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Good Science

January 2018


January 26, 2018   animal testing

 

Great Science: 2017’s Top 10

This past year was full of advances in science and policy that demonstrate exciting progress in making science more humane and human-relevant. Here are our favorites:

1. USDA database mostly restored

The removal of USDA inspection reports from their online database earlier this year left the public with no way of readily accessing these reports, preventing public knowledge of which facilities using animals had violations of the Animal Welfare Act. After great pressure from the Physicians Committee and other animal advocacy organizations, the database was partially restored. While inspection reports can now be readily accessed again, identifying information of certain violators, specifically breeders, has been blacked out. 

2. Bioprinting of human tissues 

Bioprinting of three-dimensional (3-D) human tissue allows researchers to create more accurate models of human tissues and organs to study and eliminate the use of animals. There are often differences between individuals in the effectiveness or toxicity of a given drug, mostly because we all absorb and metabolize—or break down—drugs at different rates. The differences between animals like rats or mice and people are even greater. With 3-D bioprinting, models can be made from the patient’s own cells, allowing researchers to tailor treatments to the specific person. We have reported on two different studies authored by scientists who created tissues to help assess how drugs are absorbed into or metabolized in the body. We also reported on a 3-D-printed brain model. In fact, there were 199 studies in the scientific literature this year reporting advances in creating human tissues models using bio-printing techniques, and we expect this to keep growing in the coming years. 

3. Surgical simulation advances

This year saw the rise of a new way to teach medical procedures without animals. Maximum Fidelity Surgical Simulations has pioneered a groundbreaking method for perfusing the blood vessels of human cadavers. Using artificial blood, the cadavers can be used in scenarios ranging from operating rooms to outdoor exercises for military medics.

4. Organs-on-chips

Miniature versions of human organs make up microphysiological systems, or organs-on-chips. These tiny devices, which are about the size of a USB flash drive, are designed to mimic human tissues and allow scientists to see how human cells and tissues behave. Organs-on-chips are capable of replacing animals for drug testing and the development of new treatments, as well as studying a variety of disease processes and responses. The National Institutes of Health doubled down on previous investments in 2017, providing $15 million a year for two years to scientists around the country to develop models for human diseases. They even debuted a “tissue chips in space” project. Major progress on developing these breakthrough systems was made in 2017, in studying lung cancer, cardiotoxicity, asthma and infection, vascular biology, and the blood brain barrier

5. FDA Releases Predictive Toxicology Roadmap

In December, the Food and Drug Administration released a groundbreaking Predictive Toxicology Roadmap aiming to transform the safety testing conducted for FDA-regulated products. The six-part Roadmap reflects a shift at FDA from animal-based testing toward cutting-edge human-based approaches, such as organs-on-chips, computational toxicology and read-across methodologies. Human-based approaches are expected to provide more predictive information than animal testing because they enable scientists to directly investigate how drugs interact with human cells, tissues and processes. 

6. Adverse Outcome Pathway for Respiratory Sensitization  

This fall, scientists led by the Physicians Committee’s Kristie Sullivan, M.P.H., published a paper outlining an Adverse Outcome Pathway for chemicals which cause sensitization of the respiratory tract. This dangerous condition develops often in health care, cleaning, and chemical industry workers, and causes them to experience severe coughing, wheezing, constriction of the airways, and other asthma-like symptoms that worsen upon repeated exposure to smaller and smaller amounts of specific chemicals, making work dangerous or impossible. Our team of toxicologists, immunologists, and chemists combed the scientific literature for all studies related to this endpoint, and constructed a pathway for how we think this condition develops, from exposure to chemicals at the molecular level to priming of immune cells to over-react and cause these symptoms.  

AOPs outline the state of the science for a particular toxicological endpoint (or effect, such as carcinogenicity) and make it easier for scientists to develop nonanimal approaches to test chemicals for effects of interest. Now that the AOP has been published in the scientific literature, the team is evaluating the human cell-and computer-based methods they identified to build evidence for regulatory agencies to use these methods instead of animals to identify chemicals that may cause this devastating disease. 

7. State and county officials speak out against UW’s use of animals

Live pigs are used and then killed in the University of Washington’s paramedic training program. But in January 2017, after outreach from Physicians Committee staff and members, eight members of the Washington House of representatives wrote to UW to raise their concern about the practice. A few months later, two elected officials in King County, home to UW, followed suit. The university is feeling the pressure and has agreed to pursue the development of a method to replace animals. While several human-based methods are already available for surgical airway training, UW’s decision is progress.  

8. Stem cell resource established

Human induced pluripotent stem (iPS) cells provide a human-based approach to model diseases. This year, significant advancements were made in modeling several diseases with stem cells, giving us better insight into the effects of those disease in humans. Some breakthroughs include the use of stem cells to model diabetes, prion disease, and anorexia nervosa. To continue to facilitate breakthroughs, researchers from the Human Induced Pluripotent Stem Cell Initiative created the most comprehensively characterized bank of human stem cell lines complied to date. These normal human-derived stem cells will benefit scientists by allowing them to better understand the natural variations of stem cell lines, and thus natural variations among the human population.

9. Funding for EPA research to develop alternatives supported by Congress

Research at the EPA’s National Center for Computational Toxicology is essential for spurring progress to replace animal testing with human-relevant methods, especially under a mandate from the Lautenberg Chemical Safety Act for the 21st Century that requires EPA to replace and reduce animal tests for assessing chemical safety. However, the Trump administration’s 2018 budget proposal would have slashed funding for the chemical research by 31 percent. After lobbying by the Physicians Committee and other organizations, these proposed cuts to EPA budget did not become a reality and computational toxicology funding levels were maintained, allowing the EPA to continue developing studies that protect public health and countless animal lives. 

10. Plants Found to Model Anesthetic Drug Efficacy

A very unique study published in December found that plants exhibiting touch-induced movements (such as the Venus fly-trap) respond to anesthetic drugs in similar ways to humans. The drugs apparently block the same molecular mechanisms and electrical signals at work in humans and other animals, and could represent an alternative to testing the safety and effectiveness of new drugs in animals.

We are seeking a student or recent graduate interested in promoting alternatives to the use of animals in medical research and education for our summer 2018 Replacing Animals in Research Internship. Apply today!

January 17, 2018   dementia

 

Microsoft founder Bill Gates recently announced a personal investment of $50 million in the Dementia Discovery Fund (DDF), a public-private fund supported by charities, industry, and government to diversify the search for a drug to treat dementia. Gates wants the scientific community to look beyond amyloid and tau proteins in the brain, two key hallmarks of the disease, for the causes of dementia with the ultimate goal of creating an effective treatment. He is correct that so narrowly focusing research into the role of these proteins has diverted our attention from more productive research. But his laser focus on treating rather than preventing dementia is not the only strategy to overcome this disease. The search for a drug to treat Alzheimer’s disease and related dementias has met with little success. And given the rapid rise in the incidence of these diseases, the scientific community and those who fund their work would better serve the public by shifting their focus to prevention—or, at the very least, making prevention a high priority.

We have some suggestions:

First, as we have learned in other major research pursuits, the use of animal models of disease typically fails to provide us with meaningful insights into how a disease originates and progresses in humans. Therefore, all research should take full advantage of the many innovative methods that are human relevant. We applaud DDF for its support of in vitro human-based approaches in their search for therapeutics. These include using cell-biology based approaches to find targets in human brain tissues (Cerevance), human neurons derived from induced pluripotent stem cells (Gen2), in vitro platforms to restore immune cell function (TIAKI therapeutics), and an in silico program to screen a library of more than 500,000 compounds virtually for drug candidates (DDF ChemCo).

Second, investments should be made in these underfunded areas:

  • Human brain tissue banks and resources like the Allen Cell Types Database. To better understand the causes of dementia at the population level, we need more research into the lifestyle factors that play a critical role in driving the disease, which can help explain racial-ethnic disparities.
  • A better clinical test to diagnose the disease earlier and track its progression. This will help identify patients for earlier intervention studies. If we had a disease specific biomarker like cholesterol for heart disease or hemoglobin A1C for diabetes, the development of Alzheimer’s may become easier to control. The key to finding such a biomarker will require a better understanding of the external factor(s) driving the disease in humans and strictly focusing the search in human specimens. More clinical trials assessing the efficacy of nonpharmacological interventions such as changing dietary habits, so that we can give people evidence-based advice to take control of their health.
  • Design clinical trials to include patients with multiple chronic conditions so that interventions can be broadly applicable to patients with many chronic conditions. Many drug trials exclude these individuals in order to demonstrate the specificity of a treatment for the disease. However, Alzheimer’s often occurs with other chronic medical conditions. Testing lifestyle interventions would fill this research gap and encourage patients to participate in trials before they develop any signs of the disease.
  • Use the common database for which Gates advocates to catalog links between modifiable lifestyle patterns and dementia prevalence or incidence over time in different parts of the world. Moving away from focusing on data derived from animal models and failed drug trials will help us better understand what is really driving dementia that we can change in a short period of time.

Despite billions of dollars spent, pharmaceutical companies have not been able to find a drug to even delay the onset or progression of dementia. Pfizer’s recent announcement to end its research program on developing new drugs for Alzheimer’s disease is indicative of how fruitless and disappointing these efforts have been (hyperlink to: https://www.usnews.com/news/top-news/articles/2018-01-07/pfizer-ends-res...). With the high financial burden the disease implies and the devastating impact on the patient and families, we must invest more in human studies that will help us understand how to treat and prevent this disease. If Gates devoted a mere 10 percent of his $100 million planned investment in these areas, we might spare millions of people from the crippling effects of dementia.