Victor-Herbert,-MD,-1927-2002_ajcnut

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Am J Clin Nutr 2003;77:757–9. Printed in USA. © 2003 American Society for Clinical Nutrition
Victor Herbert died in New York City on 19 November 2002
at the age of 75 of a malignant melanocytoma. He was a for-
mer president of the American Society for Clinical Nutrition
(1980–1981) and a winner of the McCollum Award in 1972
and of the Herman Award in 1986. As an established Veterans
Administration investigator, he won that agency’s prestigious Mid-
dleton Award in 1978 for “out-
standing achievement in med-
ical research for his work on
developing scientific tools to
diagnose nutrient deficiencies.”
He received the Food and
Drug Administration Com-
missioner’s Special Citation
in 1984 for “outstanding and
consistent contributions against
the proliferation of nutrition
quackery to the American con-
sumer.” In 1993 Herbert was
elected a Fellow of the Ameri-
can Society for Nutritional Sci-
ences for his “outstanding life-
time research and teaching in
nutrition.” During his profes-
sional career, he was the epit-
ome of the physician-scientist
and probably the most inter-
esting and compelling person
many of us were privileged to
know. During the many years I
knew him, I, like many in the
folate and vitamin B-12 field,
never knew what was really
true about him and what was
fascinating “Victor lore.” To
find out, I researched his web-
site (www.victorherbert.com),
articles written about him, and
articles written by him, and I obtained invaluable insights from
many others who knew him.
Herbert was born in New York City on 22 February 1927 and
was named after the Irish-American composer, who was a distant
cousin. When Victor was 10 y old, his father was killed while
fighting in the volunteer Abraham Lincoln Brigade during the
Spanish Civil War; Victor’s mother, a Russian émigré and
lawyer, died 3 y later. After several years in an orphanage, Vic-
tor lied about his age and in July 1944 enlisted at age 17 in the
US Army “to get Hitler before he killed all the Jews” (1). He
served as a Private First Class paratrooper in the 82nd Airborne
Division during the last year of World War II. On discharge from
active duty in 1946, he enrolled in Columbia University, from
which he received a BS in chemistry in 1948 and a medical
degree in 1952.
After internship and residency at Walter Reed Army Medical
Center, Dr Herbert began his academic career as a physician-
scientist at the Albert Einstein and Mount Sinai hospitals in New
York City (1955–1959), where
he made his first forays into vit-
amin B-12 and folate research. It
was there that he discovered that
vitamin B-12 requires both cal-
cium and intrinsic factor to bind
to the ileal mucosa (2) and that
he developed the first microbio-
logical assay for serum folate
(3). In 1959 he was invited by
William Castle to become his
research associate and an assis-
tant physician at the Thorndike
Medical Laboratory on the Har-
vard medical service at Boston
City Hospital. Describing his
new environment as one of “sci-
entific and emotional intensity
and exhilaration” (4), Dr Herbert
made seminal discoveries about
the clinical effects of folate defi-
ciency and continued his studies
of vitamin B-12 physiology dur-
ing his 5 y at the Thorndike Lab
(1959–1964). In the early 1960s,
the medical ward provided the
most common “laboratory” for
the observant physician-scien-
tist, and great scientific discov-
eries in clinical nutrition were
made through well-planned and
well-executed studies of patient-
volunteers who exhibited classic features of poorly understood
diseases. True to the best tradition of the physician-scientist,
Dr Herbert, with a fellow, Ralph Zalusky, demonstrated the clin-
ical relation of folate deficiency to megaloblastic anemia by
studying a man who lived on coffee, doughnuts, and hamburgers
and responded to minute (50-mg) daily doses of folic acid (5). At
about the same time, Herbert and Zalusky made the first obser-
vations of what later came to be known as the “methyl trap” the-
ory of the integral relation of vitamin B-12 to folate metabolism
in the setting of isolated B-12 deficiency in patients with perni-
cious anemia. In careful and reproducible experiments, they
showed that serum folate concentrations were typically normal
In Memoriam
Victor Herbert, MD
1927–2002
757
758 IN MEMORIAM
or even high in these patients and that the concentrations fell
with vitamin B-12 injections, whereas the clearance of injected
folic acid, measured by the microbiological Lactobacillus casei
serum folate assay over time, was prolonged and often on a
plateau. Because L. casei measures methyltetrahydrofolate, Her-
bert proposed that this metabolically active folate is unavailable
for normal metabolism, including correction of DNA and ane-
mia, and that it “piles up” in the serum because vitamin B-12 is
required for its normal utilization (6). This classic clinical study
spawned the vast and still ongoing field of research on the
importance of the B-12–regulated transmethylation pathway for
folate, homocysteine, and methionine metabolism.
To prove the link between inadequate diet and folate-defi-
cient megaloblastic anemia, in October 1961 Herbert began his
most famous prospective experiment, with himself as the only
subject, in which he consumed for the next 5 mo a diet that con-
sisted mainly of thrice-boiled vegetables. As he described in his
classic publication (7) and related to a New York Times reporter
2 decades later (8), during these 22 wk, he had his fellow Louis
Sullivan perform 8 separate substernal bone marrow aspirations
as well as multiple venipunctures to carefully catalog the pro-
gression of folate deficiency to its endpoint of megaloblastic
anemia. Midway through the experiment, Herbert awoke on
Christmas Day 1961 unable to walk. Realizing that potassium
could be leached out of his diet by its bizarre preparation and
that muscle weakness could be caused by potassium deficiency,
he downed as much saturated potassium iodide cough syrup as
he could find at home until the diagnosis could be confirmed
and treated by a colleague (4). This experiment set the stage for
the vast literature on human folate metabolism and deficiency
that appeared over the next 40 y. While conclusively proving
that megaloblastic anemia can indeed be caused by improper
diet, Herbert’s study showed how to interpret diagnostic tests
during the sequential clinical stages of the development of
folate deficiency. Because the amount of folate in human liver
was generally known, Herbert’s self-experiment established a
reasonable estimate of the minimal daily folate requirement and
hence the daily loss in a healthy man (9), which has been vali-
dated several times since by others with the use of sophisticated
isotopic studies.
During this time, Herbert found that folate deficiency was
widespread among derelict alcoholics, who are notorious for
poor diet (10), a finding that set the stage for a whole body of lit-
erature by himself and others on the relation of alcohol con-
sumption and folate metabolism. An intriguing and yet unex-
plained finding resulted from an experiment in 3 alcoholic patients
with megaloblastic anemia in which Sullivan and Herbert (11)
showed that an initial positive response to minute doses of folic
acid could be completely and reproducibly suppressed by
whiskey or wine in their typically excessive amounts. In a brief
autobiographical sketch (4), Herbert described how one of the
patient-volunteers “leapt like a cat” on a National Institutes of
Health inspector who came to Boston to find out why this
research group was spending so much government money on
Hiram Walker Imperial Whiskey.
On his departure from the Thorndike Laboratory, Dr Herbert
became the associate director of hematology at Mount Sinai
Hospital in New York. After short forays to several other institu-
tions, in 1970 he settled into a 32-y career as chief of the Hema-
tology and Nutrition Research Laboratory at the Bronx Veterans
Administration Hospital and professor of medicine at MtSinai
School of Medicine. Over these 3 decades, he trained many
future academic scientists and continued to make vast contribu-
tions to our understanding of the basic biochemistry, clinical
diagnosis, and significance of vitamin B-12 and folate defi-
ciency. A nonexhaustive list of seminal findings emanating from
his laboratory includes refinements of assays for serum and red
cell folate (12, 13) and vitamin B-12 (14), the usefulness of the
deoxyuridine (dU)-suppression test to distinguish vitamin B-12
from folate deficiency (15), demonstration of the essentiality of
intrinsic factor for ileal absorption as well as gastric binding of
vitamin B-12 (16), the complex transfer of vitamin B-12 from
R binder to intrinsic factor (17), the clinical importance of vita-
min B-12 analogues (18), and the significance of low transcobal-
amin II as an early marker of vitamin B-12 deficiency (19).
Much of this work is summarized in his 1986 American Society
for Clinical Nutrition Herman Award lecture on the folate and
vitamin B-12 paradigm (20).
Yet, amazingly, his scientific work was paralleled by a sec-
ond career as a quackbusting physician-attorney. Well before
alternative medicine crept into the lexicon of medical practice,
Dr Herbert obtained a law degree from Columbia University in
1974, and with that and his expertise as a nutrition scientist, he
challenged the “health food” and “phony drug” industries.
From then on, his curriculum vitae is fertilized with a seem-
ingly endless barrage of scientific papers, letters to the editor,
and columns in the lay press on the dangers of phony drugs and
vitamins such as laetrile (21, 22) and pangamic acid or “vita-
min B-15” (23), on the wastefulness and dangers of megavita-
mins (24), and on the burgeoning herbal and health food indus-
try (25). He was chair of the Committee on Life Sciences of the
American Bar Association for 5 y, a board member of the
National Council Against Health Fraud (www.ncahf.org), a fre-
quent witness to Congress on health and nutrition, and the
author of numerous books that debunked the health-supplement
industry (26, 27). At the same time, he also provided sensible
and accurate nutritional advice to laypeople (28).
Although accomplished in all things scientific and legal, Vic-
tor was most proud of his career as a young paratrooper in World
War II and later as a medical officer during the Korean
(1953–1954), Vietnam (1964–1966), and Gulf (1991) wars. Even
while he was establishing his academic career at Mt Sinai, he
reenlisted at age 37 in the US Army, this time in the Special
Forces (Green Berets), and served 122 d on active duty during
the Vietnam War. After his discharge from the Army as a Lieu-
tenant Colonel in 1987, a compulsion to reenlist yet again, at age
64, for a brief stint during the Gulf War in 1991 was facilitated
by the intervention of his former Fellow and then Secretary of
Health and Human Services, Louis Sullivan (1).
All who knew Victor or saw him in action share indelible
memories. Who can forget his impromptu star performances at
each and every Experimental Biology meeting? He was always
the first to the microphone with the most incisive and provocative
questions that nearly always brought a level of excitement and set
a higher tone for the discussions that followed. Just as he had
described encounters with his first mentor, William Castle, if you
were the target of Victor’s questions, “You realized the enormous
range and depth of his knowledge and his ability to communicate
it in such a way that he made you not only think but remember”
(4). Who can forget his favorite slide in his phony-diploma-mill
talk—his cat Charlie’s PhD? Or his brilliance, as when he sum-
marized in handwritten but, unfortunately, unpublished poetry an
entire workshop on folic acid (29), with intimate details of every
speaker’s contribution? To those who knew him well, he was
much more than a complete repository of knowledge of vitamins
and of health fraud. He was a true and generous friend, support-
ive of the careers of those who came after him and always avail-
able with informal legal advice or specific scientific suggestions.
He knew the best deals on hotels and restaurants in every city
you were likely to visit, and his storehouse of jokes and stories—
mostly unprintable—was legendary. While almost always con-
troversial, he will be remembered fondly by his friends and as a
scientific inspiration to all who followed in his footsteps into
clinical nutrition research.
I am indebted to Mrs Marilynne Herbert, who provided me with a true
copy of Victor Herbert’s military record and confirmation of several details of
his life, and to many friends and colleagues who shared their memories with
me during the preparation of this article. There were no financial or other con-
flicts of interest associated with this work.
Charles H Halsted
American Journal of Clinical Nutrition
3247 Meyer Hall
University of California, Davis
One Shields Avenue
Davis, CA 95616
E-mail: ajcn@ucdavis.edu
REFERENCES
1. Graves N. From WWII to Iraq, he never missed a war. New York Post,
November 12, 2001. Internet: www.victorherbert.com/NYPost.htm
(accessed 22 January 2003).
2. Herbert V. Mechanism of intrinsic factor action in everted sacs of rat
small intestine. J Clin Invest 1959;38:102–9.
3. Herbert V, Baker H, Frank O, Pasher I, Sobotka H, Wasserman LR.
The measurement of folic acid activity in serum: a diagnostic aid in
the differentiation of the megaloblastic anemias. Blood 1960;15:
228–35.
4. Herbert V. Victor Herbert: 1959–1964. In: Castle WB, Finland M, eds.
The Harvard Medical Unit at Boston City Hospital. Part 2: The Castle-
Finland era, 1951–1974. Boston: University Press of Virginia, 1983:
1016–22.
5. Zalusky R, Herbert V. Megaloblastic anemia in scurvy with response to
50 micrograms of folic acid daily. N Engl J Med 1961;265:1033–8.
6. Herbert V, Zalusky R. Interrelations of vitamin B12 and folic acid
metabolism: folic acid clearance studies. J Clin Invest 1962;41:
1263–76.
7. Herbert V. Experimental nutritional folate deficiency in man. Trans
Assoc Am Physicians 1962;75:307–20.
8. Altman L. The doctor as guinea pig. New York Times Magazine 1986;
April 6:32.
9. Herbert V. Predicting nutrient deficiency by formula. N Engl J Med
1971;284:976–7.
10. Herbert V, Davidson C. Correlation of folate deficiency with alcoholism
and associated macrocytosis, anemia, and liver disease. Ann Intern Med
1963;58:977–88.
11. Sullivan LW, Herbert V. Suppression of hematopoiesis by ethanol. J Clin
Invest 1964;43:2048–62.
12. Waxman S, Schreiber C, Herbert V. Radioisotopic assay for measure-
ment of serum folate levels. Blood 1971;38:219–28.
13. Scott JM, Ghanta V, Herbert V. Trouble-free microbiologic serum and red
cell folate assays. Am J Med Technol 1974;40:125–34.
14. Herbert V, Colman N, Palat D, et al. Is there a “gold standard” for
human serum vitamin B12 assay? J Lab Clin Med 1984;104:829–41.
15. Das KC, Herbert V. The lymphocyte as a marker of past nutritional sta-
tus: persistence of abnormal lymphocyte deoxyuridine (dU) suppres-
sion test and chromosomes in patients with past deficiency of folate and
vitamin B12. Br J Haematol 1978;38:219–33.
16. Carmel R, Rosenberg AH, Lau KS, Streiff RR, Herbert V. Vitamin B12
uptake by human small bowel homogenate and its enhancement by
intrinsic factor. Gastroenterology 1969;56:548–55.
17. Kanazawa S, Herbert V. Mechanism of enterohepatic circulation of vit-
amin B12: movement of vitamin B12 from bile R-binder to intrinsic
factor due to the action of pancreatic trypsin. Trans Assoc Am Physi-
cians 1983;96:336–44.
18. Shaw S, Jayatilleke E, Meyers S, Colman N, Herzlich B, Herbert V.
The ileum is the major site of absorption of vitamin B12 analogues. Am
J Gastroenterol 1989;84:22–6.
19. Herzlich B, Herbert V. Depletion of serum holotranscobalamin II. An early
sign of negative vitamin B12 balance. Lab Invest 1988;58:332–7.
20. Herbert V. The 1986 Herman Award Lecture. Nutrition science as a con-
tinuallyunfolding story: the folate and vitamin B-12 paradigm. Am J
Clin Nutr 1987;46:387–402.
21. Herbert V. Unproven (questionable) dietary and nutritional methods in
cancer prevention and treatment. Cancer 1986;58:1930–41.
22. Herbert V. Laetrile: the cult of cyanide. Promoting poison for profit. Am
J Clin Nutr 1979;32:1121–58.
23. Herbert V. Pangamic acid (“vitamin B15”). Am J Clin Nutr 1979;32:
1534–40.
24. Herbert V. The vitamin craze. Arch Intern Med 1980;15:173–6.
25. Herbert V. Will questionable nutrition overwhelm nutrition science? Am
J Clin Nutr 1981;34:2848–53.
26. Herbert V. Nutrition cultism: facts and fictions. Philadelphia: George F
Stickley Company, 1980.
27. Barrett S, Herbert V. The vitamin pushers. How the “health food” indus-
try is selling America a bill of goods. Amherst, NY: Prometheus Books,
1994.
28. Herbert V, Subak-Sharpe G, Hammock DA. Total nutrition: the only
guide you’ll ever need: from the Mount Sinai School of Medicine. New
York: St Martin’s Press, 1995.
29. Herbert V. Summary of the workshop. In: Food and Nutrition Board,
National Research Council, ed. Folic acid: biochemistry and physiol-
ogy in response to the human nutrition requirement. Washington, DC:
National Academy of Sciences, 1977:277–93.
IN MEMORIAM 759