Genetics, Identity and Our Changing Selves

Rabbi Geoff Mitelman: 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.

Dr. Marnie Gelbart: 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.