Human-Animal Chimeras and Developmental Biology’s Uncanny Evolutionary Potential
Biology Senior Seminar
Outline
“We live in a society for which the pursuit of Health has become a god, justifying almost anything.”
--Gilbert Meilaender. First Things. (vol. 74, June-July, 1997, 41-43)
“For human beings to mix human DNA with animal DNA would be, in my judgment, something more than “Playing God.” It would be “Playing the Devil.”
--Rev. Stanley S. Harakas, Archbishop lakavos Profesor of Orthodox Theology, Massachusetts
Biology, at least in the public eye, has made startlingly great strides in recent years, but alongside its advancements clings much “baggage”. In using the term “baggage”, I hope not to convey the sense that any restriction to biological research constitutes a retardation of humanity’s collective intellect; instead, what I am suggesting is that with any great foray into uncharted territory, certain precautions, pre-meditated difficulties, and/or anticipated implications need be properly addressed. Just as the prudent traveler plans a trip, dressing and packing accordingly, so must biologists be aware of, and make provisions for, the ever-uncertain future. The latest research in developmental biology makes international headlines and figures prominently in popular culture, yet many people remain largely ignorant as to what humans are capable of, what is currently happening and what is about to transpire. To some, the day’s cutting-edge research is considered insanely freakish, utterly unethical and diametrically opposed to our role as stewards of the earth. Many agree, however, that the potential valuable applications of this research are enormous—therefore such research cannot be neglected or ignored.
Extrapolations of contemporaneous findings indicate even more amazing, unprecedented biological advances in the future. Formerly residing in the fantastical realm of science fiction, such seemingly implausible subject-matter is now considered viable, business professionals, scientists, private interest groups and individuals all demonstrate interest in investigating further the potential benefits, problematic or unethical factors and the whole gamut of inimitable possibilities these ‘unnatural’ occurrences proffer.
Although further experimentation involving human-animal chimeras may yield valuable information—information that may save human lives and cure suffering on a grand-scale—it is imperative to properly adopt a code of ethics and define the limits to such experimentation, lest we stumble into unethical practice and become ensnared, while unbridled catastrophe reigns supreme.
What is a chimera? A chimera is an organism that displays the genetic cellular constitution of multiple organisms in its own. There is a critical difference between chimeras and hybrid organisms. A chimera has more than two parents; a hybrid is simply a combination of two different genomes in the same cell. The Chimera gets its name from the mythical greek beast that was a fusion of fire-breathing goat’s head, a snake for a tail and possessing the body of a lion (Gilbert 2001).
During the blastocyst stage of early mammalian development the only cell types present are the trophoblast and the inner cell mass. The trophoblast develops into the extra-embryonic portions of the fetus, including the placenta. The inner cell mass is the precursor to the embryo—that which will give rise to the three germ layers and all subsequent tissue structure. If an inner cell blastomere from one organism is transferred into the inner cell mass of another, the blastomere will contribute to every organ of the host embryo. It is in these capabilities of cells that chimeras can form (Gilbert 2001).
Inner cell mass blastomeres can be isolated from an embryo and cultured in vitro; these are embryonic stem cells. Embryonic cells are almost totipotent; they can aid in the formation of all cells except the those of the trophoblast, when incorporated into a host embryo—instead, pluripotent. These embryonic stem cells can be further influenced through the incorporation of foreign DNA—from any eukaryotic source. Such an engineered stem cell, if introduced to the inner cell mass of another organism, will influence every subsequent cell of the developing organism and form a chimera (Schoenwolf 2001).
Although our current position in Biology is the result of step-ladder progressions in varied scientific fields, recent remarkable events contribute to the sense that human beings are in the throes of an unprecedented biomedical revolution. Obviously such events as the first in vitro human birth of Louise Brown in 1978 and the Edinburgh scientists’ cloning of the sheep Dolly in 1997 serve as prominent markers of some achievement, but they certainly are not the results of some ignorant tinkering. These are the markers of ongoing processes in specific scientific fields, which are in turn greatly aided and advanced through collaborations, connections and findings in other related scientific disciplines (Gordon 2003).
Great advances in developmental biology, especially the identification of signal transduction factors, genetic manipulation, especially recombinant DNA technology, in conjunction with findings in reproductive medicine, especially in vitro fertilization have culminated in a more inclusive biological field—one in which formerly disparate studies intertwine in ineluctable ways.
Developmental biology has changed rapidly from the 1970’s with the advent of recombinant DNA technologies. With the discovery of homeobox genes in the 1980s and the study of signal transduction factors in the 1990s, developmental biology became endowed with new knowledge and new power; the new power allows for developmental biology to inform medicinal and genetic research (Gilbert 2001). The aforementioned DNA technologies which have provided developmental biologists new tools for their study include such essential techniques as the Polymerase Chain Reaction (PCR) method and gene insertions for the identification, isolation and purification of specific genes.
But while these disparate groups benefit from shared knowledge, each, it seems still looks to its own devices when determining the rightness of some method of action. Such trends extend far beyond the scientific field. Political, religious, and ethical groups all have opinions about continued research but sometimes poorly understand the entire picture. There exists a monstrous amount of knowledge to disseminate if one truly wants to impose some law, restriction or even opinion on such a grand subject. Before such restrictions are put in place, AND, before more research is conducted within such sensitive subjects, an exposure to the various thought processes and practices must be undertaken.
Many countries espouse continued research using stem cells citing evidence of formidable techniques being developed to fight previously incurable illnesses. With Korea, Singapore, China, the UK and Australia all putting greater effort into harnessing the power of stem cells, some feel the US is being left behind. A survey of current capabilities and accomplishments yields astounding results.
The first reported successful human-animal chimera was produced in 2003 when human cells had been successfully fused with rabbit eggs by Chinese Scientists at the Shanghai Medical University. The eggs developed for several days before the scientists harvested their stem cells and destroyed them (Ying 2003).
In 2004, researchers in Minnesota at the Mayo Clinic created pigs with human blood flowing through their veins. Experiments involving mice, whose embryonic brains were injected with human neurons have already been conducted. In these experiments only a small percentage of the animal is human—the mice for example had only 1% human brain—but plans are underway to create organs that are up to 80% human. Human stem cells have also been injected into paralyzed mice to allow them to walk (Swingle 2002).
In medicinal bio-technology, organ parts can be manufactured in animal bodies for patients. Sufferers from heart-conditions arising from faulty heart-valves can already buy replacement valves grown in pigs and cows. The insertion of these valves makes the recipient a chimera, such valves are thoroughly animal parts maintained and developed in an animal body (NAP 2005). Microbial biological research has been conducted for years in which human genes are introduced to bacteria and farm animals (Mott 2005).
Irving Weissman, alongside colleagues at the Stanford University was a pioneer of stem cell research, creating mice with fully human immune systems back in 1988. These mice were then intended for AIDS research (Mott, 2005).
The National Academies has recently issued a report outlining, though in no binding terms, what constitutes right research when it comes to stem cells and chimeras. The national Academies consist of the National Academy of Science, the National Academy of Engineering, the Institute of Medicine and the National Research Council (NAP 2005). How will countries interact when/if one stumbles upon a corporeal ethical dillema or revolutionary new technology?
Benefits of Continued Research
In a fit of irony, vast conglomerate powers vie for dominance over manipulation of the miniscule embryo and micro-organismal germ-lines. Both sides struggle amidst argument and questions of ethics and morality. To further contuse this picture the entire discussion is shrouded by conjecture and pockets of the uncertainty. Who can truly list every possibility? Who can accurately predict the future of developmental Biology? In the US current laws seek to retard the speed toward these fantastic revelations—which may not be a bad thing.
Senator Sam Brownback (R-KS), introduced senate bill 659 on march 17th 2005. Known as the Human Chimera Prohibition Act of 2005, the Bill intends to cease all activities attempting to create a human chimera. Various techniques are implicated with this proposed Bill including mixing non-human cells into human embryos. Having no co-sponsors, the bill was referred to the Senate Judiciary Committee (OLPA 2005).
Nobody knows for certain what the lies in the future but the current findings indicate vast stores of knowledge and keys to understanding disease and beyond. One of the uncertain areas lies in trying to predict the consequences of enlarging the ratio of human to animal cells in an organism. According to the National Academies guidelines committee, “These hybrid part human, part animal creatures, called chimeras, would be valuable in understanding the etiology and progression of human disease and in testing new drugs, and will be necessary in preclinical testing of human embryonic stem cells and their derivatives” (NAP 2005). Chimeras might also be used to grow organs, such as livers, to transplant into humans. Other models, currently in practice feature “pharms” where animal-hybrids manufacture human parts and are subjected to pharmaceutical tests.
In any case, most scientists agree that the more human the animal, the greater its efficacy as a working model for study—whether that study be on pharmaceuticals or growing “spare parts.” Other benefits may be gained from merely watching the mature cells interact in a living creature and sussing out subsequent medical treatments from the data. Much faith has been placed in such models’ being responsible for the discovery of a cure for Alzeimer’s and Parkinson’s disease.
As scientists learn increasingly more about early development, the more exciting the realm becomes. As new transduction factors and development-directing chemical compounds are identified and experimented on, the possibilities branch with ever-greater complexity. So what are the future possibilities? It is not unusual, when trying to decipher future events, to recall past events as models. In this wise, consider the ancient Grecian mythological creatures. Will some developed country, in the next few years, sponsor a group of research scientists to fashion, tauric creatures, engineered for specific economic, pharmaceutical or labor purposes? Can human beings create, centaurs, griffins, hippocampi, or manticores? And to what end would these organisms be created? Like Wells’ The Island of Dr. Moreau, the world may be populated by, “enhanced” animals--hybrids of human and animal—mice with partial human intelligence. Perhaps pet shops might sell “smart dogs” that, in addition to fetching sticks, could play arcade games alongside the children. But beyond the brain and beyond sub-human creatures—could we not, in the not-so-distant future, craft chimeric human-feline organisms that, in addition to bipedal stance and opposable thumbs, grew long whiskers and retractable claws? Stanford University’s Weissman cited a controversial experiment in which mice could be genetically engineered to produce sperm and eggs. Through in vitro fertilization, a child might be produced whose parents are a pair of mice (Mott, 2005).
A fundamental question to ask is at what point, with the addition of animal cells into a human genome, does that human become something else? (Meilaender 2003). This question continually plagues both researchers and ethicists, the religious and everyone in between. And the answer does not seem simple. One method of tackling the problem is to determine the balance between the potential benefits and problems.
Yet central to this argument of human-animal combinations is the question of sanctity. Do we show respect for an organism if it is manipulated into being and emerges as an grotesque experiment? Is there any respect or consideration given to a human chimera whose sole purpose is to donate organs to a wealthy human being? Other troubling factors include who will benefit from such research? Will minority’s who suffer from repression be replaced by a whole new set of beings that are truly genetically “inferior” to the human race? And even if we could somehow get over the fact that such organisms exist solely for the selfish benefit of man kind, who will reap these benefits? Will the poor and indigent of this world continue to suffer while only the very rich can be assured of these scientific advances?
Then there are problems of defining the point at which life begins. Does it begin at conception? Or when the organism has a developed nervous system? After fourteen days, or after the second trimester? The ethical dilemmas of continued research revolve around such fundamental elements as harnessing human embryos for research. The risks involved in such activities include the formation of malignant teratomas, harmful genetic mutations, and other unforeseen consequences. Moreover, if we can create a race of hybrid beings will we create laws to establish their natural rights? Will they be considered sub-human? Employed as fodder for research? Will they enjoy the same rights as humans or will they represent another discriminated minority reminiscent of the years of slavery. Will researchers grow and own legions of sub-human beings? Can we create super-human beings and will provisions exist for a Super-human bill of rights? In this scenario what happens to us—the gene-poor? Will superhumans establish a new world order, toppling this current familiar world?
All of these questions must be addressed. And there can be no doubt that unforeseen complications and problems will arise. Continued research may ultimately result in catastrophe. Yet, despite the risk, humanity cannot remain stagnant. God has given humans stewardship over the earth, is curiosity not part and parcel with this gift? As long as a fundamental respect is shown for all of creation—the belief that all things surrounding us are holy—then perhaps we can march triumphant into continued research. But certain precautions need to be taken and regulations put into effect.
In sum, as human beings, we need to create a universal code of ethics to prevent ethical violations and disaster lest we inadvertently instigate humanity’s eschaton as a result of poor ethical regulations in biological research.
Bibliography
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Gilbert, Scott F., Developmental Biology Sinauer 2003
Meilaender, Gilbert. First Things. (vol. 74, June-July, 1997, 41-43)
Mott, Maryann, Creating Human-Animals for Research, Organic Consumers forum, 2005 [website accessed Nov. 2005 http://www.organicconsumers.org/Patent/human-animals.cfm]
__________, Animal-Human Hybrids spark controversy, National Geographic News, 2005. [Website accessed November 2005 http://news.nationalgeographic.com/news/2005/01/0125_050125_chimeras.html]
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OLPA. (2005). Bill Tracking of the 109th Congress, SB 659. Retrieved November 2005: [http://olpa.od.nih.gov/tracking/109/senate_bills/session1/s-659.asp]
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