Evelyne Cerf-Pecher’s book on her father, Dr Charles Pecher. The Story in English. Part 3 of transcript

by nuclearhistory

Evelyne Cerf-Pecher’s book on her father, Dr Charles Pecher. The Story in English. Part 3 of transcript

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THE TALE could easily have ended here. His life, although much too short, had certainly been lived fully. His body of work, both in Belgium and in the U.S.A., was significant, and was preserved for ever in scientific
journals. His pioneering efforts to cure certain osseous cancerous pathologies by the use
of strontium-89 were continued by colleagues from the Radiation Laboratory who referred to him in their own publications (October 1942, cited in “Annexe IV. Sources d’information pour la cinquieme quleme partie”, and commented on at the end of “Annex I. Les publications”).

And things might have evolved, as they usually do in scientific research, with new discoveries standing on preceding ones…

But, curiously enough, in the same way his analysis of nerve fibre excitability
was lost for a long time, the strontium-89 studies also disappeared from the medical and scientific literature, for decades!

A simple reason is that this radioisotope was no longer available. War had now come to the U.S.A. (December 7, 1941) and the cyclotron had new priorities. It was “fully occupied with war work, and was not making strontium”, my mother was informed in 1943 by a letter from a colleague of her late husband.

But another reason has recently been brought to light by Paul Langley:
SR-89 became a “classified” matter under the super-secret Manhattan Project! And that would be (some are convinced of it) the actual and very compelling reason why the scientific and military authorities wanted Pecher, the “Sr-89 specialist”, to be kept in America. This is not my opinion, on chronological grounds. But I am quite certain this is the reason why the work my father did at the Lawrence laboratory was “forgotten” for so long. Thus the tale does not end with the death of my father!

In the 1970s, Paul Langley was a 17 year-old soldier in the Australian
Army. He was acquainted with military radiation detection equipment
and before long became aware of the atomic fallout arriving at that time

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In Australia from the nuclear tests carried out in the Pacific. He received
basic instruction from the army on radiations, but soon became self taught
about finsion products and general nuclear science as he discovered
the existence of radiogenic diseases. He was particularly indignant
at the poor attention paid to the health of indigenous people relative to the fallout and
this motivated him, in 1994, to search for medical knowledge
preexisted the bomb tests. This was the start of a thorough and extensive examination
of the U.S., British, Japanese and Australian declassified archives.

In 1999 he came upon a reference to “Pecher” in the context of the
Fallout and in particular to the Sr-89 which is a fission product! And from
That reference he was able to locate the 1940-1942 papers. He discovered that biological
And medical data on Sr-89 already existed at that time, that this research should have led to a new
treatment which could have given relief to many suffering patients, but that this work had been completely suppressed because of the war. This shocking finding prompted him to
write a number of polemic texts on the Internet and finally to assemble in a book
all of the information on the history of the atomic bomb, on the pre-war medical knowledge
and on the post-war developments (published in 2009 as an e-book).

Thanks to the Internet, Paul Langley and my cousin Carla were able
to meet, both being curious about Charles Pecher! And so, in time, we all
came into contact with each other. Paul e-mailed me a huge quantity of
Informntiona and documents, and this is how I learned about the fate,….
not of my father any more, … but of Sr-89! This very complex story is
summarized in the “Cinquieme partie”. Here I will limit myself to the
main points.

In September 1942, the Manhattan Engineering District is set up,
under military control, to hasten the development of an atomic bomb
(the progress of this project, to that point, being altogether unsatisfactory).
It’s code name: the Manhattan Project. Overall direction of the scientific
rrrcnrch was entrusted to the physicist J. Robert Oppenheimer. And the
study of the metabolism of the fission products was committed to the
physician and scientist Joseph G. Hamilton. Both were members of the
Radiation Laboratory at Berkeley, and both had known Charles Pecher
very well. Hamilton pioneered the medical use of radioiodine for the

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treatment of thyroid disorders, and had had many conversations with my
father. They were even coauthors of a publication.

The study of the fission products was an essential concern In the
Manhattan Project, because. .. in the event of a future detonation…. these
products would become present on Earth … ! Their properties, their dangerousness,
the ways to reduce their absorption, and so on, had to he fully
understood. Thus Hamilton promoted a number of research programs for
this purpose, and produced reports at intervals. In these secret reports a number
of fission products were mentioned, including radioisolopcs of
strontium, of course.

When the war was over, this study became even more imperative:
Atomic bombs had exploded, and now fission products had actually entered
The global environment. The control of atomic energy was transferred to
a civil administration, the Atomic Energy Commission (A.E.C.) which
maintained the wartime secrecy on these matters for years.

A.E.C. Division of Biology and Medicine promoted several projects, among the Project Gabriel
whose objective was the evaluation Radiological hazard from the fallout of debris from nuclear weapons detonated in warfare” including their geographic distribution. The 1954 report
(declassified in 1981), is particularly focused on Sr-90, which at that time was considered as the most hazardous isotope resulting from detonation (a special project had even been designed as Project Sunshine for the study of its world-wide dispersion). But studies on Sr-89 and other
radio-isotopes, as for example 1-131, Ba-140 and Ca-45, are also mentioned in this in this comprehensive report.

Only two references to Pecher can be found, but it is certain that,
within the A.E.C. his contribution was not lost: many persons who knew
of his activities were also engaged in these secret missions. At first, there
was Ernest Lawrence of course. And also John Lawrence, pioneer of the
medical use of radiophosphorus, and who had collaborated with my
father for the first medical trials with Sr-89. Then Willard F. Libby, of
the Chemistry Department, who had given permission to my father to
use his personal instruments in his private laboratory to measure the
very weak activity of radiocalcium samples (Libby would be awarded the
Nobel Prize in Chemistry in 1960). And also Robert S. Stone, chief of the
Radiological Division in the U.C. Hospital of San Francisco, who had

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authorized my father to work in his department where neutron therapy
was tested for cancer treatment (neutron rays seemed to destroy cancerous
tumors more selectively than X-rays, and my father had begun
animal experimentation on this subject before discontinuing it, as mentioned
above). But knowledge on Sr-89 was now confined to the scientific
surroundings of Hamilton, and secrecy was imposed.. . and probably
accepted as a necessity.

The constraints imposed at this time are well-illustrated by reference
37 in this 1954 report: “Letter from J.G. Hamilton to Dunham dated
Apr. 6, 1954.”The letter, Paul Langley found, accompanied “available data
from the University of California Hospital which was compiled by members
of Stone’s staff who incidentally are quite unaware of the classified nature
of this material.” And Hamilton went on to say that he warned Dr. Stone
that “it should not be discussed with anyone in the Division of Radiology
with the exception of the two of us.”

In this year 1954, at the Berkeley Radiation Laboratory, a new generation
of researchers was at work, and Pecher was forgotten. The direction
was now assumed by Hamilton, but nothing was told about this pre-war
member of the laboratory.. .

BUT THE WORK of my father had been published. It could not disappear
completely!. . . And it would not disappear: in 1976 it was restored to public
medical literature by a certain Marshall Brucer. This happy turn of events
is described in the “Deuxieme” and “Cinquieme partie”.

Marshall Brucer, M.D., had been called in 1948 by the A.E.C. to the
leadership of a new medical division in the Oak Ridge Institute of Nuclear
Science. Its purpose was to investigate the use of radioactive material
in medicine. In 1962, Brucer had to retire, but he continued to write on
the subject of nuclear medicine. In 1976, he published the no. 81 of his
Vignettes in Nuclear Medicine entitled “A History of Bone Scanning. I –
The first generation” where he asserted that the work of Charles Pecher was, in fact, the start of this diagnostic procedure (even if, as

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other authors of “the first generation” as they are called by Brucer, his aim
was therapy and not diagnostic). At the end of the article, a chronological
diagram outlines the development of this technique, placing Pecher
in the first position (the diagram also shows that in the seventies, bone
scanning was largely carried out with Sr-85 – this detail is important – I
shall come back on it soon).

In 1990, Marshall Brucer published a voluminous and thorough
textbook: “A Chronology of Nuclear Medicine” wherein a whole page is
devoted to Charles Pecher, plus many additional notes on other pages.
Here, his original work with Sr-89 as a therapeutic agent for bone metastases is fully presented, including its palliative effect on pain. And Brucer emphasizes a significant feature: “Sr-89 Becomes the Third Therapeutic Radioactive Agent” (the two preceding ones being 1-131 and P32 initiated by J. Hamilton and J. Lawrence, respectively). He mentions the fifties
fallout controversy wherein Pecher’s name was cited in connection with
his demonstration, involving two cows, of the Sr-89 transfer to milk (thus raising questions about the danger of radioactive strontium in the fallout.)
He finally reaffirms the stem position of Pecher in the bone scanning a development, and ends his analysis with “Well over 10,000 papers should have listed Pecher in their bibliography. But very few give him credit.”
Sadly, Brucer died in 1994, and I was unable to make contnct with him.

Two years before Brucer’s 1976 publication, Sr-89 had already come back
into European medical literature. This time, however, it was a rediscovery,
completely independent from Pecher’s work! And standing on another basis. Two German physicians (N. Firusian and C.G. Schmidt )had
observed that skeletal scintigraphy with Sr-85 (which was the radio Isotope they used for clinical bone scanning) produced an analgesic effect in patients with severe osseous metastases. This had motivated them to experiment with another isotope of strontium, Sr-89, by reason of beta ray emitting property. Their 1974 publication proclaimed Sr-89 for the treatment of incurable pain in patients with neoplastic osseous infiltrations .

It is worth noting that this “new” therapeutic use of Sr89 was made possible by
the development of bone scanning which, according to Marshall Brucer, originated from Pecher’s work! But that , Firusian and Schmidt could not have known: Brucer’s Vignette “History of Bone Scanning” had not yet been published!

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They knew that “The metabolism of strontium is similar to the metabolism of calcium
from which follows the affinity of strontium to the bones”,
and they were probably were aware that Pecher was the historic source of
this knowledge, for they refer to a 1950 paper of John Lawrence and
Wasserman, which in turn declared “Radioactive strontium has been shown to behave
similarly to calcium in the body”, citing a 1941 paper of Pecher.
But this 1950 paper did not enable Firusian and Schmidt to discover the 1942
posthumous paper of Pecher describing the preliminary experiments
on the therapeutic use of Sr-89 and the first successful clinical case.

Interestingly, a little sentence in this 1950 paper of Lawrence and Wasserman called
into question the medical usefulness of Sr-89: “…it seems unlikely that
radiostrontium will be a valuable therapeutic agent. ..”Curious conclusion coming
from a former collaborator of my father! Did John Lawrence had reason to
hide the utility of Sr-89 as a pain palliative in cancerous bone metastases? It is
conceivable, inasmuch as this paper was published during the period of secrecy
imposed by the A.E.C.

But another explanation is also quite plausible: in this paper Lawrence and
Wasserman had challenged another pathology, multiple myeloma, the treatment
of which had always been discouraging. The patients frequently endured pain,
and even pathological fractures, in some bones. The authors had experimented
a combination of P-32 and Sr-89, as compared with other treatments involving
X-ray therapy. But the results were not markedly better than with the other treatments,
and the combination of both radioactive elements did not prove more
effective than P-32 alone. These unsatisfying results were probably reported by
Lawrence as they were, without any deception. His pessimistic conclusion was
likely not a generality but confined only to this particular disease.

A 1994 publication on multiple myeloma sheds light upon the difficulties
encountered in the 1950 Lawrence and Wasserman study. The authors, Edwards,
Santoro and Taylor, report a case where a substantial pain palliative response was
obtained in a patient treated with Sr-89. The rationale is that the frequent osseous
metastases in patients with multiple myeloma are osteolytic (appearing as
lucent lesions in radiographs, and where strontium is not expected to concentrate
nor to have a favorable effect), but some osteoblastic activity may happen at the
periphery of the lytic lesions, detectable by bone scan, and in those cases, patients
may benefit from Sr-89 therapy (which, at this time had become regularly used
for bony metastases from breast and prostate carcinoma). The authors recommend
bone scintigraphy to identify the “patients with multiple myeloma […I who
may benefit from Sr-89 therapy.” In 1950, the year of Lawrence and Wasserman’s
paper, bone scanning was not yet available…

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Years later, in 1990, the trademark METASTRON wai registered by the firm
Amenham as a pharmaceutical and medicinal radloactive preparation
in for in-vivo use in the palliation of paln and treatment of bone metastases.
An announcement was published in the News & Views
of the European Journal of Nuclear Medicine and Molecular Imaging in August of that year.

In 1993, Metastron, in the form of injectable Strontium Chloride, Sr89 (then
marketed by G.E. Healthcare), was approved by the U.S. Food and Drug Administration, as a new molecular entity.

And in … 2010. Metastrnn is still in use! For the very same indication!
Specifically, pain relief for patients suffering from bone pain due to metastatic prostate cancer. The presence of bone metastases must first be confirmed confirmed by scintigraphy (with technetium-99m coupled with a diphosphate,
which is the present day radioactive agent used in bone scintigraphy.)

I have no information on the period between 1974 and 1990 , and thus, no information on the early clinical, administrative and commercial development of Metastron.
Sadly, though, it seems my father was the great forgotten hero of the Metastron
success story! Thanks to Marshall Brucer’s “Chronology” , however, a clear link between Pecher and Metastron has been recognized in 2000. It appeared in a historical perspective on nuclear medicine V. Ralph McCready (Surrey, U.K.). In a paragraph concerning Charles Pecher he wrote: “He would have been gratified to see the current clinical results from Metastron (89SrCl2) for pain relief from skeletal metastases from carcinoma of the prostate.” So, at least in some historian’s mind, this link exists.

These later developments in the “Sr-89 story” figure at the end of the “Cinquieme partie”, with references in “Annexe IV. Sources d’information”.

Please note some technical details: the Sr-89 in Metastron is produced by a fission in a nuclear reactor, and is used as chloride, while the Sr-89 used by my father was obtained by
deuteron bombardment of natural strontium (oxide or metallic) in a cyclotron, and the lactate anion was chosen for the clinical trials in preference to
the chloride one. The half-life of Sr-89 was indicated to be 55 days in the papers of my father, and later, in the 1950 paper of J. Lawrence. At present it is considered to 50.5 days.