World Congress on Alternatives--on AltTox

[Martin Stephens]

The 7th World Congress on Alternatives and Animal Use in the Life Sciences runs from  tomorrow night through Thursday afternoon (Aug 30 - Sept. 3) in Rome.  Congress participants are invited to post their comments on any aspect of the 7WC on AltTox--simply hit "reply" to the message string that I am starting with this posting. By the time the 7WC is over, we hope to have several messages in this string, each giving a window into some aspect of the Congress.

And if you're attending the Congress, be sure to check out the AltTox poster and listen to the oral presentation by yours truly on AltTox during the Monday (Aug. 31) lunchtime session on "Databases: Progress Report" (12:40 - 13:40 in Room San Pietro).

I hope to see some of you in Rome and read your postings - however brief - on the 7WC!

Marty Stephens

[Andrew Rowan]

Report from Rome

The Seventh World Congress on Alternatives to Animal Use kicked off with a reception at the Hilton Cavalieri Hotel in Rome on Sunday night (August 30, 2009).   Approximately 850 people are registered to hear reports and analyses contributed by more than 2,000 scientists on the 50th Anniversary of the publication of Russell and Burch’s landmark book, The Principles of Humane Experimental Technique. 

When Russell and Burch published their book in 1959, laboratory animal use was exploding (from 20 million to over 50 million animals in the USA alone twelve years later) but then, in the middle of the 1970s, laboratory animal use began to fall.   By the middle of the 1990s, world-wide laboratory animal use was perhaps at half the level it was in 1975 but then the decline in animal use began to plateau as transgenic mouse technology led to the expansion of the breeding of specialty breeds of transgenic and “knockout” mice in most major research institutions.  Laboratory animal rooms that had begun to empty filled up again.   Today, at the 7th World Congress, we are looking at the potential that we will end animal use in safety testing and risk assessment within the next decade or so and it is also likely that the transgenic mouse boom will begin to taper off in due course leading to a further decline in laboratory animal numbers during this quarter of the 21st century. 

Beginning the formal scientific program was a statement by the Vice President of the European Commission, Gunther Verheugen, welcoming the participants on behalf of himself and his colleague, fellow Commissioner, Janez Potocnik, and making clear the European Union's commitment to the 3Rs.   He noted, "Since the promotion of the 3Rs requires an approach at the global level, we have also drawn the attention of our trading partners to the 3Rs, which have become a standing item on the agenda of regulatory dialogues, be this at the bilateral or multilateral level." 

Frankly, as someone who started working on alternatives (the 3Rs) in London in 1976, I cannot believe the progress that has occurred over the past 33 years.  When one looks at the issue from the perspective of a year or two, not much seems to have changed but consider the following of my memories from 1976:-
    a)  the UK MRC turned down a request from FRAME to establish a program on alternatives because, they argued, scientists are already doing all that needed to be done on the topic;
    b) at an inquiry on the LD50, one of the scientific advisors to the UK Home Office exclaimed that there was no possibility of replacing the LD50 because it was considered a cornerstone of modern toxicology;
    c) Professor Sir William Paton, Professor of Pharmacology at Oxford University and Chairman of the Research Defense Society, asked me to come up to see him at Oxford to discuss alternatives.  However, he was chiefly interested in trying to understand why someone with an Oxford DPhil in biochemistry would have gone to work for FRAME promoting alternatives;
    d) The TOxic Substances Control Act (TOSCA) was passed in the USA;
    e) The Russell and Burch volume was virtually unknown and uncited and its original sponsor, UFAW, no longer had copies available.  One could still obtain copies (as I did) from the Animal Welfare Institute in the USA because Christine Stevens, the founder of the AWI had been a strong promoter of the book. 

Andrew N Rowan

[Martin Stephens]

Resolution on 21st Century Toxicology (see attachment)

A resolution calling upon all stakeholders "to actively and cooperatively support a global transition to a humane 21st century approach in toxicological risk assessment" is available at the 7WC for conferees to sign, as an indication of their support of efforts to implement the U.S. National Research Council's vision and strategy for "Toxicology Testing in the 21st Century" and similar visions and programs. The resolution was initiated by The Humane Society of the United States and its sister organizations, The Humane Society International and The Humane Society Legislative Fund.  It was finalized and endorsed at the Animal Protection Satellite Meeting of the 7WC, held on Sunday (Aug. 30).  It has so far been endorsed by the two co-chairs of the 7WC, Herman Koeter and Thomas Hartung, as well as dozens of conferees. Other conferees are urged to read the resolution and consider endorsing it.  The resolution text and endorsement sheet are available at the booth of HSUS/HSI/HSLF in the main exhibit area (also attached, FYI).

[Andrew Rowan]

The first full day of the World Congress on Alternatives has run its course and produced the usual mix of what one might expect at a multi-disciplinary international conference – namely some very interesting examples of progress, some useful reviews and quite a bit of “filler.”   My colleague, Troy Seidle, posted a Tweet yesterday on the recent EU/Colipa call for proposals on research on alternatives to animals where 50 million Euros are being made available by the EU and the cosmetic industry.   The aim is to develop alternatives to the use of animal testing for repeat dose, systemic toxicity testing.  (http://europa.eu/rapid/pressReleasesAction.do?reference=IP/09/1262&format=HTML&aged=0&language=EN&guiLanguage=en)    This type of new research initiative indicates that HSI’s plans to push for around $200 million a year (on a global basis for the next ten years) to develop and implement a non-animal testing program for human risk assessment and hazard identification are not out of the question.   In fact, it appears as though almost $100 million a year of private and public money is already going into alternative test development and implementation.
 
On a different issue, that involves literally millions of vertebrate animals every year, Dr Graham Whale of Shell spoke this morning about the development of alternatives to fish in ecotoxicology projects (largely involving the testing of industrial effluents that are discharged into the environment).   Considerable progress has been made in this field resulting in the German government submitting a proposal to the OECD in 2006 to approve the Fish Embryo Toxicity (FET) test as a replacement for the conventional adult fish tests (typically, early stage vertebrate embryos have been considered to be acceptable replacements to the use of adult vertebrates in toxicity tests).   In Germany, the FET test was made mandatory in 2005 and data from the conventional test using live adult fish are no longer accepted for routine whole effluent testing.  (http://www.oecd.org/dataoecd/39/62/36817242.pdf)
 
There are also cell culture and invertebrate tests that are in development and have been proposed as alternatives for ecotoxicology programs in a tiered approach to environmental safety assessment.  However, the adult fish test is entrenched in the regulatory system at the Environmental Protection Administration (see http://www.epa.gov/EPA-WATER/1995/October/Day-16/pr-188DIR/pr-188.html) and so a move to have it replaced with one or more alternative approaches will not be easy.  Nonetheless, presentations and discussions at this World Congress lead me to think that pressure to replace the adult fish test in effluent testing both in the USA and Canada would be both worthwhile and likely to succeed! 

Andrew Rowan

[Sherry Ward]

I attended several symposia today and a recurring theme was that an integrated testing strategy, in some cases composed of different in vitro/in silico methods, is the approach being developed. The concept of using an ITS approach is not new, but it is encouraging to see individual tests being specifically developed with this approach in mind.

For example, COLIPA member scientists explained ITS projects for eye irritation, skin sensitization, and genotoxicity testing. Dr. Krul reported an "improved in vitro strategy" for nanomaterial safety testing based on precision cut lung slices, an air-liquid interface lung epithelial cell model for airborne particle testing, and transcriptomics analysis using lung epithelial cells.

Reports on these developments are in various stages - some recent publications, some soon to be published, some still research being conducted.

[Sherry Ward]

More news from the WC7.

The immunology symposium on Wednesday was well-attended. Dr. Roggen chaired this session, and opened with an overview on the challenges for the in vitro assessment of immunotoxicity. Adverse chemical effects on the immune system include the following: hypersensitivity, immunosuppression, immunostimulation, and autoimmunity. Basically, the major challenge is the lack of cell-based assays that are predictive of this toxicity endpoint.

Dr. Martin presented his research approach to identify the molecular mechanisms of allergic contact dermatitis. Similarities with infections have been observed, with both activating the innate immune and cellular stress responses. Dr. Martin asked whether chemicals activated toll-like receptors. He found both contact allergens and infectious organisms act through the same pathways, activating TLR2, TLR4, and IL-12Rß12. An understanding of the molecular mechanisms, he explained, will provide for: 1) identification of contact allergens, 2) distinguishing allergens from irritants, and 3) development of in vitro assays to identify contact allergens.

Dr. Leist was a substitute speaker for Dr. Altmann, and spoke on the topic of “models for brain inflammation.” He explained that the microglia and astrocytes are the immune-related cells in the brain. The two options for cell-based microglial assays are: 1) animal or human primary microglia cultures, or 2) microglia cell lines. BV-2 cells are a microglia cell line that retain many primary cell properties. He conducted a validation of the BV-2 cell line by comparing it to microglia cells using: 1) activity (both actively phagocytize lymphocytes), 2) transcriptomics (quantitative, but not qualitative, differences seen), 3) PCR (to confirm gene expression), and 4) proteomics (also good agreement). He concluded that BV-2 cells are a model with few false positives (high specificity), but low sensitivity (more false negatives).

There were several more immunology speakers, but I had to leave to attend another session.

WC speakers/attendees are invited to elaborate on my discussions or add new ones to this discussion thread.

Sherry

[Sherry Ward]

New Patrons of the World Congresses announced:

On the last morning of WC7, Michael Balls, Alan Goldberg, and Horst Spielmann were presented with the award the official “Patrons of Animal Welfare in the Life Sciences."

This award was presented by the WC7 Co-Chairs, Thomas Hartung and Herman Koëter, at the Special Recognition Event following Michael and Alan’s plenary session presentations on “The principles of humane experimental technique....”

A Powerpoint presentation on each of the three awardees highlighted their 3Rs achievements. Now, in addition to William Russell and Rex Burch, Drs. Goldberg, Balls, and Spielmann are the “Patrons of the World Congresses.”

Dr. Horst Spielmann is one of our valued moderators of the AltTox Forums. He commented that “For me it was a big surprise and I was, of course, not properly dressed except for the FRAME tie.”

The WC7 press release is available at: http://www.aimgroup.eu/2009/wc7/files/PressreleaseSeptember3.pdf, and a photo of the “Patrons” award is attached to this message.

Other WC news announced on September 3:

At the 7th WC, it was announced that Herman Koëter and Thomas Hartung would join the Board of the Alternatives Congress Trust (ACT), which is the organization in charge of the World Congresses. Alan Goldberg resigned from the ACT, becoming an emeritus member like Bert van Zutphen did at WC6 in Tokyo. The current ACT is now composed of the following members: Michael Balls, Thomas Hartung, Coenraad Hendriksen, Herman Koëter, Andrew Rowen, and Horst Spielmann.

[Horst Spielmann]

Today Nature published a report on WC7 entilted "Toxicity testing gets a makeover- Europe aims to make chemical-exposure studies more predictive while using fewer animals", which is focusing on the joint initiative of the EU Commission and the EU Cosmetics Manufacturers Association COLIPA  to develop a modern, high-throughput approach to repeat-dose toxicity
testing. This initiative was presented at WC7 in Rome, details can be found on the COLIPA website at http://www.colipa.eu/statement.html?sid=60&id=33.
Copies both of the Nature article and of the COLIPA call for proposals are attached.
Horst Spielmann
.

[Sherry Ward]

Each attendee of the 7th World Congress in Rome received a complementary copy of “The Three Rs and the Humanity Criterion,” a revised and updated version of “The Principles of Humane Experimental Technique” book by William Russell and Rex Burch. This abridged version was prepared by by FRAME chairman Dr. Michael Balls.

The Preface of the Abridged Version reminds us that 2009 marks the 50th anniversary of the first publication of “The Principles of Humane Experimental Technique,” and is also the 40th anniversary of FRAME (http://www.frame.org.uk).

The FRAME website notes that: “The book was especially well received among foreign delegates because it was designed to help those who are not native English speakers. Russell and Burch's original sometimes uses complex language, which makes it difficult for foreign readers.”

I’m browsing through my book today and hoping I can order some additional copies for gift giving.

[Martin Stephens]

A belated notice that the World Congress was the occasion for The Humane Society of the United States to bestow the 2009 Russell and Burch Award for outstanding contribution to alternative methods.  This year's winner, chosen by previous winners of the award from among the submitted nominations, was Thomas Hartung.  Further details are in the following press release.

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 ROME — The Humane Society of the United States bestowed its 2009 Russell & Burch Award today to Dr. Thomas Hartung for advancing the development and implementation of non-animal methods in toxicity testing.

The HSUS presented the award at the 7th World Congress on Alternatives and Animal Use in the Life Sciences. Hartung is a co-organizer of the meeting. The award recognizes scientists who have made outstanding contributions toward the advancement of alternative methods in the areas of biomedical research, testing or higher education. Alternative methods are those that accomplish one or more of the "Three Rs" devised by William Russell and Rex Burch in 1959. The Three Rs are: Replacing or Reducing animal use in experiments and Refining methods so that animals experience less pain and distress.

Hartung was head of the European Centre for the Validation of Alternative Methods (ECVAM) from 2002 to 2008. He was recently appointed to two positions at Johns Hopkins University in Baltimore, Md.: director of the Center for Alternatives to Animal Testing (CAAT), and the inaugural Doerenkamp-Zbinden Chair for Evidence-Based Toxicology in the Department of Environmental Health Sciences at the Bloomberg School of Public Health. In addition, Hartung is honorary full professor at the University of Konstanz in Germany, an active affiliation he has maintained since teaching there. 

"Thomas Hartung is recognized as the world's foremost authority on alternative methods of toxicity testing," said Martin Stephens, Ph.D., The HSUS' vice president for animal research issues. "In addition to being a scientist, administrator, author, and a sought-after speaker, Thomas is also an excellent magician, and he is slowly but surely helping to make many animal-based tests disappear."

As head of ECVAM, Hartung was responsible for coordinating the independent evaluation of non-animal tests, as well as organizing efforts to promote their scientific and regulatory acceptance. Hartung accelerated the process of validating alternative methods. The test strategies developed at ECVAM will change the way safety assessments for chemicals are carried out in Europe and elsewhere.

Hartung has also helped strengthen international cooperation and coordination among national and regional validation centers.

The Russell & Burch Award is a $5,000 prize and trophy. The 2009 Award comes on the 50th anniversary of the publication of William Russell and Rex Burch's pioneering book, The Principles of Humane Experimental Technique, detailing the Three Rs approach. The first Award was given in 1991 to Alan Goldberg, Hartung's predecessor as director of CAAT.