THE HISTORY

OF

   THE
HOAGLAND
LABORATORY

BY

ARNOLD H. EGGERTH, Ph.D.
                       --.
                       s_

WITH AN INTRODUCTION BY

JEAN A. CURRAN, M.D.

  AND AN EPILOGUE BY

FRANK L. BABBOTT, M.D.

BROOKLYN, N. Y.
    1960


1123 I

When Frederick Tilney left Brooklyn in 1915, he served
for a short time at the New York Post-Graduate Hospital as
assistant to Dr. Smith Ely Jelliffe. In that same year he was
offered the professorship of nervous anatomy and neurology
at the Long Island College Hospital but declined as he had
just been appointed professor of nervous diseases at the Col-
lege of Physicians and Surgeons of Columbia University. The
trustees of the Long Island College of Medicine made him a
member of their board in 1931 as the first alumni trustee.

  In 1935 he became the first director of the New York
Neurological Institute. He died in 1938.

CHAPTER XIV

The Department of Bacteriology

T he death of Ezra Wilson in 1905 left the department of
bacteriology in the hands of Benjamin White. He knew his
own competence as a biochemist but he realized that his train-
ing in bacteriology was not sufficient for him to assume the
responsibility of directing the department and doing bacteri-
ological research. There was no thought of looking elsewhere
for an experienced director, for both Charles and Elizabeth
Gates knew that White was the man they wanted for the
position.

So it was decided that White should have a year of spe-
cialized training abroad. The death of Charles Gates did not
change this plan since White had already reached an under-
standing with his sponsors and Elizabeth Gates agreed to carry
it out. White was to receive a leave of absence from June 1,
1906, to October 1, 1907. During his absence he was to receive
a salary of $1500 a year to be increased to $2000 a year upon
his return. He would then also be given an assistant director
and a laboratory helper.

The board of trustees was very cautious about making
financial commitments. Early in 1906 the laboratory received


              m41

$5000 from the estate of Eliza E. Hoagland, (widow of the
founder) who had died in October of 1905. It had received
donations of $1000 each from Luella Hoagland, Cora Tange-
man and Charles Gates. But the experience of recent years had  .I
shown all too clearly that ever increasing deficits were in pros-  1
pect unless the research program was sharply reduced or unless     i
the Hoagland family made some substantial arrangement. Ap-     ,:
parently the trustees never tried to apply pressure on the
faculty or board of regents of the Long Island College Hospital
to make some contribution to the maintenance and repairs of      _
the laboratory.
  In the minutes of the Hoagland board, dated May 25,
1906, it was stated "that a committee of trustees Matheson and
Hill was appointed to confer with the family of the late Dr.
Hoagland and obtain their wishes as to the filling of the
vacancy in the board of trustees caused by the death of Presi-
dent Gates, and as to the future officials of the laboratory; also
to consult with them as to the supply of funds to carry out       !
the portions of the plan contained in the communication of    1
Dr. White (concerning his future salary and that of the as-
sistant director.) "
  At the ,June 5 meeting of the trustees, Mr. Matheson re-
ported that he had conferred with Mrs. Gates. She had in-
dicated that the election of Mr. William H. Nichols to the       `.

board would be satisfactory, and that she and her two sisters
would each agree to contribute $1000 a year to the laboratory.     i
She also confirmed the agreement with Dr. White as outlined   i
in his letter to the trustees. The Hoagland board thereupon
elected Mr. Nichols to the vacant seat and approved the ap-
pointment of Dr. White for the year beginning October 1,
1907.
  White left for Europe in June and the department of
bacteriology was closed down completely until his return. Dur-       '

ing his stay abroad, White studied bacteriology, protozoology
and serology at the Imperial Institute for Infectious Diseases


[ 125 1

at Berlin; from there he went to St. Anna's Kinderspital in
Vienna where he studied epidemic meningitis under Dr. Jehle.
Thence he went to the Royal Hygienic Institute at Munich to
investigate the serology of anthrax immunity under Professor
Gruber. Finally he took a course on opsonins and vaccine ther-
apy under Sir Almroth Wright at St. Mary's Hospital, London.
Upon White's return, one of his first acts was to nominate
Dr. Oswald T. Avery for the position of associate director in
the department at a salary of $1200, which was increased to
$1500 in 1909.

The story of Oswald Avery's coming to the Hoagland
Laboratory is best told in his own words:

"I was graduated from the College of Physicians and Sur-
geons in 1904. The practice of medicine did not appeal to me,
for I preferred to work in the laboratory. It happened that at
that time Sir Almroth Wright came to New York from Eng-
land and gave a lecture at the Academy of Medicine on his
newly invented opsonic technic. The New York City Health
Department was interested in this and arranged to have a
colleague of Sir Almroth give a short course of instruction to
a small group.

"I was one of those to take this course. At its completion,
Dr. William Park gave me a job doing opsonic indices for the
Board of Health at a stipend of $50 per month for part-time
work. I also found part-time employment doing milk bacteri-
ology for `the Sheffield Company. Pasteurization of milk was
just coming in; I made bacterial counts of milk before and
after pasteurization at a stipend that was also $50 per month.

"Benjamin White and I met in this way. While I was a
student at the College of Physicians and Surgeons, I roomed
with a young law student, William M. Parke, who after ad-
mission to the bar practiced for a time in Brooklyn. This
young lawyer lived in a rooming house on Remsen Street. It
so happened that Benjamin White lived in the same house,
and thus we became acquainted. White mentioned to me that


[ 1261

he needed a young doctor to be his assistant director. I re-
sponded enthusiastically and so I was invited over to the Hoag-
land Laboratory."

William M. Parke, mentioned by Avery, had been Avery's
classmate at Colgate Academy and his roommate at Colgate
University. While studying law at the New York Law School,
Parke had roomed at the house of Avery and his mother. Mr.
Parke became a trustee of the Hoagland Laboratory in 1940.

The department of bacteriology initiated a most compre-
hensive and productive program in the fall of 1907. As White
outlined it in his annual report to the trustees in May, 1909,
the department had "a general plan embracing three specific
purposes, i.e., first, to investigate bat teriological problems of
a purely scientific nature; second, to prosecute researches upon
bacteriological questions related to medical diagnosis and ther-
apeutics; and third, to aid the practitioners in the diagnosis of
obscure diseases of bacterial origin, and to prepare and fur-
nish to physicians such therapeutic agents as the laboratory
facilities permitted."

White had some very definite ideas concerning the re-
spective function of the scientific staff and the board of trus-
tees. The staff was responsible for the investigative work and
it was the responsibility of the trustees to find the means. In
other words, when money was needed for worthwhile projects,
the trustees were obligated to find it.

This attitude did not make Benjamin White popular
with the Hoagland board. Mr. William Hill, who was a trus-
tee at that time, has described him as a "kicker." On some
occasions when financial troubles were acute, the secretary of
the board rather wistfully pointed out that if White's salary
were eliminated there would be no difficulty in balancing the
budget. But White had powerful backing by the daughters of
Cornelius Hoagland, who saw in him the man who was going
to use the laboratory in the way their father had intended it
to be used.


[ 127 1

The initial plan of White and Avery was to resume the
investigation of the toxins of the typhoid bacillus that was
begun by Wilson in 1904 and on which White had done some
work in 1905. They soon decided that this was too ambitious
an undertaking and it was abandoned. As an offshoot of this
work, White published a brief account in 1908 of a small ball-
mill of his own invention that he had used for grinding the
typhoid bacilli for the preparation of toxins. Another abortive
effort was a study of the "Pfeiffer phenomenon" which did not
yield anything worthy of publication. Two other researches
were more productive.

The first was a study of the milk-souring bacteria of the
"Bulgaricus" group. Fermented milks (such as yoghurt, leban
and others) have long been a staple article of food in the
Balkan countries and in the Middle East. They had been
recently publicized by the work of Elie Metchnikoff, who be-
lieved that their consumption had a favorable effect upon
the intestinal flora because they replaced the harmful putri-
factive bacteria with the benign lactic acid producing species.

  This theory became medically very popular. The lactic
acid bacteria were called "the bacilli of long life," and fer-
mented milks were widely used in treating that vague con-
dition `called "intestinal auto-intoxication," It so happened
that the Hoagland Laboratory was then, as it is now, in a
Syrian neighborhood, and the Syrian grocers prepared and
sold "leban," the fermented milk of their native country.
White and Avery came to know some of these Syrian

grocers and they became acquainted with leban and learned
to enjoy it. Their taste for the leban encouraged them to
study it bacteriologically and this in turn led to an extensive
study of related organisms. Many years later, Avery recalled
that he had a "wonderful time" investigating these bacteria
that they obtained from all over the world, mostly in com-
mercial preparations of various fermented milks.

When this work was completed in 1909 it was published


               II 128 1

as "Observations on Certain Lactic Acid Bacteria of the Bul-
garicus Type." The authors concluded that there were two
distinct types of lactic acid bacilli which they designated as
types A and B. The type A stained homogeneously and pro-
duced up to 3.7y0 of optically inactive lactic acid; whereas in
type B, intensely staining granules were present and no more
than 1.6% of laevo-rotary lactic acid was formed. In the course
of this investigation, White and Avery accumulated a great
amount of unpublished data on various commercial fermented
milks and milk-souring "starters." These data were sent to
Dr. Wiley, Chief of the United States Bureau of Chemistry,
for use in the federal control of foods.
  In the same year, a research on "The Treponema Pal-
lidum, Observations on its Occurance and Demonstration in
Syphilitic Lesions," was completed and published. Schaudinn
had discovered four years before the spiral organism that
causes syphilis. Methods for the detection and recognition of
the "pale spirochete" were not widely known. Ordinary dyes
failed to stain this organism and inspection by transmitted
light did not reveal it.
  White and Avery investigated several methods then in
use abroad. They concluded that "dark field" examination of
fresh exudates was most reliable but the apparatus needed
was not (at that time) readily available. The principle of the
"dark field" is that when minute objects are illuminated from
the side by a strong beam of light, these objects appear very
bright on a dark background and so are readily visible. They
also tested various staining methods and found one devised
by Schereschewsky to be most satisfactory.
  During this time Avery also did some experimental work
with the so-called "Meiostagmin reaction" which was claimed
by Ascoli to be of value in the diagnosis of cancer. This was
a combined surface tension and viscosity determination, done
on the serum of the patient. The claims of Ascoli were not
substantiated by this study so the work was dropped.


[ 1291

Dr. A. T. Bristow, a surgeon of the Long Island College
Hospital, had a patient who was eventually diagnosed as
having chronic glanders. Benjamin White recovered and iden-
tified the bacillus of glanders from the metastatic abscesses.
As the patient remained chronically ill, an autogenous vac-
cine was prepared and administered. The patient recovered
and it was inferred that his recovery was hastened by the vac-
cine treatment. The report of this case was published in 1910.

Associated with Dr. Louis C. Ager, by now a prominent
pediatrician, Oswald Avery wrote a report on "A Case of
Influenza1 Meningitis." The importance and common oc-
currance of the Pfeiffer bacillus (Hemophilus influenzae) as
a cause of meningitis in children was not realized at that
time because the best methods of `cultivating this germ were
not yet known and only two or three cases of this kind had
ever been reported.

White and Avery published in 1910 an important study
entitled "Concerning the Bacteriemic Theory of Tuberculo-
sis." This work was inspired by the claims of Dr. Randle C.
Rosenberger who had said that tubercle bacilli could be dem-
onstrated in stained smears of the blood of tuberculosis
patients in all stages of the disease. This, if verified, would
be a most important finding. White and Avery examined the
bloods of fifty-one tuberculosis patients by various technics
and were unable to find tubercle bacilli in any of them. They
concluded that the acid-fast bacilli seen by Rosenberger were
not tubercle bacilli but accidental contaminants probably
coming from the distilled water.

Both White and Avery were greatly interested in the
therapeutic and prophylactic use of vaccines, and especially in
autogenous vaccines. Among others, they prepared gonococcal
vaccines for Dr. J. Sturdivant Read to use clinically. It was
concluded that they had no beneficial effect on acute early
cases of gonorrhea, but apparently had some value in chronic
infections. They also prepared typhoid vaccines and ad-


               [ 1301

ministered them to hospital personnel at the time Major
Kussell of the United States Army began using them.
  Because of his extensive knowledge of the subject, Avery
was asked to write the chapter on "Opsonins and Vaccine
Therapy" (with Dr. N. B. Potter) for Hare's "Modern Treat-
men t," a widely used text on chnical medicine of the time.
  Another field of interest was the bacteriology of post-
surgical infections, and White and Avery hoped eventually
to write a monograph on that subject. Partly to obtain material
for this projected work, clinicians from the various hospitals
of Brooklyn, and especially from the Long Island College
Hospital, were encouraged to bring their bacteriological prob-
lems to these men, and many did. Both men were very ap-
proachable and Avery was especially so. He loved to teach
and was always ready to give individual lectures to any who
came to him for information. It was a twist of fate that Avery,
the superlative teacher, never held an academic position and
never regularly taught a class of medical students.

             PART 2
      The Department of Bacteriology
B enjamin White suffered a severe hemorrhage from the
lungs in July of 1909. Avery found the characteristic "acid-
fast" bacilli in his sputum, which made certain the diagnosis
of tuberculosis. In August, White was sent to the Trudeau
Sanitarium at Saranac Lake on a stretcher. It was at first
thought that he had tuberculous pneumonia and the prognosis
appeared very grave.
  Fortunately it turned out to be less serious than at first
feared. By the end of September, White reported to the Hoag-
land trustees that he was already convalescent and feeling
better than he had felt for years. Dr. Edward R. Baldwin had
assured him that his troubles were over though he would still
need rest and care. So White asked for a leave of absence


[ 1311

until October 1910; in the following year he asked to have
that leave extended to October of 19 11.

Though White was at Saranac Lake because he was ill
with tuberculosis, nevertheless he was soon able to do a con-
siderable amount of research. Most of the workers in the
sanitarium and in the laboratory had come there because
they themselves had had tuberculosis; this was true of Dr.
Trudeau himself as well as of Baldwin, Gardner and others.
They learned to live with their disease and wouId work for
two or three hours a day, adjusting everything to that pace.

During 1910 and 1911, White actually accomplished a
great deal of research. He studied the chemistry of the tubercle
bacillus and especially its fatty constituents, and the action
of normal and tuberculous body fluids upon these lipids.
Some of the early part of 1911 was spent in Brooklyn but in
the summer months he returned to Saranac Lake where Avery
accompanied him to participate in the work.

Benjamin White, however, did not devote all of his time
to "curing" and to experimental work, for it was during this
period that he met the young lady who was later to become
his wife. This was Laura Genoa Solari, who lived at Saranac
Lake at that time because she had a sister there who was suf-
fering from tuberculosis.

While convalescing, White still directed the department
of bacteriology in Brooklyn. This he did, partly by letter,
partly by occasional visits.

In October, 1909, White secured the appointment of Dr.
Charles 2. Garside, late chief of the department of bacteri-
ology at the Lederle Laboratories, to be Avery's assistant.
Dr. Garside was actually on a part-time basis for he was also
on the staff of the medical department of Fordh$n University
where he was adjunct professor of bacteriology. On coming
to the Hoagland Laboratory, he began an investigation
of the biology of the diphtheria group of organisms. This
work was reported before the County Medical Society but


never published. He also participated in the preparation and
evaluation of bacterial vaccines, a research that was sum-
marized in an article published in 191 I. Dr. Garside resigned
in I912 to devote full time to his duties at Fordham. He died
soon after while still a young man.

At a meeting of the hospital staff held on May 11, 1910,
it was moved by Dr. Van Cott and carried that "the board of
trustees of the Hoagland Laboratory be asked to furnish a
special assistant from the department of bacteriology of the
Hoagland Laboratory to be at the service of the staff of the
Long Island College Hospital for bacteriological work in
the hospital and the making of vaccines, and that he be at
the call of the attending staff and receive the title of `Bacteri-
ologist to the Hospital' . . . . the salary of said bacteriologist
and expenses of the work to be borne by the Hoagland Labo-
ra tory."

There had already been several unofficial conferences
between White and the hospital staff, and White was strongly
in favor of such an appointment. It is very possible that he
himself originated the idea, for it was a part of the general
program for his department as outlined in his 1909 report
to the trustees. He had especially in mind two different lines
of research, both of which required abundant clinical ma-
terial: the preparation and improvement of autogenous vac-
cines, and the investigation of post-surgical infections.
White was asked to find a suitable man. He appointed
Harold W. Lyall with the title of clinical assistant in bacteri-
ology at a salary of $1200 a year. The appointment became
effective October 1, 1910. Mr. Lyall was a graduate of Brown
University with the degrees of A. B. and M. A. He had some
experience as bacteriologist doing part-time work for the
Rhode Island State Board of Health.

Lyall very soon established an efficient bacteriological
service for the Long Island College Hospital. He was warmly
praised by Dr. White for this and for his ability to maintain


11331

cordial relations with the hospital staff. The preparation and
evaluation of autogenous vaccines was under Avery's super-
vision. Referring to these vaccines in his 1912 report to the
trustees, White commented that "most gratifying results in
many cases were being obtained."

Parts of Lyall's work were reported in two different pub-
lications in 1912. One was on the blood culture findings in
45 cases of pneumonia and the other was on a rare case of
meningitis caused by the typhoid bacillus.

The department was further enlarged in 1911 by the
addition of a stenographer and librarian, Miss Barbara M.
Bradford. Among her duties was that of establishing a filing
system for the cataloging of scientific articles.

  The first portion of their work on the chemistry of the
tubercle bacillus was completed by White and Avery during
1911. This was published in 1912 under the title of "The
Action of Certain Products Obtained from the Tubercle Ba-
cillus. A. Cleavage Products of Tuberculo-Protein Obtained
by the Method of Vaughn. The Poisonous Substance." The
experimental work for this paper was done in part at the
Saranac Laboratory for the Study of Tuberculosis and in
part at the Hoagland Laboratory.

  In pursuing and interpreting this work, White and
Avery were rather carried away by a theory originated by
Victor Vaughn. This theory held that the toxic effect of certain
bacteria was due to a poisonous fraction that was split off
from the bacterial protein. Experimentally this was conven-
iently done by the action of hot alkaline alcohol, True, similar
toxic fraction could be split off from other proteins such as
egg albumen or serum protein. But in an infection it was the
bacterial protein that was at the spot. The Vaughn theory
was in vogue at that time. In the same year, 1912, White pre-
sented a paper before the annual meeting of the National
Association for the Study and Prevention of Tuberculosis, in
which he elaborated on some theoretical implications.


               [ 1341

During the early part of 1911 the outlook for the de-
partment seemed bright indeed. White had recovered his
health and was working enthusiastically as was Avery. Garside
and Lyall were eager and doing excellent work. The depart-
ment rated very high in scientific circles for its research had
been of first quality. Even more interesting and important
problems were contemplated. Yet in July of 1911 the staff be-
came uneasy and disheartened. The reason was entirely one
of Hoagland Laboratory finances.

             PART 3
     The Department of Bacteriology
E ver since 1903 the expenses of running the Hoagland
Laboratory had been greater than the income from endow-
ments and the fees paid by the college. The Hoagland family
had made annual donations averaging $3662 over the eight
year period from 1903 to April 30, 1911. Up to that point,
these donations had been sufficient to wipe out the deficits.
In the year 1910-1911, there was an unusually large ex-
penditure for repairs and improvement of the building
($3762.02 had been required for this purpose) . At the same
time, the only contribution received was $3000 from Ella
Hoagland. Dr. Raymond's report to the board, made on
May 26, stated that the income for the preceding year had
been $9630.12, including Ella Hoagland's contribution, but
total expenditures were $13,926.82, leaving a deficit of $4296.70.
Dr. Raymond estimated that the total deficit for 1911-1912
would be $6354.40. Further repairs to the building were still
needed and two new workers had been added to the payroll-
Lyall and Miss Bradford. Obviously the endowment could
not be invaded every year for such'sums as this.
  The crisis in 1911 was due to the fact that up until May
26 nothing had been heard from the Hoagland sisters. On this
date, the board of trustees directed the secretary to describe the


[I351

plight of the laboratory to Mrs. Gates, Mrs. Tangeman and
Miss Hoagland and "to ask from each, for the guidance of
the board, an expression as to their opinion and wishes as to
the future work of the laboratory," and to inform them that
no appropriations would be made until the board learned
the view of the ladies.

No word had been received by June 8 from the "benefac-
tors," as they were called by the board. But on June 17, Mrs.
Gates sent a check for $1000, so the trustees appropriated
money for salaries of the whole staff but only to October.

The members of the department of bacteriology were
quite shaken by this turn of events. What steps were taken
by Benjamin White, if any, are not known. But Oswald Avery
spent his vacation at the biological laboratories of the H. K.
Mulford Company, instructing its staff in bacteriological
technic and at the same time learning their methods of pre-
paring antitoxins, tuberculin and vaccines. Garside arranged
to return to the medical department of Fordham University
on a full-time basis. Lyall alone appeared to be secure in his
position since he would probably be retained to do the bacteri-
ological work for the hospital.

In order to understand the financial situation thoroughly,
it is necessary to appreciate the fact that there was a funda-
mental difference in the point of view of the board of trustees
and that of the Hoagland daughters.

The board believed that the laboratory should help the
Long Island College Hospital and cooperate with it as much
as possible. This view was reflected by Mr. Matheson, presi-
dent of the board, in a letter to Mrs. Gates dated June 20, 1911.
Mr. Matheson here stated that the "trustees have always
encouraged Dr. White in any definite practical proposition
he had to make that was within our means. While I am the
last in any way to complain or delay the highest ideals, I do
not sympathize with the idea that we can best serve the needs
of the community by concluding that the cause of the medical


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-I__--                           9 9


                                             t t

                       I1361

school is hopeless. I cannot escape the conviction that it is our
duty to elevate it and that we can do this best by cooperation,
and I have amply proved that both the college and hospital
and the Polhemus Clinic are agreed for cooperation."

Ella Hoagland and Mrs. Gates were far less friendly to
the college and the hospital. Miss Hoagland, who had given
$3000 the year before, made no reply to the secretary's urgent
letter. Mr. Matheson then cabled her, since she was abroad
at that time, "Must decide on laboratory's future. Can you
assist?" Miss Hoagland cabled Mrs. Gates. "Matheson's ad-
dress lost. Tell him will assist laboratory if it is kept from
hospital."

  At the time Mr. Matheson wrote his letter, the recom-
mendations of the Flexner Report had not been adopted and
the system of paying "dividends" to the faculty of the college
was still in effect. The Hoagland daughters may have been
aware of this practice, and of the contents of the Flexner Re-
port, and this may have affected their thinking on the subject
of further financial support.

Mrs. Elizabeth Gates was even more outspoken. In a
letter written to Mr. Matheson on June 17, 1911, she said,
"I do not think it necessary for me to tell you that I have
not been in sympathy with things as they have gone at the
laboratory these last five years. But Dr. White has been good
enough to tell me all the good things which seem to be ahead
of them in their work there, and of the broadening they hope
to reach under the new work planned for next year. As things
have been there, I have felt that I could not agree to any
further support, consequently I withheld my check last
autumn.

"I think Dr. White is entirely right in what he has been
trying to do in the way of `housecleaning.' From what he tells
me there has. been a change of view among some of the people
there, in whom I have no confidence. I want to be sure that
they will stick to their word. I am quite sure that both my


[I371

father and Mr. Gates would have approved of Dr. White's
course, and it will be a great pleasure to me if things could
be arranged according to his plan. Anything but have the
laboratory used as a classroom for a second-rate medical in-
stitution.

"I am quite ready to adopt the report as Dr. White sent
it to me. Rather than curtail any of the actual work of the
laboratory, I am enclosing my check for $1000 which I did not
send last September."

  Mrs. Gates' reference to `housecleaning' may be taken lit-
erally, because in his annual report of May, 1911, White com-
mented on the poor janitor service and the general dilapida-
tion and lack of cleanliness of the building, and suggested
that the college, which used three of the four floors of the
laboratory, might render some assistance.

  Mrs. Gates' bitter words were no more caustic than those
of Abraham Flexner when he made his devastating report
in 1911. Her feeling was well expressed in a letter she wrote
to Mr. Hill some years later (1922): "1 always felt that if the
laboratory were being used for the purpose my father intended,
there would not be such a drain on its funds for repairs, etc.,
and I surely would have been willing to help more. However,
since the trustees decided to make it a part of the Long Island
College, they must find funds for such expenditures."

  Nevertheless, in October of 1911, Mrs. Gates sent Mr.
Matheson another check for $2000. In her accompanying let-
ter she said, "It seems to me the trustees should make some
plan to help carry on the work there . . . I do not feel that it
is up to my sisters and myself to make good such a large def-
icit every year. The endowment fund should be raised . . . .
I am ready to contribute $10,000 to such a fund."

At a special meeting of the trustees held September 15,
1911, Drs. Avery and Garside and Mr. Lyall were reappointed
for the ensuing year and appropriations made for their sal-
aries, with a modest increase for Dr. `Avery. These men had


I138 1

spent all summer not knowing if they would have places after
October 1. Dr. White was reappointed provided funds would
become available. Dr. Raymond, in a statement to the board,
made the delicate suggestion that "if Dr. White is not re-
engaged, there will be a surplus of $1446.10." When Ella
Hoagland sent her check for $3000 later in the year, Dr. White
was reappointed unconditionally.

Dr. Raymond's estimate had been that $6354 would be
needed in 191 l-1912 over and above the probable income of
$6732.50. Ella Hoagland and Mrs. Gates had just contributed
$6000, so it was felt that the research program could proceed.

PART 4

      The Department of Bacteriology
I t was completely characteristic of Benjamin White that
he promptly asked for an increased appropriation for salaries,
apparatus, supplies and current expenses. He also asked for an
increased staff including another assistant, another laboratory
helper, a pathologist and a chemist (presumably part-time).
The pathologist was needed to prepare and study tissue sec-
tions from animals injected with different chemical fractions
of the tubercle bacillus. Dr. Frederick Tilney was temporar-
ily doing this work for him at the College of Physicians and
Surgeons.

White also suggested that it would be desirable to estab-
lish four Research Fellowships paying $500 to $900 yearly for
the training of laboratory workers and the prosecution of
current investigations.

New bacteriological research was under way even before
it was settled that the program would go on. During the
summer of 1911, Dr. Charles E. North of New York City, had
investigated an outbreak of typhoid fever in an Adirondack
camp. Most of the laboratory examinations of blood and feces
were made at the Hoagland Laboratory by Avery and Garside


[1391

and the epidemic was thereby traced to a healthy typhoid
carrier.

Avery and Lyall were also conducting an investigation
which was published as "Secondary Infection in Pulmonary
Tuberculosis." .This work was important because the medical
literature was full of conflicting claims as to the occurance
of secondary infection in this disease as established by sputum
cultures and more especially by blood cultures. Avery and
Lyall made careful cultures from the sputa of fifteen cases
and found that the flora did not differ in any significant way
from cases of non-tuberculous diseases of the respiratory tract.
Blood cultures made on five cases of bronchiectasis and 110
cases of pulmonary tuberculosis were uniformly negative.

  The authors ascribed the previously reported positive
results to faulty technics, which often resulted in bacterial
contamination of the patient's blood while withdrawing a
sample for culture. To prevent this, they made a small cut
through the skin after treating it with iodine solution, thus
permitting the vein to be entered directly with the needle
without passing through the skin (which can never be com-
pletely sterilized) . This work was done at the Ray Brook Hos-
pital for Incipient Tuberculosis, the Brooklyn Home for
Consumptives, and the Hoagland Labora tory.

During this time White and Avery made a study of the
immunity reactions to a pure substance-the crystalline vege-
table protein edestin, which is derived from hemp seed. This
they obtained in a highly purified state from Dr. Thomas B.
Osborne of Yale University. The work, when completed, was
published as Part III of a series of papers on "The Biological
Reactions of Vegetable Proteins." Parts I and II of this series
were contributed by Drs. H. Gideon Wells and Thomas B.
Osborne.

  White and Avery were able to produce in animals specific
antibodies to edestin with which they could demonstrate the
immune phenomena of precipitation, complement deviation


               [ 1401

and guinea pig anaphylaxis. Edestin, like many plant proteins,
will agglutinate the red blood cells of the sheep and man and
they showed that the antiserum to edestin would inhibit the
hemagglutination.
They also found that when the edestin-antibody precipi-
tate was washed and then incubated with fresh normal guinea
pig serum, it yielded a substance or substances that, when in-
jected intravenously into guinea pigs, produced a fatal ana-
phylactic-like intoxication, similar to that of the anaphylatoxin
of Friedburger. This field of investigation was still unexplored
ground at that time.
White had a clear concept that antibodies were respon-
sible for many of the manifestations of disease, a very modern
point of view that was brought out in a paper read before
the annual meeting of the Medical Society of the State of
New York in April of 1912.
  An extensive epidemic of severe sore throat occurred
in the city of Cortland and the village of Homer early in 1913.
This epidemic was thoroughly studied by Drs. Charles E.
North, Benjamin White and Oswald Avery. A beta hemolytic
streptococcus was recovered from patients. It was found that
over 70% of the cases occurred among the patrons of a single
dairy. In this dairy two cows were found that had acute strep-
tococcal inflammation of the udder (garget) . A streptococcus
isolated from their milk appeared identical with the epidemic
strain. Similar milk-borne epidemics due to streptococci had
been reported in Boston in 1910-1911 and in Baltimore in
1912. This study was published in January, 1914.
  Oswald T. Avery resigned as associate director of the
department of bacteriology on September 4, 1913, to go to
the Rockefeller Institute for Medical Research, where his
contributions have made scientific history. In later years, Dr.
Avery told the full' story of events leading to this step,
  In the spring of 1913, Dr. Rufus Cole, director of the
Rockefeller Institute Hospital, paid a visit to the Hoagland


[ I41 1

Laboratory. He found Avery at his laboratory bench adding
bile to a broth culture of pneumococci in order to dissolve
them. Cole explained that at the Institute they did not use
crude bile for this purpose, but bile salts dissolved in a buf-
fered solution. Avery was much impressed. He wondered at
the time why Cole had come to Brooklyn on a seemingly
casual visit. White guessed correctly that his purpose was to
secure Avery for the Institute.

In a few days Avery was asked to come to the Institute
and look it over. At luncheon he found himself seated next to
Dr. Simon Flexner, the head of the Institute. Flexner was full
of questions about his work, his training, his interests, Later
in the day, Cole suggested that there might be an opening for
him there. That summer, while `Avery was working at Saranac
Lake, he received a letter from Cole offering him a position.

Avery was not then fully aware of the gloomy outlook
at the Hoagland Laboratory, for he first declined Cole's offer.
He said he felt happy at the Hoagland Laboratory; the work
was interesting; he liked his colleagues. He liked his complete
freedom to work at what he wanted to do without being put
under pressure.

Cole, however, did not give up. He had been greatly im-
pressed by the article on "Secondary Infections in Pulmonary
Tuberculosis" done with Lyall. By the end of the summer,
Avery was persuaded to come to the Rockefeller Institute.

Thus ended six years of service at the Hoagland Labo-
ratory. As he himself said at a later time, it was here that he
learned bacteriology and here that he learned research. To
him it was "a wonderful place for a young man to get his
start." His scientific accomplishments at the Rockefeller In-
stitu te are too extensive and too well known to be mentioned
here.

Now working without Avery, White continued alone with
his studies of the lipids of the tubercle bacillus and their pos-
sible role in anaphylaxis. Previous reports in the literature

!
`i


1142 I

concerning the antigenicity of these lipids were contradictory.
It would be of the highest importance to learn of their true   I
                                                                    i

role in tubercular infection. In this investigation White care-
fully freed the fatty constituents from all associated protein

and found that they then had no antigenicity whatever when        I
                                                                        1

ipoids of the Tubercle-
LS also presented before
sociation for the Study

raid Avery as associate
.ogy. His major research
Dcci. Modern serological
tant organisms on the
re still far in the future.
d reactions appeared to

nto three main groups
red blood cells. As tests
bject to serious errors,
in which broth cultures
ythrocytes for one hour.
;hed: a hemolytic group,
id an indifferent group.
into smaller groups on
acid from the carbohy-
inulin. This paper was

ne same time-"Observa-
the Strep tococci"-LyalI
: production and nature
nown that there are two
nolytic streptococci; the
`streptolysin S." He con-
vith the bacterial bodies

      .* .        .     -7..          -- "P--- r-.
          periments in Anaphylaxis with the L
                Bacillus" was published in 1914. It wz
                 the Tenth Annual Meeting of the As
i                       and Prevention of Tuberculosis.
I                   Harold W. Lyall succeeded Osw
!
i                director of the department of bacterial
                 was on the classification of the streptocc

methods for classifying these imporl
basis of their antigenic constitution we
Classification on the basis of biologic;
be the only choice.
Lyall divided the streptococci iI
according to their reaction on sheep :
made on blood agar plates were su
Lyall devised a more accurate method
were incubated with washed sheep er;
Three clear-cut groups were distinguis
a methemoglobin-producing group, ar
Each of these was in turn subdivided
the basis of their ability to produce
drates salicin, raffinose, mannitol and
published in 1914.

In a second paper published at tl
tions on Hemolysin Production by
studied the factors that influenced the
of streptococcal hemolysin. It is now k
distinct hemolysins produced by hen
one he studied is now designated as `
eluded that it was closely associated v


[ 143 1

and was not in solution. He also noted the marked heat-
ability of this hemolysin. These two papers were submitted
as his thesis for the Ph. D. degree, which was conferred upon
him by Brown University.

The entire staff of the bacteriology department, including
Avery, was invited to spend the summer of 1913 at the State
Hospital for Tuberculosis at Ray Brook. There it began an
intensive investigation of complement fixation as a diagnostic
method in tuberculosis and syphilis. The loss of Dr. Avery at
the end of August caused the staff to abandon the tuberculosis
part of this work upon their return to Brooklyn but the
study of the Wasserman reaction in syphilis was continued.

Dr. White reported to the trustees that the Wasserman
test as done in Brooklyn at that time was most unrealistic and
unsatisfactory. This was because the hospitals and laboratories
had been using a modified method which was quite worthless.
The staff introduced the original and more difficult technic
with such good results that it was adopted by other institutions.
A course of instruction was given by White and Lyall to
laboratory workers from Brooklyn, New York, and Providence.
When the department of bacteriology was broken up, Dr.
Archibald Murray took over this work in which he had be-
come greatly interested, for he had been studying the relation
of the Wasserman reaction to the treatment of syphilis and
tabes.

PART 5

     The Department of Bacteriology
T he financial crisis of 19 11 was repeated in 1912 and
again in 1913; if anything the situation had become worse.
The trustees became increasingly pessimistic as shown by a
letter dated November 1, 1912, sent to Mrs. Gates and Ella
Hoagland.

"To the Benefactors of the Hoagland Laboratory:


--..-
1---111  ____^.^_ --_,-_- _ "_.. .  .-

11441

  At a meeting of the Board of Trustees, held this day,
the financial affairs of the Hoagland Laboratory and its
future constituted the sole object of consideration. It was
resolved that the Secretary communicate to the Benefactors
the opinion of the Board that the time has arrived when
the work of the Laboratory should be established on a
firm foundation for all time. That it is unwise to continue
the work from year to year depending on donations, but
that if it is to be continued as at present conducted, in will
be necessary to add to the present endowment at least
$125,000. The present Board feel that they would be un-
able to effect this increase, but are not willing to stand in
the way of having the affairs of the Laboratory admin-
istered by other Trustees, if such Trustees can bring about
the desired result. If this increased endowment cannot be
obtained the Board sees no other way than to curtail the
work to the amount of the income. This would necessitate
the cessation of the research work as it is now being carried
on, and the continuance of the services of the Director
of Bacteriology and his associates. In justice, however, to
them the Board desire to continue their services for an-
other year to give them time to adjust themselves to the
new conditions, but to do this must have additional finan-
cial assistance to the amount of $3000."
Early in 1913, White prepared an elaborate statement for
the consideration of the trustees. In it he pointed out that
the yearly expense of operating the Hoagland Laboratory
was $10,749, while the income was only $5020. As the build-
ing was deteriorating for lack of maintenance funds, an
annual budget of at least $14,562 was actually required. This
would be made possible by an addition of $200,000 to the
present endowment. In his Annual Report to the trustees
on May 1, 1913, White concluded with these words, "As Di-
rector, I beseech the members of your Board, a more interested


cooperation and a support which will enable us to continue
the work at the Hoagland Laboratory."
  In the fall of 1913, White revised his estimate of expenses
for the coming year. It was the last desperate effort to keep
the ship afloat. By omitting a successor to Dr. Avery, by elimi-
nating salary increases for Lyall and himself, by leaving out
all repairs for the building, he cut the estimated expenses for
the following year to $9920. The estimated income was $4910.
The usual Hoagland donation of $5000 would make up the
difference.
Ella Hoagland had contributed $3000 in 1911-1912 and
again in 1912-1913. Elizabeth Gates had given $2000 in each
of those years. The sisters were becoming more and more loath
to make up the constant deficits. Mrs. Tangeman had made
no contributions for several years. Mrs. Gates made it very
clear that she was contributing only because of Dr. White.
The fall of 1913 was the beginning of the end for the
department of bacteriology, Ella Hoagland contributed only
$2000, and an unnamed donor (surely Mrs. Gates) had prom-
ised $2010 which was to be ear-marked for White's salary.
The department limped along throughout the winter. In the
spring Elizabeth Gates gave up the fight to continue the re-
search program for which her father had founded the lab-
oratory.
Benjamin White resigned as director of the department
of bacteriology on May 28, 1914; Harold Lyall also resigned,
as did Barbara Bradford. Miss Bradford was to remain until
September to attend to the mailing of reprints of three forth-
coming publications. The department of bacteriology was
placed in charge of Dr. Van Cott, who was not dismayed at the
turn of events, but predicted that "there is a growing oppor-
tunity for constructive work in the harmonious relation with
the college, the hospital, and the medical profession of Brook-
lyn which will weld all interests together and realize in large
measure the ideals of its generous founder."


[I461

After leaving the Hoagland Laboratory, Dr. White became
assistant director of the Bacteriological Laboratories of the
New York City Department of Health. He was in charge of
the Antitoxin Laboratories at Otisville, New York, until 1918.
After an interlude in the Army during World War I, he be-
came director of the Biologic Laboratories of the Massachusetts
State Department of Health and assistant professor of bacteri-
ology and immunology in the Harvard Medical School. He
died on March 28, 1938.

Dr. Harold W. Lyall accompanied White to Otisville.
In later years he became assistant director in the Division of
Laboratories and Research of the New York State Department
of Health.

One may well wonder why Benjamin White remained at
the Hoagland Laboratory as long as he did. He had no in-
crease in salary after 1907. Because of friction with the board
of trustees, his situation was not always one of comfort. On the
other hand his standing in his profession was such that he
could have found a better position at any time.

  But White was both a sentimentalist and a man of intense
loyalties. While still a student at Yale he had been indoctrin-
ated with the idea that the Hoagland Laboratory was every-
thing that was fine and wonderful in scientific ideals and re-
search. He never wavered in the thought that his department
must remain a beacon light in medical science as it had been
in the days of Sternberg and, Ezra Wilson. Then too there was
a debt of loyalty to the Hoagland sisters, especially to Eliza-
beth Gates who had backed him up for years. As long as they
were fighting for his program, how could he give up the
struggle?

  Oswald Avery, who felt very deeply about the matter,
spoke of Benjamin White as the ideal department head, who
felt a responsibility to his people to provide them with equip-
ment, supplies and opportunity for research; the rest was left
to them. The only pressure he ever exerted was that of his own


I. 1471

example. His staff responded by giving him their complete
loyalty and by out-doing themselves in turning out good work.
Avery himself became that kind of a department head.

After the departure of White and Lyall, no more research
was ever done with the funds of the Hoagland Laboratory
save that of the Van Cott Fellowship which had a special en-
dowment for that purpose.

The life-span of the Hoagland Laboratory as a research
institution was just twenty-five years, most of them years of
great accomplishment. There had been triumphs and there
had been failures. The great triumph had been the blazing of
a trail, the setting of a pattern at a time when the independent-
ly endowed research Iaboratory was unknown. Other triumphs
were the many positive contributions made to medical science
and to public health.

The great failure was that of missed opportunities-the
opportunity to become a school of advanced education in bio-
logic science; the opportunity to secure permanently such men
as Sternberg, Kemp, Mall, White, Avery, Lyall and others; the
opportunity to continue its tradition through the ensuing
critica period; the opportunity to assure its own survival as an
jndependen t research institution similar to the Rockefeller
Institute.