 So, good morning. My name is Barbara Koenig and I'm at UCSF also. And I'm a medical anthropologist and I work in the interdisciplinary field of biomedical ethics and I'm part of the interdisciplinary team at UCSF and one of the nice things about these NSITE projects is the fact that we are working on interdisciplinary teams to try and solve some of these problems together. The presentation I'm going to do today is based on a paper that's about to appear in the journal Pediatrics in a special supplement edited by John Lantos and many of us in the NSITE project participated in that as well. And the presentation and some of the images that I'm going to show you were created by one of our genetic counseling students who's part of the project, Charlotte Young. So I want to give her credit as well. So we have our LC project at UCSF actually has four components including what I'm going to talk about today, what I'm going to talk about today are some of our work to engage stakeholders to really find the views of some of the pregnant women and other patients who might be screened with newborn screening. We also have a project looking at legal issues and some of the constitutional issues in implementing expanded newborn screening in the United States. And we also have established a National Ethics and Policy Advisory Board which is debating some of these issues in great detail. But today I'm going to talk just about one of our projects. So we all know and we heard from Cynthia Powell in the first discussion about what happens in newborn screening currently. A baby is born and then there is a newborn blood spot taken by doing a little heel prick which you can see that blood is then put on one of these Guthrie cards which is really an old technology. It's then sent to a state laboratory or a laboratory that the state contracts with. This is sort of a great, funny image of what a lab looks like. I think the state labs actually look somewhat different than this. And then currently under the current rules and guidelines we screen for a number of disorders for some endocrine disorders, for some metabolic disorders, disorders in the hemoglobin which are called hemoglobinopathies, severe combined immunodeficiency which my colleague Jennifer Puck just talked to you about as well as cystic fibrosis. And I should say that Dr. Puck was really instrumental in getting this new SKID biomarker onto the newborn screening program in California and through the rest of the country and has been a leader in that. But those disorders that are on this panel have had to meet certain kinds of criteria in order to be included which have been very, very stringent and I just want to go through those again because it's very important to make sure that we understand that. One, they had to be very well understood, very well established conditions where we knew the natural history of what happened to the condition and that they were, and the conditions were serious and also had, and then finally, where they had some kind of treatment had to be available. So we didn't generally, traditionally in newborn screening and we talked about PKU as the sort of archetypal classic example of that and expanding beyond that has been complicated and we have used a set of criteria called the Wilson-Younger criteria which were developed by the WHO in establishing that. So we all want to have the outcome being very healthy babies and so why wouldn't we just keep adding more and more conditions to the newborn screening panels? What if we could screen for more and more disorders and that's really one of the primary purposes of the NSITE network. And the whole genome sequencing, whether you do just the exome or whether you do the whole genome, although the technologies are quite different, they both have some features that make them a bit complicated, particularly they reveal a lot of additional information than those standard criteria that I just went through and that Cynthia Powell also talked about earlier. They can reveal some of these adult onset disorders, they can reveal another category of finding is what are called pharmacogenomic variants which predict response to particular drugs that might be used in childhood. So that might also be something that would be useful to include. We also know that there's a certain inherent uncertainty in some of the results that we get with sequencing and that's partly because we're constantly revealing what are called variants of unknown significance which need to be accounted for. So whole genome sequencing raises all of these different variables. So how do we deal with that? Well, one of the things we're doing in our project is to figure out a way of engaging with different stakeholders who have a stake in what the public policy about these issues should be. So you know that you're in the LC realm or the ethical, legal and social realm. If you start asking the should question, questions of how we should use some of these new technologies. To answer that and to address one particular stakeholder group, we did a series of focus groups at UCSF and we created five groups and as you'll see one group included parents of these patients with primary immunodeficiency and they were essential, they were recruited from Dr. Puck's clinic of patients who have that disorder. So that was one category. We wanted to get the voices into the policy debate of individuals who had that experience of having either been missed by newborn screening or actually where their skids was actually found and then they were treated with bone marrow transplant. The other four groups were with expectant mothers because we know if people are going to be getting all this additional information, we were working on the hypothesis that it might be a good idea to move some of this discussion into the third trimester of pregnancy rather than doing it all after the birth of the child in terms of thinking about what should be covered by newborn screening. So we created four focus groups of expectant mothers. Two groups were conducted in English and done at an academic medical center in California and we had two additional groups that were done at a public hospital and we did this purposefully to try and increase the diversity of our sample. So across all the focus groups we had a very diverse population and one focus group was actually conducted in Spanish because a large percentage of the babies born in California are born to Latina women. So we did one group in Spanish and then translated the results into English. So in the focus groups we talked to the individuals about and they were about two and a half hours long. We talked to them about five different topics. We really, we asked them about the current newborn screening program and what they thought about it. It turns out most of them, even those who had babies, didn't remember the newborn screening program. Most people don't know enough about this as a, it's really, it's very interesting that it's such an important program. It's really the first test that everyone gets but very few people know much about it. We talked to them about the potential expansion with whole genome sequencing. We talked about the types of results that could be revealed and we also talked about the general question about how they felt about whether permission should be asked of them before these tests be done, either the sort of initial clinical newborn screening which is a public health program and essentially mandated or, and this is also another issue, the later storage of those blood spots for other kinds of uses. And as many of you know, that issue has become highly controversial recently with several collections of blood spots in two different states, Minnesota and Texas, being destroyed because of concerns about this issue around permission. I'm specifically using the idea of permission rather than the more technical term of consent because I don't want to prejudge the discussion because perhaps we don't need an elaborate written consent process, maybe we need some kind of a clinical discussion. So we tried in our focus groups to leave that open. So I'm going to briefly give you some results from those focus groups and I've divided those findings into four different categories, traditional newborn screening, the questions around asking permission, return of results and storage. So just a few quotes to bring those individuals into the room. So in terms of traditional newborn screening, everyone that we talked to was very, very enthusiastic. I mean, this is because people experience it as a duty, as a duty of being a parent to participate in a program like this and get information. So traditional newborn screening was something that people were quite enthusiastic about, although they also had cautions and expressed cautions about the idea of the state maintaining collections of information, which might be able to predict their baby's future health. They also wanted to know more about it, and this is a quote from someone at the Academic Medical Center, I want to be the one who's making the decision, so having these choices and anything else being laid out to me beforehand and being able to have a good conversation with my doctor about it, I think is a very critical part. I think everyone would want something like that. So there was enthusiasm for newborn screening, enthusiasm and a great endorsement of the idea that this should not be done just after someone had delivered and at that moment of chaos. On the question of asking permission, people were divided, and so this is a very complicated dynamic. And the discussion here and the interaction between the parents who had experience of a seriously ill child informs the debate in a different way than people who are just thinking about this hypothetically. There also is some concern about lack of trust from certain populations, so we had some extreme positions like individuals saying, well, I'm concerned about this, you know, I've heard that they kill babies over at that other, on the other side of town. And so many people suggested, although they were just competing views about this, that it was a good idea, you would become more trustworthy if you were more open about what you were doing and that that was an important consideration. So I just want to read a quote from a parent of a child with primary immunodeficiency. If you haven't been in that position, it's very easy to say no. And this person was very, they were very worried about the fact that it would be so easy to say no to newborn screening, you might just want to have your baby, you might not want to avoid the heel prick even. But not taking the test would mean you wouldn't know something that could literally threaten your child's life. Even if you ask them when they're pregnant before they deliver, I don't think you're capable of truly understanding the risky situation of not doing the test. I'm glad that part was mandatory. So people went back and forth about the issue of whether this should be mandatory and how much we should rely on consent. On the question of return of results and in particular, we divided this up into categories. One category we talked about with the focus groups were pharmacogenomics, this idea of predicting drug response. And people were universally very, very enthusiastic about that. As a mother, you're going to worry about that and want to make sure they're getting the medication that works for them. There's nothing that I don't want to know. And this reflects also a very common theme, especially in the United States, the idea that information in itself is useful. The question of some of the adult onset or other disorders was more complicated as Dr. Powell indicated earlier. We actually used two case examples and talked through those in our focus groups, and those were breast cancer and Alzheimer's disease, because they're sort of classic examples of things that could be identified. One that has an action that you can, some actions you can take in the case of breast cancer, others where there are fewer things to do now, Alzheimer. And again, this discussion also revealed this tension between ignorance is bliss and knowledge is power. A lot of times, even if the condition is something that might affect you years later, there's things you can do to kind of help better the scenario. So I'd rather know, you're just going to freak me out my whole life, and then I won't get it anyway. I mean, what's the point? And they're just living your life out of fear. So people actually voiced this concern about living their lives in relationships to something that might not actually transpire. And finally, on the questions of storage, it's interesting that people immediately were not so much concerned, although they mentioned the privacy and the issue of control. They also raised something that we hadn't really considered, which was the idea that it might be useful to store this information and be used it later to benefit an individual child's health, perhaps give the information to the pediatrician. And here's an example of one quote, you know, in case anything comes up, like, say your child is epileptic and seizes and goes into some kind of a coma and they don't know why. OK, well, let's go to the genetic records and see if that child is at risk for epilepsy. So there was, again, a lot of consideration of the possibility that having this information and that it could possibly be stored for the child's lifetime. OK, if you stored it and you could go back and you could try and figure it out, some of this stuff, findings like Alzheimer's or breast cancer, those are the examples. But my decision to know information today and my decision to know information 10 years from now is not going to be the same. You're opening up a whole can of worms by asking me and then freaking me out. So again, there were concerns about having that information available and revealing essentially as a crystal ball for the future. So I'd like to conclude. Our paper summarizes several policy relevant findings. First, there's a clear preference for moving newborn screening education into the prenatal period. There were divided views on the value of formal informed consent for expanded newborn screening, a preference for return of results such as the pharmacogenomics and some concerns about revealing adult onset conditions, and then hopes as well as concerns about state mandated screening. But on the whole, people were comfortable with the state mandate to many and with the issue of not having formal informed consent be part of the clinical application of testing, which I think is interesting. OK, I'm going to now thank our collaborators at UCSF. We have a big team, including the California Department of Public Health, collaborators at UC Berkeley, such as Stephen Brenner, the Hastings Center in New York, the UC Hastings College of the Law. And we also, so thank you very much for your attention. I'm going to turn it over to, I'll let you do that. Thanks.