HEVESY NUCLEAR MEDICINE LECTURE
HenryN. Wagner,Jr.
William Osler, the medical sage of the Johns Hopkins Hospital and Medical School wrote: “In science, credit goes to the man who convinces the world, not the man
to whom the idea first occurs.―This year's Hevesy Nu clear Pioneer awardee, a true son of the Johns Hopkins,
is both a person to whom ideas first occur and, especially, one who, in the name of nuclear medicine, convinces the world of their veracity and usefulness. PERSON
Henry Nicholas Wagner, Jr., was born in Baltimore, Maryland, on May 12, 1927. He attended Baltimore schools, including Calvert Hall, from which he graduated in 1944. While at Calvert Hall, he developed an interest in medicine,
in part through
reading about the great
fighters against infectious disease, and determined to become a physician. After one year in the Coast Guard
Academy, he matriculated in the College of Johns Hopkins University, receiving an A.B. degree (Phi Beta Kappa) in 1948. During the summer following his graduation, he began to work with Dr. Curt Richter, a well-known neuroscientist at the Johns Hopkins Medical School. This research, which extended through three more summers, was concerned with methods for mea 934
suring visual responses in animals and with environ mental influences on central nervous system function. In 1948 Henry entered the Johns Hopkins University School of Medicine, graduating with an M.D. degree (Alpha Omega Alpha) in 1952. In his third year of medical school he married Anne Barrett, whom he had met three years previously at a scientific meeting when she was a junior at Mt. Saint Agnes College. One year later, their first child (Henry Nicholas III) was born, followed by Mary Randall, John Mark, and Anne Eliz abeth. He joined the Osler Medical Service at the Johns Hopkins Hospital on graduation from medical school, first as an intern and then as an assistant resident. During this period he wrote several papers, stemming from his house-staff experience, on the clinical treatment of in fectious diseases. In 1955, Henry Wagner joined Robert Berliner's group at the NIH as a clinical associate. Among his colleagues there were Eugene Braunwald and Jack Or loff. His work focused on autonomic vasoregulatory in fluences on the kidney, particularly on responses to antidiuretic hormone. Following this, Henry went to the Hammersmith Hospital for a year and worked in the Endocrine Unit under Russell Frazer. Here, through a study of iodine THE JOURNAL
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metabolism in the thyroid, he first began to use radio active materials.
Henry returned to the Hopkins the following year as Chief Medical Resident on the Osler Medical Service. When asked to join the Hopkins medical faculty, as was customary after this assignment, he told A. McGehee Harvey, then head of the Department
of Medicine, that
he wished to work on the application of radionuclides to the study of clinical problems. Harvey was not particu larly enthusiastic about this idea but agreed to provide some space along with a faculty appointment. Henry thus joined John McAfee, who was developing a radio isotope unit at the Johns Hopkins through the Depart ment of Radiology. In 1964 Henry was appointed Phy sician-in-Charge
of the Nuclear
Medicine
Division
at
physiologic and pharmacologic mechanisms—in this case, the binding of mercury compounds by renal tu bules. This was soon followed by the use of heat-dam
aged erythrocytes for spleen scanning, based on the spleen's ability to sequester damaged
red cells (3). After
the introduction of radiopertechnetate for brain Scanning by Paul Harper, the Hopkins group provided the phar macokinetic rationale for its use (4). They were also responsible in large measure for the introduction dium-ll3m
into clinical
practice
(5) taking
of in
advantage
of its property of binding to transferrin in the first in Stance. For the swift detection of pyrogens in locally prepared radioindicators, we are indebted to their de velopment of the Limulus test (6). The Hopkins Group has also had a long-standing in terest in exploiting techniques for the determination of
the Johns Hopkins Hospital. In the following sections, I shall outline the contributions of that Division to re search and training in nuclear medicine; I shall also try to provide an intellectual biography of Henry Wagner. Currently Dr. Wagner is Professor of Medicine, Ra diology and Radiologic Science in the School of Mcdi cine, and Professor of Environmental Health Sciences
cially in relation to peripheral vascular (1 1) and con genital heart disease (12). With these methods they have
in the School of Hygiene and Public Health at the Johns
demonstrated
Hopkins University. At the Johns Hopskins Hospital, he is Director of the Division of Nuclear Medicine, Physician and Radiologist. His honors include the Vik ram Surhabel Gold Medal (Society of Nuclear Medicine of India), the Georg von Hevesy medal (in 1976), and a Doctor of Science (Honoris Causa) from Washington College. His list of memberships and consultantships is long and varied.
of significant arteriovenous shunting, as was earlier be
CLINICAL SCIENTIST
In examining the considerable body of knowledge that has emerged from the Johns Hopkins nuclear medicine
regional blood flow, beginning with the demonstration in man that aggregated albumin particles could be used
to detect pulmonary embolism (7), regional hypoxia (8), and lung cancer (9). They have also used microspheres to study the distribution of cardiac output (10), espe
that Paget's
disease of bone is not the site
lieved (13). They were among the first groups interested
in the use of monovalent cations for imaging regional myocardial blood flow (14) and provided experimental validation for the technique using microspheres (15).
In other physiologically based developments, they introduced
the concept of cystic-duct
impatency
in acute
cholecystitis (16), the use of radionuclide angiocardi ography in cyanotic congenital heart disease (1 7), and that of gated cardiac blood-pool studies in the diagnosis of valvular disease of the heart (18). Earlier studies had exploited the dissociation of regional ventilation and perfusion in pulmonary embolism using radioactive gases (19). Recently they have been pioneers in the use of spiperone labeled with positron emitters for measuring
unit during Henry Wagner's stewardship, I am Struck by the way it parallels the natural history of our disci pline over the past two decades. On close inspection it is clear that the Division has both led the field in new di
dopamine receptors in the human brain (20). In terms of physical techniques and instrumentation, the group has made a number of significant contribu
rections and helped to elaborate on areas opened up by
tions. They were first to demonstrate
others. Thus, I find it impossible to separate clearly its work (with the considerable imprint that Henry's di rection has had on it) from concurrent developments in
hole imaging (21 ) and to emphasize the advantage of vertex views in brain scanning (22). The introduction of
other clinics
and laboratories.
Nonetheless,
there are
certain areas that bear the Hopkins' stamp and for which principal credit must be given to Henry and his col leagues.
The introduction of renal scintigraphy with Hg-203 chlormerodrin by John McAfee and Henry Wagner (1) and extension of the use of the agent for measuring dif ferential renal function by Reba, Wagner, and McAfee (2) were the first of a number
diopharmaceutical
of developments
in ra
science built around established
Volume 25, Number 8
the utility of pin
computers into nuclear medicine research and practice was hastened
by their
concepts
of image
analysis and the creation of functional
display
and
images (23). In
the field of radioassay they have been in the forefront of automated radiometric methods for measuring 14CO2, introduced first for the detection of bacterial invasion and later for the assay of vitamins and measurements of cell metabolism (24). More recently, they have utilized a simple radiodetector device for the generation of left ventricular time-activity curves that can be used to cal
culate ventricular volumes (25). 935
HEVESY NUCLEAR MEDICINE PIONEER LECTURE
From Henry's house-staff days he has had a long a feeling of caring and involvement and knowing that standing interest in infectious disease and its effects on Henry is concerned about them and their work.― the organism. In addition to developing methods for the And from Don Tow: “I believe that Henry's out early detection of bacteria in blood and other body fluids, standing contribution to the field of nuclear medicine has hehasexploredthereactionsof thereticuloendothelial been his effectively articulating nuclear medicine to system to infections and endotoxins (26). The Hopkins American medicine, and possibly to the world as group also introduced the use of gallum-67 in the de well.― tection and localization of abscesses and sarcoid Fred Mishkin writes: “I hold Henry Wagner in awe (27,28). for his fertile mind, his invariably incisive way of cutting Considering the productivity of the Hopkins' unit over to the core of a problem with the right question or ob the past two decades, this sampling is to a great extent servation, and his whirlwind productivity. Scientific truncated and to some degree capricious. It represents programs are continually and increasingly enriched by the view of one admirer, and other views will have a contributions from the investigations of his current different composition and emphasis. Nevertheless, I hope trainees, which he quietly masterminds. His ability to it conveys a sense of the breadth and thrust of the Divi do this year after year may be in part due to his boyish sion's contributions. eagerness in looking for solutions to common problems and delighting in being the first to find an answer.― From Frank DeLand: “When my interest in nuclear TEACHER AND SPOKESMAN medicine became overwhelming, I returned to Hopkins If Henry Adams is correct that “a teacher affects as one of the fellows in Henry's training program. There eternity; he can never tell where his influence stops,― then were quite a few of us, and we all worked diligently with Henry Wagner will certainly leave an indelible mark. Henry on various projects. Despite the pressure of work, For there is no practitioner of nuclear medicine who has an esprit de corps pervaded the Department, and we had such an accomplished and influential group of stu enjoyed the long days there. Henry is a demanding dents. Nor is there anyone who has brought the learning mentor, an excellent teacher, and possesses superior in of nuclear medicine to as many places or fostered colle tellect. His enthusiasm for nuclear medicine transfers giality in the field with such zeal. to all who come within his sphere. My association with It would be impossible to list the names and affiliations him was a time of challenge, fulfillment, and joy, and of his former residents and fellows,but I have asked some with the sustained momentum for achievement and ac of them to share with you their thoughts on Henry as complishment that was instilled under his guidance, the teacher and mentor. Their words reflect the intensity of years since have passed all too quickly.― And from Buck Rhodes: “I think Henry's many in their experience and the high value they place upon it. Buzz Nelp writes: “Henry's personality is effervescent, fluences on me are: 1. His four measures for evaluating and his ability to deal with people in
science: (a) Is it clear? (b) Is it true? (c) Is it new? and
an effective and yet kind way is most impressive. Al though I have heard Henry criticize an individual's work, I don't believe I have ever heard Henry say an unkind or derogatory sort of thing about an individual per Se, a characteristic which I admire.― From Dick Reba: “By perpetuating the principles of the scientific method in his students, Henry's concepts about science, medicine (and) clinical practice will survive. Many characteristics of a scientist are common to Henry: curiosity, common sense, application or a sense of purpose, the power to concentrate, and persever ance—which I would translate to self-discipline or a commitment to pursue excellence—and the ability to tolerate frustration as well as the ability to communicate. The fact that he is persuaded by evidence and not by intimidation, that he is determined but not intractable, I believe are all part of the secret of his successes. With regard to his trainees, I have always been impressed, as he appears to stimulate them to respond not by de manding discipline and obedience to his precise direction but rather by the logic and persuasion of personal lead
(d) Is it significant? 2. His ability to see what the simple next step is in any scientific or medical explanation. 3. His recognition that the absolute best is still imperfect. In summary, Henry is my revered teacher.― Bill Strauss writes: “Henry is charismatic. As such, I believe that his major contributions come from stim ulating others with incisive but creative criticism of their
his mind is brilliant
ership and close contact, thereby arousing in the trainees
936
ideas and from offering
sage counsel.
When Henry
would tell you an idea was no good, he wouldn't leave you with no idea. He would talk to you until a new concept emerged to replace the one that was shot down. He es tablished a training program in nuclear medicine that had both clinical training and investigative excellence as its hallmark. This model has been emulated by his former trainees in their programs, and therefore has served to set the standard for the level of nuclear mcdi cine practice throughout the world.―
From Frank Castronovo: “Henry gave everyone the impression (and correctly so) that he was thinking of their project. Henry kept the Hopkins faculty together
and we all gave a little extra because he did. His love of all people and his willingness to share his intellect make THE JOURNAL
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party is like a “who'swho in nuclear medicine.― Of
listened as intently to the lowliest medical student as he did to the most distinguished professors. Basically it was the idea that was of paramount importance to him, and he learned from everyone, incorporating first ideas into
course, some credit is due to the “who's― but much of the
his own thinking, shaping these inputs in a creative way
scientific, administrative
to obtain new insights in the field.― And, lastly, from Phil Alderson: “Henry's abilities as a teacher are not in the conveyance of specific facts, but in his approach to problems. Henry doesn't teach the
him truly unique in a profession often plagued by sd fishness and jealousy.― And from Mike Siegel: “The annual Hopkins alumni
training was inspired by Henry.
More than anything (he) was the father figure who was there to support and guide staff and fellows, with a sixth sense, unique to Henry, as to what goals to pursue.― Ken McKusick writes: “Thereare many traits of
student
what can really be found in books, but rath
Hopkins. One was his dedication to the teaching of the
er. . .how to think about problems. Henry's consistent skepticism about new techniques (especially those sug
fellows.
gested by others) forces him and all his colleagues into
Henry which came through during my several years at He surely
is a spokesman
(for the nuclear
medicine world), articulate, humorous, gracious, at ease
a persistently active academic posture. To his credit, he
in all environments and with an infectious curiosity.― From Phil Bardfeld: “As a teacher his style has been a dynamic optimism, tempered with a down-to-earth
seems willing to accept final and well-controlled facts, even when they don't agree with his own hypotheses.―
pragmatism. Henry Wagner's style as an investigator has been characterized by a vigorous integrity and an
training
of nuclear
America,
Henry
ability to get to the heart of the matter, and by a close
opment of nuclear medicine abroad by accepting a large
supervision of those who were performing
number of fellows and visitors into his Division. One can scarcely visit a country—in the first world or third without encountering a colleague who has spent some time in the Hopkins unit. And from some countries, such as Japan, they have come in flocks.
research for
him.― And from Malcolm Cooper: “Myperspective of Henry is of a man who committed himself almost totally . to
furthering
the
cause
of
nuclear
medicine.
He
has
fostered its role as a clinical scientific discipline, enabling it to stand
legitimately
alongside
other
medical
specialties.
Perhaps his greatest contribution
sub
is the in
fluence he has had upon the young people who came to train under him at Hopkins.
To some degree it was a
self-selective process, but once in, he set standards that influenced and moved people to a level of expertise with a faculty for critical enquiry that usually never left them.― Bill Klingensmith writes: “I think he has attracted (a) large number of trainees because of his dedication to research and the principles of research, and because of
his wit and sense of humor.― From Leon Malmud: “If I had to list Henry's out standing
contributions
to the field of nuclear
medicine,
In addition to the contributions he has made to the medicine
Wagner
specialists
substantially
in North
aided the devel
As his former students have testified, Henry has also been a world traveller, bringing the message of nuclear
medicine everywhere that he goes. His enthusiasm is infectious and his exposition of the relation of nuclear medicine to medicine in general so clear that it attracts those in and out of the specialty.
As a result, he has
served a number of organizations with distinction: President of the American Federation for Clinical Re search, President and Vice President of the Society of Nuclear
Medicine,
Founding
Member
and Vice Presi
dent of the American Board of Nuclear Medicine, President of the World Federation of Nuclear Medicine and Biology, President of the Johns Hopkins Medical Society, and President of the Baltimore City Medical Society.
I would focus on one, and that is his youthful, infectious enthusiasm re-evaluate
for what is new and his determination to that which is old by “stompingout myths.―
He transmits that feeling to his trainees, for whom he serves as an excellent
role model and teacher.―
And from Steve Larson: “He is one of a handful of individuals
whose personalities
have palpably affected
the discipline of nuclear medicine: through his students and fellows, his worldwide influence has been enormous. To me, for example, nuclear medicine has been given a much richer texture because of the principles which he
THINKER
I have tried in the previous sections to present a por trait of Henry Wagner as clinical scientist, teacher, and spokesman. In this final section, I shall try to probe those habits of mind that illuminate these aspects of his
character. I would guess that the general nuclear medicine community
thinks of Henry as the great advocate
of the
thesis that nuclear medicine provides functional infor
has taught me. Henry is a magnificent teacher, and I will
mation not otherwise
always
This emphasis on function, and especially regional function, has become Henry's hallmark. We have heard
feel indebted
to him for this. So much so that I
am reminded of him every day as I teach my own stu dents and residents. He listened intently to everyone, no matter what their status in the medical
Volume 25, Number 8
hierarchy.
He
readily available
about sick people.
him talk of “Nuclear Medicine in Motion― and of “functional images.― He has told us that “functions are
937
HEVESY NUCLEAR MEDICINE PIONEER LECTURE
fast processes of short duration,―while “structuresare slow processes of long duration―and that while other imaging disciplines provide the “nouns, nuclear medicine provides the verbs.― Henry himself believes that the corpus of his work is organized around the role of the autonomic nervous system in maintaining homeostasis; his scientific heroes are Claude Bernard and Walter Cannon. Certainly it is easy to see these influences in his early work on envi ronmental stress and on the role of autonomic vasoreg ulatory reflexes in the kidney. They are present in his studies on the distribution of blood flow in shock, on the effects of hypoxia on the regional pulmonary circula tions, on the control of blood flow in the extremities by
of Health, where he learned the rigors of clinical inves tigation. I conclude that it is pure Henry—probably congenital. I also think that many admire this talent for
the autonomic nerves, on the hemodynamic effects of static and dynamic stress, and in his most recent work
chyma by scintiscanning with Hg203 neohydrin. Radiology
on CNS receptors. He also believes that threading through his scientific career is an interest in infectious diseases, kindled by his reading of Paul de Kruifas a lad and nurtured by his experiences on the Hopkins ward services.
This interest also shows up in his work on en
dotoxins and the RE system, on radiometric detection, and on gallium scanning. My own view is that Henry is basically a troub lemaker.
Lest that declarative
statement
lead you to
believe I am unfit to deliver this commemorative
lecture,
I would remind you that constructive troublemakers are necessary to the full and critical development of science and to the building of a free society as well. Henry's proclivity for troublemaking expresses itself in various ways. Sometimes it is mischievous fun-poking, as in the last time we went out to dinner together and he threatened to tell the waitress that his name was Henry and that he was going to be her customer for the evening, etc., etc. Despite the potential hilarity of the situation, Anne Wagner's intervention kept him from pulling it off—which reminds me that Anne is a gracious and ef fective partner to Henry, at times keeping his spirited behavior within bounds. Today's award must be con sidered partly hers as well. I have been told that Henry was instrumental in the racial integration of the Osler Service at the Hopkins. If this is so, I would wager that some considered him a troublemaker in that affair as well. Others, I am certain, welcomed his courage in doing the right thing. Certainly, Henry is provocative—ask his many friends and col leagues, the corporators of the World Federation of Nuclear Medicine and Biology, and the founders of the American Board of Nuclear Medicine, for example. But he is provocative with a purpose, and the pots he stirs are generally good eating. I have wondered as to the source of this attribute in Henry—not Calvert Hall, where he must have been set high expectations and the concepts of service to family and community; not the Hopkins, with its devotion to higher learning in medicine; nor the National Institutes 938
troublemaking—a
few may be a little envious, since it
takes gumption and an imagination that many of us do not possess. Some of us are very fond of him because of it—others, despite it. S.JAMES ADELSTEIN Harvard Medical School
Boston, Massachusetts
REFERENCES
I. MCAFEE JG, WAGNER HN: Visualization of renal paren 75:820—821, 1960
2. REBARC,WAGNER HN, MCAFEEJG: Measurement of Hg203 chlormerodrin accumulation by the kidneys for de tection of unilateral renal disease. Radiology 79:134-135, I962 3. WINKELMAN JW, WAGNER HN, MCAFEE JG et al: Vi
sualization of the spleen in man by radioisotope scanning. Radiology 75:465-466, 1960 4. MCAFEE JG, FUEGER CF. STERN HS, et al: Tc-99m per
technetate for brain scanning. J Nucl Med 5:811—827, 1964 5. STERN HS, GOODWIN D, WAGNER HN JR, et al: In 113m—a short-lived isotope for lung scanning. Nucleonics
24:57—59, 1966
6. COOPER JF,LEVINJ, WAGNER HN: Quantitative corn parisonof in vitroand in vivomethodsfor the detectionof endotoxin. J Lab ClinMed 78:138-148, 1971
7. WAGNERHN, SABISTONDC, ho M, et aI: Regionalpul monary blood flow in man by radioisotope scanning. JAMA 187:601-603, 1964 8. LOPEZ-MAJANO V, WAGNER HN, TWINING RH, et al: Effect of regional hypoxia on the distribution of pulmonary blood flow in man. Circ Res 18:550—557,1966 9. WAGNER HN, LOPEZ-MAJANO
V, Tow
D, Ct al: Radio
isotope scanning of lungs in early diagnosis of bronchogenic
carcinoma. Lance! 1:344, 1965 10. KAIHARA S, VAN HEERDEN PD, MIGITA T, Ctal: Mea
surement of distribution of cardiac output. J Appl Physiol 25:696-700, 1968 11. SIEGEL ME, GIARGIANA FA, RHODES BA, et al: Effect of reactive hyperemia on the distribution of radioactive mi
crospheres in patients with peripheral vascular disease. Am J Roenigenol Rad Titer NuclMed 118:814-819, 1973 /2. STRAUSSHW, HURLEY PJ, RHODESBA, et al: Quantifi cation of right-to-left transpulmonary shunts in man. J Lab Clin Med 74:597-607, 1969
13. RHoDESBA, GREYSONND, HAMILTONCR, et al: Ab sence of anatomic arteriovenous shunts in Paget's disease of
bone.N EngIJ Med 287:686-689,1972 14. HURLEYPJ,COOPERM, REBARC, et al: 43KC1:A new radiopharmaceutical
for imaging
the heart. J Nucl
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12:516—519, 1971 15. PROKOP EK, STRAUSS HW, SHAW J, et al: Comparison
of regional myocardial perfusion determined by ionic potas sium-43 to that determined by microspheres. Circulation 50:978-984,
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16. EIKMANEA, CAMERONJL, COLMANM, et al: A testfor patency of the cystic duct in acute cholecystitis. Ann Intern Med 82:318—322, 1975 THE JOURNAL
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/7. HURLEYPJ,STRAUSSHW, WAGNERHN JR: Radionu clide angiocardiography in cyanotic congenital heart disease. JohnsHopkinsMedf 127:46-54, 1970
18. RIG0 P, ALDERSON P0, ROBERTSON RM, et al: Mea surement of aortic and mitral regurgitation by gated cardiac blood pool scans. Circulation 60:306-3 12, 1979 19. WAGNER HN, LOPEZ-MAJANO V, LANGAN JK, et al: Radioactive xenon in the differential diagnosis of pulmonary embolism. Radiology91:1168-1174,1968
20. WAGNERHN, BURNSHD, DANNALSRF,et al: Imaging dopamine receptors in the human brain by positron tomog raphy. Science221:1264-1266,1983
21. QUINLAN MF, WAGNER HN: Lung imaging with the pinhole Anger camera. J Nuci Med 9:497-498, 1968
analysis system (IDA) for radionuclide imaging. Radiology
93:823—827, 1969 24. DELAND FH, WAGNER HN: Automated radiometric de tection of bacterial growth in blood cultures. I Lab Clin Med
75:529—534, 1970 25. WAGNER HN, WAKE R, NICKOLOFFE, et al: The nuclear
stethoscope:a simpledeviceforgenerationof leftventricular volume curves. Am J Cardiol 38:747-750, 1976 26. GREISMAN SE, WAGNER HN, 110 M, et al: Mechanisms of endotoxin tolerance. II. Relationship between endotoxin tolerance and reticuloendothelial
inman.JExpMed
system phagocytic
activity
119:241-264, 1964
27. LOMAS F, WAGNER HN: Accumulation of ionic 67Gain empyema of the gallbladder. Radiology 105:689-692,
22. HOLMESRA, HERRONCS,WAGNERHN: A modified I972 vertex view in brain scanning. Radiology 88:498-503, 28. MCKUSICK KA, S0IN JS, GHILADI A, et al: Gallium 67 I967 23. NATARAJANTK, WAGNERHN: A newimagedisplayand
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accumulationin pulmonarysarcoiduis. JAMA 223:688-690, I973
939