Chapter 08: Discovering a Talent for Laboratory Research and an Early Research Success

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Chapter 08: Discovering a Talent for Laboratory Research and an Early Research Success

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Dr. Arlinghaus begins this chapter about his educational path with some comments about his origins in a family of immigrant stock.He notes that his mother decided that he should go to a private Catholic school, and Dr. Arlinghaus worked at a local pharmacy to make money for the school's tuition.He explains why he elected to attend the College of Pharmacy (B.S. 1957) at the University of Cincinnati, (Cincinnati, Ohio,).Dr. Arlinghaus next talks about his decision to work for his Master's and then his Ph.D. in biochemistry.He describes his dissertation research on the structure of collagen.His comments are very revealing of his approach to research problems and laboratory methods.He explains his unique discovery: that his analysis revealed a new amino acid in collagen."Pretty good for a guy who just got off the turnip truck," Dr. Arlinghaus says.The new amino acid was named, 3 Hydroxyproline.That discovery, he says, made him "the most advanced person in that department."

Identifier

ArlinghausR_02_20140402_C08

Publication Date

4-2-2014

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - Educational Path; Personal Background; Influences from People and Life Experiences; The Researcher; Evolution of Career; Character, Values, Beliefs, Talents; Portraits; Understanding Cancer, the History of Science, Cancer Research; Discovery, Creativity and Innovation; Definitions, Explanations, Translations; Professional Practice; The Professional at Work

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Tacey Ann Rosolowski, PhD:

Alright. So now we are recording and today is the 2nd of April 2014. The time is about 11 minutes after 1 and I’m in the Life Sciences Building on Holcombe Boulevard interviewing Dr. Ralph Arlinghaus. This is our second session. Thanks for making time in your schedule for me again. I appreciate that. And we dove right into talking about your research last time so --- and we kind of skipped over some background information so I wanted to go and pick that up today. Ralph B. Arlinghaus Okay.  

Tacey Ann Rosolowski, PhD:

And so I wanted to ask you where were you born and when? If you would share your birthdate with me?

Ralph B. Arlinghaus, PhD:

Let’s see. So, when I left MD Anderson, I of course took a job with Johnson & Johnson in Lahoya and they had me help them start up a company. I think I covered some of that and then I also brought a grant with me from MD Anderson. I was working on …

Tacey Ann Rosolowski, PhD:

Actually we --- we did talk about this last time. Your --- Your movement yeah to --- and I kind of wanted to go back in time a little bit if you don’t mind and talk about your --- your early background. Where you were born and then your family history. Yeah. Just because we’re --- we’re interested in getting a biographical picture of you, too.

Ralph B. Arlinghaus, PhD:

I was born in Newport, Kentucky in 1935 and …

Tacey Ann Rosolowski, PhD:

And what’s your birthdate?

Ralph B. Arlinghaus, PhD:

08/16/1935. August 16, 1935.

Tacey Ann Rosolowski, PhD:

Thank you. Okay. Is that a small town? Newport?

Ralph B. Arlinghaus, PhD:

Newport is a --- is a small town in northern Kentucky across the Ohio River from Cincinnati, Ohio. So Cincinnati is big, Newport is small. And, uh, It’s a nice --- It was a nice little town, but it went through some cleanup issues. It used to be a big gambling --- a big gam --- a gambling place. Wide open place.

Tacey Ann Rosolowski, PhD:

Interesting. Now what about your family? Was anybody in your family involved in the sciences at all?

Ralph B. Arlinghaus, PhD:

Oh no. No. My --- My mom and dad went to Catholic schools in either northern Kentucky or Cincinnati and I think my mom went to the third grade and my dad probably about the same. My mother ended up because she was one of 11 and her father wasn’t doing so well. Her father was in --- My mom’s father was in the grain business who I never knew and then when automobiles came --- came out, feeding horses grain to pull your wagon around or your buggy, wasn’t available. So his business went --- went downhill. So --- So I think my mother was third or fourth grade. She went to work.

Tacey Ann Rosolowski, PhD:

Wow. That’s pretty amazing.

Ralph B. Arlinghaus, PhD:

In what you might call a sweatshop.

Tacey Ann Rosolowski, PhD:

Wow. That’s amazing.

Ralph B. Arlinghaus, PhD:

She called it piece work. Where you make --- you make a skirt, you got a nickel. You make a pair of pants, you got another nickel. And you work 10 hours a day and …

Tacey Ann Rosolowski, PhD:

Now what’s your family background in terms of --- are you of an immigrant background?

Ralph B. Arlinghaus, PhD:

My --- My --- My parents were born --- My mother was born in Kentucky --- northern Kentucky. My father was born in Cincinnati. Their parents came over from Germany.

Tacey Ann Rosolowski, PhD:

Okay. That’s very common it seems with the --- the generation that comes over you know works really hard so the next generations can have an education.

Ralph B. Arlinghaus, PhD:

And my mom and dad they worked very hard because he was one of 12. She was one of 11. She was the youngest of 11. He was the oldest of 12 and they had to bring money in. So that the family had enough to eat, I guess.

Tacey Ann Rosolowski, PhD:

So how --- Did you go to work at an early age? How --- What was the balance of work and education?

Ralph B. Arlinghaus, PhD:

My --- My --- My dad was a --- He was blind from birth. So he was employed as a baker in Newport, Kentucky for the same bakery shop. I don’t know, 40 years and my mother had odd jobs in addition to being a housewife and taking care of five children. So she would --- she’d clean doctors’ offices. So they --- they had a hard time. So when I was --- reached high school age my mother was a very strict Catholic. And she said “Ralph, you’re going to have to go to a Catholic school. Not to the public school in Newport. I don’t want you going there. So you’re going to have to go to the Roman Catholic school, but they have --- you have to pay tuition and we don’t have the money for that. So you need to get a job.” So I was like 12 years old, right? So I got a job at a pharmacy working afternoons. Three to five afternoons a week and went to --- went to Catholic high school. And worked at that same place when I went to college. The only one of our family that went to college --- went to university.

Tacey Ann Rosolowski, PhD:

And you went to the University of Cincinnati, right?

Ralph B. Arlinghaus, PhD:

That’s correct.

Tacey Ann Rosolowski, PhD:

And you got your BS in 1957.

Ralph B. Arlinghaus, PhD:

That’s correct. So I had to pay my way through that. So at that same pharmacy that I worked all through high school, I worked that same pharmacy all through university studies.

Tacey Ann Rosolowski, PhD:

So what did you do in work at the pharmacy and is that why you ended it?

Ralph B. Arlinghaus, PhD:

I was a clerk.

Tacey Ann Rosolowski, PhD:

You were a clerk?

Ralph B. Arlinghaus, PhD:

0:06.:25 I was a clerk. I was a soda fountain clerk.

Tacey Ann Rosolowski, PhD:

Oh, yeah? So why did you select to go? I --- I mean I’m just thinking you worked at a pharmacy and you ended up going into pharmacy.

Ralph B. Arlinghaus, PhD:

That’s right. I did.

Tacey Ann Rosolowski, PhD:

So what was that about?

Ralph B. Arlinghaus, PhD:

Well, I mean --- I mean our edu --- the family and --- our education in our family was minimal, right? So I --- if I was going to able to go to college and I wanted to because my mother stressed education. Although she never went passed the third grade, she said “You need to get educated.” And so she pushed me, pushed me, and pushed me to get education. So --- So I didn’t want to go to a liberal arts school at University of Cincinnati. I picked College of Pharmacy because I was working in the --- the pharmacy and I knew something about pharmacists. so I was --- I got into the College of Pharmacy because I was a very good student at the Catholic high school that I went to and was like third or fourth in my class. I don’t remember. But --- So --- So I went to that University of Cincinnati and it was a small college of pharmacy that wasn’t part of the university. It used to be called Cincinnati College of Pharmacy and I entered in, what is that --- 50 --- ’53 September and I’m trying to think. So in ’54 the College of Pharmacy merged. Or --- Merged is probably too strong a word. Became part of the University of Cincinnati. The Dean of the College of Pharmacy --- The Cincinnati College of Pharmacy, just a small school, somehow managed to convince the un --- the big university to take the College of Pharmacy as part of one of their --- their colleges. And that was a big deal for the College of Pharmacy. And --- So the second year of College of Pharmacy I went to the University of Cincinnati and took courses with all of the --- all of the --- all of the big college courses unlike the College of Pharmacy. So it’s a new world for me. I did pretty well my first year but I did extremely well the third --- second, third, and fourth year at the university.

Tacey Ann Rosolowski, PhD:

Interesting. Yeah. So what --- what did you --- what were the courses you really gravitated for and how did you see your own abilities developing? Because that must have been an amazing, you know, here is an emersion in a whole new world.

Ralph B. Arlinghaus, PhD:

Well first of all you know we were in very small classes at College of Pharmacy, maybe 70 people. Like my organic chemistry course in the second year of College of Pharmacy at the university there was probably 600 people. The instructor, his name was Ian McGregor, spoke with a microphone in this big auditorium and I thought, man, I’m --- I’m not going to make it. But, uh --- So it turns out he gave very tough exams and I finished the exams. I was one of the few that finished. And I was --- my class average in that course was something like in the mid-90s and the average for the class was the mid-60s, maybe mid-50s.

Tacey Ann Rosolowski, PhD:

So you’d really found your element.

Ralph B. Arlinghaus, PhD:

So I --- A lot of people didn’t like me. I blew the curve so to speak. But I --- I have to tell you that I wasn’t sure I was going to make it through school so I studied all the time. I didn’t have a car. So I had to take a bus to go from Newport, go to the bus terminal in Cincinnati, walk from the bus terminal to another bus stop, take a street car to the College of Pharmacy, and then later take a --- take a street car or bus to what’s called Clifton Area of Cincinnati where the university was. So --- So I worked at that College of Pharmacy and so I was working probably 20 hours a week and taking a four --- a full course load. Back then a full course load was 18 hours and I ended up Valedictorian in my class at the College of Pharmacy so --- because I was I don’t know. I remembered everything I read and

Tacey Ann Rosolowski, PhD:

Yeah you kept at it.

Ralph B. Arlinghaus, PhD:

I asked questions and on exams I wrote it all down.

Tacey Ann Rosolowski, PhD:

Did you love it?

Ralph B. Arlinghaus, PhD:

I --- That’s too strong a word. I knew it was a means to an end. Because I --- I knew I wanted to get a college degree and after I found out I was so talented in getting grades --- in getting good grades and I decided I was going to get my Master’s degree. And I made that decision in the senior year of college. I went on and got my Master’s degree.

Tacey Ann Rosolowski, PhD:

And that --- you got that in 1959.

Ralph B. Arlinghaus, PhD:

Right. And then I decided well people told me that after the Master’s degree you don’t want to stop here. You’re --- you’re doing well and I had a good advisor who was the Dean of the College of Pharmacy, a guy name Joseph Kowaliski ) and Dr. Kowaliski ) was a --- really a good mentor for me and so I --- he helped me get into the graduate program of Arts & Sciences at the University of Cincinnati. The Master’s degree was in the College of Pharmacy. They had their own Master’s program. So then I got a degree --- a Ph.D. degree and …

Tacey Ann Rosolowski, PhD:

And that was in 1961 in Biochem.

Ralph B. Arlinghaus, PhD:

Yes. Yes. And …

Tacey Ann Rosolowski, PhD:

What was your --- your Ph.D. research?

Ralph B. Arlinghaus, PhD:

That’s another interesting story. For me interesting. I --- When --- I was part of the medical school faculty. I was not the faculty. I was --- my advisor was a medical school faculty member and he was studying the structure of collagen. And --- Yes, so I --- they accepted me into their laboratory and I --- I was asked to sequence collagen. Now back then it wasn’t known, but collagen is not one long polyprotein. It’s three long polyproteins. We called them alpha, beta, and gamma. I don’t know what they’re called now but --- and there --- so sequencing them was not --- not going to be easy. And I didn’t know that. I was naïve and so I took on that project and the guy before me who got his Ph.D., he had purified lots of fragments of collagen and he had them stored in a freezer. I don’t know if you remember the Evenflo baby bottles.

Tacey Ann Rosolowski, PhD:

No, I don’t. No.

Ralph B. Arlinghaus, PhD:

Well, Evenflo was one of the first to make bottles with nipples to feed babies, right, and back when I was growing up and so we had these 4 ounce Evenflo bottles. There must have been 25 of them in this freezer --- chest freezer and my advisor said, “Well, I want you to sequence all of those peptide fragments of collagen and I picked the first one out.” and got my Ph.D. on that first one and why. Well, back then this department --- this laboratory was kind of behind times. I didn’t know that, but I would go to the library and look at modern methods which were not available in that department. So the first baby bottle, I thawed it out and using techniques I was taught by my advisor, it looked like a dipeptide, two amino acids, based on his methods. And I was reading in the library and there was a group at Rockefeller called Moore & Stein, very famous for developing methods to separate all 20 amino acids from proteins on a single analysis which happened to be something called column chromatography. So the --- So it was a setup that wasn’t available in this laboratory --- in this department. So according to Moore & Stein from Rockefeller’s PNAS paper I needed a 4 foot 1 cm diameter glass column and put a resin called Dowex-50, pack that resin into this column that went from here to the floor.

Tacey Ann Rosolowski, PhD:

Wow so about six feet? Eight feet?

Ralph B. Arlinghaus, PhD:

Well maybe four or five feet. And then --- then it had to be jacketed and run at 37 degrees. So I had to --- I went and scrounged up a water bath and a heater that would maintain the water bath at body temperature and I got a pump from a hardware store. Pumped the water out of that bath into the column jacket and so essentially made my Moore & Stein column as they described it in their PNAS paper. So then I --- I’ll never forget this --- I did all 20 amino acids like Moore & Stein, mixed --- made an artificial mixture. You know hydroxyprolene, prolene, glycine, phenylalanine, the list goes on. You mix them all together --- put them all together and then put them on as a mixture on the column and got 20 peaks just like Moore & Stein. And I could identify which was phenylalanine, which was tyrosine, which was lusein, which was isolusein by their appearance, their elution from the column.

Tacey Ann Rosolowski, PhD:

How amazing.

Ralph B. Arlinghaus, PhD:

So there --- these 20 peaks that always eluded in the same position and the two amino acids I was in --- I was interested in --- Sorry I have this partial in my mouth. I had a tooth pulled. Waiting to have another one drilled up in there. But anyway, so two amino acids I was interested in based on the analysis from my advisor was glycine and hydroxyprolene. So I knew from my analyses from Moore & Stein, where each one of those amino acids should emerge. So I put the dipeptide hydrolysis where you fragment the --- you use hydrochloric acid, put it in a CO2 110 degrees overnight, break the tube open, evaporate down the hydrochloric acid and then you have your amino acids as free amino acids and as --- as my advisor said, “Well, you get two amino acids.” Well, that’s when things changed. The --- His analysis said it was two amino acids, glycine and prolene. My analysis said it was glycine, hydroxyprolene and something that wasn’t part of the 20 amino acids. In other words, a new peak. A new --- What appeared to be a new amino acid. So the title of my thesis was “A New Amino Acid of Collagen”.

Tacey Ann Rosolowski, PhD:

Wow. So that was a really significant discovery.

Ralph B. Arlinghaus, PhD:

Yeah for a --- for a guy that just got off the turnip truck, yeah.

Tacey Ann Rosolowski, PhD:

Yeah. I mean I’m seeing too you know just that very story because you were stressing last time you know how you always had like a --- you know, a good intuition about where to find interesting results and also a real independence. You know doing your own research, putting that together and that shows there --- right there in that story.

Ralph B. Arlinghaus, PhD:

You see this --- this guy that was my mentor was behind times. Well he didn’t know it. Then I knew it. After I went to Moore & Stein, ran the column and figured out that his two amino acids was really three amino acids, one of which didn’t match with any of the peaks of Moore & Stein. So I knew I had something new. At least I believed that. He didn’t believe me. He made me run it many times and I got the same results.

Tacey Ann Rosolowski, PhD:

Did he --- He eventually did believe you?

Ralph B. Arlinghaus, PhD:

He finally had to believe me.

Tacey Ann Rosolowski, PhD:

He finally had to believe you. Yeah.

Ralph B. Arlinghaus, PhD:

And then I crystallized this new amino acid.

Tacey Ann Rosolowski, PhD:

And I’m sorry, what was the name of the new amino acid?

Ralph B. Arlinghaus, PhD:

Well what’s in collagen is 4-hydroxyprolene. As I found out and that’s the title of my thesis, “3-hydroxyprolene – A New Amino Acid of Collagen.” So I crystallized that peak and going around to the chemistry department which I said I was --- those people knew me because I was an item. I --- I got --- I got the highest grades and I was just kind of from the moon, I guess. I don’t know. Something --- Somebody --- Some young man that was very unusual. So I got a lot of cooperation and I got in contact with some of the people that did physical chemical studies, crystallized this purified amino acid and between that and this physical chemistry stuff, I said it’s 3-hydroxyprolene. And then we --- we made 3-hydroxyprolene in the chemistry lab and compared what eluded from the --- the so-called tripeptide that was in collagen. Compared it on the Moore & Stein column and the chemically made 3-hydroxyprolene co-eluded --- co-emerged with the --- the --- the unknown 3-hydroxyprolene that eluded from the column.

Tacey Ann Rosolowski, PhD:

Hmm.. Now your next move was to --- to get some …

Ralph B. Arlinghaus, PhD:

So that --- So I got out in two years.

Tacey Ann Rosolowski, PhD:

You got out in two years?

Ralph B. Arlinghaus, PhD:

Because --- I have to say it. I was the most advanced person in that department and they knew it and then I knew it.

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Chapter 08: Discovering a Talent for Laboratory Research and an Early Research Success

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