Tag Archives: People for the Ethical Treatment of Animals (PETA)

More from PETA (People for the Ethical Treatment of Animals) about nanomaterials and lungs

Science progress by increments. First, there was this April 27, 2016 post featuring some recent work by the organization, People for the Ethical Treatment of Animals (PETA) focused on nanomaterials and lungs. Now approximately one month later, PETA announces a new paper on the topic according to a May 26, 2016 news item on phys.org,

A scientist from the PETA International Science Consortium Ltd. is the lead author of a review on pulmonary fibrosis that results from inhaling nanomaterials, which has been published in Archives of Toxicology. The coauthors are scientists from Health Canada, West Virginia University, and the University of Fribourg in Switzerland.

A May 26, 2016 PETA news release on EurekAlert, which originated the news item, provides more detail (Note: Links have been removed),

The increasing use of nanomaterials in consumer goods such as paint, building materials, and food products has increased the likelihood of human exposure. Inhalation is one of the most prominent routes by which exposure can occur, and because inhalation of nanomaterials may be linked to lung problems such as pulmonary fibrosis, testing is conducted to assess the safety of these materials.

The review is one part of the proceedings of a 2015 workshop [mentioned in my Sept. 3, 2015 posting] organized by the PETA International Science Consortium, at which scientists discussed recommendations for designing an in vitro approach to assessing the toxicity of nanomaterials in the human lung. The workshop also produced another report that was recently published in Archives of Toxicology (Clippinger et al. 2016) and a review published in Particle and Fibre Toxicology (Polk et al. 2016) [mentioned in my April 27, 2016 posting] on exposing nanomaterials to cells grown in vitro.

The expert recommendations proposed at the workshop are currently being used to develop an in vitro system to predict the development of lung fibrosis in humans, which is being funded by the Science Consortium.

“International experts who took part in last year’s workshop have advanced the understanding and application of non-animal methods of studying nanomaterial effects in the lung,” says Dr. Monita Sharma, nanotoxicology specialist at the Consortium and lead author of the review in Archives of Toxicology. “Good science is leading the way toward more humane testing of nanomaterials, which, in turn, will lead to better protection of human health.”

Here’s a link to and a citation for the paper,

Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs) by Monita Sharma, Jake Nikota, Sabina Halappanavar, Vincent Castranova, Barbara Rothen-Rutishauser, Amy J. Clippinger. Archives of Toxicology pp 1-18 DOI: 10.1007/s00204-016-1742-7 First online: 23 May 2016

This paper is behind a paywall.

Study nanomaterial toxicity without testing animals

The process of moving on from testing on animals is laborious as new techniques are pioneered and, perhaps more arduously, people’s opinions and habits are changed. The People for the Ethical Treatment of Animals (PETA) organization focusing the research end of things has announced a means of predicting carbon nanotube toxicity in lungs according to an April 25, 2016 news item on Nanowerk (Note: A link has been removed),

A workshop organized last year [2015] by the PETA International Science Consortium Ltd has resulted in an article published today in the journal Particle and Fibre Toxicology (“Aerosol generation and characterization of multi-walled carbon nanotubes [MWCNTs] exposed to cells cultured at the air-liquid interface”). It describes aerosol generation and exposure tools that can be used to predict toxicity in human lungs following inhalation of nanomaterials.

An April 25, 2016 PETA press release on EurekAlert, which originated the news item, explains further without much more detail,

Nanomaterials are increasingly being used in consumer products such as paints, construction materials, and food packaging, making human exposure to these materials more likely. One of the common ways humans may be exposed to these substances is by inhalation, therefore, regulatory agencies often require the toxicity of these materials on the lungs to be tested. These tests usually involve confining rats to small tubes the size of their bodies and forcing them to breathe potentially toxic substances before they are killed. However, time, cost, scientific and ethical issues have led scientists to develop methods that do not use animals. The tools described in the new article are used to deposit nanomaterials (or other inhalable substances) onto human lung cells grown in a petri dish.

Co-authors of the Particle and Fibre Toxicology article are scientists from the PETA Science Consortium , The Dow Chemical Company, Baylor University, and the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).

“Promoting non-animal methods to assess nanotoxicity has been a focus of the PETA International Science Consortium”, said Dr. Monita Sharma, co-author of the publication and Nanotechnology Specialist at the Consortium, “we organized an international workshop last year on inhalation testing of nanomaterials and this review describes some of the tools that can be used to provide a better understanding of what happens in humans after inhaling these substances.” During the workshop, experts provided recommendations on the design of an in vitro test to assess the toxicity of nanomaterials (especially multi-walled carbon nanotubes) in the lung, including cell types, endpoints, exposure systems, and dosimetry considerations. Additional publications summarizing the outcomes of the workshop are forthcoming.

Here’s a link to and a citation for the paper,

Aerosol generation and characterization of multi-walled carbon nanotubes exposed to cells cultured at the air-liquid interface by William W. Polk, Monita Sharma, Christie M. Sayes, Jon A. Hotchkiss, and Amy J. Clippinger. Particle and Fibre Toxicology201613:20 DOI: 10.1186/s12989-016-0131-y Published: 23 April 2016

This is an open access paper.

People for the Ethical Treatment of Animals (PETA) and a grant for in vitro nanotoxicity testing

This grant seems to have gotten its start at a workshop held at the US Environmental Protection Agency (EPA) in Washington, D.C., Feb. 24-25, 2015 as per this webpage on the People for Ethical Treatment of Animals (PETA) International Science Consortium Limited website,

The invitation-only workshop included experts from different sectors (government, industry, academia and NGO) and disciplines (in vitro and in vivo inhalation studies of NMs, fibrosis, dosimetry, fluidic models, aerosol engineering, and regulatory assessment). It focused on the technical details for the development and preliminary assessment of the relevance and reliability of an in vitro test to predict the development of pulmonary fibrosis in cells co-cultured at the air-liquid interface following exposure to aerosolized multi-walled carbon nanotubes (MWCNTs). During the workshop, experts made recommendations on cell types, exposure systems, endpoints and dosimetry considerations required to develop the in vitro model for hazard identification of MWCNTs.

The method is intended to be included in a non-animal test battery to reduce and eventually replace the use of animals in studies to assess the inhalation toxicity of engineered NMs. The long-term vision is to develop a battery of in silico and in vitro assays that can be used in an integrated testing strategy, providing comprehensive information on biological endpoints relevant to inhalation exposure to NMs which could be used in the hazard ranking of substances in the risk assessment process.

A September 1, 2015 news item on Azonano provides an update,

The PETA International Science Consortium Ltd. announced today the winners of a $200,000 award for the design of an in vitro test to predict the development of lung fibrosis in humans following exposure to nanomaterials, such as multi-walled carbon nanotubes.

Professor Dr. Barbara Rothen-Rutishauser of the Adolphe Merkle Institute at the University of Fribourg, Switzerland and Professor Dr. Vicki Stone of the School of Life Sciences at Heriot-Watt University, Edinburgh, U.K. will jointly develop the test method. Professor Rothen-Rutishauser co-chairs the BioNanomaterials research group at the Adolphe Merkle Institute, where her research is focused on the study of nanomaterial-cell interactions in the lung using three-dimensional cell models. Professor Vicki Stone is the Director of the Nano Safety Research Group at Heriot-Watt University and the Director of Toxicology for SAFENANO.

The Science Consortium is also funding MatTek Corporation for the development of a three-dimensional reconstructed primary human lung tissue model to be used in Professors Rothen-Rutishauser and Stone’s work. MatTek Corporation has extensive expertise in manufacturing human cell-based, organotypic in vitro models for use in regulatory and basic research applications. The work at MatTek will be led by Dr. Patrick Hayden, Vice President of Scientific Affairs, and Dr. Anna Maione, head of MatTek’s airway models research group.

I was curious about MatTek Corporation and found this on company’s About Us webpage,

MatTek Corporation was founded in 1985 by two chemical engineering professors from MIT. In 1991 the company leveraged its core polymer surface modification technology into the emerging tissue engineering market.

MatTek Corporation is at the forefront of tissue engineering and is a world leader in the production of innovative 3D reconstructed human tissue models. Our skin, ocular, and respiratory tissue models are used in regulatory toxicology (OECD, EU guidelines) and address toxicology and efficacy concerns throughout the cosmetics, chemical, pharmaceutical and household product industries.

EpiDerm™, MatTek’s first 3D human cell based in vitro model, was introduced in 1993 and became an immediate technical and commercial success.

I wish them good luck in their research on developing better ways to test toxicity.

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

ETA July 22, 2015: I now have a link to the magazine article.