The RT Connection - United States Army€¦ · The RT Connection A Publication of the U.S. Army...

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.. R E S E A R C H & T E C H N O L O G Y E D G E W O O D C H E M IC A L B IO L O G IC A L C E N T E R R E S E A R C H & T E C H N O L O G Y .. The R&T Connection A Publication of the U.S. Army Edgewood Chemical Biological Center (ECBC) Research & Technology Directorate (R&T) Toxicology Issue - July 2017 Approved for public release; distribution unlimited. Also inside: Predictive Toxicology Methods Save Time and Money page 8 Leveraging intercontinental relationships to enhance Army readiness page 9 Project Spotlight: ECHO “Human-on-a-Chip” page 10 ECBC Researches Metabolic Carfentanil Reactions Conducting applied research on pharmaceutical drugs to examine human reactions and potential actions for revival

Transcript of The RT Connection - United States Army€¦ · The RT Connection A Publication of the U.S. Army...

Page 1: The RT Connection - United States Army€¦ · The RT Connection A Publication of the U.S. Army Edgewood Chemical Biological Center (ECBC) Research Technology Directorate (RT) Toxicology

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RESEARCH & TECHNOLOGY

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The R&T ConnectionA Publication of the U.S. Army Edgewood Chemical Biological Center (ECBC) Research & Technology Directorate (R&T)Toxicology Issue - July 2017

Approved for public release; distribution unlimited.

Also inside:

Predictive Toxicology Methods Save Time and Money page 8

Leveraging intercontinental relationships to enhance Army readiness page 9

Project Spotlight: ECHO “Human-on-a-Chip” page 10

ECBC Researches Metabolic Carfentanil ReactionsConducting applied research on pharmaceutical drugs to examine human reactions and potential actions for revival

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2 | The R&T Connection

ECBC Team,Agility is one of the key qualities of the R&T workforce. We are quick to fill new customer needs, adaptable to different requirements and conditions on the battlefield, and can make necessary transitions without missing a beat. The Directorate has undergone several transitions in the recent months:

I am the Acting Director of R&T while Dr. Eric Moore serves as Acting Director of ECBC.

Dr. Rick Cox is now the permanent Deputy Director of ECBC R&T.

Dr. Nicole Rosenzweig is the new Chief of the BioSciences Division.

Mr. Dave Caretti is the new Acting Division Chief of the CB Protection & Decontamination Division.

As new leaders grow into these roles permanently or temporarily, our commitment to the Soldier continues. In this issue of The R&T Connection, we focus on our robust toxicology programs. Toxicology, the study of the effects of poisonous substances on the environment and living organisms, is the backbone of chemical and biological agent research. This research allows us to work toward countermeasures which save the lives of warfighters and first responders. This issue is full of all things toxicology from our physical infrastructure to the great minds of those who work here. Our cover story examines our partnership with the National Institute on Drug Abuse. This partnership allows us the opportunity to research the effects of opioids in an effort to combat the rise in drug overdoses and its effect on our community. On page

3, read about how after 60 years in the business, Dr. Harry Salem is still shaping the future of science through his stem cell research efforts. On page 9, learn about how Dr. Terrence D’Onofrio is strengthening ECBC’s partnership with the United Kingdom through his detail at the Defence Science and Technology Laboratory in Porton Down, England.

Toxic substances threaten our way of life. Understanding how they affect us and our environment can give us the answers that allow us to act quickly in times of trouble and eliminate the threat.

I hope you enjoy this issue.

Have an item for the R&T Connection? Whether it’s a technical accomplishment, an upcoming speech, an employee award or any other news story, please share it with R&T Communications via Kelly Outram at [email protected] or 410.436.2262.

Disclaimer: The U.S. Army Edgewood Chemical Biological Center (ECBC) R&T Connection is an autho-rized publication for members of the Department of Defense (DoD). Contents of the R&T Connection are not necessarily the official views of, or endorsed by. the U.S. Government or the Department of the Army.

Editorial content of this publication is the responsibil-ity of the ECBC R&T Directorate.

References to commercial products or entities in this publication, including inserts and hyperlinks, does not constitute endorsements by the U.S. Army of the products or services offered.

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IN THIS ISSUE

Get Connected with ECBC

ContentsDirector’s Dialogue page 2

Profile: Dr. Harry Salem page 3

Program Allows U.S. Army Organizations to Partner with Minority-Serving Institution to Conduct DoD Research page 4

ECBC Researches Metabolic Carfentanil Reactions page 6

Levering Intercontinental Relationships for an Enhanced Stance of Army Readiness page 9

Predictive Toxicology Methods Reduce Time and Money page 8

Project Spotlight: ECHO “Human on a Chip” page 10

Extra Credit; High School Students Gain Real Experience at ECBC page 11

News Shorts, Publications and Patents page 12

Cover page picture: ECBC scientist Michael Feasel, Ph.D., examining vial of the analog carfentanil which is a synthetic opioid of fentanyl.

Do you have a story to share?

Special Edition Toxicology Issue Director’s Dialogue

Fred Berg, Ph.D.

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Toxicology Issue | 3

A native of Windsor, Ontario, Canada, Harry Salem, Ph.D., has had a career spanning more than 60 years in scientific research and educa-tion. Dr. Salem started his tenure at ECBC in 1984 investigating inha-lation toxicology. While here, a large portion of his work has focused on the effects of chemical agents on the human body.

Salem knew he wanted to work in the science world since he was a young boy. He was exposed to the world of medicine when his grandmother was diagnosed with tuberculosis.

“The closest thing to my heart is my lungs, and since I witnessed my grandmother go through the process of having a life altering disease, I made it my life’s work to study the human body,” Salem noted.

Salem earned a Bachelor of Arts in general sciences at the University of Western Ontario in 1950 and in 1953, earned a Bachelor of Sci-ence in pharmacy from the University of Michigan. Salem returned to Canada for his graduate studies in pharmacology at the Univer-sity of Toronto, where he earned a master’s degree in 1955 and a doctorate in 1958.

In 1989, Salem was awarded the Decoration for Meritorious Civilian Service for his contributions to the field of toxicology both nationally and internationally. He has served as Associate Professor of Phar-macology at the University of Pennsylvania, Adjunct Professor of Environmental Health at Temple University and Adjunct Professor of Chemical Toxicology at Drexel University. Salem also taught phar-macology and toxicology at the University of Toronto, University of Pennsylvania, Temple University, Drexel University, University of Maryland and Rutgers University.

In 1993, he advised then U.S. Attorney General Janet Reno during the siege in Waco, Texas. Salem was awarded the Society of Toxicology Congressional Science Fellowship in 2001 and spent a year on Capitol Hill as a Congressional Advisor. He worked in the office of U.S. Rep. Jim Greenwood, who was chairman of the House Energy and Com-merce Committee responsible for oversight and inspection of the Na-tional Institutes of Health and the Environmental Protection Agency.

As Salem grew his own career in science, he always made it a priority to mentor the next generation of scientists. One of those endeavors includes working on the steering committee to create the Science and Mathematics Academy (SMA) at Aberdeen High School. As de-picted above, Salem presented Aberdeen High School with a check, from former Maryland Governor Robert Ehrlich in September 2003. $958,000 of state funding was used to build Aberdeen High School’s 3rd floor, which is now the home of the SMA. The Academy has had the opportunity to revolutionize the manner in which science and mathematics are taught. ECBC has since partnered with Aberdeen High School and most recently worked with several interns from the Academy. (Learn more about what’s going on with ECBC and the SMA on page 11).

“Working with the next generation is something I find pride and hope in; they are the future of this world and it is very important to teach them there is no need to always reinvent the wheel,” Salem added.

Some of the notable projects Salem worked on throughout his ca-reer are permeable or soft contact lenses also known as Permal-ens, the development of the cold and cough remedy Nyquil, and the breathalyzer. Salem and several ECBC colleagues are currently working with Anthony Atala, M.D., director of the Wake Forest Insti-tute of Regenerative Medicine, on a project called Ex Vivo Console of Human Organoids (ECHO), better known as human-on-a-chip.

“I really think stem cells are the future of medicine and I am very hon-ored to be able to work with such distinguished colleagues on this project. If you love what you do, you never work a day in your life. I used to say my favorite career was always the next one, but I am happy here. Around here they joke with me and tell me I am losing money by working, but to me, it is worth it,” Salem recalled.

Salem currently resides near Philadelphia with his wife, and says he has no plans of slowing down from his momentous career. In his free time, he enjoys watching Jeopardy, and volunteering with his wife at Philadelphia area nursing homes.

ProfileHarry Salem, Ph.D.After 60 years in the business, Salem continues to stay on the forefront of science

Salem presents a check from the State of Maryland to Aber-

deen High School. Funds were used to complete the 3rd floor

Science and Math Academy.

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4 | The R&T Connection

ECBC has completed another year of the Minority Serving Institutions (MSIs) Science, Technology, Engineering, and Mathematics (STEM) Research & Development Consor-tium (MSRDC) program. MSRDC is a nonprof-it corporation which was formed under Co-operative Agreement No. W911SR-14-2-0001 with the U.S. Department of the Army. Its vision is aligned with the notion of engage-ment of diversity and inclusion to pioneer creative thinking with a goal of driving change within the science and technology functional communities. MSRDC is working towards achieving these goals by collabo-rating with members who serve minority institutions to include Hispanic and Tribal communities, historically black colleges and universities and many others as defined by the U.S. Department of Education. Gov-ernment partner laboratories include the U.S. Army Communications-Electronics Re-search, Development and Engineering Cen-ter (CERDEC), The U.S. Army Materiel Sys-tems Analysis Activity (AMSAA), and The U.S. Army Armament Research, Development and Engineering Center (ARDEC).

“This consortium is a resource to give gov-ernment labs access to a diverse group of people, get a fresh perspective on technical ideas, and gain better access to students who are an untapped resource,” said Adam Seiple, an associate director at ECBC. Seiple worked with other leaders at ECBC to create the partnership between local government laboratories such as ECBC, CERDEC, AMSAA, ARDEC and MSRDC.

To receive funding, the MSIs must submit a white paper proposal addressing a desig-nated DoD investment area developed by a government laboratory. Proposals then follow a rigorous selection process, where only the best and brightest ideas are chosen to be funded. The proposal spots are highly

coveted because it allows the MSIs a chance to work alongside the ECBC scientists, to develop positive relationships with others in their field, and to develop tacit knowledge which cannot be learned through a book or exam. Jared DeCoste, Ph.D., an ECBC scien-tist from the Chemical Biological Protection and Decontamination division, served as a principal investigator on MSRDC-sponsored projects.

“This program has become a positive expe-rience for all of us and I have enjoyed my role as a mentor. When I visited both universities I made sure the students knew I was there

to help. The teams loved getting to interact with people with similar interests outside the university,” said DeCoste.

In 2016, CERDEC received 18 white papers addressing eight different topic areas. At an Army meeting Chris Hassell, Ph.D., Deputy Assistant Secretary of Defense for Chemi-cal and Biological Defense, expressed his support, and worked with ECBC to develop additional investment areas.

“Developing these topic areas is a great way for organizations to start getting involved with the program without putting funding against anything,” noted Seiple.

Decoste would like to see the program con-tinue to thrive.

“We want this impactful program to grow in scale by maximizing the engagement poten-tial to have all schools capable of writing a white paper yearly. The students and pro-fessors love what this MSRDC has provided, because they do not get these opportunities often, and they are thriving and optimizing from the experience,” said Decoste. “It is my belief the money we are spending is really going a long way.”

Program Allows U.S. Army Organizations to Partner with Minority-Serving Institutions to Conduct DoD Research

Diversityincreases creativity & innovation

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2017 MSI STEM Research & Development ConsortiumBy the Numbers

2017 Continuing ProjectsECBC FY16-FY17 Continuing Projects

1.5MILLIONDOLLARS

1.3MILLIONDOLLARS

Awarded in the first year from the Chemical Biological Defense Program

DASD Nuclear Chemical/Chemical Biological Defense (NCB/CBD) funding committed over 2 years for white paper topics for CB detection and protection

DTRA/JSTO committed funding in the first year for predictive toxicology projects.

CERDEC is reviewing 6 project proposals

Fisk University (Historically Black University)

University of Texas San Antonio (Hispanic-Serving Institution)

City College of New York (Hispanic-Serving Institution)

North Carolina A&T (Historically Black University)

North Carolina Central University (Historically Black University)

AMSAA has funded 1 project

ARDEC had a white paper call which garnered 50+ submissions

2.8MILLIONDOLLARS

PROJECTS

Included within the funding selection by the Deputy Assistant Secretary of Defense (DASD) and Defense Threat Reduction Agency/Joint Science Technology Office (DTRA/JSTO)

“Multifunctional Mesostructures for Biochemical Protection and Sensing” (ECBC Principal Investigator (PI) Jared DeCoste, Ph.D.)

“Modeling organophosphate toxicity in C. elegans through a scalable combined in vivo and in silico approach” (ECBC PI Robert Kristovich, Ph.D.)

“Rapid Processing of a BiopolymericCo-continuous Filtration Membrane” (ECBC PI Erin Durke, Ph.D.)

“Using the Hard and Soft, Acids and Bases (HSAB) Theory to Predict Organophosphate Target Interactions” (ECBC PI Robert Kristovich, Ph.D.)

“Absorbents for use in Building-Integrated Plant-Based Dynamic Filtration Media for Removing Chemical Warfare Agents” (ECBC PI Jared DeCoste, Ph.D.)

“Novel Technology for Detection and Prediction of Air-Borne Chemicals” (ECBC PI Mike Kierzewski)

“High-Content Organ-On-A-Chip Assay: Predictive Nerve Toxicity Model for Organophosphates” (ECBC PI Waleed Maswadeh, Ph.D.)

“Exploring Chemical and Bio-Sensors Operating at the Quantum Frontiers” (ECBC PI Robert Kristovich, Ph.D.)

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6 | The R&T Connection

The United States is battling a crisis with an increased number of drug over-dose death due to the addition of opioids, such as fentanyl and carfentanil into drugs of abuse. A 0.001 milligrams (mg) dose of carfentanil is enough to incapacitate someone. Michael Feasel, Ph.D., ECBC Toxicology and Ob-scurants Branch, has been studying the metabolism of carfentanil as well as the isolation and structure of the metabolites formed after introduction to the body.

Feasel’s study stemmed from a 2012 Defense Science and Technology Lab-oratory (DSTL), United Kingdom, publication which referenced carfentanil and remifentanil being utilized to quell the Moscow theatre hostage crisis in 2002 (see sidebar on next page).

Carfentanil inhibits neurons by activating the opioid receptors in the body and shutting down the respiratory and central nervous systems. Naloxone, an anti-overdose drug, works by reversing the effects caused by a narcotic. A 2 mg dose of naloxone can revive an overdose victim, but it has been reported that multiple doses of naloxone may be required for a carfentanil overdose.

If one could be certain of the amount of naloxone needed to resuscitate a carfentanil victim, lives could be saved in both the narcotic usage and the defense communities. Feasel has proposed studies at ECBC to research such effects of removing the drug from cell receptors using substances such as naloxone.

ECBCResearchesMetabolicCarfentanilReactionsConducting applied research onpharmaceutical drugs to examinehuman reactions andpotential actions for revival

“These opiod exposures are not only a chemical

defense issue, but they are also a public health issue”ECBC scientist Michael Feasel, Ph.D., conducts testing to study

the metabolic effects of carfentanil.

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“Higher potency versions of naloxone are available, however the Food and Drug Administration has not seen a need to get them approved for human use, until now. These ultra-potent opioid exposures are not only a chemical defense issue, but they are also a public health issue,” Feasel reported.

Feasel, who recently received a Ph.D. in toxicology at the University of Maryland, Baltimore School of Medicine, approached principal investiga-tor Marilyn A. Huestis, Ph.D., then-chief of chemistry and drug metabo-lism at the National Institute on Drug Abuse’s (NIDA) Intramural Research Program about a collaboration on identifying carfentanil metabolites in carfentanil. Huestis recognized the epidemic and need to research carfentanil, and agreed to collaborate with Feasel and Robert Kristovich, Ph.D., ECBC Molecular Toxicology branch chief.

Feasel worked in NIDA’s labs for weeks incubating hepatocytes, common-ly referred to as human liver cells, in a two-dimensional (2D) platform. Twelve metabolites were identified in total and the hepatocyte incuba-tions showed slower clearance, providing some insight into the duration of carfentanil’s effects on the human body. Recent biological studies have shown cells forming on their own adhere to each other forming spheroids. Feasel conducted a follow-on study incubating carfentanil with three di-mensional (3D) liver spheroids. In this instance the spheroids closely re-sembled a human liver organ versus the 2D platform which was similar to an individual cell.

“By using a 3D subculture we are enabling the access to realistic data or in vivo metabolism,” observed Feasel.

Conclusions on this study have not yet been made as Feasel and his team are in the process of analyzing the data.

As carfentanil continues to make headlines the research being done at ECBC is vital as more information is brought to light about the substance.

“My goal with this study was not only to understand this opioid, but to also bring the process and techniques of generating metabolite libraries to ECBC” remarked Feasel. “ECBC could apply the technique to unknown compounds which may be of interest to the CB defense community.”

On October 23, 2002, 40 Chech-en militants seized the Dubrovka Theatre taking over 800 hostages for 4 days.

Three days later, Russian spe-cial forces released a mysterious aerosol into to the HVAC system of the theatre.

Rescue workers were not told what the hostages were exposed to, thus they did not immediately know how to treat the victims. 129 deaths were

caused by a combination of the aerosol and inadequate medical care.

In 2012, a study from DSTL used items of clothing and urine from three British survivors and concluded the agent was a mixture of carfentanil and remifentanil.

Russia has not made an official statement clarifying or denying what the study DSTL concluded.

Moscow Dubrovka Theatre SiegeMichael Feasel, Ph.D., and Acting ECBC Director Eric Moore, Ph.D., discuss effects of carfentanil exposure and its relation to warfighters.

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8 | The R&T Connection

Scientists at ECBC have developed a predic-tive toxicology method which could make toxicology testing faster, cheaper, and more accurate. General toxicology is a process which analyzes the adverse effects of chem-icals on living organisms. The current pro-cess which can take months or even years to assess, begins with testing on animals and initially, is only able to detect and compare lethal dosage to its test species. Predictive toxicology begins with an in silico or com-puter assessment process.

“While the system is not exactly broken, objectives with the U.S. Army and DoD communities have changed; they not only want to be proactive, timely, and accurate, but there is a need to remove excess animal testing from the equation,” said Robert Kris-tovich, Ph.D., branch chief of Molecular Tox-icology at ECBC.

In predictive toxicology, toxicology signa-tures are defined first in the in silico stage. If a substance is projected to have a high toxicity it can progress to the next in vitro or in human cell culture stage. During this process, models of different types of cell cultures and animal tissues are used to de-termine physical property calculations or predictions. This stage also allows for high content analysis (HCA) to occur.

“This is an important step because here we begin to define the requirements for mammalian species assessments. If we can observe the reactions we can make an educated decision on which mammal to conduct the testing on, if needed. This is in-

strumental because it allows us to make a guided decision through the animal system, removing the guesswork, allowing the need for animal assessments to be limited,” stat-ed Michael Feasel, Ph.D., of the Operational Toxicology Branch.

More than 70 million chemicals are found within the Chemical Abstracts Service (CAS) database, a division of the American Chemical Society, which collects and dis-seminates all publicly disclosed substance information. Kristovich and his team spend

time conducting research based on the chemicals in CAS some of which date back to the 1800’s. According to the CAS website, about 15,000 more chemicals are added daily to CAS.

Kristovich noted, “The power to calculate the toxicity of 70 million substances could take up to 25 years, and this is not count-ing the 15,000 new chemicals added daily.

Within our predictive toxicology model, we are able to cut the process of analysis of a substance to hours, if not days, which is light-years ahead of the previous process. This is great news for the DoD community because we can provide real-time decision making information allowing the Army to make informed decisions saving Warfighter lives and money.”

“Pictured [above] is an image of a human liver cell line based spherical organoid fol-lowing application of a mitochondrial toxic chemical. The HCA is beneficial because it allows for measurements of many cells to be taken at set times. Traditionally analysis was limited to measurements on a single cell. The analyzer is able to define the pe-rimeter (photos 1 and 2) before taking mea-surements at a specific endpoint (photo 3). It really is a powerful technique we are able to utilize,” Kristovich added.

Predictive toxicology has the opportunity to operationalize the Army chemical commu-nity for a stance of readiness with its ability to answer questions from the field about threat potential in a matter of moments. As the number of discovered chemical com-pounds continues to grow, the predictive toxicology approach will allow the DoD to focus research on finding threats which are currently unknown due to the cumbersome process.

“The U.S. Army and DoD... not only want to be proactive, timely, and accurate, but there is a need to remove excess animal testing from the equation”

Predictive Toxicology Methods Save Time and Money

1 2 3

- Robert Kristovich, Ph.D.

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Leveraging Intercontinental Relationships for an Enhanced Stance of Army Readiness U.S. Army research chemist Terrence D’Onofrio, Ph.D., through U.S. Army ESEP, fosters collaboration to operationalize chemical warfare research.

Over the course of two years, Terrence D’Onof-rio, Ph.D., a U.S. Army research chemist with the ECBC R&T Directorate, has conducted ensem-ble-level research in partnership with the U.K.’s DSTL through his participation in the Engineer and Scientist Exchange Program (ESEP). This collaborative effort has been extended due to its unprecedented benefit for both the U.K. and the U.S. This program allows D’Onofrio to live and work in Porton Down, England, in a tradi-tional exchange setting. Not only has D’Onofrio become fully immersed in the culture and life-style in the U.K., he has shared with them one of his most prized achievements, his third patent, The Low-volatility Agent Permeation method. Patented in May 2015, it is an invention critical to chemical agent protection testing. The system is the DoD standard testing method, and has now become adopted as the U.K. international standard.

“The ability to be physically present during ev-ery facet of exploration has been vital to the success of this partnership,” D’Onofrio said.

Interoperability is the typical way in which lab-oratories share information but as a visiting scientist D’Onofrio has been afforded time and intellectual freedom to probe issues in relation to Army readiness.

“To help facilitate data exchange and promote collaboration at the scientist level, I developed a mechanism to share listings of recent ECBC and DSTL reports between the nations. In this way, scientists in both locations can gain insight into recent developments. Showcasing the reports to the broad community enables parallel ef-forts for new collaboration and data exchange,” D’Onofrio commented on the ease of informa-tion sharing and technical reach back capabil-ities. This teamwork gives senior Army leaders the ability to call upon ECBC, as needed, to as-sist with data that is required to make chemical warfare agent protection.

The ability to be fully immersed in the culture and work at DSTL is the key to ESEP. D’Onofrio has been able to be present for Porton Man and Porton Man 2 manikin development. Porton

Man is a capability which enabled ensemble testing against actual chemical agents. The upgraded Porton Man 2 allows for a program-mable range of motions at various speeds, po-sitions, and orientations to wind.

“The original capability movement was limited to either marching at a single speed in a single orientation relative to the wind, or to standing still. Cumulative breakthrough was measured via passive dosimeters. There are also six re-al-time sensors placed in strategic areas of the body. These have given us the capability to measure the breakthrough based on the specif-ic actions and orientation for each ensemble as it is happening. This research was groundbreak-ing and has never been seen before,” D’Onofrio said. “Only with full participation in every aspect of the testing was I able to gain an understand-ing of the process, a critical step in understand-ing the data and how the ensemble performs.”

While ECBC and DSTL are similar in aspects, they have different organizational structures and unique national research priorities. The DSTL workforce is smaller, and the scientists spend more time in the laboratory, with larger ranges of activities to cover as they interact with a broader community.

“Covering all aspects helps focus the research on what is needed for the Warfighter. This ap-proach has taught me to think more broadly about the direction of research and potential stakeholders,” D’Onofrio mentioned. “One of the main lessons learned from this DSTL as-signment was to focus on strengths and lever-age collaboration to mitigate risk to programs. With each partner focusing on the aspects they do best, programs have a greater likelihood for success .”

ECBC scientists and engineers have been forg-ing new partnerships through the ESEP pro-gram for more than five years. ECBC personnel have spent time working for partner organiza-tions in Germany, Chile, the Netherlands, and many others. International scientists also have the opportunity to live in the U.S. and work at ECBC as well.

ECBC’s Terrence works in the lab on the Porton Man 2 manikin

in the U.K.’s DSTL as part of his participation in the ESEP.

Mid-career level Army engineers and scientists in Career Program 16 can apply for an ESEP assignment. Applicants may arrange for a position from one of 16 countries, including the United Kingdom, France, Germany, Japan, South Korea, Australia, Canada, Singapore and Chile.

Participants should:Be in General Schedule pay grades 12 through 14 (or equivalent) at the time of deployment.

Hold a minimum of a bachelor’s degree.

Have at least four years of technical ex-perience in industry or military/government.

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Scientists at ECBC are continuously on the forefront of exper-imental testing and success. Being the Army’s premier center for chemical and biological research comes with a passion of always wanting to uphold the guiding principles of science while conducting experiments under rigorous developmental testing phases. In doing so, ECBC scientists and toxicologists are constantly updating and improving their processes to pro-vide world class solutions to real world chemical and biologi-cal threats. An example of this mission is the Ex Vivo Console of Human Organoids (ECHO) or “human-on-a-chip” program. A partnership between ECBC and five research universities was formed in 2013 to fulfill a DoD requirement. The partner-ship aggressively pursues the three R’s - refine, reduce, and replace - in regards to the use of animals in toxicity testing of chemical warfare agents.

The five-year research project, which currently is in year four, has been funded by the DTRA, and features a stage of in vitro human organ constructs; the brain, liver, heart, and

lung, in communication with each other via integrated “blood vessels”. The platform allows for measurement of the effec-tiveness and toxicity of drugs and a human organs ability to process them.

Harry Salem, Ph.D., ECBC’s chief scientist for life sciences, ex-plains that the project is the future of medicine as we know it. “The ability to research and test toxicity on stem cells ver-sus animals is a game changer for the study of toxicology and pharmacology. We can now detect, decontaminate, and de-velop countermeasures with higher levels of confidence than ever before. Not only are we exploring the ability to save lives but we are doing it in a timelier fashion and for less money; it is a win for everyone,” Salem said.

Russell Dorsey, Ph.D., an ECBC research microbiologist noted, “The human-on-a-chip is currently undergoing another itera-tion with hope of simplifying its operation while increasing its output by twenty-fold.”

Project SpotlightECHO “Human-on-a-Chip”

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Seniors at the Science and Mathematics Academy (SMA) at Aber-deen High School are able to garner laboratory experience through an internship program at ECBC. The SMA is open to Harford County high school students, and seniors spend their final year in the pro-gram working with a mentor employed in a STEM-related indus-try to develop a capstone project. Christopher Phillips and Janna Madren-Whalley of ECBC’s Toxicology division served as mentors at SMA, working with Aberdeen High School seniors Priscilla Lee and Joey Healy. Lee and Healy worked on real-world scientific applica-tions alongside ECBC experts to complete their Capstone projects. Both students this year feel the benefits from having the research laboratory capabilities in their hometown backyards.

“Working with Mrs. Madren-Whalley and her team has truly been an invaluable experience,” Lee said.

Healy is appreciative for the opportunity to expand his knowledge in toxicology, and noted, “Mr. Phillips has been very supportive and helpful throughout my senior capstone project. He introduced me to high content imaging and analysis systems and helped guide me when I got stuck or confused by certain parameters in the software.”

Lee and Healy co-authored a poster for the 2017 Society of Toxicolo-gy (SOT) Conference this past March, involving the high content anal-ysis of a 3D human liver cell model. It is rare for high school students to present at SOT, a conference that is attended by world-class tox-icology experts and Washington D.C. policymakers. Neither of the students have had opportunities similar to this and both spoke very highly of their endeavors.

“The SOT Conference was my first experience ever at any type of sci-entific meeting. Throughout the session, I was able to present my project to many professional scientists from not only the country, but the world. It was an amazing experience,” Lee noted.

This experience has led these high school students to start thinking about pursuing master’s degrees. “My work at ECBC has confirmed my interest in a career in the scientific field. I was able to learn ba-

sic lab technique and this professional scientific setting gives me an advantage over many other students my age as I enter college next year,” Healy said.

Lee agreed when she noted, “I am extremely grateful ECBC has helped prepare me for my undergraduate college experience.”

“Having the opportunity to teach students about what we do here at R&T has been both a privilege and a pleasure. The SMA at Aberdeen High School is a wonderful program and I am very happy we have been given the chance to partner with them. The students are very eager to learn and have bright futures ahead of them. I am grateful to have been able to play a part in their educational journey and look forward to the next group of students to join us,” Madren-Whalley commented as she reflected on the time spent with Lee and Healy.

As seniors graduating from the SMA magnet program both Lee and Healy had their capstone projects featured in the school’s gallery walk on 23 May 2017. The gallery walk was open to public and end-ed with an award ceremony. Lee was selected by the Academy as one of only five students to give an oral presentation on her proj-ect in addition to her poster presentation. Lee received the Donna M. Clemmons Award, presented to the student for exemplifying the Spirit and Purpose of the SMA. Healey was awarded The Brian Sim-mons Award, presented to the student demonstrating honorable character and ferocious integrity.

Other students who partnered with ECBC this year include:

Kendall ArcherMentors: Stanley Ostazeki, Ph.D., Alex Jestel, Elizabeth Corriveau

Jack DonnaMentors: Ken Collins, Ph.D., Terry Roop

Afsa SimpsonMentors: Stephanie Padovani, Mike Ellzy, Ph.D., Carmen Adrover

Extra CreditHigh School Students Gain Real Experience at ECBC

ECBC Acting Director Eric Moore, Ph.D., engages with

Science and Mathematics Academy students Joey

Healy and Priscilla Lee

Page 12: The RT Connection - United States Army€¦ · The RT Connection A Publication of the U.S. Army Edgewood Chemical Biological Center (ECBC) Research Technology Directorate (RT) Toxicology

12 | The R&T Connection

Patents

PublicationsNews Shorts

Michael Kierzewski, Steven Lagan, and Nirmala Pinto, ECBC MSA Branch assisted with preparations for an upcoming Early User Assessment (EUA) of chemical, biological, radio-logical and nuclear (CBRN) enhancements to One Semi-Automated Forces (OneSAF). The EUA will be used to evaluate the correctness and appropriateness of the current round of improvements that have been made to the software. ECBC and the Joint Program Executive Office for Chemical and Biological Defense are invested in the successful implementations of these improvements because they will enable higher-fidelity analysis of the operational impacts of CBRN hazards, materiel, and doctrine.

Jared DeCoste, Ph.D., and Christopher Karwacki, Ph.D. attended the 253rd American Chemical Society (ACS) Conference in San Francisco, CA 2-6 APR 17. DeCoste presented a talk entitled “Enhancing the uptake of oxygen in metal-organic frameworks” in the Inorganic Chemistry Division, Chemistry of Materials: Metal-Organic Frameworks Section. Karwacki was formally elected as secretary for the ACS Division of Colloid and Surface Chemistry to aid in building collaborations with emerging scientists in the fields of surface science and catalysis.

Douglas R. Sommerville presented his poster, “Review & Assessment of Phosgene Mam-malian Lethality Data & the Development of a Human Estimate,” at the recent 2017 Annual Meeting of the SOT, which was held in Baltimore, Md., March 13-16. The SOT Conference was the first time that the poster was presented in a public forum. ECBC developed the human estimates for the lethal effects of phosgene inhalation (and published in a tech report in 2010) from a review and statistical analysis of existing mammalian lethality data. An al-lometric model was used to fit the data and extrapolate for a human estimate. The work was funded by the Department of Homeland Security’s Chemical Security Analysis Center (CSAC), and the original technical report (with some modification) has just been recently cleared for public release (as CSAC-16-015). Stephen R. Channel, Ph.D., Leidos, Linton, Ind., is also a co-author (both poster and technical report).

“A Microporous Amic Acid Polymer for Enhanced Ammonia Capture”Accepted for publication in the ACS Ap-plied Materials and Interfaces. This work was conducted jointly between ECBC, The University of California, Berkeley, the University of Copenhagen, and Lawrence Berkeley National Laboratory.

“MOFabric: Electrospun Nanofi-ber Mats from PVDF/UiO-66-NH2 for Chemical Protection and Decontamination,”Published in Applied Materials & Interfaces. The manuscript is a joint effort between personnel from ECBC and the Defense Threat Reduction Agency, and focuses on integrating a zirconium-based metal-or-ganic framework (MOF) into a non-woven fabric material. This is the first publication that showcases the activity of MOFs in fab-ric against chemical agents dosed in a real-istic environment, and is also the first step toward development of new, low-burden protection systems. The journal article is available online: http://pubs.acs.org/doi/abs/10.1021/acsami.7b01621

Patent No. 9,617,256Awarded to ECBC Scientists Steve Harvey, Ph.D., and Mark Guelta, entitled “OPAA FLF- A Mutant Enzyme with Increased Catalytic Efficiency on VX.” The patent describes a mutant version of the Organophosphorus acid anhydrolase (OPAA) enzyme. OPAA has been shown to be effective in detoxi-fying organophosphorus-containing com-pounds, such as nerve agents. Compared to the wild-type enzyme, this mutant ver-sion has approximately 40-fold increased activity on nerve agent VX.

Patent No. 9,500,568Awarded to Daniel G. Wise, Ph.D, entitled “Inflatable Inlet for Aerosol Sampling.” The patent relates to air sampling, and sampling of air containing aerosol particles, focused to conditions where storage and remote controlled or automatic deployment of aerosol sampling devices are required.