It's interesting in terms of vaccine to wonder why there's all this excitement and all this interest in essentially a new form of vaccines at this time. And as Jim indicated, the vaccines that we're now dealing with are today are considered through a relatively new method of producing vaccines and that is using recombinant DNA technology to use a vector and put in a desired gene that will express an antigen that will immunize somebody. Now if one goes back historically and you think in terms of recombinant DNA when it got started and the horror stories that were told about what was going to happen and the indication was that if we ever did the sort of thing that we're doing now that instead of having a vaccine, a virus that didn't produce anything, if you put in a foreign gene it's going to make it a horror and the world will be dead very soon. Well clearly this isn't true. Then the next question one might ask is why since there have been so many successful vaccines do we even need a new method? I mean after all we're still basking in the glory of eradicating smallpox with a vaccine. There's been tremendous success with poliomyelitis with a vaccine, with measles, with mumps and a variety of others. So the question then is why do we need this new technique? What I'd like to do today is to discuss the objectives of what new vaccines are about and how we're going to look at it. First I'd like to review what a successful vaccine is. Then I would wish to discuss the successful vaccines that we have today and finally what major vaccines we need and why don't we continue making them the way we made successful vaccines before. If we're going to have a good vaccine, whether it be a vector vaccine or the old one, in the first place it must be one that does not produce any adverse reactions. Now they can be of several types. One they can be of just the direct effect of the vaccine that one gives. In other words, even with vaccinia and the vaccine with smallpox, children that had congenital cellular defects in their immunity had very severe reactions often leading to death. One can look at another type of reaction, even the successful flu vaccine today. It's not unusual 12 to 24 hours after receiving the vaccine to have a syndrome very similar influenza. But there can be even worse things and that is two types of vaccines that had been made, one against respiratory syncytial virus and one against measles virus, which was a commonly made vaccine by an activation in activating the virus from aldehyde. What happened is these people got perfectly good antibody responses and had no direct effect as a result of the vaccine given to them. But year, two years afterwards, if they got the natural disease, the disease was actually much more severe than the common one, than the ordinary disease that these viruses would produce. And also there are some vaccines or experimental vaccines in which subsequent immunization had become worse. Now clearly the vaccine, if it's going to be successful, must produce the appropriate immune response in the appropriate time. Ordinarily we've been accustomed to looking at neutralizing antibodies. But we're now facing at least one disease, AIDS, in which this may not be adequate and that we may need to produce an immunity of a cellular type, particularly if the infecting virus enters in cells rather than its free virus. And finally a successful vaccine must have immunity of sufficient duration. Now what are, how do we come to this reaction? Now I'm not going to go into this slide in detail, but it's important to understand what neutralization is because the ability of a vaccine that produces humoral immunity, that is antibodies that circulate in our blood, must be able to neutralize the virus. And so one must make an antigen in every viral protein, of every protein of a virus that's antigenic and makes antibodies, does not produce neutralizing antibodies. So it's very important to understand exactly what neutralizing antibodies are. And I find going around the country and even giving some lectures in people's courses places that there's great confusion about viral neutralization. So I thought that I would bring it up today at this group. It's a reversible reaction. If you add antigen and antibody, if I can do better with this, they tell me, the virus when it reacts with the antibody follows a law of mass action, which means that it forms an antigen-antibody reaction which is then reversible. The most important part is that it follows single-hit kinetics. I can't see it on that screen, that's the problem. That is that it doesn't require large amounts of antibodies to neutralize the virus particle. It takes some place and it depends upon the virus between one and four antibody molecules. It doesn't require a huge amount of antibody and you can understand the need for a successful vaccine. For the antibodies to be effective, we cannot have in our blood over any period of time antibodies that will neutralize at very high concentrations. You can't cover all the sites on the virus with the antibodies. It really only takes one to four antibody molecules to neutralize a virus. It's not an antibody that necessarily prevents absorption of the cell because every virus has a large number of components by which it can attach to a cell. If it required that every one of those attachment sites was covered by an antibody, we would have great trouble in attaining an antibody type. It could have accomplished this task. It's not antibodies that merely produce aggregation of the virus. In some way, and this is a step which is the heart of the matter in which it's still not fully understood, in some way that one to four antibody molecules prevents the encoding of the virus so that the genome of the virus can get into the cell. Now that's what our vaccine must satisfy if it's going to be one that produces humoral immunity. So we must determine what is the antigen that produces neutralizing antibodies before we begin to make vaccines. And unfortunately for some of our major diseases today, that still has not been determined. Now here are the successful vaccines that we have today. It's quite clear that the most successful one is smallpox. It has had tremendous success. It's the first vaccine that was ever developed and it's been our most successful because it has indeed eradicated the disease. Poliomyelitis has been extremely successful. Both the live virus vaccine and the killed virus vaccine which has been used differently in different parts of the world have both had prominent success. So we don't have to argue whether one should have a killed virus vaccine or a live virus vaccine on the basis of poliomyelitis but really on the disease and the virus that we're working with. The live virus vaccine from measles has likewise been extremely successful as has that for rubella, yellow fever, which is another very old one. Adnoviruses, although it's not commonly used as a vaccine, is widely used in the armed forces to prevent disease that recruits get and that has been an extremely successful vaccine. Rabies has had a somewhat varied history and the complete benefit of rabies vaccine as we use it today is still not as clear in humans. It's certainly a very valuable vaccine in animals. We're just getting to the use of hepatitis A and B vaccines and from the experimental data and they've not been widely used yet. Certainly hepatitis B, done with the surface antigen of the virus, appears to be quite a successful vaccine and hepatitis A also seems to be following. And again, varicella zoster virus, which produces chickenpox, has not been used extensively yet but it's been used in a very critical population. That is, young children who for one reason or another are getting transplants and getting drugs that suppress their immunity and they, to prevent reactivation primarily of the varicella zoster virus, they have been immunized and it's been very successful thus far. Well now if that's so, what then are the vaccines that we really need today? And clearly heading the list is the causative agent, at least I believe is the causative agent AIDS and I didn't see Peter Duisburg walk in so I guess it's all right but I can still say that. But that is, we all recognize as a very serious disease and one in which a vaccine is badly and tragically needed. Non A, non B hepatitis which is now the prominent type of hepatitis that is affecting the world. Also commonly most often transmitted in blood transfusion is badly needed as is hepatitis D or the delta agent which is commonly carried along with hepatitis B. Road of viruses which can produce very severe disease, gastrointestinal disease in children as being prominently worked on here at the NIH by the leaders of the world in the field and the same holds for respiratory syncytial virus which is a very severe respiratory disease in young children and that too is receiving great attention here at the National Institutes of Health. Parainfluenza virus which is closely related in the same family as respiratory syncytial virus also produces severe respiratory diseases in children and we all know about the common cold virus. We've been wishing for a vaccine to produce the common cold for many years and it's really a very difficult field because there's at least 113 it's probably more different types that are immunologically distinct viruses, rhinoviruses that produce the common cold so that becomes very difficult. Some recently that is within the last few years adenoviruses that produce the most severe gastrointestinal disease in children types 40 and 41. Dengue virus has been haunting us for a long time and if one read the newspaper a couple of days ago we realized that it's becoming prominent again and the world would be very much better off with a Dengue virus vaccine. Two other encephalitis vaccines Eastern equine encephalitis which is not uncommon in the United States and certainly more common in other parts of the world. Japanese B encephalitis and the string of herpes viruses. Herpes simplex one and two, cytomegalovirus, Epstein-Var virus clearly one could add more and you recognize this is just diseases of humans. If one thinks in terms of the diseases by which a vaccine would be very important then the animal in the veterinary world this becomes a huge list. So what are we going to do about it? I want to recall for you what the successful vaccines were and you see it's not entirely clear as to whether live virus that is a tenuated virus or killed virus vaccine is going to be the most successful. Smallpox was eradicated using an attenuated virus it really wasn't even a smallpox virus but a very closely related virus which was many a virus which was employed dating back to the days of Yenner. Poliomyelitis you can have either a living or killed and we've been through this so there's no clear evidence as to what type of virus was needed but we think in terms of some of the diseases that I showed you in the last slide and it becomes clear that we couldn't possibly approach a disease such as AIDS with a virus that was living because we'd have no way to test its virulence it would be impossible to know whether it would produce disease or whether it was even though we played with a lot of genes I think the possibility of testing a virus that was alive in humans would be impossible and we have no good animal model to date we couldn't even think it would be very difficult although the agencies may tell us different that it may be very difficult to even test a killed virus vaccine in humans even if we thought we had a chance of doing it so if we think in those terms then that gives us a clue as to why there has been such great interest generated in vector vaccines now by a vector vaccine what we mean is choosing a virus as the vector that is a virulent or essentially a virulent and that's why Bernie Moss and his colleagues particularly look to vaccinia virus now I hope none of congressman Dingell's representatives are here because I'm going to produce or do a lot of perjury today and this first slide is certainly an example of it because Bernie Moss gave it to me so I'll give him credit I may forget to give credit to everybody else's whose slides I use but none of the work is my own now the way that this vaccine is made is to I have to take a course to run this thing don't you it's like playing computer games there we are now what one does is take a bacterial plasma cut the gene out that expresses the antigen that one wishes and that's there in black that's the foreign antigen and you can pick out that gene and the antigen that it will produce the gene that produces the antigen one wants from any virus using recombinant DNA techniques and putting it into a plasma which is a bacterial plasma and replicating it there in large amounts then one can take and the way Dr. Moss and others have done this commonly is to co-infect a cell with the plasma and with vaccinia virus and by doing that one will get the gene the foreign gene that you're interested in this really doesn't show as well get the foreign gene that one is interested in to recombine with the vaccinia virus now these this is done very cleverly because the foreign gene is put into the into the is contained on either end with the thymidine kinase gene also taken from the the thymidine kinase gene is first cloned into the bacterial vector the plasmid then the gene that you want is inserted within that region then when one transfects the cell by recombination with the DNA of the vaccinia virus recombination within the terminal regions that contains the thymidine kinase gene now by inserting the foreign gene within the thymidine kinase gene it produces and recombining within that it produces a defective thymidine kinase virus now this has using the thymidine kinase gene on either end there's two things for you when having a deletion in it one it permits the recombination of that and secondly it gives one a selective marker because the virus that does not have the thymidine kinase gene is not inhibited by such compounds as bromodoxyuridin which ordinarily will prevent the DNA of the vaccinia virus from replicating so it acts as a selective marker so you're not having a mixture of the recombinant virus and wild-type virus and this is a very common way in which the vaccinia virus has been used and as you'll see later that the same method is being employed with other viruses now this is another perjury in Brian Murphy who lent me this slide is sitting here in the audience and it's a way in which the vaccinia virus is being used to reconstruct a vector vaccine with the respiratory syncytial virus and the same technique was done was used see the thymidine kinase the here is the thymidine kinase gene the respiratory syncytial virus G protein was inserted within the thymidine kinase gene and also they used other genes to permit selection of this since the thymidine including the Lax-Z gene now in that way the virus one gets a the G protein which produces neutralizing antibody for respiratory syncytial virus inserted within the vaccinia virus now this virus is then used in the same way in which one would immunize a person against vaccinia and one theoretically will get antibodies to the vaccinia virus as well as to the G protein of the respiratory syncytial virus and those antibodies should neutralize the virus when it enters if it's of high enough concentration and as we'll talk about some of the problems that this gives us subsequently now if the vaccinia virus is so good for vaccines why do we deal with other viruses why don't we just use vaccinia virus for all vectors and not bother with other vaccine vectors the major reason is that one gets immunity against the vaccine once it's used against the vector and so you can't repeatedly use it and necessarily get good infection any more than after you use the vaccine one get one does not get infected infected with smallpox for a period of time so I think that no matter what vectors we use we're probably going to have to have a whole library of different vectors in order to escape the immune response of each one and one of the common ones for the same reason that vaccinia has been popular is adenovirus it's been very well proven in the armed forces that there are strains of adenovirus which can be fed to humans very easily and not produce disease because it's been a very successful vaccine in the armed forces and millions and millions of people have been immunized with the various types without any adverse effects so this became a very useful also very useful vector and again the adenovirus has been done by somewhat different technique and that is a large segment of the adenovirus and here you can see running from 76.8 map units to 100 map units that is the entire right hand end of the of the genome has been cloned within the PBR plasma so that large amounts of it could be made and then inserted in a very region one can insert a foreign gene as we see here now that is being done in a region and I'll point it out to you in a moment called the early region 3 and the region that's a very convenient place to insert it is that that region although it plays a real role in the pathogenesis of the disease it's not a region that's essential for replication of the virus one can insert there and the virus will become a very effective replicating virus then by a different type of recombination this piece of the DNA from adenovirus from 76 point the whole all about one quarter of the viral genome is cut out of the plasma and co-transfected into cells with the wild type DNA it's cut in a single place that goes from 0 to 85 now this sort of overlap permits a recombination event so that one then obtains an intact living virus with the new gene inserted in the region that we call the early region 3 and as put here now here it says envelope and that could be the influenza envelope gene it could be the hiv envelope gene it could be from a variety of the of other viruses where neutralizing antibodies are made against that gene this is just another example of how it can be done this was done by Paul Hung and his group at Wyeth and the H.S. stands for hepatitis surface antigen which is the antigen which is necessary for producing immunity to hepatitis B virus and it's put in it's inserted into the same region of the genome the E3 region which you see up there and I say that whole region can be deleted without any effect on the viral replication so that the same amount of viruses made whether that region is in or not and two different types of vectors were made the E region was was deleted entirely or almost entirely and the new gene put in there or it was made as a vaccine as you see here using the deleted E3 with the hepatitis or as shown above without any deletion the advantage of using the deleted virus is that packaging is much more efficient in other words in many viruses the coating of the virus is a very rigid structure and so only a very specific amount of DNA or the genome is allowed to enter there if the virus is going to assemble properly so the advantage of deleting essentially the amount of virus the amount of genome that you're putting in in the foreign gene permits much better packaging of the virus by this type of of vaccine has an advantage where you delete that region and then put in the new genome the new gene and this is just another example of of a different type of insertion and that is an insertion in which they made which was done with both the hepatitis B surface antigen or the HIV envelope and it was done by insertion at the terminal region now this virus because of the packaging limitation that I mentioned previously has some real disadvantages because the packaging is much more difficult but in general it has worked to a relative extent and there are other other ways these vectors have been made using the adenovirus in what we call the E1B region and others in which we call the E1A region and the success of those has not been demonstrated as yet but they are being attempted and tried at the present time now as I said these are two viruses in which there's widespread immunity or widespread immunity develops particularly in the adult population so that you can't continue to use them as vectors and a whole variety of other viruses are being attempted and here's one in which the varicella zoster virus has been used in order to as a vector now the procedure is almost identical to that employed with vaccinia virus and that is the gene the gene that one wanted was cloned in a bacterial vector and then it was by recombination the it was done within the again within the thymidine kinase gene of the vaccinia of the varicella zoster virus and by again homologous recombination the new vector was prepared and here is the the new with the all of the varicella zoster virus except the new gene which was inserted and this happens to be the eb virus glycoprotein against which neutralizing viruses may now the eb virus is particularly important because it's the virus that produces infectious mononucleosis and it may have some role in a variety of different lymphomas and that is not quite as clear to everybody now I guess that's then there is one other use of viral vectors which is different than for humans which is different from that that I've mentioned this also I have obtained from Brian Murphy and that is the use of the of a virus called the baculovirus baculovirus is a plant virus the value of using it to make large amounts of antigen is one can replicate this virus to extremely high titers in plant cells in cell culture if you insert a gene such as here the type 3 para influenza virus within the baculovirus one can make very large amounts of protein in the cell culture and then purify that protein to use it as a vaccine in other words you're making a vaccine out of purified protein it's been shown with a variety of proteins that one can make except very effective vaccines that way for example one can make a very effective vaccine for influenza virus out of the hemagglutinin gene product the hemagglutinin of influenza virus it's not done because it's not it costs a lot to do it and therefore the pharmaceutical houses apparently have not desired to make a vaccine that way but one would eradicate as far as one can tell the bad reactions that one gets to are presently used vaccine so it's it probably this type of even though it's not as convenient to use as a vector such as adenovirus where one can feed it or vaccinia virus where one can merely scratch the skin this requires injections and therefore is much more difficult to use particularly on a worldwide basis in a number of the developing countries so how widespread this will be but my guess is that in the future in this country that it will be successfully used could I have the lights please that was the last slide now this isn't all of the viruses that are being tempted to use as vectors there are many more for example poliomyelitis virus has been shown that it can be a very successful vector herpes simplex virus can be used as a vector whether that can be attenuated efficiently in order for it actually to be used in the population is not clear and one can go through a whole list of viruses where we have the ones that are particularly value are those in which we already have an attenuated viral vaccine from a virus to use that as a vector and that's one of the advantages of poliomyelitis virus we have the live virus vaccines they've been shown to be at least relatively safe there is a rare reversion but it's not a very common event and it depends upon how severe the disease is that you're trying to prevent as to whether one will ever use it but we certainly have found poliomyelitis to be a very successful vaccine even though there are occasional reversions and occasional disease produced by the vaccine itself we've done an extremely good job in lowering the incidence of poliomyelitis and even eradicating it in some small countries so it's my prediction that there will be a number of different viruses used as vectors but I think that in almost all of the cases there are going to be viruses one in which you can prove the safety of them and probably most likely those in which the safety has already been proven by a variety of other clinical trials and again I'll repeat the advantages of having a variety of vectors is that we're going to have a lot of diseases out there that we're going to want to prevent and so we want to be able to change vector after vector to escape the immunity that the previous viral vector would produce now there's both good news and bad news relative to the virus vector business the good news is that using all of the modern technology of molecular biology and molecular biology they're really quite easy to construct and if we have the right vector we can do very well certainly in cell cultures these recombinant vaccines are very well expressed both the antigens for both the vector and the new viral gene are both very well expressed and usually in experimental animals they produce good antibody production against both of them the other good news is that it appears that these live viral vectors just as the live virus vaccines produce both cellular and humoral immunity and if we have diseases in which that combination is advantageous or if just cellular immunity is alone is what is really needed it appears that it will be possible to do this with the viral vector vaccines then what is the bad news the bad news is that examples that have now been tested in the proper animal models we don't always get the same antibody production that we got in other events even though in cell culture they're perfectly visible and I don't think that Dr. Murphy will mind that I say that this has been one of the problems with respiratory syncytial virus in a vaccinia vector although it made good antibodies in simple tests such as in mice when put into the chimpanzees where they could be challenged with respiratory syncytial virus good immunity was not produced to the respiratory syncytial virus antigen the reasons for this it doesn't mean that it can't be solved the reasons are still somewhat unusual but again it's the idea is why one wants to go to a variety of viruses and perhaps this can be solved by just having a different viral vector now maybe the way the antigen was produced could be inserted or there may be a very different reason for it and this has to be it theoretically it should be an extremely effective way of producing it now the other part of the bad news is that I'm not sure it is bad news if one looks at the adenovirus where one delutes the deletes the E3 and you look in certain animal models this actually does something and increases the virulence produces a much more severe disease than the wild type virus now this seems unlikely to happen in the general population of humans because the viruses with deleted E3 regions are very common in our population and yet there's absolutely no evidence that in the diseases produced that they have become the predominant virus to produce the disease so even though in an experimental model it may appear to increase virulence it may well be that in the general population it's not going to have any when fed or even as spread in the respiratory root that it will actually do this so that animal models and humans may not always be the same things and eventually even though some people may object both to our use of animals and to our use of humans eventually if you're going to produce a vaccine one is going to have to get back to the humans in order to test it now there's there's obviously problems that we have to face but I think the hopes are high I think there's good reason to be encouraged and hopefully we'll be able to have new and good vaccines against the viruses that are still plaguing thank you


Unfortunately over the last five years we've been dealing with undue creativity and onboarding on illegality and we're having to deal with the hangover from it. In the same sense, we've had a situation where we've had creativity in patent rolls and in large strategics who are looking to utilize a court that was never intended for these kind of cases with the International Trade Commission's court where they are only, if they find infringement, the only thing they can do is issue an injunction. They don't have the ability to apply appropriate remedies. And as a result, you have trolls that don't have standing to get an injunction in the district court utilizing this ITC court and we've got dozens of cases that are actually being brought by trolls and companies like Microsoft and Apple are also using it as a complement to their district court cases to apply pressure because in that situation, when you're faced with the potential loss of access to the U.S. market, you will sign a royalty agreement that is not market because it's not about the licensing and litigation is not about necessarily the nature of the patents that are being asserted and litigated. That's part of it, but you have to think about the context. Ownership by the most cash-rich companies in the world of patents that could also be held by a small, medium-sized enterprise places those patents in a very different position and a much more dangerous position for open source and for the Linux community. Okay, perhaps it seems to me there's a common theme here. We've been talking about the successes in the world of openness, but they are being overshadowed by larger changes, particularly of legal systems that just can't cope with the modern world in terms of the sharing that's going on and the way that those systems are abused. I wonder if anyone's got any questions at this point about some of those issues that have been raised? Yep, can we have a microphone, please? Thanks very much, gentlemen. So one comment and one question. To Simon's point at the beginning, the question, why so much bad law so recently or why so much bad regulation so recently? One, I mean you mentioned the fact that the internet is profoundly changing the relationship between creator and consumer. It's also profoundly changing and going to change much more the relationship between citizen and government. And I think that one of the things that's happened in the last two years is that government has woken up to that fact. And so we're no longer just dealing with corporate lobbying, we're also dealing with governments who are recognizing that their interests are profoundly challenged but for example by looking at what went on in the Arab Spring in early 2011 and looking at how networks of loosely organized people can achieve profound change regardless of whether the government is involved or not. And I don't think that that's a coincidence. And my question, which is more to Keith, is your analysis seems very insightful. Do you have any proposals for remedies to this situation? Thanks very much. Regarding the ITC, we've actually been actively lobbying over the last 12 months. There's I don't know how much detail people want to get into but I'll try and keep it at a high level. The 1934 Act for the ITC actually created a provision whereby products that were created that uniquely enable innovation and enable economic benefit for the national economy that those should be kept out of ITC's essentially hammer and so that you wouldn't adjudicate a case there or even if you did find infringement, you would kick it back out to the district court for ultimate application of a remedy because the economic detriment to the US and its competitive position would be such that you wouldn't because of the public interest being served you wouldn't allow for an injunction to issue. We are claiming that we've had papers prepared by economists at Oxford as well as by legal scholars in the US to talk about how the public interest should be invoked in situations where Linux and open source based products are the subject of a litigation in the ITC. In this way, we remove one of the arrows from the quiver of large strategics and of trolls that are attempting to sue based on Linux to be able to slow or stall Linux. I mean, understanding the context of this is very important. This is, we were going to have multiple platforms and I should mention that hearing Mitchell's comments earlier about a new OS coming out, which is a far more open OS coming out from Mozilla is incredibly encouraging because we wanted to see Web OS get traction in the market. We wanted to see Tizen get traction in the market, but it seems like it's somewhat stalled. We wanted to see the platform that the Mego platform, which essentially was bought out by Microsoft when they made an investment in having Nokia essentially exclusively use their platform. These were other platforms that for one reason or another have not caught hold in the marketplace. So it's a one front war. It's a lot easier when you're in the game of working potentially collaboratively with other large strategics to be able to layer on total cost of ownership to get to the point where it's uneconomic to utilize the only mobile Linux platform out there. And so we're looking at the effect. It's not that Android represents Linux per se. It represents a utilization of the Linux kernel, but there's lots in there. If you look at the stack, the Linux kernel is way down there and what people are suing on is way high in the stack. So it's really not Linux, but in so far as they're eliminating a Linux product from the market, it's concerning to us. Okay, thanks very much. I'd also like to turn your comment into a question for the panel. Do you agree that the governments of the world have woken up and are now the enemy? So listening to your comment there, I've been very pleased over the last year the degree to which for example the UK government has sought comment on new legislation or at least parts of the government. There's people from UKG in the audience who've done a fine job in that regard. Nonetheless, when I see new legislation starting out in the UK Parliament, it seems to me the only voices that have been incorporated into it have been the voices of corporate lobbyists. And it seems to me that the role of government in preparing that legislation has been to crystallize the consensus of corporate voices without considering the needs of citizens who are both creators and consumers. So while I agree with you that it's started, I still feel there's no one in government speaking for me. And the difficulty that produces is that when we're talking about European legislation, I can't afford to come here to join in a think tank that's happening in the Parliament building or that's happening in some other city in Europe. There are people in this audience who are paid to travel all over Europe, stay in hotels and sit in committee meetings. I know, because I used to be one of them. But the citizen-creator consumer is not in a position to come and participate semi-full-time to full-time in consultative activity. And mechanisms for citizen feedback that rely on being able to understand there was a questionnaire about a bill in the UK Parliament recently that was about 26 detailed fuzzy questions that required an essay answer that would have made a thesis for a doctorate look moderate. And now it was good, it was consulting the citizen, bad, no citizen was in a position to respond to the consultation. And so you're doing a good job to open up, but it's just not working because the only people who can really participate are the paid lobbyists who are already perfectly well-represented in the legislation, thank you. In your world, no. Well, I can see that you are suffering from consumer blouse, which is being always in the minority, in the corner, and never having your voice heard as consumer lobbyists, this is something that is always happening. It's interesting that now with the openness theme, the, as you call it, the enemy, maybe might be changing for us. In the past it was the big corporations, now maybe it's going to change, or maybe the people suffering from the consumer blouse are different than in the past. Maybe we are going to get it all at the end of the day, I don't know. But what is interesting for me is that you said that this issue about the consulting, the consultation, the fact that now the process is open, at least at the European level, there is more and more the use of these online tools to make the people participating. But it is true that it is a double edged or double kind of meaning because the tool might be open, but the questions themselves are very, very difficult to understand and ourselves as the organized consumers. Sometimes we have a difficulty because the question is asked to an individual, so you are asked to sometimes really answer yes or no as an individual person and it is difficult to represent the collective point of view. On the other hand, sometimes the question is really a PhD kind of question. So it is really sometimes more the form than the substance behind and therefore there is an open process, but is the result really incorporating the openness element? I'm really not sure. But again, I can say that you can live with consumer blows. Some people like it as well. And it is really great now that more and more people are trying to influence the process of regulation as well. Two very quick remarks. First, what we've seen recently is public outrage of people very, very unexpectedly came forward and protested against pieces of legislation that frankly I wouldn't have hoped people could care, but we cannot rely on outrage because at some point people will be resilient and not very saturated for this. You cannot always call danger, danger, danger for the seventh, eighth, tenth time people will not respond. So those people pushing for this kind of formation of infinite patience and infinite means to push it. Second thing is these outrage was somewhat solicited or enhanced by some intermediaries. Some people are hosting content, hosting services, providing the flow of information. Those companies or those service providers are constantly attacked by attempts to reform under two main headlines. First is while protecting children and second is piracy or protection of the content. So I see a parallel between those people, Google and others and Wikipedia soliciting outrage and being attacked and having a force to be those people had liable for what flows into the pipes. Any other questions arising? Gentlemen over there please. My name is Oliver Birken from Germany. I was wondering on a more local level with far more global effects, whether 2012 is actually the end of the year of openness. The smart phonification of desktops and notebooks also known as Windows Secure Boot where we keep losing control over the computers and what's going on on these machines on our desktops in our private living rooms and offices. Do you have any opinion?


Okay, here we go. Next item on the list for my running gear in 2019 that I love the most. How you doing everyone? Onward and upward to 2020. Where does the time go? I can't believe it's December 15th when you're watching this. Got my scissors. Got this box. It connects to today's topic about my top running gear of 2019. Now, how do you even define running gear? That's such a vast, broad way to categorize any gear that we use as runners. It's easy to, it would be tempting to say, running gear is anything, any piece of gear that we use while running, but what about recovery gear?  All this gear that we use as runners, except shoes because we've already covered shoes over the past four days, road shoes, trail shoes, but now it's just the little things. We could be talking about shorts, socks, hats, hydration vests, watches, heart rate monitors. I won't be doing that, but it's vast. So today, actually let's do it. We're going to open up this box. All right, here we go. So we're going to open these up. Now, this is an important point before we get into this, and shout out to Running Warehouse for getting this off to me, is that how did I go about deciding what is my top running gear of 2019? It's really, it's pretty simple for me. It's what was most durable, what brought the most value to me as a runner, and what did I use the most? Okay? Like, sometimes you buy a piece of gear and it sits on the shelf and you're like, wait a minute, I haven't used that for the last three weeks. Did I really need to buy that? So that's really kind of my basic thought process behind what running gear really stood out to me this year. So here we go. Oh my goodness. Pulling it out. One, two, three, Running Warehouse. Thank you so much. Okay. So I am running high volume right now, getting ready for Houston, and my legs are tired. I'm a little sore, which means I need to recover. So a couple of the items that are in my top running gear of the year, yes, of course, is connected to recovery, including what is in here, more compression sleeves. That's right. Thank you, and shout out to Compress Sport. You guys know, actually I'm wearing them right now. I have calf sleeves on right now. So we've got running shorts. We've got, let's see, what is this, the, yeah, more half tights. Oh, I love half tights. Bottom line, shout out to Compress Sport. Here we go. And even some socks from Compress Sport. Again, just trying to push the envelope when it comes to recovery. So this is my number one item, and it's so funny because I have them on right now. For you right now, that right now, those are compression sleeves in case you've never heard of these. And the company is Compress Sport, the ones that I love the most. And they treated me so well in 2019 with helping my legs recover from all the vertical, from all the pavement in the last month getting ready for Houston. So there you go. Number one, compression sleeves. All right. All right. Away we go. Okay. So back to the, real quick, back to the support system of long distance runners from yesterday's blog. We talked about that.  You know how it is. Like in the summer, it's like you've got shorts, you've got a shirt, socks. It's pretty simple, pretty straightforward. In the winter, laundry goes way, way, way up. So that is what we're working on here in the, here in the background. But right now I'm heading out the door, going to try out these half tights from Compress Sports and I will get you some more intel on this company, which I will just say is based in Switzerland. All right. So shout out to the Swiss out there. Actually, let me know if you're from Switzerland. I'm not sure. There's a guy, I've seen a couple of comments from Switzerland, but anyway, shout out to Switzerland. I appreciate it. All right. Let's go. Get ready. Okay. Next item on the list for my running gear in 2019 that I love the most. Now this is not a new, like many of you probably already own this and use it daily. I use it daily and many of us need to stay connected to our families or our office, our work all the time, which means yes, you are carrying your phone with you everywhere, including when you run for safety reasons up in the mountains. That's why I carry the phone up there. So here we go, foot belt. That's right. It's actually called flip belt. There it is. I don't know if you, I'll spell it there on the screen as well. And to put it on, you just step into it. It's kind of funny, but it just goes right around your waist like that. And then you get your phone. Hopefully you can see this. See there's a little, little hole there. And there's actually one, two, three, four. So you can put gels in here, your car keys, your phone, and it's crazy. You'd think that your phone wouldn't fit in this little belt very easily. Watch this. See, just like that. See that? There's a little hole in there. And I always stick the screen out just to help keep a little bit of sweat off of it. And then I just slide it in just like that. And then it's kind of off to the side and that's kind of awkward. So then you just slide the belt to the back of your back and it sits in there perfect. And the reason I like flip belt. So I also have Nathan and now compressed sports, but I haven't tried this one out yet. I will do that soon is that I like the flip belt company over Nathan. Nathan's is just stretching out way too much after only like a month and a half of using it and it doesn't hold the phone as secure to your body compared to the flip belt company. Of course I went with neon green and it's just perfect. There's a lot of different ways to carry your phone when you're running, but I have found this one to be basically the most secure and the easiest to get on and off. So flip belt is my running gear item number two of 2019. And again, I know many of you already own something like this, but it's been amazing this year. Oh man. Okay. Now I'm almost ready. Let's go. And I'm back from the run. All right. Shout out. If you have never seen this t-shirt, this is the original Seek Beauty t-shirt. Shout out to Jeff down in Arizona. He made this shirt for me over a year ago. So Jeff, if you're watching, I hope you're doing well. Thank you for making this, getting the ball rolling in the merchandise department. Okay. So the run today, six and a half miles, about eight 40 a mile, beautiful recovery day on a Saturday. Feeling good about that. Okay. And again, my top running gear of 2019, I have used compression technology in the past, especially in college, but that was 10 years ago when I was running a lot. And now that I'm running a lot again, I'm realizing how much I just need to take care of the body. So again, these are my shorts that I wear with the compression around the quads. And these are my calf sleeves that I wear right there. And I don't wear them all the time, usually, usually every day for about three hours. And then I take them off, let the legs kind of breathe a little bit, and then I'll put them back on if I'm really sore or tired from a long run, especially. And what happens is the compression increases the blood pressure in that region of the leg, that area of the leg that is being squeezed, which helps bring more blood to that area. It also helps reduce swelling in that area. So it's all, I don't know. Like there's a lot of science out there. You can read a lot of different studies about compression in recovery. I'm a believer, but go do the research so far, so good for me from the compressed sport technology. And again, shout out to Running Warehouse for the gear that showed up today. Okay. And again, one more time, the flip belt, oh, it just worked amazing today. I'm just going to put the phone in one more time for you so you can see it one more time, although it's a lot easier to do when you're, when you have the flip belt on. Let's see. So you know, I actually went, so I'm like a, my waist is pretty small. I think I'm like a waist size, like, I want to say like 28, 29-ish. And so I went with extra small just so you know, I would go maybe a size down just so you know. Okay. So there it is, sliding into the flip belt, and then eventually it disappears and you don't even know it's, it's there. And the build quality is there from this flip belt. And I will just, I forgot to mention is that they do have in one of these four pockets, they do have a, basically a key chain holder so your keys don't fly out and you don't lose them, but, but the, and these days, so many cars don't even have keys anymore. They just have that one technology. My car definitely does not hold on. There it is. I found it. This guy. So you can clip your key right onto that hook so they, it does not fall off. And there is the price down below for you on the title. Okay. And moving on to my next item, my top running gear of 2019. Of course it's a recovery item, or you could also say a, like a workout item, like, you know, you can use this in different ways. It's my stability disc by power systems. I love it. I used it in college. I used it in the gym for the last four years. And finally I said, enough is enough. I need one of these at my house.  If you want all of my ankle strengthening exercises, you can go check that vlog out from about 10 days ago and this thing's amazing. It just, it stretches my calf and my sole is so, so well. So anyway, this is my stability disc. That is item number three, my top running gear of 2019. And last but not least, I decided to go with four. I almost just went with three, but I couldn't resist sticking this guy into the mix because you know, if I'm willing to pack this item, drum roll, if I'm willing to pack this item to Amsterdam, to New York City, to Argentina, to New Hampshire, you know I love it. That's right. It's the Hyper Ice Viper 2.0 Vibrating Foam Roller. I love this thing. I absolutely use this every day, sometimes three times and four times a day when I'm just a hurting unit and you can use it without the vibration. So just like a normal foam roller or let me just turn it on real quick. You can use it with it and it has three different settings. So this is the lowest. I usually start on one and then eventually bump it up to two. I rarely use three. Three is pretty intense. So one is just like amazing for the warm up, but then after the hard run, after the hard workout, I usually bump it up to two and I use it for my calves, my quads. It's just and I like I used it in the airport and some people were a little freaked out that I was rolling around on the airport floor in Amsterdam. But listen, I was such a hurting unit, like really a hurting unit after the Amsterdam Marathon. My legs were done and I pulled it out and I think it actually helped me simply make it back to my house so I could walk through the airports because I had so much lactic acid that built up in the first half of that Amsterdam marathon that this guy, I really feel like it saved me. So there you go. Those are my four items that I love from the 2019 running gear lineup. There you go. There you have them. Question of the day. What is your top running gear item of 2019? There's so much. We could talk all night. Maybe we'll do a live stream maybe this week about running gear. I think we should before Christmas hits, we'll do a running gear discussion on a live stream. I will let you know when that happens because I'm intrigued to hear what all of you have to say, what all of you have purchased because you could oh and I want to make one more point and then I will sign off is that you don't need all of these items to be a runner. I just want to like in high school, I had nada. I ran a cotton t-shirts, cotton socks, and I ended up walking on to the University of Colorado cross country team. So this stuff is nice. I think as I get older, I need to focus more on recovery. But at the end of the day, all we need is a pair of running shoes. So don't feel like I don't want you to feel like you have to get these things to be a runner. You're a runner just by putting your one foot in front of the other, getting out the door, getting some air in those lungs and having a good time and getting the getting the wind in your hair as I like to say. But anyway, that's the question of the day. I love you. Thanks for being here. Thanks for watching. Oh, tossing it back to we'll toss it back to the ankle strengthening on the right and we'll toss it back to the foam rolling a blog on the left where I walk you through how I use this guy right here. All right, you guys rock, see beauty, work hard and love each other. See you tomorrow.


Would you say that, I mean, I think I answered my own question. Would you say that applies to bodily, physical issues as well? And of course, yes, I'm sure it does. I'm asking because these last couple of years to me have been really hard with the physical body. And that was the last stand my ego had with me. Because I've enjoyed good health for my whole life, pretty much. I've had episodes of weird things, but I've been doing the course for about nine years. I've been applying the course for about nine years and forgiven this with everything. And I mean, it's been so easy for me at times to forgive the things people say or do and the things in my mind or the emotional. But when it came to the body, it was like, oh, the buck is stopping here for me. Then it became personal. It got real personal and I was really miserable with that. And my miracle came recently. I think it was about a week or so. I woke up and I realized I'm not the body. It's not personal.  Or if a little bodily thing have come up, it's like I can look at it and just go, cool, I'll just take an asking for that.  It's nothing. And it's been such a beautiful shift. But I was just asking, I guess, in your experience or any of you, if that dark night of the soul is how it's arisen. Because I've had the mental, emotional depression and all of that. But the physical ailments and even the certain things like a rush of heat will come through my body and I'll just sweat like crazy. And it's very uncomfortable. And I'm just like, damn. And it's usually right when I'm starting to meditate. You know, something that just tries to keep me off track. And then it's like, OK, just let that go and come back. Let it go and come back. So I think I got to my question. But if you want to, I respond. That's fine. Today's lesson really addresses the body pretty directly. And I try my best. And the, just don't work on it. The ego just, it feels to me like it's its last stand. And it's not letting go easy. And when the lesson said you'll know that you were successful when you no longer feel your body, it just doesn't happen for me yet. I think we all have a lot of stories you're talking about and you're talking about where we had to come to such a state of allowance that, OK, it's going to look however it looks and it's going to feel how it feels. But I'm going to do this. I'm going to apply this lesson. I'm going to apply this principle.  But there's a lot of denial and repression that's going on. So it's quite typical when that's the case that it's projected onto the body. Instead of being held in mind, it seems to, that's a very strong tactic, like drawing forth a witness, a witness of weakness or pain or frailty. Kind of like the ego is saying, oh yeah, you think you're waking up? We'll try this one on today, you know? It's like knocking down to your knees or some kind of nausea or whatever. And the best part about it is when you just give it over to spirit, you say, this be you in charge. I am not in charge of my awakening. In fact, of course, the miracle says you cannot wake yourself unless you can't allow yourself to be awakened. I love that, you can't allow. So when I was doing the workbook lessons, when I came to lesson 136, sickness is a defense against truth. That's the one where I came home, I put the food in the microwave, I had nausea, and I got this diarrhea feeling and I raced down the hall, went to the toilet, and then on the toilet began the meditation. Sitting on the toilet. You see how practical Jesus is? Drive you right to the toilet. You have to be on your knees, you've got to be sitting there.  And then I started to allow related thoughts because it's quite a large lesson, it's a very long lesson.  And I let those ideas come. And then I just prayed to Jesus, I said, okay, here we go. Practical application, I'm on the toilet, and I've got the diarrhea and nausea, and I went in, and what he did was, he took me down way into my mind where it took kind of the branching of the road, where it was either that sickness was a reality and in that case, Jesus who I'd followed since a little child had been lying to me all the way along and in a course of miracles. So it came down to whether sickness was real or whether Christ was real. I could see that one would be true, the other one couldn't be. It couldn't both be sickness and Christ. So I just went down, down, down, down, down into my mind to get to that point where they were side by side. And do I love the Christ or do I love the sickness? That was really what it came down to. And I remember sitting in the toilet and then these tears started to pour down my face because I was like, I love Jesus. I loved Jesus. I want the Christ to be real more than I want this witness of sickness and boom, it was a miracle. It was a miracle. Instantaneous, it wasn't like the 48 hour bug, the 24 hour bug, all that learned worldly stuff. And boom, it just, those are the kind of miracles that convince us of the power of our mind, of the power of the Holy Spirit. It's not some kind of intellectual thing. I had to actually follow it down into my mind. I had to drop down where I could see them side by side. And when I could do that, then, oh, you better believe I could choose the miracle. And that's important. Even when you have physical symptoms or after a pretty healthy life and it starts to come at you pretty strong, that's the time for faith, to really carry it through all the way.


Sorghum is the forgotten grain. The United States is actually the number one producer of sorghum, but it's typically not used to produce food for American consumers instead. It's produced mainly for feeding livestock, or as pet food, or even building materials. But it's actually eaten as a staple in other parts of the world, such as Asia and Africa, where it's been eaten for thousands of years, making it currently the fifth most popular grain grown after wheat, corn, rice, and barley beating out oats and rye. Because sorghum is gluten-free, because it can be definitively considered safe for people with celiac disease, we're starting to see it emerge as an actual human food in the US, so I decided to look into just how healthy it might be. Protein-wise, it's comparable to other grains, but since when do we have to worry about getting enough protein? Fiber is what Americans are desperately deficient in, and sorghum does pull towards the front of the pack. The micronutrient composition is relatively unremarkable. Here's how it rates on minerals, for example. Where sorghum shines is on polyphenol content. Polyphenols are plant compounds associated with reduced risk of a number of chronic diseases, including cancer. Cardiovascular diseases, neurodegenerative disorders, and even all-cause mortality. And if you compare different grains, sorghum really does pull ahead, helping to explain why its antioxidant power is so much higher. Now, sorghum gets its grainy little butt kicked when it comes to fruits and vegetables, but in terms of compared to other grains, a sorghum-based breakfast cereal, for example, might have like eight times the antioxidants than a whole wheat-based cereal. But what we care about is not antioxidant activity in a test tube, but antioxidant activity within our body. If you measure the antioxidant capacity of your blood after eating regular pasta, it goes up a little. If you replace 30% of the wheat flour with sorghum flour, it doesn't go up much more.  See there are multiple types of sorghum. There's black sorghum, white sorghum, and red sorghum. This is how they look in grain form. There's evidently a yellow sorghum, too, and a red sorghum, and especially black, have like legit fruit and vegetable level antioxidant activity. The problem is I can't find any of the colored ones. I mean, I can go online and buy red or black rice, purple, blue, or red popping corn, and purple or black barley, but I can't find red or black sorghum. Hopefully someday, but you can find white sorghum for about $4 a pound. I mean, it doesn't have any unique health-promoting attributes. It's promoted as an underutilized cereal whole grain, with the potential to assist in the prevention of chronic disease. But what is the effect of sorghum consumption on health outcomes? An epidemiological study in China found low esophageal cancer mortality rates in areas that ate more millet and sorghum compared to corn and wheat. But that may have been more due to avoiding a contaminating fungus than from the benefit in the sorghum itself. I mean, though it's possible. I mean, just as oats are the only source of avanathomides, which give oats some unique health-benefit sorghum. Even white sorghum can contain unique pigments known as 3-deoxyanthocyanins, which are strong inducers of some of the detoxifying enzymes in our liver and can inhibit the growth of human cancer. Cancer cells grow in a petri dish compared to red cabbage, which has just regular anthocyanin pigments. But note that white sorghum didn't do much worse than red or black, which have way more of the unique 3-deoxyanthocyanin. So maybe it's just a general sorghum effect. I mean, you don't know until you put it to the test. Sorghum was found to suppress tumor growth and metastasis in human breast cancer xenographs. What does that mean? The researchers conclude that sorghum could be used as an inexpensive natural cancer therapy without any side effects, strongly recommending the use of sorghum as an edible therapeutic agent, possessing tumor suppression and anti-metastatic effects on human breast cancer.  Yes, the human tumors grew slower in the mice-fed sorghum extracts and blocked metastasis to the lung, and did the same for human colon cancer that, again, was in mice, which can't necessarily be translated to how human cancers would grow in humans, since, for example, not only do these mice not have a human immune system, they hardly have any immune system, and they're bred without a thymus gland, which is where cancer-fighting immunity largely originates. I mean, how else could you keep the mouse's immune system from rejecting the human tissue outright? But this immunosuppression makes these kind of mouse models that much more artificial, and that much more difficult to extrapolate to humans. And that's a lot of what we see in the sorghum literature in vitro data, like in test tubes and petri dishes, and rats and mice. There had just been this critical missing piece of the puzzle needed to link laboratory data to actual benefits in humans missing that is, until now. Thankfully, we now have human interventional studies which we'll explore next.


We won tents. They were very useful with 800 small tents. They were sleeping there, only a couple of hours, getting out for a day. They were staying there gathering in just units, so to say. One for creative digitization, another for building robots. There were gurus, so to say, invited the question and answered it. And the whole procedure was going on. I was just walking with my people. And at a certain moment the guru was standing there, reading lips. And I was asking my people, who is that? And he said, you are only familiar with Steve Jobs when you were in Smith's and with Steve Bollman, but this is a new generation, so to say. And he addressed to his young people and he said, look at them. They are the past generation. Well, perhaps that's me. It was not the delegation I was with, for that were my excellent people. But he said, and if they are not doing their utmost, they are the lost generation. And then later on I was just discussing with those youngsters. By the way, the youngest was 14. He had already three inventions. He had started two companies and they were discussing with each other and with their computer. And at a certain moment I said to one, come on, you are sharing your secrets. Why are you sharing your secrets? For it is your invention, you should have. And he started to laugh and he said, you are indeed another generation to put it nicely. We are sharing, for at the end of the day, the two or more of us are getting a better result. And that is absolutely not the first time, but it was a clear message for me. In this field it is completely different from what I had as experience that the older generation is teaching the younger generation being an economist by training and so on and so forth. In this field it is the younger generation that is teaching me. So now we are just thinking over and organizing, trying to organize instead of very wise professors as advisors and I still am a professor impressed by your knowledge and your wisdom. But I need those youngsters on the board of advice for doing the job properly and I need you so I sincerely hope that the fellowship will be acceptable for you. Thank you.