In the September 6, 2008 Newsweek article, “We Fought Cancer…And Cancer Won”, author Sharon Begley discussed the ongoing scientific battle against cancer. She noted that although some genetic breakthroughs have occurred since cancer research began in 1971, Begley cites the many other unsuccessful and costly attempts scientists have made to try to better control and eliminate the disease in humans. Her examples help illustrate a crucial reason why our attempts to cure cancer have failed – research has relied on the use of nonhuman animal models to solve a human-centered disease.
NEAVS/Project R&R Science Director Jarrod Bailey, PhD expanded on the need for human-based research in his response letter to Newsweek:
Sir:
Sharon Begley’s “We fought cancer…and cancer won” [1] revealed the misuse of $200 billion devoted to cancer research. This is evidenced by the failure rate in humans of anti-cancer drugs passing animal tests, which is 95% [2, 3] – and those few drugs that do make it are often poor.
The reason for this is simple: animals are not humans. Even in chimpanzees, our closest relative, at least twenty genes implicated in human cancer are significantly different [4]. The ras gene, involved in many human cancers, works very differently in mice [5]; and another gene that promotes cancer in mice restricts cancer growth in humans [6].
While animal research has provided little to elucidate human cancer, more relevant, human-specific research has saved lives and led to progress – as illustrated by Begley’s article. Scientists now have cutting edge methods we could only dream of a few years ago, that can delve deep into human cancers and deliver treatments and cures. Tissue banks can provide human tumor samples from which the activity of thousands of genes can be deduced in days – implicating those involved in tumor formation. This research has delivered important data on breast, colorectal, pancreatic and brain cancers already [7, 8].
The drug Gleevec was almost abandoned when experiments in dogs revealed liver toxicity. Due to encouraging prior experiments using human cells, canine data were ignored and Gleevec proceeded to clinical trials – and is saving lives [9]. The case for human-based research and against animal-based investigations is strong. Combined with preventive programs (fifty percent of cancers are avoidable [10]), we have a genuine prospect of reversing the increase in cancer and saving millions of lives. Scientists who persist with animal models must leave them behind. If they do not, our failure to make progress against cancer will continue.
References
(1) Begley S. We fought cancer…and cancer won. Newsweek, Sep 6. Available: http://www.newsweek.com/id/157548
(2) Thomas G. Roberts, Jr, MD, MSocSci; Bernardo H. Goulart, MD; Lee Squitieri; Sarah C. Stallings, PhD; Elkan F. Halpern, PhD; Bruce A. Chabner, MD; G. Scott Gazelle, MD, MPH, PhD; Stan N. Finkelstein, MD; Jeffrey W. Clark. Trends in the Risks and Benefits to Patients With Cancer Participating in Phase 1 Clinical Trials. JAMA. 2004;292:2130-2140.
(3) Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery 2004;3:711-5.
(4) Puente XS, Velasco G, Gutiérrez-Fernández A, Bertranpetit J, King MC, López-Otín C. Comparative analysis of cancer genes in the human and chimpanzee genomes. BMC Genomics. 2006 Jan 26;7:15.
(5) Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT, Der CJ, Counter CM. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes and Development 16: 2045-2057, August 15, 2002.
(6) Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L. A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer. Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9697-702.
(7) Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An Integrated Genomic Analysis of Human Glioblastoma Multiforme. Science. 2008 Sep 4 [Epub ahead of print].
(8) Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses. Science. 2008 Sep 4. [Epub ahead of print].
(9) Groopman J (as stated in The New Yorker): republished in Ridely, Matt (Ed) The Best American Science Writing 2002. Harper Perennial 2002. Pp 352: ISBN-10: 0060936509.
(10) Dobson R. Most cancers in Europe avoidable. BMJ 2007;334:62, doi: 10.1136/bmj.39087.526794.DB.
Pepper: (left) in her 5X5X7 ft. lab cage at LEMSIP; and, (right) on her sanctuary island at Fauna
Eleven years after their rescue from HIV/AIDS and other research, Sue Ellen, Rachel, Pepper, and others are now ambassadors for Project R&R: Release and Restitution for Chimpanzees in U.S. Laboratories, a national campaign to end the use of chimpanzees in invasive biomedical research. Their anniversary, celebrated at Fauna – the first sanctuary to accept HIV-infected chimpanzees – comes on the heels of research showing that the failure to develop a successful HIV/AIDS vaccine for humans can be attributed to the use of chimpanzees.
“An Assessment of the Role of Chimpanzees in AIDS Vaccine Research,” published this month in the international journal Alternatives to Laboratory Animals (ATLA), showed that most of the vaccines developed to date were tested in chimpanzees who endured decades of experiments. Almost all of the vaccines protected chimpanzees from HIV infection, but none were successful in humans. Investigation of the reasons chimpanzees are a poor model for HIV infection led the paper’s author, geneticist Jarrod Bailey, Ph.D., to conclude that “claims of the importance of chimpanzee research for human health are misleading and a call to return to their use is without scientific justification.”
As a result of rescues like that of Sue Ellen, Pepper, and others, the world is coming to know chimpanzees who suffered dearly in research. Gloria Grow, Fauna founder and Project R&R co-chair, notes, “Nearly every day, for eleven years, I have watched the effects of laboratory use on chimpanzees. And throughout this time, I thought if people only knew them, their stories, this use and abuse would stop. Now, with research showing how useless their suffering was, the point will be driven home: all the rest need to be released as well.”
The past decade has seen changes in the perception and use of chimpanzees in research. U.S. laws/policies now prohibit euthanasia for a lab’s convenience; require permanent protection from future use once “retired;” and have ended federal funding for breeding. Funding for chimpanzee research has declined while public outrage over their use has grown, and a recently introduced bill calls for an end to their use in invasive research in the U.S. (the Great Ape Protection Act [GAPA]) – promising to add the U.S. to the list of eight countries that have already banned or severely limited chimpanzee research.
According to Theodora Capaldo, Ed.D., Executive Director of Project R&R, “With chimpanzee research we have all lost – millions of wasted taxpayer dollars and failed science. The real costs have been borne in the pain and suffering of a species, so close to our own. Individuals we know and care deeply about, like Pepper and Sue Ellen, are no different from the 1,100 others remaining in U.S. labs – some for 40 or 50 years. They too deserve sanctuary before it is too late. As a psychologist who cares deeply about people as well as other species, I see the tragic legacy of chimpanzee use in research, and I am convinced that only by protecting them and ending their use in biomedical research will we also be successful in helping humans.”
NEAVS/Project R&R made a factual and sharp response to an editorial in Nature Medicine (Volume 14, Number 8) – “When less is not more” – that advocated widespread experimentation using nonhuman primates (NHPs).
Our response, entitled, “Nonhuman primates mean less, not more, human medical progress” is authored by Jarrod Bailey, Ph.D., Project R&R’s Science Director and NEAVS’ president Theodora Capaldo, Ed.D. with co-authors from the HSUS and BUAV. The piece provides scientific rebuttal of points made in favor of NHP research in the Nature editorial. In particular, it highlights evidence of the failure of chimpanzee use, citing data from Project R&R’s investigations; addressing humane and ethical issues as well as promoting the use of scientifically superior alternatives.
NEAVS/Project R&R takes seriously our responsibility to fight science with science and set the record straight whenever, in our opinion, rhetoric and bias are passed off as good science. There are two sides to every story and it is time our side is heard. If you are a medical doctor, veterinarian, or scientist, join us in our “information campaign” by responding to any science/medical articles that you believe are incomplete or inaccurate!
“A return to the use of chimpanzees in AIDS research and vaccine development is without scientific justification,” according to a paper released today in the journal Alternatives to Laboratory Animals (ATLA). “An Assessment of the Role of Chimpanzees in AIDS Vaccine Research” concludes that vaccine responses in chimpanzees are not predictive of responses in humans, and that claims of chimpanzees’ critical role and importance in AIDS vaccine development are without foundation.
The publication comes on the heels of recent vaccine failures in late-stage clinical trials, including one vaccine that appeared to increase vulnerability to HIV infection in human clinical trial participants, though the vaccine had proven safe and effective in tests in nonhuman primates. Yet some scientists are calling for a return to the use of chimpanzees, despite their previous failings.
Other scientists doubt that a return to their use would lead to likely success. According to the paper’s author, geneticist Jarrod Bailey, Ph.D., Science Director for Project R&R: Release and Restitution for Chimpanzees in U.S. Laboratories: “At a cost of billions of dollars, most of the 85 AIDS vaccines created to date have been tested in hundreds of chimpanzees who endured decades of experiments and laboratory confinement. Almost all of these vaccines protected chimpanzees from HIV infection, but none has worked in humans. Claims of the continued importance of chimpanzee use are therefore misleading. For the millions of people at risk of AIDS, as well as the chimpanzees, we must move toward more humane and scientifically superior methods.”
Chimpanzees have proven to be a failed and dangerous model for humans in not only AIDS research but in areas such as heart and cancer research as well.
In a May 2008 essay in Nature, NIAID Director and AIDS expert Dr. Anthony Fauci, when reflecting on the era of HIV/AIDS, noted: “We must learn from our missteps, build on our successes in treatment and prevention, and renew our commitment to developing the truly transforming tools that will one day put this scourge behind us.”
According to Dr. Bailey, “The search for such a critically needed ‘transforming tool’ cannot include a return to using chimpanzees, one of the greatest ‘missteps’ in the history of AIDS research.”
