January 17, 1962

Dr. Luther lerry

Surgeon General of the United States

U. S. Public Health Service

Department of Health, Education and selfare
washington 25, D. C.

Dear Dr. Terry:

On August 24, 1960, Ihe United States Public Health Service Com-
mittee on Live Poliovirus Vaccine made the following statement in its
report to the surgeon General:

"Ihe Committee considers that of the strains available for perparing
live oral poliovirus vaccine, the Sabin Type 1 and Type Il strains possess
the most favorable laboratory and field characteristics and recommends
their use. ihe Committee also recommends the use of Sabin Type III strain
which is satisfactory from the point of view of neurovirulence although
it has less than optimum immunogenic capacity and shows a tendency to
change its neurovirulence characteristics after passage in man. ihe com-
mittee urges the continued search for a superior Type Til strain. cli
Candidate strains other than those of Sabin which have been studied ex-
tensively are of greater neurovirulence for monkeys than the selected
reference.” (A lot of Sabin Type I attenuated virus was chosen as a
reference strain by the Committee.)

the Sommittee’s statement was followed by a public announcement by

the Surgeon General endorsing Sabin's strains at the exclusion of other

available attenuated strains. My objection to the decision was based on
pre L. Terry Page <
the fact that avallable laboratory data were insufficient to warrant

the uncrthodox procedure of declaring superiority of one group of strains
over another by an official government body. 1 had no objection to the
choice of the reference strain, but 1 was concerned that the Committee's
decision would lead to government fostering cf exclusive manufacture of
Sabin's products by all Pharmaceutical Companies interested in production
of live polio vaccine. This, indeed, occurred.

My protest to the Surgeon General was referred back to the Committee
on live Virus Vaccine and on October 18, 1960, I wrote te Doctor Roderick
Murray requesting that ne call a meeting so that my colleagues and I could
discuss the problems with the Committee. Or. Murray replied tc my Letter
on Uctober 30 Indicating that he had reservations about holding a meeting
with my colleagues. I repeated my request on November 4 and December 3,
but received no reply.

in the meantime, more extensive investigations conducted during 1960
and 1961 by manufacturers and independent scientists revealed several new
facts related to the Sabin's attenuated polio strains. Griginally, the
vommittee felt the neurovirulence for monkeys was the most important
laboratory criterion available and that the Sabin strains showed less
neurovirulence than the other strains. It has been demonstrated that the
Sabin strains give variable results with regard to neuropathogenicity in
monkeys, and, that in fact, several lots of Type 1 and Type Lil vaccines
nandled by the same or by different laboratories were much more virulent
for monkeys than the reference virus.

This factor alone should have invalidated the criterion chosen by

the Committee on August 24, 1960, to exclude strains other than Sabin's
Dr. L. Terry Page 3
as "of greater neurovirulence for monkeys than the selected reference".

However, even more urgent is the problem of Sabin's Type III virus
which was proved to be notoriously unstable after a Single passage through
the human intestinal tract. work conducted at The «istar Institute led
to the development of a new attenuated type Iil strain which was derived
directly from the original W-Fox Type I11 strain used for successful
vaccination of 7 V2 million people.

This new WM-3 strain of type Ili-virus does not change after passage
through human intestinal tract and is obviously superior to the existing
Type Iif strains including Sabin Type 111 which was endorsed with reserva-
tion by the Committee in 1960.

On April 14, 1961, 1 wrote to Dr. @urray telling him of our success
with production of poliovirus vaccine in human diploid cell strains and
of our development of a new genetically stable type 3 strain. In view
of the fact that On August 24, 1960, the Committee urged “the continued
Search for a superior Type ill Strain", | expected that this information
would elicit a response. Nevertheless, the letter remained unanswered.

Finally on May 23, 1961, I made another plea ts be heard. ihis re-
sulted in a meeting held at DBS on June <3, 1961. The full vomaittee, my
associate, Dr. Stanley a. Plotkin, and 1 participated. At that meeting
i discussed the success of mass immunization of 8 million people with my
Type 1 strain and told of the development of an attenuated Type III (vi-3)
which does not change after passage through the human intestinal tract.

Although the Committee appeared interested in the data which I pre-~
sented, it was still quite obvious to me that it would be impossible for

any manufacturer to display interest in the production of a new Type III
Dr. L. Terry Page 4
vaccine with characteristics superior to those presently available until
the original, exclusive endorsement of Sabin's strains would be publicly
amended. iherefore, on July lz, 1961, [ wrote to Dr. Murray and the Com-
mittee members and referred to the need for definite and public steps to
alter the official position on the acceptability of only one group (Sabin)
of strains for vaccine production. In response to this letter, a Committee
member wrote to Dr. Murray statings “Any strain, ....seeeee0s, should be
approved, if data are presented and confirmed to show that the strain
possesses properties of a vaccine virus which are equal, ox superior, to
those of the Sabin Type I LSc reference strain. I would have hoped this
is clear to everyone Interested, but if it is not, then you should con-
sider a public statement to this effect."

Unfortunately, no public statement has been forthcoming. in fact, I
never even received a reply to my letter of July ie.

i feel that it is imperative that the paragraph of the Committee re-
port referred to at the beginning of this letter be withdrawn and that a
new public statement be made. This statement, based on facts made avaii-
able in print and to the Jommittec, should meke it clear that the strains
which I developed could be licensed if they met the criteria established
for the reference strain. Thus, the problem of exclusive licensing and
manufacturing fostered by the obviously unwarranted statement of August 24,
1960, would be eliminated, permitting organizations to work with my strains.

I trust tnaat you will give this matter your sericus consideration and
that a public statement will be forthcoming.

Sincerely yours,

Hilary Koprowski, 4. D.,
Director