So, for so long we talked about NMR methods, various kinds of techniques which are developed over the years and now we are ready to go into the applications of these methods into the area of structural biology which is the main theme of this course, NMR in structural biology. So, we have prepared the ground with methods. So, now we are going to see how they can be applied in structural biology. So, therefore, we will have to prepare a little bit of ground for the biology itself. What do we mean by structural biology? What sort of molecules we are going to look at? So, that will be the theme now onwards. So, we are going to spend a little time on introducing the different concepts and different biological molecules. And everybody knows that especially the biologists, they will know that the central dogma in molecular biology is described in this particular manner. Every cell has a DNA which is there inside the nucleus and this is the hereditary material. So, different individuals have different DNAs. So, therefore, the hereditary comes because of this molecule. So, the offspring will be similar to the parents and this is because of the similarity of the DNAs and therefore, it is in fact used to identify people on the basis of their DNAs. And then DNA is then transcribed into another molecule, the DNA stands for deoxyribonucleic acid. So, nucleic acids are the kind of polymers and then these ones are transcribed into another kind of a nucleic acid which is called as RNA. This is the ribonucleic acid and this actually is the process called transcription and different segments of the DNA are transcribed into a certain molecules RNAs we will describe that little bit later. And those segments which are transcribed are called as the genes in the DNA and then they form RNA and this comes as what is called as the messenger RNA. This process is known as transcription. So, this process is known as transcription and from the messenger RNA you have what are called the proteins. So, there is a kind of a code in this which is called as the genetic code and this genetic code describes what kind of a protein has to be produced and you know the proteins are made up of amino acids there are 20 different types of amino acids and a set of 3 units of RNA codes for one particular amino acid and they have the 20 different amino acids are coded by different codes these are called as the genetic codes and then this process of expressing the information in the RNA into the proteins this is a process which is known as translation. And then proteins are actually the biological machines actually for a long it was thought that proteins are the biological machine but today we also know that sometimes RNAs can also be function carry out function biological functions but the general belief has been for me which is true that proteins are the real biological machines and they carry out the biological functions inside the cell. So, now to explain this little bit more so they have the DNA which is a long polymer which is a long polymer it has more than a billion molecular which is huge molecule DNA this is the polymer and it is very very very very long. So, it has approximately 10 to the power 9 units and these are called as nucleotides. So, on this DNA there are certain segments small small segments and these are called as the genes there is a lot of other things also inside the DNA and these are the genes and from the genes you get what is called as the RNA. And this is called as the messenger RNA there are three different type RNAs they are messenger RNA then the tRNA and then you have the ribosomal RNA. So, if I want to draw the cell here you have the nucleus and this contains the DNA this contains the DNA and the mRNA and these things that actually happened inside this this is other thing which is called as the cytoplasm here. So, the genes are expressed in the form of mRNA this that is a particular mRNA there are other kinds of RNAs which are called tRNA and ribosomal RNA and tRNA is involved in the translation process from here. Here this is then it goes to the proteins here this is the process of translation and from here to here this is the gene this is the transcription and the translation generates the proteins. So, now ultimately our objective will be to understand the structures and how this process is happened of course this is very complex there will be many, many different kinds of proteins involved in every step and it is an extremely complex process. Clearly the and there is a kind of a synergy in all these actions of these various proteins and the nucleic acids and one needs to understand this synergy in order to understand that we have to understand the structures structures and the dynamics of these molecules. So, this actually constitutes the main theme of structural biology and protein there are also other molecules inside your cell and these are small molecules which are the source of energy or metabolites. So, the food you eat is actually degraded into various kinds of small molecules and these are the marker we have the ions and things like that. So, but biologically we will be concerned with the these macromolecules which are the DNA segments then you have the RNA segments then you have the proteins the ribosomal RNA is present inside the what are called as the ribosomes and these are the machines where the actually the proteins are synthesized. So, these are the areas these are the kind of a powerhouse where the proteins are synthesized mRNA comes inside the ribosomes and then there is a tRNA which also plays a role inside there and the ribosome also contains many proteins therefore the whole thing is a big complex is a big assembly and the structure of this ribosome is also an important aspect to study. So, individually one looks at the molecules the nucleic acid segments mRNA segments the tRNA segments and the proteins. Now, the this idea of this process of understanding the structures was of course an important topic and several people had worked on it and there are various kinds of empirical rules which had evolved and on the basis of what is called as a fiber diffraction fiber diffraction data these three people these three people brought out a model of the DNA the structure of the structure they proposed a model of the DNA structure and they got the Nobel Prize for that in physiology or medicine 1962. See for the discovery of the molecular structure of DNA which helps all one of the most important of all biological riddles that is the replication process why is it a hereditary molecule how is it that the offsprings are similar features as the as the parents. So, why is the DNA so important what is the structure how is the information transferred from one from the parent to the offsprings and that is retained in the same manner. So, that was an important riddle in biology and these people gave an answer to that in the form of the structure of the DNA molecule. So, what did they propose they showed that the DNA is a on the basis of the fiber diffraction data. So, they showed that the DNA is actually a double helix. So, is wound like this then you have the another one which is also going parallel I cannot draw this properly here, but this is a double helical structure which they proposed and that actually became an important contribution for understanding double helix. There are certain rules as to how the double helix is found we are going to look at all of those but they based their arguments on the basis of the fiber diffraction data. Fiber diffraction does not give you such very high resolution at the atomic resolution it does not give that information. It only gives the kind of a symmetry elements what are the kind of symmetry elements in the molecular structure. So, either in any proper symmetrical spacings of certain items certain spacing of certain groups what kind of a structural elements may be present inside the big polymer. Because you remember this is a very big polymer and in these we have these two people Francis Crick and Morris Wilkins these were the crystallographers the diffraction the ones we interpreted the fiber diffraction data and Watson was a chemist who actually built the model of this using ball and stick models. So, the and then actually turned out to be such an important contribution that they got the Nobel Prize in 1962. So, now we have to go into understanding the structures of these molecules in greater detail. So, before we actually go to that let us look at these various biological function in a little bit more detail and that is indicated here. So, here now here also it makes an introduction to NMR because there is an article written here in analytical chemistry for metabolomics and metabolic profiling and it also has describes what are the various elements in structural biology. So, you have the genome to metabolome. So, this is the genome the DNA that is the DNA which is also called as the genome here and there are typically about 30,000 genes inside the DNA in a particularly typically in a living cell cell there are about 30,000 genes. Now, these 30,000 genes and they are characteristic of the individuals that define what is called as the phenotype and then you have of course phenotype all the things also contribute to the phenotype. Now, this genome is transcribed into what is called as a transcriptome. So, you have 30,000 genes which are expressed and produced 30,000 mRNAs. So, these are 30,000 this is called as a transcriptome. So, this is very characteristic of every individual every cell has his own transcriptome therefore this becomes an important thing to study what is the process here from here to here and then from these 30,000 transcriptomes you produce nearly 100,000 proteins. So, which means that one mRNA is producing more than one protein in other words there is what is called as a mRNA splicing. So, therefore, different combinations of the mRNAs are made here and not only they produce individual proteins but some kind of a alterations in the mRNAs and joining cutting them joining them things like that and that results in producing nearly 100,000 proteins in a particular cell and this is called as the proteome and there are also certain changes happened after the translation some modifications happen and those are called as the post translational modifications. These are important events that happen in biology and they are required for particular processes in the biological function and then from here you have this metabolome the proteome deals with the metabolome that is the various kinds of molecules small molecules which are interacting with this. So, the metabolites are those which are the food you eat which is degraded into small molecules there are ions and there are nearly 40,000 small molecules which are actually present in a cell and these are upregulated these expression levels are upregulated downregulated and things like that depending upon the disease conditions depending upon the nature of the individuals. It depends upon the environment, diet, age, lifestyle, drug, disease and therefore one has to target various molecules in this category. So, you can sometimes you may have to target here, sometimes here, sometimes here, sometimes here and therefore all this contributes to the research in drug development, disease control and these are dependent on the environment, the lifestyle, age, etc. So, therefore it is a huge topic to study all of these ones. There are many challenges and of course now the NMR has come of age to provide solutions to many of these situations. So, in order to see how one can apply NMR we will have to go into the details of the individual molecular structures. So, let us begin with the RNA structure or the DNA structure as I said the DNA is a polymer it is made up of nearly 1 billion units and what are these units these are called as the nucleotides. So, the nucleotide is described in this manner it is a phosphodiester linkage here, this has the sugar ring here, this is the sugar ring, this is a 5 membered sugar ring as you can see this is and then you have a certain kind of a base here there are 4 different types of bases which we will describe soon sometimes 5 and if in the DNA has a particular kind of a base called the thymine whereas the corresponding one in RNA is called ursl it is and then you have the phosphate group here and this phosphate group this continuous this is the monomer unit of the DNA and this repeats itself this repeats itself through the polymer what changes in this the only thing that changes is this base from one unit to another unit there is a change in the base which are of the base and that is called as the DNA sequence as you go from one unit to another unit DNA base changes and that is the one which is the information carrier the sequence of the bases that are present in the DNA that is the information carrier and this has a certain chain direction here. So, we represent this as the chain direction going from n minus 1 and n and n plus 1 it goes in this direction. So, therefore, we write it as 3 prime so this is a 3 prime and this is the 5 prime and here see these are atoms are labeled in this manner the sugar ring sugar ring is labeled in this manner this atom is called the C1 prime the C2 prime C3 prime C4 prime and C5 prime and then the C5 prime of this unit is attached to the phosphate group here this phosphate group and this phosphate group is attached to the C3 prime end here at this point. Now, you see there is an oxygen here all of them have an oxygen and this C3 prime attaches with through the phosphate group to the 5 prime end of the next nucleotide and therefore, this is the base sequence goes on. So, this is the 5 prime one end is the 5 prime end other end is the 3 prime end the chain goes in this direction 5 prime end to 3 prime end. So, the nucleotide one particular nucleotide unit this is n this is in this is from one 5 prime end to the other 3 prime end. So, include the phosphate group of this into this unit and the next one of this goes to the next unit. So, therefore, this is the 5 prime to 3 prime sequence typically when you write the DNA sequence you write in this manner. So, in going from 5 prime to 3 prime what is the DNA sequence you write the various bases which are present in this nucleotide unit and that is called as the DNA sequence. So, this is the monomer of the of the entire polymer there are about 1 billion of this kind of things. Now, you can imagine how much how long this would be. So, if you consider the bonds here number of bonds here. So, from here to here how many bonds are there. So, this is 1, 2, 3, 4, 5, 6, 7. So, these many bonds are there. So, typically length if you consider the length of each bond is approximately let us say 1.5 angstrom then the total will be approximately 10 angstroms from here to here it will be really 10 angstroms. Now, the 10 angstroms into 1 billion so, this is 10 to the power 10 angstroms then you can imagine how long this will be if you take when 10 to the power 10 angstroms and how much is 1 angstrom 1 angstrom is 10 to the power minus 8 centimeters. So, this will be 10 to the power 2 centimeters that is about 1 meter. So, the DNA length DNA length will be approximately 10 to the power 2 centimeters if it is completely linear it goes like that it is complete if it is be after 1 meter. However, you see the size of your cell is just about a micron 10 to the minus 6 centimeters. So, then and then the nucleus is even smaller than that now how is this entire DNA packed inside that small space inside the nucleus. So, which obviously means that the molecule adopts a very folded structure all kinds of folding things happen there and it is completely wrapped around in various ways and so that it is packed inside the nucleus and this has to be unpacked when it has to be expressed when the protein has to be and the mRNA has to be produced it has to be expressed. So, it has to be unpacked and then the proteins have to be produced therefore, you can imagine how complex is this whole process is and a lot of this the a lot of research therefore, goes on in trying to understand all of these and how can NMR contribute in this is what we are going to see. Now, this is a little bit of a explanation is somewhat more detailed at atomic level. So, you can see here the atoms are listed here where 1 prime 2 these are the carbon set this is the ribose ring this is the ribose ring here see the 1 prime 2 prime 3 prime 4 prime C 4 prime and then the O 4 prime this is an oxygen here and then at this point you have the 5 prime carbon carbon is attached to a phosphate group here. So, we have a 5 prime OH group and that corresponds to the phosphate and the deoxyribose this is a deoxyribose the deoxyribose means that at the C 2 prime position here there are two hydrogens these two are hydrogens here therefore, this is the CH 2 group the CH 2 group is there is a hydrogen and the C 1 prime this is actually connected to this oxygen and this C 4 is also connected to this oxygen and C 1 prime here is connected to the base from here the base goes and then the C 3 prime is connected to an oxygen and in the case of the RNA there will be small difference here in the case of RNA you will see that the 2 prime position here also has an oxygen. So, there is one hydrogen and one oxygen in the case of RNA that is a ribose nucleic acid. So, therefore here in the C 2 prime in the case of DNA there are two hydrogens these are labeled as H 2 prime H 2 double prime and in the case of RNA you only have H 2 prime you do not have H 2 double prime and all of these also have a proton on this there is also a CH 3 on this CH 3 there is a proton on the C 3 there is a proton which is called as H 3 prime and on the C 1 prime also there is a hydrogen which is called H 1 prime and likewise on the C 4 prime there is a hydrogen which is called H 4 prime and on the C 5 prime there are two hydrogens which are indicated here and these are the two H 5 prime and H 5 double prime that is better seen in this picture here. So, H 5 prime and H 5 double prime. So, therefore there are a number of protons. So, therefore one can study using proton NMR what is the kind of a structure of this individual nucleotides are. Now, what are the bases as I said the one prime is connected to the base. Now, there are four different kinds of bases or the rather five here see this is adenine, gonine, cytosine and thymine these are the four which are present in DNA. In RNA thymine is not present it is replaced by a uracil. Now, you see these are all these two are called purine rings. So, this is a purine structure here you have a five membered ring and a six membered ring joined here this is the purine structure and these are only the six membered rings these are called as pyrimidines. So, the basic entity in organic chemistry this is the pyrimidine here and these are two purines and the uracil is also a pyrimidine and it has two oxygens here and same is true with the thymine the difference between thymine and uracil is that you have a methyl group in the case of a thymine whereas, in uracil there is a hydrogen here at this point there is a hydrogen and all of these there are hydrogens here in this point there is a hydrogen here there is a hydrogen here there is a hydrogen and so on so forth. So, these are the structures of the basis and those are indicated in a color coded man here. So, all the nitrogens are blue here and the oxygens are in red and the hydrogens are in white and the carbons are in green. Notice here there are NH2 groups here the cytosine has NH2 guanine has NH2 and adenine has NH2 all of these are hydrogens NH2 groups and they also have amino protons the guanine has an amino proton that is the NH group here and the thymine also has a NH uracil also has a NH. Therefore, so far as the nitrogen is concerned there are amino groups and the amino groups and there are also some nitrogens which do not have a proton attached. So, the cytosine has it is at this point that actually these ones are attached to the carbon these NH is actually will get this hydrogen will disappear and it will be attached to the sugar ring similarly and this will be attached to the sugar ring base will be attached here and the sugar will be attached here and like that here. So, this is how the structure of the DNA and the RNAs are built. So, this is the same molecular structure of the bases given in a more explicit manner. So, therefore, now this is a kind of a summary of what I explained for so long and that is the primary structure of the DNA or the RNA. So, this sequence goes like this. So, as I indicated earlier so, you have a base here and this is the ribose ring or the deoxyribose ring whatever in the case of only the carbon skeletons are shown the protons only are shown for the CH2 groups here but there are protons here, protons here and protons there those ones are not shown. So, you have the phosphate group here. So, therefore, this is called the phosphodiester linkage we have a phosphodiester linkage in this this is called the phosphodiester linkage because there are two ester groups there phosphodiesters. So, every dinucleotide has a particular phosphodiester linkage here. So, you have the CH2 this is the 5 prime end and this is the 1 prime here 1 prime attached to you see as I told you earlier at the at this amino at this nitrogen these bases are attached. Similarly, the pyrimidine at this nitrogen the base the sugar rings are attached and likewise. So, this is at the that this nitrogen the sugar is attached and so on so forth. So, in the purines the sugar is attached to the 5 membered ring and in the pyrimidines it is attached to the 6 membered ring at this position and to repeat you have this 1 prime group here this is the 2 prime in the deoxyribose you have 2 hydrogen here and there is 1 hydrogen at the 3 prime and the 4 prime there is 1 hydrogen here and this repeats itself in the all along the sequence. So, in a linear sequence this is how the structure is made. Now this is shown in a color coded manner here. So, where the how the DNA sequence is found you have the 5 prime phosphate group here and then there is the base attached to the sugar ring. So, the phosphodiester this is called as the backbone okay. So, the phosphodiester linkage this is called as the backbone of the DNA. So, the deoxyribose ring here ribose ring here. So, all the ribose ring in the phosphodiester linkages they constitute what is called as the DNA backbone and the bases are indicated here C, G, A, A, T etc. etc. So, this find the sequence of the DNA and this is called as the DNA backbone okay. Now what this people said Watson Crick and Franklin and all of these they proposed this model that the DNA is not a single strand but it is a double strand and that is how the hereditary information comes hereditary property comes because of this that is that if you have a DNA and these this is a molecule exists as the double helix what happens in the double helix there is one strand runs like this from 5 prime to 3 prime end and the other strand runs in the opposite direction 5 prime to 3 prime end and these two nucleotide units the two strands are held together by so called hydrogen bonding between the bases and these are called as the base pairs. So, you have the CG pair here the TA pair here GC pair here CG pair here they also observed that C can pair with G and T with A and no else okay. So, therefore there this is the model which they put up and of course this was based on previous information inside available to them that okay the number of C is equal to the number of G is the number of T is equal to the number of A is in the DNA. So, on that basis actually they had put up this model then you have the C and the G are hydrogen or paired together through hydrogen bonds and there are three hydrogen bonds between C and G and there are two hydrogen bonds between T and A and so on. So, this is how the model goes that the only certain bases will form pairs okay. So, now you see if this DNA breaks apart suppose you the two strands separate out and in the daughter of springs if the new DNA is synthesized on the basis of one DNA strand naturally the other strand which will come will have the complementary sequence. So, if the sequence goes C T G C A the complementary strand will have to have this sequence here that T G C A G it has to have that therefore the information is transferred from one molecule to the other molecule. If this is the parent molecule during the process of replication the DNA strands separate out and each one of them actually become the starting point for the new DNA molecules to be synthesized when the new molecules are synthesized they maintain this complementarity of the base sequences and that is how the offspring get the same kind of DNA information and that is called as the heredity. Okay, now this is explicitly shown in a little bit more clear manner the two doubles the two strands are running in this manner you see you have the 5 prime n of one chain which is going like this one DNA chain is running like this and the second DNA chain runs like this they are intertwined they are wound together in a kind of an intertwined fashion and then you have these base pairs that are happening between the two strands. You have the phosphate backbone and you have the base pairs which are there between two strands which are running in opposite directions. So, this is how the hereditary information comes in the DNA molecule and to show explicitly what sort of hydrogen bonds are there and this slide shows you the particular way the hydrogen bonds are formed A and T there are two hydrogen bonds formed here this is the thymine immunoprodons and goes here and the oxygen here goes to the NH2 proton of this of the purine here the purine has an NH2 here these are the amino protons and this is the ketogrop here this is the oxygen of the thymine which pairs with this and here is the amino group of the amino group of thymine pairs with the nitrogen of A and therefore this is how the hydrogen bonds are formed in this similarly in this case you have the amino of cytosine going to the oxygen of the guanine and the oxygen of the cytosine goes to the amino of the grossine and then there is an NHN hydrogen bond G amino where is to the nitrogen of the because you see the color code here. So, what is the color code the blue is indicating the nitrogen and the red is indicating the oxygen therefore these actually clearly tell you what sort of hydrogen bonds are formed between the A T and the G C pairs. So, this has been the basic discovery which actually led to the Nobel Prize to Watson Crick and Wilson. So, we will stop here.


Nancy and I are delighted to again host an evening that brings Americans and Canadians together. No gathering could be more enjoyable. Nothing is less unusual. Canadians and Americans congregate the world over on the least provocation. An inviting border has made us close and easygoing neighbors. The essence and the strength of the relations between our two countries are people. Our people naturally get along well together. We share our triumphs and victories as we share our adversities. And when at times we spar, we do so without ranker and we work out our differences. May this very special and productive spirit of cooperation remain in place. As John Diefenbaker so ably put it, our peoples are North Americans. We are the products of the same hope, faith and dreams. When your visit comes as we are on the threshold of a major event, important and historic to you and me and the nations we lead, I speak of our recently signed free trade agreement. Years ago, British Admiral Beatty voiced the sense of our trade agreement when he explained what defends our common border. Quote, nothing but the sound common sense and sound goodwill of two practical nations. Well, our new agreement makes much common sense and sets the stage for much goodwill. We shall avoid the perils of protectionism and gain the advantages of each country producing what each is best able to bring to market. Generations of Canadians and Americans will know you as the farsighted leader and proposed who proposed the free trade agreement. It will prove to be as big and as important as the magnitude of our bilateral trade. It signals to our trading partners that we are sincere in our belief that lowering tariffs and trade barriers is clearly the only answer to the distortions growing in world trade. Your visit has allowed us to address issues other than trade. We share common concerns regarding the many aspects of the environment. Progress is being made. There is yet much we can do to make our shared continent a more comfortable and healthy place on which to live. We've had important discussions of questions of peace and security. Canada's role is critical for the security of the Atlantic community. Canada's contribution to NATO is to be increased, which all your allies welcome. And I have seen at first hand, Brian, the constructive contribution you've made personally in alliance deliberations like the NATO Summit in March. This is our fourth and my final summit. They started high on the ramparts of Quebec and we've never lowered our lofty goals and objectives. I regret, however, that I could never reach those same high notes that the Prime Minister's voice so easily raced in song. These have been enjoyable meetings, useful meetings, and they've created bonds between us that have been seen as refreshing as they have been hopeful to the execution of my office. In the process, you've won my respect for your wise counsel and admiration for your leadership. Mr.  You've achieved an important constitutional breakthrough. You have seen the Canadian economy grow and unemployment fall during your tenure in office. You have achieved a special place in history with our free trade agreement. Above all, you've been a strong and persistent advocate for Canada, liberally applying your adage that we can disagree without being disagreeable. You have taught all of us about Canada's point of view on issues important to Canada while at the same time being a good neighbor and a firm friend. There can be little doubt that relations between the United States and Canada have prospered these last four years. And I thank you for both the effort and the success. And now, excuse me, just one second, to the Queen of Canada, to my good friend and good neighbor, Prime Minister Brian Mulroney and Mrs. Mulroney, and to the enduring bond between our two North American peoples. Mr. President and Mrs. Reagan and Sherzamy, I rise to propose a toast to the President of the United States and the First Lady. I rise also, in a personal sense, on behalf of Mila and myself, to toast our friendship with Ronald and Nancy Reagan. For just as this is a glittering occasion of state, it is also a special one for us. This visit marks the last time we will be under this roof at a state dinner as guests of the Reagan's. This is not to say, Ron, that I have no expectation of being here again. Subject to the approval of the voters in Canada, this year or next. And we'll be seeing the Reagan's again at the economic summit in Toronto in June. But this is the last of our home and home visits, which began in Quebec City in 1985. I believe these annual meetings begun by our two administrations have now become part of the institutional framework of Canada-U.S. relations. I suppose that too much can be made of special relationships between countries, and too much could probably be made of personal relationships between leaders. I don't think that's the case between these two countries or these two leaders. I suppose that we can sometimes exaggerate the importance of special relationships between certain countries or personal relationships between certain leaders. But the fact is that Canada and the United States are one another's best friends and largest trading partners. It's also a fact that Ronald Reagan and I happened to hit it off at the beginning and have got along ever since. This is not to say that either one of us has ever lost sight of the national interest of his own country, but it has helped us define the mutual interest of both our countries. And often, as we did on one or two issues today, we will disagree while continuing the search for common ground. Those of us who hold elective office are called politicians. There's no dishonor in that, but I have seen Ronald Reagan the statesman. I want briefly to speak to that tonight from the perspective of a friend in the eighth year of his presidency. We're looking tonight at a period in American and world history that will in large measure, when the day is done, be known as the Reagan era. For the first time in almost 30 years, an American president is completing two full terms of office. The Reagan years have been a time of peace and prosperity. There have been moments of great difficulty and regional crisis, but the peace has been preserved. When Ronald Reagan came to this house as president, he was accused of saber rattling. In the event, while strengthening Western security, he paved the way for historic arms reductions in the INF agreement and opened the door to strategic arms reductions. This is the legacy of a man of peace. The forthcoming Moscow summit is a significant opportunity for the further reduction of east-west tensions, and the president goes with the hopes and prayers of all his allies for another successful meeting with General Secretary Gorbachev. For as the president himself has said, a nuclear war cannot be won and must never be fought. When Ronald Reagan came to this house, the world was on the brink of the deepest recession in half a century. As he prepares to leave it next January, the United States and Western economies are in their sixth consecutive year of unprecedented recovery and expansion. When he leaves office, his popularity will be undiminished and his place in history secure. I want to just say, parenthetically, something that happened to me in August of 1987 was a Sunday, and I was reading The New York Sunday Times, and I was struck by this headline. And here's, I think, a direct quote, although I'm speaking from memory. The quote is, Reagan's popularity plummets to 59%. You see, right there, one sees the fundamental difference between Canada and the United States. It's language. Plummet clearly does not mean the same thing in Canada as the United States. Now what I did that day, after I finished reading The Times, was I called the president up. He was at Camp David. I said, did you read The Times? He said, yes, I did. And he didn't sound so enthusiastic. I said, I don't know how to break this to you, but on a good day, Margaret Thatcher, Helmut Kohl, and I together would be happy with 59%. Look it, I'll settle for 39%. Every leader of a democracy knows the turbulence and the challenges that free societies exemplify. Every leader worth his salt knows the joys of high accomplishment and the sadness of hopes unfulfilled. But history is usually generous to those who showed leadership, who brought prosperity, who strengthened freedom, and who kept the global peace. Ronald Reagan has done these things while never losing his engaging manner and his warm good humor. When you look around this house, you get a sense not only of history but of serenity and continuity and of how much Nancy Reagan has contributed to that. She has brought her own brand of commitment and elegance to the White House. She has brought as well her own sense of public purpose to addressing the tragedy of drug abuse not only in your country, but throughout the Western Hemisphere. As a prime minister and a head of government, I know something of the pressures and tensions on relationships and families that come with these jobs. And of all the world capitals, nowhere is the curiosity greater and the pressure higher than here in Washington. In this unique and demanding climate, Nancy Reagan has been more than a model of grace. She has demonstrated exemplary qualities of loyalty and resolve, which I believe are to her great credit. On an occasion such as this, one speaks briefly of the achievements, the agenda between our countries, and I'll be very brief. The agenda is comprehensive. The issues are complex and the solutions are, as President Kennedy once said, in regard to Canada-U.S. relations, neither easy nor automatic. As for the achievements, there is still work for you, Mr. President, to get the free trade agreement ratified by Congress. This is a tremendous accomplishment. The largest trade agreement ever negotiated between two sovereign countries, and it opens up a world of new possibilities and prosperity for both our peoples on both sides of the border. And one of the reasons we made that agreement is that President Reagan believed in the initiative from the beginning and stayed with it to the end. Engraved on the mantlepiece of this room, there is a quotation I believe from the first occupant of this house. I quote it because it applies to the present occupant of this house. May none but honest and wise men, President John Adams wrote, ever rule under this roof. Ronald Reagan has been both honest and wise, and for us and for Canada, he has been a good and a valued friend. Ladies and gentlemen, I ask you to rise as I propose a toast to the President of the United States and Mrs. Reagan. The President, Mrs. Reagan. Love is like a resting place shelter from the storm. It exists to give you comfort. It is meant to keep you warm. It invites you to a stronger sea for some a way of living, for some a way to feel, and some say love is holding on. Some say letting go. Some say, some say they... Perhaps love is like the ocean full of conflict, full of pain, and it's cold outside, from the winds, if I should live it for my memories of love. Thank you, Bruce and Larry. Great to have you back at the White House. It's always a pleasure to hear you. Thank you, Mr. Bruce. A highly versatile artist. Bruce Hubbard began his career at a place that most artists dream of on Broadway, and his debut was in Leonard Bernstein's musical 1600 Pennsylvania Avenue. Bruce, maybe that explains why you're always so much at home here. From Broadway, Bruce toured Europe. He made numerous off-Broadway appearances, and he made his film debut as a gangster in Francis Ford Compola's Film Cotton Club. Highlights of Bruce's 87 and 88th season include performances with the Finnish National Opera and in Moscow. You know, Bruce, first, I followed you to 1600 Pennsylvania Avenue, and now, next month, I'll be making my own debut in Helsinki and Moscow. Thanks for a great lead. But seriously, hearing you again was a great treat as it always is, and we thank you, both of you, for a very wonderful evening. Thank you.


This study compared two different types of satellite sensors to measure the correlation between nighttime light and gross regional product, GRP. The Defense Meteorological Satellite Program's Operational Linescan System, DMS-POLS, was the only sensor available until the launch of the visible infrared imaging radiometer suite, VIRS, sensor on the Suomi National Polar Orbiting Partnership, NPP, satellite in October 2011. The study found that the VIRS sensor had a higher correlation with GRP than the DMS-POLS sensor, indicating that the VIRS sensor is better at measuring economic activity. This finding provides a basis for using the VIRS sensor to accurately estimate economic activity in areas where census data is unavailable or difficult to obtain. This article was authored by Chang Li, Xiaoling Chen, Shili, and others.


Today, my colleague Teresa and I are thrilled on behalf of Premier Clark and our colleagues in the Government of British Columbia to announce that we are providing $1 million to help forge that partnership with the Aerospace Industries Association of Canada on a project designed to solidify, coordinate, amplify and expand our efforts. I believe and obviously our province believes and I know lots of people in this room believe that Aerospace is certainly the best job creator I've ever seen and I'm very happy to be involved. We know the Aerospace and Aviation Industries are critical as we work to grow our economy, to provide high-paying jobs for families in every region of our province. Today is a great day just not for Canadian Aerospace and BC Aerospace but it's also a great day for BC taxpayers and for the economy of British Columbia because what we're doing through this agreement is really about jobs, economic prosperity and building a truly pan-Canadian Aerospace industry.


Hello, and welcome to Three Questions, a new series in which we feature new scientific publications and ask the authors, one, what they've contributed to the community, two, why it's important, and three, what's next on the horizon for discovery. I'm your host Mark Webber, and today I'm delighted to welcome Tian Min Xu and Abhishek to represent their team in discussing their new publication in the 2021 International Conference on Machine Learning. Tian Min is a postdoc at MIT, advised by Josh Tenenbaum and Antonio Tarraba. Abhishek is a research software engineer at IBM Research, and both are part of the MIT IBM Watson AI Lab, which has funded this work as part of an effort focused on developing what we call machine common sense. Welcome, gentlemen, and thanks so much for joining us today. We have your paper, which is Agent, a benchmark for core psychological reasoning. And we'd love to ask you first, what have you contributed in this publication this week? Right, first of all, thanks for having us here. So in this work, we are interested in building a benchmark to evaluate how much and where machine can understand core concepts in interest at college. So just to give you a little bit of background about interest at college, it is basically the ability to reason about mental states of other agents by watching their actions. So mental states includes the goals of agents, their beliefs, and their desires. And such ability actually comes naturally to people. Even preverbal inference can understand many core concepts about interest at college. For example, babies actually understand that the agent has a goal. And in order to reach that goal, you need to find the most efficient path with respect to some vertical constraints. And then in such a way, agent can maximize its reward and minimize its cost. So the question here is that we actually don't know whether machine agents that we build nowadays, such as robots, can actually understand this kind of core concept. And there's no way to evaluate currently. So we want to fill in this gap by presenting this benchmark to the machine and the community. So specifically, the way we design this kind of trials to test machine agents understanding about core psychological reasoning is very similar in a way that we design the experiments to test whether babies can understand such concepts. So there have been many studies in development psychology where people design experiments specifically to test whether and when babies can understand core concepts such as goals, beliefs, desires of an agent by just watching their behaviors. And we copy and develop a bit more trials in a similar way as people design the trials for babies. But then now we're presenting for machines. And then test machine, test by the machine actually can also understand such concept in the same way as babies do. We have a hypothesis which is actually the core social understanding builds upon your core physical understanding. And if a machine learning model want to succeed in our benchmark, such model also need to have a basic concept about how the physical world works. And just as we're showing these are very nice videos about how babies understand these kind of situations. Exactly. And I want to pull up the data set that you guys have created. And Abhishek, perhaps you could walk us through some of this a little bit. So in the goal preference task, we usually test whether what kind of object preference the agent prefers. So in goal preference, you usually have two objects on either sides. And we show the model, the video that the agent prefers one object over the other. So this forms the feminization video or the behavior expected behavior. And then in testing, we show them two videos. One where the object goes towards the goal object that was not preferred before. And then the other case, it did go towards it. So one forms the expected behavior and other forms the surprising behavior. So these kind of videos they use on the baby studies to see if babies understand preferences of the agent. And that's exactly what we're doing in this case where we're showing machine learning model these videos and see if machine learning model also understands preference of that agent. Right. And so there's four different scenarios in the data set. Goal preferences, action efficiency, unobserved constraints, and cost-reward trade-offs. John Min mentioned where an object might be jumping over something. So first you teach through familiarization, and then you say, okay, it's surprising if they're jumping when there's no object to jump over, right? Yes. And those are those common sense things that we take for granted as humans. But babies have to learn in their first 18 months. And so do AI models, right? Yes, exactly. One of the things that excites me that this paper represents a line of work that is really focused on this first 18 months of human developmental psychology. And the various stages of maturation and intelligence that take place over those 18 months. And so I'm hopeful this is not the last paper we'll be talking to you guys about, but we'll get to talk to you about a number of different papers with you and your colleagues who are working on this. Let's ask the second question. I want to bring this into the real world. So intellectually, this is super interesting, but in a short term and a long term horizon, what are you seeing as a real world impact potential for this kind of work and how does that energize you to continue on this? Right, so essentially it's related to my personal goal as a researcher. So ultimately, I want to build robots that actually can understand humans and then help humans in different situations. So in order to build robots that actually can develop such powerful social intelligence, they have to have to wait to infer the mental state of humans. So obviously, we are doing something like that in this benchmark. But then similar like we are watching basically very simple admissions. They are far from the real human activity that we see every day in real life. However, the idea here is that the principle that we use to infer agents in such simple admissions is actually the same kind of principle we use to infer the mental state of real humans in real life. So real humans also have goals. They may have different goals. They don't have such simplified goals, but they have goals nonetheless. And they want to reach the goal in the most efficient ways, right? So those principles are basically the same. Now the question is that if we build some models that have some kind of structures and knowledge about agents in these simplified environments, how can we scale that up to real worlds? I think that's still an open question. We have some ideas, but it's still on a very early stage. But I think coming up with a solution that can help us solve problems in simple worlds may give us some insight about how we can solve problems in the real world. Very good. Yeah, and thinking about those two, those latter two scenarios of hidden constraints and trade-offs, those are so fundamental to even basic human intelligence, and human common sense. And they're quite complex when you take them into more advanced settings versus a very simple setting. So I see that as being really relevant. What about you, Abhishek? What aspect of the real world impact and are you excited about and where do you see this going over the next couple of years? So as an engineer, I'm really interested in transparent systems. And the way I look at this whole project and the way it fits into the whole machine common sense project is this kind of systems would form the low level intelligence or intelligence that come to basic conclusions. And these kind of systems would be used for building more complex intelligence. So a system that is able to tell you exactly how it came to a conclusion would be much more attractive to everyone rather than a black box system that you just cannot know how it came to a conclusion. So for me, a system that can understand basic goals and desires could be used to build a much more complex social interaction machine that not only has real world application, but that is much more reliable than today's systems. And do you think the real world applications are limited to robotics or what other kinds of applications do you think are relevant here? I think any kind of interaction. So the interaction doesn't have to be just conversational or robotics, but this could be part of a fleet of self-driving cars, for example. I mean, when you drive a car, you sort of have some kind of etiquette or manners you have to maintain, or it could be a chatbot talking to a customer service, or it could be anything like a robot working in a logistic warehouse. So any kind of machine interaction, this kind of system would definitely help make that a much more social interaction. And when we think about the ability to reason about costs, about trade-offs, and there's nothing stopping us from exploring the area of ethical AI and understanding the different cost functions involved in human ethics and making some of those trade-offs from a machine common sense standpoint. Is that right as well? So I think there's definitely a very great opportunity for us to either call current studies or either as machine researchers to try to think about how we can actually capture the kind of complex costs and rewards that people have in our society and how we can build our system that can adapt to those kind of rewards and costs. Exactly, yeah. Very good. And so to close us out, what's next on the horizon beyond this paper and what do you hope comes out of this paper and what are the unsolved questions and answers that we need to discover? So one of the things we're hoping for is not just the AI community or ML community to think in the sense that building more general or explainable systems. So our data set would encourage people to build models that can not only understand to do a task, but rather to understand the underlying principles that govern the whole process of coming to a conclusion. And so we hope that our data set in conjunction with other data sets could be used to build models that are much more understanding principles of the whole interaction. So this is basically the first step towards building benchmark for machine social intelligence. But there are other aspects of social intelligence that we're not capturing in this benchmark. So for example, we also have the ability to research about other people's perceptual access. So for example, what other people cannot see and then also infer the beliefs of other people such as what people think about the world. Now, there are also other aspects that goes beyond where we can infer about the humans' mental states. For example, I do have an understanding about your mental states. Now what? Now I can try to help you, right? But then how can develop a good plan to help you? That's another kind of aspect of the social intelligence that we also want to build. The connection between the inference about my mental state and my goal preferences, my trade-offs, and the planning side, the intelligence of how do I organize my actions in order to support your actions, your needs. Exactly. So imagine you have a robot helping you in the home. The robot may have no clue sometimes that what you actually want to do. But then robot can still help you. Maybe the best way to help you in that situation is just to reorganize your home, like clean up all the messages you left. And then maybe that's the best way to help you. But in order to do that, your robot actually need to infer what you want. And then you also have a sense about uncertainty about that inference. So it's actually a very complex problem. And then that's definitely something we also want to build either as a benchmark or as better models. Well, I know in the MIT IBM Watson AI Lab and the campus of MIT and Harvard, there's a lot of great AI planning experts, including ones that we have funded. And hopefully there's opportunities for collaboration with these two fields and to come together and for an integrated approach once the time comes. I'm sure it's already started. Yeah, definitely. Well, this has been such a pleasure and an honor to speak with you, gentlemen. I know you represent a larger author team of people who have been working together. So I want to thank them and all your collaborators as well as DARPA, which is supporting this line of work. We look forward to seeing those next phases. I'm very excited about how you guys are looking to combine this physical common sense, social common sense and then have an eye on the horizon toward how these are going to connect to planning so that we can develop AIs that are actually supportive and helpful to human beings and all kinds of real world scenarios. So thank you again. And well, until next time, be well and good luck with all of your research. Yeah, thanks. Thank you. Bye, everyone. Bye.


It's a real pleasure to be here. I'm Tom Cullis, and I'm from the Uniformed Services University of the Health Sciences in Bethesda. And during this session, we're going to explore further some issues that have been brought up earlier about, what's the military's role in all of this? And how does the United States military engage in the Asia-Pacific region specifically in the lower Mekong region? And explore some of those issues. Perhaps get a word about the US military support of the USAID Office of Foreign Disaster Assistance efforts in the Philippines that are currently going on. And to address this, it's our pleasure today to have Rev. Colin Chin, who's the US Pacific Command surgeon. Dr. Chin has worked in the Asia-Pacific area for about the past 15 years, and one guys or another. He was stationed in Okinawa as a gastroenterologist at our hospital there. He has been the Marine Forces Pacific surgeon, in which capacity he's worked with disaster response and health issues in support of the Marine Corps throughout the Pacific area, including many health engagement operations. He was the officer in charge of the US military tri-care office in the Pacific region, which looks at the military's health care delivery plan in that area, and currently is back in the Pacific at the US Pacific Command as a surgeon. So we welcome Rev. Colin Chin. Dr. Colson, thank you very much for that introduction. And Dr. Morrison, thank you very much for inviting me to be here with this August panel. I appreciate you bringing me back from Hawaii to here to the DC area, but it truly is a privilege for me to represent US Pacific Command at this very important and vital symposium. Since I have the pleasure and the honor of presenting during my presentation one hour after we all had lunch, and for those who are jet lagged, I decided to do things a little bit different. You're going to have a very short, I trust you, very short presentation of what PACOM is all about and what I and my staff do in the surgeon's office. So here is the area responsibility for US Pacific Command. It encompasses half of the Earth's surface. It encompasses a wide area, as you can see, encompassing over 50% of the world's population. Three of the largest nations in terms of population reside in our AOR. And three of the largest economies are in the Asia Pacific region. However, also seven of the poorest countries in terms of economy are in this area. So it's a very large and diverse region, and we like to say it stretches from Bollywood in India to Hollywood in Southern California. So with that, there are several threats to health in the region that we deal with, starting with natural disasters. As evidence in the Philippines last week, every year there is some form of natural disaster that will occur in the Pacific, whether it is a typhoon, an earthquake, a tsunami, or a volcano that's erupting. It occurs in the Pacific region. And if a disaster is declared by the country and the US ambassador in the region in the country also declares a disaster, USID takes the lead for the US government, and DOD is a supporting element for the US effort. So we have natural disasters, but we also have very high population densities, the emergence of mega cities, as well as a water quality in some areas that may not be the best. So you combine these factors, as well as the deforestation that you heard earlier, which then human populations going into the forest are then exposed to emerging or novel viruses and other diseases, sets up a situation in which disease transmission is very easy and creates problems for the population there. In addition, as these countries are increasing their economic abilities, their standard of living increases, and with that, the aspirations to follow Western lifestyles and Western diets. And of course with that comes what we've been experiencing here in the United States and in the Western societies, the plague of noncommunicable diseases. So the obesity epidemic that we have here in the United States, the problems with hypertension, diabetes, heart disease, and what we're seeing is these countries are now beginning to see these problems. So what do we do in US Paycom Command Surgeon's Office? These are my priorities. I think it's very important for peace and stability in the region that engagements between the Chinese and US militaries are peaceful and productive. And health is a very easy way for that type of relationship to develop and to build. And that is what we are doing today as I speak. Engagement with China is my number one priority. But closely following that, as we heard here, I thank Dr. Ort for your question about malaria elimination and what is the military role. Well, we are heavily engaged in this. And I would like to discuss that further when I talk with Dr. Cullison. So there's more to follow on that. As we saw last week, health response to disaster is a major effort at the Paycom Surgeon's Office that we participate in. Do we have a role in the Philippines right now? The fact that I am standing here before you means that, no, right now, as we get the information from USID folks on the ground, that from a health perspective, DOD is not required at this time to respond. Now, DOD is providing significant logistic support to the Republic of the Philippines. They've asked for heavy and medium lift to transport supplies, equipment, food. We are asked for search and rescue teams. We have asked to provide imaging to provide our aircraft and our altitude aircraft to survey the area of devastation to give the planners a better idea of exactly what the level of destruction is required and what planning efforts need to occur in the future. But as it stands right now, there is no requirement for DOD to provide any medical response teams. And then finally, I'll say that emerging infectious diseases is another large area of interest for us. Obviously, about five years ago, when avian flu was a very hot topic, we were very much engaged with that. Dr. Cullison was engaged in some of those efforts. And we use our military labs, AFRIMS in Thailand and the Naval Medical Research Center Asia which is now headquartered in Singapore, to work with regional labs, labs such as the Institute Pasteur in Cambodia, Institute Pasteur in Laos to work together on disease surveillance, vector control, and vaccine research. And we're also working with, again, the countries in the Mekong, as well as the entire AOR, to help them achieve the World Health Organization and now international health regulation standards. So we are, again, working very closely with those organizations to achieve those goals. So how do we do that? Well, we partner. Now, in the past, I would say that DOD has probably been criticized and probably rightfully so that we worked in a vacuum. We just sort of did what we did and didn't consult or collaborate or communicate with anyone else. Even among our four services, we were guilty of that. We would have a marine unit go to a country and do a health engagement. A month later, there would be an Air Force team that would go to the exact same location, do the exact same thing. And the question would be then asked, did we accomplish anything? The answer is no. Because the goal back then was to do some things we called med caps.  Did we build capacity for that local health system? Did we build capability for that country? By doing that, the answer is no. Because a week later, the kids are bathing or playing or drinking the polluted water. They're reinfected with their worms. By pulling all the teeth, we may have just put out out of business the local dentist and providing eyeglasses put out of business the optometrist. So we're changing our approach now as we engage with our partner nations in terms of trying to work with them to build their capacity and capability. No longer are we doing med caps and dent caps, we're doing subject matter expert exchanges, we're doing academic exchanges. Again, trying to build capability capacity. And we're also trying not to do this in a vacuum. We try to do this with our US government interagency partners, some of which I have listed there. This is not an all-encompassing slide. You don't see your logo. That doesn't mean that we don't work with you. We try to work, again, a whole of government approach. So it's not just DOD going in by themselves. We go in working, if you go to the embassy, I met with many of the ambassadors, met with many of the country teams and say, how can we work with you and your team to better coordinate DOD's effort for your effort, Mr. Ambassador, for your goals for this country? So that is our new approach. Likewise, again, we work with several NGO organizations. We work with private organizations, private universities, again, with a whole of government approach and likewise in the country, trying to use a whole of government approach as well. So I'll take malaria, for example, in many countries, and it was alluded to in the malaria panel, that the Ministry of Health may have a national program for malaria elimination. And several times, the military, that nation's military may not be invited. So what I'm trying to do is work with that military, work with the ambassador to get the Ministry of Health, the Ministry of Defense together so that we can include the military as part of a national effort. Again, for a whole of government approach, not just a whole of US government approach, but whole of government approach for our partner nation. So Pacific Partnership is a prime example of one of our many engagements that we do in the AOR. This stemmed from the 2004-2005 tsunami, as you may or may not recall, about the huge tsunami that affected a huge part of the region, Indonesia, Thailand, all the way into the, I think to the Maldives. And we responded initially with the USS Abraham Lincoln and the USNS Mercy. That opened a lot of eyes, that event, because poles were taken in Indonesia before, in which the favorable rating for the United States was 20%. After our response to the tsunami, it was over 60%. Admiral Mullen, when he was the Chief of Naval Operations, wanted to kill the hospital ship program that the Navy had. When he was Chairman of the Joint Chief of Staff, he said he's glad that he did not kill that program. So since then, we have an annual program, it's called Pacific Partnership. Every year, we either send the Mercy, or we send a large amphib to go over several months, to several of the countries in the region, and we rotate that. It's not always the same country. Working on disaster response preparedness, not just for us, but for our partner nations. I think, even though it's been a devastating event for the Philippines, from the typhoon, and again, time will tell, but I think their response has been tremendous, because I'll look back to, again, US military medical has not been asked to come. They're taking care of many of these issues on their own, so we will see. So I just wanted to tee up these topics for you to give you an idea of what we do in US pay-com, and I look forward to the discussion with Dr. Colson, as well as your questions, and I leave this last slide for my colleagues, members of the audience, who come from the warmer regions of the world. As you're shivering here, I see lots of people with heavy overcoats. Think of the picture here, hopefully that will warm your hearts. Thank you very much. Colin, thank you very much. The military has been accused of not following humanitarian principles, humanity, neutrality, impartiality. Is it reasonable to expect the US military, or any other military, to follow the same principles that NGOs might follow, or the ICRC, or other totally neutral organizations? What is the role of the US military at large, and how does health play in that role, particularly in the Pacific? So thank you for that question. Let me first respond to how does health, what is the role of health in the Pacific? And I'll get back to the President's Rebalance Initiative. I think health plays a huge role, at least in the US government's response for the rebalance, is that we play a huge role in that, because we all think about in terms of the rebalance, in terms of DOD, is shifting aircraft, shifting ships, shifting large units. And that is happening. However, as Admiral Lachler, the US Pacific commander, has mentioned several times, in public cases, mentioned to me, is that health is, in many respects, leading the rebalance efforts in US pay comm, because, and as I said before, and I alluded before, that health is considered non-controversial, health can be considered safe, in several of these countries, in which we're having emerging relationships, and health can open doors for military to military health engagements that are not open for traditional military to military engagements. So for example, Mirrenbar, that is a country that is emerging with their new democracy, but because of the history of that military, there is the human rights abuses from that military in the past, we have to be very careful in DOD in what types of engagements that we can have. There are some openings in the legal profession that are starting, and there are initial discussions about can health be the next step? And so in August of this year, we participated in a multilateral health engagement in Thailand, hosted and led by the Thais, with us invited, and Mirrenbar Medical, military medical folks were invited, to discuss tropical disease topics, as well as disaster relief. So that is an area where, again, the answer is how does health play a role in the Pacific? I think that is one very important area. And to answer your first question, we need to follow all the standard rules of conduct. We can't just go into a country and do what we want to do. We do have to follow all the standard rules. I mean, Secretary Russell was just here, he just talked about what the State Department does in terms of diplomacy is not altruistic, it's in the United States' best interest, and I think it's safe to assume that people who wear a uniform are there to represent their country, and it is about advancing that country's issues. And in that regard, we've had a lot of talk about malaria, we've had a lot of talk, sort of some allusions to the overseas labs, to Namru and the Navy Medical Research Center Asia. Explain a little bit about what the military's interest in infectious disease was initially in terms of force health protection, how that evolved into permanent overseas labs, and how that's kind of evolved into a national capability that the United States and others can use, and the host country can use. But we did something selfish, and it turned out to be something that other people are using now. Right, obviously, we will do things that obviously is good for the US military, but it does translate into good things for our host and partner nations. But going back to, let's go back to the beginning, why is the military involved in infectious diseases? It just goes back, just think of some of the, just again, let's start with malaria, Panama Canal, the efforts to build that canal multiple times in the past were thwarted by malaria, but it was a US Army physician who solved that problem, and we were able to build that canal as a nation, which obviously benefited the United States, but then benefited the world, because now we have this canal. But one of my charges as a command surgeon is the health of our active duty forces. And so we will go to areas in the world in which there are significant infectious disease threats. And so I have to read, so it's in our interest to do research in infectious disease for surveillance, vaccine research, treatment research, prophylaxis and prevention, so that we can deploy a healthy force who will not get ill while they're deployed. Historically in the wars that we have had, it's something we call non-battle diseases, meaning infectious diseases was the main reason why military members could not fight. It wasn't from wounds or injuries from battle, it was from infectious diseases. So that's really the genesis of why the U.S. military is involved in infectious disease research and then coordinates to why do we have overseas laboratories? So we have, the Army has a joint U.S. Army, Royal Thai Army, AFRIMS, Armed Forces Research, Institute of Medical Sciences. It's based in Bangkok, Thailand. They have been there for over 50 years. A joint Thai U.S. Army lab that's done tremendous work in Thailand and in terms of all sorts of infectious diseases, malaria, dengue, tuberculosis, you name it. The reason why is because that's where those infectious diseases are located. If we located that lab here in the United States in which we don't have those infections or these infectious diseases on a day-to-day basis, I think it'd be very hard to provide truly groundbreaking research. You have to go where those diseases are located and also I'll make a comment that even though our infectious disease specialists are securely trained and they have great knowledge, book knowledge of all the infectious disease out there in the Mekong, the doctors who treat these infections on a day-to-day basis have much to teach us on how to manage those diseases. So that's why we have our lab. So we have the lab in Bangkok. We also have the Navy Medical Research Center Asia which is now in Singapore. That has a history of I think 60 to 70 years and they have been through and former commanding officer Dr. Daniels standing right here right in front of me but they have been actually started in the Philippines. They went to Indonesia and now they are very briefly headquartered in Honolulu but we have reestablished them in Singapore but they also have a hub in Cambodia and also they have some people working in the Afrim's lab and there's possibilities that we may be able to expand throughout the region, other satellite laboratories and we're looking at that. We could talk about a lot of things but we have a few minutes left so let's take a few questions from the audience. We have two Navy guys here so the Air Force told me they wanted a pair of time. So Colonel Chambers. Good afternoon, Lieutenant Colonel Allen Chambers of the Air Force International Health Specialist Program. First Admiral Chen, thank you for your leadership and guidance on these important topics that affect all of us. Our organization in particular is at one challenge I'd like to ask you about. You talked briefly onto the podium in that as we've noticed working with a number of countries in a variety of continents especially hosting an educational forum for disaster preparedness where we attempt to bring representatives from both the Ministry of Defense and Ministries of Health together. Many times it becomes apparent that that's the first time those participants have sat together on the same table. So my question for you sir is how can the military and I'm speaking specifically with me and Marv at other countries in mind sir as we engage with other countries in your AOR how can we help encourage them to facilitate a dialogue, to better coordinate and prioritize initiatives between the Ministry of Defense and the Ministry of Health. Thank you. Okay, other questions in the back back there. Sorry, Adam Cameron Scott from University of Sydney. I'm actually over here doing a study on civil military cooperation in health security. So this is very fortuitous. My question really is there's a lot of debate on both sides of public health and the military about the right or the purpose of military engagement in health issues. Talking with some of the people here in DC as well as some of the locations. When I asked them what is the value that the military bring almost unanimously the first thing that comes to mind is seems to be the money and the resources. So I'm just interested in your perspective other than you've already mentioned research other than that what areas do you see as the military bringing value adding given that trust seems to be such an issue. Let's take one more. Hi, Jill Gay, What Works Association. And the military has been a leader on HIV vaccines, so especially in Asia. Could you talk about what the military is doing vis-a-vis HIV in specifically Myanmar and Laos? Thank you. So we've got, how does US military engage other countries, military to military and military to military to other parts of the country and how do we encourage discussions? What does the military bring besides money? Is that right? The question that we discussed earlier is the military tends to do episodic engagement. The development agencies tend to be there long term. The one exception to that is the overseas labs. So how does the episodic engagement facilitate or compete with the ongoing engagement? And then HIV in Myanmar and Laos. So let me, so first of all on Myanmar and HIV. Again, this is a very early relationship that, so we haven't done anything specifically with HIV. But right now we've only discussed tropical diseases and disaster relief. We have to take that a step at a time. I have to make sure that I'm not stepping ahead of US government policy in regards to engagement with Myanmar. But obviously that's a disease of interest, disease of concern. So what I think we would do, once we get to a point, we would perhaps follow the model that we have used in Vietnam. In which we have done a lot of success. And Vietnam has had tremendous success in working the AIDS and HIV issue in Vietnam. And use the PEPFAR program. So I think that would be how we would, again, given the right time, how we would engage HIV in Myanmar when the time is right. That would be the model that I think I would look at. As far as our engagements with other militaries, I mean, I may be a little bit biased here, but I think there is a lot of benefit to doing that. We don't go to a country unless they ask us to go there. I don't force a program upon a host nation military unless they ask for it. We will provide them visibility of the different types of programs that we have and we'll see what are you interested in. So for example, with China, they're having problems obviously now with non-communicable diseases. And they have come to us when I have academic exchanges to work on that problem. The other thing that we can help benefit is to provide an avenue for them to work with their counterparts in their civilian sector. Because as I mentioned earlier about the malaria issue, many of these nations, militaries, are not included in the discussion. And so I come to forums like this and hear how much of a problem it is. And as I look at the military population, I see that that is a mobile population. Just like the migrant workers, they are also very mobile. They are going to the border regions where there's drug-resistant malaria. They then go home for leave. So they go from that high endemic area back to their city, where they're from, where the village where they're from, maybe in which there is no drug-resistant malaria, but they're infected. So maybe they're bringing it. So also they, many of these militaries are using monotherapy as their program. So we're trying to open their eyes to the fact that that is probably not the best approach. And perhaps combination therapy is the way to go. And many of them are coming to the realization that they need to do that. And we're encouraging them and helping them and giving them in contact with the right people to develop a program, getting them in contact with their Ministry of Health. Make sure that they are interlinked with the national program. Another area of concern, which I think will be beneficial, is many of these countries are engaged with or want to be part of the UN Global Peacekeeping mission going to Africa. Okay, so they're at the border regions. Some of their people may be infected with drug-resistant malaria. They don't have programs right now to test their troops before they send them. We're actively engaged with them, encouraging them. You need to have a screening program and a treatment program and they were assisting them with that effort. Because I think the worst thing we could do, and I think it's great that they're engaged in the peacekeeping program, but then to send their folks over to Africa and that that is one of potential vehicles to introduce drug-resistant malaria to the African common. So those are just some examples of how we're trying, how I think it's beneficial that we are engaged, heavily engaged and actively engaged with our host nation militaries. What about the question of working with other organizations and I'd add to that, are there areas besides infectious disease, such as trauma care or some other military specific things that the military engages in? Right, so we've had, the U.S. military has had 12 years of war in the Middle East and we have learned huge lessons on management of trauma and the results of trauma. So very recently we have gotten inquiries from Singapore, actually, because they have some patients who are triple amputees, not a result of IED injuries, but they have some triple amputees and they wanted to know what is our approach to managing long-term of these patients? So we're sending a rehabilitation team from the Walter Reed National Military Medical Center in a couple weeks to Singapore to, again, as a subject matter expert exchange, to have a symposium on this and then my goal is, because Singapore has a very robust healthcare system, but we have other countries in the Mekong in which perhaps as a result of this bilateral exchange, we can then develop a multilateral exchange because I heard some questions about the mine issue in Laos and Cambodia. So I think that's something where we can help. I know these countries are, it's an issue and we would like to share our experience of knowledge from the last 10 years to these countries. I think we have time for one more round of questions if we could in the back. At first, I'd like to thank you for the slide of the warm horizon there. Secondly, let's say you get the green light to do Mill Mill Health Collaboration in Myanmar. What are your concerns or what are the sensitivities and consideration of partnering with a state that is party to ongoing conflicts? You talked about democracy and past human rights abuses, but it's a government that's only in name civilian, same actors as you know. And secondly, there are still ongoing conflicts. And secondly, we just met with the president last week who said that he's ordered his military to honor the ceasefires, but that if it's not carried out in the field, it's not necessarily because it's not the state's will. So you may be partnering with the state, but implementing in the field where local officers are not following state command. Other questions? Well, let me, so as I alluded to, this would be a very delicate relationship that we would, if we do engage more into it. An area of concentration that I probably would stick to in the beginning is drug resistant malaria. That is one of the epicenters of this problem. And I think that's the one that I think I would focus on. Fully understanding the problems with the military in Myanmar, their past history. And as I said before, I am not gonna get forward of US government's intent. And obviously we coordinate very closely with OSD policy and all sorts of these types of issues. Even before our multilateral engagement hosted by Thailand, we checked, we made sure that we got approval from OSD before we did that. So again, it's a very sensitive issue. And it's a delicate issue. We fully acknowledge that and we will take those precautions before we engage. And so that's, again, as I said, we will start with malaria. And as I said, go very slowly. I'm delighted to see so many US military folks here, including General Schoolmaker, the former Surgeon General of the Army. Thank you very much for coming. And Admiral Chin, thank you very much for your comments. We very much appreciate having you here. Thank you, thank you very much. Okay. Thank you. About the brand new... Oh, yeah, I love that. I want that.