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The Art of Germline Mutagenesis

Technical Outline of Recent Advance
in Human Recombinant Possibility

With a Commentary on the Problem of Aesthetic Enhancments when Presented with a Newly Accessable Genepool


Art and Biolab






Human GLGT (Germline Gene Therapy) is today's utilitarian coinage. Tomorrow it may be called Human Recombinant Possibility, PostHuman Species Breeding, Eugenic Consumerism or WetHacking. This paper is an attempt to describe recent advances in transgenics and offer a commentary on the future uses of this technology. The first section explores some of the recent advances in Life Science that enable computer aided sequences of proteins to effect permanent, heritable alterations on animal and human subjects. The second section deals more with the process of choosing what gets done with this thrilling and dangerous technology, utilitarian, artistic et al.

If we begin by looking at the technologies that go into the genetic manipulation/creation of new transgenic organisms, we should begin to see how these can be applied to human genomes. That starts by understanding what stem cells are and how they effect germ cells. Embryonic Stem Cells come from the earliest phases of an embryo and they are the stems from which all the other embryonic cells originate (in humans, the post zygotic blastula is harvestable until the end of the first trimester.) We are all pretty used to the idea of our entire genetic code being in each of our cells but did you ever wonder how these cells ended up differentiating? Why don't fingers grow wherever they want to? And how did all these different kinds of cells end up coming out of a pair of tiny gametes? Well, half of the answer lies in the fact that "Stem cells are pluripotent -- that is they can give rise to specialized progeny cells by restricting which genes these cells express."1 ** The other half of the story is based on a process called morphogenesis or intercellular communication (induction) which could be another entire paper.

The cells, themselves, are not specialized (tabula rasa?) but all of the developed cells that go into the creation of an organism are the specialized daughter cells of these few embryonic stem cells. A cultured cell line composed of ES cell lines can unlock a cheap and fairly unlimited source for replacement of most tissue types (i.e. heart, liver, bone, brain). Since ES cells are taken before an immune system has developed, they do not suffer from rejection in the case of organ transplantation. The ES cells are also very flexible and even aid in the process of genetic engineering. Most importantly, they are easily accepted into other embryos in the blastomere stage. This makes ES cells prime candidates for vectors in Embryonic gene therapy, one of the doorways into the human germline which we shall discuss soon.

To ground this in the real, lets review the orgins of two of the first publicly acknowledged cultured human stem cell lines:

John Gearhart of Johns Hopkins University, Baltimore Maryland has cultured fetal stem cells from the gonadal ridge of several aborted fetuses. The cell lines are growing in culture as we speak. He would like to use them for medical applications. This is the kind of fetal tissue research that has been denied federal funding until recently. This is also the kind of research that dangerously pairs the most vehement anti-abortionists with the kinder but not always gentler Green Activists, consecrating some strange bedfellows, i.e. Jeremy Rifkin/Earth First meets Jerry Falwell and the Moral Majority. Regardless, Geron corporation has licensed this technology.

James Robl of Advanced Cell Technology and UMass at Amherst wanted to avoid the use of aborted fetuses from what were previously viable babies. Instead he fused the nucleus of a human cell with the enucleated cow's egg. The nucleus started dividing but it never got to a differentiated stage. In this way, ACT has avoided the ethical dilemmas of using previously viable fetal tissue as experimental tissue. These human embryos are not viable inside a cow so harvesting them is less of right-to-lifer's muckraking fantasy. Unfortunately, Dr. Robl did not avoid skating the thin edge of a moralistic morass. President Clinton wrote a letter to NBAC saying he is "deeply troubled" by the "mingling of human and non-human species." Geron Corp. has licensed ACT's technique as well.

Currently, somatic gene therapies utilizing manipulated human stem cells are in the pipeline. The techniques are somewhat convoluted but the results so far seem to be promising. The offending gene must be isolated, transcribed and replicated. Then alterations must be studied until a cure seems to work in experimental trials. During trials, geneticists use a variety of vectors or transmission schemes to get the new genetic sequences into the patient's body. Viral vectors commonly used for gene therapy today include genetically weakened Adenoviruses (AV), Adeno-associated Viruses (AAV), Herpes viruses and Retroviruses (like AIDS). NonViral vectors include direct injection, bombardment and transfection. Novel vectors include foods and body commodities like potatoes (nutriceuticals), tobacco, nose sprays, aerosol sprays and now a new anti-balding shampoo from Monsanto. Stem cells are the latest addition to this list of trasmission schemes. They are in the process of being engineered to aid in the cure or treatment of Cystic Fibrosis, Diabetes, Heart Disease, Cancer and Depression. In fact, Geron Corporation has entered into a five year, multi-billion dollar joint venture with Roslin to further explore human stem cell therapies.If, however, an enginnered vector is introduced into an embryo before it has achieves differentiation, all or most of the germ cells (goanads) in that organism will carry the alteration. This process, the performing of somatic therapy on embryos before they have differentiated is what germline genetics is all about. ES Germ cells are a subset of ES cells that have specialized to the degree that they are the stem cells that will produce the organism's gonads (sperm or ovum) They are the source of heredity and once altered a generational cascade begins that is generally thought to be permanent, irreversible and capable of effecting all subsequent generations. In animal experimentation these are the kind of cells that are regularly used to create transgenic chimeras. The process is practiced regularly in the production of transgenic fish, frogs, mice, rats, sheep, pigs, cows, horses and monkeys but it has not been reportedly tried on humans. Through nuclear transplantation of 'choice' cell lines, lab animals are replicated and then interbred in order to insure the sem-stability of mutagenesis.

"This develops into a chimera in which a proportion of cells in most of all of its tissues carry the altered genes. Because those tissues can include the cells that give rise to sperm and eggs, repeating these experiments on humans would break the biggest taboo in modern genetics: manipulating the human germline to induce genetic changes that can be passed down the generations."2

While we suspiciously eye the local IVF clinics, lets talk about some germline examples from recent history. Two morphologically charismatic new species include the successful birth of a geep (a hybrid mosaic of both goat and sheep.) The Geep is a microinjected mix of two embryonic cell lines in one egg. This is known as mosaicsim. The Green Flourescent Zebrafish made from a mutagenesis between a GFP jellyfish/plasmid chimera injected into zebrafish embryo with Xenopus Elongation factor as a promoter. This makes the experimental Zebrafish a chimerical mix of plasmid (bacteria), Frog (Xenopus), jellyfish and zebrafish. (It is important to recognize that the vectors of somatic gene therapy are also germline organisms as they are self replicating. The distinction of somatic refers not to the vector/organism but the intended use of these organisms as vectors.) How would you respond to a similar process on a voluntary, informed human subject? How about an unborn baby?In September, 1998, French Anderson from the USC Gene Therapy Labs initiated a discussion about his plans to take gene therapy to a new level. He would like to do gene therapy on human embryos in utero. He has met with the FDA and the RAC (recombinant advisory commission) to discuss what will be the next phase of gene therapy. He is worried that this process might 'go germline' by accident. The introduction of a software based strand of genetic code into a developing zygote/blastomere/fetus may add that 'normalized' gene to every cell in a genetically abnormal baby's body. And, this might include it's germline cells. This consequence would effect the heredity of all of this child's kindred and our shared global gene pool for all following generations.

"Germline gene therapy will be done because of human nature. ... None of us want to pass on to our children lethal genes if we can help it. And that's what's going to drive germline therapy."3

And this is where the ethical conundrum begins. The question is not just whether we want to create human transgenic chimeras to stop potentially lethal birth defects. The potential uses for this technology are not just therapeutic. Therapy in the field of Biotechnology might be a catch all phrase to ensure a benevolent reception of a benevolent pursuit by a benevolent grant committee. And, to be honest, these therapies are a real and present need for a mutated, disordered species. But Human Germline Genetics has consequences that reach far beyond simple utopianism.

Whether we are talking about scientific, artistic, consumer or cultural choices, we are talking about aesthetics. This is the rebirth of something we had hoped was becoming passé, Eugenics. Since the Second World War, the idea of cleaning up the genepool has been taboo. Today's Eugenics movement has been fragmented into animal husbandry, family planning and sociobiology. But with the new advances in human reproductive technologies, these three fregments are gathering around private InVitro Fertilization labs. Gene enhancement is the new wave of eugenics and it comes with more pitfalls than possibilities. Bacteria, viruses and parasites are being engineered to act as vectors for medical cures. Using the same methodology, these targetable vectors can also be engineered to cause novel disease and disorder. Attempts at enhancement could lead to entirely new species and considering popular ideas about enhancement, we may be born with bad taste written all over us.

"And the other thing, because no one really has the guts to say it... I mean, if we could make better human beings by knowing how to add genes, why shouldn't we do it?"4

This juncture may be the artist's entry point into the debate but lets not over estimate any aesthetic superiority in this realm. Eugenics or master racing is an aesthetic decision based on physical, mental, emotional and cultural bias. If an artist presents alternative aesthetics, reacting to fickle dominant trends in taste and worth is this any 'better' a choice? The genetic, scientific return to master racing is concerned with trendy health and is stained by the effect of Nazi health stratagems. If instead, an artist were to craft a lifeform with plaid buttocks four tongues a horse cock and a fiendish countenance, this might serve as an example of possibility, enervation and/or pure actuality. It would not be condoned by any health professionals but it would have cognition and choice, possibly to lead a baroque symphony of dementia and reformation. Much more exciting to look at, but is there a better choice about our future form, consciousness, divergence? Is there a verifiable context for applicable superior choice? And... is taste or preference of any kind inherently fascist?

Genetic enhancement sounds scary because Eugenics has a nasty history of involving genocide. Humans just don't seem to know when too much is too much, even when they're just tidying up. But if you look at the literature of Sociobiology or read some advertising copy from an animal husbandry site on the web, you'll find that we already practice positive Eugenics on all of the major commodity plants and animals. We breed our meat for tenderness, why shouldn't we breed ourselves for intelligence or good looks? The point of presenting you with all of the most recent technology is to underscore the fact that the ethical debate is important. Although, the point may be moot because ethics imply humanity and the technology implies posthumanity. Ethics may be moot before humanity becomes unrecognisable as the speed of innovation in the BioTech realm is quickly bringing us to a point where it is not debatable any more. You can buy your own gene sequencer on the WWWeb at www.perkin-elmer.com starting at $80,000. Just think of the children's toy market alone.

Every new technology has both positive and negative uses. For every miracle cure we have an new pollution or weapon. Artists and Philosophers have been instrumental in creating imaginary idealisms that have wrought considerable hardship on those of us who are abnormal. Other Artists and Philosophers have attempted to absolve humanity from its crushing and destructive perfectionism. The more cynical artists have take the role of the Devil's Advocate, revealing that the relationship between beauty and representation often has more to do with the process of sadism and deformation. I consider Genetic Engineers to be artists of the flesh and for that reason, I expect all these genres to exist within the human germline before long.

There may be a reluctance to embrace the multifaceted faces of BioPandora, but this is the end of isolation, the boy in the bubble will not go unscathed. This is not a question of Democratic choice, or budgeting more or less expensive entertainment value. Demographics may determine even Federal Funding of commercial-science R&D, but this genetic world is going freeware or doubleDare snareWare, wet and slimy grimeWare, encapsulated crimeWare. Not that DuPont and Monsanto and the rest of the Fortune 500 don't have a GoogleBillion Dollar hand to play in the shaping of Choice/Fear/Fetishism/Idolatry and now the shape of consumers to come. But this is life and life is loose and squiggly and nonconformist and uncontained.

Although there has been a lot of talk about biological weapons of mass destruction these days, esp. pertaining to Iraq, I haven't heard to much about the use of Genetics to make these enhanced weapons. Neither is it often mentioned that Saddam Hussein was backed by the Department of Defense and then Head of the CIA George Bush to fight the war against Iran and all his Biological weapon technology came from America before the Gulf War. The fact that America signed the (BTWC) Biological and Toxic Weapons Treaty in 1975 should have stopped the US from helping fund the Iraqii bioweapons program. If Spain can extradite Pinochet for war crimes after the fact then maybe the American soldiers who have contracted Gulf War Syndrome should be able to take George Bush to the War Crimes Tribunal in the Hague for breaking the BTWC and exporting biological genocide upon his own citizenry? My final question, does this also make George Bush and his thick skulled son honorary Germline Public Artist?

-eMutagen 1999






1: Pg 337 Human Genetics, Concepts and Applications, Ricki Lewis WCB/McGraw Hill 1997

2: Human Embryos Carring Altered Genes -- New scientist 19 July 1997

3: Dr. French Anderson excerpt from a presentation at UCLA's Engineering the Human Germline Symposium, June 1998

4: James Watson, excerpt from a presentation at UCLA's Engineering the Human Germline Symposium, June 1998