Download 01 - `Humanizing` Animals

Teaching Responsible Conduct of Research (RCR): A Resource Guide for Professional Science Master’s Degree Programs
Case Studies from Biology and Biotechnology
Case: ‘Humanizing’ Animals
Discipline:
Biology and Biotechnology
Ethics Topic:
Animal Studies
Case Subject Matter:
Chimeric Animal Studies
Controversy:
‘Humanizing’ Animals
Authors:
Michele Hom, Sara Wingate
Jenny, a molecular biology doctoral student, is contemplating instructions her PI gave her that
morning. The approval and executive decision finally come through – begin inserting human stem
cells into the developing brain cortex of fetal murine embryos in utero and continue inserting human
stem cells into embryonic cortex of multiple generations of the same murine progeny. It had been a
long decision proposal caught in the middle of multiple discussions, debates and concerns over the
past several months. Substantial research concluded that creating a new murine animal model to
emulate human-like brain physiology and function would greatly enhance pre-clinical in vivo
research efforts to discover and develop new potential drug therapies to treat Alzheimer’s disease.
Current Alzheimer’s animal model have proven inadequate for this debilitating disease and have not
yet been fully analyzed. Much research is being conducted on the possibility of utilizing chimeric
animal models to increase the correlation of pre-clinical animal model research to results that could
be predicted in clinical trials in human research subjects. Jenny’s PI is one of the leaders in this
research.
It is generally accepted that certain animal models may not produce the same outcomes when the
same experimental drugs are tested in human subjects and fuels the controversy that challenges the
validity of animal models and their biological systems compared to human physiology when
pharmaceuticals are tested in preclinical trials, therefore these results should be disregarded. There is
no guarantee that any results obtained when tested on animals would have the same result in
humans. Understanding this discussion and with the advent of biotechnology, the decision to
produce murine models with a significant percentage of human neurons would present more
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Teaching Responsible Conduct of Research (RCR): A Resource Guide for Professional Science Master’s Degree Programs
realistic data when assessing pharmaceutical therapeutics and the impact on the human (mouse)
brain.
Jenny’s PI proposed to develop a chimeric murine model for Alzheimers would include murine and
human DNA. Jenny is a conscientious doctoral student who has done a substantial amount of
animal studies but recognizes her obligatory responsibilities of her academic status and the possible
consequences of objecting to research directives give to her by her PI. She is concerned with the
possible effects of combining human stem cells with murine developmental fetal brain matter that,
as has been contemplated in the literature, could conceivable produce animal subjects not only with
the desired human neurological characteristics but also with unintended human developmental
conscious characteristics. Such a development would call into question the very meaning of human
vs. animal as it is understood and defined today.
Jenny, however, being concerned about her pending doctoral dissertation and graduation, decided to
forgo her intrinsic morality concern and develop the murine models as instructed knowing full will
that these mice and their future progeny could have fully humanized brains. Though concerned, she
presumed the project would be OK and assumed her supervisors and PI had a thorough
understanding of the significance and possible risks this study entailed. She also speculated that
even if a mouse had a humanized brain, the weight at 0.4 grams would be inconsequential compared
to the 1400 grams that a human brain is composed of. One issue she did not consider was the
consequences of creating a mouse with neurological function that might impart an unintended
consequence of producing a murine species with consciousness that was more human than mouse.
A couple years passed and Jenny, now a Ph.D., moved to a post-doc position at a leading medical
center. Amy, who replaced Jenny, is conducting a study that involved the use of the progeny of the
murine models Jenny produced using human stem cells. As she prepared to euthanize one of the
mice observed the mouse lie down in a “fetal-like” position and appeared to look directly at her.
Amy, who had no prior knowledge of the previous experiments, had never before observed such
human-like behavior and became concerned that these murine subjects were curiously unique – and
in fact too unique based on the literature. She contacted the local papers with her observation their
capabilities of almost human-like behavior. She created quite a controversy stimulated by the media,
that resulted in the entire laboratory and the research being produced being discontinued. This not
only affected the researchers but also the Alzheimer’s research that, through the use of these human-
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Teaching Responsible Conduct of Research (RCR): A Resource Guide for Professional Science Master’s Degree Programs
like animal models, had become the standard for Alzheimer’s in vivo drug testing and have
produced two novel therapeutics about to enter first-in-human clinical studies.
Teaching Questions:

Does this research violate second-order moral questions regarding the very nature and
purpose of Morality itself?

Should the research to develop an animal model with a humanized brain for Alzheimers
research been allowed to continue?

Should it have been a concern that human consciousness produced in a non-human species
could be an unintended consequence of the research?

Now that immutable human-like characteristics have been observed and confirmed what
should be done with the research, with the progeny, and with the experimental data,
processes and know-how?
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