 Okay, now the fun begins. By the way, I told you we were going to have some individuals who are both articulate and actually have some opinions and you can start to get that sense. They're certainly not shy, but I thought they were both terrific presentations to set the stage. We are going to just, I'm going to throw a couple things out for a little bit of discussion, but then we're going to take a break probably within about five or 10 minutes because we want to hear from you. And in addition, I would also say that during the break, one thing I recognized is there was some science that got covered along the way, some terms that maybe didn't get to find. If anybody in the audience has a question, especially a fundamental question, what does this mean or what do they mean by that? Feel free to come up and find us at the break and we'll happily answer that question, especially around some fundamental concepts. So I want to just, actually there were lots of things I could ask to get this going, but it was interesting sitting next to each of them during the other presentation, and they're feverishly taken down. I mean, they're borrowing paper from me, a lot of ink goes back. So I guess I want to start, and I'm going to ask Robert to start since Susan's talk went first. Name the one thing at just sort of a core that you disagreed with most in what she had to say. And some of it you covered, but if you were going to crystallize it in sort of one sentence, what was the thing you have the greatest disagreement in what Susan had to say? I think the greatest disagreement is somehow tying the abuses in history to the medical use of genomics. I mean, yes, that's true, but I just feel like those were selective examples, and we could dig around for examples in a lot of other domains that represent pure evil in the world that have nothing to do with genetics and genomics. And reciprocally, what fundamentally you disagree with the most in what he had to say? That we're dealing with frightened patients and lazy doctors, and we gotta shape these doctors up, get them in there hunting these incidental findings, performing all these analyses, and somehow doctor knows best when I think, boy, I may trust patients and doctors more than you do Robert, which is astonishing to me, because I do trust them to make good decisions with patients thinking not in a fog of fear, but really thinking about what results they are prepared to deal with. Okay, so I wanna start on pacisimus, because I like both of those things that I heard and it was some of the things I was thinking as well. So let's actually start with the latter one. So I wanna know, I wanna know, Robert, you know, how do you react to that? Because I'm not sure, maybe part of it I will say, as a physician, my disclosure would be, I didn't hear him saying that, so I'm just curious how you would respond. Well, I agree, I don't think I said that. I think, so, I think. Play the tape. And there is a tape, there is a tape, and you could all watch it afterwards on the Genome TV channel at YouTube, and I will get there later, go ahead. The framework here, I think, is that professional societies have for decades made professional guidelines or recommendations to try to improve the practice of medicine. So this is one of 10,000 such guidelines that gradually try to nudge doctors. They're not lazy or stupid, but they need to be guided by the professional societies, that's the fiduciary duty of the societies, to improve their practice parameters. So really, it's rather ordinary what we did. We created a practice parameter and made a set of recommendations that laboratories search for this information and deliver them to the physician. Then the physician can contextualize them, and I'll say more about that in further exchanges, I'm sure. Susan, I'm curious to hear from you how you would respond to this issue of that some of your arguments were in the past, you're digging up sort of historical legacy issues, and the world has changed a bit, and yet you wanna go back to sort of this historical figure. I would. I wanna. So I hereby summon the spirit of George Santayana, that those who forget the past are doomed to repeat it. That's my first response. My second is a lot of what I said isn't at all in the past. The fact that NIH was really stepped up to the plate just last year and convened a special panel to control the lax genome is enormously important and a recognition that there is something special about genetics and whole genomes, and they do need to be protected. They do need to be handled sensitively, and that's really dealing with the legacy of the past. That's just one of many examples. It's not all in the past. We still have issues going on in Native American populations, including the Navajo, I could give you a long list, the Havasapai, as you know. There is ongoing concern, difficulty even conducting genetic and genomic research, because there still is a problem in getting that true partnership and respectful collaboration to happen. You buy that? Oh yeah, I agree with her completely, but I don't think that there's more discrimination or insensitivity in genetics than there is in, let's say, mental health world, where there's tremendous insensitivity, there's tremendous discrimination. There's historical mini and maxi atrocities based on people with mental health problems. The difference is that there isn't millions of dollars for ethicists to write about and study the historical or current abuses of mental health ethics. And there is in genetics. It's an incentive. So is it wrong? Absolutely. Is it spectacularly different? No, not so much. I need to intervene that you noticed, Robert, I did something different. I did not say that genetics and genomics was the only sensitive type of medical information and I was the one who said mental health, substance abuse, there are even laws that give that extra protection. So I didn't exceptionalize genetics all alone on Mount Olympus. It's one of a category of things though it has a special history. So genetics is different but not so different, something like that. And I think actually that's one of the themes and it's almost what you just said because that's what I sort of got to say. I think it's hard to argue that genetics is different. I mean everything's different from something else. The question is whether it's spectacularly different from other medical information. One of the things I want to get clarity on is picking up on something that Robert also took exception with where you were talking about the air rate or the air is associated with it. And I'm particularly curious to unpack this a little because I'm trained as a laboratory medicine doctor, clinical pathologist, where clearly we're getting it right when you do a blood test, you do a chemistry test is critically important. But I also know that better and better technologies get you better and better and more accurate information. So is it your contention Susan that we will never get it right in terms of genomic information or are you simply saying that in here circa 2014 it's not quite accurate enough to totally rely on? And I think that's an important point because I would agree with you that today, everything's not perfect yet, but I don't think we should paint a brush of negativity across genomic information because it'll never be accurate enough because I think if you follow any medical technology it evolves with time it gets better and better. So I just want to get clarity on that. Yes, and I was doing two things. Number one, I was virtually quoting you from the 2011 nature piece where you said before genomics really moves full scale into the clinic, we've really got to get it more accurate. We do have an error transition to get through so that's agreeing with your second statement. But the other thing I'm pointing out is in the world of incidental findings, you know, and they're not just genetic and genomic. If you look for example at studies imaging the brain or imaging other parts of the body, they too encounter incidental findings. So we were looking for this, but oh my gosh, this looks like potential pathology. What should we do? And what we have found in that domain too is sometimes it's a false positive. And we have to be very cautious about inflicting that on people. You know, when Robert's committee, the ACMG came out with the incidental findings guidelines, there was I think a very important paper. I mean I was on it, but I wasn't the lead author. Wiley Burke was the lead author. Basically saying, you know, one thing that the committee did right was they were upfront. They said we really don't quite have an adequate evidence base to recommend all these 56 genes for what is in effect opportunistic screening, which is a fancy way of saying, well while we're sequencing your genome for one thing, your cancer, we're gonna just take that opportunity to look at some other stuff. That there were some difficulties in doing that. Because a lot of what we know about the penetrance of certain genes, for example, we've discovered by looking at symptomatic populations or populations where we knew it was a problem in the family, not just the general public. So we do have some evidence gaps and we need to pay attention to that. Be cautious. Yeah, so this is setting the stage. Let me make one point, especially since you quoted me. I feel I have to at least make the point. I completely agree that there's evidence gaps. I completely agree that we have to worry about accuracy. And I think it's interesting because some of the studies that Robert showed that Seek and I forgot the other name off the top of my head, these are exactly studies that are trying to examine this and to close that evidence gap and to improve those errors and to figure out what we're doing. So I don't think certainly any of us, and I'll let Robert speak for himself, but I don't think the field of genomics believes that everything is here and now for full-scale clinical deployment. But what we're trying to do is develop a set of studies that will refine this so that down the road to be defined how many years it will be in a position to be deployed. So I think we should also separate on this discussion the here and now versus where we're gonna be five, 10, 20 years from now. Okay, so we've set the stage. You can see lots of issues we can unpack further and we're gonna want you guys to get involved. So we're gonna take a break now. There's refreshments outside. I think there's index cards outside or something to write on. And please write down your questions and then I'm gonna pick some of them and we're gonna come back in how long? About 20 minutes? 15 minutes. We're gonna come back and we're gonna start to ask some of your questions of these two speakers.