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
Bibliography-
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