Well, good to be with you all. Thank you for coming this morning. I haven't written a book on the subject, but my life has entwined a lot of places and events part of this story ever since. And I'll give you insight into that in just a bit. This is a picture of the Trinity test itself, first nuclear bomb ever exploded in history. Below it is a picture from Mesa Verde. This is the Cliff House, Colorado. And I'm going to just briefly touch on the Anasazi because of the culture about where this laboratory was placed. I'm going to be speaking to you in three different sections, just briefly on the siting of the lab, then on this whole aspect of World War II, the development of the nuclear weapons themselves, and finally wrap it up with a brief epilogue, including some of the Pacific nuclear testing in which the Navy was involved. So at any rate, we'll touch on that a little bit as well. Before we get started, though, one of the things I have always enjoyed in giving this lecture is having some of the veterans who had been present in the Pacific at the time come up afterward or their descendants to share their experiences with me. And that to me has been a very valued part of my own pleasure in doing this. And I've already had the pleasure of two of these this morning before the rest of you arrived. So I look forward to hearing from some of you afterwards if you'd care to share those with me. So with that, let's go on. I mentioned my life involving places and people. At university, I attended a lecture given by Dr. Robert Oppenheimer who was a memorial to Einstein who had died the preceding year. I walked into that lecture hall, I sat down. I didn't understand a word Oppenheimer was saying about the theory of relativity. I'm not sure I still would. But at any rate, it was quite fascinating talking about Einstein. Little could I have guessed that some 32 years later this blue-collar kid from New Jersey would be out there hired to implement a new federal program at that lab. Between that point here in 1956 and here in 1988, I was stationed in Pearl Harbor, at Sink Pack, for a couple of years. I was there during the Pueblo crisis in the war room at the time. I can tell you why we were unable to respond to that, but I won't, it's not part of this. But the other thing too, I took eight corporate trips to Japan for my company. And we had plans both in Tokyo and also down in Kura City adjacent to Hiroshima. So I've seen Hiroshima, I've spoken to and with many Japanese, had my own answers to why we dropped the bomb. Should it have been done right or wrong? Some of you might have seen a letter to the editor I wrote on August 21st in Providence Journal that said, a bomb, right or wrong, my opinion, decidedly right. And if you have questions, I'll share my thoughts on that with you. So at any rate, let's go on. Where was the lab sited? This is the Four Corners area of New Mexico. Here's Mesa Verde. Here in the north Rio Grande Valley is Los Alamos. The Rio Grande River runs down here. We've got Santa Fe. Santa Fe was developed in 1610. It's the oldest capital in the United States. It's also the highest capital in elevation, 7,000 feet. Here is Lamy, it is down in here. This is the railroad site where all those supplies were being brought in by train. You can see that they would have been brought to Santa Fe, taken up through here, through San Aldefonso. Some of them were taken directly across this way. Others because of a heavy bridge had to be brought up this way to where the lab was sited. This is rugged country, quite rugged country. Valleys, hills, et cetera. All right, okay, there we go. Here you can see Los Alamos. It's on what is called the Pajarito Plateau. You've got the Rio Grande down along here. It's about 400 foot high cliffs. And then this long, gentle slope here of the plateau. Mountains along here, up to 11,000 feet. And here is the largest volcanic caldera in the world, the Valle Grande Caldera. The reason I show you this slide is because from what I was given to understand in World War II, we had battleships that would fire shells weighing as much as a Volkswagen. And they could fire them roughly 28 miles. At the time, that was probably one of the most successful and powerful munitions that we had. Get this, this volcano back in its day was taller than Everest. When it blew roughly a million years ago, rocks the size of cars landed in Kansas 300 miles away. Think about that, the force it took. It was the second most powerful geologic eruption in the course of world history. So with that possibly in mind, we were about to create the most powerful weapon known to mankind. And look where we put it, okay? In addition, this was a weapons site long before that because the Indians used to come into this area, they settled it along this plateau, 20 to 30,000 of them. And they would take obsidian from the lava flow to make spear points and knives, flush scrapers and things like that. So it was a weapons site very early on. All right, to give you a sense of that country, here is the top of the plateau, Pajarito Plateau, those mountains behind which is that called Dara. This is called Free Holies Canyon. How many of you have been to Los Alamos or out in that region? A couple of you. How many of you have served in the Pacific at the time of this war? Couple of you, all right. How many of you have been out there at all? Many of you, I'm sure. How many of you are descendants of those who were in the Pacific at that time? A few of you, all right. Just trying to get a sense of what you are and where you know from. At any rate, there were Indian Pueblos built along this cliff and they would have looked like this, which standing on top, looking down, here is the Pueblo. You can see the different rooms that would have been completely surrounded by a high wall was defense against marauding Indians. So that was one of the types of dwellings they had. They also farmed on top of the plateau and here is another small series of buildings for one of the dwellings up there just to give you a little bit of a sense of that region. As I said, there were as many as 30,000 Indians living along this plateau at the time. Back around 1100, they moved out again and they went to the Pueblos where they are located now. So that's an introduction to the site, the power of the volcanic explosion and the weapon that we were going to create. So I'm gonna set this now in the Pacific Theater each of the years from 1938 to 1945, going to give you a little touch of the theaters, German and Europe rather and also Japan and what was happening in the nuclear programs in the world. So here are 38, Japan's been warring in China since 31. They control a good portion of that country. They recently taken nine king and I'm sure all of you have heard about the rape of nine king. Japanese was a very brutal occupation but in Europe, there were some interesting things going on at that time. For one thing, in August, the German military mobilized and they occupied the Sudetenland. You might recall as a consequence, Chamberlain from Britain visited there and in essence allowed that to happen. The rationale being given by the Germans was that this Sudetenland is settled essentially by Germans anyway so we were simply going to take them back into the nation and it made sense, it was a form of rationale. At the time, diplomatically it was sort of a no harm to anybody thing, well they took what was, should have been theirs anyway. I think there was another reason and I'll share that with you now. In that same year, this Dr. Otto Hahn, a German physicist, announces the discovery of the phenomenon of nuclear fission. In this, what you would do is to break up a single heavy element, in this case uranium, into smaller elements and tremendous amount of energy released. He discovered the basic phenomenon. As a consequence of that, Germany begins to research on weapons that would eventually result in nuclear fission. When Hahn announced this to the scientific community in Europe, of course what happens is that some of these scientists say, oh, you know, this could be weapons, Germany knew it. They could be very powerful, Germany had not yet evinced exactly what it was going to do, but then look what happens. One of the European nuclear scientists by the name of Leo Szilard, who was a student of Einstein's, calls Einstein alerts him and Szilard came to the US, that's the other thing. When Germany began this program in earnest, they began in essence capturing nuclear physicists from various German countries. They actually went out, grabbed them and brought them into Germany. When water this got around in the nuclear physicists' community, many of those European physicists began to leave to come to either Britain or the United States, and Szilard was one of them and he came to the US. He gets to Einstein and he said, I think you have to alert the US government to the fact that this is very dangerous. And Einstein did. Now at the time, back here in 1939, Einstein was at the Institute for Advanced Studies in Princeton. FDR does write that letter to Roosevelt. In August 2nd, 1939, look at that date. Look at that date. And here he tells him, Szilard leads me to know that this element uranium may be turned into an important source of energy. Could be used to create powerful new weapons. I think you might want, you don't tell the president what to do, you suggest. You might think it desirable to have some permanent contact made amongst your scientists. And finally, I understand Germany stopped the sale of uranium from the Czechoslovakian mines. Do you know where those mines were? In Sudetenland. Now, if Germany had announced to Europe, we've taken Sudetenland so we can have a new, potentially very powerful source of weapons to destroy you, what do you think the response of Britain and France might have been? Quite a bit different than it was. So I just point this out to you because when I read this, I went, oh wow, look at that. All right, and look at the date. One month later, Germany invades Poland. One month after Einstein writes his letter to FDR, Germany invades Poland. And of course with that, France and Britain both declare war against Germany and we are off and running. Now, the term Blitzkrieg means lightning. You've often heard of the Germans referred to as Huns. Okay, I'm half Hungarian. I'm part Hun. That's an insult to both peoples. The Asians were, I'm sorry, the Huns were distinctly Asians, the Germans were not, but the reason the British and the French gave them this title was because of the speed in the power with which the Huns had attacked way back in the fifth century AD. We're talking 20, 1500 years before it was not forgotten and they likened it to those attacks. So when we talk about events and people and thoughts and how the history has influenced the present, cultures don't forget. You know, the Russians have never forgotten the Mongol invasions, have they, to this day? And here you see it too. All right, war is declared and of course the Soviets invade Poland and eventually they are expelled from the League of Nations. What's going on in nuclear program in the US? Nada, we were not taking sides. 39 Pacific Theater, Japan continues to do what it's doing in China, starting to move through the Pacific Islands. At the time there was certainly no threat to the US interests, plus our people simply wanted no part of another European world war. And Congress knew it and so did FDR. But things continue, it gets a little bit more difficult to accept when you begin looking at what Germany was taking, all right? And they had allied with Russia. They already had an agreement on how to split Poland. And of course the only force countering them at the time is Britain and it's allies, it's colonies. 1940 Pacific Theater, Japanese forces are pushing now down into Indochina. In response, the US cuts off oil exports. This is tantamount to a declaration of war, but it was not formal. At the time there were formal protocols and one of those was you declared war before attacking anything. Declared war before attacking. Germany violated that when they went after Poland. Japan would as well. In 1940, by the end of that year, we look at the world, you can see Britain. The US is not formally in, but is definitely supplying Britain with weapons, armed goods, food, other things, all right? And we can see where the Japanese are moving out more and more into the Pacific. Russia has now moved up and taken Latvia, Estonia, Finland. Things are quite a mess in the world right now. Becoming a matter of considerable concern. Still, the US is not involved, but we're supplying our allies, in essence. We have definitely sympathies in this. It's known both to the Germans and to Japanese. All right, so finally now in 1941. Japan threatens the British colonies, but December 7th, the day that we'll live on and our cultural memory forever, as will 9-1-1, they attack Pearl Harbor. And with that, the war is on. Now, when I was in the military, I sort of told they had cleared the sink pack, but I was stationed and based up in Schofield Barracks, right up in the middle of the island. And the Japanese planes, when they came in, came through Koli Koli Pass, which is on the west side of Schofield Barracks. It's a big dent in the, I think it's the Waianae Mountains or Kolaos. I can't remember which one, it doesn't matter. But they came right over Schofield and they destroyed all the fighter planes on Hickam Airfield, which was right across the street from Schofield. And from there, they just continued right straight down into Pearl Harbor, probably took them a minute to get there, not much more than that, and proceeded to, of course, bomb Pearl Harbor. And within days of that time, they invade Burma, Borneo, Philippines, Hong Kong, Guam, Wake Island, look at how they expanded out into the Pacific. At this point, America has to respond and we did. We did. Finally, we declare war. FDR declared it a day of infamy for the simple reason that by virtue of what he referred to as a sneak attack, it was infamy because the Japanese had a peace delegation in Washington at the time negotiating with us for a peace in the Pacific theater and then they pull this stunt. This is one of the rationales I could use against those Japanese militarists I encountered in Japan on occasion, you know, who started this? Who started, we finished it, but we didn't start it, you did. And of course, just a few days later, we declared war on Germany and Germany invaded Russia. So here, Germany chooses at that point in 1941 to divide its forces. This was a very bad decision. It was a bad decision throughout the course of history and it occurred in more than one great civilization too. Hans made that big mistake back in the 5th century and go into that at another time, not now. Anyway, so when we go from there, finally, yes. Germany declared war on the US first. Yes, they did, thank you.  I don't wanna lose you after 45 minutes. So I can't cover it all. Anything I don't cover, you're welcome to pick up on Q and A, I'd be delighted to stay as long as you like to pick up on 70's points. But at any rate, finally in 1941, FDR does begin the formal organization of the nuclear weapons program in this country. And he orders that this Office of Scientific Research and Development come together to organize all the uranium fission research in the US to achieve a nuclear chain reaction. Okay, and to do this as quickly as possible. Now, at the same time, it sets up commission, both the military and university leaders. What's interesting is that this guy, Oppenheimer, from University of California Berkeley, a theoretical nuclear physicist, had already been organizing many of the conferences of the university nuclear physicists in the country for a period of about two years. So the scientists had informally been meeting for all this time, they were preparing to gather and know as much as they could. But in addition, the key here is Groves. General Leslie Groves, Army, West Point graduate, actually he was an MIT graduate, he was an engineer. He was the guy who designed and oversaw a building of the Pentagon. And after that effort, FDR appoints him to head the military portion of this effort and in actuality, he was really over Oppenheimer, although they learned to cooperate together. Finally, the US nuclear program is launched. 1942, Germans in the Axis countries continued to advance. Germans are pushing now into the Soviet Union. All right, it's not looking particularly great. Japan, they're continuing to extend their empire now down through the Dutch East Indies into some of the British colonies and pushing into Australia and heading for New Zealand and Australia. But they weren't there yet, nor did we want to see them get there. At the same time in 42, Groves is appointed to head that nuclear program, I mentioned that before. Over both civilian and the atomic, and the military side of it, Oppenheimer has now formally chosen to head the development of the atomic bomb. And the two of them come together, and interestingly, although being such unlikely people, they both developed a very healthy respect for one another. You know, why? Because they were both high emails, very different fields, but they came to respect that. They were both decisive, they were both charismatic, they were leaders. They developed a very, very good working relationship. But they had to choose a place where to put this facility that was going to develop the bomb. And they were looking for a place that had met a couple criteria. It had to be far from any population centers, still needed access to pop transportation centers so they could get supplies to it. And it had to be a place where the security could be pretty strong around it. Oppenheimer says, well, I know of a place out in New Mexico. When I was a boy, I was sent there. It was called a ranch school. It was up in the middle of nowhere on the Pajarito Plateau. He was there for a few years. It was a place where the wealthy sent their young boys to make men out of them. These kids lived in tents the year round. They had a lot of hiking, a lot of camping. I can't help but think that they also knew something about the geology of that region. They knew that they were on a volcano. And it might be, I don't know, I've never read this that he said, well, if they withstand a volcanic explosion and we don't know what forces of nature we're about to release, this might not be a bad place to put it either. And it did meet the other criteria. So in November of 1942, we finally decide to take that site. The government does, claims it, and they begin construction of that lab at the very end of 1942. Watch what happens in the short span between then and the middle of 1945. 1943 in Europe, the German-Italian troops surrender in North Africa. Any of you ever wondered why the Germans kept going to Africa? In part, yeah, another good reason too though. Going back to the Roman Empire, when the German barbarians brought the collapse of the Roman Empire, we all have thought, and I did too, that they came south from Germany, right? And they deposed the emperor and they took over that empire, coming down from the north. No. They came from Africa. It was a tribe called the Vandals. And the Vandals controlled North Africa from the Nile Valley to Tunis. They had come into that area in the early fifth century. And they controlled it. They controlled the whole western Mediterranean with the navy. And Nile Valley, Sicily, and North Africa were the three great granaries of the Roman Empire. They produced much of the foodstuffs that fed the Empire. And the Germans now had two of them and eventually took Sicily. They controlled the food source for the whole Roman Empire. They lost control of that. In the seventh century to the Eastern Roman Empire. But I found it rather fascinating to read that. They attacked out of Sardinia and Corsica. And they took the Roman Empire down. But at any rate, Soviets also stopped the German advances along that entire front and began finally to push back into Europe. The Allies landed Sicily and Italy. Bombing raids increased. But Churchill and Stalin and Roosevelt meet in Tehran, Iran. Iran was a neutral nation at that time. And you can see that we must have had some confidence in how things were going because imagine what it took to get our president around all of that warfare up into Iran at the time. Could not have been particularly easy, but they did it. In the Pacific, a lot of island hopping going on. American forces driving the Japanese from these places. New Guinea, Attu and the Aleutians. The only American territory ever occupied by Japan from Torawa. All but three of the American battleships were now back in service. And finally, I believe it was Navy planes, brought down the plane of Admiral Yamamoto, commander of the Japanese forces. We had cracked the famous Japanese purple code. All right, at the time and we were able to go get that plane and take it down. In this country, we're organizing to build that lab. Starts in Santa Fe.  It didn't look like anything now and it doesn't look like anything, or it doesn't look like anything then it still doesn't. And I was out there when I was there. Here you can see it. This is now, it's got a big plaque on it saying, this is where Los Alamos was founded. This is where it all started. This was the early administrative head. And a woman heading that program was a widow by the name of Dorothy McKibbin. At the time, she was 38. Oppenheimer hired her because she was known to be a very good administrator and volunteer efforts in the city of Santa Fe. And she seemed to know everybody who was anybody in the region, which was a good thing because she had to find places to put up all these scientists that were gonna be brought into the lab. You know, the hotels couldn't handle them. They didn't want them in the public.  Where do you put them? You put them on ranches that are sitting out in the middle of nowhere all around the city of Santa Fe, up in the mountains, out on the plains. And she took care of all of that, this hiring. Interesting stories about when they brought people in there and they walked into this place and they would say, where are we? Look around. But at any rate, some interesting things, in addition to being in this very non-ospicious place, there was one post office box at which everybody at the laboratory got their mail. Everybody, box 1663. And Sears Robot complained after the second Christmas at Los Alamos because they had sent over 400 catalogs to box 1663 and they said, we refuse. What have you got out there? How big is that box? We're not sending anymore. Also, to hide the identity of the scientists being hired at the time, all of them were employees of the University of California, not the Department of Energy. And this was to, in essence, hide what our effort was to do. And that's still the case today. That's where my pension is from, is University of California. So at any rate, it's kind of an interesting side story there on that thing. But to give you a little bit of a sense, again in the lab, how you get there, you would drive out of town. This is the old Ottawa Bridge. Here you can see, I was telling you those maces, parito plateau at the top. Here's your 400 foot drop. You drive up through these valleys, you get up on top and Los Alamos will be located on the top. But back in those days to get there, you had a one lane dirt road. And going up these various plateaus to get up there, you had switchbacks. And some of the old switchbacks were still not used, but they were there. And I looked at those and I thought, my God, they brought the bomb down on that. That had to have been the most terrifying experience you can possibly imagine, except for one that I'm gonna share with you in a little bit. But that must have been quite something. What were people in the city told? When you looked up there, to this day, you can still see that there's something going on up there. You can tell there's a city. They weren't blind in those days, they knew it too. But what was it up there to do? Well, it was up there to create new powerful explosives for artillery shells. And it's a good thing they used that example too, because there were an awful lot of booms that were going on up there and they weren't nuclear in nature either. They had high explosives required for a lot of the elements of the bomb that I'll share with you in just a little bit. And they looked up there and that place was called the hill or the lab, the hill. And the device itself was referred to as the gadget. Never the bomb, it was the gadget. So they would drive up there and when you got to the top, there was your gate, main gate. I think it's still there, off to the side. And once you got through there, you were down a rabbit hole, proverbial rabbit hole. This is the old Fuller Lodge, it's still there. That was the main building of the Boys Ranch School. That's where most of the instructors lived and it was used also for classrooms. Now it's still there, it has a museum in it now, it's a lovely building, but most of the people were not so fortunate. The military lived then as they still do in barracks. I lived in one of the first two weeks I was out there. That was when we walked into it for the first time, I had a little two room apartment with bathroom, my wife cried. You're gonna be in this for a whole summer because we were out of the house built out there, but it would be 10 weeks later, no, anyway. But this is where the married couples were, whoopee indeed. Yeah, and you don't hear, and a lot of wives cried when they got there too, believe me. It's not much bigger than one of those either. But they used the old brown, black Betty stoves to cook on, they could burn charcoal, wood, coal, just about anything. They were used for heat, they were used for cooking. Interestingly enough, as I said, many of these scientists were married, a lot of them had children. And as a consequence of this, Oppenheimer was keenly aware of the importance of the role of women at Los Alamos in taking care of hearth, home, and husband. And as a consequence of that, he involved himself to an unusual degree in meeting their requirements to keep, not only happening, but to keep their husbands functioning with what they had to do, plus a lot of those wives also worked in the lab as administrative secretaries and various other functions. So they were part of his workforce. He actually at one point had to come up with a six priority list of which women would get help on housekeeping or baby care. Six categories for the women. On top of everything else he's trying to do. Why? Because he felt that they were that critical to what he was trying to achieve.  Here are just a couple of them, okay? Niels Bohr, Danish, very famous man, winner eventually of the Nobel Prize. He escaped Denmark just before the Nazis invaded it, the night before they invaded. And he fled and finally made it to Britain. Edward Teller, Hungarian, brilliant nuclear physicist, advocate of the hydrogen bomb. He would become Oppenheimer's great thorn in the side. Terrible, terrible person. I had private lunch with him on two occasions at his request. The first one being I was there at 1988 and he said to me knowing I was half Hungarian and he was, he wanted to know how the Hungarian kid was gonna open this lab up.  But I explained to him what I had in mind and he went, oh, well that'll be interesting. About two years later he came back and by that time we had a very successful program actually going. We had a lot of companies come. We were having at least one a day because we had something to offer. And he said to me, how are you doing this? The whole tone was much different. It was fascinating. Got to chat with him a little bit about what it was like back then. Enrico Fermi, an Italian nuclear physicist, he would create the first actual chain reaction that was controlled in the nuclear reactor. Finally Richard Feynman, an American, Princeton graduate, PhD. This guy was the imp of the laboratory. He took great pleasure in completely confounding all the security measures that the security people from the military would put in place. They'd put something in place and he would go and get through it somehow. And then he would come back and point out to them what they had to do to make it better. So he couldn't get through it and neither could anybody else. But at any rate, they learned to accept that but he still drove them crazy. And apparently they really needed that. Now the one thing that Eisenhower, Oppenheimer did, he declared Sundays was a no work day. He would not allow anyone to work. And they didn't. Why? They had to let off steam. The pressure and tension was incredible. They could not, the men were forbidden to speak to their wives about what they were doing. So the only thing they could talk about over the dinner table really was entertainment for the weekend. Parties, parties were a big thing. Drinking, a lot of drinking, a lot of drinking, a lot of affairs, a lot of children born. Including to Oppenheimer, they had one as well. In fact they had so many children being born up there that they had to build a second hospital and bring in pediatricians.  And all of them, all of them had the same birth certificate. No birth certificate reads Los Alamos. You were born in Santa Fe at the time. All right, so anyway, there was a very, very different kind of place. Now as we know, the military certainly puts a great premium on keeping things quiet. No science, you have to open it up. You've got to share and learn the learning you do. And they did this at weekly meetings, bringing in their division leaders and what have you. And it worked very well because the speed was of the essence as it is with me. So major scientific questions that were coming up. You can read these, I'm not gonna take you through. But the key to all of this was the availability of materials. And Uranium 235 was available in nature barely. It took a ton of naturally occurring Uranium 238 to produce one half pound of Uranium 235 that fissionable material used in the bomb. Plutonium did not exist, naturally it had to be created and it was. So there was literally no ability to test the materials that they were going to use. Here we got the fission process. Oh, I can't go back that way. I don't want to go back. Anyway, it doesn't matter. What was the design of the bomb? Design of the bomb was what they called a gun triggered fission. It took a bullet of Uranium 235 on one end. You had a sphere with a hollow in it on the other end. You had explosives that blew that thing down into the other sphere. And by cause of the impact that freed up neutrons that caused this fission explosion. Gave rise to it. So when they were listening to all of these booms from explosives, it was because they were testing these charges that were going to be propelling this type of shot, right? But keep in mind, it has to be controlled because what you don't want this thing to do is to blow the whole bomb apart, you know? So this was very tricky design in terms of material, et cetera. All right, this is what the lab looked like then at the time. Here you got your various, your plateaus. Here is the lab over here. The town is on this side of this canyon. Here's your Caldera. There are the mountains. Very rugged place. D-Day, allies take Athens in the rooms. D-Day comes. Biggest amphibious operation we under Paris. December comes the Battle of the Bulge. Pacific theater. Our troops are taking most of these bases. Landing on late D. Japan's last aircraft forces are defeated. US enjoys total air supremacy in the Pacific at the time. Program in this country, the Manhattan Project, is enormous, involves some 30 different organizations. Groves is running a whole program. Well, Salamos is but one of them, but it's the critical one because everything is brought together there. Key programs still issues how to release the energy at just the right time. Oak Ridge says we can't produce enough for but one bomb. You're only gonna be able to make one bomb at the time. But Oppenheimer sides then to focus on the plutonium bomb. We could make plenty of them. And Groves finally says no, I want a uranium bomb too. And with this, suddenly Oppenheimer has to hire another thousand people to get them up there to focus on these two different bomb designs because the plutonium bomb was so very, very different. I won't go into this, but it's the fusion process that Teller said. Hydrogen bomb is a fusion process. We're two things coming together to create one. Fish and you have one thing that's split apart to create two or more, very different. But both of them depend on neutrons, how they're used and how they generate. At the lab, you do have a unique culture as you might guess. Where the military and the civilian are separated. The decided class system sets up. Your status in the lab pretty much determined you're standing in the community. Still does that way, I can tell you that. Lab work dominated everything. And nobody retires from that lab. They retire, they come back into Emeritus and they keep on going.  Chronologically in January, we defeat the Germans at the Battle of the Bulge and the Soviets take Warsaw. In February, it's the great meeting at Yalta with Roosevelt Churchill and Stalin. They decide how we're gonna break up Germany. You know, what Poland's gonna get out of it. The division of Berlin into four parts. In fact, they're gonna require unconditional surrender from Germany. March the US troops cross the Rhine. Mussolini's killed, the Soviets take Vienna. And in April, Hitler commits suicide. Big thing, FDR dies shortly thereafter. Amazing. And when he does, Truman becomes president only to find out that then that we have this project with this enormous scientific effort going on that he was completely unaware of. Look at the date. April, when was the bomb dropped? August. Look at the decisions he was forced to make coming from a position of absolute ignorance. I mean, what he had to do, in my opinion, is absolutely awesome. In May, Germany surrenders. They do meet the unconditional thing. And with this, many of the scientists on that project at Los Alamos said, you know, we hired on in order to defeat Germany. They surrendered. You know, why do we have to keep doing this? And Oppenheimer had to get them to agree. He said, you took an oath. And that's one of the things I wanted to mention to you, too. How do you unite a group of diverse scientists from many countries into one program? They weren't gonna sign anything. What did he do? He made them take an oath on their profession as scientists that they would see this project through to its end. They took an oath, and they met that oath. And he reminded them of that. You promised that you would do this. You took an oath. I am holding you to it. We are not done. But the emphasis shifts now to Japan. And here in July, July 17th, the August 2nd, Potsdam Conference now in Belgium, instead of having Roosevelt present, you've got Truman. And he's there meeting with these big leaders who have been involved since the very beginning. Here's the new man on the block. But he has to face them. But he has an ace in the hole. That's, he's waiting. He's waiting. In the Pacific, you know, taking Okinawa, Iwo Jima, liberate Manoa. We demand Japan's unconditional surrender in Japan, and it refuses. Here's something most civilians do not realize is the preparations for an immense invasion of Japan. The U.S., Britain, and the Allies were prepared to invade in November, first week in November, with a million and a half men. And prepared to take one third of them in dead and wounded. Think about that. They estimated that somewhere between five and 10 million Japanese would die in the process. But in addition to this, what's not known is that roughly 10,000 Japanese a day civilians on the Japanese islands were dying of starvation or sickness. So when people say, you know, should we have dropped the bomb?  And they go, tell them about this other cost. 10,000 people a day. And you extend it from August to November. That's 90 days. 900,000 plus five to 10 million. Yes, it might have been a horrible thing, but wasn't it wiser to, in essence, drop that bomb, more merciful, and it's creed? Oh, it was shocking, oh, in a big way. But at any rate, most people are unaware of that. Occasionally, I'll have Americans also challenge why we did that. And I'll ask them, do you have any relatives who fought there at the time, or are you the descendant of one? And some of them will say yes. And I said, do you realize you might not be here? No, think about that. If your father or whatever had not survived that, you would not be here. And they start thinking a little bit. Okay, at any rate, the US begins final production of that bomb. We set up to have the Trinity test. Some scientists again, wanted a great big demonstration, but it was argued against because Oppenheimer says, well, what, if the Japanese look, oh, I'm gonna think it's a big boom. You can do that with munitions. You don't have to have something like a nuclear thing. This at any rate is the little boy weapon, life size, real size. This is the uranium type bomb, that gun trigger, most reliable of the two type of bombs that were gonna be used. This is the other one, the plutonium, the fat man bomb, much more complex material requirements. Look at all the different types of explosives they've got. The timing was critical. It almost makes you wonder how they ever got this thing to work. But this is what they first used at Trinity. And again, we only had enough for one bomb. So at any rate, on August 16th, at White Sands, they set this tower up on the day before that, the 15th, bomb is being hoisted up here, 100 feet high, and it dropped. It dropped. And you went, ooh, what happened? Well, they had thought about this. You know what they used to cushion it? A bunch of army mattresses, 10 feet thick. This bomb weighed 10,000 pounds. So they had about 10 feet of mattresses under it to catch it, and it did. So they get it up there in the night before, they gotta rig it up, there's a thunderstorm threatening. Thunderstorm was threatening. So what did they do? They have an explosives engineer stay up there with it. Overnight, in case lightning hits the bomb. And when I read this, I thought to myself, and what do you think might've happened? They didn't know, but at any rate, he had to arm it any rate, but any of those other circuits could've gone off. And if it had, he would've had, he would've had no story to tell us to send this. He wouldn't have had any. But at any rate, the following morning, finally at 5.30 in the morning, the bomb is detonated. By the way, he'd left the tower by that time. And there is your first picture of the first nuclear explosion in the history of the world. At the time that was dropped, Oppenheimer's quote, I have become death destroyer of worlds from the Bhagavad, Vita, and Indian Brahmin story. Groves was said to have commented, we must keep this a secret. One of his troops said, or he said, general, they've heard it in five states. It was attributed to a blow-up of a munitions bomb. But one of the scientists at the time at the site said, my God, we're gonna drop that on a city. And as you know, we did. Water this was conveyed immediately to Truman, still at the Potsdam conference. And as a consequence of this, suddenly the United States stiffened its resistance to a lot of Russia's demands being made out there. Because he knew we had this weapon. The Russians would find out shortly about it, but they probably were not aware that the bomb had been tested successfully. The following day, the following day, the parts of the little boy were sent by the cruiser Indianapolis, also by bomber, to Tinian Island. I'm sure most of you are aware of what happened to the Indianapolis. A few days after it delivered its load, one of the most terrible losses of ship life in the Pacific at the time. But at any rate, it was there. And a few days later, the plutonium bomb was again sent by bombers into that area. So here's Tinian, the distance from it to Hiroshima, approximately in August 6th, 1945, the very first bomb. It's about 5,700 miles and not much longer to go to Nagasaki a few days later. Here's the Enola Gay bomb being loaded. And on the big day, August 6th, that bomb has dropped. Plans on Hiroshima, demolished it. Get your question later if you have one. Demolished it completely, killed something on the order of the estimated 70, 80,000 people. One of those people that it didn't kill was the sole surviving member of a family who was now the R&D director at Arto at our plant and quarry city next to Hiroshima. That morning, about an hour before that happened, he was sent by his family. And his family lived almost right under the central point, the bombing site aiming point. To a relatives about a mile away. And he had left the relatives house. There was a wall between him and that where the bomb went off. He was at the time, six years old. Said I was walking along the road. Suddenly he said, the sun rose in the west. It was an incredibly bright light. I looked, I went, what? And he said, when I woke up, I was covered with gray ash. And I looked across the street. The wall was still by him. I looked across the street and everything was gone, including the home of his relatives. And he walked out beyond the end of that wall and looked down the main road that to this day you can stand on. I stood on that corner, by the way. Look straight down that road and there's the building. I'll show you in the next picture. I'll show you now. That one. That one. Look down, there it is with the dome, the whole thing. And he said, the city was on fire and gone. And he said, and I realized my family was gone too. He eventually came down with cancer. And he said, I'll die. He said, I have never told a story to an American in English. And he wasn't, I was being spoken to me through an interpreter. He could speak it. He said, I just vowed I'd never talk to an American directly. And he didn't. As we know, it wasn't enough to convince the Japanese to surrender. It wasn't enough to convince their military people. Their civilian, the emperor, was ready to call it quits. The military said, no. So, what happens? A couple days later, boom, the plutonium bomb gets dropped. And that was even more powerful. It might interest you to know that we had 140 total pounds of uranium used in Little Boy. We had approximately seven pounds of plutonium used in Fat Boy, Fat Man. Okay, the degree of destruction was even greater in the plutonium bomb. But that, those were the only two bombs we had left. The Japanese had not surrendered. I mean, imagine, we would have had to have gone in. Because we had no more. That was it. So at any rate, with that, of course, look at Nagasaki, it's gone. It was just incredible. War is over, Japan surrenders. Interestingly enough, it was not an unconditional surrender. The one thing that allowed us to have the Japanese surrender is that MacArthur had enough wisdom to allow the Japanese to retain their emperor. If we had not done that, they would have continued fighting. But he was their symbolic leader in head. And by acknowledging that and allowing him to continue to rule, but he really did not, MacArthur ruled Japan, make no mistake. Symbolically, they remained a nation. And they accepted surrendering. And they've been a very loyal ally ever since. But back in this country, this is a quote from the co-pilot of the Enola Gay. My God, what have we done? So Americans were keenly aware that we had really done something that was rather frightening. Epilogue, some events since that time. Less than a month after the bomb was dropped in Nagasaki, we had the first American casualty, at Los Alamos. He dropped a 10-pound ball of uranium. And it went critical on him in a small thing. It didn't result in nuclear blast, but it sent neutrons pouring through the room and he died of radiation poisoning very quickly. In 1946, Los Alamos was designated a permanent site for US nuclear research. The reason for that is, of course, when Japan surrendered, scientists had no further reason to be present. And a lot of the European ones wanted to go home. Or go into American universities to try to hold together those people. Oppenheimer said to the government, you've got to do something to assure these people they have a career left. So it was designated a permanent site, which it continues to this day. It's not the only one. 47, he's made director of the Institute for Advanced Studies at Princeton. But look at this, in 49, Russia explodes its first bomb, nuclear bomb, four years later. And I think we all know that there was a lot of spying that had gone on. If I had two hours, I'd tell you a lot more about that, but we don't. If you have questions, we can talk about that a bit later. But the Atomic Energy Commission strips Oppenheimer of his security clearance. Interesting things on that. But finally in 92, a Russian delegation visits Los Alamos for the very first time. And I was there. And it was quite a day. Quite a day. Two buses come in. Now, Americans had visited the Russians nuclear research facility first. Our director, Dr. Siegfried, or yeah, Sieben Hecker had gone there and he invited them to come. And he had two buses. We had a band. We had our two senators and our three representatives and our governor and everybody was there. And there must have been at least 1,000 people from Los Alamos, myself included. It was a big day. It was a beautiful day. And those scientists got off of that bus and they were, I can't believe I'm here, you know. But by that time, a lot of the lab was about as open as a college campus. About 60% of it was like a university. You could walk around. We could bring company people there. We could tour them through. I did that, you know. And now it's kind of closed back up because of the one holy case that you possibly read about. Yeah, security's gotten a lot tighter. But at any rate, I was asked by John to give you a little preview of the Navy's role in this. And I did. I've got some six slides, run through them quickly. But in this period between 1946 and 58 and the Marshall Islands, we conducted some 67 nuclear tests. And the Navy was a very big and important part of that. The objectives, of course, they wanted to find out what would happen both by air and underwater explosions, okay? They were using initially some Hiroshima-type and thermonuclear hydrogen bombs. They wanted to test some new nuclear materials. One of them called dry lithium bombs, new designs. Higher yield weapons and delivery systems, you know, out of submarines, missile bombs. Finally radioactive fallout in the ships on land and Navy personnel. Oftentimes the latter was not thought about until some of them were dying and contracted it. And I know of one individual in this room whose father eventually contracted cancer and to be sure he was not the only one, either. A lot more of you were affected by that. But at any rate, that was quite a big deal. Conducted, here's where the test work was in the South and West Pacific. This is the Baker Underwater Test 1946. This is the first series of two bombs. First one was Abel, an airburst bomb. This was about 500 feet above the border. These are part of the 90 ships that were all told, used in these things because we wanted to find out what would happen to ships. You know, we knew what would do on land. What would happen on the ships? Look at this. This column of water would go on to become a mile wide. Okay, it rose high in the atmosphere. They said there was a mist extending out. That was moving at 60 miles an hour. And they said it just destroyed everything in its path, including some battleships. Is that the Mariana's? No, look at that. This is still all in the Marshall's. In the Marshall's, okay. Yeah, okay. And here you have a number. You can see the various incendiary ships. But it was an incredible explosion. And this was not one of the biggest ones either, I might add. 1952, the Ivy King series. This is a uranium plutonium bomb. 500 kilotons, okay. One of the largest fish and bomb ever tested of its kind. Rows 11 miles into the stratosphere. Frightening thing. Operation Ivy, the first thermonuclear bomb. You can see that the cloud is quite different. This was a land detonated bomb. Million tons, 10.4 million tons. Not thousands of tons, but millions of tons. More than the Hiroshima. I think it was 750 times more powerful than the bomb that level Hiroshima. Test Bravo, we used something called a dry thermonuclear bomb. It used lithium to accentuate the uranium present in the thing, you know? And this detonation was the most powerful we ever think. 15 million tons of TNT were blown, the equivalent of. And it's astounding. A few years later, of course, we're firing them out of submarines on missiles. Spy program, we don't really have time for that.  Now it's primarily in the maintenance and verification and civilian, all kinds of things, including interestingly, the human genome. Osalamus was a pioneer now. What's the impact, the effect, radiation on the human people, on people? And out of this, of course, came the ability to interpret the human genome. This was my area, tech transfer. We really don't have time for that, but a lot of good things to do was sponsored by our two senators. I was hired, I was told I was one of the first hired out of industry and not the first to run such a program in a federal laboratory. It was quite challenging. But finally, here again, is the culture that preceded that. Osalamus, Indians also board caves into the soft, tough of those areas. That culture lasted 150 years. This one is now 70 years. Now, how long, much longer will it continue? Who knows if it's not blown up by enemies, it might be out there a while. That's it. I thank you for your patience. I know I'm over. I tried to cut it down, but I'm happy to answer Q&A. How did I know you would be the first one to ask? I don't know. My father was one of the structural engineers at Paduca that put up that facility there. I never knew what he did. What did he do? Well, what did he do? No, this is a good question. When you went up there, figured they had built a city up there initially of about 3,000 people. What did they have there, really?  Just enough for the people who were on the faculty of that institution.  They had to build all of the military barracks. They had to build something to supply water. They needed a source of electricity. They had to bring in heat materials. They had to erect a fence. They had to erect a lab. They had to bring up and install equipment. It was an amazing thing, and they did it, if you think about it, in approximately six months, most of it. Is that right? Yeah. I mean, when you think of the effort that was going on, how do you hide that?  And then, of course, you got all this boom, boom, boom going on. Anyway, I think what they were able to do was astounding. That's a great sense. Thank you. Thank you. That's right. Are you familiar with the TV series called Manhattan? I've heard about it. I haven't seen it yet. I was wondering if it's any degree accurate, but it's a multi-part, starting its next season, I guess, all about the Los Alamos. What station is that on, by the way, channel? It's not in USA, maybe USA, or one of the cable networks. All right, okay. Maybe that's probably why I haven't seen it listed in the Providence Journal. So one I sent you a review on. Okay. Yeah, there's certainly a lot of myth out about that. A lot of misinformation, too. I've read some stuff that goes, say what, you know. Others? Yes? I was on board a Jeep carrier in Hunters Point, Naval Shipyard, 1948. And the destructive force on that ship, the Jeep carriers were a merchant ship, the landing deck. It blew all the steel out under it. It took the corners of the flight deck and bent them up. Oh. And of course, as I mentioned earlier, would that have been still radioactive? Oh, yeah. That's one of the things that came out of it, is that the degree of radioactivity that the ship's experience was such that it made them unusable. I think the Navy had been hoping that if one of their ships had been anywhere near one of these explosions, and they would have been able to clean it up and reuse it. And when you think of it, how do you find that out? You send men on board to do it. Okay, and when you do that, you have exposed them to considerable amounts of radiation. And probably this is where many of them contracted radiation sickness and eventually died. One of my friends died at age 35 who was with me. Yeah, I'm not surprised. Actually, John Kennedy's father died of cancer. I'm not sure at what point, but he told me about that. Any other questions? Thank you, Will. Thank you.


Right, so I'm going to talk about the role of surgical resection in the management of advanced kidney cancer It's kind of strange You know, there's a saying in Texas You know sort of like closing the barn door after the horses have already left Doesn't make a lot of sense to do surgery in the setting of metastatic disease But I hope to convince you and show you that there definitely is a role Both for the resection of the primary tumor as well as for potentially resection of metastatic disease and in fact arguably surgery or You know the old heel with steel is better than any chemotherapy that we have to offer you If we were having this meeting ten years ago, I wouldn't have a whole heck of a lot to talk about I could actually show you this slide and then go sit down because we really had nothing to offer patients with metastatic disease Patients who had localized or locally advanced disease were largely treated with nephrectomy and those patients who presented with Metastatic disease usually underwent nephrectomy because we had nothing else to offer you And then then we get systemic therapy usually with a immunotherapy that was Largely ineffective and the median survival for patients with metastatic disease was about a year But it's a new era in the treatment of kidney cancer There have been somewhere around 12 to 13 new treatments that have been approved for the treatment of kidney cancer in the last 10 years And so the real question is is there still a role for the first surgical resection of patients who present with metastatic disease in light of all these novel therapies that we have that have prolonged patients lives What we do know about these agents is that they are not home runs they don't cure people Their base hits at best But we do have plan a plan B plan C and D and so on But at the end of the day patients ultimately become resistant to these therapies and ultimately they will die of their disease So what is the proper integration of surgery and systemic therapy in the setting of patients who present with metastatic disease? Well, I like to illustrate this conundrum with two cases that really show How difficult it can be to select appropriately for surgical resection and patients who present with metastatic disease? First patient is a 62 year old white male who presented with blood in his urine He had some minor medical problems some minor previous surgery He had a performance status of one so performance status just basically means how active you are with your cancer So performance that is zero means you have absolutely no symptoms related to your cancer performance status one as you have some symptoms But it doesn't affect your daily life Performance status two means you spend less than 50% of your day sitting or lying down as a consequence of your cancer Performance status three means you spend more than 50% of your day lying down or sitting down because of your cancer Performance status four means you're bedridden and performance status five means you're dead So this patient had a performance status of one and you can see on this CAT scan on the right kidney This locally advanced tumor involving the right kidney and you can see these little nodules in the lung bilaterally That represent metastatic disease to the chest So this patient had some anemia had an elevated LDH which is a blood test that we get to sort of give us a measure of overall disease and The remainder of the labs were normal and the patient had no other evidence of metastatic disease aside from the nodules that were present in the lungs So the patient underwent what we call cytoreductive nephrectomy, which means that patient underwent surgery to remove the primary tumor Here's the pathology Follow-up scans at six weeks showed some modest progression of their pulmonary disease So basically they couldn't get any therapy for six weeks while they were recovering from surgery and we expect their metastatic disease to grow But the patient was ultimately started on synitinib, which is one of the new targeted therapies. They required a dose reduction due to toxicity Ultimately at 14 months out and I remember what I said before was the median survival was one year This patient's already lived 14 months after surgery They were changed over to Everleamus, which is an mTOR inhibitor and now they're actually over three years out and still doing well In contrast, this is a 73 year old white female Who presented with fatigue and anemia? She also had a performed status of one some minor medical comorbidities and She had basically similar labs to the first gentleman that I presented to you She too had a locally advanced tumor involving her right kidney and bilateral nodules in the lung that represented metastatic disease So she underwent a right radical nephrectomy and at the time of surgery We actually noted a mass in a right fallopian tube, which turned out to be metastatic kidney cancer she also had some positive nodes and On final pathology her tumor demonstrated what are called sarcomatoid and rabdoid features and basically that just means a Very aggressive form of kidney cancer that wasn't recognized on the imaging that was done prior to surgery She had three out of ten lymph nodes that were positive But all of our surgical margins were negative meaning we removed all disease present in the abdomen She returned one month later with a performance status of four. Remember that means she's completely bedridden She was admitted through the emergency center for failure to thrive her labs were all out of whack Here's her scan. She has massive recurrence in the retroperitoneum. Here's tumor involving her liver and her vena cava There's tumor over here involving the ribs There's met to the liver Again massive recurrence despite having negative margins And ultimately the patient never got any systemic therapy no chemotherapy whatsoever when she died of disease 45 days after surgery Arguably did not benefit at all from cytoreductive nephrectomy So you can see that these two patients presented exactly the same and yet had two very different outcomes and the question is is there any way That we can avoid That second scenario Well the group from UCLA were one of the first to demonstrate the benefit of surgery and again, I would argue that Back in the day surgery was offered largely because we didn't have anything else to give you But they noted that those patients who underwent nephrectomy or even better Nephrectomy followed by immunotherapy had a significantly better outcome than those patients who were treated with their primary tumor in place So this prompted the conduct of two randomized trials one done in the United States one done over in Europe Where patients were randomized to radical nephrectomy followed by interferon, which was the systemic therapy du jour versus interferon alone and Both the European trial shown here as well as the United States trial shown here Demonstrated that patients who underwent cytoreductive nephrectomy had a doubling of their survival relative to patients who were treated with their primary tumor in place And it suggested that somehow some way this primary tumor was Influencing the overall behavior of their disease and that by removing it patients could have a better outcome well the group again from UCLA noted that In a furan is largely thought to be a rather ineffective therapy It basically makes you feel like you have the flu all the time and Response rates are only about 5% And so they said well, you know If you could offer patients of better therapy and in their minds at the time Interleukin 2 was a better therapy Surgery followed by better therapy would result in better outcomes for patients And in fact they plugged in in their retrospective database They plugged in the entry criteria for the SWAG trial the trial done in the United States And they noted that patients who received dial 2 arguably a better therapy Did better following nephrectomy Well as I said at the start of this talk, we now have 13 better therapies, so Surgery followed by all these different better therapies should really result in a better outcome for patients What's interesting though is that's not we're not practicing what what we preach You look at this slide This shows the utilization of cytoreductive nephrectomy in the United States over time The new targeted agents were introduced in 2005-2006 and you can see right at that time cytoreductive nephrectomy was on the decline So while we believe that the research shows us that surgery followed by better systemic therapy would result in better outcomes It would appear that in at least in the community People don't believe that they think that systemic therapy alone is the best option for patients And that's also shown in this Mayo Clinic study where you can see the blue bars in the top graph Decline over time showing the decreased utilization of cytoreductive nephrectomy in the era of targeted therapy Well, why would you not want to do a cytoreductive nephrectomy? Well, I can tell you that having done literally thousands The morbidity and the mortality potential is significant. These are big operations It's only been proven beneficial in combination with interferon, which arguably is an inferior therapy that we don't use really anymore It's possible that the patient may spend the rest of their life on this earth recovering from that surgery And as I showed you in that second case Patients may actually have rapid disease progression after surgery never even get systemic therapy And maybe these new therapies result in primary tumor regression. So maybe there is no role for cytoreductive surgery anymore What are the potential benefits? Well, it can alleviate or prevent local symptoms related to the primary tumor. Although in my experience, that's quite rare It may eliminate a main or at least one source of further metastatic progression Meaning that once the tumor is gone, it can no longer send cells out where out into the rest of your body It may alleviate systemic symptoms related to cytokines or perineoplastic syndromes and With one swipe of the knife we can actually remove more than 75% of your tumor burden in one operation Despite using this modality for literally decades. We have absolutely no idea how it even works We do it, but we don't know why patients benefit from it. Is it a reduction in the major portion of tumor burden? Is it some sort of immunologic phenomenon where somehow surgery exposes new antigens or removes some sort of immunologic sink? There have been hypotheses that perhaps it alters the metabolic milieu and that's somehow anti-tumoral Or perhaps it's some sort of endocrine or paracrine phenomenon where we're removing a tumor that is secreting growth factors That ultimately cause disease progression Well, there are data that indirectly give us some hints as to how cytoreductive surgery works We did this study a retrospective study looking at patients with non-clear cell versus clear cell histology And what we noted was in the setting of non-clear cell histology Cytoreductive surgery really did not demonstrate a benefit So from my perspective that tells me that just removing tumor is Not the answer. There's got to be more to it than that. Otherwise, we would have seen a benefit in non-clear cell histology And these are some intriguing data out of that SWAG study that I showed you the randomized trial looking at nephrectomy followed by interferon versus interferon alone And what they looked at was the patient's postoperative creatinine, which is a measure of kidney function and they categorized patients as anyone who had a change in their creatinine an increase in their creatinine which Would be translated into a decline in renal function and compared them to patients that did not and And they noted that the patients who had a decline in their serum or it's hard an increase in their serum creatinine had a significantly better survival relative to patients that did not and suggested that perhaps this Relative azotemia or relative renal insufficiency was somehow anti-tumor So back in the day we used to see patients and we'd look at their tumors under the microscope and we'd see these tremendous lymphocytic infiltrates where their immune system was Infiltrating the tumor would say wow this guy is going to do really well his immune system is killing this tumor and In fact, we were exactly wrong those patients as shown here who had marked Lymphocytic infiltrates did the worst relative to those that did not and now with further research We know why that is Because the tumor cells were actually turning off the immune system as the tumor attacked it We now know that the tumor expresses molecules that interact with the immune system and can shut them down And actually that is the basis for the novel new immune checkpoint blockade inhibitors that we're using in the clinic Where we can block that interaction and no longer allow the tumor to shut down the immune system Is there any clinical evidence for the systemic influence of the primary tumors such that removing it would remove that influence while Kidney cancer is famous for perineoplastic syndromes where patients present with a whole host of different Symptoms that are completely unrelated to their primary tumor, but are related to growth factors that are secreted by the tumor We've all heard of spontaneous regression of metastatic disease, which I've seen twice in my career Reportedly it happens one to two percent of cases and It's only associated with clear cell histology and As I showed you in my second case Explosive progression of metastatic disease can also follow surgery Thankfully, it's rare, but when it happens, it's memorable So is there any role for seder-reductive surgery in the setting of targeted therapies these new targeted therapies that we have well They're currently our two randomized trials trying to answer that question This is a trial called the Carmina trial which currently is ongoing in France where parents are Patients are randomized to an effrectomy followed by synitinib versus synitinib alone This trial has been going on for 10 years. They still haven't reached their accrual goals. And in large part I think it relates to the fact that Most people believe that seder-reductive surgery does still play a role. And so patients are unlikely or unwilling to be randomized And arguably when this trial finally does read out The question is Will it even be relevant will we even be using synitinib to treat patients with metastatic kidney cancer? Because it's going to be probably another five to seven years before this trial actually reads out if it ever does Another trial that's ongoing or was ongoing is this trial looking at the timing of surgery in the setting of systemic therapy So basically patients were randomized to upfront surgery followed by synitinib Versus two cycles of synitinib followed by surgery followed by continued synitinib So it doesn't ask the question should we do surgery it asked the question when should we do surgery? But again, the problem with this trial is that it closed because no one was entering patients So in the setting of targeted therapy, we have no level one evidence to suggest that surgery plays a role The problem is I have clinic Wednesday. I can't wait for these trials. I have patients that are going to show up with metastatic disease What do I tell them? Do I tell them that there is no role or we don't know what the role is? Do I enter them in a clinical trial? How do I manage them? Well, there is retrospective data that gives us some clue as to whether or not surgery does play a role in the setting of targeted therapy In the setting of metastatic disease These are data from the expanded access trial that was conducted by Pfizer when synitinib was being developed And they looked at patients who had prior nephrectomy not necessarily site reductive nephrectomy But had their kidney removed at some point in the past and compared them to patients who were treated with their primary tumor in place And you can see that there was a doubling and the response rate for patients who had had a prior nephrectomy And those patients who had a prior nephrectomy had a improved progression free survival and an improved overall survival Relative to patients who were treated with their primary tumor in place. Their survival was almost double Admittedly retrospective, admittedly biased, but does give us some indication that controlling the primary tumor does play a role in the management of these patients These are data from the Dana-Farber Institute Where they looked at patients who presented with metastatic disease with their primary tumor in place And they noted again a doubling in the survival for patients who underwent site reductive surgery prior to systemic therapy Now again the reason why these patients in the in the no group didn't have surgery is suspect They were probably poor surgical candidates. They probably had advanced disease But it still gives us some indication that controlling the primary tumor is important in the setting of metastatic disease And this is data that we published more recently looking at the SEER database, which is a large collection a national collection of Patient data and we noted again that those patients who had site reductive surgery had a significantly better outcome in the setting Or the era of targeted therapy although the SEER database doesn't actually tell you what specific therapies those patients received That's not to say that everyone should have site reductive surgery as I showed you in that second case that I presented that I made the wrong decision in that woman and She died as a consequence so patient selection clearly clearly is critical in Employing surgery for patients who present with advanced disease One of the first groups to demonstrate that was a group out of Tufts University Where they noted that those patients where you could remove more than 75% of their tumor burden Absence of brain liver and bone metastases Good performance status and clear cell histology did well with site reductive surgery and then they use those criteria prospectively and Selected 28 patients for site reductive surgery deferring 61 patients who didn't meet the criteria and 93% of those patients went on to receive systemic therapy with an excellent response rate in the era of IL-2 More recently we looked here at MD Anderson at 566 patients who were treated with site reductive surgery between 1991 and 2007 And we compared them to a group of patients who received only systemic therapy alone with their primary tumor in place And we compared outcomes Now the bent here at MD Anderson is to treat patients with surgery if at all possible So you can imagine that the patients that we did not treat with surgery were the worst of the worst And in our hands the worst of the worst survived 8.5 months So we went back to our surgery group and we said okay If we did surgery on you and you did not at least survive 8.5 months, then we probably didn't help you with surgery And then we asked the question well, what factors what clinical factors can we use to predict your survival after surgery? and What we noted was that those patients who presented with a low serum albumin an elevated LDH the presence of liver metastases Symptoms that were related to metastatic disease such as bone pain cough related to pulmonary metastasis and so forth and Nodal involvement meaning involvement of the lymph nodes by cancer either in the chest or in the abdomen and A locally advanced t-stage all of these factors Were associated with an adverse outcome And what we noted was in our study that if you had three factors or less Your outcome was better than the people that received only systemic therapy But if you had more than three of these factors your outcome was the same or even worse Than the patients who received systemic therapy alone And so now prospectively we use these criteria to better help us select patients for surgery and Help us avoid the consequences associated with that second case that I showed you This is another study out of Canada Where they looked again at factors that predicted for outcome and patients who underwent cytoreductive surgery and came up with some Very similar findings the presence of anemia elevated calcium levels elevated white blood cell levels elevated platelet levels poor performance status and a diagnosis to treatment time of less than one year meaning that you Presented in gut treatment in less than one year from from your presentation all of these were associated with outcome So with regards to cytoreductive nephrectomy Cytoreductive surgery does improve survival in properly selected patients The goal of surgery should be should be to remove the majority of tumor burden with one surgical procedure Poor performance status the presence of liver brain or bone mats The presence of nodal metastases and the presence of sarcomatoid histology all predict a poor outcome And in that situation those patients are probably best served by receiving upfront systemic therapy Followed by possibly delayed surgery if they respond So I wanted to talk just a very little bit about surgical resection of metastatic disease So this is not resection of the kidney But resection of metastases be they brain mats bone mints lung mints what have you So a little bit about the epidemiology of metastatic kidney cancer 63 to 65,000 patients are diagnosed yearly of those 30% present with metastatic disease and even those patients who present with localized or locally advanced disease 30 to 40 percent of them are destined to ultimately get metastatic disease so you can see That metastatic kidney cancer is a real health problem 13,000 patients per year die of metastatic kidney cancer and The rate of kidney cancer is increasing by 2% per year What are the challenges associated with the management of metastatic disease? It is not responsive to most chemotherapies It's not responsive to radiation therapy at all. In fact radiation is only used for paliation of pain The remark the minority of patients respond to cytokine therapy, which is interferon interleukin 2 the old systemic therapies Even with the new targeted therapies complete responses are rare these agents do not cure they control but they don't cure and I would argue that surgical therapy when possible Represents the best form of treatment and is better than any chemotherapy that my medical oncology colleagues have to offer Heal with steel as they say is certainly the best option for patients with metastatic disease when it's appropriately applied So just a couple studies that have looked at this and the biggest problem with these studies that you have to take with a grain of salt Is that they're all retrospective? Meaning that we looked back at our experience as opposed to taking patients Prospectively as they walk on the door and randomizing to surgery versus no surgery Which probably can never be done because there's just not enough patients to actually complete a trial like that So in large part patients who underwent surgery. There's a selection bias. They underwent surgery because they had favorable disease Probably had good performance status We're very eager to proceed with surgery and so all of those things could impact the outcome So there are numerous studies retrospectively published in the literature, but the outcomes are really impressive Here's one from Sloan Kettering where patients who underwent a complete metastasectomy the five-year overall survival rate was 44 percent Almost half of the patients were alive five years after surgery, which is unheard of in the setting of metastatic disease particularly in that era Here's another study again out of Sloan Kettering where any patient who had any metastasectomy the five-year overall survival rate was almost 50 percent This is a study out of the Mayo Clinic where they looked at over a thousand patients any patient who had a metastasectomy five-year overall survival 44% very impressive And again another study out of the Mayo Clinic where those patients who could undergo complete metastasectomy their five-year cancer specific survival So that's not even overall survival. It means being disease-free five years out from the surgery 45% So in highly selected patients where sir aggressive surgical resection can be accomplished The outcomes can be excellent So just to delve into a few more of the details This was the study out of Sloan Kettering two hundred and seventy-eight patients 57% of patients had lung metastases 19% had bone Complete resection was accomplished in 59% incomplete in 41% And in patients who had a complete metastasectomy their five-year overall survival rate was 44% This is from the Mayo Clinic 727 patients again, you can see the distribution of metastases They were able to accomplish a complete resection in 26% the five-year overall survival and the cohort was 15% This is a more recent study out of Sloan Kettering 129 patients you can see the distribution of lung and bone metastases They were able to get a complete resection in 31% None was performed in 66% and when they compared the two the five-year overall survival for the group that had any surgery for Metastatic disease was 49% with a median survival of 45 months This was a study of more than 1300 patients with a variety of different metastatic deposits They did not report on whether or not the patients had a complete versus incomplete resection But they did note that any patient who had any metastasectomy their five-year overall survival was 44% And their median survival was 44 months, which is quite impressive relative to the group that did not undergo Metastasectomy where their survival was only 20 with 22 months And then lastly, this is the more recent study out of the Mayo Clinic 887 patients Complete metastasectomy was accomplished in 14% of the patients They looked at timing location number of metastatic sites and performance status relative to outcome and that's shown graphically So those patients who had a complete surgical resection their median survival was 4.8 years versus those Without complete resection the median survival was only 1.3 years shown graphically here And in patients who only have lung metastases, which is thought to be very favorable in metastatic kidney cancer Those who had a complete surgical resection median survival cancer specific survival was almost 75% And patients without lung metastases who underwent complete resection had a significantly worse outcome But still better than those that could not have their disease completely resected with a median survival of 32.5% Asynchronous metastases meaning they developed their metastases Distant from when they had their primary tumor those patients who underwent complete resection again had a significantly better outcome If you had two metastatic sites if they could be completely resected You did significantly better than again those patients who could not have complete surgical resection of their metastatic disease And that also held true for those patients who had even more than three Metastatic sites meaning like long bone liver or or other organs What is clear is that you should go in there? Trying to swing for the fences Meaning that the completeness of the surgical resection is the most important factor that predicts outcome If you go in with and they have five metastases and you only resect three you're probably not doing that patient of service So resection of complete metastatic disease was associated with the best outcome in all of these different studies Performance status is also important. It's important to operate on patients who are healthy and doing well And in this particular retrospective study performance status was a strong predictor of outcome with regards to metastasectomy And then finally this was a systematic review looking at all of these different studies and the role of metastasectomy You can see from all these different bars over here on favors metastasectomy side That all these studies were able to demonstrate that surgical resection of metastatic disease was associated with an excellent outcome in Properly selected patients So in summary complete resection when feasible I would argue represents the best option for selected patients It's better than any chemotherapy. We have to offer you Incomplete resection remains beneficial, but I would argue systemic therapy probably is a better option than just resecting part of the disease But we need to keep in mind that metastasectomy is a reasonable option in patients with solitary or Oligometastatic meaning very minimal metastatic disease Who are good surgical candidates? And so with that I'll close I'll be happy to answer any questions that you have and then we'll take a Break for about 15 minutes any questions at all Okay, why don't we take a break for 15 minutes and then we'll start with the second half of the program. Thanks very much


Welcome back to Whittling for Beginners, Whittling with Salty. This time we're going to put all of our skills together that we have learned so far, and we're going to work on carving the ball in the cage. Now in order to do that, this ball is going to have to be a little bit smaller than the one that we carved on the end of the stick. And how do we figure out the size? Well, that's not too difficult. On the end of one of your sticks, on either end, draw your little quarter inch square sticks that are the cylinder, the cage on the outside corners. The largest that your ball can be is the distance between the two corner posts. In this case, it's 7 eighths of an inch. Now round it off, it could be a little bit bigger, but we'll stick with 7 eighths of an inch. Now the smallest that it could possibly be is 5 eighths of an inch, otherwise it will slip out between the posts. So you have a little bit of slack from 7 eighths of an inch to 5 eighths of an inch. So we'll draw a little circle the size of 7 eighths of an inch, and we would lay that out on our stick. We have drawn the quarter inch corners all the way around. So when they are our circle pattern, right in the center and mark, and that will mark over the top of your corner posts, of course, but that's immaterial, you're not going to carve there anyway, mark that all the way around. Now at the top of the circle pattern, make a straight mark and of course a stop mark up here where your spacer is, and the first project then is to empty out that space in between. Everything in between on the top has to be emptied out. To do that, we'll have to finish drawing our quarter inch mark on the side of our stick. We'll sketch, make a little marker as their edge. We want to get the top edge of our ball and lay it on there, space it about in the center, bound it with your pencil, and taking your knife, make stop cuts. This one is partly done already. We'll make stop cuts and cut down, first cutting out the corners, as we did before when we made our first attempt at doing interior carving, carved down so that you free up that corner post, and we have to do the same thing here.  Another stop cut, another slice, just keep repeating the process. Be careful not to take too big a chunk.  It was not supposed to do that. That's one of those flaws in the wood that I was talking about before. Now if this was a good project, we would recover that piece and glue it back in before we went any farther. That's another reason to always try to keep the top of your workbench fairly clean, because if you break something off and your wood chips are six inches deep, it's really hard to find something that's that small. If your workbench is fairly clean, then it's not too difficult. In this case it doesn't make a great deal of difference. Now we do the same thing on the other end, finish cleaning this out, make our stop cut, a slice, another slice, and we get down to where I went too far there. I want to do the first one up here on the top of the ball. You could do it on the other end too, it wouldn't make that much difference, except that you have to be very careful where the center of the ball is that you don't cut too deep. It's more prudent to empty out the top half above the ball first and then the bottom half we can do later. Once they have those those down, then it's a fairly simple task of making a slicing cut, taking out a chip, another slicing cut, take out a chip, make another slicing cut. And there we are through. And then we would do the same thing on the final side.  Just small chips and just keep working away at it from side to side and we'll have to clean out these other corners anyway so we might as well do it now. Work that down, have the corner free before you know it and have that whole piece out of there. This is kind of putzy work, it takes a long time because you just have to get a little bit out of the time and you kind of have to break things loose and you don't want to spoil your carving as you're doing that so you have to be a little bit careful. But that's the key to doing good work all the way through is to be careful. Not much left, we just have to clean out the corner here and we can start working on our ball. Actually as you get more skilled you won't need this much room. You could probably in this space here you could probably carve two or three balls, one on top of the other but when we're beginning and it's nice to have a little bit of extra room. Learn how the knife works and how the wood lays and clean out the little corners. Now we have the whole top cleaned out and at this point we'll have to take our pencil and kind of carefully mark an X right in the center that will be the center of the top of our ball and of course that's easily done because you can sight across from post to post. What we're going to do now is to start to work on rounding the ball and we have our pattern I'm going to outline it here just the corners that we can work on it's going to be that all the way around so we can kind of cut the corner down like we did when we started on the end of the stick with our first ball we do the same thing all the way around like a little bit at a time it wouldn't hurt at all if you did like you did on your first ball if you made a center line right across the ball so that you wouldn't get confused and cut too far down on any one side we will just work the top of the ball just the way you did on the end of the stick except that you have corners that you're going to have to clean out and that's not going to be too difficult because as we do the bottom then we'll begin to round the ball in this direction also when we start on the bottom half of the ball then we will be working a little bit differently we'll make a stop cut on the bottom we'll clean out our bottom corners just like we did up above and then we will start cutting the bottom of the ball and working it down all the way around so that we cut down toward the center so that the ball is sitting on a peg afterwards you can actually cut that corner completely loose from the bottom of the ball all the way to the stop so that the ball is sitting on a big fat peg we'll do the same thing then on the other side we'll just work that down but I think you should have the idea while you do that then you do the same thing on the bottom half when you get these cleaned out then you would start carving your ball and as you round it off then you begin to carve down so that you take off that peg don't forget to use your gauge you can reach in there and you can gauge whether or not that's getting round and you can do the same thing on the sides as you're rounding that ball off when you get the bottom and the top and you can mark those off from the center of the ball and begin to round that off then it's easy enough to get in there and round off the top and the bottom of your ball just in case you don't get this done by the next show we will be able to finish up our ball clean out the corners first and always when you're doing this then you have a good solid stop so that you don't break anything out and so we're coming up to the end we'll have to finish this carving the ball project in our last session but if you want to get started on it work carefully take your time use the same skills that you learned on the first few projects and you will not have any trouble so until next time be careful keep your knife sharp and we'll see you there


Hey you guys, so this is a follow-up to my comparison of the four stylers again I compared the cream of nature lotta body main choice and texture ID by doing a perm rock set now the perm rock set itself itself came up nicely I did love my curls however the next day things didn't turn out so well so to try and preserve the curls I placed my hair in mini pine apples and used a satin bonnet now all I'm gonna do is gently remove the goody stretchy bands shake my head around to loosen up the curls one side of my head is not holding up so well it's gonna be the cream of nature and texture ID I do have an official review of the texture ID line I'm not a fan of this line you guys I think that the products itself are better on looser curl patterns two type three type I don't think they were as well for four doesn't mean that they won't but for me personally I haven't been a fan so anyway I'm going to try and loosen up these curls as much as possible I did not do a lot of over manipulation I just try to stretch out my hair to get some type of some type of hairstyle going on I'm gonna play around my hair to figure out what I'm going to do I will say is I experienced quite a bit of frezz on the side of the cream of nature texture ID side you're gonna see that right there and again the curls did not hold up you can see the main choice and lotty body did fairly well so again I'm gonna continue to manipulate my hair not doing a lot because I don't want any more friends to figure out what type of style I'm going to come up with so yeah I'm just gonna pin the side of using the cream of nature perfect edges control gel and use two large size bobby pins to just secure that area up now y'all why did not tell me I had no idea some debris fell on my lip girl just throwing off my whole makeup game but it's okay I don't know how that happens or you have to excuse that again just using two large bobby pins to secure that up a little fluff and that's it because this side yeah this side she's kind of struggling she's kind of struggling I'm gonna turn around to the back here in a second but first I want you to see the side of my hair now to remind you the cream of nature did not dry all the way and again I use the same amount of product so you see that there a little frizzy now I'm gonna show you the crown of my head and then I'm going to turn towards the back so you can definitely see the difference between the texture ID versus the lot of body here we go yeah the texture ID is already giving me some frizz so at this point I would not be able to wear this another day it would be a high puff for tomorrow so I hope you guys enjoyed this video thumbs up comment like take care


Open your eyes. What is God already showing you? What Metaphorical lifeboat are you missing?   You've got to be