Monday, March 11, 2013

Vivisection in the Name of Genetics and Gene Therapy

Over the first nine days of July, 1997, I protested the use of monkeys at the Washington (then) Regional Primate Research Center by leafleting for 16 hours a day outside one of the main entrances to the building that houses it. ("The Warren G. Magnuson Health Sciences Building is part of the University of Washington in Seattle, Washington and the world's largest single university building with a total floor area of 533,000 square metres (5,740,000 sq ft). Although the building is made up of over 20 wings built over more than 50 years, the interior hallways are fully connected." Wikipedia).

While there with the Ape Army, I had the opportunity to visit with a number of passersby who stopped to talk with me about the issue. One of the people I talked with was a PhD student who talked to me about the impending completion of the first-ever sequencing of a multicellular organism's genome. Scientists published the Caenorhabditis elegans genome the following year.

The student believed that this event would mark the beginning of the end of the use of animals as models of human biology. He reasoned that knowing C. elegans's genome would lead to an immediate cascade of insights and a deep understanding of gene function that would be able to take full advantage of the human genome when it was eventually published.

These were not the wild imaginings of an overly excited doctoral student. His optimism was shared widely throughout mainstream science. Unfortunately, he was wrong.

As it turns out, the chemistry underlying the genome, of even the simplest organisms, is wildly complex and has yet to be understood.
Exactly how many genes make up the human genome remains a mystery, even though scientists announced the completion of the Human Genome Project a decade ago. The project to decipher the genetic blueprint of humans was supposed to reveal all of the protein-producing genes needed to build a human body.

“Not only do we not know what all the genes are, we don’t even know how many there are,” Steven Salzberg of the University of Maryland in College Park said October 11, [2011], during a keynote address at the Beyond the Genome conference, held in Boston. [More than a chicken, fewer than a grape. ScienceNews.]
In spite of the very limited understanding of gene function, vivisectors are richly rewarded with tax dollars to study the action of genes in animals. For instance:
DESCRIPTION (provided by applicant): Macaque monkeys are the most important animal model for AIDS vaccine development and are increasingly being used in biodefense research. An individual's immunogenetics can profoundly influence susceptibility to AIDS viruses and other pathogens. Indian-origin rhesus macaques have the most thoroughly characterized immunogenetics; however, their availability for research is extremely limited. Chinese-origin rhesus macaques, cynomolgus macaques, and pig-tailed macaques are increasingly relied upon to alleviate the shortage of Indian- rhesus macaques. As studies with these macaques become more common, there is a newfound appreciation that they may offer compelling advantages over Indian-origin rhesus macaques for specific studies. To study cellular immunity to AIDS viruses and biodefense, a comprehensive understanding of major histocompatibility complex (MHC) and killer immunoglobulin receptor (KIR) genetics is required.... PUBLIC HEALTH RELEVANCE (provided by applicant): Macaque monkeys are widely used in the development and testing of prophylactic vaccines against AIDS viruses and pathogens with biodefense potential. Major histocompatibility complex (MHC) and killer immunoglobuline receptor (KIR) genetics influence susceptibility to these diseases. We will sequence novel alleles and define their functional attributes in macaque populations used for infectious disease research. (From Title: IMMUNOGENETICS OF MACAQUES USED FOR BIODEFENSE AND AIDS RESEARCH Project Number: 8R24OD011048-08. O'CONNOR, DAVID H. Awardee Organization: UNIVERSITY OF WISCONSIN-MADISON. Total Funding for 2012: $554,521)
The very complex chemistry underlying the functioning of genes is undoubtedly involved in many if not all biological phenomena. In spite of the massive public expenditures, research, and significant media hype regarding genes, genetics, the genome, gene therapy, epigenetics, etc. there still isn't a deep or firm understanding of exactly how they are involved. At best, our knowledge is cursory. The precise mechanism and control of the seemingly infinite details of biology remain largely a mystery.

This plain fact has far reaching ethical implications. The one most germane to the topic of using animals in harmful experiments is that idea that there isn't a good or even a logical reason to use animals as tools in research on genetics, the function of genes, or the mechanisms of gene-controlled or mediated biological function. Looking for gene-influenced effects on the biology of animal models of human disease and health isn't worthwhile without the requisite knowledge of the chemistry underlying all gene-influenced phenomena.

Because so little is understood about the functioning of genes, the choice to use mice, monkeys, or mole rats to study the way they function -- rather than using plants or fungi -- can't be supported by a rational argument that claims even a hint of ethical grounding or a concern for the animals being used.

A very large sum of tax-payers' dollars is made available annually to scientists who want to create and consume ever more mutant mice, but the money flowing from the public coffers doesn't justify hurting and killing animals.

Consider this explanation for why someone would harm animals in the name of genetic research:
Bipolar disorder (BPD) is a psychiatric disorder characterized by episodic mania and depression. It is a common mental health problem, with an estimated lifetime prevalence of approximately 1–5%. A meta-analysis of family, twin, and adoption studies found that relatives of BPD patients have a 10-fold higher risk of the disorder than those without relatives with BPD, demonstrating that BPD has a strong heritable constituent. Though ongoing efforts to elucidate the genetic basis of BPD using varied approaches have yielded promising results, a convincing molecular etiology of BPD remains elusive. There are at least a few good reasons for this difficulty in finding a genetic basis for BPD. First, BPD is a complex disorder at the molecular level, involving perturbations of not just single genes, but of systems of genes. Second, it may be more proper to speak of bipolar disorders in the plural; the pathology may have multiple heterogeneous molecular bases, a hypothesis consistent with the multiple heterogeneous findings in different genome-wide studies of BPD. Third, deriving mechanistic explanations of human psychiatric disorders using classical genetics presents difficulties due to practical constraints on experimental power and the possibility of epigenetic components of these disorders.

Because a convincing BPD molecular etiology poses significant technical and theoretical challenges to human geneticists, animal models for BPD have a strong potential to extend understanding of this disorder. (A new mouse model for mania shares genetic correlates with human bipolar disorder. Saul MC, Gessay GM, Gammie SC. PLoS One. 2012.)
Who hasn't heard of gene therapy? It'd be great if I could get an injection of some new genes that would replace the ones in the cells that comprise the fascia of my left hand (and now my right) and stop their over zealous production of collagen. But that isn't going to happen anytime soon. We just don't know enough about the mechanics of how the molecules that comprise DNA and RNA work to affect biological systems. We know they do -- somehow -- but the fundamentals and the details elude us.

For all the hype, gene therapy for any malady remains the stuff of science fiction. Or fictional science in the case of most labs using animals as genetic test beds.

The big news on the gene therapy front is that the European Union has for the first time (anywhere) approved the use of a gene therapy. Glybera was developed by Amsterdam-based uniQure for patients suffering from a very rare lipid-processing disease called lipoprotein lipase deficiency (LPLD). The condition apparently affects only one or two people in a million.

The U.S. Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale.

In order to actually modify, re-engineer, or build new genes and gene networks that will have therapeutic value we will have to have a depth of understanding that is somewhere over the horizon.

The study of genetics or the genetics underpinning disease in humans does not requite the use of animals.

The real work in genetics and its promised ramification, gene therapy, is cell-based; the species of the organism from which the cells come is of no consequence given our current knowledge. If we understood genetics well enough, we could, theoretically, build essentially any kind of cell we wanted and could enhance any characteristic of interest. We could analyze an organism's genetic code, spot problems, and replace, eliminate, or even enhance any characteristic of interest.

Not only are animals unneeded, but their use in research that purports to be studying a specific disease or family of diseases thought to have a genetic component frequently entails the generation of so-called animal models of this or that human malady that are misleading and wasteful. This doesn't make good sense from a problem-solving or funding perspective.

Almost uniformly, induced conditions in animals are said to have some similarity to the human condition, but very few are anything more than somewhat similar. Perhaps as the result of this inappropriate tool-use, as it were, gene therapy hasn't proven to be helpful. The scientists conducting these experiments are hardly to blame -- other than for their cruelty -- for the lack of progress; they don't understand the real fundamentals of the very complex system they claim to be studying. No one does.

The fundamentals are likely to be the same for all gene-mediated life.

These fundamentals are as likely to be gleaned from studying plant cells as they will be from studying the biopsied cells of an animal with an induced or even a naturally occurring malady.

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