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U N I T E D S T A T E S A T O M I C E N E R G Y C O M I

ATOMIC ENERGY AND CANCER
by ,
H. Friedell
Date of release: March 26, l9h6
This document is for official use.
Its issuance does not constitute authority
for declassification of classified copies
of the same or similar content and title
and by the same author.
Technical Information Division, Oak Ridge Operations
AEC, Oak Ridge, Tenn., ll-5-h8--750—ll98l
ATOMIC'ENERGY AND CANCER
By E 0 Erie dell
I am.very pleased to have an opportunity to discuss with you
vthis evening the concomitant developments in medicine and biology which
occurred in exploring.the field of atomic energy and which aided in the
culmination of its primary objective, the Atomic Bomb, Since the activi-
ties of the Manhattan Project have become known, those of us in medicine
and particularly those of us interested in Cancer have become alerted to
the possibilities of the useful application of information gained in the
course of development of the Manhattan Project to various fundamental bio-
logical problems,
'Emphasis to the present have been almost entirely on the destruc-
tive uses of atomic energy -- and properly so -- since the objective of
the Manhattan Project was to develop an atomic bomb which would contribute
to an early close of the war° The results have etched their place in
history.' However, this tremendous release of energy which has been made
possible by the attack 0n the nucleus will not be reserved for destructive
ends, There is another side of the story of atamic energy, a portion of
which I would like to discuss tonightp >
Although it appears that immediate uses for power, heat and etc°
are still distant, the harnessing of atomic energy for useful purposes is‘
now within our grasp, The unleashing of nuclear energy is certain to
have broadened our-horizon and made it brightero
Before we survey the techniques, the information, and the mate-
rials uncovered during the course of the.Atom.Bomb Project which might be
applicable to the prdblem of Cancer, I would like to show you an unusual
film of the effects of the atomic'bomb, a harbinger of the terrOr and
chaos that will surely occur in future conflict° The full.impact of the
destruction of the atomic bomb has probably not yet been felt -—- politic-
ally, socially, economically, When it is, we will conclude that we must
eliminate the use of atomic energy for destructive purposes° This seems
-possible only by eliminating war itself,
Movie of the Atomic Bombing of Hiroshima,-
Broadly speaking, one might accept as a satisfactory solution
to the Cancer problem, positive means of preventing the development of
malignant tumors and allied diseases, or efficacious therapy which direct-
ly corrects the basic disorder, It is obvious, that in order 'to do this,
we must learn more of the fundamental nature of the development of neo-
plasms --- their etiology, their biochemistry, the metabolic factors gov-
erning their growth, In other Words, their fundamental physiology.
Although I hope to point out certain primary lines of approach, I feel
that it would be presumptuous for me in this uncharted field, to indicate
how atomic energy will influence future cancer research and at what points
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the attack should be pressed. Instead, I prefer to tell you something of
the character of the medical and biological developments which occurred
in producing the atomic bomb and hope-that this as yet uncatalogued mass
of information may stimulate us in our untiring quest. ‘
Early in the development of the Manhattan Project, it was recog-
nized that many problems would arise which had not been previously en-
countered. These were concerned chiefly with: a) the production and
handling of radioactive material on a stupendous scale, and b) the process-
ing of uranium.compounds, and the fabrication of'uranium.metal. Uranium
is an.extremely toxic material when introduced into the body.
On organizing the Medical Section, the extensive industrial in-
stallations and the large clinical facilities made it necessary to develop
two large divisions to implement these activities --- an industrial medi-
cine division and a clinical division. .A third division, a research divi-
sion, had already been instituted in order to investigate the medical and
biological aspects of the various problems, anticipate the hazards to
health, and.institute the necessary safeguards. Of primary interest to
the group here, are those developments which were made in the field of
medical and biological research.
In the research program, two primary problems as indicated be-
fore existed: -
l. The prdblem.involving the chemical toxicity of uranium.and
a great many other related compounds. Briefly, this required the estab-
-lishment of tolerances for respiratory, gastro-intestinal and skin absorp-
tion, a study of the methods whereby these materials could gain an entrance
into the body, the development of the protective devices, and procedures
for regular assay of these various materials. 'The mechanism.of uranium
toxicity was also studied.
2. The research on the radiation aspects are perhaps more '
directly applicable to Cancer research and therefore deserve elaboration.
In general, the investigations were pursued along the following categories:
a. Estimation of the Safe Levels of Radiation; Because
of the tremendous amount of radioactive materials andfradiation.of all
types which were developed in the various operations, it was necessary to
establish the accepted tolerances for radiation more securely. Studies
were therefore instituted for gamma rays, neutrOns, beta rays, and alpha
~particles. Specific tolerance levels for radiation other than Photons
(x-rays and gamma rays) and neutrons were not previously established. The
daily permissible radiation levels for alpha_particles and Beta rays are
especially difficult to fix. Since alpha particles and Beta rays are
primarily of significance if introduCed into the body, the kind of radio-
active element, the rate of decay, the energy bf the particle and local-
ization of these elements in the tissues are important. (Skin effects
due to external Beta rays may constitute an impertant hazard.)
As you may-know, the established tolerance for gamma rays and
x-rays is .l roentgen per day. The daily permissible dose of neutrons is
.Olr (neutrons). Our data Obtained by investigating many species of
animals indicates that these levels arc'safe, and that definite.
safety factors are incorporated'withinwthem.i In order to establish a.
tolerance level, or better, a daily permissible does, it is necessary to
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determine all the possible effects of radiation, This includes general
data on survival, specific effect on the hematopoietic tissue, specific
effect on the reproductive system.(the hematopoietic system.and the gonodal
_tissues are most sensitive to radiation) once the date of development of
tumors, lymphomas and blood dyscrasias during the lifetime of the animal,
It has been possible to show that, in general, in large amounts external
radiation and internal radiation due to the deposition of various radio-
active materials can produce tumors once in the case of radioactive mate-
rials, these tumors develop at the points where the radioactive materials
localize, '
b° Study of the Mechanism.of‘Raddation.Effects: The
empirical establishment offtOIerance levels for radiation by studying sur-
vival, etc,, is certainly a simple and direct apProach, Nevertheless,
profound knowledge of radiation injury would not be possible unless fur=
, ther studies into the mechanism.of the biological effect of radiation.were
made° At present, the progress into the mechanism.of radiation effect
has not been extensive, but certain fundamental data have been accumulated
in regard to the behavior of the various basic and enzyme systems, There
have also been studies on liver metabolism, kidney functions, blood cell
metabolism, etc,
c° Metabolism.of Radioactive Materials: In order to
understand and anticipate-some of the effects of radioactive elements
introduced into the body, something of the metabolism.of the fission prod-
ucts_( about 30 elements in the middle of the periodic table which are
produced in the atomic energy) needed clarification, It was also neces-
sary to investigate certain alpha particle emitters which included pluton-
ium and radiumo 'It was necessary to know their mode of entry, the charac-
ter of their radiation, the tissues in which they localize, and the manner
in which they are deposited in these tissues, and their excretion from.
the body, 'Under the auspices of Colonel Stafford L, Warren, Chief of the
Medical Section of the Manhattan District, and particularly under the direc-
tion of Dr° Robert S, Stone, who was primarily concerned with the pluton—
ium.project, a great deal of information on the fission products, pluton-
ium, radium.and.uranium, has been collected, These data.should serve as
a fine background for-further development in the study of radioactive
materials in the body°

d° Therapeutic Measures: At the present time, we
know of no specific therapeutic measure for combatting excessive radiation°
Therefore, great emphasis was placed on preventing personnel from.encoun-
tering damaging amount, In general, the approach has proven extremely
effectiveo Nevertheless, some knowledge of the efficacy of various
forme of therapy would be a desirable adjunct to our other information°
The primary attack has been along the lines of understanding the metabo-
lism.of sensitive tissue such as the hematopoietic structureo

e, Assay cf Radioactive Materials Deposited in the
Body: _One of the very important studies in the research program of the
Manhattan.Project Medical Section, is the development of methods for the
assay of excessive deposition in the body of radioactive materials of one
type or another, As you well know, excessive amounts of radium deposited
in the body can be estimated with a fair degree of accuracy by measuring
radon, a gaseous daughter product of radium, present in the expired air,
Similarly, by assay of the urine and other excreta for radioactive ele-
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ments, the amount of these elements deposited in the body may be estimat-
ed. In order to do this, we need good excretion data, estimates of the
tolerance levels, knowledge of the deposition in the body of these mate=
rials, etc. I am pleased to say, that in a number of these problems, sat-
isfactory solutions were developed.
SLIDES
I have here very briefly tried to indicate the general character
of the medical research program.of the Manhattan Project. We may now
properly ask how this was related to the problem.of Cancer. ‘What is the
usefulness of materials used in atOmic energy as the approach to Cancer?
Can the tremendous amounts of radiation be useful for cancer work? Why
and how are the various devices used for producing fissionable materials
such as the uranium.piles, the electro~magnetic separation methods,
diffusion methods, useful for our purposes? The two general avenues which
appear natural and promising for exploration are first, the application
of the materials and information to cancer therapy, and second, the study
of the metabolism of malignant tumor by utilizing the materials and tech-
niQues for the pertinent investigation.
Although the efficacy of radiation in the therapy of cancer has
been fairly well established and although no revolutionary feature has
appeared in regard to the use of external radiation or radioactive mate-
rials, unheard of amounts of radioactive materials of one sort or another
can now be used'both for external radiation and for internal therapy.-
This definitely promises to enhance our-progress in the treatment of tumors.
We have now an abundant and wide range of radiation energies and radio-
active materials which can be selectively localized in tumor tissue.
1. By introducing various materials into the pile and making
use of the tremendous flux of neutrons, elements like cobalt and tantalum,
which on activation have high energy photons, can be made available in
large amounts for radiation purposes similar to that which the radium
ypack now serves. Materials like tantalum, can possibly be made into the.
form of needles and kept activated in the pile. They can then be used in
the body for the various purposes that interstitial radiation is put to.
2. Specific radioaCtive materials such as P32, Sr89, 1131, can
be produced in great abundance. Before the war, P32 was coming into use
in leukemias and polycythemias. Sr89 had been used experimentally for
Bone Tumors, because of its localization in the bone (its metabolism is
quite similar to that of calcium). Il3l of course, localizing in the
thyroid may prove an important adjunct in thyroid malignancy. It has
already been used for Hyperthroidism.
3. Any of the various materials that can'be made radioactive
I l the pile or are produced.by fission in the pile, might conceivably be
synthesized into compounds which would be localized in tumors. Obviously,
this is as yet a fond hope, and at present, no one has been able to produce
an element or compound which is selectively localized in tumor tissue. If
this were possible, a tremendous amount of radiation could be localized in
tumors by this method. In addition, it might be possible to introduce ele-
ments into tumors which could be activated by neutrons and the resultant
release of ionizing energy would be very destructive to the tumor tissue.
For example, boron capturing a neutron will split up into several alpha
particles, releasing a tremendous amount of intense ionization.
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Exciting poSsibilities do not lie in the use of radiation from
the new radioactive\materials alone however. They lie also in the fact
that we are now in a position to make tagged elements in great abundance.
These tagged atoms are isotopes of the ordinary atoms, having the same
chemical behaviour. Thegrcan be recognized however, by certain additional
and unique characteristics. In general, there are two types of tagged
elements —~- the stable and unstable isotopes. The unstable isotopes are
,radioactive and therefore can be identified by detecting their.ionizing
*radiation. _The stable isotopes, having an increased mass, may be detected
by devices such as the mass spectrdgraph,which take advantage of the
different masses, These tagged elements will undoubtedly evolutionize
our ideas on fundamental metabolic problems, and specifically in the case
of Cancer, they offer great hope in understanding its fundamental biology.
Radioactive isotopes can in general be utilized in the following
broad ways: '
‘a. By introducing into a living animal, by isolat-
_ing tissue and examineng~itaaeeemesuntanTeeheadldq¥fifianhmng,remeeamfor
the quantitative deposition of the tagged element. -


b. By utiliZing radioactive elements which emit gamma
vrays. ~These can then be detected outside the body by suitable instruments,
without disturbing it in any wayigg,. , -
o. By utilizing alpha and Beta emitters to effect
photographic emulsion. This method can be used to localize elements in
tissues and possibly even cells, by making radio-autographs from thin sec=
tions of the tissue to be studied.
d. Tracing radio-elements to study character and rates
of biochemical reactions, iYLi» ediatemetabolism, exchange processes, se-
cretion and excretion, reversibility, etc.
- From the biological view point, the elements which are.of inter-~
est group themselves in the following.general order of importance:
a. Carbon
b. Nitrogen, Oxygen, Hydrogen
Sulphur (almost entirely in inorganic compounds)
Calcium, PhoSphorus, Iron
Sodium, Potassium, Mg, Cloride
Carbon easily heads the entire list.
Many of these unstable radioactive elements, such as Cl“ and H3,
together with P32, Strontium139 and Iodine131, were known prior to the
development.of the Manhattan Project. ’However, because of the tremendous
scale on which uranium piles may be constructed, it may be possible to pro-
vide them in great abundance and provide them for.many fields of research.
Radioactive isotopes, such as phosphorus, calcium, strontium and
iodine and the stable non-radioactive isotopes, such as carbon, hydrogen,
oxygen, and nitrogen, have previously been used with great success in estab-
lishing complex and unknown behavio":‘ certain metabolic processes. The
element, carbon, is of particular interest to biologists- biochemists .hin-
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physicists and other scientists, because of its fundamental position in all
our vital life processes.' The basic and vital process of photosynthesis,
upon which all life depends, may possibly be successfully attacked by tracing
the element, carbon, throughout this cycle. w I
From.the point of view of cancer research, the application of
these isotopes to cancer investigations, offers some hope of eradicating
many of the hiatuses which existed in our knowledge of the.vital processes
of the tumor cell. The effect of various chemicals on tumor growth, the
role of enzyme systems in tumor development, the part that specific elements
in the diet may play in the Cancer Prdblem, and the activating impetus of
certain carcinogenetic agents Will now come under more careful scrutiny.
This,.of course, is to mention only a few directions of investigafiifln.
The carbon atom and the hydrogen atom, now recognizable in the midst
of their complex activities, will immediately suggest many approaches. In
the case of Cancer cells whose metabolism may differ from normal cells in
only a few though fundamental details, and.where inquiries of the most search-
ing and exacting nature are required, a highly critical tool for general
use now appears.
SUMMARY: I fear I have presented no startling or arresting information
on the attack of the Cancer PrOblemw However, we have in general, brought
.to'your attention two fields for development:
1. The First is the opportunity for improving the therapeutic
approach. New radiations and new radioactive materials in an abundance
which were not previously imagined, are now possible. These can'be used
for external radiation, for interstitial radiation and as radioactive mate-
rials in specific compounds which may be localized in various tissues.
(Phosphorus, strontium, and iodine). A corollary to this is the possible
introduction into tumors of elements which are, so to speak, triggered.by
neutrons to release large amounts of ionizing radiation.
2. A Second and perhaps more important approach has been made
possible by ability to produce radioactive isotopes in abundance to study
the unwarranted behavior of the cancer cell. The key in this prdbably lies
in the use to which.we may put Cl“, but other elements (Hydrogen, Nitrogen,
Sulphur, etc.) will be useful.
The success of the Manhattan Project in achieving its goal was
certainly accomplished by difficult and intensive effort, but its success lies
primarily in the fact that its development was based on certain fundamental and
substantial corner stones. These were among others, the discoveries of
fission and its attendant release of energy, the identification of fission-
able materials, and the recognition of the possibility of a chain reaction.
Although we have not uncovered such fundamental corner stones in the approach
to the cancer solution (perhaps from.my limited vantage point, I do not
recognize or appreciate them), real progress can be made by united and inten-
sified efforts. We must impartially explore all fields, we must encourage,
organize and coordinate unhampered.biological research. We must maintain a
continuity which best assures full integration of all the data and informa-
tion Which may be developed. Once we gird ourselves to the task and pursue
relentlessly all approaches, these fundamental corner stones will be un-
ocvered and the solution we seek will not be denied us.
END OF DOCUMENT

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