Eisele's earned monkey's trust with patience, expertise 

by Russel Meyer, editorial intern

Steve Eisele, a supervisor in the Reproduction Research Services Unit, stood calmly and compliantly in an examination room waiting for his patient.

Properly gloved, masked, and goggled, Eisele was ready to perform a prepartum examination on a pregnant macaque. The monkey was expected to give birth within the next day or two. Although she appeared as settled down as her neighbors on this Saturday evening, she still was not quite ready for her exam.

"This is going to take a few minutes," Eisele said as he awaited his cue. "Usually she presents her leg so I can feel the position of the fetus. She’s the one that has to make the first move before I can examine her." In the next few moments, the macaque raised herself from her seated position, backed toward Eisele, and lifted her leg toward him.

Eisele has been caring for nonhuman primates at the UW-Madison since May 1959, first for the Harlow Primate Lab and then for the Primate Center. He currently provides about 500 monkeys. His knowledge and expertise have made him an important contributor to advancing biomedicine, animal care, and animal conservation.

Eisele’s devotion to primates, and his collegial associations with the researchers who have studied them, has allowed him to master the skills and procedures necessary for providing special care to breeding females at the WRPRC. The prepartum examination he was conducting that Saturday night in February was just one example of that mastery.

"Now she’s just about ready," he said. "She’s presenting her underside." The pregnant macaque, in a sort of balancing act with one leg slightly elevated toward Eisele, remained still as he felt for the position of her baby. "That’s perfect," he explained, "the head is down. Now we can listen for the fetal heart beat."

Eisele held a Doppler sensor to the animal’s stomach after she assumed a crouched position. "We should pick up the heartbeat right about here," he said. The Doppler device filled the room with a loud, rhythmic pulsing. "That’s about 160 beats per minute… good… everything is on schedule… now I have to examine her cervix," Eisele said.

The mother-to-be raised her leg toward Eisele again, resuming her earlier position. "You can see how she’s helping me in relation to what I’m doing," he pointed out. Eisele palpated the macaque’s cervix. "The cervix is starting to flatten," he said as he finished the examination. After a change of gloves, Eisele rewarded the monkey with some grapes, a banana, and a "good girl."

Eisele concluded that the pregnancy was normal and added that the macaque may take another day before giving birth. "I really didn’t feel contractions, so I’m not sure if she needs another day," he said. "The only thing I know now is that this is going to be a normal delivery," he added.

Eisele explained the steps of the prepartum exam in simple terms, much as he describes his role at the WRPRC. "My job is to produce conceptions and then go from there," he said. Yet his job is complex. He has an intimate and practical understanding of the entire primate life cycle. His skills are numerous and crucial to both the WRPRC.

Eisele has made himself invaluable to the center by mastering the ability to identify the reproductive status of females through examining their skin color. Through years of observing physiological patterns in rhesus monkeys, he has developed a system for visually grading the cyclic changes in swelling and color intensity of the estrogen-sensitive skin on a female’s thighs during her 28-day menstrual cycle. Ei Terasawa, Ph.D., leader of the Neurobiology Research Group, describes this ability of Eisele’s as "a rare talent."

His visual evaluation method, which is verified by hormonal tests, can help him determine the proper time for arranging breeding or artificial insemination of the females. He can tell whether a rhesus female is ovulating by looking at the color pattern and intensity on her thighs. "Her color increases as her ovaries become more active," he said.

This system is helpful in monitoring the progress of all pregnant females at the center and in pinpointing fetal age for developmental studies. Ted Golos, Ph.D., leader of the Reproduction and Development Research Group, said of Eisele that "the center’s veterinarians have been relying for decades on Steve’s judgments during those last uncomfortable days of pregnancy to determine how soon to expect the baby or whether a Cesarean section may be indicated."

His color grading method is also used prior to another technique that may have already made a significant impact on the course of biotechnology and molecular medicine. Eisele played a crucial role in the center’s former Gamete and Embryo Core by establishing a nonsurgical embryo recovery procedure, also called the "flush" technique.

"This has been a pivotal development at the center and, in a way, in the pathway of molecular embryology in the next ten years," Golos said. "Steve probably played the largest hands-on role in these efforts." Eisele worked with Polani Seshagiri, Ph.D., and John Hearn, Ph.D. in developing this method, Golos added.

James Thomson, V.M.D., Ph.D., also used one of Eisele’s flushed embryos for his research with rhesus embryonic stem cells. "His experience with the monkey cells led directly to the development of human embryonic stem cells, which may be a milestone as we move into the next century of biotechnology and molecular medicine," Golos added.

Solidifying the method of nonsurgical embryo recovery under Eisele’s direction has also benefited the center’s reputation, according to Golos. "This methodology reestablished the leading position the center had historically enjoyed in primate reproductive biology," he said.

Eisele uses his color grading skills to help determine when a designated "flush-female" is to be impregnated and when her embryo is to be flushed. The principles and equipment of the flush technique Eisele uses for rhesus females is almost identical to the flush technique used for obtaining live human embryos. A tiny catheter and tubular device, called a cell sampler, are inserted through the cervix. Flushing media is forced through the catheter to literally flush the embryo out of the uterus and into the cell sampler.

This method of flushing live embryos from the uterus has advantages, for both the monkeys and the researchers, over the surgical removal of embryos. First, the flush technique is nonsurgical, so the monkeys avoid any risks associated with surgery. Second, the flush technique can ideally be performed on impregnated females once a month, making more embryos available for researchers than by surgery. Following the establishment of the flush technique, "we were making embryos available during a 12-month period, rather than seasonally," Eisele said.

Flushed embryos are used mainly for research projects, but if they are not in demand by researchers they can be surgically implanted in a surrogate mother. Transferring a female’s embryo to a suitable surrogate mother may be desirable if the former has a history of unsuccessful pregnancies or lacks nurturing skills.

In the last couple of months, Eisele has been working with hormonal treatment techniques that may lead to a nonsurgical method of transferring embryos to surrogate mothers in the breeding colony. 
He explained that progesterone is given supplementally to aid in implantation.

The progesterone is thought to increase cohesion between the uterine wall and the embryo. "We’re trying to prepare the uterus for the embryo," Eisele said. "We want the most optimal uterus at the time of implantation."

The monkeys who received supplemental progesterone had been given it by injection or by small capsules implanted beneath the skin. The subcutaneous capsules allow progesterone to be present in the monkey’s system at more consistent levels than by periodic injection.

The embryos that were recently transferred to mothers given progesterone had not been flushed but were fertilized in vitro. Eisele said that these particular in vitro embryos were used because they had reached the more mature, blastocyst stage of cell growth. "Everybody thought they looked so good in vitro. They were really progressing, these really looked gorgeous," he said. Embryos that reach the blastocyst stage are thought to stand the best chance of surviving in the uterus and have been used for human embryo transfers, according to Eisele.

Eisele said that two successful embryo transfers had been achieved by WRPRC researchers doing related work in the mid-1980s. These led to the first documented IVF-derived nonhuman primates, from the lab of Barry Bavister, Ph.D.

Eisele serves as a frequent consultant to other research facilitites. He has contributed to the body of primatological literature by co-authoring over 35 research articles that deal with topics in rhesus reproduction, development, and animal care. 

One article that appeared in the Journal of Medical Primatology [5(5):284-95, 1976] documented his work in using ultrasound to determine fetal health and position during pregnancy in rhesus monkeys. He has co-authored articles on social and sexual compatibility of paired monkeys. These appeared in Laboratory Animal Science [38(4): 506-07, 1988] and the Journal of Experimental Animal Science [34(2): 73-76, 1991]. 

He has also co-authored articles on the embryo-flush work that appeared in the American Journal of Primatology [27(1): 58, 1992; 29(2): 81-91, 1993].
 
 
 

Robert W. Goy Memorial Service brings family and friends from across the miles

by Jordana Lenon

And, thus, he expressed his thanks to the 150 people assembled the afternoon of March 14 at the Monona Terrace Convention Center to honor his father and help his family move into Spring, and into the next phase of their lives.

Robert Goy’s family and friends, coming from both coasts and many towns and universities in between, spent that Sunday afternoon listening to words, music and even their own laughter as they recollected fond memories of Bob, Barbara and their children, Michael, Peter and Betsy, and shared the many ways Goy had influenced their lives.

Robert W. Goy—husband, father, grandfather, scholar, scientist, artist, musician, and bringer of new ways of thinking—died Jan. 14, 1999, in Madison. He was 74. His lifetime achievements were featured in the last issue of Centerline, in a special insert by colleague Kim Wallen, Ph.D.

Following bagpiper Al Smith’s opening tribute and welcoming remarks by son-in-law Jim Bane, four close friends delivered their remembrances of Goy. For two hours, people whose lives he influenced listened, not only to the verbal memories, but to the mellow tones of J.S. Bach played by friend and Madison cellist Parry Karp. After each speaker finished, Karp played from the 3rd Suite for Solo Cello, framed by a backdrop of gliding birds over blue waves and melting March ice, as those listening reflected on the words just said or on their own personal memories.

"Bob was my mentor," said Kim Wallen. "He shaped my view of science. The force of his intellectual and personal presence had an impact like no one else." Wallen described how Goy’s artistic sensibilities helped him see things in research that others missed, and how he shared with his students not only his science, but his home life and his hobbies, even teaching Wallen during the course of one week the art of wax casting.

"In Madison, the Goy household became the gathering point for the whole lab," Wallen recounted.  "New members stayed there while finding living space, and there was a seemingly endless stream of people who came in and out of the house…Fittingly, in the back yard, there was a teepee that Michael had erected in preparation for a trip to Northern Michigan, but it emphasized the gathering as that of a tribe, a spirit that Bob cultivated throughout all of the time that I knew him."

"One of Bob’s most frustrating characteristics was that praise and gratitude always made him uncomfortable," Wallen closed. "One never felt that he was able to express to him the impact that he had had on our lives…so for one last time, thank you, Bob."

Neurologist Elliot Valenstein, a graduate student when Bob was a postdoctoral fellow at the University of Kansas in the 1950s, next spoke of his and his wife Thelma’s friendship with the Goys, of fishing trips and lettuce diets, and of Goy’s and Arnie Gerall’s work with guinea pigs in Will Young’s lab.

"This work showed for the first time that offspring could be radically changed by hormones…The work really changed the way people thought about hormones and they became organizers of the nervous system rather than the triggers that activated behavior. Loads of people around the country began to work on these properties, replicating the initial results and certainly expanding them." Goy himself at this point expanded the research into working with primates, first in Oregon and then at Wisconsin.

"Bob and Barbara made a good life here in Madison," said Valenstein, who retired at the same time as Goy. "Bob was extremely proud of the school that Barbara started, the school devoted to introducing young children to the arts. He was proud of his whole family, all of them have done so extremely well."

Arnie Gerall spoke next. He reflected on meeting Goy in 1946, prior to their working together in Kansas, while he and Goy were comparing notes on an experimental psychology class at the University of Michigan. He also shared a story about a memorable trip to Japan, of attending a banquet with Goy where the same type of fish was served for six or seven different courses, but prepared differently each time. "That evening in our hotel room, we both learned the medicinal value of saki," he said.

"Intellectually playful, whimsical, quixotic, extraordinarily talented and astute," Gerall went on to describe Goy. "My students really adored him. He always had meetings, where he would seek them out and talk them out and make them feel that they were doing something worthwhile."

Speaking of the depression and war generation in which young Robert Goy was raised, David Miller, retired Columbia University mathematics and statistics professor and Goy’s friend of 52 years, described him using words from Tom Brokaw’s new book, The Greatest Generation: "Brokaw characterized this generation as being persons who fought for what they believed, accepted responsibility for their actions, did not blame others for their misfortune and met their social obligations, and, yes, I think Bob Goy was a perfect example of that…I think that his way of living will echo to subsequent generations."

Others in attendance sharing memories of Bob Goy and his family included David Goldfoot, Ph.D., who practices clinical psychology in Madison; Dan Joslyn, Ph.D.,  who worked with Goy in Oregon and Madison and is a retired clinical psychologist with the Veteran’s Administration; John Vandenbergh, Ph.D., a professor at North Carolina State University in Raleigh; Malcolm Young, son of Will Young, mentor of Bob, Elliot and Arnie, and a lawyer in the Washington D.C. area; and Joe Kemnitz.

Kemnitz, now WRPRC interim director, related how he came to know Goy in the mid-‘70s as a graduate student. He remembered how Goy "took in all of these people and brought them into his own personal family" and how Friday evenings at Bob and Barbara’s house "was always a remarkable environment of warmth and conviviality."

So, too, was the environment that Sunday on the shores of Lake Monona.
 
 

Gleanings 

In the news

Neil Binkley, M.D., Paul Kaufman, M.D., and Molly Carnes, M.D., are among those physicians named as The Best Doctors in America, 1998-1999, through a peer-review survey by Woodward/White, Inc., and reported recently in Madison magazine.

Grants, appointments, awards

Ted Golos, Ph.D., received a grant from the NICHD to study factors regulating trophoblast differentiation. The two-year, R03 grant is awarded for innovative, high risk-high benefit research. 

Ned Kalin, M.D., Richard Davidson, Ph.D., and Thomas Grist, M.D., associate professor in the
Departments of Radiology and Medical Physics, were awarded a Dana Foundation Grant to study the "Effects of positive and negative emotion on cardiovascular function in normal and at-risk populations."

David Watkins, Ph.D., received notice of a $497,274, five-year grant award, "CTL-based vaccines for the AIDS virus." Project collaborators are investigators Ashley Haase (Minnesota), Steve Wolinsky (Northwestern), Yoshi Kawaoaka (Madison), John Altman (Emory), Deborah Fuller (Powderject), and David Allison (Columbia).

Theresa Duello, Ph.D., was selected to chair the Endocrine Society’s Minority Affairs Committee. The national society is in its third year of providing endocrinology short courses at selected institutions to heighten awareness of and training in endocrinology. Duello will serve a three-year term beginning June 1999.

Stacy Schieble, a student assistant in the Clinical Pathology Lab for more than two years and a senior in the Medical Technology Program, received a $1,000 Alice Thorngate scholarship. The scholarship is awarded annually by the UW’s Medical Technology faculty to an undergraduate senior who displays the most expertise and promise in the field of medical technology.

Amy Usborne, D.V.M., assistant research animal veterinarian in the Pathology Unit, won a Young Investigator Award for her Nov. 19 poster presentation at the annual convention for the American College of Veterinary Pathologists in St. Louis, Missouri. Her presentation, titled "Abnormal circulating lymphocyte morphology in cynomolgus monkeys infected with simian retrovirus type D (SRV)," won the Naturally Occurring Disease category. Her SRV research was funded by Abbott Laboratories.
 

Promotions

Ted Golos, Ph.D., received notice of promotion to associate professor of obstetrics and gynecology. He was appointed assistant professor in the Ob/Gyn Department in 1995. He has been a scientist at the Primate Center since 1987. His promotion is effective July 1.
 

New staff

Ryan Derflinger, lab animal technician, marmoset area (Have to get date from Marlene Monday).
Jody Helgeland, B.S., associate research specialist, Immunology and Virology Core Lab, Jan. 19.
Bianca Mothe, research assistant, Immunogenetics, Feb. 1 
 

Departure

Christine O’Rourke, D.V.M., head of Animal Services, plans to depart the Primate Center (date) to accept a position as a senior research veterinarian at Wyeth-Ayerst Pharmaceutical Research in Chazy, New York. Dr. O’Rourke came to the WRPRC from the University of Michigan and Parke-Davis in 1995. "Chris has done an outstanding job building our veterinary research and clinical program here at the center and we will miss her tremendously," said Interim Director Joe Kemnitz.

In Memoriam

James Reese, 79, of Madison died Dec. 21, 1998. He managed the Business Office at the WRPRC from 1968 until his retirement in 1984. He is survived by his wife, Anita, two daughters, Lori, of Madison, and Frances, of Rochester, New York, and two grandchildren.

(Also, see insert on the Memorial Service for WRPRC Director Emeritus Robert Goy, this issue.)
 

Seven-center review

James Bell and Patricia Fail from James Bell Associates, Stephen Seidel, Dr. John Strandberg and Barbara Perrone from NCRR; and an expert review panel consisting of Drs. Steven Raper and Thomas Kuehl visited the WRPRC Feb. 1 and 2 as part of a review of the seven NIH/NCRR Regional Primate Research Centers to evaluate the overall Primate Centers program. This was the second of the seven site visits. The visit was one step in a process of information gathering and analysis—focusing on operations and resource infrastructure—that will continue for several months.
 

Nobel Laureate visitor

Nobel Laureate Torsten Wiesel visited the Primate Center Feb. 16. The emeritus president of The Rockefeller University and former Harvard Medical School neurobiologist shared the Nobel Prize for Physiology/Medicine in 1981 with David Hubel and Roger Sperry. Wiesel had delivered a lecture on campus the previous day in celebration of the 25th anniversary of the UW’s Neuroscience Training Program.
 

1998 Scientific Research Highlights

Find them on line at:
http://www.primate.wisc.edu/WRPRC/crh.html