Ethical Issues in Bioinformatics

Below are the ‘notes’ from the ethics class from Bio68.

These are really ‘notes to self’ to stimulate discussion and thought, rather than informational, factual notes. Feel free to muse over some of the concepts and decide what you will do when you are confronted with the real scenario later in your academic life.

(stress the value of a well supported argument with background, your view, & justification. You will be in positions of power sometime and will need to persuade others to accept / consider possibly unpopular points of view)

What are we studying – what is the goal of this work?

Understand the genome
Predict structure / function / ds / phenotypes
Betterment of society?

How are we going about this?

Learn new things – algorithms
New ways of thinking
Develop new techniques, wet & dry labs
So lots of new methods / mechanisms will / have been developed that will impact issues not associated with bioinformatics. Example – moon mission spin offs (other than tang!)
So – the work that we do will impact not just bioinformatics but other, as yet unknown areas.

What will / has bioinformatics enabled us to do that we couldn’t do before?

Understand how a genetic ds works
Classify orgms / people based on genes / proteins
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 +ve for enhanced cholesterol synthesizing protein, what would you do?

How would you/someone else utilize this technology?

List of +ve & -ve outcomes of use of bioinformatics on board.

Discuss some of these outcomes

Are worst case scenarios really likely – look at examples from the past – automobile, radio waves /cell phones, nuclear power, internet (porn, time wasting?), Invitro fertilization – Louise Brown, now = stem cells.
Do we always predict doom? Should we?
NB – in the view of someone in 2025, uarrays are old ! ie technology changes fast, and what used to be scary is quickly outdated by a) non realized fears, or b) something new to worry about.
- In many cases, do the benefits outweigh the detractions?
- More good than bad = ok. As these are hypothetical issues – for systems that have not yet existed - How MUCH good do we want before allowing something with potential harm?
- Should we err on the safe side or the experimental side? Pros & Cons of each?
- Can you stop these once you start? Cannot put the genie back in the bottle!

Medical (Obvious concerns) – possibly leading on from above

Medical records – should bioinformatics data be included in these?
If Included in medical records? Access by whom? Px, md, family, businesses? Justify each. POV from each. (assign instant roles to class members & get them to defend/propose action).
Screening of newborns / fetuses? For what?
Should newborns be screened for genetic ‘problems’. What is a ‘problem’?
- Example of what, as a parent, you would like to know about your child.
Preselection of embryos
- if fetus has ‘problem’? – terminate (natural/artificial? Cure?)
- Right to death / life based on bioinformatics data – you know that your newborn will die soon, should you still let it be born?
Bioinformatics and (genetic?) medicine
- What traits can be identified by bioinformatics?
- Ask class to ie stand on desk / shout / elvis = show range of personalities = range of genotypes. What is better? Extrovert / introvert? Evolutionary advantages?
What genetic diseases could be identified by bioinformatics?
- Should they be equally important?
What is the difference between a disease and a trait?
- Should they be treated differently? Why?
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.
    - Poll class for their wish for a ‘incapacitated’ termination of life.
    - Who should decide, you, your family, the government? Eg - Florida coma case.
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 px, severity of ds. 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 / relationships
  - Add more here

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.

Who is paying for all this research? = public taxes mainly

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 HGP & bioinformatics data where no-one is the ‘same’.

Stereotyping

discuss/propose 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. (Line up around class for height?)
compare between 2 individuals of same culture/population – what pheno / biochem diffs are there? Do examples in class – allergies, lactose, other foods, diabetes, color blindness, flat feet, !!!

New technology

Miami nightclubs – transponder implant with credit card info. Pets with id chips.
- Is this the way of future medicine?
- Px 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?

Politics & workplace

identify the civic questions or problems addressed by this course / sub topic. (Ie - affirmative action, minorities, special services, individuality, impact of environmental factors).

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’ - ie, 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?

Disability

What is a disability? 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.

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.

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?
- Get class to suggest expts.
- 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’?
- (Project? Find a trait, and compare to known genetic influences, ie melanin genes, serotonin promoter repeats, Fragile X repeats vs phenotype. Alz mutation vs age of onset, Huntington’s repeats vs age of onset & severity. Project goal is to show (or not) correlation between genotype and phenotype. Impt either way.)

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?

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

Evolution? Eugenics?

Role of bioinformatics data on understanding of evolution

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).
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?

Cases / Roles

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

United Airlines

Screen pilot applicants for neurological issues / addiction genes / depression / heart problems etc etc = anything.
Why would ual want to do this?
Safety of 00’s 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.