Brown University shieldBrown University

New Models for Drug Discovery and Toxicity Testing Reducing the Use of Animals in Research

Leader:  Jeff Morgan - Molecular Pharmacology, Physiology & Biotechnology

Drug discovery, the process by which pharmaceutical companies discover, test and bring to market new drugs is a very long and very expensive process. Research with animals is critical to this process. But, there are major problems that need new innovative solutions. Several worldwide trends have made this an area of high importance and one in which interdisciplinary problem solving is needed.

1.      The new drug pipeline is drying up. Pharmaceutical companies are in need of new more accurate models that better predict a drug's efficacy and a drug's toxicity.

2.      The drug discovery process is very expensive. New in vitro models are needed to reduce the cost of animal testing.

3.      Animal testing is not always an accurate predictor and drug failures are very expensive.

4.      Regulatory agencies are actively discouraging the use of animals in research. Europe has banned the use of animal testing for all cosmetics and this trend is continuing.

5.      There are ethical issues surrounding the use of animals in research that influence public acceptance and the public’s support of research.

6.      Human cells are becoming available. The breakthrough of induced pluripotent stem cells (iPS) is yielding human cells of specific tissues (cardiomyocytes) and with specific defects (Parkinson neurons).

7.      Tissue engineers are making 3D tissue equivalents. These tissue equivalents are being transplanted to patients and they are being used for toxicity testing. These models are currently being adapted to high throughput.

8.      Microscale technologies are miniaturizing all lab procedures. The lab-on-a-chip technology is impacting numerous fields including in vitro models of tissues and diseases.

9.      Computational models are being applied to these problems. There is great interest and potential for using in silico methods to model the myriad biochemical responses to toxic agents.

10.  Pharmaceutical companies are investing in this area and agencies such as NIH, FDA, and DARPA are calling for new proposals. 

This team of HHMI-Brown Scholars will gain hands-on laboratory experience with a new method for culturing living cells in three dimensions (3D) and investigate its potential application in several areas. They will learn the underlying fundamental knowledge and will gain hands-on experience with the following lab skills:

  • Mammalian cell culture including aseptic technique, cell counting, cell passage, cell cryopreservation
  • A new 3D cell culture technology
  • Brightfield, phase contrast, fluorescent and time lapse microscopy
  • Quantitative image analysis

This team of HHMI-Brown Scholars will also learn about:

  • The multi-step process of drug discovery
  • The regulations covering the safety testing of new drugs and medical devices
  • The use of animals in research
  • The worldwide efforts to reduce, refine and replace the use of animals