2. Outline
I. Overview of Xenotransplantation
II. Objectives of Xenotransplantation
III. Rationale
IV. Previous Research Discussion
V. Biotechnical Challenges
VI. Safety
VII.Ethical Concerns
VIII.Pros and Cons of Xenotransplantation
IX. Summary
X. Conclusions
XI. Resources
3. Overview of Xenotransplantation
• There is a demand for organs across the United States and the
world. according to the Food and Drug Administration
“FDA”; ten patients die each day in the United States while on
the waiting list to receive lifesaving vital organ transplants
• Xenotransplantation is the theoretical transplantation of any
living cells, organs or tissues from one animal species to
another recipient
• Xenotransplantation began in the 17th century to see if human
and animal organs were interchangeable. There was no
success then , and even today, the longest living person with
an animal organ transplant lasted only 293 days, unconscious
4. Objectives of Xenotransplantation
• Scientists hope that success in
xenotransplantation will offer a
more efficient way to find
donors for people in need
• Other objectives include
– Using animal cells to help
stroke, and other victims
– Reducing the need for
Embryonic Stem Cell Research
5. Rationale
• Both Conventional and nonconventional organ transplantation can
result in chronic / acute organ rejection due to antigen variations
• Previously conducted research involved the examination of T-cell
recognition of “xeno-antigens” to see whether or not certain antigens
were shared across species
• Cross-species differences in transplantation antigen processing and
presentation of a unique murine(mouse) barrier antigen H47. H47
antigen is not recognized by human T-cells as foreign, thus not killed
• The goal of this project is to examine the validity of further
xenotransplantation research. Current progress involving this
procedure is minimal as clinical trials are only focusing on
transferring animal cell lines in human recipients (not full tissues or
organs)
• Biotechnical, ethical and safety concerns will be examined and
presented in order to determine whether or not this is a valid research
endeavor
6. Previous Research Highlights
• Previous research involved an examination of a unique
antigen(protein fragment) known as H47
• H47 was transfected from a mouse cell line into human cell
line(transgenic modification)
• Expected to observe cell death due to T-Cell Screening
• Cells survived; T-Cells did not screen cells as “non-self”
• Research focused on determining why T-Cells did not screen cells
as foreign
• Technical research focused on examining gene expression levels
of H47 antigen in transfected human cell lines
• Possible that H47 antigen is “conserved” across species
• Conserved antigens are peptides that are shared between species
thus would not elicit an immuno-response
• This research could benefit in the development of therapeutic
drugs to prevent antigen-induced organ rejection
8. Biotechnical Challenges of
Xenotransplantation
• Immunological Challenges
– Antigen Induced Organ Rejection
– T-Cell Screening
– Variability in Gene Expression Levels
– Variability in Antigen Processing
9. Biotechnical Challenges of
Xenotransplantation Continued
• Physiological Concerns
– Physical Differences across species
• Size of the source animal’s organs in comparison to those
of the recipient Orientation of the organ in the human
recipient compared to the donor (ex. vertical orientation
of the pig heart in humans versus a horizontal orientation
in pigs);
• Growth rate of the transplanted organ in humans versus
the natural growth rate of the organ in animals and the
life expectancy of the donor animal compared with
human life expectancy (ex. will the organ survive for the
rest of the life of the human or need to be replaced at a
later stage?)
10. Safety Concerns
• Viral “zoonosis,” or disease passed
from animal to human, is the main
risk associated with
transplantation. Implanting
infected animal tissues directly
into humans would allow viruses
direct access to human tissues, this
access combined with the immuno-
suppressant drugs associated with
transplant surgery make the human
completely susceptible to the
disease, and may allow it to mutate
and create a disease as formidable
as Ebola or AIDS
• PERVs-Porcine Endogenous
Retroviruses (PERVs)
• Porcine (pig) tissue is currently the
common research model for most
xenotransplantation experiments.
PERVs have been thought to pose a
particular risk because they cannot
be removed from porcine tissue.
Thus, although other viruses can be
managed by the introduction of pre-
transplantation viral screening
techniques this is not the case with
PERVs
11. Ethical Concerns
• Human Ethical Concerns
– Genetic Manipulation
– Risk in clinical trials
– Transplanting of Human Genome in other organisms
– Potential deadly development of zoonosis
– Human use of animals in “organ farming”
– Religious Issues involving human life/genetic code
– Slippery-Slope…what will xenotransplantation lead to?
• Animal Ethical Concerns
– Transgenic animals no longer “unique”
– Animal Rights
12. Pros/Cons of Xenotransplantation
Pros
Success in the field would help
thousands worldwide receive organs.
Scientists may save countless
human lives by doing stem cell
research on animals rather than
human embryos
Continued study may reveal more
about genetics, such as shared genes
between species
Continued research may reveal
patterns of gene expression/ antigen-
T-Cell response
Cons
An incurable zoonosis may
develop and become deadly
Vast amounts of research time and
money are invested, yet there is
almost no success
Animal Rights may be violated.
Humans may begin practice of
“Organ Farming”
Further Research may lead to
further genetic manipulation
13. Summary
• Xenotransplantation
– Still in the research phase of development.
– Biotechnological issues
• Antigen-induced organ rejection, physiological/structural differences and
problems associated with the development of transgenic organisms are just
some of the major challenges facing this potential procedure.
• Safety associated with diseases, organ rejection rates
• Lack of therapeutic drugs to help with organ rejection in xenotransplantation
– Ethical Concerns
• Human Safety, Genetic Manipulation Concerns, Unnatural modification of
organisms, Animal Rights Concerns
• Society and the scientific community must decide whether or not animals exist
for human gain or do they deserve basic rights. It also must be considered that
this type of genetic modification which would be necessary to “grow” organs
to match a recipient is unnatural. If biomedicine begins to manipulate other
creatures genetically, where will this end? Some may have concerns that this
may lead to the direct genetic modification of humans; and this is a prospect
that spurs fear in those against such research.
14. Conclusion
• I can not support xenotransplantation as a viable
alternative to conventional organ transplantation
• While I initially supported the research, and worked
for three years on a NSF-Funded project involving
Xeno-antigens; the technical, safety and ethical
concerns about the procedure have guided me to
change my opinion on this area of biomedical
research
• It is also my belief that the human genome should
not be used to manipulate the genomes of other
species; I find this unethical, and careless
