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USA: The Wizard of 3Rs – Alan M. Goldberg’s 75th birthday and retirement from CAAT

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

Center for Alternatives to Animal Testing

John Hopkins Bloomberg School of Public Health

615 North Wolfe Street, W7032

Baltimore, MD 21205, USA



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