Fertility training at the Jones Institute

with DR. RICHARD SCOTT
Hello, I am your host Dr. Andres Reig. Welcome to episode 1 of FertiliPod, the podcast where we discuss current topics and the latest research in the field of reproduction with some of the world's leading experts.

In this episode we have Dr. Richard Scott as our special guest. Dr. Scott is a professor and the REI Fellowship Director at Sidney Kimmel Medical College of Thomas Jefferson University. He was also a founding partner of Reproductive Medicine Associates of New Jersey and now serves as the CEO of IVIRMA Global. Dr. Scott has authored over 500 papers and abstracts and has won numerous awards throughout his career. Dr. Scott is joined by, the Chief Scientific Officer and Chief Medical Officer at IVIRMA, Dr. Emre Seli.
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Podcast Transcript

Dr. Emre Seli:
Dr. Scott, thank you so much for joining us today. I have listened to your account of the Jones Institute and how wonderful it was in the past, but it is a privilege to assist you in sharing this information. Can you please start by telling us how Jones Institute started and who were Georgeanna and Howard Jones before founding the Institute?

Dr. Richard Scott:
Howard and Georgeanna Jones actually were at Johns Hopkins University for what many would consider a career. In fact, they were forced to retire from Johns Hopkins based on a mandatory retirement age of 65, which existed at the time. As they were married, they allowed Georgeanna to stay, so she was 65, and Howard to stay until he was 67 because of Georgeanna. But then they were forced to retire after a very distinguished career there, where they made many contributions. Many don’t know, but Bob Edward spent the summer of 1966 there, and I believe it was ’66, and went through some of the very earliest attempts at IVF when they knew they had to capacitate the sperm. People believe, and perhaps it’s true, that there were some human in vitro fertilizations obtained in the late ’30s and early ’40s, but they didn’t know to capacitate the sperm, and it’s hard to imagine that those indeed were normally fertilized oocytes that made embryos.

Dr. Richard Scott:
Ultimately, of course, its successes came much later with Dr. Edwards back in the United Kingdom, but Howard and Georgeanna were part of that small circle, part of that group of small group of individuals who knew that bypassing the pelvis, dealing effectively with tubal disease and endometriosis, which were the predators that impaired our patients the most in those days, because most of them were still in their twenties, that ultimately would lead to the success of IVF and all the places we are today.

Dr. Richard Scott:
But at any rate, the Jones Institute began as Howard and Georgeanna Jones moved to Norfolk. They had grown up in Baltimore, but they loved to sail. They had a boat out in Norfolk, and they had a very good friend in the form of Mason Andrews. Mason was their first fellow at Hopkins in the late 1940s and had helped start the medical school in Norfolk. He was chairman and really founder of the academic department of OBGYN at the university hospital there and the medical school and eventually Mayor of Norfolk, deeply involved in the community, deeply committed to improving healthcare for all.

Dr. Richard Scott:
But as the story goes, Howard and Georgeanna were literally moving in. They had bought a house in Norfolk, and you can see a video of it. They have it at the Jones Institute. I’m sure it’s widely available, where people are moving furniture into their house. And on that particular day, Louise Brown had delivered in the United Kingdom. So the concept of a test tube baby, in vitro fertilization was a very hot news topic. The news, of course, called Mason because he was kind of the know all, be all person for anything related to women’s healthcare in the region, and he sent them to Howard and Georgeanna. They went to their new house, again, while they were not settled. They were in casual clothes. And Howard goes out to deal with the press and they asked him questions.

Dr. Richard Scott:
At the conclusion of the interview, which was interesting, they said, «Do you think we could ever do anything like this here?» And paraphrasing, but more or less his answer is, «It just takes money.» There were people watching that day, and I’ll hesitate to mention the name, because I don’t want to violate anyone’s privacy, but a very wealthy philanthropic person in Norfolk area had a daughter with bilateral blocked tubes. And the next day they saw the news clip. The next day they’re on the phone with Mason. And within days after that, there was a plan put in place to create the Jones Institute or what became the Jones Institute and to build the United States’ first in vitro fertilization program, not just for academic purposes, but truly to help patients have babies.

Dr. Richard Scott:
And so it’s amazing how serendipitous some beginnings are. They were at the end of their career and they began what would last almost 40 years. 39 years Howard worked in the Institute and worked in the field of in vitro fertilization before he unfortunately passed away at the age of 104. So actually that would have been 37 years, but at any rate a very long time.

Dr. Emre Seli:
Long enough.

Dr. Richard Scott:
Georgeanna’s age.

Dr. Emre Seli:
Definitely, definitely long.

Dr. Richard Scott:
So that’s really how it began.

Dr. Emre Seli:
That’s an amazing story. In addition, I think they early on, they started contributing to the science of ART. And we will come to what you have done and what you have seen as you arrived, but what did they do before you arrived there? Like, I think a few years –

Dr. Richard Scott:
An enormous amount before I arrived there. So Howard and Georgeanna, of course, they’d been close collaborators. And in this small group of people, one from Australia and a couple from England, themselves in the US, who were trying to figure out how to do IVF, and Georgeanna was the first to really come out and say, even though there had been failures with ovulation induction in the past, that a single oocyte was probably not reproductively competent at any age and any female. And to make this system efficient enough to be practical, we were going to need to do ovulation reduction. Now again, the original attempts in England had been with ovulation induction, and the Australians had played with this some, but Georgeanna was a true master endocrinologist. Her medical training was actually one year of residency and a one-year fellowship in medical. There was no medical endocrinology. There was no OBGYN then to train in. And so Georgeanna really advocated and then developed-

Dr. Richard Scott:
Really advocated and then developed all the normative data, all the knowhow on how to do ovarian stimulation for normal ovulatory women. There was no experience before that. They only induced ovulation in anovulatory women. The concept of superovulation was really very novel at the time, and she developed much of that. All the different response curves, how to avoid hyperstimulation, and basically set the foundation for the stimulations that we still do today. All of that was done at the Jones Institute and all under Georgeanna’s guidance.

Dr. Emre Seli:
And when did you arrive to Jones Institute and who were you then at the time you arrived? I guess you were not very knowledgeable about ART. And no one was so.

Dr. Richard Scott:
Truly at the ground state. I mean, you have to just imagine the lowest possible level. So I came there in the summer of 1987. By then, the Institute was an exciting place. They were bringing a lot of patients from all over the world and doing IVF. A lot of scientists came from all over the world to study there, do sabbaticals there. In fact, I shared an office with someone who was already very far into their academic career in Israel, a gentleman named Daniel Navot. When I was a fellow, because he was considered a foreign fellow, even though he was really quite distinguished in his academic career and had a New England Journal article on the first donor egg pregnancies in women with no ovaries, and so there were just a lot of incredibly talented people there, and one of the things that Georgeanna and Howard did is that they always made certain that the fellows, the youngsters, people with really almost no background and very limited funds of knowledge, had the opportunity to interact with all these incredible people, both the faculty within the Institute, but also all the visitors.

Dr. Richard Scott:
So I had a chance when I was a fellow to sit and talk with Bob Edwards for hours about whatever I wanted to talk about, and Eli Adashi. I got Eli Adashi to sit down and really beat it into me what insulin growth factor was and what it probably meant. Before that day, I’d never heard of insulin growth factor, and by the end of the day, I could quote some of the literature. How fortunate is that? I got to speak to just… I won’t bore you with the list because it is long and extremely distinguished, of people who came there and interacted… Ann Winson, the list goes on and on. It was really exciting.

Dr. Emre Seli:
It’s amazing and you were at the beginning. And what was the work day like for you as a fellow?

Dr. Richard Scott:
So the fellows days started early. We started at six. We were there a little before the attendings to get monitoring done. Now, if I can digress just for a moment and tell you what monitoring was in 1987. So we had radioimmunoassays, not the high-speed ELISAs of today, these were true radioactive immunoassays, and we had ultrasounds, but the core of the faculty had trained in an era when those things were not available. How do you monitor a cycle if you can’t do an ultrasound and you don’t get any blood work? And the answer is that had all been derived by many people of which of whom Georgeanna was one, but also many people in Israel and Europe and a number of spots. And they monitored women by their biologic assay, their bioassay for estrogen effect. So they did cervical mucus scores to see if their cervical mucus highly hydrated, had quaternary ferning.

Dr. Richard Scott:
And they did pignotic indexes on the vaginal mucosa to see whether or not you saw large squamous cells in very few of the very small, highly nuclear, large nuclear cells. Can you imagine being a first-year fellow with really no RA training and you show up the first morning and they say, «We have 85 patients that you need to do a vaginal pignotic index and a cervical mucus score on, and we really need it to be done before eight.» So those were the days that we did those. We didn’t really stop doing those until middle of my second year. And so it is amazing how accurate they can be. The rule of thumb was when they had a 90% pignotic index with superficial squamous cells in quaternary ferning, that was called the biologic shift. Go three days past the biologic shift, it hit them. It’s almost always correct. If you find yourself out there without electricity except for maybe a microscope and you need to monitor people, you actually can. Maybe it’s not as precise, but it works pretty well.

Dr. Emre Seli:
Much less expensive of course.

Dr. Richard Scott:
And very, very cheap. We still did ultrasounds after that and then we did blood work. The fellows would take the blood work downstairs. And in many cases, for those of us who were interested, we ran the blood work. We even iodinated some of our own assets. So it was a little different now than the auto analyzers we have that give you a result in 15 or 30 minutes, but it was very exciting. Seeing the follicles grow was just extremely, extremely exciting. It was a great time.

Dr. Emre Seli:
How about after that? You do those and then what do you do? Did you see patients with them or?

Dr. Richard Scott:
We would go and see patients with them. And we would go and sit and with the patients and take some of the initial histories and then go sit with Howard and Georgeanna and it was so great to watch them get information from the patients and make them feel comfortable. There by then, 50 years of clinical experience was very evident and they could look at a patient and tell what they needed to know. And they could look at a patient and know how to explain things. Some people, if they were asking the time, they told some people how to build a watch. Others, they just told them, «Look, it’s two o’clock. That’s all you need to know. You’re going to be fine.» And it’s what the patient needed. They were true clinical masters. It was wonderful.

Dr. Emre Seli:
And then how about retrievals, et cetera? I think they were quite different.

Dr. Richard Scott:
Retrievals were very different in those days. They were laparoscopic when I was first there and to do a retrieval, took three, that’s right, three physicians plus a scrub tech, plus a scrub nurse, plus the anesthesiologist. And so you would do a laparoscopy. Remember, you’re putting in that big trocar and somebody who’s got big ovaries. They felt it, they’re up out of the pelvis in many circumstances. Where we would put in the trocar and put in the scope. There were no robots. And we would put in the scope frequently. The physician is looking, the attending physician is looking through the scope. Some used the TV set, but most didn’t. And then one person would help with the aspirations holding the needle and would be the sucker in essence. So there were no automated pumps. You had a 30 CC syringe.

Dr. Richard Scott:
And when they said pull, you did this. All those years of training, this was fellow activity. That was fellow training. And that’s pretty much all we did was pull straight back as you can see that in your mind’s eye. And then another fellow, that was the second year fellows job because you wouldn’t do that as a first year fellow. The first years fellow’s job was to – you would put in a second port and hold onto the ovary by the uterine ligament to try to hold it still. And then your job is to be what’s called the statue, hold it perfectly still. So we would do four, six, eight, 12, someday retrievals where the first year fellow would never see the ovary and their job was to hold that probe still, hold that grasper still for hours. And we did. And then there was a screen from the microscope in Lucinda Deek’s lab in the room so you could see the eggs come up and everybody was always holding the grasper still and trying to look for the eggs. And it may sound silly now, but I have to tell you, it was so exciting And Georgeanna on the tough cases, the low responders, Georgeanna would cheer for the eggs. So we were always very excited when we did something well enough that Georgeanna would cheer for the eggs. It was really a lot of fun.

Dr. Emre Seli:
That’s amazing. That’s amazing. How about the research projects you worked on as a fellow there? Or others? I know there were good other fellows.

Dr. Richard Scott:
People should know about the giants in our field, and the Jones were of that rare breed of true giants. Maybe we’ve had four or five in our field in history, and they are two of them. So I would love to talk about what existed there.

Dr. Richard Scott:
Research was driven mostly by the fellows, some by the foreign fellows, a few by the PhD postdocs, but mostly by the MD fellows. And even if someone had a great idea, they typically gave it to one of the fellows and said, «Go run with this.» But we all had our own ideas. We’re all trying to figure stuff out. It was very early days. Almost everything was new and novel.

Dr. Richard Scott:
But at 6:00 AM on Friday, except for the fellow monitoring, they had to go do their cervical mucus scores. At 6:00 AM, Friday, all the faculty came in and met over by the research labs. We have Gary Hodgen and Nancy Alexander and Bob Williams and Keith Gordon, Howard and Georgeanna Jones, David Archer, Zev Rosenwaks, Hannibal Costa, Sue Hill-Washer was an outstanding contributor, always. This is like the heaviest of heavy hitters in our field, in the world at that time. You’re talking to people with hundreds and hundreds of publications and tens of millions of dollars of grant money. And they would come and they would listen to the fellows’ ideas, and we would prepare a one page white paper on what we wanted to do and why, and what was required. And then slides, back when slides were mostly typing out on a piece of paper whatever you wanted to say, taking a picture of it with a camera, and then running to the photo store to get them rapidly developed, because that’s where all the slides came from. There were no digital projectors.

Dr. Emre Seli:
Oh, real slides.

Dr. Richard Scott:
One of the fellows always brought orange juice or juice to drink. And the Joneses always brought donuts. There was a little bakery near them they loved, and they always brought donuts. Every Friday at 6:00 AM, we would present our work and they would critique it. And I presented the original idea to run the day three MSH samples retrospectively based on some ovarian response data that Sue Hill-Washer generated to see if it would predict clinical outcomes. All I remember is Howard Jones telling me, «Richard, you’re never going to build a career telling people how they can’t get pregnant.» But maybe ovarian reserve testing turned into a little something far from perfect. A little something.

Dr. Richard Scott:
But the great part was you got those very direct criticisms, frequently Hodgen or Sue Hill or somebody who ended up at the board redesigning your study. But you would walk out of that conference at 7:30 with a funded project. I need $30,000 to go buy the assay’s to do this. And I’m going to save these samples to do this stuff. Done.

Dr. Emre Seli:
This is incredible for today’s world.

Dr. Richard Scott:
Done. There was funding for research there, and the beauty was the money was there. The horsepower amongst the faculty was there. And they all came together to make sure the fellows stayed busy. I was no busier than anyone else. I wrote 28 papers. I was on 28 publications at a two year fellowship. And there was just that much going on there. It was really fun.

Dr. Emre Seli:
Unbelievable. They also had the patient volume to do all those studies.

Dr. Richard Scott:
Right, we were doing about a thousand retrievals in a year when the whole rest of the country combined wasn’t doing that. So it was a great, great place for asking and answering questions.

Dr. Emre Seli:
I think we talked about why Howard and Georgeanna are so important, but I know you’re especially fond of Georgeanna Jones. Can you tell a little bit more about her? Why is she so important in the field as a mentor and as a scientist, and some memories of her?

Dr. Richard Scott:
Georgiana’s one of those people who just has special genius. I’ve had the good fortune of meeting some Nobel laureates in my life, and some other really outstanding scientists. And I just don’t think they’re like Georgeanna. She could just look at something and it’s like she could see the molecular structure, she could see the endocrine dynamics. And her genius was really just unequaled.

Dr. Richard Scott:
My very favorite part of my fellowship would be the afternoons, the very late afternoon. It’s 5:00, 5:30. It’s the end of the day. You’re tired. Howard was always going off to some management meeting that the Institute needed. Georgeanna thought they were all, she put it, «silly, and I’m not going to this.» That’s the way she would put it. And she didn’t. And nobody, including Howard, tried to make Georgeanna do what she did not want to do. That was not possible.

Dr. Richard Scott:
But I would go knock on her door and say «Georgeanna, do you have a minute?» And she would always be reading. She edited OB/GYN surveys, so she would be reading articles. She would invite me in always. And I would say things like «Georgeanna, how did you figure out what estradiol was?» Or, «How did you figure out that gonadotropins come from the pituitary, and there’s two of them.» And all these things. «How did you figure out the stages of implantation? Where did you get your ideas about the luteal phase?» People think the luteal phase defect with all the complexities go in that, come from deficits of two or three days, depending on who you believe. Georgeanna described it in the ’48 JAMA before the dating paper. There had been a dating paper published in ’38 Science, but before the serious dating paper was published in 1950 by -. She didn’t include individual dates. You know why? Because she thought that the dating wasn’t accurate enough to sign individual days. And everyone disagreed with her for many years until Murray and the group at UNC showed that she was right in 1948 and has been right all along.

Dr. Richard Scott:
Just as many special moments. She always took time to spend time with the fellows. She had very sharp claws. Eli Adashi had been there one time and given us a talk just for the fellows. It was completely over our head, completely beyond our understanding. And afterwards Georgeanna stayed to kind of, she would always stay after the visiting speakers came to quiz us about what we learned and what we thought. And should we incorporate this into our research? Wonderful, wonderful times, but none of us understood anything. And I remember here looking right at me after I answered a question wrong and slamming her fist down on the table and saying, «Such genius is wasted on unprepared minds,» and stormed out of the room. It was like, wow, your favorite person in the world, mother, grandmother, and mentor all telling you you’re worthless all at once. But she was wonderful. And there are so many stories like that.

Dr. Emre Seli:
Wasn’t she also the first division chief of course?

Dr. Richard Scott:
Yes. OB/GYN departments were really evolving through the 20s and 30s. Midwifery had always been either independent or a nursing program or a part of pathology. And gynecology had always been like urology and orthopedics, part of general surgery. And the thought of bringing women’s health together took several forms over those years. But the first true department that we would consider a modern department was at Johns Hopkins, led by Woodruff. And it was just a department of OB/GYN. And then Woodruff felt like it was so disparate that they needed high-risk obstetrics. They needed GYN-endocrine. That’s what it’s called in those days is gynecologic oncology. They needed GYN oncology. But of those, he felt the most different and the least prepared within the department was GYN endocrinology. So, GYN endocrinology, what we would call RE today, was the first ever division and the first ever true OB/GYN department ever. And Georgeanna was very young, very, very young still. Gosh, she was little before 30, I believe. And she was sitting one night at dinner and had a phone call from Woodward while she’s eating, being with Dr. Howard. I think she was 28. And he asked her, he was forming a division of gynecologic endocrinology, and she liked to be the division director. And she just thought for a moment and said yes. And that was the end of the conversation. She’d hung the phone and went back to have dinner. So it’s interesting that Georgeanna was the first ever division director of the first ever division of reproductive endocrinology, and of course led much of the way after that.

Dr. Emre Seli:
How about her thesis? When he was in college? I think she has an amazing thesis, which is hard to believe, but exemplifies how brilliant she is.

Dr. Richard Scott:
Yes. Hopkins had a requirement for people to have a thesis project to get an MD in those days. And you had three to four years to finish medical school, but that included your thesis project. So Georgeanna at the time had always been interested in reproduction, even though OB wasn’t a thing per se. And at the time the prevailing wisdom was that pregnancies were maintained. They knew there was a hormonal basis for it, which required. They knew that you needed a corpus luteum from animal data. But the thinking was that the pregnancy sent a signal to the pituitary and we knew the pituitary from the cases where people have Sheehan’s or panhypopit for some other reason. They knew the pituitary was necessary for reproduction. The Germans have postulated that the pituitary was the source of what eventually became known as ACG. It wasn’t known yet, but eventually became known.

Dr. Richard Scott:
Georgeanna said, no, that’s nonsense. It has to come from the pregnancy. Whereas otherwise people would be getting pseudo-pregnancies anytime something was wrong with the pituitary. So she didn’t believe that as a third year med student, with all these senior professors in the world all saying she’s wrong. So in a matter of a couple of months she went down to the slaughter houses on the docks in Baltimore, and got all these parts from cows and parts from cows and pigs, took them back up to her little research lab in the endocrine department at Hopkins, put them through what is basically a still, isolated all the components for the placenta, and started objecting different animals and proved that the hormone that maintain pregnancy did not come from the pituitary but in fact came from the placenta. And so can you imagine overturning the entire world’s vision of pregnancy maintenance in two months? Not only she did that, but she did a bunch of fractionation things and proved that it was water-soluble and approximate molecular weight.

Dr. Emre Seli:
As a medical student.

Dr. Richard Scott:
So not bad for a couple of months as a med student.

Dr. Emre Seli:
Which I think will bring me to my final question, which is what principles do you apply as an educator, as scientists? Because I know you are a demanding PI and I know you have high standards and I understand it partially at least, if not fully comes from Georgeanna, what you have seen it with the Jones Institute. So how do you negotiate those principles also with today’s life balance. It’s not an easy task because the world also changes.

Dr. Richard Scott:
The world changes, fellows change, expectations change, but I have to tell you, I find it very hard to compromise on the principles that Georgeanna taught us. I will mention those in one moment. If I can quickly tell you about the day I graduated fellowship.

Dr. Emre Seli:
Oh, wonderful. Please do.

Dr. Richard Scott:
I just went to say goodbye. You’re going around, you’re saying goodbye to all the attendings and thanking them for all they did for you, which was a lot. And Georgeanna looks up at me very serious. And so she goes, «You have to train people. I trained you and now it’s on you.» And that was it. That was her goodbye. There was no other goodbye. That was it. It was a challenge. It was a requirement. It was a burden. And I took it very seriously then and I hope I still do today.

Dr. Emre Seli:
You definitely do.

Dr. Richard Scott:
Georgeanna always felt like if a fellow comes, you owe them your very best and you have to give them access to your most critical thinking and the best teaching access to all the other smart people you know. So if you have a chance to go somewhere, take the fellows with you. If you have smart people come in, make sure they spend time with the fellows and their fellows have a chance to see their brilliance and all that they have brought to the field. And then more than that, just ruthlessly, dogmatically challenge the fellows. She was a big Socratic method teacher. She used to always say that a lecture was when the notes of the professor become the notes of the student without going through the mind of either. So she loved to ask questions and she loved to make you explain things, and she believed when you can explain them to her that you truly understood them. And so those are all guiding principles that I hope I’ve carried on throughout my career with residents and fellows alike. And I certainly hope it’s part of our fellowship period today.

Dr. Emre Seli:
Well, they definitely are. And I do observe you working with the fellows and that’s definitely what you do. Thank you, Dr. Scott, this was incredible. I hope the current and future trainee will enjoy it as much as I did. I hope they do, because I think the ongoing ideas about what is correct and what is not in science may change, but I think the basic principles remains the same and you’ve been very lucky. And thank you for sharing those with us.

Dr. Richard Scott:
Very lucky and thank you for including me. And thanks to Howard and Georgeanna. I owe them so much.

Dr. Emre Seli:
Absolutely. Thank you.

Dr. Andres Reig:
This has been another episode of FertiliPod by IVIRMA. Thank you so much for listening. Tune in next week for more research and topic discussions and all things reproductive medicine. See you next week.


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