Genetics, Identity and Our Changing Selves: A Presentation by Marnie Gelbart, PhD

Genetics, Identity and Our Changing Selves: A Presentation by Marnie Gelbart, PhD


Welcome, everyone, to our last series of webinars
about using science as a Jewish professional. My name is Rabbi Geoff Mitelman, I’m the
founding director of Sinai and Synapses, and I’m thrilled to be here with the AAAS Dialogue
on Science, Ethics and Religion, and Clal, the National Jewish Center for Learning and
Leadership, in partnership to be able to help Jewish rabbis and cantors and educators learn
about some of the most interesting and exciting and dynamic science, and to be able to apply
that in their own communities. And we also have to thank the John Templeton
Foundation for their support. It’s now my pleasure to introduce our guest
speaker, Dr. Marnie Gelbart, who works for the Personal Genetics Education Project at
Harvard University. She is leading initiatives for advancing national
awareness about the benefits, as well as the ethical, legal and social implications, of
knowing one’s genome, which is becoming more and more prevalent in our society. She’s the scientific advisor for pgEd’s
curriculum and leads professional development trainings and classroom workshops for teachers
and students. She received her B.S. in biology from Haverford
college and her PhD in molecular and cellular biology from the Fred Hutchinson Cancer Research
Center. And Dr. Gelbart, we are thrilled to be able
to learn with and from you here this afternoon. The questions of genetics and personal genetic
enhancement, and our ability to be able to increase who we are, enhance who we are. It raises some incredible opportunities, some
incredible ethical challenges, and I know you are at the forefront of a lot of these
conversations, so we’re thrilled to be able to learn from you here this afternoon and
I’m going to turn the floor over to you. Great, well, thank you Geoff, and thank you
to Sinai and Synapses, Clal, AAAS and DoSer for inviting me to be here. It’s really a fantastic opportunity. I think I’m equally excited to be here to
learn from you all, getting your thoughts in the discussion, so I will do my best to
to keep my presentation on time so that we can have plenty of time for some discussion. I’d like to start out, before I switch my
screen here, just to share a personal story about how I went from being a researcher in
genetics to my current position at PGEd, and taking more of a role in education and awareness. And that’s when I was – because when I
was a postdoctoral researcher here at Harvard Medical School, and that was when I became
pregnant with my older daughter. And I’m Ashkenazi, and I went to my doctor
for one of my early appointments, and they offered me carrier testing to see if there
were any variants, particularly several that are prevalent in Ashkenazi populations, to
see if there was – I had any variants that I might pass on to my daughter associated
with some serious diseases. And at that moment, I said yes, and they drew
15 vials of blood. And for me, that was a profound moment, a
vulnerable moment, and one where I thought to myself, “I have a lot of questions, but
I have those questions because I have a lot of knowledge from my training.” And it became a personal mission of mine,
and one that really led me to switch career paths and come to PGed, to be involved in
sharing knowledge, raising awareness, and being a part of a much broader question about
these new technologies and how they’re used. So it’s very special for me, personally,
to be here, as well as professionally. So let me go ahead and share my screen. So this is the website of my group, the Personal
Genetics Education Project. For those of you who are calling in, our URL
is pgEd.org. We are based in the Department of Genetics
at Harvard Medical School, and we were founded about 12 years ago out of a sense that the
field of genetics was moving so quickly – I think to many in our field, we’ve really
been surprised that it has gone even faster than anyone thought. And that these technologies can be potentially
transformative, some of my colleagues think, transformative for medicine. But we also know they raise a number of ethical
issues, as Geoff mentioned, and genetics has a terrible history of genetics or, sorry,
a terrible history of eugenics, which our Jewish community knows very well. And that was fueled by a lot of misunderstanding
about the science, and also horrible judgement that some groups passed on to others. And so pgEd came into existence out of a feeling
that scientists need to do much better this time in speaking up, in making sure our communities
are informed, and informed so that communities can be part of a much wider dialogue about
the benefits of technologies, the implications, so that the scientific community can hear
voices from all communities, around our nation and around the globe, about how these technologies
are used. So just briefly, and I don’t know if many
of you are on the phone, but I just wanted to share some of the resources that we make
freely available on our website, so if you can’t see this, you can go to our website
and download a series of lesson plans that we developed for teachers that touch on a
number of different topics. I’m showing here – I think we have 10
or so that are online today, and we’re currently working on a series on genetics and identity. And what I’m going to focus on broadly today
is three sets of technologies that are driving, you know, so much of what pgEd is doing, and
bringing about –there’s major implications for individuals, their families, future generations,
so broad societal impacts. The technologies that I’m going to be focusing
on are the technologies that are making it possible to know much more about our own genetic
makeup, and here I’m showing with the symbol of of pedigrees that are commonly used by
geneticists and genetic counselors to look at inheritance patterns within families. And that we are walking around as individuals,
and individuals with families, with DNA that brings, you know, pieces, that we carry pieces
of DNA from our ancestors, and genetics is just one piece of the puzzle. So our identity, our health, is shaped by
so much more than our genetics, but our genetics is increasingly coming into that conversation,
because we can have so much more access to our genetic information. The second set of technologies I’ll talk
about is how genetics is increasing the amount of information we can know about future generations,
and even parents able to have a say about the genetic makeup of the children that they
want to have. And I’ll close with some of the newest technologies
that have caught a lot of attention for genome editing and making changes, very deliberate
changes, to our genomes. So here what I’m showing is the technological
leaps in genome sequencing. So in 1990, scientists started working on
this human genome project, it took 13+ plus years to be able to – and cost over three
billion dollars to have an initial map of the human genome, to decode the genetic makeup
of a single individual. Now, about 25 years later from when this all
started, we can sequence a genome in three days, and there’s at least one company that
makes – you can get your full genome sequence for $999. The goal, ultimately, for this to be really
clinically as useful as possible, is for sequencing to be feasible – sequencing a genome – within
hours. And we are certainly not there yet, but the
goal has to be to continue to drop the cost till genome sequencing is free, so that issues
of access are – so we can alleviate issues of access, so that there’s equity in how
these technologies can be, how these technologies are available to our communities. There are some companies that have developed
DNA sequencers, like the one shown here, that can fit in the palm of your hand. If you can see, this particular sequencer,
called the MinION, can fit, can just plug right into the USB port of a computer. And some scientists think that one day this
kind of sequencer is going to be available at your local drugstore, so that this really
has the chance to democratize how people are able to access genetic information. So what can genetic information do for us? I’ll highlight a few examples of this idea
of precision medicine, and how genetic information can inform diagnosis and treatment of disease,
as well as preventative medicine. Here I’m showing CYP2D6, which is an enzyme
in the liver that helps to metabolize codeine into morphine. And there are many known variants, 100 and
counting in the CYP2D6 enzyme that exist in human populations, that affect how well different
individuals are able to metabolize codeine into morphine. For some individuals, they’re very poor
metabolizers, maybe five to ten percent of us, and these are individuals who might go
to their doctor, be prescribed Codeine, and actually get very little therapeutic effect
of the medication. And for others, maybe a few percent of people,
they’re rapid metabolizers, they actually metabolize codeine into morphine so quickly
that it actually can be toxic, even life threatening. And so for these individuals, they should
never, ever be prescribed codeine, and so having access to that sort of information
can be very informative for those individuals. More generally, you know, genetics can – I
think we’re really at the early days of understanding how genetics can inform the
kinds of medication that may work better for us or be dangerous. So just at the beginning, but one area where
this is really an application quite a bit right now, is in treatment of cancer, to have
more targeted therapies that are less toxic. These aren’t cures, but I can say from personal
experience in my family that they can offer, you know, for some people, a quality of life
that might not be possible with more toxic treatments like chemotherapy. And so there’s a lot of hope that this will
continue to grow. Here I’m showing you a little boy in Wisconsin
named Nicholas Volker. He is a child who, like many others right
now, or like many others today, have an illness that really defies explanation and a definitive
diagnosis by their doctors. Nicholas had an inflammatory bowel condition
unlike anything his doctors had ever seen. He underwent over 100 surgeries by the age
of four, and the only thing the doctors knew for sure was that if they didn’t figure
something out, that Nicholas was going to die. And so this was back in the late 2000’s,
I believe, maybe a little later than that, but they did something pretty unheard of at
the time, which was to try and sequence Nick’s genome, or a portion of Nick’s genome, to
see if they could figure out what was going on. It is like searching for a needle in the haystack
but they were able to find a mutation to make a causative link to his illness, and it pointed
the doctors towards a treatment – a path of treatment, and because of that, Nicholas
is alive and well today. [He] still has some consequences of his illness,
but I think this was life-saving for Nick. Now, this is, you know, a pretty rare story. Nick is the first person ever where genome
sequencing pointed to not only to a diagnosis but to a treatment. This is a rarity, but it’s where people
in the field of genetics hope they can improve. Then I wanted to turn to what genetic information
might do for healthy individuals. And there are many ways that individuals can
access their genetic information, both through their doctor’s office, through a research
project, through – in the Jewish community, there are certainly community-based genetic
testing initiatives, and also consumer initiatives, or consumer genetics where companies are marketing
genetic tests to consumers. There are a number of these companies, and
a lot of variation in what they test for. Some test for serious health conditions, like
inherited predispositions for cancer, heart conditions, Alzheimer’s predisposition – to
ancestry, to nutrition, and some of the lighter side of genetics – of how likely, what athletic
ability, what kind of sport I should put my seven year old in. There’s a lot of – I guess I should say
these tests are different in what they do, some sequence an entire genome or a portion
of the genome, some look just at specific places in the genome that are known to vary
frequently among people. And these are called single nucleotide polymorphisms,
or SNPs. And there’s certainly different ways that
people respond to finding out about their genetic information, and and depending what
they find out may lead to drastically different kinds of behaviors. So there are certain variants in the BRCA1
and 2 mutations that are particularly prevalent in Ashkenazi populations, and for a woman
who finds out that she carries one of these in her genome, she might consider undergoing
a prophylactic mastectomy. And for a woman who finds out she doesn’t
carry one of these three variants, there’s concern – what does someone take away from
this information? So, you know, a woman who tests negative for
these three variants still has a risk of developing breast cancer in her lifetime, she just may
not have this set of inherited predispositions. And so the F.D.A. is thinking a lot about
how to regulate access to – regulate what kinds of consumer genetic tests are being
sold. And so that’s something I think we’ll
continue to see developing over the coming years. And there are some questions about how other
kinds of tests, one for athletic ability, for example, should be regulated, because,
you know, genetics is one piece of the puzzle. Our environment, our life experiences, our
access – it plays a great role in who we are, and so what – are there, who should
be deciding what kinds of information people can seek out? And how useful that information is, and how
reliable and predictive that information is. There’s great variability. So this is something that’s developing right
now. One of the concerns that some people have
about accessing their genetic information is how it might be used against them. And so here, I’m highlighting a piece of
legislation that was signed into law in 2008 by then-President Bush, the Genetic Information
Nondiscrimination Act or GINA. GINA is a piece of legislation that took Congress
14 years to pass, but protects against discrimination based on a person’s genetic makeup or family
history. It protects against genetic discrimination
by employers and in health insurance. So there are certainly areas that are not
covered by Gina, but it is a start for thinking about how people can make use of their genetic
information while avoiding some potentially unwanted consequences of stigmatization and
discrimination. And this is an area, too, there are people
who are very interested in having GINA expanded to cover long-term care insurance, disability
insurance, and so forth. There’s also been some movement that could
strip away some of GINA’s protections, and so this is ongoing. So I turn now to what we can know about the
genetic makeup of future generations. I mentioned before my personal story with
carrier testing. There’s 18 carrier tests currently for diseases,
or for variants, that are particularly prevalent in Ashkenazi populations. There are tests for variants associated with
diseases in other populations, and this kind of carrier testing, pre-conception, and premaritally
and post-conception, has been a part of why diseases like Tay-Sachs have really decreased
significantly in Jewish populations, this kind of screening and awareness about this. There are ways that genetics can be used also
for parents to have some sort of say in the children that they wish to have. Here I’m showing an embryo that was created
by in-vitro fertilization at the eight-cell stage, and if you can see on your screen,
a single cell is being removed for genetic testing. And once genetic testing is done on embryos,
then doctors can decide, based on that information, which embryos to implant in a woman. And this technology, which is called preimplantation
genetic diagnosis, can be used to avoid passing on serious genetic disease like Tay-Sachs,
and has been applied in other ways that I’ll talk about in a moment. Another way that many women are finding out
more about the genetic makeup of the fetus that they’re carrying is through something
called noninvasive prenatal testing, or NIPT. And this is a way of learning about the genetic
makeup of a fetus from small fragments of fetal DNA that are normally circulating within
the bloodstream of a pregnant woman. This cell-free fetal DNA appears as early
as five weeks of gestation, and after a woman delivers the baby, the cell-free DNA disappears
almost immediately. So it’s a way to non-invasively get some
information about a fetus that a woman is carrying. It can be used to look for extra and missing
copies of chromosomes, such as in Down syndrome. It can be used now to look at smaller regions
of the genome, but with less accuracy. And doctors tell me that this is one of the
fastest- growing medical tests, most rapidly adopted, and millions of tests have now been
performed worldwide. There’s – you know, women may choose to
seek out this information for a variety of reasons, or not seek it out, and for some
women who, based on what they find, may consider abortion, I think doctors really want people
to know that noninvasive prenatal testing, while much better than previous screening
tests, is not diagnostic, and if a woman is considering termination, she is strongly encouraged
to go for confirmatory testing by amniocentesis or chorionic villus sampling, CVS. So all of these reproductive technologies
get at the idea that genetics is now putting in our hands a capacity for selection of who
is born and who is not born. And there are many – and it’s getting
late, but there’s many different opinions on how, what kinds of diseases, whether early
childhood or those that onset later in life, whether we should select for sex, physical
characteristics. There’s many different thoughts on how and
what kinds of selection is or is not OK, where to draw the line, who decides. And this is certainly something that I imagine
may come up later. OK, so I will speed up a little bit just to
talk about genome editing, which is now taking us from a place where we can read a human
genome, to take the information that a person is carrying around, and actually using a number
of technologies called genome editing, to change that information. And this is technology that – one in particular
you may have heard of is called CRISPR, it is really talked about a lot because of its
ease of use and low cost. It has really revolutionized the kinds of
genetic research that is happening in institutions like Harvard Medical School. There are many applications. One that’s being looked at in pigs is to
increase, or to see if pigs might be a suitable source of organs to address global shortages
for organs for donation to people who desperately need them. And scientists are looking at pigs because
their organs are comparable in size to human organs, and so that might be a source. Scientists are using CRISPR to see if they
can eliminate dormant viruses within the pig genome that might reactivate in humans, or
any other immune factors that might cause rejection. There’s another way [with] CRISPR, and I’ll
just go through this quickly, just that CRISPR, might be used to control vector borne diseases
such as malaria, dengue, Zika, Lyme disease, and something called gene drives, and I’m
going to skip over that in the interest of time. But really, people are thinking about how
CRISPR might be used in humans as well, both in tissues of the body to address disease,
to make genetic changes and repair variants that are causing disease and to do that in
a fully formed human, where we’re making changes in cells that won’t be passed on
to future generations. And scientists think that they can do this. We are beginning to see reports where this
is being tested in humans, particularly in isolated blood cells, making modifications
in those blood cells, putting them back into the body, and there are clinical trials underway,
and even a couple that have been approved, in August and October for, treating certain
kinds of cancer. There’s many conditions that could be treated
this way, inherited forms of blindness, muscle diseases, blood diseases, lung diseases, liver
diseases, cancer – the potential for treating disease is something that has people very
excited about where this could go. But these technologies are also raising a
lot of questions because of the potential for germ-line gene therapy, genetic changes
that could be passed on to future generations. And so I’m just wrapping up here to say
that this is the subject of a lot of ethical debate amongst many stakeholders, scientists
included, about whether making genetic modifications to future generations for the purposes of
treating disease, for the purpose of enhancement – you know, where do we draw the lines,
and who decides? And I’ll just say that a panel that was
convened by the US National Academy of Sciences gave a yellow light to human embryo editing
recently. Earlier this year, they said “you know,
we’re not going to say no.” The initial thought was “let’s have a
moratorium so that we can think about it,” and now the recommendation is that we need
to proceed really, really slowly here. There needs to be a lot of public input, long-term
follow up, oversight – but you know, but let’s see what we can learn from research
when there’s no other reasonable alternatives to this, and only when it’s restricted to
genes associated with a severe disease. So this is moving – this is starting to
move ahead very slowly and cautiously, but it is something that we’re starting to see
some publications about. So I’m just going to wrap up and say this
is my pgEd team. Most of us are based in Massachusetts, my
colleague Dana Waring is up in Maine. and then here is our Web site and I hope,
Geoff, that you will send out my e-mail address and, you know, links to our information to
everybody here.

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