When Robots and Metabolism Collide: EPA and Partners Announce Transform Tox Testing Challenge Semi-Finalists

By Kevin Kuhn

When I tell my friends about chemical high-throughput screening and the Transform Tox Testing Challenge, I always start with the robot. Why? Because people love robots.

Tox 21 robot at work

Robot in action at the National Center for Advancing Translational Sciences (NCATS) where it is housed.

The Robot, i.e. the ultra-high-throughput robotic screening system (pictured) is just one example of a suite of automated systems designed to test and screen chemicals. The system identifies chemicals’ potential for trouble faster and cheaper than ever before, and without the need to test on animals.

Thanks to these automated systems and Tox21 (a cooperative effort uniting EPA, the National Institutes of Health (NIH), and the Food and Drug Administration), we have run thousands and thousands of experiments to see how chemicals affect cells, their processes, and the proteins that do the work. It truly is some amazing research.

Of course, it wouldn’t be research if the system was perfect. Here’s the rub: cells used in EPA’s current lab tests do not typically break down or metabolize chemicals like they would in the body. This means that these tests may overlook chemicals that could be metabolized into a more toxic form. We need a robot-friendly way of making our lab tests act more like the human body when evaluating chemicals’ toxicity.

To find a solution, EPA, NIH’s National Center for Advancing Translational Sciences (NCATS), and the National Toxicology Program, headquartered at the National Institute of Environmental Health Sciences, launched the Transform Tox Testing Challenge in January.

Now we are thrilled to announce that we are awarding a total of $100,000 to ten semi-finalists for their amazing ideas. Descriptions of these promising proposals are available here. The semi-finalists have brought the best of modern technological approaches to bear on the problem, and we couldn’t be more excited about the ideas.

Right now these proposals are simply ideas on paper, but thanks to the challenge prize money, these solvers will have the opportunity to develop their plans into working prototypes and enter Stage 2 of the competition. EPA will host a workshop for the semi-finalists in July so that they can meet one another, learn more about our great set of screening systems, and potentially combine their talents to strengthen their Stage 2 entries.

With the possibility of solving this problem on the horizon, we’re one step closer to improving toxicity testing and protecting human health better than ever before. And, to be honest, that is even cooler than the robot.
For more information: transformtoxtesting.com

 

About the Author: Kevin Kuhn, Ph.D. is an advisor to the Chief Innovation Officer in the U.S. Environmental Protection Agency’s Office of Research and Development and  manages the Pathfinder Innovation Projects – a competition that provides seed funding for EPA research scientists to pursue high-risk, high-reward research. Learn more about EPA Innovation at: https://www.epa.gov/innovation.

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

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Linking Up: Making Every Day Earth Day

By Tom Burke, Ph.D.

Today marks my first Earth Day as the Deputy Assistant Administrator for EPA’s Office of Research and Development. This is the one day of the year when people around the world unite to celebrate our planet, and I’m thrilled to be at a place where strengthening the links between a healthy environment and healthy communities are at the forefront of everything we do.

Eagle parents tend to their eaglets.

Eagle parents tend to their eaglets.

I began my day today checking in on the month-old eaglets up near Codorus State Park in Pennsylvania. The chicks are flourishing and provide a wonderful metaphor for the remarkable progress that has been made since the first Earth Day 45 years ago. What started as a collective unease about the state of local waterways, polluted lands, and haze-obscured views across urban neighborhoods was soon amplified in screaming national headlines about rivers on fire, and Rachel Carson’s best-selling book Silent Spring outlining the dangers of the indiscriminant use of the chemical pesticide DDT.

Such events helped spark the realization that when it comes to our environment, we are all in this together. And it was science—much of it led or conducted by EPA researchers—that taught us how to turn environmental concerns into action.

By understanding how particulate matter and other pollutants in the air relate to asthma rates and longevity, between lead exposure and childhood development, and between disease and contaminated water, local public health officials know what steps they can take to better protect people.

That track record for responsive science is why EPA labs are always among the first called when environmental emergencies strike, such as the BP oil spill in the Gulf of Mexico or when harmful algal blooms threatened Toledo’s drinking water supply. EPA expertise is counted on to help local officials identify hazards, know what tests to conduct, and when to issue or lift health advisories.

And what’s more, that same expertise is also driving innovative research that is not only helping communities become more resilient today, but developing the tools, models, and solutions to lower risks and advance sustainability for the future. Just a small sampling of examples include:

  • Our researchers have teamed up with colleagues at NASA, NOAA, and the U.S. Geological Survey to develop ways to tap satellite data to monitor water quality and better predict harmful algal blooms.
  • Empowering scientists and communities alike to tap a new generation of small, inexpensive, and portable air sensors to track air quality through The Village Green Project and others.
  • Our Healthy Heart campaign helps cardiac healthcare professionals use existing and emerging research to educate their patients about the link between air quality and their health—and to take action to avoid exposures during “ozone alert” days.
  • Advancing sophisticated computational toxicology methods and technologies through partnerships such as Tox21 to usher in a new paradigm of faster and far less expensive chemical screening techniques.
  • Providing data and mapping tools such as EPA’s EnviroAtlas that help community planners and other citizens identify, quantify, and sustain the many benefits they get from the natural ecosystems that surround them.

I started my own career conducting environmental investigations and epidemiological studies, and working closely with county and city health officials. These officials are on the front lines of environmental health and our communities depend upon them. Providing support by linking them to the data, tools, and innovative solutions mentioned above is one of my top priorities as EPA’s Deputy Assistant Administrator for our Office of Research and Development.

That will take a continued commitment to communications and translation of our science to action, all part of keeping the critical link between a healthy environment and healthy people at the forefront of our thinking. Sharing our work with public health professionals is one way we can work together to make every day Earth Day. And that’s something we can all celebrate.

EPA Deputy Assistant Administrator Tom Burke

EPA Deputy Assistant Administrator Tom Burke

 

About the Author: Thomas Burke, Ph.D. is the Deputy Assistant Administrator of the Office of Research and Development as well as EPA’s Science Advisor. Prior to coming to EPA, he served as the Jacob I. and Irene B. Fabrikant Professor and Chair in Health, Risk and Society and the Associate Dean for Public Health Practice and Training at the Johns Hopkins Bloomberg School of Public Health.

 

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.

Ushering In a New Generation of Chemical Screening

By Richard Judson

I work with EPA colleagues and other scientists around the world to integrate advances in biology, biotechnology, chemistry, and computer science to evaluate thousands of chemicals. Part of our research is supporting EPA’s Endocrine Disruptor Screening Program, exploring the potential for chemicals to disrupt normal growth and development in humans and other animals.

The work we do is helping usher in a new generation of faster, more efficient, and far less costly chemical screening methods. We use automated technologies, called high-throughput screening assays, to expose cells and proteins to chemicals. We then screen them to identify any that exhibited changes in biological activity that may suggest the potential for endocrine disruption.

My partners and I are excited to announce that we have recently published two papers on results of our work. We used the innovative methods described above to screen chemicals for their potential to mimic normal estrogen hormones, substances that direct development and reproduction. Exposure to chemicals that mimic estrogen pose a range of potential health risks, including birth defects and certain types of cancer.

The first paper, published in Nature Scientific Reports, describes the results of screening approximately 10,500 chemicals. The screening included 88 duplicates of the same chemicals, which validated the reliability of the assays. It also included 39 reference chemicals—those whose estrogen-receptor activity have been well established through traditional testing methods. Using the reference chemicals showed that the assays could accurately identify chemicals that were both positive and negative for their ability to mimic natural estrogens.

Robotic arm moving samples for screening

Robotic arm moves samples for automated chemical screening, part of the Tox 21 collaboration.

This paper is a product of Tox21, a federal collaboration pooling expertise and resources among EPA, the National Toxicology Program (National Institute of Environmental Health Sciences), the Food and Drug Administration, and the National Center for Advancing Translational Sciences (NCATS). Tox21 was established to study how high-throughput screening methods can be used to evaluate thousands of chemicals. These assays were run on the NCATS ultra-high-throughput robotic screening system (pictured).

The second paper (selected by the American Chemical Society’s Environmental Science and Technology journal as an editor’s choice) describes the results of screening 1,814 chemicals (including 36 reference chemicals). The screening was performed using a panel of 13 high-throughput estrogen receptor assays that use a diverse set of cell types and assay technologies.The results indicate that such a panel can accurately predict estrogenic responses. It demonstrates how the resulting data could be used for chemical prioritization as part of the Agency’s Endocrine Disruptor Screening Program.

In December 2013, we publicly released our high-throughput screening data through user-friendly web applications called interactive Chemical Safety for Sustainability (iCSS) Dashboards. I encourage anyone with an interest in this research to take a look at the data and to also participate in EPA’s Second ToxCast Data Summit. The summit is scheduled for September 29-30, 2014 in Research Triangle Park, NC.

The goal of the summit is to bring together the user community (industry, non-governmental organizations, academia, governmental agencies and more) to present their ideas for ways to use the large amount of high-throughput screening data to help inform chemical policy and regulatory decisions.

About the Author: EPA scientist Dr. Richard Judson develops databases and computer applications to model and predict toxicological effects of a wide range of chemicals. He is a member of the EPA Computational Toxicology research team where he leads the effort in bioinformatics. Dr. Judson has a BA in Chemistry and Chemical Physics from Rice University and an MA and PhD in Chemistry from Princeton University.

Information About the Papers

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway. Ruili Huang, Srilatha Sakamuru, Matt T. Martin, David M. Reif, Richard S. Judson, Keith A. Houck, Warren Casey, Jui-Hua Hsieh, Keith Shockley, Patricia Ceger, Jennifer Fostel, Kristine L. Witt, Weida Tong, Daniel M. Rotroff,2 Tongan Zhao, Paul Shinn, Anton Simeonov, David J. Dix, Christopher P. Austin, Robert J Kavlock, Raymond R. Tice, Menghang Xia. Nature Scientific Reports

Predictive Endocrine Testing in the 21st Century Using in Vitro Assays of Estrogen Receptor Signaling Responses. Daniel M. Rotroff, Matt T. Martin, David J. Dix, Dayne L. Filer, Keith A. Houck, Thomas B. Knudsen, Nisha S. Sipes, David M. Reif, Menghang Xia, Ruili Huang, and Richard S. Judson. Environmental Science & Technology

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.