2013 Director’s Messages

Select a 2013 message from the list below:

Feb. 26, 2013: Translation Is a Team Sport

In the five months since I took over as NCATS director, I have visited with a wide variety of constituents who have a stake in what we do — patients, grantees, companies, and scientists and physicians across NIH and elsewhere — and it has become clear to me that many, perhaps most, do not fully understand what “translational science” is. This knowledge gap leads to mystification at best, and misconception at worst, about what NCATS is doing and will do.

It is understandable in many ways; after all, NCATS is new and was designed to fill a critical need that complements the work of the other NIH Institutes and Centers. But for NCATS to be successful, our constituents must understand our science and mission. To that end, now and in the future, I will use recent examples of NCATS’ work to illustrate what translational science is and how it differs from the basic research and clinical medicine that flank it in the research ecosystem.

One key feature of translational research is this: translation must be a team sport. Many of the greatest discoveries in fundamental laboratory research, and the best care of individual patients, are brought about by individuals who specialize in particular areas of science or medicine. I personally have been privileged to do basic research and provide clinical care. However, the translational process is so multifaceted that no one person, no matter how committed or talented, can succeed alone.

I am a fan of sports analogies (apologies in advance), and I often say “fundamental research is like golf, but translation is like football.” Although all the players aren’t on the “field” at the same time, each of their contributions is critical for success. The winning team must have not only brilliant individuals but interdependent team players to score the “touchdown” of a new intervention that improves human health in a tangible way.

This kind of teamwork recently enabled the creation of a brain-computer-interface technology that allows paralyzed patients to move a robotic arm using only their thoughts. This remarkable work, published in The Lancet and featured on CBS’ 60 Minutes, was possible only because of the contributions of many members of a diverse research team. The collaboration relied on help from four federal agencies ― NIH, the Department of Defense, the Department of Veterans Affairs, and the U.S. Food and Drug Administration (FDA) ― along with support by a private foundation, a private company and two academic research centers including the University of Pittsburgh, funded in part by NCATS’ Clinical and Translational Science Awards program.

In another great example of teamwork, last month NIH launched a clinical trial to test a treatment for a devastating childhood neurological disorder called Niemann-Pick disease type C. This project moved from the laboratory to the clinic swiftly due to a collaboration of researchers in 10 different disciplines, from genetics to neurosurgery, and from four NIH Institutes and Centers, three academic institutions, several patient-oriented nonprofits and family support groups, and a pharmaceutical company. Scientists from NCATS’ Therapeutics for Rare and Neglected Diseases program contributed to and coordinated the team’s work.

Simultaneously, NCATS-supported research teams are creating entirely new ways to make the therapeutic development process faster, cheaper and more accurate. For example, NCATS’ Tissue Chip for Drug Screening program has partnered with the Defense Advanced Research Projects Agency and the FDA to develop microfluidic systems using 3-D human tissues that more accurately will predict potential toxicities of new drugs, thus addressing one of the primary reasons that drugs fail in development.

In each of these examples of NCATS’ ongoing efforts, we have sought not only to catalyze collaborative development of new interventions, but also to establish new technologies and paradigms that can be implemented broadly to improve the efficiency of the translational process for all.

I look forward to sharing more of NCATS’ translational science achievements with you as we continue to evolve. Since our mission is fundamentally collaborative, NCATS also will be highlighting ways we can hear from you and how you and your organization can get involved. I look forward to working with all of our partners as we continue to re-engineer translational science to deliver life-saving interventions more quickly to more people.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

April 26, 2013: Partnering with Colleagues in Industry to Accelerate Therapeutics Development

My previous Director’s Messages have emphasized that translation is a team sport, describing my ongoing discussions with leaders from academia, government, industry and patient advocacy groups. The feedback from these conversations helps NCATS focus its priorities on the areas of greatest need and build the teams necessary to solve complex translational science problems that can prevent and delay the development of health-improving interventions.

Last year, NCATS reached out to the Biotechnology Industry Organization (BIO) for its advice on the top challenges and opportunities in therapeutics, device and diagnostics development. BIO leaders canvassed the organization’s members to identify the system-wide translational problems they find most difficult and most important for NCATS to address. Following are some of the recommendations that resulted, and how NCATS’ programs address each area of focus.

Identify biomarkers that better predict how patients will respond to therapies. NCATS is working with disease experts in academia and industry and with the Food and Drug Administration (FDA) on ways to identify biomarkers, show how they can predict response to an intervention, and demonstrate their effective and efficient use in the regulatory approval process.

Develop predictive pre-clinical efficacy and toxicity testing methods. The majority of drug candidates fail in early (Phase II) clinical trials because they don’t prove effective enough to treat a specific disease. But these candidates still can be a source for new medicines if researchers demonstrate that the drugs are safe in people. Finding other potential diseases to treat with these partially developed drugs is the goal for NCATS’ Discovering New Therapeutic Uses for Existing Molecules program — an alliance involving eight pharmaceutical companies.

NCATS leads two federal collaborations designed to improve ways to predict how effective or toxic a potential drug might be in humans:

  • The goal of the Toxicology in the 21st Century (Tox21) program, which includes collaborators from the FDA, Environmental Protection Agency and National Toxicology Program, is to develop data-driven protocols that predict which chemical compounds have the potential to disrupt processes in the human body that may lead to adverse health effects.
  • NCATS’ Tissue Chip for Drug Screening program is a partnership with the Defense Advanced Research Projects Agency and the FDA. Through this program, researchers are developing 3-D human tissue models that mimic the structure and function of human organs. Once developed, researchers will use these models to predict whether a candidate drug, vaccine or biologic agent is safe and effective in humans in a faster, more cost-effective way than current methods.

Improve patient recruitment, clinical trial design and the institutional review board (IRB) process. Patient recruitment, novel clinical trial design and IRB harmonization are three areas of focus for the Clinical and Translational Science Awards (CTSA) program that NCATS leads.

Take a leadership role in working with the FDA to develop and validate novel approaches to drug development. From its inception, NCATS has worked closely with colleagues at the FDA across a wide range of regulatory science issues. For example, in both the Tox21 and Tissue Chip for Drug Screening programs, experts at the FDA help us explore how these technologies can be used to assess drug effects prior to approval for first-in-human clinical studies.

I want to thank each of you in the academic, nonprofit, biotechnology, pharmaceutical and venture capital communities who have and continue to contribute time, experience and advice to help NCATS focus on the most pressing issues in translational science. I look forward to continuing these discussions with both current and new stakeholders so that NCATS can align its resources most effectively with the public and private sectors to speed scientific innovation and improve human health.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

June 18, 2013: Translation in Three Dimensions: The 3Ds of NCATS

Much has been written about scientific and operational problems that limit our ability to develop and deploy new and effective interventions to improve human health. Much less has been written about potential solutions to these problems — and that’s where NCATS comes in. We focus on developing these kinds of system-wide solutions.

However, we also know that a goal to develop technologies and models that might improve some aspect of the translational process is simply not enough. Rather, we must demonstrate that these solutions improve the efficiency or effectiveness of an intervention through real-world examples. And if we are successful, we cannot assume that others will adopt these new technologies; instead, we must disseminate the translational advances proactively so that the broader research community can understand, apply and benefit from them.

To illustrate these principles, consider the Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) program. Today, NIH and NCATS announced the first project awards for this crowdsourcing effort to explore potential treatments in eight disease areas using existing pharmaceutical compounds.

New Therapeutic Uses addresses several specific hurdles in the translational process:

  1. The urgent need for medicines to treat the several thousand known diseases that do not have effective therapies approved by the Food and Drug Administration (FDA).
  2. The large number of partially developed molecules that failed partway along the lengthy and difficult path to making a new medicine.
  3. The complicated process of negotiating agreements between parties that want to work together, particularly pharmaceutical companies and academic investigators.

To address these obstacles, we seek potential solutions by gathering broad input about New Therapeutic Uses from across the research community (see the new Request for Information to submit your feedback). New Therapeutic Uses is an outcome of a meeting (PDF - 114KB) of NIH, pharmaceutical and academic leaders in 2011. The proposed approach was for NIH to serve as a matchmaker between pharmaceutical companies, which had molecules that were safe but not effective for their original disease target, and academic scientists, who had new ideas to use these molecules to fight other diseases.

To realize this vision, NIH worked to develop (the first D) two components: (1) standardized template agreements to help NIH, academic scientists and pharmaceutical companies work together efficiently and (2) a mechanism to “crowdsource” ideas for new therapeutic uses from the broad academic community.

To demonstrate (the second D) that academic-industry matchmaking was feasible and effective, NIH worked with eight pharmaceutical companies that volunteered compounds as test cases in the New Therapeutic Uses pilot program, launched in May 2012. The companies made detailed information on 58 molecules available on the NCATS website, and they committed to releasing needed data and supplying each compound at no cost to NIH or the investigators.

Ultimately, nine proposals were chosen for funding and announced today. These awards, supported by the NIH Common Fund, go to investigators at academic institutions across the country. During the next two to three years, these scientists will collaborate with the pharmaceutical companies that developed the molecules to test new therapeutic uses in patients with common and rare diseases.

When these studies are complete in the next few years, we will know if these ideas truly could become new treatments. But already this bold experiment has produced general insights that we can disseminate (the third D) to the research community to improve the translational process.

By applying the 3Ds to the “wisdom of the crowd” in the New Therapeutic Uses program, NCATS has served as the crucial matchmaker for fundamentally new scientific partnerships to bring more treatments to more patients more quickly. Stay tuned for more exciting developments!

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

Aug. 13, 2013: Exploring the Promise of Extracellular RNA Communication

A major NCATS mission is to develop new technologies and models that scientists in many different fields can use to advance translational research and ultimately improve health. Given the enormous opportunities and needs in translational science, we are particularly interested in “game-changing” technologies that could revolutionize the field. Extracellular RNA (exRNA) communication, a recently discovered type of cell signaling, is one such new area. Scientists previously believed that RNA worked mostly inside the cell that produced it, but recent findings show that cells release certain types of RNA that travel through body fluids to affect other cells. ExRNA appears to have many functions in the body and may play an important role in health as well as in a wide range of diseases.

Though still in its early days, exRNA looks to be another of those remarkable discoveries of a naturally occurring process that has enormous translational potential — like RNA interference (RNAi) and stem cells. Stem cells can renew themselves and transform into many different cell types, and they are being used in many of NCATS’ programs to develop drugs more safely and effectively. RNAi is a process by which the activity of genes can be selectively decreased; scientists use RNAi in the laboratory to study the effects of individual genes and are developing RNAi-based therapies, particularly for cancer. Here at NCATS, our program in genome-wide RNAi screening has developed new methods that are driving reliable large-scale studies of gene function and identification of new therapeutic targets.

ExRNA appears to hold the same potential for transforming translational research, but scientists still know very little about its basic biology, functions and roles in disease. To address this need, NIH developed a new trans-NIH program funded by the NIH Common Fund called Extracellular RNA Communication. Today, NIH announced that it will award $17 million this year for 24 research projects designed to improve scientists’ understanding of exRNA and investigate its role in a variety of diseases, including many types of cancer, bone marrow disorders, heart disease, Alzheimer’s disease and multiple sclerosis. NCATS will administer 18 of these awards to develop biomarkers from exRNA found in body fluids and to create new therapeutic strategies for using exRNA in developing and delivering treatments.

The ExRNA program also illustrates a point I make often, about the intersection of fundamental and translational research and how each benefits the other. Discoveries in basic science feed forward to translation, just as translational discoveries often illuminate fundamental mechanisms. ExRNA is both a type of cell-to-cell communication and a route to disease understanding, diagnostics, biomarkers and therapeutics. Like the DNA formerly known as “junk” (the DNA residing outside of genes that we now know has important functions), exRNA was formerly thought to be functionless cellular debris. There are undoubtedly many other such discoveries waiting to be made that will transform both our understanding of ourselves and our ability to intervene when things go wrong.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

Sept. 12, 2013: Effective Pre-Clinical Collaborations Enable Translational Innovations

In an increasingly multidisciplinary research world, innovative scientific advances require effective collaborations. As I often say, translation is a team sport. These partnerships — among academia, government, industry and nonprofits — enable and speed the development of promising interventions to prevent and treat disease.

Collaborations are especially important when it comes to developing treatments for rare and neglected diseases. Private companies may not pursue new therapies for these diseases because of the low anticipated return on investment. One way to lessen this scientific and financial risk — to “de-risk” a project — is to share the work with partners.

NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program is designed to do just that. TRND creates research partnerships between NCATS scientists and academic investigators, nonprofit organizations, and pharmaceutical and biotechnology companies. These therapeutic development partnerships reduce the risks, time delays and costs of advancing treatments for rare diseases into the first stages of clinical testing. Once projects are “de-risked” to this stage, companies are more willing to adopt them and invest the still-considerable resources needed to complete development and achieve regulatory approval.

We often think of TRND as a “bridge” to get rare and neglected disease therapeutics from the idea stage to the proof-of-principle stage. Another NCATS pre-clinical development program that uses a different collaborative model is, appropriately, named BrIDGs (Bridging Interventional Development Gaps). BrIDGs provides targeted contract access to drug development resources that allow academic, not-for-profit and small business collaborators to generate the data needed for an Investigational New Drug (IND) application to the Food and Drug Administration.

Today, NCATS reaches two important milestones with these programs. First, NCATS is holding its first Research and Development Day in Cambridge, Massachusetts, showcasing projects and technologies from TRND and BrIDGs for an audience of biopharmaceutical companies, venture capitalists, angel investors, foundations and others interested in potentially adopting the projects and completing their development, manufacture and marketing. I am enormously gratified by the work that the TRND, BrIDGs and partner scientists have done to move the candidate treatments being showcased today much closer to use in patients — and to attract much interest from the biopharmaceutical community.

With TRND and BrIDGs projects ready to “graduate” from NCATS at R&D Day, we accept four new projects into the TRND program today. NCATS selected the projects for their potential both to treat specific rare diseases and to help TRND scientists uncover new information that can be shared with researchers developing therapeutics for many other diseases. This group of projects also marks the TRND program’s first use of stem cells and its first collaboration with a large pharmaceutical company, Eli Lilly and Co., to co-develop a treatment for a rare disease.

Two of the four projects involve innovative therapeutic approaches to developing a treatment for retinitis pigmentosa, a severe form of hereditary blindness. A third project focuses on a potential treatment for hypoparathyroidism, a syndrome that leads to a persistent lack of calcium and the need for high-dose supplements that can damage the kidneys. The remaining project involves development of a treatment for a heart disorder associated with LEOPARD syndrome, an extremely rare genetic disease that can lead to early death.

With today’s milestones, NCATS moves one step further to achieving its mission of developing, demonstrating and disseminating new technologies and models that will transform the translational process and thus speed the delivery of more treatments to more people more quickly. Thank you for your interest, and I hope you will return to our website often to keep up with the exciting developments in all of NCATS’ programs and to partner with us in our work. We look forward to hearing from you.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

Oct. 22, 2013: Clinical and Translational Science Awards Catalyze and Speed Translational Research

In recent years, basic scientists have made breathtaking advances in our understanding of the human body’s biology and chemistry. The human genome has been sequenced, stem cells understood and RNA interference discovered. All of these advances have been celebrated for holding enormous promise for improving human health. But the road from promise to achievement of health impact — what is called “translation” in medical research terms — is long, complex and full of obstacles. For example, it can take 14 years or more before a basic discovery leads to a new treatment. Another decade can pass before that intervention is available to all patients who need it.

Speeding up this process is a top priority for NCATS, and the Clinical and Translational Science Awards (CTSA) program is key to our efforts. The CTSA program supports a national consortium of medical research institutions that work together to improve the way clinical and translational research is conducted nationwide. CTSA institutions develop new tools, methods, resources and services that catalyze research progress. Because translation can’t happen without cooperation and collaboration across disciplines, CTSA institutions also lead training and career development for a new breed of team-oriented scientists and clinicians focused on translation.

The CTSA program is NIH’s largest single investment in clinical research. Today, NIH announced more than $79 million in fiscal year 2013 funding to support 15 CTSAs. The 2013 awards expand the CTSA Consortium to include Dartmouth College in New Hampshire, extending the program’s nationwide network to 31 states and the District of Columbia.

NCATS is continuing to evolve the CTSA program to meet the needs of clinical and translational investigators and the communities they serve. In June 2013, the Institute of Medicine (IOM) issued a report of its findings following an in-depth review of the CTSA program. Its recommendations included formalizing and standardizing the evaluation processes for individual CTSA institutions and the program as a whole, advancing innovation in education and training programs, and ensuring community engagement in all phases of research.

We already are making strides toward addressing these priorities. NCATS has assembled a working group of stakeholders to guide program changes and implement the IOM report’s recommendations. One of the group’s first tasks is development of clear, measurable goals and objectives for the CTSA program that speak to critical issues across the full spectrum of clinical and translational research.

All of these efforts will no doubt strengthen the CTSA institutions, further enabling their leadership of national efforts to enhance the efficiency, quality and safety of translational research and the translation of scientific findings into interventions that improve human health.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

Dec. 17, 2013: Improving Health and Accelerating Drug Development Through Predictive Toxicology

We all are aware that chemicals can be helpful or harmful to our health, but the systems we have for evaluating those effects are, like so many aspects of translational research, inefficient and often ineffective. Chemicals can be more than just life-saving (e.g., penicillin) or life-ending (e.g., cyanide). Most frequently, chemicals can fall into either category, depending on the context and the dose. For example, the drug warfarin is effective both at preventing stroke in humans and at killing rats.

Toxicity — a chemical’s ability to produce harmful effects in animals or humans — causes nearly one third of drug development failures and can produce harmful health effects from chemicals in the environment. Scientists cannot tell in advance whether a compound is toxic because they usually don’t know how it affects the molecules and cells of the body.

If scientists could better predict which chemicals may be harmful, they could produce safer drugs and chemicals more quickly and efficiently. In this quest, NCATS partners with the National Toxicology Program at the National Institute of Environmental Health Sciences (NIEHS) and two other federal agencies in an initiative called Toxicology in the 21st Century, or Tox21. The collaborative effort began in 2008 among NCATS, NIEHS and the Environmental Protection Agency (EPA), with the Food and Drug Administration (FDA) joining in 2009. The program grew out of a 2007 National Academy of Sciences report, Toxicity Testing in the 21st Century: A Vision and Strategy, and a commentary in Science co-authored by NIH Director Francis S. Collins, M.D., Ph.D., which emphasized shifting toxicity testing from animals to tests called “assays” that use cells and biochemical components. This shift may improve scientists’ ability to predict toxic effects from chemicals more quickly and efficiently. (In addition to Tox21, NCATS’ Tissue Chip for Drug Screening program also is designed to improve toxicity testing.)

Through the Tox21 program, researchers are testing 10,000 drugs and environmental chemicals for their potential to affect molecules and cells in ways that can cause health problems. The compounds undergo testing in the high-speed robotic screening system at the NCATS Division of Pre-Clinical Innovation in partnership with our Tox21 collaborators at NIEHS, EPA and the FDA. One of the most effective ways to enable translational research improvements is releasing data to the public, so all Tox21 results are made available in the National Library of Medicine’s PubChem database as well as in public NIEHS and EPA databases.

Today, EPA announced the release of new toxicity data on 1,800 chemicals from its ToxCast library, which is part of the Tox21 library of 10,000 chemicals. The scientific community can access this information on a new Chemical Safety for Sustainability Dashboard, a user-friendly, Web-based system. As part of this data release, the EPA is launching a data challenge, asking the scientific community for innovative ways to use the new data to predict negative health effects.

Also this month, the Tox21 partners are celebrating winners of the program’s NIEHS–NCATS–UNC DREAM Toxicogenetics Challenge, which resulted in a greater understanding of how a person’s individual genetics can influence their body’s response when exposed to widely used chemicals.

Tox21 is a great example of the NCATS approach to scientific and organizational problems in translational science. Scientifically, Tox21 researchers focus on improving toxicity testing across a broad diversity of drugs and chemicals to look for effects applicable to any organ system or disease. Organizationally, Tox21 is teamwork at its best: multiple federal agencies with complementary expertise tackling a complex chemical, biological and data-heavy challenge by leveraging existing resources. For example, NCATS scientists adapted one of the existing high-speed robots at the NCATS Chemical Genomics Center to test the Tox21 compounds.

Strategies like these highlight how NCATS is developing, demonstrating and disseminating improvements in translational science, creating a whole that is greater than the sum of its parts. I hope you will follow the developments in these toxicity programs as they propel better treatments and better health.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences