EPA Scientist Dr. Robert Kavlock Honored for Advancing Alternatives to Animal Testing

Congratulations to Dr. Robert Kavlock, a leading figure in the advancement of alternatives to animal testing, who was recently honored with The Humane Society of the United States’ 2017 Russell & Burch Award. The award, which recognizes scientists who have done outstanding work to move science away from using animals in harmful research and testing, was presented on August 20, during the 10th World Congress on Alternatives and Animal Use in the Life Sciences in Seattle, Washington.

“Robert Kavlock has been at the forefront of the development of alternatives to animal testing,” said Dr. Kate Willett, The HSUS’ Director of Regulatory Toxicology & Risk Assessment, Animal Research Issues. “He’s a leader of the Tox21′ revolution within EPA to develop rapid, non-animal methods for assessing thousands of chemicals, an approach that now serves as a strong foundation to move us entirely away from the use of animals in this area, sparing millions of animals from significant suffering.”

Dr. Kavlock is the acting assistant administrator for the Office of Research and Development at the United States Environmental Protection Agency, and the Acting EPA Science Advisor. He was previously the Director of the National Center for Computational Toxicology (NCCT). During his tenure, he led the ToxCast program which has made significant scientific contributions toward the use of mathematics and computer modeling to assess and predict how toxic substances are (known as computational toxicology) as well as enabling important regulatory changes that have resulted in fewer animals being used in testing.

Since 1991, The HSUS has presented the Russell & Burch Award every two to three years, awarding a total of 15 scientists for their role in advancing methods that will improve science and decrease animal suffering, ultimately replacing the use of animals altogether. Recipients of the award receive a $5,000 prize and trophy.

EPA Tox21 ToxCast World Congress on Alternatives

Sleepless in Seattle: An update from the World Congress on Alternatives and Animal Use in the Life Sciences

Our experts will be working round-the-clock in Seattle this week at the World Congress on Alternatives and Animal Use in the Life Sciences! Over the next several days, staff from The Humane Society of the United States, Humane Society International & The Humane Society Legislative Fund will be at the vanguard of the discussion at this global event that brings together the world’s foremost experts on animal testing alternatives & animal welfare from industry, government, non-profits & academia.

Are you in Seattle, too? Please visit us at our booth (#309) and plan to attend the following events! Somewhere else in the world? Check out what we’re up to below and view the World Congress program.


• 10:00 a.m. – noon
“Introduction to Adverse Outcome Pathways and the AOP Wiki” Satellite Meeting
Sheraton Seattle, Aspen Room
10:00 a.m. Introduction to the OECD AOP Programme and Online Training course – Kate Willett, Human Toxicology Project Council
10:40 a.m. Building AOPs for Neurotoxicity: Perspective from an Academic – Ellen Fritsche, IUF – Leibniz Research Institute for Environmental Medicine
11:20 a.m. Demonstration and Hands-On Activity with AOP Wiki – Kristie Sullivan, Physicians Committee for Responsibility MedicineSponsors: Human Toxicology Project Consortium and the Physicians Committee for Responsible Medicine


• 12:15 p.m. – 1:15 p.m.
“Tracking the successful implementation of Tox21 principles.”
Room 6ABC, Board number A43
Poster presenter Vicki Katrinak looks at how the chemical safety testing landscape has changed over the past ten years, as toxicologists embrace new, non-animal testing strategies.

• 12:15 p.m. – 1:15 p.m.
“Legislative process toward animal testing bans for cosmetics in Brazil.”
Room 6ABC, Board number A44
Poster presenter Antoniana Ottoni discusses how the Brazilian authorities aim to implement validated alternative, non-animal tests for commonly used toxicological endpoints and reviews plans to ensure the regulations are updated before the deadline of 2019.

• 2:00 p.m.
“Implications of the Recent 2016 Amendment of the Toxic Substances Control Act (TSCA) on the Development and Implementation of Non-Animal Methods.”
Session II-2: Government Driven Legislation – EDSP/TSCA; 1:15 p.m. – 2:45 p.m.; Rooms 613-614
Speaker Catherine Willett will explain how animal testing could actually increase under the new chemical safety act, and describe how co-ordinated efforts are needed to exploit non-vertebrate models and other evaluation tools to prevent this.


• 10:30 a.m.
“Challenges in implementing the Frank R. Lautenberg Chemical Safety for the 21st Century Act: A perspective covering stakeholders, the U.S. Congress and the current Administration.”
Session IX-4: Global Regulatory Updates; 10:00 a.m. – noon; Room 607
Speaker: Sara Amundson

• 12:15 p.m. – 1:15 p.m.
“Modeling the human airways: from physiology to pathology.”
Room 6ABC, Board number A65
Poster presenter Lindsay Marshall shows how laboratory models using human cells can be used to look at the function of healthy airways and demonstrates that the models can be adapted to enable the study of airways disease, such as cystic fibrosis.

• 12:15 p.m. – 1:15 p.m.
“iPSC and 3D tissue technologies powerful alternatives to animal models for brain disease research”
Room 6ABC, Board number A77
Poster presenter Marcia Triunfol reports on an exciting, HSI-sponsored workshop held in Brazil earlier this year. Brazilian and international scientists discussed the potential for 21st century technologies to replace animals in brain research.


• 12:15 p.m. – 1:00 p.m.
“A ‘bottom-up’ approach to accelerate new opportunities in alternatives and Adverse Outcome Pathway (AOP) practice in China”
Room 6ABC, Board number C81
Poster presenter Tina Qu reports on the progress made in promoting non-animal technologies in China, including the recent roll-out of an AOP-training program.

• 10:45 a.m.
“Towards a 21st-century roadmap for biomedical research and drug discovery”
Session IX-8: Global Efforts Moving Towards Replacement of Animals;
10:00 a.m. – noon; Rooms 619-620
Speaker Troy Seidle describes the application of pathways-based approaches to understand chemical safety and details how a series of workshops sponsored by The Humane Society of the United States and Humane Society International have introduced this concept to other stakeholders – describing the main recommendations from these events.


• 10:48 a.m.
“The Human Toxicology Project Consortium: a private-public partnership to promote development and acceptance of pathway-based science”
Session IX-6: 3Rs Communication and Advocacy; 10:00 a.m. – noon; Rooms 619-620
Speaker Catherine Willett will describe the work of the Human Toxicology Project Consortium (HTPC), which aims to advance a biological pathway-based approach to toxicology. She will explain how HTPC intends to achieve this through scientific activities, communication, and advocating for financial and legislative support.

• 11:45 a.m.
“Deletion of scientifically redundant animal test requirements in the agrochemical sector: the case of the 1-year dog study”
Session IV-1: Predictive Safety Approaches Role in the Design of Inherently Safer Chemicals; 10:00 a.m. – noon; Rooms 615-616
Speaker Marco Corvaro will explain how the ongoing global effort to end a test that has been proven redundant illustrates how challenging it can be to enact regulatory change. He will also discuss strategies to improve the use of modern approaches to testing and risk assessment.

• 11:46 a.m.
“A campaign to end invasive chimpanzee research and retire all chimpanzees to sanctuaries: successful strategies and lessons learned”
Session IX-6: 3Rs Communication and Advocacy; 10:00 a.m. – noon; Rooms 619-620
Speaker Kathleen Conlee will take us from 2006, when The Humane Society of the United States launched their campaign to end the use of chimpanzees in invasive research, to today where numbers of chimps in labs have dropped and research chimps are finally being retired to sanctuaries.

AOP tutorials AOPs non-animal tests toxicity testing alternatives toxicology World Congress on Alternatives

Human Stem Cells for Studying ALS

Recently, the potential of stem cells in ALS research has been revealed in the laboratory and in the clinic. Induced pluripotent stem cells (iPSC) are stem cells, often derived from adult human skin cells, that can be turned into other types of cell – including nerve cells (see picture). In a ground-breaking laboratory study in 2014, iPSC-derived motor neurons from people with an aggressive form of SOD1-related ALS were shown to have increased electrical activity compared to motor neurons made from iPSC from people who did not have ALS. The ‘ALS neurons’ did not live very long in the lab, but correcting the SOD1 mutation reduced neuron hyperactivity and increased their lifespan.

Read more…

digital illustration neurons


AOP learning opportunities at SOT 2017

The Human Toxicology Project Consortium will once again co-sponsor an Adverse Outcome Pathway-training at the Society of Toxicology’s (SOT) annual meeting in Baltimore, Maryland. On Tuesday, March 14, from 5:00PM-7:00PM, registrants can take part in our Hands-On Seminar: Creating an Adverse Outcome Pathway in the AOP Wiki, which HTPC is co-sponsoring with the Physicians Committee for Responsible Medicine (PCRM).

At this seminar, participants will have a chance to deepen their understanding of the AOP Wiki (Version 2.0) and gain experience entering an Adverse Outcome Pathway.  Attendees will work through a case example in small groups.  In addition, participants will get a preview of an online course on AOPs and the AOP-Wiki that will soon be available here on the HTPC website.


5:00-5:20: International Efforts to Identify, Standardize, and Apply AOPs (Kristie Sullivan, PCRM)

5:20-6:00: A New Online Course on Adverse Outcome Pathways (Catherine Willett, HTPC)

6:00-7:00: The AOP Wiki 2.0: Demonstration and hands-on exercise (Stephen Edwards, US EPA)

The seminar will take place in the Constellation Ballroom A – Hyatt Regency Baltimore, 300 Light Street.  Please register in advance with Kristie Sullivan at PCRM: ksullivan@pcrm.org


At this SOT gathering, HTPC is also once again co-sponsoring (along with the Center for Alternatives to Animal Testing [CAAT] and the Human Toxome Project) the well-regarded satellite meeting, Updates on Activities Related to 21st Century Toxicology and Related Efforts.  As always, the meeting will feature a number of invited presentations, but also leave time for an “open microphone” segment in which participants are welcome to give brief presentations on germane topics, with or without a few slides.  This satellite meeting takes place Thursday, March 16 from noon to 4:30PM at the Lord Baltimore Hotel.

The draft program is as follows:

12:30 Box lunch (for pre-registered participants) and welcome, Thomas Hartung (Johns Hopkins University)

13:00 Invited speakers (10 minute presentations each followed by 5 mins. of discussion)

  • ToxCast Update – Russell Thomas (US Environmental Protection Agency)
  • EDSP21 Update – Stanley Barone (US Environmental Protection Agency)
  • Tox21 Update – Richard Paules (US National Toxicology Program)
  • TT21C update – Rebecca Clewell (ScitoVision)
  • NICEATM Update – Nicole Kleinstreuer (NICEATM)
  • EU Tox-Risk Update – Robert van de Water (University of Tuebingen)
  • NAS Report on Using 21st Century Science to Improve Risk-Related Evaluations – TBD
  • Evidence-based Toxicology Update – Katya Tsaioun (EBT Johns Hopkins)
  • CAAT’s Read-across Initiative and Human Toxome-related Activity Update – Thomas Hartung (Johns Hopkins)
  • Human Toxicology Project Consortium Update – Catherine Willett (HTPC)

15:15 Open microphone for additional presentations and discussion

16:00 Adjourn

Box lunches will be available to those who have pre-registered. Contact Jamie DeRita.


Also at this year’s SOT meeting, HTPC coordinator Catherine Willett will present a poster on HTPC’s soon-to-be-released online training course on adverse outcome pathways. Look for her poster, “Advancing the Development of Quality AOPs Submitted to OECD’s AOP Knowledge Base (AOP-KB) and the AOP-Wiki” during the Late Breaking Poster Session on Thursday, March 16, from 9:00AM to noon (late-breaking abstract #3441; Poster # P413).

AOP tutorials AOPs HTPC partners Meetings & Events

Human Cell Atlas: The next frontier

Reprinted from the October 2016 AltTox Digest; used by permission.

Now that the human genome has been mapped, the next frontier is to map the human cellular phenotypes. An understanding of all the types of human cells and how they interact in the various tissues and organs will provide the new level of understanding of human biology needed to accomplish medical breakthroughs, understand physiological processes such as human development and aging, and understand pathophysiological processes such as disease and toxicity.

Cells are the basic building blocks of all human tissues and organs. Beginning in the embryo, cells divide and begin to specialize into the different cell types that make up the human body.

General estimates identify several hundred major cell types, however, new methods of characterizing cells show that even within what appears to be a homogenous population there is great variability.

The technique used to identify cells at the level of the single cell is single-cell messenger RNA sequencing (RNA-seq), where every messenger RNA species in a sample is sequenced and identified.  Credit: Genome Research Limited

The technique used to identify cells at the level of the single cell is single-cell messenger RNA sequencing (RNA-seq), where every messenger RNA species in a sample is sequenced and identified. Credit: Genome Research Limited

Recent government funding initiatives have spurred innovation and progress in studying cells at the level of the single cell. In 2014, the US National Institutes of Health (NIH) awarded $7.9 million to 25 projects studying various aspects of single cell analysis as part of the Single Cell Analysis Program (SCAP).

On October 13-14, 2016 an international group of renowned researchers met in London to discuss building the Human Cell Atlas. The Human Cell Atlas will be more than just a catalogue of static cell types. Like SCAP, it involves addressing the many challenges in characterizing human cell heterogeneity.

For more on single cell analysis and the new international effort to develop the Human Cell Atlas, see the entire article, “The Human Cell Atlas: An international effort,” on AltTox.org.

alternative toxicity testing Human Cell Atlas Single Cell Analysis Program

Can Organs-On-Chips Repair The Flawed System Of Drug Discovery?

Reposted from Life Science Leader.

By Trisha Gladd, Life Science Connect Editor

There is an ecosystem of many stakeholders who play a role in the discovery of new drugs, and each of them have a vested interest in making the drug discovery system work successfully and efficiently.  Yet, the realities of a flawed system are evident in the facts and figures.  A Phase 1 clinical trial for one compound can cost close to $15 million and take years to complete. Data published on www.fdareview.org also shows that only about 10 percent of drugs entering Phase 1 trials actually make it to market, which translates to considerable financial losses for those in the other 90 percent.


Recently, a wide range of these stakeholders – from pharmaceutical companies and academic researchers, to disease foundations and CROs – have signed on to work with Emulate, Inc., a privately held company at the forefront of a new technology, called ‘Organs-on-Chips.’  James Coon, CEO of Emulate, and his team of scientific researchers, designers and engineers are aiming to change the way drug candidates are evaluated in the laboratory by using Organs-on-Chips technology an alternative to today’s cell culture and animal testing techniques.  In the past week, two new collaborators have joined forces with Emulate: a CRO, Covance Drug Development, and a major cancer research center, the Ellison Institute for Transformative Medicine at USC.  This adds to the growing list of partners – including Johnson & Johnson, Merck, the Michael J. Fox Foundation for Parkinson’s Disease, and the government defense agency DARPA – who are putting their hopes and expertise on the line to advance Organs-on-Chips technology into the mainstream of the drug-development process.

Coon says one of the reasons so few drugs make it to market is due to the conventional in vitro models and animal models currently being used by the pharmaceutical industry. To identify viable drug candidates, these models rely on data points from static human cell cultures in plastic dishes that do not represent the broader living biology of human tissues and organ systems, or on studies in animals that do not always directly translate to human biology. Organs-on-Chips technology offers a new approach.  By placing living human cells in an engineered microenvironment that recreates what’s happening within tissue systems, Coon says the technology offers the ability to create the smallest functional unit of a human organ, which gives a biological context that is much more effective at predicting human response than today’s cell cultures or animal testing.

Organs-on-Chip is a technology originally designed by Donald E. Ingber M.D. Ph.D., founding director of The Wyss Institute for Biologically Inspired Engineering at Harvard University, and Dan Dongeun Huh, Ph.D., assistant professor in the department of engineering at the University of Pennsylvania, that combines microfabrication techniques and engineering principals to create living, functioning human organs inside engineered microenvironments. Measuring in a size similar to a AA battery, each chip is made of a clear flexible polymer that contains tiny hollow channels lined by living human cells. Just as if cells from a patient’s body were biopsied and then studied, these translucent devices can be created by scientists to use as a window into the inner workings of human organs.

Since spinning out of The Wyss Institute for Biologically Inspired Engineering in July 2014, Emulate has evolved its Organs-on-Chips technology to become a commercially-viable product platform for use in industry.  By housing the Organs-on-Chips within an automated system Emulate offers a way for researchers and product developers to not only conduct experiments that are predictive of normal human physiology, but they also can create different disease states within the Organs-on-Chips to help determine appropriate therapeutic intervention. This lab-ready automated system includes three components: the Organs-on-Chips, the instrumentation that automates the use of those chips, and the software apps that allows scientists to collect and analyze data.  Because Emulate is integrating their Organs-on-Chips technology into a ‘plug-and-play’ system, end users can easily conduct experiments to meet customized needs within their own labs.

“In collaborations announced over the last year, industry leaders, such as Merck, the Michael J. Fox Foundation and Johnson & Johnson, are recognizing that the Organs-on-Chips technology can be valuable in predicting human response in applications throughout the drug development process and are now engaged in using the technology for a wider range of applications,” says Coon. “This includes early-stage processes, such as discovering new drug targets and understanding disease mechanisms, as well as late-stage testing of the efficacy and safety of new drug compounds.”

How Would Organs-on-Chips Impact The Future Of Animal Testing?

While it seems Organs-on-Chips has the potential to eliminate animal testing, Coon says that, as of right now, that is unlikely. “We live in a world where there is a regulatory system in place that is built around standards using animal testing,” he explains. “As a result, some of our early partners are using Organs-on-Chips to augment their existing pre-clinical models, and over time, we may be able to increasingly replace animals in the development process.” When it comes to the three guiding principles supporting the humane use of animal testing in scientific research—replace, reduce, and refine—Coon says Organs-on-Chips can play a role in each area. “By serving in a role side-by-side with animal testing, the technology can generate human-relevant data that has the ability to guide the refinement of the animal models that are selected for regulatory submissions,” explains Coon. “This could ultimately reduce the ineffective or unnecessary animal studies as well as the number of animals required.”

Consistent with the way new standards are accepted for regulatory filings with FDA and other agencies, the Organs-on-Chips technology will be evaluated for future adoption for regulatory uses as the body of data using Organs-on-Chips continues to grow over time. As of right now, it is a technology that is used part of the R&D process, and continues to be evaluated for adoption as a standard practice for regulatory filings.

Industry Partnerships Drive Commercialization Potential

In 2015, Organs-on-Chips was named the overall winner of the London Design Museum’s Design of the Year award. This marked the first time this award was presented to a product from the field of medicine. Some of pharma’s biggest names also have recognized the potential of this technology. As mentioned, Emulate has entered into a strategic collaboration with Merck. Together, the two companies are working to deploy Organs-on-Chips across certain Merck drug discovery programs with the goal of improving models of human inflammatory diseases and better predicting human response of therapeutic candidates. In addition, Johnson & Johnson Innovation and Janssen Biotech are also in a strategic collaboration with Emulate to use Organs-on-Chips to drive the clinical goals for three Janssen R&D programs.

When it comes to partnerships, Coon says one of the things they have been careful about very early on is not chasing money. “Our goal is to strategically align with companies that help us advance our core business, which is to develop the technology platform, the instrumentation, and the software,” he explains. “All of our partners have brought not just funding but also expertise.,. These partnerships allow us to have the kind of insight that offers a jump-start to move forward in different therapeutic areas we wouldn’t normally have access to.”

Emulate continues to have an active collaboration with The Wyss Institute as well. This includes a $37 million agreement between The Wyss Institute and the Defense Advanced Research Projects Agency (DARPA) to integrate 10 human Organs-on-Chips to study complex human physiology. This project provides foundational research that opened the door for Emulate to envision its overall mission, which is to develop and commercialize the Organs-on-Chips technology into an automated system that is used by industry to emulate human biology, in order to understand how diseases, medicines, chemicals and foods affect human health. “Everything we’ve done with DARPA has given us the insight to not only be able to deliver technically on the science and the biology, but to also scale manufacturing of the chips up and create a stronger foundation for product development,” says Coon.

Emulate is expanding its current product portfolio, which includes Lung-Chip, Liver-Chip, Intestine-Chip and Kidney-Chip, for additional organs such as Skin-Chip, Heart-Chip, Brain-Chip. As the product platform becomes widely adopted and more researchers are using it across multiple industries, Emulate will need to be able to produce millions of chips to move closer to launching Organs-on-Chips as a commercial product. A major step toward the commercialization of Organs-on-Chips was made earlier this year when Emulate secured $28 million of its Series B financing to accelerate its technology into a commercially-available “Human Emulation System.” As stated in a press release on its site, the financing will position Emulate “to accelerate its R&D effort, expedite the launch of its products and expand strategic relationships with industry and academic partners in order to evolve the company towards profitability.”

Since the early stages of research at the Wyss Institute in 2009 to Emulate’s founding in July 2014, experts from design, engineering, medicine, biology, and the physical sciences have shared a common goal of working together to develop Organs-on-Chips to create transformative change. As Emulate continues to advance its product platform, the industry will move closer to a solution that helps develop new therapeutic solutions for patients and offers a less costly way to develop innovative medicines. In addition, the company is also currently working with partners to develop Organs-on-Chips with individual patient stem cells, for use in precision medicine and personalized health applications. Through a focus on improved disease understanding and accuracy of human response, Organs-on-Chips drives efficiency at all levels of drug development and offers possibilities in patient care the industry has yet to see.


Credit: The Wyss Institute at Harvard University

disease-in-a-dish organs-on-chips