It is with deep sadness that we announce the death of our esteemed colleague and friend, Franz Paul Gruber, DVM, PhD, who passed away on April 12, 2023 in Münsterlingen, Switzerland after a prolonged illness.

He will be greatly missed by his colleagues and friends at the Doerenkamp Zbinden Foundation as well as by many collaborators in the field of alternatives to animal experiments. Franz was a veterinarian who dedicated his entire career to promoting animal welfare and alternatives to animal experimentation. He worked as an associate professor at the Free University in Berlin, academic director of the animal research facility at the University of Konstanz, member of the scientific advisory board of the SET foundation, scientific advisor of Animalfree Research (then FFVFF), editor-in-chief of ALTEX, and CEO of ALTEX Edition and of the Doerenkamp Zbinden Foundation. He was still active as the President of the Doerenkamp Zbinden Foundation, president of ALTEX Edition and Co-President of Ärztinnen und Ärzte für Tierschutz in der Medizin. Franz’ life achievements were recently celebrated in an editorial published on occasion of his 80th birthday (ALTEX 40, 1). With his passing, the 3Rs field has lost one of its most dedicated pioneers.

Thank you, dear Franz! Our time with you was an inspiration and a great privilege to us all. You will be greatly missed!

The 2022 Doerenkamp-Zbinden (DZ) Price was awarded to Andrea Terron on occasion of the ASPIS meeting in Sitges (Spain; 24.-25.11.2022). The award speech was given by M. Leist (University of Konstanz) and recognized in particular the achievements of the winner concerning “implementation of NAM for food safety assessment”. Andrea Terron is a pathologist with 20 years of experience in industry, and his > 10 years of work at EFSA showed him the limitations of animal-based data in regulatory toxicology. Two highlights of his work on the implementation of NAM are the neurotoxicity assessment of compounds on basis of a newly-generated AOP, and the work with OECD to establish procedures for developmental neurotoxicity (DNT) assessment on the basis of NAM. Andrea chaired a working group to establish AOP:3 “parkinsonian motor deficits as consequence of mitochondrial complex I inhibition”. He brought this AOP not only to the highest validation level, but also continued on practical applications, and on creating a publication format that may be exemplary for transparent communication of AOP (Terron et al. (2018) Arch Toxicol 92, 41-82). To provide material, data and experience for a draft guidance on the use of in vitro data for DNT assessment, he organized EFSA projects, working groups and the communication with OECD. Some of the initial work has been published (Blum et al. (2022) Chemosphere 311, 137035), and a draft OECD guidance is at advanced stages. Altogether, the work of Andrea Terron has shown that difficult toxicological domains can be assessed by NAM and that applied case studies can pave the way towards regulatory implementation. With this achievement, Andrea Terron joins a long row of price winners from academia, industry and regulatory authorities. The DZ foundation looks forward to more price suggestions in the future. The award is one of the foundations main instruments to create awareness for the importance of the replacement of experimental animals and to highlight the great achievements in this field.

Prof. Thomas Hartung, Head of the Doerenkamp-Zbinden-Chair for Evidence-based Toxicology at Johns Hopkins Bloomberg School of Public Health in Baltimore, USA, received the EuroTox Merit award 2021. He received the award in recognition for his distinguished and long career in European Toxicology. Prof. Heather Wallace, President of EUROTOX, who presented the recognition at the Opening Ceremony of the Virtual 2021 EUROTOX Congress in September 2021, emphasized that Prof. Hartung is the perfect match for the award considering his professional career, contributions in the areas of evidence-based toxicology and alternatives methods to animal testing.

The EUROTOX Merit Award aims at recognizing a distinguished career in European toxicology. It is presented annually at the EUROTOX Congress to a European toxicologist with a long and outstanding career in the discipline. Emphasis is put on individual contributions strengthening the science of toxicology and their achievements in academia, public service or industry.

Nominations for the Doerenkamp-Zbinden Prize 2021 are now open. The origins of the DZ Foundation (DZF) lie in the award of a yearly prize for distinguished services to animal protection in science. Despite repeated reorientation of the Foundation, this prize has always been retained. The prize serves public relations, raises the level of awareness but also defines the Foundation’s position. Single persons, teams as well as institutions can be suggested for the prize. The suggestions are treated confidentially. Next to scientists, persons in the fields of animal protection or philosophy, public persons as well may be awarded the DZ-Prize in so far as they have distinguished themselves in the sense of the replacement and reduction of animal experiments. The prize is bestowed with 10.000 CHF and can be divided.

Franz P. Gruber on behalf of the Foundation Board

In honor of the centenary birthday of our foundress, Hildegard Doerenkamp (1920-2020), the Doerenkamp-Zbinden Foundation for AnimalfreeResearch organized on the 9th November 2020 a video conference with the current and former professors of the university chairs of the foundation.

Marcel Leist,

Doerenkamp-ZbindenProfessor for In vitro Toxicology and Biomedicine, University of Constance, Germany, since 2007

Bas Blaauboer,

Doerenkamp-Zbinden Professor for Alternative Methods in Toxicology, Utrecht University, The Netherlands, since 2008

Pierre Cosson,

Doerenkamp-Naef-Zbinden Professor on Alternative Methods to Animal Experimentation, University of Geneva, Switzerland, since 2009

Thomas Hartung,

Doerenkamp-Zbinden Endowed Chair for Evidence-based Toxicology, at the Johns Hopkins University, Baltimore, USA, since 2009

Mohammad A. Akbarsha,

Gandhi-Gruber-Doerenkamp Chair at the Mahatma Gandhi Doerenkamp Center for Alternatives to the Use of Animals in Life Science Education at the Bharathidasan University, Tiruchirappalli/Tamil Nadu, India, since 2009

At the end of the conference the five professors were awarded the Doerenkamp-Zbinden Prize 2020. The prize was given in acknowledgement of their outstanding work in development and promotion of alternatives to animal exeperimentation and testing. It is an honor prize and the awardees do not receive any money. For Thomas Hartung it was his second time to receive the Doerenkamp-Zbinden Prize. Together with Albrecht Wendel he was awarded the Doerenkamp Zinden Prize in 1996.

Moderator

Franz P. Gruber

President of the Doerenkamp-Zbinden Foundation

Loganathan Gayathri1,2,3, Mohammad A. Akbarsha4,5 & Kandasamy Ruckmani1,2*Gliotoxin (GT) and fumagillin (FUM) are mycotoxins most abundantly produced by Aspergillusfumigatus during the early stages of infection to cause invasive aspergillosis (IA). Therefore, wehypothesized that GT and FUM could be the possible source of virulence factors, which we put totest adopting in vitro monoculture and the novel integrated multiple organ co-culture (IdMOC) ofA549 and L132 cell. We found that (i) GT is more cytotoxic to lung epithelial cells than FUM, and(ii) GT and FUM act synergistically to inflict pathology to the lung epithelial cell. Reactive oxygenspecies (ROS) is the master regulator of the cytotoxicity of GT, FUM and GT + F UM. ROS may beproduced as a sequel to mitochondrial damage and, thus, mitochondria are both the source ofROS and the target to ROS. GT-, FUM- and GT + F UM-induced DNA damage is mediated either byROS-dependent mechanism or directly by the fungal toxins. In addition, GT, FUM and GT + F UMmay induce protein accumulation. Further, it is speculated that GT and FUM inflict epithelialdamage by neutrophil-mediated inflammation. With respect to multiple organ cytotoxicity, GTwas found to be cytotoxic at IC50 concentration in the following order: renal epithelial cells < type IIepithelial cells < hepatocytes < normal lung epithelial cells. Taken together, GT and FUM alone and incombination contribute to exacerbate the damage of lung epithelial cells and, thus, are involved in theprogression of IA.AbbreviationsDMSO Dimethyl sulfoxideFUM FumagillinGT GliotoxinIC50 Concentration at which 50% of cells are deadIdMOC Integrated discrete multiple organ co-cultureIA Invasive aspergillosisMTT 3-4, 5-Dimethylthiazole-2-yl, 2,5-diphenyl tetrazolium bromideROS Reactive oxygen speciesAspergillus fumigatus, the abundantly distributed saprophytic fungus, is a weak pathogen. Generally, A. fumigatusreleases air-borne, dormant, buoyant microscopic conidiospores in copious amounts, so that a person wouldOPEN1Department of Pharmaceutical Technology, University College of Engineering, Anna University-BIT Campus,Tiruchchirappalli, Tamil Nadu 620024, India. 2Centre for Excellence in Nanobio Translational Research(Autonomous), University College of Engineering, Anna University-BIT Campus, Tiruchchirappalli, TamilNadu 620024, India. 3Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous),Tiruchchirappalli, Tamil Nadu 620002, India. 4National College (Autonomous), Tiruchchirappalli, TamilNadu 620001, India. 5Mahatma Gandhi‑Doerenkamp Centre for Alternatives, Bharathidasan University,Tiruchchirappalli, Tamil Nadu 620 024, India. *email: ruckmani@aubit.edu.in

Vaiyapuri Subbarayan Periasamy 1,2, Anvarbatcha Riyasdeen 1, Venugopal Rajendiran 3,Mallayan Palaniandavar 4, Hanumanthappa Krishnamurthy 5, Ali Abdullah Alshatwi 2and Mohammad Abdulkader Akbarsha 6,7,*1 Department of Animal Science, Bharathidasan University, Tiruchirappalli 620024, India;vsperrys@gmail.com (V.S.P.); anfariyas@gmail.com (A.R.)2 Department of Food and Nutrition, College of Food and Agricultural Sciences, King Saud University,P.O. Box 2460, Riyadh 11451, Saudi Arabia; alshatwi@ksu.edu.sa3 Department of Chemistry, School of Basic and Applied Sciences, Central University of Tamil Nadu,Thiruvarur 610005, India; rajendiran@cutn.ac.in4 Department of Chemistry, Bharathidasan University, Tiruchirappalli 620024, India;palaniandavarm@gmail.com5 National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore 560065, India;krishna@ncbs.res.in6 Mahatma Gandhi-Doerenkamp Center (MGDC) for Alternatives to Use of Animals in Life ScienceEducation, Bharathidasan University, Tiruchirappalli 620024, India7 Research Co-ordinator, National College (Autonomous), Tiruchirappalli 620001, India* Correspondence: akbarbdu@gmail.com; Tel.: +91-979-0995-854; Fax: +91-431-2481-997Academic Editors: Diego Muñoz-Torrero and Beatriz De Pascual-TeresaReceived: 26 August 2020; Accepted: 29 September 2020; Published: 1 October 2020

Abstract: This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II)complex [Cu(tdp)(phen)](ClO4)—where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline—to twogenotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-).The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The specialfocus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS.The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruptionof mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, andincrease of ROS generation, followed by apoptotic death of cells during early hours and a late onsetof necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypicallydifferent breast cancer cells is attributed to a strong association through p53-mitochondrial redox—cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 aredesirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the

Culture Three-Dimensional Multicellular Tumor Spheroids

Perumalsamy Balaji, Anbazhagan Murugadas, Arunachalam Ramkumar, Ramasamy Thirumurugan,Sellathamby Shanmugaapriya, and Mohammad Abdulkader Akbarsha*Cite This: https://dx.doi.org/10.1021/acsomega.0c02508 Read OnlineACCESS Metrics & More Article Recommendations

ABSTRACT: We are standardizing protocols to develop eggwhite (EW) as a cost-effective platform for culture of threedimensional(3-D) multicellular tumor spheroids for application inunderstanding tumor microenvironments and drug screening. Inthis article, we describe several physical and physiologicalcharacteristics of EW to use it as 3-D cell culture platform. Fieldemission scanning electron microscopy revealed the presence ofdifferent microstructures. Hydrodynamic size distribution dataindicated nano- and micron-sized particles. Rheological measurementsrevealed the viscosity and viscoelastic behavior appropriatefor maintaining cell viability and supporting 3-D cell growth underhigh-sheer conditions. It was found that thereis no autofluorescence,a requirement for imparting transparency and formicroscopic observations of the spheroids. The EW facilitated the development of 3-D tumor spheroids, with an emphasis ofdifference in cell proliferation and intercellular cytoskeletal organization between two-dimensional and 3

The DZF founded the Doerenkamp-Naef-Zbinden Chair at the University of Geneva, Switzerland, in the year 2008. The Foundation sponsored the activities of the chair for a period of the first five years. Among many other projects, the chair holder, Pierre Cosson, initiated a project to produce recombinant antibodies and created a database providing information about available recombinant antibodies. The idea of the project has been to simplify access to and intensify the use of the recombinant antibodies as an alternative method to the immunization of animals. The project has been a success story. Now even COVID-19 researchers use the antibodies from Geneva.

More information:

https://web.expasy.org/abcd/

https://oap.unige.ch/journals/abrep

The German Research Council (DFG, German Research Foundation) has awarded the most prestigious Ursula M. Händel Animal Welfare Prize to Marcel Leist and Thomas Hartung, two endowed chairs of the foundation, for their lifework to replace animal testing. The prize of 80,000 Euro will support the work these pioneers of alternatives to animal testing.

The foundation was created on the private initiative of the two namesakes, Hildegard Doerenkamp († 2011) and Prof. Gerhard Zbinden († 1993), then head of the Institute for Toxicology of the Federal Institute of Technology and the University of Zurich in Schwerzenbach/Zurich. Following intense discussions twenty years ago, the foundation started to support the creation of in total five chairs for alternative to animal experiments world-wide. In 2006, a „Foundation-Professorship for In vitro Methods for the Replacement of Animal Experiments“ was installed at the University of Konstanz. Since April 2006, Marcel Leist is "Doerenkamp-Zbinden Professor" at the University of Konstanz, and the Land BW has taken over this professorship as regular department. In 2009, the "Doerenkamp-Zbinden Endowed Chair for Evidence-based Toxicology" was established at Johns Hopkins University, Baltimore. Remarkably, the University committed to maintain this chair as long as the University exists. “The accolade to the foundation’s professorships confirms that the vision of the founders was right: there was a large unmet need for high quality academic research on alternative methods” says Franz Gruber, a trained veterinarian and president of the Doerenkamp-Zbinden Foundation since 2004.

The two professors, Marcel Leist and Thomas Hartung, were now awarded by the German Research Council (DFG, German Research Foundation) the Ursula M. Händel Animal Welfare Prize for their lifework. The €80,000 prize is awarded to researchers who improve research animal welfare in line with the principles known as the 3Rs of alternatives: Replacement (of animal experiments with non-animal methods), Reduction (of the numbers of animals used for a particular experiment), and Refinement (reducing pain and distress of laboratory animals). Thomas Hartung, MD, PhD, Director of the Center for Alternatives to Animal Testing (CAAT) at the Johns Hopkins Bloomberg School of Public Health,  and Marcel Leist, PhD, co-director with Hartung of CAAT-Europe and Chair of the department of In Vitro Toxicology and Biomedicine at the University of Konstanz, have been selected from nine nominees. “It is a day of pride” says Franz Paul Gruber, a trained veterinarian and president of the Doerenkamp-Zbinden Foundation since 2004. “It shows that the strategy of the Foundation worked out and we have made a lasting mark”.

Over the course of their career, Hartung and Leist have developed a number of alternative methods, including for liver inflammation, neurodevelopment and pyrogen testing. These have substantially contributed to replace animal testing by alternative methods. Most recently, they addressed so-called read-across methods, which use information on similar chemicals to avoid testing. Most remarkably, Hartung’s group showed in 2018 that artificial intelligence and big data can outperform nine of the most commonly used animal tests in toxicology – they use in Europe alone more than 500,000 animals at 200-300 million Euro of testing costs per year. Noteworthy, the method has already been implemented in chemical legislation, as e.g. Australia starts using the method already from 1 July this year. Beyond the development of alternative methods, the two awardees have promoted teaching on alternatives, a number of workshops and conferences, the journal ALTEX as well as a number of programs to foster stakeholder consensus. The latter include Good Cell Culture Practice, Green Toxicology, the Human Toxome Project, the Evidence-based Toxicology Collaboration, the Industry Refinement Working Group and several others.Noteworthy, Hartung was the head of the European Centre for the Validation of Alternative Methods (ECVAM) of the European Commission in Ispra, Italy, from 2002-2008. The validation studies started at this time contributed to more than 20 OECD test guidelines for alternative methods, the ultimate goal for alternative methods for chemical safety.

The award is the capstone for a series of prestigious prizes given to the two researchers, which include the  Doerenkamp/Zbinden Award for replacement of animal experiments, US Society of Toxicology Enhancement of Animal Welfare Award to both, the Russel & Burch award of the Humane Society of the US to Hartung, a number of LUSH awards to both and their team members, the EuroGroup for Animals – Act4Animals Award to both, the Felix Wankel international award for Alternative Methods to Leist and the German Ministry Award for replacing animal experiments to both.

Franz Gruber calls on other philanthropy to join the efforts to sustain these chairs and create many others. “This is the time to make a lasting change in the laboratory use of animals by educating the next generation of researchers and by showing that high-quality research on human-relevant alternatives is the way forward to end animal experimentation”, he says.

Contact

Franz P. Gruber

franz.p.gruber@doerenkamp.ch

Press release by the German Research Foundation (DFG)

www.dfg.de/en/funded_projects/prizewinners/haendel_prize

More information about the Chairs and CAAT

https://www.biologie.uni-konstanz.de/leist/

https://www.jhsph.edu/faculty/directory/profile/2308/thomas-hartung

https://caat.jhsph.edu

More information about the Doerenkamp-Zbinden Foundation

http://www.doerenkamp.ch

From the Doerenkamp-Zbinden Chairs in Konstanz/Germany and Baltimore/USA and ALTERTOX in Brussels a guest editorial was published in the Archives of Toxicology:

Harnessing the power of novel animal‑free test methods

for the development of COVID‑19 drugs and vaccines

https://doi.org/10.1007/s00204-020-02787-2

Mohammad Abdulkader Akbarsha, former professor of the Gandhi-Gruber-Doerenkamp-Chair in Tiruchirappalli/Tamil Nadu/India published with several colleagues an article concerning

https://doi.org/10.1016/j.ica.2020.119783

It is our pleasure to announce that a project ran by the Doerenkamp-Zbinden Chair in Utrecht, the Netherlands, has been crowned by a PhD thesis. The thesis entitled „ ANIMAL TESTING, 3R MODELS AND REGULATORY ACCEPTANCE - Technology Transition in a Risk-averse Context“ by Marie-Jeanne Schiffelers provides an in-depth analysis to understand why the acceptance and use of 3R (replace, reduce and refine) models in the regulatory domain is a highly challenging process. This study addresses a number of issues in the field of 3Rs and their regulatory acceptance and provides an in-depth insight into the topic answering the following questions:

• How can regulatory acceptance and use of 3R models for risk assessment and efficacy testing purposes be defined?
• Which theoretical perspectives are needed to comprehend and enhance this process?
• Which factors influence the regulatory acceptance and use of 3R models?
• How do these factors influence the regulatory acceptance and use of 3R models 
• How can the process of regulatory acceptance and use of 3R models be optimized?

 This exceptionally refined work has just been published and is available for download.

Click here to download >>„ANIMAL TESTING, 3R MODELS AND REGULATORY ACCEPTANCE - Technology Transition in a Risk-averse Context“<<

The Doerenkamp-Zbinden Foundation-sponsored Mahatma Gandhi-Doerenkamp Center (MGDC) for Alternatives to the Use of Animals in Life Science Education, with the Gandhi-Gruber-Doerenkamp Chair for Life Science Education and In Vitro Toxicology, established in July 2009 at Bharathidasan University, Tiruchirappalli in India, with People for Animals (PfA), Chennai, as a supporting partner, has been working tirelessly in the cause of animals in India, particularly in the domains of education and training, chemical risk assessment, drug discovery and cosmetics testing. Tenured for five years, the Center / Chair was scheduled to be wrapped up in June 2014, since the Foundation was not in a position to support its continuation. However, the incumbent Chair was able to self-generate small funds such that the activities could be continued until March 2016. In the mean time, in order to sustain the activities of the Center after this date and encouraged by the Foundation, PfA, and the Vice-Chancellor of the University, the incumbent Chair put enormous effort into mobilizing financial support from an Indian Government Funding Agency. Now, it is heartening that the University Grants Commission (UGC), New Delhi, has sanctioned an amount of INR Five Crores (INR 50 million) under the “Center with Potential for Excellence in Particular Areas (CPEPA)” scheme for a “National Center for Alternatives to Animal Experiments (NCAAE).” This Center will essentially be a continuation of the MGDC, with much more emphasis on courses as well as research on alternatives, but without the Chair. The following shall be the objectives of NCAAE, India:

- To establish a national repository and reference point of literature on animal alternatives and to keep it up to date; to provide access to the literature to the stake-holders.

- To establish a repository of digital and simulation alternatives for dissections and animal experiments, introduce newer digital alternatives, to update them regularly and train the stake-holders in these alternatives.

- To establish the facilities for and provide training in in vitro alternatives; to establish co-culture facility and 3D culture facility; to bring up new technologies / variants of existing technologies so as for India to be at least self-reliant in respect of products and processes; to facilitate scientists / researchers with these facilities and to apply these technologies in research and risk assessment; to provide training to stake-holders.

- To provide an in silico alternatives facility and training; to introduce newer in silico tools and newer applications for existing tools; to facilitate scientists / researchers with these tools; to provide training.

- To offer academic programs on “alternatives.”

- To support networking of individuals, institutes and labs engaged in contributing to alternatives; to conduct seminars, symposia, conferences and national and international congresses on alternatives.

DZF, PfA and the Founder-Chair are very proud that this facility, which will blossom and prosper into a force to be reckoned with, was seeded by them. Thus, DZF and PfA will have a permanent and coveted place in the history of the alternatives movement in India.

Mohammad A. Akbarsha

Mahatma Gandhi-Doerenkamp Center (MGDC) for Alternatives to the Use of Animals in Life Science Education & Gandhi-Gruber-Doerenkamp Chair for Life Science Education and In Vitro Toxicology, Bharathidasan University, Tiruchirappalli, India

The Mahatma Gandhi-Doerenkamp Centre (MGDC), based in Tiruchirappalli, Tamil Nadu, for Alternatives to Use of Animals in Life Science Education has been awarded a  Humane Science Award. The award is given by People for the Ethical Treatment of Animals (PETA) India and coming just in time for National Science Day on 28 February. It recognises the MGDC for, among other successful efforts, their monumental progress in pushing for humane legislation and reducing and eliminating animal testing via educational workshops for teachers, researchers, veterinarians and physicians.

“The exceptional strides made by the Mahatma Gandhi-Doerenkamp Centre are modernising research and preventing millions of animals from being cut up in classrooms”, says PETA Science Policy Adviser Dr Chaitanya Koduri. “PETA’s motto reads, in part, that ‘animals are not ours to experiment on’ – a philosophy that this group are making a reality by helping students use exclusively modern and humane research methods.”

In the past five years, the MGDC has sponsored more than 60 workshops at institutions across India, educating teachers at the high school through university levels on modern digital dissection simulations, which produce better results in the classroom than archaic animal-based methods. The group have also teamed up with PETA to push for changes in course curricula through the University Grants Commission and Medical Council of India, sparing the lives of millions of animals every year.

The MGDC has tackled high-level research as well, holding 17 intensive 10-day training sessions on cell culture techniques and in vitro technology, educating nearly 300 researchers and scientists on modern, animal-free methods. The MGDC’s work with SkinEthic Academy in France has also resulted in three workshops, helping to integrate 3-dimensional in vitro methods that take the place of animals in cosmetics tests.

The "Center for Alternatives to Animal Experiments in Europe" (CAAT-Europe) was honored with the Lush Prize for its "CAAT-Europe Policy Program". This is the highest prize given for lobbying and policy interventions promoting the use of alternatives to animal testing.

The independent scientific organization CAAT Europe, headquartered at the University of Konstanz is awarded the prize for its proactive commitment to providing scientific information to the European parliament in Brussels. Dr. Francois Busquet, who coordinates the scientific information work of CAAT-Europe in Brussels, accepted the €50,000 prize in London.

CAAT-Europe aim is to bring together decision makers from politics and business with scientists in order to demonstrate scientifically sound alternatives to animal testing in product and safety testing. "We work independently of industry, government and animal welfare organizations and can therefore provide interest-free scientific results and research. We aim here to always keep our finger on the pulse of consumer protection" says Prof. Dr. Thomas Hartung, co-director of CAAT-Europe.

CAAT-Europe proactively communicates to Parliament members and offers conferences and workshops in the European Parliament. Since 2012, discussions in the field of lifesciences were led with more than 100 members of the European Parliament and ten workshops were organized.

In 2013 CAAT Europe became the official external consultant (STOA) of the European Parliament. "We are proud of that that we brought with our “Policy Program” scientific animal-free test methods to the level of the European institutions and that CAAT-Europe at the University of Konstanz has become a leading institution in this field in Europe," says Prof. Dr. Marcel Leist, head of CAAT-Europe.

The Society of Toxicology (SOT)* — the world’s largest and preeminent association representing the field of toxicology — is recognizing the field’s top researchers and scientists today through the announcement of recipients of 2015 SOT Awards that honor individuals who are advancing the field of toxicology.

Marcel Leist, the head of the Doerenkamp-Zbinden chair of in-vitro toxicology and biomedicine, is being awarded the 2015 SOT Enhancement of Animal Welfare Award. This award honors a SOT member for contributions made to the advancement of toxicological science through the development and application of methods that replace, refine, or reduce the need for experimental animals. Dr. Leist’s laboratory focuses on in vitro toxicology, specifically mechanisms and systems related to neurotoxicity.

*The Society of Toxicology (SOT) is a professional and scholarly organization of scientists from academic institutions, government, and industry representing the great variety of scientists who practice toxicology in the US and abroad. SOT is committed to creating a safer and healthier world by advancing the science of toxicology. In recognition of distinguished toxicologists and students, SOT presents many prestigious awards each year.

Happy 75th birthday to Alan Goldberg, a father of the present success of the 3Rs in the world, a good friend, mentor and visionary thinker, honorary member of the scientific advisory board of the DZF.

Thank you, dear Alan

The Doerenkamp-Zbinden Foundation board members, Eduard, Franz, Marcel, Norbert, and Thomas

The Foundation Office, Vera and Goran

In November 2014 we celebrate the 75th birthday of Alan Goldberg, an iconic figure in the field of alternative methods. Coincidentally, one of the most beloved films of all time, The Wizard of Oz, shares this anniversary. Our story takes place in Maryland, not in Kansas, and it was not a storm that transported Alan into the alternative world but the Cosmetic Toiletries and Fragrance Association (CTFA), which in 1980 was looking for help to make a credible contribution to reduce animal use. And thus began the journey to the Emerald City along the yellow brick road through a land where animals and humans spoke to and helped one another (well, except for the flying monkeys). While it’s tempting to translate the companions found on the way – the Scarecrow, Tin Woodsman, and the Cowardly Lion – to some of the characters Alan teamed up with on his way, let’s not overdo the analogy.

Anyway, Alan fits neither the role of Dorothy (who in the end is only a dreamer) nor the wizard (who is exposed as a fraud). Still, what seemed like a fairytale for many when he created CAAT in 1981 has become a reality in 2014: More research is done in vitro than in vivo. A PubMed query on publications in 2014 (January to September) with the term “animal” results in 70,000 papers vs. 190,000 with the term “cell.” The use of animals in drug development continues to decline, as is most clearly evidenced by the 25% decline between 2005 and 2008 in Europe. Alternative approaches are now mainstream science – and Alan Goldberg was pivotal in making that happen.

He led CAAT, the premier 3Rs center in North America, for 27 years, created Altweb, the most prominent website in the field and began the series of international World Congresses on Alternatives. Now Alan is retiring from his role as Chair­man of the CAAT boards in the US and Europe.

All great journeys have a beginning. Alan got his PhD in pharmacology from the University of Minnesota in 1966 with an interest in the cholinergic nervous system. At the time, the importance of acetylcholine (Ach) in the nervous system was first being understood but there were no chemical assays to measure it. He decided he wanted to develop an assay sensitive enough to measure ACh in a single spinal motor neuron in order to study neuromuscular physiology. He applied to the laboratory of Richard McCaman at Indiana University, a laboratory dedicated to microchemical techniques and the nervous system. He went to McCaman’s laboratory at the Psychiatric Research Institute at Indiana University (Indianapolis) as a postdoctoral fellow for one-and-a-half years and then accepted an assistant professorship position in pharmacology at IU. Alan continued to work with McCaman and in 1973 published a paper describing a radioenzymatic assay for ACh. The sensitivity was so high that the test could measure the content of a single motor neuron, and the assay has been used for at least 35 years. Few assays have such longevity.

Alan was recruited by Hopkins in 1969 to the Department of Environmental Health Sciences, Division of Toxicology, to continue his studies on cholinergic-related systems and their relationship to pesticides and heavy metals. Most of the pesti­cide studies attempted to understand organophosphate delayed neurotoxicity and were the first use of tissue culture systems in mechanistic toxicology. Alan’s work contributed to a better standardization of tissue culture systems.

Alan’s heavy metal studies focused mainly on lead toxicity. At the time the grant was funded, a young environmental engineer, Ellen Silbergeld, became a postdoc in his laboratory. Their studies pioneered the understanding of early lead exposure hazards and lead’s effect on the developing brain.

In 1980, The Cosmetic Toiletries and Fragrance Association (CTFA, now PCPC, the Personal Care Product Council), wanted to respond to consumer concerns about animal testing for cosmetics. They approached the Johns Hopkins School of Hygiene and Public Health (now the Bloomberg School of Public Health) for help. D. A. Henderson, the school’s dean, knew of Alan’s work using tissue culture and asked if he would be interested in organizing such a program.

Gareth Green (Chair of Environmental Health Sciences), D. A. and Alan met to discuss how to develop the proposal. Ga­reth (with Alan’s participation) ran the EPA grants program. They knew that small grants ($20,000) could be spread over many laboratories at Hopkins and other institutions to develop a foundation for in vitro toxicology. “We would not be creating a giant laboratory at Hopkins,” Alan recalls, “but could tap into the best scientists worldwide to develop the in vitro methodologies that could become the basis for test development. The vision became clear. CAAT would focus on developing in vitro cell-based assays to replace animal tests for regulatory purposes.” Since then, CAAT has awarded more than 300 grants totaling over $6 million.

The CTFA grant that established CAAT was funded on September 21, 1981, with a press conference announcing the center and its anticipated programs. The press coverage was enormous and the center was off and running. “We had been advised to have security present because of the animal activist community,” Alan recalls with a smile. (CAAT has worked closely with animal welfare organizations throughout its history.)

Two other Hopkins faculty members, Henry Wagner and Franklin (Frank) Loew, joined the team. Their first major ac­tivity was putting together an advisory board, organizing its first meeting and planning to solicit grants. Frank suggested approaching Andrew Rowan of the Humane Society of the US to be a member of the board so that the animal protection community would be represented. Andrew would also serve as Alan’s mentor on animal protection issues. The team also realized they needed academics specializing in eye and skin physiology, representatives from government regulatory agencies (FDA, NIEHS, and EPA) and industry sponsors. D.A. and Gareth identified and recruited the government rep­resentatives. They approached the FDA commissioner, who appointed Gerald Guess to represent them, John (Jack) Moore (an Associate Director of the EPA) and Paul Kotin, the first Director of the NIEHS, were asked to participate. All three joined the board. The academics included Lowell Goldsmith, the chair of dermatology at Rochester, and James (Jim) Mc­Culley, of Dallas South West Medical School. From industry they invited Norman Estrin, a representative of the CTFA, and Leon Golberg of the Chemical Institute of Toxicology (now known as The Hamner Institutes for Health Sciences).

The board sought to create a comprehensive and honest animal protection agenda. All of the board agreed that a fundamental component would have to be rigorous scientific research. Leon Golberg initiated one of the most important discussions. If CAAT were to actually replace animal testing with tissue culture methods, he pointed out, it would need to develop assays using human cells in culture. This understanding was prophetic and absolutely correct. Funding research to provide consistent human tissue culture models became a focus of the research program. Human cells in culture and 3D models are now commercially available, in part because of CAAT’s vision.

Other CAATprograms included an in vitro laboratory, organized by John Frazier, a grants program, symposia, technical workshops, and an 11-volume book series. The communications program was then developed as it became apparent that the public was truly interested in alternatives. The symposia series developed into the World Congress on Alternatives and Animal Use in the Life Sciences. The first was held in 1993 in Baltimore and the ninth was held this year (2014) in Prague.

Alan Goldberg directed CAAT from its founding in 1981 to 2008. Upon my request he stayed with us as Chairman of the Board, and soon after Chairman of the European Board. Now, almost six years later, it is time to say farewell. “Every farewell combines loss and new freedom,” the aphorist Mason Colley said. While we will dearly miss Alan’s daily presence, we hope that while enjoying his new freedom he will remain available for occasional advice and assistance. We now identify him as Founding Director (Emeritus).

L. Frank Baum, in The Wonderful Wizard of Oz, wrote: “... And remember, my sentimental friend, that a heart is not judged by how much you love, but by how much you are loved by others.” Alan, his great work, and his generous heart, are clearly loved by many. We wish him a wonderful journey ahead.

Thomas Hartung, MD, PhD

Article was published in ALTEX 4/2014, pp547-548

The Doerenkamp-Zbinden Foundation has continued to actively support a number of projects in the field of alternatives to animal testing in biomedical sciences. Furthered activities are either projects performed within the frame work of the Foundation’s chairs or have been independently supported as projects with a significant impact on the promotion of alternative methods. Up to now numerous projects have provided significant results which have been published either in form of scientific articles in prestigious journals such as ALTEX or doctoral dissertations. For example, reports on the activities and achievements of the t4 (transatlantic think thank of toxicology) project have regularly been published (please read more about the project at the following link: http://www.doerenkamp.ch/en/default.html?id=96).

A paper on another project furthered by the Foundation which has been running at the University of Geneva has recently been published in ALTEX. This paper entitled “Use of in vivo biotinylated GST fusion proteins to select recombinant antibodies” provides an insight into the project and procedures dealing with the selection of recombinant antibodies using in vitro models. As the results suggest this model has a strong potential to replace animal immunization for the development of specific antibodies. (for more info please click the following link: http://www.altex.ch/All-issues/Issue.50.html?iid=147&aid=4)

The Doerenkamp-Zbinden Chair at the University of Konstanz in Germany has just provided the scientific community with an article titled “Generation of genetically-modified human differentiated cells for toxicological tests and the study of neurodegenerative diseases”. The focus of the paper is determination whether genetic modifications in the proliferating state of LUHMES cells could be used for experiments in the differentiated post-mitotic neurons. For more information please visit the ALTEX website at which the full text of the article is available free of charge (http://www.altex.ch/Current-issue.16.html?aid=2).

Another project supported by the Foundation has recently provided a publication in the field of in vitro assays. The publication entitled “Biokinetics and repeated exposure in in vitro assays: A detailed study into the behavior of chlorpromazine and diazepam in different cell systems” is a doctoral dissertation defended at the University of Utrecht, the Netherlands. 

For more information about the dissertation please click on the figure (left).

The Doerenkamp Zbinden Foundation is happy to be able to share with you the outstanding results of its projects published in a renowned scientific journal on alternatives to animal testing such as ALTEX and hopes to continue doing so for many years to come.

The Doerenkamp-Zbinden Foundation was created in 1985 on the initiative of a wealthy Canadian citizen with German origin, Hildegard Doerenkamp (1921-2011) who at that time lived in Switzerland, and Prof. Gerhard Zbinden (1924-19933), a world-wide recognized toxicologist from the Swiss Federal Institute of Toxicology and the University of Zurich. They both had one goal: “all unnecessary animal experimentations, particularly those involving dogs and other companion animals, should be replaced with modern and clinically-relevant testing systems". The Foundation has been a real success. After a university chair in Erlangen in Germany, which was privately started and financed by Hildegard Doerenkamp, additional five university chairs have been established worldwide. These chairs in Konstanz (Germany), Geneva (Switzerland), Utrecht (The Netherlands), Baltimore (USA) and Tiruchirappalli (India) have been directly founded and financed by the Doerenkamp-Zbinden Foundation. In Tiruchirappalli has even been built an institute named a “Mahatma-Gandhi-Doerenkamp Center for alternatives to the use of animals in life science education". Alongside with the university chairs the Foundation supports big and small research projects in which it has been up to now invested more than 30 Million Swiss francs. The percentage of the foundation’s management costs is very low and lies under 10% of all annual costs.

Donors who would contribute in financing of the university chairs are sought. The means in the amount of circa 600’000 Euros annually, which the Foundation cannot gain anymore over its investments in the banks in Switzeland and Germany, are needed. Contributions may be made via the tax-exempted Foundation or directly to the university chairs. The sponsors may influence the name of a chair if desired.

Please be free to contact the foundation’s office.

Doerenkamp-Zbinden Foundation

PD Dr. Franz P. Gruber

Weinmanngasse 86

8700 Kuesnacht ZH

Switzerland

fpg@doerenkamp.ch - www.doerenkamp.ch

On 23rd of April 2012 the Board of the Doerenkamp-Zbinden Foundation approved a 2-year extension of the t4 project (transatlantic-think-tank-toxicology). The goal of the project is to, following the developments of the toxicology field in the USA (Tox 21c), bring topics such as animal-free toxicology research to be intensively discussed in Europe too.  With the extension of the project the Doerenkamp-Zbinden Foundation provides an attempt to replace the discontinued ECVAM-Workshops. All t4-Reports and t4-Workshop-Reports will be published in ALTEX (Alternatives to Animal Experimentation www.altex.ch)

The concept

t4 is a collaboration of the toxicology oriented DZF chairs and was created with the following aims:

• to analyze current tools and programs and model / forecast the likely outcome with regard to safety and economic burden (cost/benefit analyses)
  
• to compare different approaches on an international scale (especially transatlantic) and support harmonization
  
• to further the concept of an evidence-based toxicology (EBT) following the role model of evidence-based medicine
  
• to develop and assess the conceptual needs to enable the change of approaches (predictive toxicology, integrated testing, systems toxicology, organotypic and stem cell cultures)
• to create and maintain information platforms (AltWeb, ALTEX, TestSmart workshops, etc.) to further the paradigm change in toxicology
  

The Project „Modeling of pathways of developmental neurotoxicity as pilot of a paradigm shift for regulatory safety assessments of chemicals – phase 2” will be financed by the Doerenkamp-Zbinden Foundation for the time period of one year. This is a bridge payment as the final decision about the future funding of the project is expected from NIH (National Institute of Health, USA). The furtherance initiates the start of laboratory work at the Center for Alternatives to Animal Testing (CAAT) at the Johns Hopkins University in Baltimore and will be realized in a close cooperation with Doerenkamp-Zbinden Chair at the University in Konstanz in Germany. 

The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) has received a $6 million grant from the National Institutes of Health (NIH) to pioneer potentially revolutionary new methods for toxicological testing to improve human health and reduce animal testing.

CAAT Director Thomas Hartung, MD, PhD, and his team at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, along with partner Agilent Technologies and noted scientists from government and industry, received the funding for a consortium to develop a new technological methodology for mapping the molecular pathways of toxicity within cells. Funding for the project comes from the Common Fund’s NIH Director’s Transformative Research Projects Program (R01), which is designed to support exceptionally innovative, high risk, original and/or unconventional research that has the potential to create or overturn fundamental scientific paradigms.

Current toxicological testing relies on a patchwork of 40+-year-old animal tests that are expensive (more than $3 billion per year), time-consuming, and often provide results of limited predictive value for human health. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides, and drugs) has led to a backlog of more than 80,000 chemicals for which potential toxicity remains largely unknown.

Scientific understanding of how genes, proteins, and small molecules interact to form molecular pathways that maintain cell function has evolved rapidly, thanks to advances in molecular and computational tools. Pathways that lead to adverse health effects when perturbed are referred to as pathways of toxicity (PoT). “Mapping the entirety of these pathways—which I’ve termed the ‘Human Toxome’—will be a large-scale effort, perhaps on the order of the Human Genome Project,” Hartung says.
As a first step to mapping the Human Toxome, Hartung and his collaborators have proposed comprehensively mapping the pathways of endocrine disruption, a perturbation of the hormonal system that can cause tumors, birth defects, and developmental disorders. The physiological pathways of the endocrine system are relatively well understood, making PoT identification simpler than for other potential targets. The team will develop a common, community-accessible framework that will enable the toxicology community at large to comprehensively and cooperatively map the human toxome using integrated testing strategies that combine “omics” (transcriptomics and metabolomics) data with computational models. The consortium will also create a public database of PoT, enabling full access to researchers around the world.

Along with Hartung, the other principal investigators include James Yager (Bloomberg School of Public Health); Robert Kavlock, Director of the National Center for Computational Toxicology at the U.S. Environmental Protection Agency (EPA); Michael Rosenberg, Director of Genomics Software Life Science Group at leading systems biology technology provider Agilent Technologies; Mel Andersen, Associate Director of the Hamner Institute for Health Sciences; Kim Boekelheide, Professor of Medical Sciences at Brown University; and Albert J. Fornace, Jr., Molecular Cancer Research Chair at Lombardi Comprehensive Cancer Center, Georgetown University Medical Center.

Additional information on Thomas Hartung and the Johns Hopkins Center for Alternatives to Animal Testing may be found at:
http://caat.jhsph.edu

After a short, severe illness, Ms Hildegard Doerenkamp, cofounder of the Doerenkamp-Zbinden Foundation, passed away on 21 February 2011 at the age of 90. She had been living by herself in the Black Forest, Germany, no longer wanting to endure living in retirement homes or hotels. She was self-sufficient and had finally regained her independence, which she had valued highly all her life.

Ms Doerenkamp loved the outdoors. She enjoyed farming and managed farms in the lower Rhine area, Germany, in Graubuenden, Switzerland, and in Nova Scotia, Canada. Looking back she always called the fifteen years she spent in Canada, where she also took on Canadian citizenship, the best years of her life. Her Canadian neighbors, who were very sad to hear of her sudden death, wrote me: “She was a great lady with a zest for life and great determination. We are very sad to have lost a good old friend.”

After Hildegard Doerenkamp first met Professor Gerhard Zbinden in 1982 (he died far too soon in 1993), she became increasingly fascinated by scientific animal protection. Together with him she founded the Doerenkamp-Zbinden Foundation (DZF) in 1985. In recent years, six university chairs for alternatives to animal experiments were established in Erlangen (Germany, paid by Ms Doerenkamp personally),  Konstanz (Germany), Utrecht (The Netherlands), Baltimore (USA), Geneva (Switzerland) and Tiruchirappalli (India), with the support of the DZF. The history of the Doerenkamp-Zbinden Foundation is detailed at www.doerenkamp.ch.

It was her highest maxim that the DZF should always be completely independent. It collects no donations and accepts no money from the state or from industry. This independence of political fashions and other pressures, which ensue from external financing, will be upheld after her death in accordance with her wishes. Ms Doerenkamp gladly accepted advice and suggestions, but never without an in-depth analysis of them. She read a lot (an enthusiastic ALTEX reader from the first hour) and asked a lot. Often, her highly specific questions even led one to question, whether one had really understood all details of the subject oneself. She made no secret of her special love of dogs and, with the sovereignty of age she flouted philosophical objections to preferring one species over another. She enjoyed baffling her discussion partners with her statement that she cared least about primates – they being too similar to humans, with whom she really did not get along at all. Of course she never missed qualifying such statements with irony. She was confidant enough to also laugh about herself. Ms Doerenkamp suffered from bad hearing. When the Allies attacked Cologne she refused to use the air raid shelter and lay down in the grass in her parents’ garden. The shock waves of the bombs severely damaged her hearing. Conversations with her were always conducted with pencil and paper, the work of the Foundation was managed over years by an almost daily exchange of faxes. 
The Foundation was her life’s work; she regularly, especially in the years of the global economic crisis, asked after the financial state of the Foundation and was relieved that the careful investment strategy she had demanded let the Foundation glide easily through these difficult years. She was glad to repeatedly add additional donations from her private fortune when the Foundation would have been unable to found a university chair from its own reserves.  

With Hildegard Doerenkamp’s passing we have lost a great lady. She was honorary senator of the University of Erlangen/Nürnberg, memorial plaques honor her at the Institute for Companion Animals at the Faculty for Veterinary Medicine in Utrecht and the Bloomberg School of Public Health in Baltimore, in India the newly built Center for Alternative Methods, which was financed by the Foundation, was named the Mahatma Gandhi-Doerenkamp-Center. But apart from these honors, she has the far greater gratitude of all those, whose life she influenced decisively, whom her convictions and support led to adjust their (scientific) direction. In this it was always important to her that her contribution led not only to the protection of animals but also to better medicine for humans developed using more humane research methods. 

Ms Doerenkamp prepared her passing in detail. She categorically refused intensive medical care to prolong her life. Her urn will be buried on her former farm in Canada. Our trip to perform this last mandate will be a melancholy one. May she smile down upon the further progress of her life’s work with increasing pride.
Our sympathy is with Ms Doerenkamp’s daughter.

Franz Paul Gruber,

*in the name of the foundation board, the scientific advisory committee and the office staff of the Doerenkamp-Zbinden Foundation as well as the Doerenkamp chairs in Erlangen, Konstanz, Utrecht, Baltimore, Genf and Tiruchy