The Human Plutonium Injection Experiments

had been diagnosed with oral lesions, necroses of the jaw, and anemia, died early

and painful deaths.

That ominous coincidence prompted a very quiet, factory-management-sponsored

investigation in 1924.  In 1925, a second (though this time not so quiet) investiga-

tion was conducted by Dr. E. L. Hoffman, a physician working on behalf of the

New Jersey Consumers’ League.   Hoffman suggested that the deaths signaled a

new occupational disease probably caused by the radioactive materials in the paint.

Dr. Harrison S. Martland, the local county’s chief medical examiner, began an in-

dependent investigation of Hoffman’s hypothesis.  He examined two young dial

painters with jaw necrosis and severe anemia, and when they died some months

later, Martland performed the autopsies.  He found radioactivity in both bodies.

Martland also discovered radioactivity in the body of a company physicist who

died at about the same time.  He studied five other patients with symptoms of jaw

necrosis and anemia, and based on the detection of radon gas (a decay product of

radium) in their breath, diagnosed them as probably having the new disease.  The

findings of the three investigations were published in 1925, and all came to the

same conclusion:  The ingestion of radioactive materials in the luminous paint was

the probable cause of a new type of occupational poisoning.  Although the diagno-

sis and the conclusion were initially resisted by company members and others,

more deaths quickly confirmed that the cause of the disease was poisoning by ei-

ther the inhalation or ingestion of radium compounds.  The habit of licking the

brushes was forbidden, and other practices at the dial-painting plants were suffi-

ciently modified such that very few new cases of occupational radium poisoning

occurred after 1930.

Dr. Martland, in his 1925 paper, was correctly able to outline the origin, symp-

toms, and pathology of radium poisoning.  Unlike ordinary poisons, such as ar-

senic, which impair or kill an organism through chemical action, radium causes in-

jury through its radioactivity.  Most of the radiation emitted is in the form of

energetic alpha particles.  In living tissue, alpha particles typically travel about 50

microns, or about 5 to 10 cell diameters, and deposit their energy within the cells

The Human Plutonium Injection Experiments

228

Los Alamos Science Number 23  1995

Young women in the radium-dial

painting industry in the 1920s.

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through ionization processes.  The resulting damage can result either in direct cel-

lular death (necrosis), or possibly in the generation of genetic mutations that initi-

ate the development of cancer or tumor formation.  (Alpha particles are not much

of a biomedical threat if the radium or other radioactive source is outside the body.

Barriers such as our clothing or the outer dead layers of our skin are effective

shields against alpha bombardment.)  When radium is ingested, the majority of

material is rapidly excreted.  However, since radium is chemically similar to calci-

um, a significant fraction is absorbed into the bloodstream and deposited mainly in

the skeleton.  The amount that remains within the body is called the “body bur-

den,” and it is effectively an internal radiation source.  The continual alpha-parti-

cle bombardment of the bone-forming and blood-forming cells evidently caused

the severe bone lesions and anemias seen in the dial painters.

In a 1929 paper, Martland observed that the cases of radium poisoning fell into

two distinct groups: those acute cases in which symptoms appeared relatively soon

after the exposure and ended in a rapid death and those cases in which the disease

seemed to follow a much slower course.  In the first group, later designated as

cases of acute radium poisoning, the patients exhibited severe necrosis of the jaw

bone, osteomyelitis (inflammation of the bone), crippling lesions of the bone, and

severe anemia and leukopenia (depletion of white blood cells).  Patients exhibited

those symptoms anywhere from 1 to 7 years after having worked steadily in the

industry for at least one year, and death came within months of the appearance of

the symptoms.  Acute radium poisoning was associated with body burdens (mostly

deposited in the skeleton) of from 10 to 100 micrograms of radium and mesothori-

um.  The body burdens of those fatal cases were estimated in rather rough fashion

during post-mortem examinations.

The second group of patients, followed by Martland and other colleagues well into

the 1950s, were identified as suffering from chronic radium poisoning.  Those dial

painters appeared to be in good health for about 5 to 15 years after exposure.

During that time, however, they were harboring a silent, slowly progressing bone

necrosis that would lead to rarefactions, holes, and mineralization within the skele-

tal system.  The frank clinical symptoms that eventually appeared included the

loosening of the teeth, followed by infection of the jaw bones, pathological bone

fractures that occurred spontaneously or as a result of trauma, that healed very

slowly, and that produced bony deformities, and finally cancers of the bone and

adjacent structures.  The cancers appeared anywhere from 12 to 23 years after ex-

posure and were very often fatal.  Those that suffered chronic radium poisoning

were found to have residual body burdens of radium between about 0.7 and 23 mi-

crograms, which was much lower, on average, than those associated with acute ra-

dium poisoning.  

In the late 1920s the diagnosis of radium poisoning was done by Martland and

others on the basis of the detection of radioactive gases, either radon (radon-222)

or thoron (radon-220), in the breath of patients.  Those inert gases are produced in

the skeleton by the decay of radium-226 and radium-228 (mesothorium), respec-

tively (see “Radium and Mesothorium”).  From the bone, the gases diffuse into the

bloodstream where they are transported to the lung and exhaled.  Martland used

his measurements of radioactive gases as a sort of flag that indicated whether or

not a patient had been internally exposed to radium.  He did not use this method

to quantitatively assess the amount of radium inside the patient.

A sensitive quantitative means for measuring the radium body burden was not de-

veloped until Robley D. Evans entered the nascent field of radium toxicology.  In

The Human Plutonium Injection Experiments

Number 23  1995  Los Alamos Science  

229

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1932, Evans was a graduate student in physics under the famous Robert Millikan

at Caltech.  His thesis work involved, among other things, the development of

highly sensitive accurate techniques for measuring radium and radon in geophysi-

cal samples.  Following the scandal associated with Eben Byers’ death, a repre-

sentative from the Los Angeles County Health Department, inquiring about how

to prevent such occurrences in California, was referred to Evans.

Evans became interested in the uptake, metabolism, and excretion of radium in liv-

ing persons and realized that the key to studying those problems would be the

ability to accurately measure the amount of radium present in the living body.

However, the alpha particles emitted by radium are only weakly penetrating and

cannot be used to measure the radium body burden; they simply do not make it

out of the body.  Therefore, Evans’ idea was to measure what became known as

the in vivo body burden by an indirect approach.  Instead of measuring the alpha

particles from radium, Evans would make measurements pertaining to three of the

daughter products of radium (see “In Vivo Measurements of Radium”).  Evans de-

veloped the technique in 1934 at MIT.  It was many times more sensitive than pre-

vious techniques, allowing measurement of body burdens as small as 0.1 micro-

gram.  It was also easy to apply and was eventually used by all those involved in

clinical studies of radium poisoning, including, of course, Dr. Martland.

Toward the end of 1940, the United States was gearing up for World War II, and

radium-dial instruments were being produced in large quantities.  Evans was again

approached, this time by the U.S. Navy, about the subject of radium standards.  (It

is said that a captain in the Navy Medical Corps paid Evans a visit and insisted

that he either provide the Navy with safety standards for radium-dial painters or

face being inducted into the service where he would be forced to produce them.)

Evans became part of nine-member committee formed by the National Bureau of

Standards.  Also on that committee were Martland and two other researchers who

had done quantitative work on radium toxicity.

By February 1941, the committee had collected accurate information on the resid-

ual body burdens of 27 persons as well as their state of health.  The 20 persons

with radium body burdens in the range of 1.2 to 23 microcuries of activity, or 1.2

to 23 micrograms by weight (by definition, 1 gram of radium has an activity of 1

The Human Plutonium Injection Experiments

230

Los Alamos Science Number 23  1995

Robley Evans in his

laboratory at MIT.

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The Human Plutonium Injection Experiments

Number 23  1995  Los Alamos Science  

231

In Vivo Measurements of Radium

The technique by which Evans measured the

in vivo radium body burden required

two measurements, one involving the rate at which radon is expired in the breath

and another involving the intensity of gamma rays emitted from the body.  Togeth-

er, these two measurements provided all the information that was needed to deter-

mine the amount of radium in a patient’s body.  

Radon, the first daughter of radium, is an inert gas.  As such, it tends to diffuse

from the skeleton into the bloodstream where it is transported to the lung and ex-

haled.  Since one gram of radium is known to produce 2.1

3

10

-6

curies of radon

per second, the rate of radon exhalation can be used to measure the amount of

radium in the body that produces the expired radon.  Evans therefore developed a

precise version of Martland’s "breathalyzer test" to make an accurate measure-

ment of the rate at which radon is exhaled.   Exhaled air was collected and its

radon content determined in an ionization chamber by measuring the alpha emis-

sions from the radon decay.

That technique only measured a fraction of the body burden because some of the

radon decayed before it could be exhaled.  To determine the total body burden, a

second measurement was necessary.  Evans had to look farther down the decay

chain of radium, past radon, to two gamma-emitting radioisotopes, lead-214 and

bismuth-214.  Because gamma rays are penetrating, they are easily detected out-

side the body.  Evans used a “homemade, copper-screen-cathode” Geiger-Müller

counter to measure the intensity of the gamma-ray emissions from the whole body

and then worked backwards to determine the amount of radium required to pro-

duce that intensity.  By adding the results of Evans’ two measurements, the total

in vivo radium body burden was deduced.

The photograph above shows the

breathalyzer test used by Evans to

measure the amount of radon being ex-

haled per second.  That amount turned

out to be about 50 per cent of the total

radon produced per second and thus

reflected about 50 per cent of the total

radium body burden.

The photograph at left illustrates the

“meter-arc” method for measuring the

fraction of the radium body burden that

could not be determined from the

radon test shown above.  The body of

the radium patient was positioned

along an arc so that the gamma-ray de-

tector was about 1 meter from the fore-

head, shoulder, abdomen, knees, and

toes.  The detector measured the

gamma rays emanating from the pa-

tient’s body.  Those gamma rays were

produced by lead-214 and bismuth-214,

radioiosotopes located below radon in

the radium decay chain.  Thus, they

originated from radon that decayed be-

fore reaching the lungs.

---

curie), showed various degrees of injury, whereas the 7 persons with body burdens

less than 0.5 microcurie showed no ill effects at all.  Evans proposed to the com-

mittee that the tolerance level for the radium body burden in radium-dial painters

be set "at such a level that we would feel perfectly comfortable if our own wife or

daughter were the subject."  With that thought in mind, the nine members unani-

mously decided to set the tolerance level at a factor of 10 below the level at which

effects were seen, or 0.1 microcurie.  On May 2, 1941, the standard for radium-

226 was adopted in the National Bureau of Standards Handbook, seven months

before Pearl Harbor and two months after the then secret discovery of plutonium.

Although the tolerance level of 0.1 microcurie was based on residual body burdens

measured 15 to 20 years after intake, in practice it was used as the maximum per-

missible body burden at the time of intake.  The initial body burdens of the sub-

jects in Evans’ study were typically about 10 to 100 times larger than the residual

burdens he measured.  Therefore, an additional safety factor of about 10 to 100

was built into the standard.   In 1981, 40 years after the standard was set, Evans

reported that no exception to the standard had been found among some 2000 ob-

served radium patients.  That is, no symptoms were ever observed for persons

with body burdens of 0.1 microgram or less.  That conclusions still holds today.

In 1944, when plutonium began to be produced in kilogram quantities, the experi-

ences with radium forewarned scientists about plutonium’s probable toxic effects

and provided an essential quantitative basis for the creation of a plutonium stan-

dard.  Robert Stone, the head of the Plutonium Project Health Division, made the

earliest estimate of a permissible burden for plutonium by scaling the radium stan-

dard on the basis of the radiological differences between radium and plutonium.

Those included the difference in their radioactivities and that of their daughters

and the difference in the average energy of their alpha particles.  The result indi-

cated that, gram for gram, plutonium was a factor of 50 less toxic than radium,

and the standard was set to 5 micrograms.  

In July 1945, Wright Langham insisted that the 5-microgram standard be reduced

by a factor of 5 on the basis of animal experiments that showed that plutonium was

distributed in the bone differently, and more dangerously, than radium.  Thus, the

maximum permissible body burden for plutonium was set at 1 microgram.  That

limit was chosen to protect plutonium workers from the disasters that had befallen

the radium-dial painters.  As part of the effort to understand how to measure the

plutonium body burden in living persons and to remove them from work if the bur-

den got close to the limit, the human plutonium-injection experiments were carried

out.  (The story of those experiments is told in “The Human Plutonium Injection

Experiments.”)

Following those experiments, discussions at the Chalk River Conferences in On-

tario, Canada, (1949 to 1953) led to further reductions in the plutonium standard

to 0.65 micrograms, or 40 nanocuries, for a maximum permissible body burden.

Since then, no further changes have been made, in part because no ill effects from

plutonium have been observed in any exposed individual with the exception of one

person—an individual with a body burden around the permissible level who died

of a rare bone cancer that possibly was caused by plutonium.  

As stated in the introduction, there is a dirth of information about the risks of plu-

tonium.  Consequently, the risks for plutonium-induced cancer of the bone, liver,

and lung are based on the human data gathered for radium, radon, and thorium, re-

spectively.  The data gathered for radium-induced cancers (see Figure 2) are very

The Human Plutonium Injection Experiments

232

Los Alamos Science Number 23  1995

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interesting in that they appear to

have a threshold—no bone cancers

exist below a cumulative skeletal

dose of 1000 rad, or 20,000 rem,

which would be the 50-year dose

from a body burden of about 2 mi-

crocuries per kilogram of body

weight.  This is the best data avail-

able on the induction of cancer from

a bone-seeking alpha-emitter, and so

it is natural to suspect that similar

threshold-like behavior may exist for

plutonium.  Fortunately for those

who work with it, the truth of that

conjecture may never be determined.

 

Further Readings

Harrison S. Martland, M.D.  1929.  Occupational poisoning in manufacture of luminous watch dials:

general review of hazard caused by ingestion of luminous paint, with especial reference to the New Jer-

sey cases.  Journal of the American Medical Association 92: 466-473, 552-559.

Robley D Evans.  1943.  Protection of radium dial workers and radiologists from injury by radium.

The Journal of Industrial Hygiene and Toxicology 25, no. 7: 253-274.

Joseph C. Aub, Robeley D. Evans, Louis H. Hempelmann, and Harrison S. Martland.  1952.  The late

effects of internally-deposited radioactive materials in man.  Reprinted in Medicine 31, no. 3: 221-329.

Robley D. Evans.  1962.  Remarks on the maximum permissible deposition of plutonium in man, and

the safety factors in the pivot point radiation protection guide of O.1 

µ

C of radium in man.  Health

Physics 8: 751-752.

Robley D. Evans.  1981.  Inception of standards for internal emitters, radon, and radium.  Health

Physics 41, no. 3: 437-448.

Richard F. Mould.  1993.  A Century of X-rays and Radioactivity in Medicine with Emphasis on Photo-

graphic Records of the Early Years.  Bristol and Philadelphia: Institute of Physics Publishing.

Roger M. Macklis.  1993.  The great radium scandal.  Scientific American, August 1993.

William A. Mills.  1994.  Estimates of human cancer risks associated with internally deposited radionu-

clides.  In Internal Radiation Dosimetry: Health Physics Society 1994 Summer School, edited by Otto

G. Raabe. Madison, Wisconsin: Medical Physics Publishing.

Susan Quinn.  1995.  Marie Curie: A Life.  Simon & Schuster.

The Human Plutonium Injection Experiments

Number 23  1995  Los Alamos Science  

233

Figure 2.  Radium-induced 

Cancers

This plot, as originally presented in a

1974 article by Robley Evans, shows

radiation dose versus incidence of radi-

ation-induced bone and head carcino-

mas in over 600 radium cases studied

at MIT.  The plot suggests a threshold

of 1000 rad, or 20,000 rem, to the skele-

ton for the induction of bone and head

cancers.  Because the latency period

seems to increase with decreasing

dose, Evans suggested that this result

be interpreted as a “practical thresh-

old”—at lower doses the latency period

might be longer than the lifetime  of

the individual so that malignancies

never become manifest.  Evans’ idea of

a practical threshold is still considered

viable, although two cases of bone

cancer with doses below 1000 rad have

appeared in a cohort of 4000 individu-

als exposed to radium (see “Radiation

and Risk,” pages 100-101).

0

1

10

100

1000

Cumulative dose (rad)

10000

100000

10

20

30

40

50

60

70

Cumulative tumor incidence (per cent)

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Document Outline

• The Manhattan Project and Its Need for Plutonium
• Worries About the Health Hazards of Plutonium
• Working With Plutonium
• Plutonium Animal Studies
• Planning for the Human Injection Studies
• The First Human Experiments with Plutonium
• Further Human Plutonium Injection Experiments
• Results of the Injection Experiments
• Changes in the Maximum Permissible Body Burden
• Additional Data from the Plutonium Patients
• A Recent Analysis of the Excretion Data
• Implications of the Plutonium Injection Studies
• Acknowledgements
• Further Reading
• Sidebars
  • The Making of Plutonium-239
  • Manhattan Pr oject Sites In volv ed with Human Plutonium Injection Experiments
  • The Medical Researchers
  • A Swallow of Plutonium
  • Detection of Internal Plutonium
  • Polonium Human-Injection Experiments
  • A Cross-Check of Analytical Procedures
  • Louis H. Hempelmann—1914-1993
  • Estimating Effects of the Injection Dose
  • Wright Haskell Langham—1911-1972
  • Consent in the Human Plutonium Injection Experiments
  • A Computer Analysis of Plutonium Excretion
  • Radium–the Benchmark for Internal Alpha Emitters
    • Radium and Mesothorium
    • In Vivo Measurements of Radium
    • Further Readings