A Conversation with David Housman

WENDY: It is my privilege to introduce my friend David Housman as today's speaker in the ongoing Conversations with Scientists series. I admit I was a little surprised when David asked me to introduce him today. I went back and looked at some of the old talks, and these talks are usually presented by someone who has known the speaker for many decades, often throughout his entire career at MIT, and sometimes even going back to shared college experiences. David finished his PhD before I was born, so our relationship is considerably shorter. But I will say that making an unusual decision is, in fact, completely typical of David.

He does things his way, regardless of convention and always for his own very good reasons, which leads me to wonder why he asked someone who only knew him during this decade to give him this introduction. David, what are you hiding? Jokes aside, David is the kind of colleague who inspires a loyal and lasting friendship. And as proof of this claim, when I contacted several senior colleagues at MIT who collectively have known David for over 200 person-years, none of them had an embarrassing story to tell you about David this morning. Instead, I was told that he is a wonderful colleague, a great contributor to our department community, a dedicated professor, as if any of this prevented him from doing anything fun in the last 45 years at MIT.

Then, at the last minute, Harvey responded to my request. I guess no matter how successful you are, you can always count on your private investigator to embarrass you. And David should look worried. But when Harvey called me, he had already decided to give him a very gentle and loving introduction. And all I'll tell you about what Harvey told me is this: When you get a chance, ask David what happened to the goat. DAVID HOUSMAN: Oh, the goat, of course. WENDY: No, no, no, no, you have to give me my two minutes. If there's one thing I've learned from my years teaching 750 with David, it's that he expects you to do your homework.

He has very high expectations of his students and I include myself in that group. And that's why he thinks too much about us to give us useful information. Although the night before I took my first class with David, he sent me about 200 pages of background reading on phages. On the contrary, last night he didn't send me any useful reading, such as a CV or a biography. Therefore, any glaring inaccuracies or omissions in the brief story of David that I am about to tell are entirely the fault of Wikipedia. David was born somewhere in the late 1940s or possibly early 1950s.

He tells funny stories featuring Brooklyn characters. And so I infer that he may have spent some formative years there... DAVID HOUSMAN: What are you talking about? WENDY: --before heading to Brandeis, where he earned his bachelor's degree in 1966 and his PhD in 1971. Now, somehow, before he finished his doctoral studies at Brandeis, he was already working here in Harvey's lab. And that story sounds complicated, so I won't touch it, but he can touch it. After a brief period in Canada working at the Ontario Cancer Center, he returned to MIT to start his laboratory at the newly formed Cancer Center here in 1975.

Now I am not going to attempt to summarize David's long and already very distinguished career. . . He would take all the time from him and not do it justice. He has published nearly 400 articles in his quest to understand the genetic basis of human diseases. I'm a little confused about the exact number of papers because, for some reason, sometimes David includes his middle initial on the papers and sometimes he doesn't. I spent a good five minutes trying to figure out the rhyme or reason for this, for example, are articles published in months ending in R published with E or are they determined by the number of authors, even or odd?

I'll close on a personal note. Although I have only known David for seven years, those have been very important years for me and David has left a lasting impression. He is one of the warmest, most generous and least pretentious scientists I have ever met. It has been a great pleasure to teach with him and learn from him. And without further ado, I present to you David. DAVID HOUSMAN: Well, thank you Wendy and thank you all for coming. And at the end there will be a quiz. Oh, okay, I can change that and we can just... I'll do the test over the course of an hour.

But it's nice to be back in this room where, for several years, I taught medical genetics in the HST class and, in fact, also videotaped the classes, because, from time to time, students would get a pager telling them that the autopsy was now and that I had to leave. So we filmed the classes. But I usually brought at least one dog to each class. And I guess there's no one who remembers those days, but you know. Yeah, they were mostly well behaved and you can see that on the videotape, because they're... yeah. But today, I guess what I want to start with is having gone over some of the other

conversation

s with the scientists.

Lets start by the beginning. And yes, I was born in the 40s, in fact, 1946 to be precise. And I want to start at the beginning, because it may help give a little insight into how I ended up working in this field. And it turns out, and I didn't really understand this until quite a bit later in my life and in my mother's life, it was actually my mother who was really behind everything. That is always true in many families. But in my case, to make a little return trip, I also have to take you back to New York.

How many of you grew up in New York? And who actually went to public schools and received SP classes? AUDIENCE: What kind? DAVID HOUSMAN: The SP. AUDIENCE: That didn't exist when I was there. DAVID HOUSMAN: No, they did, Lisa. They did it, because my mom, who was born in 1911, graduated from high school at the age of 15 for the same reason that many people in New York, including me, graduated from high school at the age of 15. years. What they do is compress the seventh, eighth and ninth grades into two grades. So you can be a little kid and end up coming to, say, Brandeis and end up in a dorm that's on a floor that includes the entire Brandeis football team, which was an interesting experience.

Because, at that time, Brandeis no longer had a football team. So these graduating seniors were, in fact... well, graduating is a bit of a loose term to use... these graduating seniors were, I would say, substantially interested in things different from where I was and substantially bigger than me. It was an interesting experience. And I gather that my mother had the same experience moving from secondary school to Hunter College in 1926, at the age of 15. And I only realized late in her life that what she really wanted to do was what we do. And the way I realized this was that when she graduated, it was already the beginning of the Great Depression.

She got a job in a hematology lab and would travel an hour and a half by ferry and so on to Staten Island from Brooklyn, just because that's what she wanted to do. And then the possibility arose of having a longer lasting job that could pay something and she became a teacher. She became an English teacher. But that didn't stop him from being interested in what we do. And we'll jump ahead to the 1950s. So I have to say that she also had a tremendous interest in nature and a tremendous willingness to just go out and do whatever she could do.

So I think before she graduated from college or right after, she got a small scholarship to go to the University of Michigan and study at the ornithology labs up in northern Michigan, not in Ann Arbor, but almost in the U.P. . . And I was able to find him a PDF of her report from... I think it was 1930 or something like that. And I was so excited about it. And once she established herself as a teacher, she went out alone to the national parks and fearlessly took the train alone or with a couple of friends wherever she went.

And the story, of course, that affects me the most is in 1938, the school year ends, and she alone took a boat from New York to France and then took a train through Germany on her way to Russia, where, actually, to Riga. and Latvia, where her family is from, changing trains in Berlin at the time. And again, later in life, I learned this story. And she told me that the sound of stormtrooper boots going up and down the platform as she changed trains in Berlin was one of the scariest things you could imagine. But she was a tough girl.

And whatever, I was getting there, I got to Riga and I saw the whole family for the last time. Anyway, that little vignette also reminds me to say that the scientific experiences I experienced were largely influenced by many amazing scientists. And I can't help but think of Salva as one of the first on that list, that she left Europe, escaped and somehow managed to reestablish herself here after whatever it was. And I also think of Mario Capecchi and his five years of wandering as a homeless, parentless child in Italy. And anyway, that was the world I was born into.

And I think that many aspects of the experience that I have had throughout my life bring me to that. And I'd like to keep track of... I ended up doing what I think my mother really wanted to do and she dragged me when she was seven or eight to the Brooklyn Children's Museum so she could take a microscopy course. , which I actually found very useful, because almost as long as I can remember in my entire life in science, I've been looking at the scope. And they have been different things over the years. And I'll get to that, I guess, depending on whether I ever get out of my fourth year.

And I guess the other thing was that my mother, who was also continuing her teacher training, went to a science course at Columbia. And it shouldn't have taken much longer than seven o'clock or something, because after that, I wasn't going anywhere with my mom. I could get around New York on my own. And that was it and I did it. But I can still imagine the slide that Dobzhansky showed. Dobzhansky taught this course. I can't believe a person like Dobzhansky is sitting there teaching two high school teachers. But there it was. And I remember looking at the screen and seeing that drosophila head that could have essentially reappeared on Jeff Goldblum in The Fly or something.

It seemed absolutely monstrous to me. But having said that, I understood. And it was kind of under the surface, because at age 13, I guess, I took the exam for special schools in New York. Does anyone here go to Bronx Science, Stuyvesant, or Brooklyn Tech? No? Anyway, I tried out, I could have gone to Stuyvesant. It was like being within walking distance of the Lower East Side where I grew up. But no, Bronx Science had a new building. Oh, it was an hour away by subway. You name it, it's the best place to go. So I took the exam and ended up at Bronx Science.

And it was great, because you could spend the entire morning from the moment you finally got your seat on the D train working on your calculus homework or whatever. It's a little disconcerting, though, because yes, in fact, you had to be at school at 8:10 in the morning, even when it was five degrees, and if you were late twice a month, you got punished, which meant that you had to go and be there at 7:00 in the morning, which meant... so to get there at 8:00 in the morning, I had to leave the house at maybe 6:30 in the morning. or something like that.

So I used to explain to my friends that I actually left before the moon came up, let alone the sun. Anyway, there I was at Bronx Science. And it was an experience, because they were really bright kids. It was like MIT, except I wouldn't say they took steroids, because I don't think most people actually synthesize steroids at the appropriate levels. It was an interesting experience. And they put me in this math class with the best kids in town. And like a kid won $192,000 on a $64,000 question, but he wasn't the best math student in the class. The best math student in the class was a boy who ended up going to Princeton and becoming a physics professor at the age of 19.

As far as I can tell, he's still there and doing well. Anyway, there I was. And I must say that I had not yet realized that biology was going to be my destiny. And I liked mathematics, chemistry and a little bit of what was happening at that time, I mean the outside world. The freedom riots had just begun. We were a group that went to the Woolworth building and tried to express some support for the people who were being arrested at the lunch counters and such. And that has happened throughout my life. And in fact, when I think back to my childhood in New York, I was talking to Wendy before the talk about the fact that when I started in the lab, everyone smoked and everyone smoked in the lab.

But I was explaining that... well, obviously, that changed. But the thing is, if I get lung cancer, it won't be from smoking either in or out of the lab. As I remember, it must be from growing up in New York, since our next president is apparently also from New York, we couldn't see out the windows. The reason we couldn't see out the windows was because we had screens on the windows. And does anyone remember driving down FDR StreetIn New York? Any? Nobody? Along the East River? OK yes. Then you come to 14th Street, where the remains of what used to be the Con Edison power plant now stand.

And the Con Edison power plant would spew black carbon dust all over the city, especially if you were downwind, like we were on the Lower East Side. The air was filled with black particles, probably more carcinogenic than any cigarette smoke. Anyway, I survived that. And I guess... God bless you, Wendy... and I guess, at that point, I graduated high school and it was time to go to college. MyBoth parents had attended New York City colleges, which were tuition-free. And my mother's family was pretty poor, so there were times when she had to borrow a nickel from her friends to get home on the subway.

And I haven't talked about my dad, but he might when we get back to math or something, because he was a math geek. He was a math professor and he loved going to NYU and taking math courses at the Quran Institute, one of the best places for math, for fun. But that's what he liked to do. But the other thing he did was he had been a math teacher and then World War II started. So he joined the military and got involved with radar and actually went through MIT, ended up doing all kinds of radar and then other electronic engineering stuff after the war.

He says... well, we're not going there, but that's okay. But anyway, I guess that side of where I come from is the idea that I really like doing math and I loved learning things and then going over them with them. And he would have a unique way of explaining it. And I really appreciated, for example, Snell's law that changing the refractive index of a beam of light changes its angle. And he explained it very well, I thought, in terms of an army marching and then, at an angle, into a swamp or something that slows the army down.

The part of the army that finds it first will be turned, because it goes slower than the part of the army that does not. And then the rest of the army catches up to him. The entire army now marches at a slower speed and in a direction that is at an angle to the original direction. And the extent of that change will be the difference in the rate of change - the speed of the army. Anyway, I'll get to the more current stuff shortly. And I have Harvey and Tom here in the front row to come up with what were perhaps my first scientific papers.

So this is good. But I want to stop anyway. Then I came to Brandeis. I wasn't sure what I wanted to do. And I had forgotten how much... I remember what it was like. My mom loved biology, so I was studying math, chemistry and things like that. But it turned out that in the second year she had a blank spot in the program. And it turned out that MIT's introductory biology 701 terms fit. I took it. And this was, at that time, about 10 years after DNA actually arrived. And it was amazing and I was really surprised by this.

But it was an introductory course and now I really wanted to learn more. So the next year I took...let's see...I took two chemistry courses. I took organic and P-chem. And I think I ended up taking P-chem while I was on it for some reason. I don't know why, but I needed someone and I couldn't find anyone else to do it. And for some reason, at that point in my life, I knew how to do differential equations. Please don't ask me to do one at the end of this session, because I don't think I can do any more.

But I've heard it's not necessary. You can just put it on the computer and it comes out. Anyway, when I was a junior, I ended up taking a genetics course, which still reflects for me what genetics is, the beauty of genetics, and the fundamental reason why genetics is so central to things. It's taught by a guy named Chan Fulton, who I've still kept up with over the years. But the point is that we use two basic texts, Sturtevant and Beadle, which is a text from the 1930s, but beautifully designed. And then we used classic papers in genetics, starting, of course, with Mendel, but including all the key papers and finding out how it was actually done.

Again, that fly-eye I saw when Dobzhansky gave the course was now central. And I still, sorry, those of you who are studying big genetics, I still get that fly eye when I talk about epigenetics, because I think what Muller published in 1930 is still key to understanding how epigenetics works until the end. extent to which we understand it. So I really wanted to talk about that. Anyway, there we are, getting ready to graduate from Brandeis. What I am going to do? I was almost...how old was I?...almost 19. And the amazing thing was, I was actually old enough to drive a car and own a car.

Well, growing up in New York... again, New Yorkers... I'm the only member of my immediate family... my sister doesn't drive, my mom doesn't drive... of course, that little incident when my uncle I was trying to teach him how to drive the old Model T at Cornell and he stopped on the train tracks, maybe it has something to do with that. My father never drove, although he sometimes traveled to the suburbs to go to work. But he could drive. And not only that, but the people at Brandeis said, Do you want to stay around here and do some graduate work for a while, and figure out what you want to do?

Sure, why and. And not only that, but they were willing to pay me so I could pay for the car. So anyone who receives a stipend from the NIH might remember how much it was in those days, Nancy. Oh, I remember it vividly. $2,400. $200 a month. And I got an apartment off campus with three other students. And it was really financially scary when the landlord raised the rent 10% from $100 a month to $110 a month, which, split four ways, raised it from $25 to $27.50. Well, for those of you who have experienced Waltham, you may not consider it a high rent district, but I do.

I thought if we were going to do this, maybe it would be better to live somewhere where interesting things happened. Then my college roommates moved to Cambridge. And I said, what the hell? I have a car. I can drive to Brandeis and back and big deal! So I moved to 223 Broadway. Now 223 Broadway is just above the garment district, if you want to visit the Locust Classicus. And it was an interesting place, let's say. Of course, all of Cambridge has improved now. But let's say that in terms of accommodations, Waltham's $100 a month apartment was probably a luxury place compared to them.

Alright, anyway, here I am living in Cambridge, but traveling to Brandeis. And I had to do several rotations. So my first rotation was in the lab of Attila Klein, who was a plant biologist. And it was particularly exciting, because it was in the sub-basement of the original science building, which I refer to occasionally, for those of you who were taking 750 in the same area where the Model E head was placed two feet into the cinder blocks. when the piano string broke. But fortunately, I was told that then they upgraded the armor on the Model E. But anyway, I spent almost a three-month rotation grinding in the dark with a mortar and pestle and in complete darkness, not even far red light, these etiolated bean seedlings .

And then we would illuminate them. It turns out that we are looking at the induction of transcription. But anyway, RNA was new then, so we weren't really worried about it. Anyway, I had a great time there. But then I thought maybe it would be cool to emerge from the darkness into the light. So my next rotation was in a lab involved in DNA repair. And that brings me back to where I'm particularly glad Nancy is here and a little bit about why I asked you to introduce me, Wendy. And that's what I rotated in a laboratory.

It was run by a certain Grossman... no Alan, maybe he wasn't ready for it then... Larry Grossman. But I spent my entire rotation and maybe some more working with a, quote, "research associate" named Inge Mahler. And Inge was an extraordinary person and it was truly a pleasure to interact with her and learn from her. And it's really that experience, working with what, at the time... Graham, can you help me with this... but we call it Micrococcus lysodeikticus. And I think it's Micrococcus radiodurans now, right? Yeah, well, we didn't know they were going to call him. And this was a bacteria that was isolated, I believe, originally from the depths of nuclear reactors God knows where.

And there we are. Oh, I forgot to mention that not only did Inge smoke, but she smoked non-stop. And there we are among the inhabitants of the nuclear reactor and sitting there. And if someone smokes all the time, you have to smoke with that person. But it was great. And then one more rotation before I see how I ended up here and what was going on with it. So I also rotated again with a research associate who was, at the time, the wife of one of the professors in the department. And that was Raquel Sussman. And Raquel was almost iconic in the sense that she isolated the first...correct me if I'm wrong, Nancy...the first temperature-sensitive mutant in lambda in terms of the lambda repressor, 857.

Oh, yeah. AUDIENCE: She did it. She did. She was never recognized for it. DAVID HOUSMAN: Right. And that's just kind of going back to my mom and going over my experiences. Alright. And again, I'm really pleased, essentially, with what I think you, Nancy, have done and, collectively, with what I see has happened in the world of our field, at least, in terms of women being able to be so essentially equal and adequately valued, as they were not when I started in this field. And I put these women that I learned from on that pedestal where, for better or worse, I'm going to put my mother and wish she could have joined you today.

But anyway, the way I ended up here starts in Illinois. Okay, Harvey, I'm trying. I'm trying. So it turns out that Saul Spiegelman, originally from New York, certainly, if a scientist from New York named Saul Spiegelman had moved to Illinois and actually established, I think, an iconic laboratory where all kinds of molecular biology were being done. And one of the things that was being done at the time was finding better ways to do DNA hybridization. And until Spiegelman's laboratory emerged, DNA hybridization was performed in liquid. It had great value, but it also had some limitations. And Spiegelman had a student, whose name was David Gillespie, who had originally, I think, worked at Cold Spring Harbor before coming to Gillespie's lab.

And what he had done for his thesis was figure out how to attach DNA to filters and then hybridize DNA to filters. And this turned out to be a very important change in the way this work was done. But then he decided to hell with the postdoc. I'm just going to look for a faculty position. And he got a teaching position at Brandeis while I was a student and had just finished my rotations. And we had a new building, which I'll come back to in a minute. Then there was Gillespie, who, by the way, was about 4'11, but he was an excellent athlete and really a very, very coordinated guy, etc.

And then rumors started circulating around Brandeis that, oh, Gillespie had hired a student to set up his lab. And then it turns out that, of course, when the dust clears and his lab is set up, it's Gillespie who is the student. All right, Gillespie was an ambitious guy. And he decided that what he wanted to do was understand molecular biology, which was reasonable. So, taking a page from Raquel Sussman's C1857 mutant, she said, oh, what I think I'd like to do in my new lab is isolate temperature-sensitive mutations in E. coli and then figure out what macromolecular process was being affected by these mutations. individual, and then find out what's going on with DNA synthesis, RNA synthesis, protein synthesis, and membrane synthesis.

And actually, four of us who were in that grad school class thought, oh, this would be fun. And then we all migrated to Gillespie's lab and each of us was assigned a macromolecular process. So, Al Jacobson, who some of you know, got RNA synthesis and still does it. Of course, I went to high school with Alan. When he was in high school, he actually worked mostly under cars, but that's something he wants to hide well. And then David Patterson, who ended up being director of the Eleanor Roosevelt Cancer Institute in Colorado, achieved membrane synthesis. And that kind of eliminated him from talking to any of us, because that meant that what he had to do to chromatograph his membranes was go into the cold room and do various types of chromatography.

And I think what we all learned that was certainly relevant to my later life is that it turns out that the brain has a lot of membranes. And it turns out that when the air you breathe has a lot of membrane solvents, you get a headache. So Patterson was left trapped alone in the cold room with the solvents on him tomembranes. And then another guy, Dana Boyd, ended up doing DNA synthesis and spent the rest of his scientific life pretty much doing it. And he finished RNA synthesis. Well, this may not have been many years after Nirenberg and Matthaei and poly-U, but it was after the ability to use RNA phages... give it your particular name, M13, R17, whatever, and understand not only how Poly-U synthesis, but real initiation and synthesis of real membrane proteins... real protein synthesis.

So I took out the books and set it up in the lab. The poly-U-directed synthesis of polyphenol alanine worked very well. No mRNA-directed synthesis worked at all. And I worked on this. And of course, when it doesn't work, you think it's you. I thought it was me. We'll get back to exactly what it is in a minute. But that's how I ended up here, because one of my roommates at 223 Broadway was a graduate student in this department. And since I was complaining that Poly-U works but M13 startup doesn't, he said, obviously you should come talk to this new MIT faculty member who came from the MRC in England and was at... he was at Rockefeller with Norton Zinder before that.

He's been doing this for years and should be able to figure out how to do it. So I came and talked to Harvey. And I will get to where the goat is... I may not get to where the goat came from... I will make the goat come in. Don't worry. We will reach the goat. And basically, Harvey was very generous and couldn't solve the problem right away. He said, I really don't know why it doesn't work for you. But if you come and spend a little time in the lab, we can certainly figure out what we can figure out and maybe we can get you to have a reaction that works.

And yes, maybe there are other things we can do with this once we get it going. Is that a fair description of it, Harvey? AUDIENCE: Yes. And it was three years before Brandeis realized you were missing. DAVID HOUSMAN: Harvey, I don't think they ever realized he was missing. No, actually, we'll go back to my demise at Brandeis because, in fact, under Harvey's tutelage, my extract worked. Now, one thing you need to know in case you have to make E. coli extracts yourself and then start protein synthesis is, again, you have to go back to the cold room.

But thank God, not in total darkness, but in the light. And let's go back to the mortar with which I was crushing the etiolated bean seedlings. But you grind your E. coli with Illumina, which is basically... it's just material, metal material or whatever. And I don't actually know what Illumina is, Harvey. Yeah, okay, great. This is good. I should have asked you a few years ago. But all I knew is that you put the Illumina in the mortar, you put the E. coli that you had grown in the mortar and you had the buffer. It's always good to add the right buffer.

And then you grind in the cold room until you hear the right sound. Now, speaking of our attempts these days to be as inclusive as possible, what happens, Harvey, if you're deaf? How do you know if you found enough extract or not? There's no... It's okay, because I've dealt with the issues of blindness a lot, particularly with my friends with retinoblastoma. But I haven't really thought about how you find out. Anyway, Harvey taught me and it worked. And also, the reason maybe they didn't realize I was gone was because I found out why it didn't work out at Brandeis.

So Brandeis had just gotten a new biology building, which, by the way, dates back so long that I think it's already been torn down. But that being said, they had placed a glass still on the roof of the building, so he could get glass distilled water into his lab more efficiently than if he had to install his own individual glass still. And then, unfortunately, they forgot that the pipe leading to the lab faucet was glass. And when I was finally able to do the cross-control experiment that I subsequently taught in the project lab for decades, why doesn't my PCR work?

Well, let's test each of your reagents and find out what's going on. It was the water. Harvey had a Milli-Q type device in the lab that would deionize the water. There was a small light that would turn on if the amount of metal in the water was too large, which was enough. And everything worked after that. And then we started finding other things that were interesting to do and hanging out in the lab and talking a lot. And at that time it was a joint laboratory with Baltimore. And then we talked about all kinds of things.

And among other things, we would talk about the beginning of protein synthesis and eukaryotes, because basically David's lab, the Baltimore lab, was dedicated to eukaryotic biology. Well, the problem was that no one could understand exactly how this worked. And there are all kinds of theories. But one day, on a foray to Brandeis, I don't know exactly why he was there, a yeast geneticist named Fred Sherman from the University of Rochester gave a talk. And in this talk, Fred talked about the long and short cytochrome C mutants that his lab had isolated. And what his lab had discovered was that sometimes these mutants started with the amino acid methionine.

And sometimes they wouldn't. But when you looked at the data, as he showed it, it became very clear to me that essentially what Alex Varshavsky came to call me and govern was actually working. And it must be the methionine tRNA that was also being initiated in eukaryotes. At that time, Tom had been doing a lot of work on Met-tRNAAm and Met-tRNAf. And then I went with Tom or we went with Tom. I really can't remember it. Okay, well, yes. We'll get to some of the interesting turns of events. It looks like this is as far as we'll go.

But anyway, Tom had yeast Met-tRNAm and Met-tRNAf. And the logical thing was to make a starter extract with yeast. So he brought yeast to the lab, which Harvey thought was fine. Manny, on the other hand... remember Manny Goldman? Do you remember? So the guy who worked... the grad student at the bank next door, he was an interesting guy. I don't have time to go into details, but the bottom line is that he preferred the smell of my yeast to his E. coli. So what he would do is ask me for enough of my culture to fill this inhalation vial.

And then while I was working in the lab, I would open the vial and smell it. And God knows those were the days when people smelled all kinds of things. I can go into a completely different story about this. But the bottom line was that Manny was very happy that he brought yeast to the lab. But he wasn't so happy because my yeast extracts didn't start and we really weren't sure why. I think it was a long period of time before we really found out why. And I don't want to get into this, but it's just what was happening at the time.

But it turns out I ended up in front of the Xerox machine. I don't know if any of you know what that is. But apparently Xerox is changing its name. Then I'll have to change the name of whatever it was. And there was a graduate student from the seventh floor lab, Marcelo Jacobs-Lorena, a Brazilian, who was working on hemoglobin. And we are next to the photocopy machine, photocopying our papers. And I was telling Marcelo my story of misfortune. And he said, oh, you should try the tRNAs in my Wittig system, because I know it initiates, because I can label the amino-terminal peptide.

That's how we did it and it worked. And I think we could go into detail about the document that emerged, but we won't, because I think we have to get to the core issue. AUDIENCE: You should have mentioned that it was in the wild and it got a lot of publicity. DAVID HOUSMAN: Okay, I'm glad you did it, Harvey. AUDIENCE: I asked the letter of the genetic code. DAVID HOUSMAN: I appreciate that. But in the goat, we were interested in... so the problem is that, for the rabbit, methionine is the initiating amino acid, but then it is cleaved.

And we thought we'd like to find a situation where we could start a methionine where it wouldn't be cleaved. And it turns out that the amino acid sequence of goat and sheep hemoglobin C, which is the hemoglobin that is produced when they are somewhat anemic, is methionine. And therefore, we could do with the goat the things that we were doing with E. coli. So we have a goat. The goat lived at Harvard Medical School. And the goat had a roommate and the roommate was a ram, considerably larger. The goat was very cute and small. The ram was large and had a rubber stopper, almost the size of the bottle.

And it was a real introduction to real biology to go and visit the ram and the goat. I don't think we ever found out exactly what the ram was doing. But apparently he was doing pretty well, so people would come visit him and pay for him. End of story. From the goat, however, we learned some biology. And it turns out that smaller animals can become very anemic and still develop quite well. But it turns out that larger animals don't become so anemic that they don't have the high reticulocyte count that you can get from a rabbit.

And so the goat, despite significant efforts to make it anemic, was simply not cooperating. AUDIENCE: Do you want me to tell you the story of how to bleed the goat? DAVID HOUSMAN: Look, Harvey, if it comes to that, then I have to, and I don't have time for that, finish the story by bleeding the duck. And let me tell you that bleeding a goat is easier than bleeding a duck, because goats, as far as I know, don't have wings. If you want to tell the story, this is your chance, man. AUDIENCE: No, no, no, keep going.

DAVID HOUSMAN: But I wanted to tell the goat's true story for the rest of its life. All right, then remember Manny. Okay, so Manny actually lived in Sudbury, not far from where Babe Ruth supposedly spent his time when he wasn't on the field when he was with the Boston Red Sox. And he was in the field near a farm. And when it became clear that the goat couldn't really be justified by the NIH budget, Manny offered to have the goat join him in the field. It's true. And we're running out and I'm sorry, but I feel like I should at least finish this story.

So I loaded the goat into the back seat of the new, now somewhat old car, which you remember I bought when I received my NIH stipend, and drove it down Route Nine toward Sudbury. And luckily or unfortunately there were no video cameras at that time that could capture the expressions of the other drivers when they saw the goat in the back seat of the car. But suffice it to say that we arrived in Sudbury. And we unloaded the goat and took it to Manny's cabin in the woods. Well, okay, this, unfortunately, leads me to discuss, say, the habits of male graduate students.

And I think Manny was living alone at the time. But I think the evidence in favor of the fact that he lived alone is that his sink was full of dishes that he someday planned to wash. Well, the goat came to Manny's house, saw what he was possibly going to experience for the rest of his life, decided that maybe Harvard Medical School would be better after all, jumped into the sink, basically stomped until he destroyed every plate. what did you find. Manny owned it and then proceeded to leave. Now that I remember the story, the goat was eventually relocated to a farm near the highway where everything was fine.

I'm not sure exactly, I think there was a sale at Stop and Shop on dishes that allowed Manny to essentially eat again. But that. I'm really sorry it took so long, because I was hoping to get to all kinds of things that I didn't get to, like how I started working on human diseases and things like that. But on another occasion. I appreciate that you listen to me and stay here all the time. That's all.