Human Transgenesis - Definitions  Technical Possibilities and Moral Challenges
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Human Transgenesis - Definitions Technical Possibilities and Moral Challenges

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resistance to transgenic drugs is much less intense if not non-existent.
As an example, almost all antibiotics that are currently being produced by pharma-
ceutical companies are transgenically obtained. Since the 1980s, all human insulin,
growth hormones and various blood clotting factors have been biotechnologically
produced—made by microorganisms that were genetically modified to express the
factors that they produce (Walgate 1981; Toole et al. 1984; Akinci et al. 2010). Today
more than 250 biotechnology health care products, vaccines and diagnostic tools
produced by genetically modified microorganisms and plants exist; many are being
used by patients on a daily basis (BIO 2010). In 2006, the European Commission
approved the first mass-produced drug generated by a transgenic animal: a recombi-
nant human antithrombin, an anticlotting protein that is secreted into the milk of
transgenic goats. Similarly, the US Food and Drug Administration (FDA) has ap-
proved the commercialization of a recombinant human C1 inhibitor, a drug used to
treat hereditary angioedema, produced by transgenic rabbits (Choi 2006). While
many people purchase food only when the company label states that no transgenic
components are included, the same does not apply to medicinal purchases, although
the word “recombinant” is obligatorily present on the drug information label.

Human Transgenesis: Technical Possibilities and Moral Challenges

Uzogara (2000) noted that religious and cultural concerns are frequently associated
with the opposition to GMOs, and even when these aspects are not clearly present, the
simple and crude fear of the novel or the unknown accounts for the public resistance
to transgenic organisms. GMO critics have asked the following question: “Should
scientists be allowed to cross nature's boundaries by cloning microorganisms, plants,
animals, livestock, and possibly humans?” (Woodard and Underwood 1997).
Answers given to this question often reveal a basic fear motivating a general aversion
to transgenesis: one associated with the taboo against “unnatural” human genetic

2.1 Transgenesis in Prokaryotes

As described above, HGT and transgenesis involve the mating-independent transfer
of genetic material between phylogenetically diverse organisms. Although trans-
genesis is referred to as a biotechnological approach to HGT, these two phenomena
are identical from a purely mechanistic, molecular point of view. HGT has been
recognised as a major force driving genomic evolution (Andam et al. 2010).
However, its importance to the evolution of eukaryotic organisms is frequently
overshadowed by the much higher prevalence of gene transfer in bacteria (Koonin
et al. 2001). Recent studies have suggested that HGT is a common and relevant
feature in the evolution of all living organisms, including humans. HGT was first
described during an outbreak of dysentery in Japan. The disease was caused by
bacteria of the genus Shigella, and scientists were astonished by the rapidness with
which antibiotic resistance emerged. It turned out that resistance genes were being
transmitted laterally among members of the bacterial population (Akiba et al. 1960).
Even so, it was only with the advent of comparative genomic studies that biologists
recognised the full extent and impact of HGT in prokaryotes, which caused bacterial
evolution to depart from the traditional tree-like phylogenetic structure and form
instead a web-like evolutionary history (Doolittle and Bapteste 2007).

Bacteria and other related organisms are quite promiscuous in terms of their ability
to absorb and integrate foreign DNA into their own genomic repertoire. This is
accomplished using an array of different strategies that include (inter alia) taking
up DNA molecules that are soluble in their environment, exchanging DNA mobile
elements called plasmids through specialised tubules (in a process known as conju-
gation), and using viruses as vectors to exchange DNA pieces among infected
bacteria (Thomas and Nielsen 2005).

Based on the speed by which prokaryotes are able to laterally transfer genes, the
impact of HGT on bacterial evolution becomes quite clear. In fact, key events in the
geological and biological history of our planet are intrinsically linked to bacterial
evolution and consequently to HGT as a major evolutionary mechanism. The appear-
ance of photosynthesis and photosynthetic organisms, for instance, radically shaped
life on Earth by increasing the global distribution of available atmospheric oxygen,
thereby allowing for the development of larger, more complex forms of life. The first
photosynthetic organisms were bacteria, and the distribution of genes related to
photosynthetic processes among diverse groups within the bacterial domain is a
result of the combination between vertical inheritance and lateral gene transfer events
(Hohmann-Marriott and Blankenship 2011).

F.G. da Fonseca et al.

2.2 Transgenesis in Eukaryotes

When compared to gene transfer in bacteria, HGT in more complex organisms is
substantially less frequent. The chief reason relates to the segregation of reproductive
cells (germ cells) from somatic cells in most multi-cellular eukaryotes. To be trans-
mitted from parents to offspring and potentially become fixed within a population, a
foreign gene would have to be inserted into the genome of a germ cell, a much rarer
event as compared to gene insertion into somatic cells. Although the segregated
germline is a strong limitation to HGT in animals, it is certainly not an absolute
one. Indeed, cases of HGT in eukaryotes are being described at an increasing rate and
may account for many adaptively significant traits (Keeling 2009).

The question here is: how could foreign DNA be transported laterally among
diverse complex eukaryotic organisms? Current studies have indicated that the
eukaryote genome is littered with non-coding pieces of DNA termed transposable
elements (TEs) or transposons. TEs are discrete pieces of DNA that possess the
ability to move from one locus to another in the genome and frequently duplicate
themselves in the process (Schaack et al. 2010). Not only can TEs integrate within the
“host” genome, but they can also jump to other genomes to generate HGT events, as
first demonstrated in fruit flies (Daniels et al. 1990). The inherent ability of TEs to
mobilise and integrate into various genomes suggests that they are perfectly prone to
HGT, or in this case, horizontal transposon transfer. The exact mechanisms by which
TEs can be transported between organisms are not completely known, but the idea of
parasites working as vectors for these mobile genetic elements has been proposed (cf.
Gilbert et al. 2010). Eukaryotes can be infected by a multitude of parasites that invade
different hosts and eventually carry TEs with them. In this respect, viruses have been
considered potent HGT vectors because of their ability to transduce and recombine
host DNA and because of their access to eukaryotic cells, including germline cells. A
powerful and illustrative example of how viruses could bridge HGT events was
presented by the work of Yoshiyama et al. (2001). These authors reported the
presence of a specific transposable element in the genomes of the parasitoid braconid
wasp and its lepidopteran host, in which the wasp's eggs are deposited and develop.
In this case, a type of virus termed Polydnavirus seemed to transfer the mobile
genetic element between the two insect species. These viruses have established a
symbiotic relationship with the braconid parasitoid wasp to suppress the immune
response of their lepidopteran hosts and allow the undisturbed development of the
wasp's eggs. The Polydnavirus resides in the wasp's genome as an integrated proviral
DNA. In the ovaries, the viral DNA is able to direct the production of new virus
particles that are injected into the lepidopteran host with the parasitoid eggs. Thus, a
TE present in the viral genome could be transported from the wasp to the butterfly to
create the