 Thank you, Jean, for inviting me, and thank you to the NIH for giving a philosopher an opportunity to deal with these issues. So I'm going to be presenting work that came out of an NIH-sponsored working group that produced the volume that Jean mentioned, which is the forward, which is the button, this. Okay, so I very much like this quote from Professor Lee Kemp that describes microorganisms impact just about everything, animals, plants are merely along for the ride. And what this says to me is your study of the human microbiome and the microbiome in the world has really changed our view from the human being the center of our focus to actually were kind of insignificant compared to the microbiota around us. So going on to LC issues, you all know about the scientific background and goal of the HMP. So getting to the LC issues, an important issue is identity. So finding out that there are all these critters living on you and in you, people can find that kind of yucky disturbing, and that could change how we think of ourselves at least for a few minutes when you first hear about it. So the idea of self-identity may change because all these critters that live in us and on us are changing very quickly. They transform themselves. They have a very short life cycle. So what will that do to our concept of ourselves? Well, probably not very much. In the previous slide you saw these photos. Let's go back there for a moment. These are photos of grandmother of a colleague of mine, and you can see the philosophic issue of how can you remain the same person as you change over time? And we get used to the idea that we change over time and the idea of the microbiome in us changing as we age probably will not be that transformative to us all together. The bigger issue is going to be thinking of ourselves as much more part of the environment and not so distinct and separate from it. So it will require us to pay a lot more attention to our environment. As is already mentioned, we've been very good at wanting to kill off the microbes and focusing on we've got to get rid of them. We've got to stay clean and eliminate them and now we've gotten this new positive view of the microbes. They're our friends. They'll what makes us healthy and probably both views are somewhat of distortions and this very positive view will maybe lead people to buy a lot of probiotics and maybe teach mothers to have their children eat dirt. Both of them probably a little bit off the deep end. Another important ELSI issue is the issue of privacy or confidentiality and I've tried to distinguish them. So privacy is a concept from common morality. It typically defines what's in our thoughts, what's in our bodies, what's in our bedroom behind the closed door, behind the locked door of our house and that's a private domain. In medicine we talk about a slightly different concept called confidentiality and in the literature these two concepts get blurred and confused and I think it would be very useful particularly for science to keep these ideas separate. So confidentiality in medicine defines an artificial space that we create for doctor-patient communication. But when the doctor shares the information from the patient with the doctors who are taking over the 24-7 care of the patient or when the doctor shares that information with a colleague who's more expert in inflammatory bowel disease, we don't think of it as a violation of confidentiality. The clear space is defined by a need to know, not by a particular individual speaking to another and we're very good at protecting that confidential space in medicine based on need to know. And the question I want to raise here as an ELSI issue is whether this concept of privacy from common morality is more appropriate to thinking about biomedical research or the concept of confidentiality, the biomedical concept of professionalism. And you notice we have this idea of confidentiality in other professions, certainly the priesthood, but also in law. So when the lawyer hands off the papers to his assistant or his secretary, there's no violation of confidentiality because all of the people involved accept that the information will be shared. So I'm pointing out here that this distinction between privacy and confidentiality is probably important to keep in mind and probably in science we want to uphold the idea of confidentiality from medicine rather than privacy. Now this comes up a lot in sharing samples for studies of the human microbiome. So certainly we know now that individuals might have unique metagenomic genotypes and that makes the human microbiome very attractive to Homeland Security and to the FBI that could use it just like fingerprints. And we've already seen some of this appear in TV crime dramas where they've used the microbiome to track down the criminal or the poop on a ship I saw was used to disprove some theory of who committed a crime. So it's already in the media and it will be coming soon to Homeland Security and the FBI. So certainly we want some kind of protection for science that deals with human microbiome. We want some kind of protection similar to Gina, but not exactly because there are problems with Gina and probably we want the samples that we collect for human subject research to be subpoena proof so that they couldn't be used in criminal investigations and they couldn't be used in immigration investigations and people will feel safe in donating their samples and contribute to the research. Another important ...did this go? Another important issue related to ELSI is property and the concept of property is a socially constructed concept and some features of the microbiome make us think of it as property. So it looks like a treasure. It comes from us. It's in us and on us and you generally need permission to take people's samples. Other features of the microbiome tend to make us think of it not like property. Like discarded items. The things we throw in the garbage or flush down the toilet. So what is human microbiome property law? So if we think about property law, we have our understanding of property law come from three different philosophic directions. So most popular in the United States with the Libertarians is the Lockean view that if it's in your body or on your body it's yours. If you've mixed your labor with it, I don't know, by digesting the food then it's yours and nobody should muck with your property. Another view we get from Rousseau is that whatever is here is the bounty of the world and it should be shared for all of us for the common good, the way we put up all of your findings on a commonly shared website. And a third view of property, not very much discussed or as popular, is actually much closer to what we use. And it's the idea of property that we inherit from Thomas Hobbes. And this idea is out there, the state of nature, the Garden of Eden, nobody owned anything. We make up the rules. And we make up the rules of ownership to be governed by what's useful for us and those rules can change based on what we find to be useful. So property law is a dynamic patchwork. And laws and policies related to the microbiome should be designed to avoid harm to individuals, promote the social good, and avoid undermining important social projects. And there have already been numerous cases related to property that have come up with the human genome. You've seen some of these chakrat, I don't know how to say chakratberry, certainly myriad genetics which just settled, but it's been around for a while. The story of Heronry et alax was very popular about a year ago and John Moore's spleen samples for leukemia treatment. All of these have been controversial cases related to property rights in the human genome. And I don't know of no such cases related to the human microbiome, but they're sure to come. So thinking about ELSI, another important issue is of course human subject research. And if we think about human subject research related to the human microbiome, there are at least three kinds of research. So there's the focus of the HMP, which is the collection of samples from a broad spectrum of subjects to answer very general questions about what is the human microbiome. Then there's the examinations of individuals to understand the role of microbiota in the development of specific diseases. So you're looking healthy and healthy normals and disease people and try to see how their microbiomes differ. And then there are already some interventions using probiotics and bacteriophages to try to cure diseases or at least ameliorate symptoms. So I think these are very different kinds of research and they raise different kinds of issues. So the first kind, the general observational studies, focuses on these general kinds of issues. And they are done largely using biobanks and you're going to advance knowledge gained from microbiome studies for broad application. The most critical feature of these studies is that once the samples are collected, biobank research will pose only negligible physical risks. So once they have your saliva sample or your blood sample or your stool sample, there is no harm involved. And two important points follow from this. So first the samples come from multiple sites on a very large number of individuals often. The studies are very time consuming and costly. And then for them to have a significant research payoff, samples and data have to be widely available to researchers for use in many studies. So the American people are investing hugely in these projects. We, the American people, should want to get good bang for our buck so we want this material to be used. The second kind of research that compares the healthy normals and the diseased people is again largely observational and it involves comparison. So again, very little harm is involved. The third kind of research, which could be like infectious disease research or drug development research, certainly could involve risks even though people want to describe probiotics as being safe. There could be risks and we don't know what will happen. So I think there are important LC lessons to learn from this analysis is that not all studies require the same level of oversight and different rules may be appropriate for different kinds of research. Right now we have one set of rules that apply to all of it. So biobank studies and informed consent and this is a very hot issue and being discussed all around the bioethics, research ethics world about whether informed consent should be required for each reuse of a sample that's in some sort of biobank. And what our working group concluded was that informed consent is not always ethically necessary because the research using previously collected microbiome samples involves only hard to imagine de minimis risks of harms. So this is a radical departure from standard regulations of research ethics that says that say informed consent is absolutely essential and what we think is maybe not. Certainly it's essential when you're doing something that's high risk imposes people to some kind of dangers but when there's no danger, vanishingly small amount of danger, we don't think there's a need. The benefits of findings to future patients could be significant and then once you've stored something in a biobank it's difficult time consuming and often impossible to re-contact the sample donors and get their consent. And if you think about informed consent and all the requirements to get genuine informed consent people have to consent to the specific uses of their sample and it's just not reasonable. So we publish this in an article in American Journal of Bioethics, the most read bioethics journal. Now related to this issue of informed consent is public health and privacy protections. So we already have surveillance in public health and surveillance is a very important tool in public health and then we have public health measures and quality assurance and quality improvement activities. All of these involve collecting data and they all provide a social good that could be very significant and the risks to humans involved in these studies is just not there or de minimis and there are very, very small risks to infringements on privacy. Now we currently have regulations that distinguish public health surveillance, quality assurance and quality improvement from research and public health surveillance, quality improvement and quality assurance are listed as exempt categories. So according to current regulations you do not need informed consent to be able to undertake these activities but if you look at these from a philosophical point of view they're all scientific activities. They all employ data collection and analysis and draw conclusions on that data and they're all designed to produce quote generalizable knowledge. So the regulations distinguish generalizable knowledge from other knowledge, I think all knowledge is generalizable. In the medical literature, the medical literature is full of case reports on single cases and they're published because other people can use them and learn from them and apply them. So all knowledge is generalizable so these distinctions actually make no philosophic sense. Now biobank studies, wait, we did this, so biobank studies, public health quality assurance and quality improvement already employ very significant confidentiality protections. The NIH does offer things, certificates of confidentiality but they have no legal bite to them. So we do need some legally sanctioned mechanism to protect the confidentiality of study samples and studies but if that were fixed then we, I don't think we have a need for informed consent when there's no real risk to humans. And when obtaining it would be difficult. Another ELSI issue has to do with harms and one problem is this use of antibiotics and antibiotics are terrific when they kill bad bacteria but they might not be so terrific if they kill good bacteria and we just saw we may not be completely resilient after the use of multiple doses of antibiotics. So antibiotic use has already been linked to the development of some diseases and some conditions recently that have not been as prevalent before like obesity, inflammatory bowel disease, allergies and asthma. So people have thought that there's some association between these things. Now one last issue I want to talk about for a minute is probiotics and the human microbiome. So probiotics are defined as live bacteria that are said to be safe and a health benefit. That's according to the World Health Organization definition of probiotics. However they're not evaluated by the FDA for their safety or efficacy because they're categorized as a dietary supplement. So the only way you can get into trouble is if it turns out that what you put on the label somebody complains about and it's found to be false. But manufacturers are not required to provide any information about the product's ingredients. They don't have to list the strains and you will know that strains of bacteria could be particularly important. They're not even required to say whether they're alive or how much is in a pill. So we don't know very much about the products being sold as probiotics or prebiotics. We don't know what they do. We don't know whether or not they survive to get to the gut. We don't know how long they survive, what effects they have on patients or what effects they have on others. Now if you were the manufacturer of a product, one of these probiotics and you could sell it and people wanted to buy it because of all the hype of the microbiome and you could sell it without proving that it does anything at all, that would be terrific. If you try to prove that it's effective, it might not be and it cost a lot of money to go through the test. So the manufacturers are very happy with the status quo but is the status quo good for society? So there's this other new kind of therapy. I understand that people in Yonkers are working on developing it but there is a place in Georgia. Georgia not the state in the United States but Georgia up by Russia where they're actually providing phage therapy. So these are viruses that can disintegrate cells and people think that this could be an answer to problems of using antibiotics. You can just put some phages on a surgical site and that will destroy the bacteria or people with bed infectious diseases can get their diseases cured by introducing the right phage that will destroy the bacteria that's causing their illness. Now synthetic biology could be used in the future to improve the effectiveness of phages and probiotics and they could expand the life span of bacteria and viruses. They could make probiotics and viruses more resistant to mutation. So one problem with phage therapy is we've got the phage that works that kills the bacteria we don't want but by tomorrow it may have morphed into something that no longer works. Synthetic biology could also help make probiotics and phages that can survive to transport. So it could be very useful but all of these things could be also dangerous. So in conclusion scientists are just beginning to understand the human microbiome. A great deal will have to be learned before the microbiome interventions become feasible and bacteria have already altered the planet. They've created our environment for us and they can alter the planet in the future so caution and foresight is in order. That's it. Thank you. And I think again just because we're running a little behind on time if anyone does have questions for Dr. Rose she'll be available during the break and be happy to take them then.