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Alternative Methods
Computer modeling techniques
In Silico research, multimedia CD-roms and models
Research teams around the world are working on biosimulation and ‘virtual humans’. These models are designed to predict drug metabolism and metabolite interaction with any given organ.
BioSim http://www.biosim-network.net/
BioSim is a European Union-sponsored Network of Excellence on biosimulation. It aims to improve drug development and provide alternatives to animal testing.
A 3-D virtual human heart model developed by Leeds University, U.K. will be distributed through BioSim. Currently, it is being used to simulate the effects of a commonly used heart drug (lidocaine).
Pharmaceutical companies such as Roche have already used biosimulation to approve heart drugs and find new uses for existing drugs (eg. Pegasys http://www.pharsight.com/library/MODELS_THAT_TAKE_DRUGS.pdf).
Biographics Laboratory 3R http://www.biograf.ch
The Biographics Laboratory 3R is a non-profit research organisation. It develops computational technologies with the aim of reducing and replacing animal tests in the biomedical sciences.
Their research is currently focused on the prediction of adverse effects triggered by drugs and chemicals. They have developed VirtualToxLab™ an “…in silico tool for predicting the toxic (endocrine-disrupting) potential of existing and hypothetical compounds (drugs, chemicals, natural products) by simulating and quantifying their interactions towards a series of proteins known to trigger adverse effects using automated, flexible docking combined with multi-dimensional QSAR.”
Center for Cardiovascular Bioinformatics and Modeling (CCBM)
The centre aims to develop “new methods for the representation, storage, analysis and modeling of biological data, and to use these quantitative approaches to better understand cardiovascular function in both health and disease.”
Entelos http://www.entelos.com/
A commercial company that provides computer models of virtual patients for drug research. The system “improves the success rates of clinical trials, and helps bring therapeutics to market faster.”
Fetal Charlotte
http://ww.aspects.net/~fetchar/Index.html
Computer modeling of the physiology of human fetuses.
Hurel Corporation http://www.hurelcorp.com
HμREL® is a microfluidic “biochip” with separate, yet connected compartments. The compartments contain a sample of tissue from different parts of the body. “The compartments are linked by microchannels through which a blood substitute flows. The test drug is added to the blood substitute and circulates around the device; thus mimicking what goes on in the body on a micro scale. Sensors in the chip feed back information for computer analysis.”
HμREL® is “compatible with virtually any type of traditional in vitro assay modality (mass spectroscopic, immunohistochemical, immunofluorescent, gene expression, and others).”
Lhasa Limited http://www.lhasalimited.org/
Lhasa Limited is a not-for-profit company and educational charity. They develop expert computer systems for predicting whether a chemical is toxic. They have also developed software which predicts the “metabolic fate of chemicals”.
NETWORK Engineering virtual tissues and organs http://www.cbiol.leeds.ac.uk/netapp.html
Leeds University integrated biology project is involved in developing human virtual tissues: heart, uterus and spinal cord.
Physiome Project http://www.physiome.org/
The National Simulation Resource (NSR) Physiome Project is the worldwide effort to collect information on physiology, pharmacology and pathology of humans and to present this information via computer modeling.
SIMCYP http://www.simcyp.co.uk
Simcyp’s pharmacokinetic software provides a modeling tool for “…drug absorption, distribution, metabolism and excretion (ADME) in virtual populations”. The software even allows simulation of patient variability. “Simcyp Paediatric” allows predictions of pharmacokinetics in neonates, infants and children.
Simulab Corporation http://www.simulab.com/
Producers of medical and surgical simulators. For example, the TraumaMan® System is an anatomical human body form, designed for students to practice several surgical procedures. This simulator is approved by the leading Surgical Education Society as an alternative to live, non-human models or cadavers for their Surgical Practicum of their leading Trauma Training Course. The TraumaChild is a high fidelity soft tissue simulator designed to train advanced trauma surgical skills. This simulated five year old human breathes, bleeds, and has replaceable tissues for a first cut experience. It is also approved by leading surgical societies for the medical curriculum.
Solidus Biosciences http://www.solidusbiosciences.com/
Solidus have developed DataChip (Data Analysis Toxicology Assay Chip) and MetaChip (Metabolizing Enzyme Toxicology Assay Chip). These are ‘In vitro’ tests using glass slides with DNA chips designed to mimic human reactions to potentially toxic chemical compounds. Computer analysis is used to evaluate the metabolic reactions which yield rapid identification of both harmful and useful substances and allows individualized patient therapy. (See also SimuGen http://www.simugen-global.com/)
Topkat http://accelrys.com/products/discovery-studio/toxicology/
Toxicology Prediction by Komputer-Assisted Technology (TOP-KAT) was originally developed by Health Design Inc.
Topkat is a computer software program that measures toxicity, mutagenicity, carcinogenicity and teratonogenicity.
Here’s a partial list of DS TOPKAT users
• Amgen
• Buckman Labs International
• US Centers for Disease Control and Prevention (CDC)
• Heath and Welfare Canada
• US National Cancer Institute (NCI)
• US National Institute for Occupational Safety
• Pfizer
• National Institute for Public Health and Environment, Netherlands.
• US Environmental Protection Agency (EPA)
• Vertex Pharmaceuticals
• Walter Reed Army Institute of Research
• Wyeth Pharmaceuticals.
http://accelrys.com/products/datasheets/ds_topkat.pdf
Multimedia
NORINA: Norwegian Inventory of Audiovisuals
http://oslovet.veths.no/fag.aspx?fag=57&mnu=databases_1.
An English-language database with approximately 3,800 visual aids on alternatives. Also includes dissection alternatives - at all levels from junior school to University.
Australian Initiatives
On-line Respiratory Control Practical
Dr Laura C. Minasian-Batmanian and Gautham Jayachandran have designed a novel interactive practical, which allows students to question and understand the roles of various chemical, mechanical and nervous factors important in the regulation of ventilation.
Batmanian, L. 2005. An innovative, interactive, self-instructional, online alternative to replace a face-to-face respiratory control practical. British Journal of Educational Technology.36, 335-337
On-line Cardiovascular Control Practical
This on-line, interactive practical was also developed by Dr Laura C. Minasian-Batmanian. It will replace the use of approximately 250 rabbits per year at the University of Sydney. The practical will reduce animal-based learning and thus promote alternatives to animal experimentation in teaching at universities.
