Critical Issues in Bioinformatics and Computing - Genome Tools

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BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

BINF705 Research Ethics Spring
2012

Ethics at the Interface of Computer Science and
Biology



Jeff Solka Ph.D.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

Acknowledgements


Part I


Critical Issues in Bioinformatics and Computing


Someswa Kesh, PhD, Professor in the Computer Information
Systems and Wullianallur Raghupathi, PhD, Associate professor
of Information Systems


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2047326/



Part II


Continued discussions on bioinformatics ethics


http://www.dartmouth.edu/~cbbc/courses/bio68/notes/Ethics_Rog
erYoung.html

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

Dilbert of the Week

Critical Issues in Bioinformatics and
Computing



BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

What is Bioinformatics?


"Bioinformatics" is defined by the National Institutes of Health
as the “research, development, or application of computational
tools and approaches for expanding the use of biological,
medical, behavioral or health data, including those to acquire,
store, organize, archive, analyze, or visualize such data.”
1



BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

The Integrative Nature of
Bioinformatics


Its interdisciplinary and integrative approach draws from fields
such as mathematics, physics, computer science and
engineering, biology, and behavioral science. The generally
accepted subdisciplines include (1) development of new
algorithms and statistics with which to assess relationships
among members of large data sets; (2) analyses and
interpretation of various types of sequences, domains, and
structures; and (3) development and implementation of tools
that enable efficient access and management of different types
of information.
3

5

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Ethics at the Interface of
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The Triad Model


Computing professionals, including developers,
programmers, consultants, and vendors, should be
concerned with building and testing robust applications
and performance issues such as correctness of data,
reliability, and real
-
time processing, and integration and
management of data deployed to serve multiple purposes
simultaneously.


Users, including molecular biologists and other scientists
in the life sciences, are concerned with data input and
user interfaces, analysis and analytical tools, and
interpretation in a shared, global environment. Not only
are new genetic tests and procedures required, but
clinical information must also be integrated and analyzed
continuously to facilitate identification of adverse
reactions. Furthermore, the ability to immediately detect
promising new drug applications as well as bring new
products rapidly to the market are significant challenges.
At this time, users are constrained by incomplete,
piecemeal tools with poor usability. A primary objective is
to work with the other groups in developing sophisticated
applications and analytical tools that facilitate fast
querying and data mining. The sharing of resources
without reinventing the wheel is another challenge.


The public at large is concerned with implications of
potential medical applications, ethics, privacy, potential
misuse of data, and public and social policies. Almost
every citizen is involved in these issues, including social
workers, legal and medical professionals, lawmakers,
patients, and other participants, including pharmaceutical
companies and healthcare providers.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and Biology

The Triad Model


The intersecting area in
Figure 1

depicts
overlapping roles and responsibilities of
participants in the application of the triad model.
For example, the public should decide what can
and should be ethical and legal. This will directly
place limits on the type of research the user
may perform. The user, on the other hand, can
and should join this public debate. Once it has
been decided
what

can be done, the
relationship between the user and the
computing professional comes into play to
determine
how

computing technology can assist
the user. This is not a static relationship, but
rather a dynamic equilibrium, where the
participants in the model will have to decide on
the point of equilibrium at a particular point in
time and in a specific social context.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Iceland


A law passed in the late 1990s enabled creation of a medical
database that includes medical and family history records as
well as genetic information on all Icelanders.


The database was contracted out to a third
-
party biotechnology
firm.


Questions have been raised regarding violations of medical and
personal privacy; medical stereotyping of individuals, families,
or the entire population; potential discrimination based on
medical or genetic data; and a monopoly on medical research
and drugs by large companies.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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“For Sale: Iceland’s Genetic History,”
Oksana Hlodan


Who has the right to access and use our personal genetic data?


Who controls the data?


If medical records are used as a community resource, should they not
be available to all research facilities within the community?


Will the medication for a disease discovered through population
genetics studies be available to the participants?


Can anybody own pieces of our genome through patents, copyrights,
and so on?


Should genetic testing be done, and how scientifically reliable is it?


How will other citizens perceive an individual whose genetic tests
reveal a potential disease?


Will the data lead to discrimination?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and Biology

Generalizations of the Triad Model


The triad model described here can be generalized for the larger field
of health information management (HIM), which encompasses all
aspects of the healthcare industry, including the flow of information
therein.


The participants would include patients, healthcare providers (including
physicians, nurses, health maintenance organizations [HMOs],
insurance companies, hospitals, pharmacies, and medical testing
agencies), and federal programs such as Medicare.



The gathering, storage, processing, and dissemination of the disparate
and complex medical information generated by the overlapping
interaction between these entities will result in the need to address
privacy and security issues.


The dynamics of the interaction and the resultant outcomes can be
studied using the triad model.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and Biology

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

Challenges of Data Formats


Regarding data standards, the emergence of the
macromolecular crystallographic information file (mmCIF) and
extensible markup language (XML) provides standards that can
produce a common format for data.



It is critical that the bioinformatics community either decide on
or gravitate toward one common format that will make data
sharing vastly easier.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Data Sources


Federated database or data warehouse



The three primary sequence databases: GenBank (NCBJ),
Nucleotide Sequence Database (EMBC), and the DNA Databank
of Japan (DDBJ).



These are repositories for raw sequence data, but each entry is
extensively annotated and has a features table to highlight the
important prospects of each sequence. The three databases
exchange data on a daily basis.
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Ethics at the Interface of
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Advanced Methodologies


Data mining for patterns is essential for newer discoveries.


Pattern recognition algorithms and neural networks have been applied to
bioinformatics research.


Neural networks can also be applied to classification as well as decision
problems.
11



Other artificial intelligence
-
based algorithms, like case
-
based reasoning (CBR),
can be useful in this regard.


“Deep computing” for bioinformatics research, implies the use of powerful
machines executing sophisticated software based on innovative algorithms to
solve complex problems like mapping, modeling, and visualization.


From a hardware perspective, both a supercomputing approach and a
distributed computing approach have been used in bioinformatics. Grid
computing allows geographically distributed organizations to share applications
data and computing resources.
12

While the distributed approach is less
expensive, it raises further issues endemic to distributed processing and data
distribution, particularly those over Internet services.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and Biology

Data Access


GeneX, an example of a system that helps with the storage,
organized retrieval, and analysis of gene expression data.


Among the most important software tools for the understanding
of DNA and protein sequences are sequence similarity and
alignment tools such as Basic Local Alignment Search Tool
(BLAST) and a sequence alignment algorithm using a flat file
format known as FASTA.
Figure 2

is a sample screen capture of
the BLAST interface. One can visualize the complexity of the
back
-
end databases and the front
-
end query tools with which
BLAST deals. These tools allow one to compose an unknown
sequence with a database of sequences from other organisms
that are better understood. These programs report the hit in the
database, along with the estimated statistical significance of the
hit.
13

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Interfaces


To facilitate access, several tools have been
developed or are works in progress. These tools
include GeneX, an example of a system that
helps with the storage, organized retrieval, and
analysis of gene expression data. Among the
most important software tools for the
understanding of DNA and protein sequences
are sequence similarity and alignment tools such
as Basic Local Alignment Search Tool (BLAST)
and a sequence alignment algorithm using a flat
file format known as FASTA.
Figure 2

is a
sample screen capture of the BLAST interface.
One can visualize the complexity of the back
-
end databases and the front
-
end query tools
with which BLAST deals. These tools allow one
to compose an unknown sequence with a
database of sequences from other organisms
that are better understood. These programs
report the hit in the database, along with the
estimated statistical significance of the hit.
13

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Operational Requirements


Availability

continuous access to the distributed data
warehouse and Web sites


Security

appropriate controls for access and information
assurance


Data protection

loss of data is decidedly unacceptable, and
backup is critical


Data mobility

data need to be available to the right user, at
the right time, in the right place


Data purpose

the same data may have multiple purposes
and views


Data sharing

access to all information by all participants


Real
-
time availability

data must be available at all times in
a global setting
15


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and Biology

Public/Ethical Concerns


Bioethics

The moral and ethical implications in the application of bioinformatics to
genetics. For example, is the manipulation of human cells via genetic engineering contrary
to the laws of nature and religion? Cloning is yet another issue.


Intellectual property

The ownership of the human genome is probably the most critical
issue. Researchers at universities where a great deal of bioinformatics research is done
should clarify intellectual property issues with the university. Ownership of the successful
experiments performed “in silico” (via the computer chip) is an unresolved question.


Responsibility

Who is responsible for the results? When errors cause injury or damage,
who will be responsible?


Access

Who should have access to the data and for what use? Should law enforcement,
insurance companies, HMOs, and employers have access?


Privacy

How will privacy be protected? Who controls the information? How will
conformance to laws like HIPAA be enforced?


Standards

In terms of gene therapy, what is normal and what is a disability or disorder?


Technology access

How will the digital divide between those who do and do not have
access to expensive technologies be reconciled?


Outsourcing

How will outsourcing affect the field? Given the sensitive nature of research
in bioinformatics, what additional legal and intellectual property rights issues will develop?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of Computer Science and
Biology

Continued Discussions on
Bioinformatics Ethics



BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

What will / has Bioinformatics Enabled Us to do that we
couldn’t do Before?


Bioinformatics can predict the future


But are these predictions/classifications accurate?


Do we know enough about the mechanisms of gene expression
to warrant changes in behavior / action based on microarray
data?


If you had a test and result was +6 for enhanced cholesterol
synthesizing protein, what would you do?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Medical Concerns


Medical records


should bioinformatics data be included in
these? If Included in medical records? Access by whom? Person,
md, family, businesses? Justify each.



Bioinformatics and (genetic?) medicine What traits can be
identified by bioinformatics?


Introversion versus extroversion.



BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Testing


Presymtomatic testing for genetic diseases

as an adult would you want to
know? Why?




Would knowledge of your genotype promote your self
-
understanding? Would
you then be able to realize your potential, or modify your behavior to adapt to
known weaknesses?


If you knew that eg Hunt / BRCA would kill you at age 45, how would that
affect your outlook on life?


Justified euthanasia


plan ahead?


Huntington’s, parkinson’s, alzheimer’s etc.


Iincapacitated’ termination of life.


Who should decide, you, your family, the government? Eg
-

Florida
coma case.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Cures


Bioinformatics allows for detection of genetic ‘diseases’ Once you have detected
a ‘disease’, should you cure it?


Discuss the ethical issues of curing such
‘diseases’ (ie sickle cell) that are advantageous in other environments


At what cost to society, to px? Benefits? Age of prognosis, severity of disease.


Examples of obvious cure, and then less so (CF, MS, Alz, Hunt, blind, deafness,
intelligence, reproduction, colorblindness (job limiting), body build, height, hair
baldness, eye color …..)


Class to define, & justify, treatable diseases.


What is the impact of an individual being able to know their ‘at risk’ genes on
demand ($500 and 48 hrs?)


Psychological


Employment


Health care


Social / relations


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Medical Training


Should new technologies


such as bioinformatics


be regulated or adopted in the medical
world?


Should MDs be familiar with bioinformatics?


How will MDs cope / deal with this extra information. How have they handled past increases
of information? (PCR, lab tests, new drugs…)


Is this just too much information for mds.


How much bioinformatics should be taught to medical students?


Who here is premed?


How are you going to use bioinformatics info?


Is the current system of health care in the US prepared for such information


Is the concept of health ‘insurance’ outmoded here where individuals are denied /
accepted by insurance companies based on their predisposed risk to genetically based
medical problems?


Who will be ‘at risk’? (poss instant role of ins company & family)


NB


health insurance is a factor in US mainly.




BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Public Self Perception and
Acceptance


Case


gm food


pros & cons. What has been the reaction of public to
gm food? Too complex for public? Scared of the unknown? What is a
‘normal’ human genotype? Does different = wrong How different is
wrong enough?


Who want to admit to their mutations?


Color blind, balding, myopic, …….


What is the public / politician perception of ‘normal’ How does the
public/a group react to someone/another group who is ‘different’?


scared, hostile.


Will ‘difference’ become overused and lose it’s stigma, as everyone is
classed as ‘different’ to everyone else? How will public perception of
‘difference’ alter over next decades with constant use / referral to
Human Genome Project & bioinformatics data where no
-
one is the
‘same’.

BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Stereotyping


What are the ethical, legal and social implications of assigning such
genetic/sequence data to individuals, groups, cultures and societies around the
world.


Will groups be evaluated based on their genetic profile? will populations /
cultures / individuals be identified by their genotype, rather than their
phenotype (as it is now)?


will this increase / decrease racism/sexism etc?


What is the genetic difference between different human cultures? Pick any two
& hypothesize on differences


phenotypically, biochemically.


Once an individual’s genotype is easily available, will there be genetic
discrimination? Is there such discrimination now?


Are their really different groups of people / individuals, or are we all really just
part of a continuum? Example of height, iq? Skin color, hair color, eye color.


If we consider 2 individuals of same culture/population


what pheno / biochem
diffs are there?


Some examples might include allergies, lactose, other foods, diabetes, color
blindness, flat feet, !!!


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Implications of Biometrics


Transponder implant with credit card info.


Pets with id chips. Is this the way of future medicine?


Is the prognosis with chip containing medical data


safer, no
mixups, scanned, monitored.


Current pacemakers


checked by computer over phone.


Will people be easily scanned/tagged this way?


Individuality, ‘freedom’? ACLU?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Implications to the Worplace


Are you defined by your genetic sequence?


Will employers require a specific genotype / gene in employees? Can
they request this like a drug test?


What is a ‘minority’? How is it defined? How is it likely to change in a
society where genotypes are easily determined and where everyone is
a ‘minority’ with regard to a certain gene?


Should we base ‘minority’ status upon the degree of deviation from
a genetic ‘norm’


i.e., the more mutations you have,


and are
therefore more different to the ‘norm’, the greater the claim you
have to minority status and special / advantageous treatment.


How many mutations, and to what extent? Should we measure
genotype or phenotype?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

What is a Disability and What is
Normal


What is a ‘disability’ when the same genetic change may confer alternative advantages?


How is it defined? How is it likely to change in a society where genotypes are easily
determined?


What happens if, for example, there is a genetic test for ADD? Will some people with the
phenotype be diagnosed as without the genotype (as this is very much a subjective
‘disease’) and therefore not be eligible for health coverage on this, or will some people be
diagnosed with the genotype, but not the phenotype and therefore be stigmatized with a
‘disease’ that they do not show any symptoms for?


What will be the actions of the pharmaceutical companies that make ‘ridalin’? What is
in their best interest
-

how will they act politically?


What are the implications of separating genotype and phenotype on discrimination?


Currently, we discriminate based on looks, right?


Do we discriminate based on data? (wealth, power, connections, titles? Phds? Now
genotype?) Example
-

BRCA1 predisposition, Huntington’s gene, Alzheimer’s etc,
intelligence genes.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Abilities


Find the genes for intelligence. Would you be pre
-
selected for
schools like Dartmouth? Would you want YOUR children to have
extra intelligence genes / be positively/negatively selected
based on their genotype



Sports, enhancement



Looks / beauty


subjective across groups / cultures.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

The Esoteric Aspects of This
Science


If everyone of a particular species is slightly different genetically, how much
genetic difference is required to be a different strain / race / sub species /
species / etc.



What experiments / analyses would you perform to answer these questions?


Perform phylogenetic tree analyses on wild type and mutant genes in
humans (ie cftr, brca1, apoe3/4 etc). note degree of change and compare
amount to that seen between a single gene between two different species.


How do you distinguish between several/many mutations that have no
effect, and one mutation that has a large phenotypic effect. Which one
is more ‘different’?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Bioinformatics and Pharmaceuticals


Can you tailor drugs to work with a specific genotype? Should
the genotype of patient be known before taking a certain drug?



Does this enhance the effectiveness of the drug, or invade the
privacy of the patient?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

Bioinformatics and Gene Therapy


Will the ability to quickly, accurately and cheaply determine an
individual genotype promote gene therapy as a medical
approach?


What other technological barriers need to be overcome before
this information is medically helpful? Ie


what are the current
barriers to gene therapy?


Future developments


Can we alter / enhance / prevent certain developmental
stages? Replacement organs? Ears, skin, kidneys …


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Bioinformatics and Evolution
-

I


Will bioinformatics help fill in the ‘gaps’ in our evolutionary knowledge?


Can we predict what gene & proteins might look like/function in species
that we have no evidence for? The missing link?


Evolution studies are currently based on features or traits
-

should it be revised
to be a genetic reflection of our ancestry? Ie bergey’s manual.


Linking hard data with population genetics


P2+2pq+q2 predicts, based on statistics. bioinformatics will allow instant
screening & real numbers.


If the genetic data from a population can readily be analyzed (the
real

data,
not just probabilities as before), can / should the genetic future of the
population be predicted?


Should that future be manipulated for the ‘good’ of that society? (Obesity,
cancer, diseases due to inbreeding (Ashkenazi Jews & Tay Sachs is an
example of where this works in a pre
-
bioinformatics era).




BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Bioinformatics and Evolution
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II


Darwinian theory, natural selection, survival of the fittest, does
this need to be modified? What is the ‘fittest’? What does this
mean from a sequence data point of view? Least mutation?
Most mutation?


With genetic information easily available, will this alter the
evolution of the human species?


Will partners be chosen based on genotype rather than
phenotype?


How are partners chosen now?


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology

Case Studies (Hospital)


Will you commence prescreening of fetuses for use in prenatal
(pregnancy) counseling?



What do you need to know before doing this? What are the
needs/gains for the px and the costs/gains for the hospital?




Gen counselor, hospital lawyer, GM of hospital, parents,
unfaithful wife!, husband, parents of husband with history of
heart ds


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Case Studies (United Airlines)


Screen pilot applicants for neurological issues / addiction genes
/ depression / heart problems etc etc = anything.



Why would you want to do this?



Safety of of passengers is at stake. Can UA require this? Safety
= increased costs. But better PR (our pilots are safer than
yours!)





Pilots, UA gm, lawyers for each party, passengers, geneticists,
mds.


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
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Case Studies (School Bus Drivers)


School bus drivers


Applicant screened for drugs etc


also genetic screening


show predisposition for stroke, poss danger to children if driving
bus? No symptoms


Applicant, school district manager, school lawyer, union leader,
ACLU representative, spouse of applicant (50 yrs married, no
problems, healthy), children (need more drivers, w/o = waiting
increased for children, reduced bus routes)


BINF705 SPRING2012 SOLKA
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Ethics at the Interface of
Computer Science and Biology