[Instructor] In this module, we're going to
go over some of the basics of the ethical,
legal, and social implications
of genetics and genomics.
And I've titled this as a primer as we're not going
to go into significant amount of detail in any one
of these components, but it's more to raise your level
of awareness and to get you thinking
about these different issues and their implications.
And some of these that are specifically related to genetic
and genomic information,
that's even more distinct from other health information that
I'm sure you've had situations where there are
ethical, certainly ethical implications and privacy concerns
and confidentiality concerns.
And those are also the same
with genetic and genomic information,
but there are some additional considerations on top of that.
So by way of introduction, just want to,
to put it in the context that genomic information is central
to each person, yet it also applies to relatives,
future children, and even to entire ethnicities
or races or communities.
So while you might find out some information about a person
through genetic testing, it also may in some ways
provide some information about others
who may not have given consent to,
or may not have been asked about doing a genetic test.
But some of their information may also become
obvious from the genetic test results of a patient.
So this certainly will raise some ethical
considerations that are specific to genetic information.
Genetic and genomic information requires additional
consideration for its impact on patients, family members,
communities, religious groups, ethnicities and races,
and society as a whole.
Genetic diseases and predispositions cannot be cured
and some genetic diseases are degenerative
or have limited effective therapeutic interventions.
And this will certainly play a role
in patients making those decisions about what they want
to know and what they don't want to know.
And, you know, for some, I think, I mean this
for everyone, this is just a personal decision.
How much do you want
to know not just about your health status now,
but in the future?
And if there isn't an intervention as of now
that can directly mitigate any of
the health concerns that are coming down the road
that can be predicted from genetic testing,
how does that affect a patient's decision about whether
or not they want to be tested?
And again, it gets back to the question
of not only do they want to be tested,
but would their family members also want
to have the information that this is something
that's running in, that this is, you know, genetic mutation
or a modification that is running in their family.
So certainly that can have some strong
psychological impacts and special care and consideration
must be taken when collecting, testing,
interpreting and explaining genetic information
as always, you know, it needs to be done
in the context of each particular patient being
unique and their specific circumstances.
So we're talking about ELSI, that's just short for ethical,
legal and social implications,
and this is an acronym that's used a lot
for in genomics.
There was a group that was assembled
to specifically monitor the ethical, legal,
and social implications of the human genome project
as that was progressing, significant amount
of the budget was set aside for that group
to continuously monitor what was going on,
how these technologies were being employed,
and the implications both those that could be predicted
and those that that occurred with, that hadn't been thought
of prior to introduction of these technologies.
So these groups have been around for some time
and continuously are evaluating situations
and putting out recommendations
for the implementation of these technologies
or their regulation, any laws that need
to be passed in order to protect,
to protect citizens from any
infringements upon their rights.
And also to, you know, to ensure
that our society is moving in what we deem,
as a society, as an ethical direction with this type of,
with these types of advances.
So as with all ethical considerations, it is critical
to keep in mind the issues of justice, privacy, autonomy,
beneficence, and non-maleficence.
And it's always a balance with these
and rarely is it clear that you can
find a situation where all of these
are in everyone's best interest.
But it really is just a balance of finding a way
to end up where there's the greatest good
and the least amount of harm.
Considerations given to both intended
and unintended consequences,
positive and negative outcomes and effects
on those who are advantaged and disadvantaged
with the best solutions being those
that least infringe on the values of those involved.
So of course these are issues
that I have no doubt you deal with
regularly in your practices
and have significant amount of experience
and understanding with it.
The genetic considerations, it's no,
it's no different from those in that they,
it still requires the balance
and consideration of all the different parties
that may be involved
and the intended unintended consequences.
Here, my goal is more to just raise the awareness of
what some of those intended and unintended consequences
may be and who it may affect
and beyond even just the patient.
So it's of course necessary to balance privacy
and confidentiality of patient information with the duty
to warn of a significant health risk which may be mitigated
through health interventions
to relatives against a patient's wishes.
So this is one of those challenging ethical situations.
And honestly there isn't a clear guidance
that can be provided so that in every situation
you'll have an absolute answer.
But the recommended approach is really just
discussing possible outcomes
with the patient before testing
so he or she is aware of what the tests may reveal
about relatives and so that you can potentially reduce
those issues when the test results come back in.
And I know there are many situations in which
you may not be there when the decision is being made about
whether a test is going to be carried out on a patient.
And so you may not be a part of those conversations
if those conversations even existed for a patient,
but you may deal with the aftermath of that.
But this is more of, in an ideal world,
the best situation is really to discuss
and be upfront with all of the
possibly foreseeable intended and unintended
results that may come from a genetic test,
which would also include potential information about a
patient's relatives.
And certainly there are,
that is up to the patient
as to whether or not he or she would choose
to inform his or her relatives about
potential health consequences
that may result from their genetic test result,
which would tell them, for example,
that a genetic disease is running in their family
or is present in their family.
Well, that also it means that there's
a high likelihood that others in their family may also have
this disease or have a high likelihood
of having children with this disease.
The recommendations really follow the idea
that if there is something that can be done about
either the development of the disease
or to mitigate the disease by acting earlier, you know,
as early as possible with that information,
then that may raise a duty to warn.
Also if it would result in some
serious health implications for potential family members,
then it certainly needs to be considered
what the duty to warn is versus the patient decision.
And if the patient's decision, if they can,
if the patient is willing to reconsider potentially
informing relatives.
That's of course the best approach to take
is certainly to have the patient inform their family members
and for them to know upfront that
what the information from their genetic test may reveal
about their family members as well.
And there's unfortunately no clear direction
to just provide in every situation is with any kind
of ethical issue that may arise.
So this is one of communicating clearly upfront
as much as much as you have power to do that,
as much as you're able to do that with a patient
before a genetic test is ordered.
And then afterwards to discuss with the patient
and to encourage him or her
to communicate with family members any information
that may be truly relevant to their health.
So genetic testing results,
health information about family members
who have not given consent to testing
may be revealed in a patient's genetic test results.
So here's an example, if a patient tests positive
for Huntington disease allele,
remember, Huntington disease is a neurodegenerative disease
that doesn't really become symptomatic
until a patient is in his or her thirties or forties,
but they have the disease allele from
the moment of conception.
So the genetic test would always come back positive even if
they don't yet have symptoms of the disease.
So let's say for example, a patient tests positive
for Huntington disease allele, let's say he knows
that there's Huntington's disease in his family,
maybe his grandfather had Huntington's disease
and he is concerned that, you know,
he may have it though he,
let's say it's from his father's side of the family,
say his father did not want to test himself,
does not want to know
because there really isn't any intervention
that can be done to prevent Huntington's disease
from occurring.
And so the father doesn't want to know.
But then the son, let's say this is the patient,
the son does want to know
and has a Huntington's disease test
and it comes back positive.
This indicates that, in this case,
given that his paternal grandfather would have Huntington's
disease, that that means his father also must
have it as well.
And so now the son has possession of information,
knows something health related about his father
for which his father never gave consent.
So this is the kind of information
that can actually be very easily deduced from genetic test
results that even a patient,
his or herself can figure out some of these things
without further consultation.
So it raises again, some sticky situations potentially
where family members are not in agreement as to wanting
to know this kind of information.
And potential psychological impact of genetic test results,
both good and bad are unique for each person
and may not be the same within a family unit.
Some feel empowered in knowing, others may suffer depression
or hopelessness, and there's just really a
broad spectrum everywhere in between.
It may result in anxiety if they don't have the test
and say there's something running in their family.
They don't, they haven't had a genetic test,
but they, you know, they feel anxious in not knowing
and they would much rather have the test
and know one way or the other.
For others, it may be that they just don't want to know.
People's preferences going into it
can certainly have an enormous impact on how
they would respond to that kind of information
or whether they would want
to have a genetic test done at all.
Religious, cultural and historical beliefs may influence
how a patient or the family approach
genetic testing as well.
And I'm sure you've experienced this with some
of your patients who either in their family,
in their families in the past
or in others that they know they've had bad experiences
or there there's some beliefs
that their information might be misused
or that there's mistrust with healthcare providers
or with healthcare system.
And that certainly
can also manifest itself in terms of their responses
to either suggestions for genetic testing
or to the results of their genetic tests.
So all of these are important considerations
to keep in mind.
So what do we have to protect us from discrimination?
This is called the Genetic Information Non-Discrimination
Act or GINA for short
and genetic discrimination, as we're defining it,
is the misuse of genetic information.
In 2008, GINA was passed
to provide federal legal protection from employment
and health insurance discrimination on the basis of genetics
or genetic information.
According to this federal law, it is illegal
for health insurance providers to set prices
or decide whether you can get health insurance
and illegal for employers to make decisions about hiring,
firing, job assignments or promotions
either based on either of these
based on genetic information.
So there are certainly some exceptions to this
and we'll talk about that in a moment.
But in general, that's the spirit of the law is
to protect citizens from loss of health insurance
or increasing in the price cost of premiums as a result of
genetic test results either directly for disease
or disease susceptibility that the person does not
yet have manifest.
Same thing is true for employment.
So they wouldn't want someone to say, for example,
have a Huntington disease genetic test
and have it come to be that their health insurance
is suddenly canceled and they can't find employment
because no employer wants to pay the cost
for their healthcare or pay the cost
for basically training them with the idea that well,
this person is bound to a degenerative condition
and so we wouldn't want to invest in this person to come
to work here if in the end they're going to end up sick.
So certainly these protections are absolutely critical
and this was a major step forward
in the clinical setting for incorporating genetic testing
and also from a research perspective
that having these protections in place makes it much,
makes folks much more comfortable with participating
in genetic research studies
because they're not as concerned
that their information might be used
to deny them health insurance coverage
or as a means for termination of employment
or not getting a job or not getting promoted.
And when we talk about genetic information with respect
to GINA, what does that mean?
Genetic information includes family health history,
the results of genetic tests, the use of genetic counseling
and other genetic services
and participation in genetic research.
So this would also include the pedigree
that you might be doing for a patient and their family.
That information cannot be used
by health insurance providers to, you know,
in any way for a disease that's not manifest.
And same thing for employment.
Again, there are a few exceptions
and we'll talk about those.
So what does GINA not cover?
We're gonna talk about it in a lot more detail
in the separate slide deck that I'm including,
but basically it does not,
so health insurance providers can make
underwriting decisions.
These would be setting premiums, determining coverage,
et cetera, using genetic information related
to a current state of health.
And this is what we would call a manifest disease.
So if a patient is symptomatic
or being treated for a genetic disease,
this can be used by health insurance providers.
Genetic diseases are not excluded
from the health insurance providers being allowed
to use those for preexisting conditions or to set premiums.
But the must be symptomatic.
So it cannot be a genetic test that would show, for example,
a predisposition to a disease
or that, again, going back to Huntington's disease,
that a person will eventually become symptomatic.
They cannot use that alone, it would need
to be in combination with an exam
and their clinicians healthcare team
diagnosing them based upon symptoms based upon the
manifestation of the disease, not just a genetic test.
So if a patient has a genetic test which predicts
or indicates increased likelihood of developing a disease
but is not yet symptomatic of the disease
this cannot be used.
So an example would be BRCA1-2 testing in a patient
who does not have cancer cannot be used,
cannot be used to influence health insurance or employment,
but a diagnosis of breast cancer can be used.
So if you, if a patient goes
and does not have cancer, has the BRCA1-2 test,
gets the results,
it is positive that information cannot be used
to influence health insurance.
However, if a patient goes in,
is diagnosed with breast cancer,
has a genetic test and finds out that he
or she has BRCA1-2 mutations,
then that can be used mostly solely because of
the patient having a manifest disease of breast cancer.
So what else does it not cover?
It does not cover other types of insurance
including life insurance, disability insurance,
and long-term care insurance.
There are certain states that have laws in place to protect
these types of insurance from,
to protect individuals from discrimination
and these kinds of insurance.
In addition to not covering other types of insurance,
GINA does not cover certain groups including military,
federal employees enrolled in the federal employment health
benefit plan, veterans with healthcare
through the VA and individuals covered
by Indian Health Services
as these individuals are all covered
by similar anti-discrimination policies already in place.
And many of them, including those for the military
and federal employees are actually more protective in a way
or I should say more broad in their coverage
than is GINA.
So they supersede the protection provided by GINA.
There are some interesting other considerations in the
military though, and that's actually,
there's an interesting paragraph or so
in the textbook that you'll read about military use
of genetic information and how it's actually used
and openly really shared
that certain individuals who have, for example,
sickle cell anemia
or sickle cell trait, those who have G6PD,
other kinds of genetic diseases
that put an individual at higher risk under stress.
Conditions, say physical stress conditions, they,
because for sickle cell trait, if they are under conditions
where there are dehydrated, under severe heat,
they're much more likely
to suffer severe health conditions as a result of that.
So the military actually gives them
like separate arm bans during certain kinds
of practice or training I should say,
that will let those who are running the training programs
know so to, in a way, to try to protect them.
However, there are certainly issues there.
I mean I'm sure you can imagine some of the issues there
with privacy, but military is its own system
and GINA does not actually apply to that.
The other group that actually is not covered from the
employer side of the equation would be employers
with fewer than 15 employees.
So this is kind of an important exemption
and one that I think is really relevant
because if an employer,
basically if it's a small business
or an employer that only, you know, that only has a handful
of employees, they are not held to the same standards of
GINA as larger employers.
And so this may be certainly a legitimate concern
that patients may have if their employer is
a smaller employer or if their employer even has,
you know, a history of using this type
of information in employment decisions.
However, you know, there still may be some protection
in place from other laws
and from equal opportunity commission as well.
And so, but GINA itself does not directly cover,
does not directly include employers
with fewer than 15 employees in their
employment non-discrimination.
So when we talk about GINA,
you may also be thinking about HIPAA
and we will look at this in the other slide deck as well,
but GINA's primary concern is not with privacy
but with the use of information for discrimination.
So HIPAA as you're very aware is more about privacy
and confidentiality
of health records and health information.
GINA is much more concerned about the use of
that information for discrimination
and some aspects of GINA attempt to limit the flow
of information to insurers and employers.
But these are mostly restrictions on what insurers
and employers may ask for from individuals.
For healthcare providers, HIPAA continues
to govern the way health information may be disclosed.
All right, so what else can we
find out from genetic testing?
It's not just the intended results, as I mentioned,
it's also potentially these unintended results.
So what are we talking about with unintended results?
These are broadly called secondary findings
and these can include any number of results
that can come out of a genetic test.
And it depends upon a number of things.
So it depends upon if the genetic test is very specific,
is it just looking for a particular snip or particular
allele that is known to be associated with one disease
and only one disease,
or is it the in the direction that a lot of research
is headed, which is more broadly sequencing larger regions
and not just focusing on say, a single snip
or a single allele.
What else can that information tell us?
Well, in addition to that,
it can actually inform non-paternity, which is a,
folks are very anxious about
or nervous about that information coming out
and the implications for the family units
and the implications, the psychological impact for all
of the individuals involved.
It can basically be a really challenging situation
for the families to deal with.
In general it's recommended
that non-paternity is not revealed,
is not revealed even if the information comes back from a
genetic test, say a clinical geneticist
or genetic counselor is looking at the information,
say they tested, they took a sample from
the parents and then they took a sample from the child
and they were trying to determine if the child
has the same alleles as,
or has which alleles from the parents.
'Cause let's say mom was found to be a carrier
for cystic fibrosis and the supposed father
was also a carrier for cystic fibrosis
and they want to know if the child is as well.
They'll test these specific alleles for that
each parent has both of their alleles
and they'll test both alleles from the child.
And if the child has an allele that is not found
in either of the father's alleles,
that is an indication of non-paternity.
So that, it's generally determined that
that information is not to be shared
unless it is requested by everyone involved.
But short of that which it is not shared
unless that of course is the reason for the test.
But other than that, it's not shared.
That being said though, that information may be,
may come out from the genetic test, so the genetic counselor
or the clinical geneticist may be made aware of it
and may ask the, typically would ask the mother if she
would want that information shared or not.
In addition, it can actually provide some,
it can actually demonstrate that incest has occurred
and that goes down another path that you know,
that if you were working specifically in a genetics setting
where you know you're a genetics counselor
or a clinical geneticist,
this may be a situation that you would face.
I imagine it's not something you're gonna face on a
regular basis simply because in order to determine
that incest has occurred,
you would need to have taken samples not just from the
presumptive parents but also from the child.
And there would need to be comparison
between the two parents.
And in order to come back to say that the parents were that,
say for example the father of the child
who is being tested also happens to be the father
of the mother.
That information potentially can come out,
but it doesn't usually come out in a typical test,
that would be something where they're doing
a much broader kind of assessment
of the genetics of the child.
Say, for example, there's an illness that
hasn't been identified or isn't clear what it could be.
And so they're looking more broadly at many different
markers in the child's genome.
They want to compare that back to the parents,
in that case that information may come out,
certainly may come out and depending upon
the nature of the situation, you know,
there are different kinds of responses
that could come along with that.
But basically that it's unlikely
that it would actually be a situation you would be faced
with unless you were involved in basically
the counseling after a test result came back.
That would be, again, a non-standard test.
Something that would be looking more broadly
for potential genetic abnormalities that might be related
to some disease phenotypes that hadn't been identified.
So in any case, those are two
that potentially information could come out from genetic
testing, but it's unlikely that,
unless you are a genetic counselor
or a clinical geneticist,
that you would be privy to that information.
But certainly patients might feel, or patients
or family members might feel a little nervous
or very nervous, even anxious,
or very concerned about this information coming out.
So what other secondary findings are possible?
Other disease susceptibility alleles
found especially important in
whole genome sequencing approaches.
So while you may be going in looking for
what's causing the, you know,
what would be the genetic basis
for this patient's particular disease,
they may also discover that in their,
that they also have susceptibility
or another genetic disease that they were not looking for.
This is once again goes back to more
of those non-standard genetic tests
where they're looking very broadly
or sequencing large regions.
Then there's the possibility that
that information might come out.
In a standard genetic test,
that's not gonna be something you
would likely be faced with.
That would be more of a genetic research in a situation
with genetic research going on
that something like that might come out.
Alleles of a single gene may be associated
with multiple diseases, remember this word, pleiotropy?
Well that's when a gene, alleles of a gene,
can be associated with multiple diseases.
So testing for one disease may reveal susceptibility
to other diseases as well.
And even if a person says,
"Well, yeah, I want to know if I have the disease,
"the allele, that makes me susceptible to,
"you know, this one disease,"
they haven't necessarily given consent
or that they have discussed the potential implications
of the other disease that might be associated
with that allele as well.
And this is the case for some of those HLA gene,
a patient who had an HLA test result
and it had, and the patient had this particular haplotype
or, you know, essentially allele
that was the result of it.
And that may indicate an increased likelihood
of narcolepsy.
Haplotype that came back from that
is not only associated with increased likelihood
of narcolepsy, but it also may be associated
with an increased risk of multiple sclerosis,
among other disorders as well.
And so with HLA typing, it is,
even though you may just be interested in narcolepsy, say,
it also may inform a patient
or inform the healthcare provider certainly about a
potential increased likelihood of multiple sclerosis
or other diseases.
So that certainly should be discussed upfront
with the patient before the the test is conducted
to find out what he or she would would choose to learn about
and also to just confirm that they would still want
to undergo the genetic test knowing
that that other information is really tied
to that same test for, in this case for narcolepsy.
So it gets a little complicated
and it's not just as simple as I'm only going
to test for this one disease
because you very well may also be
informing multiple other diseases.
And it doesn't just stop there
because we also think about future research studies which
may change or expand the interpretation
of today's genetic test results.
But again, once you have a genetic test done at any stage in
your life that test result will always remain,
will always remain true to that person.
So that person will always have that allele.
So if later on genetic research shows that the allele
that we've been testing for for cystic fibrosis
is also somehow related
to an increased likelihood of developing,
you know, anxiety disorder
or an eating disorder
or something like, that's not the case,
but I'm just making something up
to use as an example,
then that patient now knows something about his
or her herself that they didn't actually,
you know, didn't actually think about
or consent to necessarily from the beginning.
And that's not something we can control.
That's not something we can control other than
to potentially inform the patient that, you know,
it's possible that at any, at any time in the future,
future research may implicate those alleles
in susceptibility to other diseases as well.
So social implications, and there are many,
but just a few to give a few examples.
Genetic research can reveal differences in allele
frequencies between different ethnicities or races.
So remember allele frequency,
that means how common a particular allele is
in a specific population
and we're talking about races or ethnicities.
There's more marriages typically happen within those
groups and so you maintain those alleles that are
present in those particular groups in higher proportion.
For example, the Ashkenazi Jewish population has a higher
proportion of certain genetic disease alleles than
the general population.
And that's actually true with any population.
You take any population and find a subset
of genetic diseases that are gonna be more common
in that population.
Well it can certainly apply
directly to health, but it can also apply to behavioral
predispositions and certain groups may be subject
to discrimination as a result.
One example of that, it would be the Maori people
of New Zealand were found to have a higher frequency
of an allele of the MAOA gene once thought to be associated
with antisocial or aggressive behavior.
This has since been disproven,
but this negatively impacted the perception of the Maori
and increased discrimination against them.
So not only this example,
but certainly there are also examples of researchers
who are looking into all alleles of certain genes
that are associated with higher intelligence or higher IQ
and then going and looking at frequencies
of those alleles in different groups of people.
So in different races for example.
And identifying that, say there was one research study
that looked at a couple of genes that were,
one gene in particular called microcephalin
that had an allele that was tentatively associated
with higher intelligence, which was since disproven,
I can't stress this enough, was since disproven
to not have any association with intelligence.
It was actually associated with slightly larger head size
but not with intelligence.
That allele though was found to be in higher frequency,
so more common in Caucasian populations of those of
Western European descent
and was found to be in lowest frequency in those
of African descent.
And you can imagine, you can imagine
how this information was misused
and even perverted and still is today.
You can still look online
and you'll still find some of this hanging around
even though it's very much been disproven
scientifically that it takes very little to give people
who want to have a bias and want to discriminate,
it takes very little to feed into that
and that was one that certainly did.
So there are broad reaching implications outside of science,
outside of healthcare that that can apply to large groups
of people and can feed into discrimination.
Also, those who test positive for genetic disease
or predisposition face feelings of social isolation,
depression, grief, anger, guilt,
among many other possible psychological impacts
including relief and reduction in anxiety
depending upon the person.
Because again, you know,
if they were worried about whether they have the disease
allele or not, and they get tested, they find that
they are, well at least they don't have
to worry about whether they are or not anymore.
They know and they can take some steps.
That's the way some people react.
Other people will react in completely different ways.
As I'm sure you've all experienced
with giving health information, test results,
to different folks.
You get a a wide range of reactions.
So what about the cost of genetic tests?
Genetic tests can be very expensive,
as I'm sure you probably already know,
typically costing from hundreds
to even thousands of dollars.
GINA does not compel health insurance providers
to cover the cost of genetic tests in in any way.
So it's not as though it's actually making it easier
for patients to get genetic tests from
a financial perspective.
It simply just protects them from the information
that results from those genetic tests from being used
against them in any way.
In just this past June, the US Supreme Court ruled
that DNA in its natural form cannot be patented.
So why do we care about patenting?
Well this was important, this was actually a milestone
because that basically is going to open the door
to competition in genetic testing
and there increased, potentially increased
their availability.
So as you may be familiar, Myriad is the name of the company
that had a patent on the BRCA1-2 mutations
that were associated with increased likelihood
of breast cancer.
So now they can no longer hold those patents,
those patents are no longer valid.
As a result, other genetic testing companies can now start
to test for those very same mutations or alleles
and do that at a much lower cost than Myriads
original costs in thousands of dollars even
for those BRCA1-2 tests that now
there are companies that will have the opportunity
to come in and compete
and that should increase the availability
and also reduce the prices for
genetic testing moving into the future.
Alright, so speaking of genetic testing,
one last point I wanted to discuss is the
direct-to-consumer genetic testing.
And you've, you may have heard of this.
You may have even had some patients coming in
and, you know, handing you printouts of something
that they got from, you know, a mail-in kit
to find out if you have the gene for this or that.
And as you remember, we all have the same genes.
It's not the gene for this or that,
it's the allele for this or that,
but still that's probably what they say.
And I just wanted to take a moment to talk about
direct-to-consumer testing and I included
a publication on direct-to-consumer testing
and there's some position statement
as well from the International Society of Nurses
and Genetics in the required reading folder.
And they provide some guidance there as well.
But companies offer genetic testing directly to the consumer
on specific traits, ancestry, health related information
and other novelty outcomes including whether
or not you would be able to curl your tongue or.