegal. In order to help define the role that federal and state law enforcement agencies play in the regulation of marijuana laws in each state, James M. Cole, the deputy attorney general, released the Cole Memo in August 2013. This memo instructed U.S. Department of Justice attorneys and law enforcement to focus on eight priorities in enforcing the CSA against marijuana conduct. Issues not pointed out in the memo were to remain under the states’ jurisdiction. These eight points in which federal agencies should regulate marijuana-related issues include [4]:  Preventing the distribution of marijuana to minors  Preventing revenue from the sale of marijuana from going to criminal enterprises, gangs, and cartels  Preventing the diversion of marijuana from states where it is legal under state law in some form to other states
  • 7. APRIL 2015VOLUME 8, ISSUE 2 Page 7 THE iNFORMER  Preventing violence and the use of firearms in the cultivation and distribution of marijuana  Preventing drugged driving and the exacerbation of other adverse public health consequences associated with marijuana use  Preventing the growing of marijuana on public lands and the attendant public safety and environmental dangers posed by marijuana production on public lands  Preventing marijuana possession or use on federal property More recently, a bipartisan group of senators introduced a marijuana reform bill on March 10 (S.683). The bill is sponsored by Rand Paul (R-KY), Cory Booker (R-NJ) and Kirsten Gillibrand (D-NY) and aims to make it easier for states to allow medicinal marijuana. Measures in the bill include (1) downgrading marijuana from a schedule I drug to a schedule II drug, (2) loosening restrictions on the transportation of marijuana between states, (3) allowing banks to provide services to marijuana businesses, (4) encouraging the National Institute on Drug Abuse (NIDA) to broaden access of marijuana for research, and (5) allowing doctors with the Department of Veteran’s Affairs to recommend marijuana in states that already allow it [1]. What are the current concerns regarding marijuana legalization? To date, little research has been conducted to examine the health and safety of marijuana. Because of the increased acceptance of marijuana use and the push for legalization, a greater emphasis has been placed on understanding the science behind marijuana addiction liability, effects of long-term use, and the effects of marijuana on the developing brain, among other issues. A complete list of studies supported by NIDA examining the health and safety of marijuana can be found on their website [5]. In addition to concerns regarding the impact of marijuana on health, other concerns arise in regards to the presence of marijuana in society. For example, what is the most appropriate test for determining if a vehicle driver is under the influence of marijuana? What is a reasonable limit for drivers of vehicles? How should the concentration of marijuana in edible products be regulated, and what should be the limits? Research investigating the most accurate detection methods for marijuana in the body, reasonable limits levels of marijuana in the body that do not impair one’s ability to operate a vehicle, and drug metabolism could all provide insight into policy regarding these questions. How might science inform marijuana policy in the future? One way in which NIDA plans on contributing to the understanding of the health risks and benefits of marijuana use is though the funding of a longitudinal study that will track a large sample of young Americans from late childhood, prior to first exposure to drugs, to early adulthood. Neuroimaging of these individuals is proposed to help clarify how and to what extent drugs of abuse, including marijuana, affect adolescent brain development. However, much more must be accomplished to fully comprehend the health and safety issues resulting from widespread marijuana legalization. Whether smoking or consuming marijuana has therapeutic benefits that outweigh its health risks is still an open question that science has not yet reconciled. Additionally, the ability to isolate plant extracts and/or develop synthetic drugs may completely eliminate the need for legalization of the marijuana plant. Regardless, as science involving marijuana health and safety continues to advance, laws regarding medicinal marijuana and other marijuana-derived compounds will continue to evolve. It will be crucial these scientific developments guide policy laws regarding marijuana use in the future. References 1. Ingraham, Christopher. “The senate marijuana reform bill would bring federal policy in line with medical research.” The Washington Post. 10 March 2015. 2. “Drug Scheduling.” Drug Enforcement Agency. 2012. 3. “Drug Facts: Is Marijuana Medicine?” National Institute on Drug Abuse. December 2014. 4. Cole, James M. “Memorandum for all United States attorneys.” U.S. Department of Justice. 14 February 2014. 5. “NIDA research on the therapeutic benefits of cannabis and cannabinoids.” National Institute on Drug Abuse. March 2014.
  • 8. APRIL 2015VOLUME 8, ISSUE 2 Page 8 THE iNFORMER A Hypothetical NIH Equipment/Instrument Library When it comes to the issues a postdoctoral fellow might care about, I believe each one would be able to list a few right away. Aside from landing a permanent position, and enjoying work and life, getting a nice publication is surely on the top of most fellows’ wish lists. Just as Galileo’s telescope launched modern astronomy, employing a novel method in research typically leads to a nice paper in a relatively short period of time. Unless one develops a new technology by him- or herself, most of the time new technology requires acquiring a new instrument. Life science instruments are usually very expensive, particularly the new ones – they often cost much more than our annual salary/stipend. It is also worth noting that instruments are often only used for a brief period of time before they are relegated to a corner to collect dust. This is not uncommon given the nature of scientific projects: After a paper is out the whole project might be closed. Therefore, sharing instrument and equipment is a good option. It can save funds for the institute, and save researchers the trouble and time of purchasing a new instrument. Core facilities are a great example of the benefits of sharing expensive instruments. However, at some point, we inevitably encounter a situation where a piece of equipment is unavailable. If you are lucky, you might find that the instrument you want is in the laboratory next door. More than often, you are not that lucky, and you have to persuade your advisor to agree to purchase it. This follows writing an equipment application without a guarantee that it will be approved. Then, if it is approved, the instrument arrives at your door a few months later, at which point, you might not need it anymore because you have already taken a painful alternative method to answer your question or you have simply moved on to another seemingly more promising project. So, what can be done to solve some of these problems, and make fellows’ lives less miserable? One way is to establish a NIH Equipment/Instrument Library. Similar to a regular library, equipment could be checked out, and after the project is completed, returned to the library. As the first step, information about all of the instruments at the NIH should be deposited into the library, so that researchers can know if a particular instrument is available on campus. This database would also provide fellows with access to an expert on the instrument should they have any questions. Creating this list should be easy given that all of the expensive instruments on campus have a decal number. There would be many benefits to establishing an NIH Equipment/Instrument Library. Such a system would allow easy tracking of how frequently instruments are used. Creating such a library would also clear out more laboratory space, as individual labs can store the unused equipment in the library and locate it later on if needed. This is in contrast to the current surplus program, where you cannot get an instrument back after it is surplused. The NIH Equipment/Instrument Library could save the NIH a lot of money, which might be used on other projects or to compensate fellows better. In the mean time, what a fellow can do when he or she needs equipment but doesn’t want to purchase it? (1) One can send out an email to the many NIDDK fellows email lists, which are unfortunately not easily combined. (2) One can make a phone call to the manufacturer and ask for a sales representative who can tell you if a group on campus purchased the instrument. (3) One can find a company that can help analyze samples for you. If you have other options, please contact me and I might include it in a future issue of our newsletter.
  • 9. APRIL 2015VOLUME 8, ISSUE 2 Page 9 THE iNFORMER A Syringe Full of Trust In 2014, the United States saw a significant increase in measles infections according to the Centers for Disease Control and Prevention (644). For comparison, in the last 12 years there were never more than 250 confirmed cases per year and as of this writing there are 173 confirmed cases in 2015 [1]. This is both alarming and confusing because measles was declared eliminated in the United States in 2001. Refusing to vaccinate has allowed this highly contagious virus to gain a foothold in the United States once again. Even worse, vaccine refusal rates continue to rise despite overwhelming evidence for the safety and efficacy of the measles, mumps, and rubella (MMR) vaccine [2-4]. The measles virus belongs to the family Paramyxoviridae, which contains single-stranded RNA viruses. Measles is highly contagious and is spread via aerosolized droplets from sneezing or coughing. Just to highlight the highly contagious nature, it is estimated that 9 out of 10 people living together will contract the virus from a single infected individual [5]. Symptoms typically include fever, cough, runny nose, and several days later, a flat red rash. The majority of complications arise in children as secondary infections such as pneumonia can occur in about 1 out of 20 cases [5]. The measles vaccine has led to a 75 percent decrease in in deaths from measles since 2001 [5]. So the question is why is there a refusal to vaccinate against this highly contagious virus? As it turns out there is no correct answer, but let us attempt to understand the various reasons and what can be done to gain the publics trust in vaccines. Victims of our own success As illustrated above, the measles vaccine is highly effective in preventing the spread of the virus and for several years the total number of cases in the United States never exceeded 100. A successful vaccine campaign has made this disease very rare and consequently many Americans no longer perceive it as a threat. However, outside the United States the disease is still highly prevalent and was responsible for approximately 145,700 deaths worldwide in 2013 [6]. This is sad news considering the preventable nature of this disease and provides a compelling picture of what can happen in the absence of the vaccine. Unfortunately, the nation received a wake- up call when an outbreak occurred at a Disney theme park late last year. According to the CDC, among the 110 California patients about half were confirmed to be unvaccinated [7]. The virus has spread to several states and now many foreign countries are dealing with similar outbreaks. Sadly an 18-month child has now died in Germany as a result of a measles outbreak. It is important for Americans to realize that this is a very real threat across the globe as Europe alone noted 32,818 cases in 2013 [8]. With international travel now commonplace the massive distance is no longer a protective barrier against this highly contagious virus. Preying on fears Without a doubt, one of the most common reasons for vaccine refusal is a concern that vaccines will harm the child. These concerns also tend to cluster in small areas of like-minded individuals and create hotspots for a potential outbreak. These worries can lead to outright refusal, delayed vaccination, or selective inoculation with certain vaccines that are deemed safe by the individual. This refusal is strongly associated with fear and emotion, which can cloud logical and rational thinking. This has been documented by several experts and has been coined as “probability neglect” [9]. American legal scholar Cass R. Sunstein explains it as an outcome that is so terrifying that one will equate the level of terror with the likelihood that it will occur. Unfortunately, a single scare can cause lasting terror. In 1998, Andrew Wakefield published a paper linking autism and inflammatory bowel disease to the MMR vaccine. It was quickly discovered that Wakefied falsified the data and was setting up an elaborate scheme to profit from new medical tests and subsequent litigation [10]. However several years following this false report, vaccine rates in England and Wales fell dramatically [11]. Unfortunately, anti-vaccine advocates continue to keep this myth alive and attempt to link autism to other vaccines as a grand governmental conspiracy.
  • 10. APRIL 2015VOLUME 8, ISSUE 2 Page 10 THE iNFORMER In addition, many question the vaccine components, claiming that they contain toxic levels of chemicals such as aluminum and formaldehyde. The truth is that vaccines undergo extensive and continuous surveillance by the CDC. The Vaccine Safety Datalink collects and organizes data from nine U.S. health care institutions encompassing over 9 million individuals. The VSD can rapidly monitor vaccine associated adverse events and the system can be updated weekly. In fact, the VSD was instrumental in identifying real adverse events such as the 197 children in a cohort of 1.8 million that developed thrombocytopenic purpura after receiving the MMR vaccine [12]. Despite this strong oversight and safety protocols, fear continues to motivate the anti- vaccine movement. Politics have now entered the arena and further complicate the issues. Recently, statements from Sen. Rand Paul (R-KY) and Gov. Chris Christie both suggested that individuals and parents “should have some measure of choice” when it comes to vaccinations. Even the ongoing debate to make vaccines mandatory has grown ugly, with the anti-vaccine movement calling such measures a violation of basic human rights. On the other hand, many public figures have taken to the airwaves to persuade the public to get vaccinated, including a hilarious but convincing monologue by talk show host Jimmy Kimmel. As health experts we need keep the public focused solely on the facts about vaccination. Let’s just talk… In a perfect world, health officials could effectively address worries while preserving public trust. Unfortunately, this is a difficult balancing act and controversy continues to linger. One of the hardest things to do is to effectively communicate uncertainty. Meteorologists deal with this everyday and the solution they have come up with is called the “wet bias.” Nobody gets angry when meteorologists predict rain and it turns out to be a sunny day, but people go crazy if it rains when it was not predicted. Unfortunately, in medicine you cannot continually overstate the risk of adverse events because this can cause more harm than good. There are always inherent risks involved in medicine, whether it is a delicate surgical procedure or simply prescribing a drug. It is vital to build trust around the issue of vaccines by candidly discussing the real risks alongside the dangers of the disease. But is also important to empathize and listen to the parents’ concerns. Much of this debate has caused scientists and health care experts to go on the defensive, which can widen the gap even further. We need thoughtful, rational conversations – not angry yelling matches. A good example is the Vax Northwest partnership with the University of Washington, which is recruiting parents to act as peer-educators to increase vaccine adoption within the state. The goals for this program are to support health care providers and develop relationships focused on productive conversations with hesitant parents. It may be impossible to convince everyone that vaccines are necessary and safe. But we need to approach hesitant individuals without anger or judgment. After all, scientists are trained to be skeptical and critical even in the face of compelling data. So perhaps we should have patience with individuals that are exercising critical and skeptical thinking. Trust is not built rapidly. We must be diligent in delivering the facts either good or bad while maintaining respect, and avoiding being pulled into the controversy. References 1. Centers for Disease Control. Measles Cases and Outbreaks: January 1 to March 13, 2015. 2. Smith M and Woods C, Pediatrics. 2010; 125(6): 1134-41 3. DeStefano F, Price CS, Weintraub ES. Journal of Pediatrics. 2013 4. Klein N, et al., Pediatrics. 2011; 129(5): 809-14 5. Centers for Disease Control. The Pink Book: Course Textbook. May 2012. 6. World Health Organization. Measles Factsheet No. 286. February 2015. 7. Zipprich, et al., MMWR. 2015 8. World Health Organization. WHO Epidata. 16 December 2014. 9. Sunstein, C. (2002). “Probability Neglect: Emotions, Worst Cases, and Law,” Yale Law Journal 112, 61-107. 10. Godlee F, Smith J, Marcovitch H: Wakefield's article linking MMR vaccine and autism was fraudulent. BMJ 2011, 342:c7452. 11. World Health Organization. Immune surveillance, assessment and monitoring. 2014 12. O'Leary ST, Glanz JM, McClure DL, Akhtar A, Daley MF, Nakasato C, Baxter R, Davis RL, Izurieta HS, Lieu TA, et al.: The risk of immune thrombocytopenic purpura after vaccination in children and adolescents. Pediatrics 2012, 129:248-255.
  • 11. APRIL 2015VOLUME 8, ISSUE 2 Page 11 THE iNFORMER Adler-Wailes DC, Alberobello AT, Ma X, Hugendubler L, Stern EA, Mou Z, Han JC, Kim PW, Sumner AE, Yanovski JA, and Mueller E. Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits. Int J Obes (Lond). 2015 Feb 12. doi: 10.1038/ijo.2015.17. [Epub ahead of print] Francis TC, Chandra R, Friend DM, Finkel E, Dayrit G, Miranda J, Brooks JM, Iñiguez SD, O'Donnell P, Kravitz A, and Lobo MK. Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress. Biol Psychiatry. 2015 Feb 1. 77(3): 212-22. doi: 10.1016/j.biopsych.2014.07.021 Huang CJ, Kraft C, Moy N, Ng L, and Forrest D. A novel population of inner cortical cells in the adrenal gland that displays sexually dimorphic expression of thyroid hormone receptor β1. Endocrinology. 2015 Mar 12. doi: http://dx.doi.org/10.1210/en.2015-1118 [Epub ahead of print] Kravitz AV, Tomasi D, LeBlanc KH, Baler R, Volkow ND, Bonci A, and Ferre S. Cortico-striatal circuits: Novel therapeutic targets for substance use disorders. Brain Res. 2015 April 8. doi: 10.1016/j.brainres.2015.03.048. [Epub ahead of print] Ma X, Xu L, and Mueller E. Calorie hoarding and thrifting: Foxa3 finds a way. Adipocyte (2015, In press)
  • 12. APRIL 2015VOLUME 8, ISSUE 2 Page 12 THE iNFORMER Welcome New Fellows Fabian Bolte Alberto Cecoon Dahong Chen Visiting Fellow, Germany Visiting Fellow, Italy Visiting Fellow, China PhD, University of Muenster PhD, University of Verona PhD, University of Oklahoma Liver Diseases Branch (Rehermann) Bldg 10 Laboratory of Chemical Physics (Clore) Bldg 5 Laboratory of Cellular and Developmental Biology (Lei) Bldg 50 Sucharitha Iyer Muthukumar Kannan Shailesh Kumar IRTA Visiting Fellow, India Visiting Fellow, India PhD, Thomas Jefferson University, PA PhD PhD, Institute of Microbial Technology, Chandigarh Metabolic Disease Branch (Agarwal) Bldg 10 Laboratory of Cellular and Molecular Biology (Prinz) Bldg 8 Laboratory of Biochemistry and Genetics (Maisson) Bldg 8
  • 13. APRIL 2015VOLUME 8, ISSUE 2 Page 13 THE iNFORMER Welcome New Fellows Virginia Meyer Marisa Rubio Mrinmoy Saha IRTA IRTA Visiting Fellow, India PhD, University of Denver PhD, Yale University PhD, Oregon State University Laboratory of Chemical Physics (Clore) Bldg 5 Laboratory of Cellular and Molecular Branch, Bldg 8 (Hinshaw) Laboratory of Bioorganic Chemistry, Bldg 8 (Appella) Birong Shen Pengfei Tian Visiting Fellow, China Visiting Fellow, China PhD, Peking University PhD, University of Copenhagen Laboratory of Cellular and Molecular Biology (Furano) Bldg 8 Labor Laboratory of Chemical Physics (Best) Bldg 5 Not Pictured: Adrienne Greenough IRTA PhD, Duke University Genetics of Development and Disease Branch (Proia) Bldg 10