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User:MaynardClark/Nonanimal Research Roadmap

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"Strategic Roadmap from Animal-Based Research Models to Nonanimal Research Alternatives" In short: "Nonanimal Research Roadmap"

What elements are necessary for this project to fully succeed? Does any part of this effort stand apart from the others, or is the entire replacement, refinement, and reduction effort historically synergistic? "Strategic Roadmap from Animal-Based Research Models to Nonanimal Research Alternatives"

How does one set out, for otherwise unengaged persons (of intelligence and learning), the challenges and prospects, not blithely, but grimly and realistically, what would be needed to make significant progress in such a project (if indeed the cards ARE stacked against such a hope WITHIN the biomedical research establishment, which they may not be)? The cost of using animal models is considerable and a potential disincentive to using them where nonanimal research models are available and of equal or better knowledge production efficacy.

Areas to Consider:

  • Research Direction - definition of RD in order to identify 'knowledge gaps' vis a vis R&D
    • Importance of knowledge gaps: A Socratic dialogue distinguished 'known unknowns' and unknown unknowns' (in the phrasing of Donald Rumsfeld. In the NRR (nonanimal research roadmap), the recognition and identification of knowledge gaps is foundational for defining and redefining 'research direction', timing, and emphasis. Without resolving strategically important knowledge gaps in methodology, we won't get there - the road to the development of nonanimal biomedical research methods cannot be followed to its long-term goal - the development and validation of each nonanimal research method. Sponsored researchers may produce the knowledge of their sponsored projects, but methods researchers will not produce validated nonanimal research methods.
  • Comprehensive Map of the Animal-Based Models to Replace, Refine, or ...
  • Historical sense of the struggle to do the full map of things we do in the intertwined efforts?
  • Sense of Mission
  • Engagement of 'vivisectors' (those who use animal-based models in biomedical research) who may know what KINDS of knowledge they want or believe they need, and what they WOULD want from a nonanimal model.
  • Commitment to the legitimacy of the scientific endeavors (at least some of them?)
  • Parity with other ways to reach the overt goals of the biomedical research (e.g. better human health outcomes for both individuals and populations)?
  • Should researchers and research strategists consider alternative ways of achieving improved health for individuals and populations (rather than by using the biomedical models?
  • What analytical tools should be included in the toolbox for later use by bright, promising, well-prepared young persons who are considering careers in roles committed to improving the quality of human living?
  • Which nations are likely to contribute significant talent (long-term) and funding (long-term) to such efforts (India? China? Switzerland? Germany and other nations in the EU?)? How can American institutions tap or 'opportunize' such potentials to build such facilities in advance of global recognition of such a venture's desirability?
  • Asking questions in human-relevant ways so that (i) fewer (or no) animals are used (ii) because animal models would not helpfully model the knowledge area that is to be explored.

Non-animal testing techniques for medical purposes are efficient and far advanced. Alternatives to animal testing make use of medical imaging, microdosing, metabolism simulation, biochips, mathematics, visualizations, and other methods. These more advanced techniques give great insight, otherwise not offered by use of animal testing. The human mind is capable of solving problems related to medicine. If humans are able to determine the chemical composition of distant galaxies, imagine the potential for non-invasive technology for modeling tissue interactions.

This type of research also may prove to be cost effective, while increasingly improving both the speed of conducting research and the quality of the research results.

The way and redundancy in which animal testing is carried undermines the capability for human innovation. Animal testing also desensitizes participants, and it influences the idea of the lack of value for life,[1] which further reduces the quality of this type of research. Research from animal experimentation is limited, since animals do not have "all the same maladies as do humans."[2]

Approximately 9 out of 10 medications that qualify by the expectations for animal testing later fail human trials.[3]

Optical: medical imaging and microscopy

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Medical imaging can give great details of the inner workings of the human body. This method is far more efficient than animal dissections for determining effects on living tissue. Dyes that can cross the brain-blood barrier can be used to improve medical imaging for human observations,[4] and dyes can be used for in vitro observations as well.

Microdosing uses medical imaging to see how the body metabolizes miniscule drug amounts.[5] This is an example of an in situ human observation. In situ is taking observations without harm to an organism while it is alive.

Magnetic resonance imaging

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Common magnetic resonance imaging (MRI) machines have resolution ranges in millimeters. Experimental MRI resolution has been improved to detect images on the micrometer scale. A 10 nanometer resolution MRI technology is in conception that could be fitted to existing MRI machines.[6]

Hyperspectral imaging

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Hyperspectral imaging (HSI) is being developed and standardized for use in advanced biological sensing.[7] It appears to have unprecedented detail of living tissue, displayed on a hyperspectral image projector. Hyperspectral imaging already has uses in astronomy, mineralogy, physics, agriculture, surveillance, environment, chemistry and other sciences.

Nanosensor imaging

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Nanosensors are able to detect cellular activity, with the aid of dyes. Cultured cells are grown in a laboratory, then nontoxic dyes display to nanosensors the metabolic activity of the cells. When a chemical is toxic to the cell, the metabolic activity of the cell reduces or halts, sometimes as the cell dies.[8]

Medical ultrasonography

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Medical ultrasonography can image in real time, but at a lower resolution than other imaging techniques. It is completely safe.

Microscopy

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Recent advances in microscopy allow observation of cell interactions with pharmaceuticals,[9] and allow the measure of oxidative stress on cells.[10]

Biochip

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Organ on a chip is a biochip layered with organ-specific tissue. Medication safety and pharmacokinetic drug interactions can be tested on it.[11] Using biochips are less costly and less time extensive than animal testing. Another added benefit of using biochips, is that less training is required for use of this approach. Biochips are an example of in vitro laboratory testing.

There is a new technology that allows for cells to be suspended in air. A nontoxic magnetic filament is placed inside the cells to allow them to levitate, and this is useful for improving toxicity testing on cells.[12]

Another recently developed technology uses a different type of biochip to separate microscopic organisms or cells based on size. Centrifugal force is generated by lasers to separate particles by size.[13] This has uses for: "medical diagnostics; testing food, water and contaminated soil; isolating DNA for gene sequencing; crime-scene forensics; and pharmaceutical manufacturing."[13]

Organs on a chip

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Main article: Organ-on-a-chip

The Wyss Institute for Biologically Inspired Engineering (US) intends to develop in-vitro organs for drug screening and thereby eliminate the use of animals for this type of testing. One model is the "lung-on-a-chip".[14] This combines microfabrication techniques with modern tissue engineering and mimics the complicated mechanical and biochemical behaviours of a human lung.

Various ethical and practical, scientific questions emerge concerning proceeding with organelles as replacement models of disease and function.[15]

Bioethicist Arthur Caplan of New York University Langone Medical Center said he worries that researchers will rush to use organoids in lieu of animal models before the former have been properly validated.

Those issues include:

Biosensors and electronics

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Information can be relayed to a microchip from magnetic sensing that detects biological reactions.[16] Thousands of sensors can be placed on a small area to detect microscopic reactions.[16] Uses include drug testing, protein interactions, and cancer detection.[16] It is capable of sensing on a smaller scale than was possible before.[16]

Applied mathematics

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In papyro is an experiment done on paper, which in this case is by math.

Math can be used to find out which peptides, by attachment, will be effective against viruses. Math use reduces the vast amount of peptides that would have to be tested.[17] From here, the peptides could be further engineered.[17] This is speculated for use with other types of microorganisms.

Mutation patterns by bacteria can be documented, then formulated.[18] Future mutations can be calculated using these formulas.[18] Other disease patterns, for instance leukemia activity, can also be charted, for timing of medication treatments.[19]

The electric and dimensional properties of catalysts can be indexed and sorted.[20] Mathematical formulas are then used to identify the effective compositions for new pharmaceuticals.[20]

Computer simulation

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In silico is doing an experiment in simulation, and this can overlap with in papyro.

The brain of a mouse has been simulated on a computer at a reduced speed and scale,[21], and, of course, there is growing future potential for this and similar techniques. Simulating viruses and their interactions with other organisms has been done before. This research method considers the simplicity of viruses, compares them with complex organisms, and then makes them easier to simulate.[22] Protein interactions of larger organisms can also be practically simulated.[23]

Helmet design based on head injury susceptibility, physics and function can be improved using computer simulation. Simulations can be done comparing injuries without helmets to helmets and their modifications.[24]

There is a computer programming language that is based on biology, named little b, than can be useful for biological research.[25]

Mannequin simulation

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The use of test mannequins can help students practice crucial skills before performing medical procedures on real patients. Mannequins that simulate real conditions are highly effective and efficient at teaching, and they are a standard at medical schools.[26]

Sample analysis

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See also: Medical diagnosis/Lab-on-a-chip

Sample analysis can be of urine, swiping, fine-needle aspiration, blood, or other sample. Spectrochemical analysis is one way of determining the metabolites or other chemical medium through light frequency analysis. Direct analysis can also be made of, chemical reaction, pH, specific gravity, or other measure.

More than 3,000 chemicals can now be detected in urine, from the previous quantity of 100 chemicals, and this number is expected to grow continuously.[27] Medical conditions, drug use and nutrition can now be better analyzed and diagnosed through urinalysis. This improvement in urinalysis may allow it to replace many other body fluid analysis methods.

 

Biochips to diagnose diseases in tissue or blood samples may largely replace test-tubes. The entire lab can be conducted on the chip, called lab-on-a-chip, rather than add external tubing to detecting or measuring devices.[28]

Researchers are developing a way to test glucose levels of saliva, as a way of replacing blood tests to measure glucose.[29]

Diagnoses can be made more quickly and more accurately with biochips. Cancers can be detected through biochips before symptoms occur.[30]

Using existing resources

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By using existing known safe ingredients, testing is usually unnecessary for many products.[31]

Status and progress

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Over 100 million animals are experimented on each year.[32][3]

90% of 1,000 biomedical researchers surveyed in 2011, believed animal research was a necessity.[32]

As of 2013, animal testing for cosmetic products has been banned in the European Union, [33][34] India,[35] and Israel.[36] The sale of cosmetic and toiletry products tested on animals has also been banned in the E.U. Over 1,000 companies worldwide have banned using animal testing in their products.[35] In Japan, replacements for cornea testing have recently made an advancement that may replace animal testing there.[37]

A gallup poll of 1,000 random Americans was taken in 2013 for opinions of animal medical testing, and it manifested an estimate of increasing disapproval ratings.[38][32] 41% of adults, including 53% of women, and a majority of younger adults believed medical testing on animals to be morally wrong according to this poll.[32][38] These figures are a significant increase from 2001 data.[38][32] A separate nationwide poll in the United States in 2013 showed about a 70% strong disapproval of conducting cosmetic testing on animals.[31]

In 2014, São Paulo state in Brazil banned animal testing for cosmetic and personal care products.[39] As of March 2014, H.R.4148 - Humane Cosmetics Act was introduced to U.S congress which proposes the restriction of ingredients tested on animals in cosmetic products in the United States.[40] The definition of cosmetic by the FDA for the United States' purpose only is "(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap."[41] Also in March 2014, the End Cruel Cosmetics Bill was proposed to Australia's Parliament.[42] China plans to remove mandatory animal testing requirements for cosmetics in June 2014.[43]

Multimedia

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  • Hyperspectral imaging of intestine cells at varying wavelengths.

Research initiatives

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SEURAT-1

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SEURAT-1 is a long term strategic target for "Safety Evaluation Ultimately Replacing Animal Testing".[44] It is called "SEURAT-1" to indicate that more steps have to be taken before the final goal will be reached. SEURAT-1 will develop knowledge and technology building blocks required for the development of solutions for the replacement of current repeated dose systemic toxicity testing in vivo used for the assessment of human safety. SEURAT-1 is composed of six research projects, which started on January 1, 2011 and will run for five years. These projects will closely cooperate with a common goal and combine the research efforts of over 70 European universities, public research institutes and companies. The collaboration between these six research projects, the dissemination of results, the cooperation with other international research teams, and the continuous updating on research priorities will be facilitated by the coordination and support action project "COACH".

SEURAT-1 was developed through the Framework Programme 7 (FP7) research initiative and was created through a call for proposals by the European Commission (EC) that was published in June 2009. The Cosmetics Europe industry offered to match the EC's funds to make a total of EUR 50 million available to try to fill current gaps in scientific knowledge and accelerate the development of non-animal test methods.

Euroecotox

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Laboratory animals are not restricted to rats, mice, dogs, and rabbits, but also include fish, frogs and birds. Research into alternatives to replace these species is often neglected, although fish are the third most widely used laboratory animal used for scientific purposes in the EU.[45] This is also the field where until now only two alternative tests exist worldwide: One guideline, OECD TG 236,[46] and one guidance (OECD series on testing and assessment 126)[47] are so far available.

Euroecotox[48] is a European network for alternative testing strategies in ecotoxicoloy. It was funded by the Seventh Framework Programme (FP7) of the European Commission Environment Programme. The main objectives of the Euroecotox network are: To contribute to the advancement of alternative methods of ecotoxicity testing in Europe. To promote the validation and regulatory acceptance of new alternative ecotoxicity methods. To facilitate the networking of research groups working in the field of alternative ecotoxicology. To provide a gathering point for all stakeholders involved in the development, validation, regulatory acceptance and final use of alternative ecotoxicity testing strategies. To act as the one voice for alternative ecotoxicity testing in Europe.

AXLR8

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AXLR8 is a coordination action funded by the European Commission Directorate General for Research & Innovation under the 7 Framework Programme 7 (FP7) Health Theme. The European Commission is currently funding a number of research consortia to develop new 3Rs (replacement, reduction and refinement) test methods and strategies as potential alternatives to the use of animals in safety testing. Monitoring of these 3Rs activities at pan-European, national, and international levels is vital to facilitate swift progress. AXLR8 aims to fulfill this growing need by providing a focal point for dialogue and collaboration.[49] Humane Society International is part of the consortium.


Nonanimal Research Roadmap Strategists

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Oxford Centre for Animal Ethics

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The Oxford Centre for Animal Ethics, founded in England in 2006 by Andrew Linzey, a member of the Faculty of Theology at the University of Oxford, and cofounders Ara Paul Barsam, Mark H. Bernstein, Scott Cowdell, Susan Pigott, and Mark Rowlands, released in March 2015 the 8-page report, Normalising the Unthinkable: The Ethics of Using Animals in Research, which argues several points.

The Ferrater Mora Oxford Centre for Animal Ethics is named after the Spanish/Catalan philosopher, José Ferrater Mora.[50] or Josep Ferrater i Mora (in Catalan).

The Oxford Centre for Animal Ethics promotes ethical concern for animals through academic study and public debate, and it aims to create a global association of academics who are willing to advance the ethical case for animals.[50] To that end, it publishes an academic journal, the Journal of Animal Ethics, jointly with the University of Illinois.[51] It has also established an animal ethics series with Palgrave MacMillan.[52] The centre held an International Conference on the Relationship between Animal Abuse and Human Violence at Keble College, Oxford in 2007.[53]

Andrew Linzey is the centre's director. Advisers include Stephen R. L. Clark, Roger Crisp, Roger Fouts, Robert Garner, A. C. Grayling, Hilda Kean, Jeffrey Moussaieff Masson, Bernard Rollin, and Steven M. Wise. Honorary fellows include J. M. Coetzee.[50]

However, their report, Normalising the Unthinkable: The Ethics of Using Animals in Research, brings me to MY earlier position, the question of how knowledge is to be sought or to be acquired (in a useful and dependable way). How are biomedical knowledge searches to be organized?

Short of some mechanisms for researching ethically acceptable methods, where are we left in this conversation?

We have lots of 'information' - and much (most) of it isn't being applied or implemented effectively, but ... is there justification for continuing research, and of what kind?

But then, if one disembowels vivisection, do significant portions of the nonmedical and nonscientific public decide to revert to brutality in fashion, food, and culture? e.g. medical researchers wearing fur and leather in order to desensitize the public to compassion toward animals

ISKCON used to counsel that, short of a CULTURE of compassion (which sectarianism does not provide us), we have no foundation for sensitivity. Is that a correct assessment?

The scientific anti-vivisection movements has shifted much of its argumentation toward the utility of the nonanimal research toolbox. Is that really the way to conceptualize the array of human moments in searching for reductionistic elements of understanding?

So many consider the effort to find clear elements of mechanisms and processes.

Post-diagnosis interventions are very costly; we're truly not preventing as much medical suffering as some of us wish could be prevented.

Multimedia

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  • Hyperspectral imaging of intestine cells at varying wavelengths.

See Also

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References

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  1. ^ InterNiche, InterNiche
  2. ^ "Medicine". Britannica. Vol. 23. University of Chicago. 1993. p. 800. 0-85229-571-5.
  3. ^ a b Biomedical Research, HSI {{citation}}: Cite has empty unknown parameter: |1= (help)
  4. ^ "McLean Researchers Report on a New Nanotechnology That May Enhance Medication Delivery and Improve MRI Performance", McLean Hospital, Harvard, 2012 {{citation}}: Unknown parameter |month= ignored (help)
  5. ^ alternatives to animal testing, Peta
  6. ^ A new paradigm for nanoscale resolution MRI has been experimentally achieved, University of Illinois, September 27, 2013
  7. ^ Allen, David (April 9, 2012), Hyperspectral imaging: Shedding new light on wound healing, NIST
  8. ^ Dr. Mohr, Gerhard (Jan 02, 2012), Fewer animal experiments thanks to nanosensors, Fraunhofer-Gesellschaft {{citation}}: Check date values in: |date= (help)
  9. ^ "Faster testing of new pharmaceuticals". Fraunhofer-Gesellschaft. 2014. {{cite web}}: Unknown parameter |month= ignored (help)
  10. ^ "Optical techniques examine toxic agents in cells". Scientific Reports. Ecole Polytechnique Federale de Lausanne. 2013. {{cite web}}: Cite has empty unknown parameter: |1= (help); Unknown parameter |month= ignored (help)
  11. ^ "Wyss Institute researchers create living human gut-on-a-chip", Lab on a chip, Harvard University, March 27, 2012, doi:10.1039/C2LC40089H
  12. ^ Magnetically levitated tissues could speed toxicity tests, Rice University
  13. ^ a b New biochip technology uses tiny whirlpools to corral microbes, Purdue University, 2013 {{citation}}: Unknown parameter |month= ignored (help)
  14. ^ "Lung-on-a-chip". Hansjorg Wyss Institute for Biologically Inspired Engineering. Archived from the original on 2014-02-02. Retrieved 27 January 2014.
  15. ^ Lewis T. Will Organs-in-a-Dish Ever Replace Animal Models? The Scientist. July 19, 2016. Accessed July 20, 2016
  16. ^ a b c d New biosensor microchip could speed up drug development, Stanford researchers say, 2011 {{citation}}: Unknown parameter |month= ignored (help)
  17. ^ a b Emery, Chris (2011), Math may help calculate way to find new drugs for HIV and other diseases, Princeton University {{citation}}: Unknown parameter |month= ignored (help)
  18. ^ a b Boyd, Jade (2013), Drug resistance: ‘Baby steps’ can pay off big, Rice University {{citation}}: Unknown parameter |month= ignored (help)
  19. ^ Ternes, Ellen (2008), Math Could Help Cure Leukemia, Universityof Maryland {{citation}}: Unknown parameter |month= ignored (help)
  20. ^ a b Sigman; Harper (2011), Building better catalysts: Chemists find new way to design important molecules, University of Utah {{citation}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Mouse brain simulated on computer, BBC News, 2007 {{citation}}: Unknown parameter |month= ignored (help)
  22. ^ Researchers simulate complete structure of virus–on computer
  23. ^ Pain, Paromita (2013), TACC supercomputers simulate organization of membrane proteins at cell surface, University of Texas {{citation}}: Unknown parameter |month= ignored (help)
  24. ^ Traumatic brain injury patients, supercomputer simulations studied to improve helmets, Sandia National Laboratories, 2012 {{citation}}: Unknown parameter |month= ignored (help)
  25. ^ Biology enters 'The Matrix' through new computer language, Harvard Medical School, 2008 {{citation}}: Unknown parameter |month= ignored (help)
  26. ^ Travis, Scott (2009), Medical simulators can breathe, bleed, give birth -- and help students hone skills, Sun Sentinel {{citation}}: Unknown parameter |month= ignored (help)
  27. ^ Researchers find the key to what's in our pee, University of Alberta, 2013 {{citation}}: Unknown parameter |month= ignored (help)
  28. ^ New blood analysis chip could lead to disease diagnosis in minutes, University of California Berkeley, 2011 {{citation}}: Unknown parameter |month= ignored (help)
  29. ^ Biochip measures glucose in saliva, not blood, Brown University, Jan 23, 2012
  30. ^ Sagoff, Jared (May 9, 2008), Biochips can detect cancers before symptoms develop
  31. ^ a b Ianni, Niki (March 12, 2013), New Poll Shows Majority of Americans Strongly Oppose Animal Testing for Cosmetics, the Humane Society of the United States
  32. ^ a b c d e Foley, James (February 17, 2014), PETA Study Reports Growing Opposition to Animal Testing in the US, Nature World News
  33. ^ EU bans sale of all animal-tested cosmetics, BBC News, 2013 {{citation}}: Unknown parameter |month= ignored (help)
  34. ^ EU Set to Ban Animal Testing for Cosmetics Forever, Reuters, 2013 {{citation}}: Unknown parameter |month= ignored (help)
  35. ^ a b Singh,, Vijay (June 29, 2013), India bans cruel animal testing for cosmetics, activists elated, the Times of India{{citation}}: CS1 maint: multiple names: authors list (link)
  36. ^ Rodricks, Andrea (December 2, 2013), The “Necessity” of Cosmetic Animal Testing, Encyclopedia Brittanica: Advocacy for Animals
  37. ^ Japanese scientists see end to animal testing with artificial cornea, Reuters, 2013 {{citation}}: Unknown parameter |month= ignored (help)
  38. ^ a b c New study shows growing opposition to animal tests, AAAS, February 16, 2014
  39. ^ Brazil's Sao Paulo state bans animal testing, AFP, January 2014
  40. ^ H.R.4148, Congress, March 5, 2014
  41. ^ 21 U.S.C. 321, FDA
  42. ^ Bainbridge, Amy (March 17, 2014). "Australia urged to follow EU ban on animal testing; Greens to move bill in Senate this week". Australian Broadcasting Corporation News.
  43. ^ Dayu, Zhang (November 15, 2013), China considers end to mandatory animal testing on cosmetics, CNN
  44. ^ "SEURAT-1 - Towards the Replacement of in vivo Repeated Dose Systemic Toxicity Testing". Seurat-1.eu. Retrieved 2014-02-26.
  45. ^ "Sixth Report from the Commission to the Council and the European Parliament on the Statistics on the number of animals used for experimental and other scientific purposes in the member states of the European Union COM(2010) 511/final 2" (PDF). European Commission. 2010. Retrieved August 20, 2013.
  46. ^ "Alternatives To Animal Testing" (PDF). oecd-ilibrary.org. 23 Jul 2010. Retrieved 24 Apr 2014.[dead link]
  47. ^ "SHORT GUIDANCE ON THE THRESHOLD APPROACH FOR ACUTE FISH TOXICITY". Organisation for Economic Co-operation and Development (OECD). Retrieved 27 January 2014.
  48. ^ "euroecotox.eu". euroecotox.eu. Retrieved 2014-01-27.
  49. ^ "Home| AXLR8". Axlr8.eu. 2012-10-10. Retrieved 2014-01-27.
  50. ^ a b c "Welcome", "Advisers", and "Honorary Fellows", Oxford Centre for Animal Ethics, accessed 25 May 2012.
  51. ^ Bingham, John. "Calling animals 'pets' is insulting, academics claim", The Daily Telegraph, 28 April 2011.
  52. ^ "The Palgrave Macmillan Animal Ethics Series", Palgrave Macmillan, accessed 25 May 2012.
  53. ^ Linzey, Andrew. The Link Between Animal Abuse and Human Violence. Sussex Academic Press, 2009, p. 9.
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