Radiation Hormesis

Hormesis . . . what an interesting word. What does it mean?
Hormesis is both a term and a phenomenon. Rooted in the Greek language, it can be translated into "excite" or "stimulate", referring to the stimulatory effect of various agents on living organisms. This stimulation is often equated with a "beneficial" effect, although as we will see later that this is not necessarily so. In fact, it is extensively argued when it comes to our favorite topic - radiation.

Where did the term originate?
It appears the term "hormesis" itself arose in the 1940's after two scientists reported that the growth of fungi were stimulated at low concentrations by a certain substance. Of course, many hormetic-type responses were noted prior to 1940 without the benefit of the term to describe their findings!

Why is a discussion of this topic so important when we talk about radiation and radioactivity?
The reason is quite simple - it offers a counter argument to the linear, no threshold dose hypothesis or "LNT" and associated "As Low As Reasonably Achievable" (ALARA) philosophy described in other sections of this chapter on "Radiation Risks". Both LNT and ALARA are a fundamental principle in today's practice of radiation protection; we base our programs on the assumption that no dose, no matter how small, can be considered absolutely "safe".

Well now, this sounds like a really interesting topic. Where should we start?
First, be aware that while this topic is devoted to radiation hormesis, this need not be so. Stimulatory effects can also be found in other (i.e., chemical, toxicological, and pharmacological) agents that, when delivered in low quantities, might excite or stimulate physiological processes.

Okay. But I notice you mentioned "low" quantities.
You bet! It appears that many agents stimulate living biological systems at low "doses", but once a certain threshold is reached, detrimental effects begin to appear. One good example is plain ‘ole water. Water, in moderate amounts, is healthy and is needed by the body. However, excessive ingestion can have harmful or even fatal consequences.

So radiation hormesis specifically refers to what?
Well, as described in Dr. Daniel Gollnick's textbook, Basic Radiation Protection Technology (3rd edition), it refers to the "production of any physiological effect of radiation which is observed at low radiation doses which cannot be expected based on extrapolation downward from the toxic effects of high doses".

That's nice. Now could you please translate Dr. Gollnick's statement?
Certainly. He is simply saying that harmful effects occur at high doses of radiation, a known fact, and that extrapolation from these high doses to "zero" dose still infers at least the potential for detrimental effects. Therefore, any effects observed at low doses that run counter to this expectation indicate a hormetic response is present. Put another way, hormesis can be described as a process whereby low doses of an otherwise harmful agent (radiation!) could result in stimulatory or beneficial effects.

And what effects would that be?
Three particular effects have been presented in the literature.  These are increased life span; increased growth and fertility; and a reduction in cancer incidence.

So can we conclude that radiation is essential for health?
It is a bit premature to state that radiation is absolutely required for good health, but there is no reason to believe that it could not be. Therefore, in concert with a discussion of hormesis, the concept of a radiation "deficiency" must be mentioned.

Excuse me?
Just as vitamins are taken by many people to promote good health, the argument can be made that some small amount of radiation is required on a consistent basis to also ensure good health. This argument has in fact been made by hormesis proponents time and time again. And if that small amount of radiation exposure is not provided (i.e., a deficiency), ill health could result until the radiation exposure is restored!

I understand that according to the linear hypothesis, the relationship between dose and effect at high doses is extrapolated down to "zero" without the existence of a threshold. With that in mind, what would a graph of a hormetic response would look like?
First, remember that a typical dose response curve will be labeled as "harmful effects" (or something similar) on the "Y axis" (vertical axis) while the radiation dose will increase along the "X axis" (horizontal axis). So according to the LNT hypothesis, as the dose increments along the X axis, the harmful effect or risk, increases proportionally. In other words, for every unit increase along the X axis, a unit increase in risk results.

Okay. I have the picture. Now what would the hormetic graph look like?
In a hormetic response, instead of progressing in the "up" direction along the Y axis (harmful effects), head in the opposite or "down" direction, labeling that part of the Y axis "beneficial effects". As the dose initially increases from zero, the data are plotted below the X axis in the beneficial region. As the dose continues to increase, the beneficial effect diminishes, demonstrated by watching the dose response curve head back up and then landing directly on the x-axis.

What if the dose keeps going up? Then what?
Increasing the dose any further is considered the start of the harmful effects region.

As you described it, it looks like a threshold exists before harmful effects or an increased risk appears. Am I right?
You are exactly right! Negative effects do not begin at zero dose, but will occur at some other point along the curve. In between zero and this dose, whatever it might be, is where a hormetic response occurs.

I think I understand the curve you just described, but where could I go to see such a curve?
Check out Dr. Gollnick's text; the one I described to you previously. In his third edition, Figure 17 on page 110 shows a linear and a hormetic response curve.

Is there another way to describe the dose response relationship for hormesis?
Yes. Let's assume that a control population starts with a radiation deficiency of zero or 100%, meaning that population is receiving "just enough" radiation exposure. As the dose to that population increases, any hormetic responses will result in a stimulation or health benefit values that are greater than 100%. So a value of 130%, for example, as plotted on a curve, means there has been a 30% stimulation, or a 30% healthier population.

Ok. But didn't you say this can't last forever?
That's right. As the dose continues to increase, the shape of the curve starts back heading downward again . . . toward the 100% control setting. And if it continues down, it drops below the 100% benchmark, resulting in a radiation deficiency.

Is there a term to describe when the curve rests right on the 100% mark?
As a matter of fact there is. You might hear specialists in radiation-related health effects call this the "zero equivalence point" or "ZEP". This is an impressive, and somewhat fun-sounding acronym, but it means nothing more than the point when you have neither a stimulation nor a deficiency. You are simply equal with the "control".

Once again, I think I follow you, but does Dr. Gollnick's book describe this curve as well?
He sure does! Again, citing the third edition, be sure to take a look at the hormetic response curve in Figure 15 on page 107.

Just about everything I read in the newspapers emphasizes the negative aspects of radiation exposures. Why is hormesis never mentioned in those articles?
For now, anyway, the International Commission on Radiological Protection (ICRP), the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), and other bodies are not terribly interested in the lack of radiological harm observed, for example, in high natural background regions of the world such as Ramsar, Iran or the Kerala region of India. (People living in these parts of the world receive radiation exposures that are 10 or more times higher than the average member of the U.S. population!) They also don't seem to be paying attention to the possible inverse relationship between household radon exposures and lung cancer to name another. In part, this is due to what they claim to be a lack of data justifying its adoption.

Well, that seems fair, doesn't it?
There is no doubt that accepting hormesis after several decades of adopting the LNT hypothesis would require a true "leap of faith" by these scientific groups and certainly by the regulatory agencies that review and typically adopt their recommendations. It is definitely reasonable to assume that that "leap of faith" would only occur after extensive and credible scientific evidence was forthcoming.. In fact, Dr. Bernard L. Cohen, in his May, 1987 paper entitled "Tests of the Linear, No-Threshold Dose-Response Relationship for High-LET Radiation", which appeared in the Health Physics Society Journal, said it a bit differently. Dr. Cohen stated that"Failure of the linear, no threshold theory is a necessary condition before hormesis can be accepted."

Tell me more about why there is a lack of interest in and acceptance of radiation hormesis by the scientific community.
Okay. Let's go back a ways to a paper entitled "Radiation hormesis: the demise of a legitimate hypothesis", written in the journal "Human and Experimental Toxicology" in the year 2000. According to the authors, there are several reasons leading to the lack of acceptance of hormesis. In brief, these include a lack of agreement on how to define the concept of hormesis and how to, quantitatively, describe its dose response curve. Another reason is a general lack of acceptance by radiation scientists regarding the concept of chemical hormesis, which is more advanced, substantiated, and generalized than in the radiation domain. A third reason is that there is so much criticism of low dose stimulatory effects that research opportunities are hard to come by. A fourth reason is the on-going criticism of the hormetic concept by leading scientists who were active in the 1930's. There is also the failure of a poorly-designed U. S. Department of Agriculture experiment in the late 1940's for researching low-dose plant stimulation using radiation . . . that experiment failed to support the hormetic hypothesis. Put all of this in the context of the general public's steadily-growing fear of radiation, and there you have it; no real urgency to pursue radiation hormesis and its incorporation into radiation safety programs.

What kinds of things are the scientific agencies actually saying?
A good example of what I mean is what ICRP said on page 12 of its 1990 recommendations (Report No. 60). The conclusion was: "There is some experimental evidence that radiation can act to stimulate a variety of cellular functions, including proliferation and repair. Such stimulation is not necessarily beneficial......Most of the experimental data on such effects, currently termed "hormesis", have been inconclusive, mainly because of statistical difficulties at low doses. Furthermore, many relate to biological endpoints other than cancer or hereditary effects. The available data on hormesis are not sufficient to take them into account in radiological protection."

Well, I'd like to keep an open mind nonetheless. What argument can be made that radiation is perhaps beneficial to life?
The argument goes something like this. Go back in time to approximately four billion years ago when all living things were "immersed" in a natural radiation environment approximately five times higher than it is now. Radioactive decay processes are responsible for the fact that the natural radiation background has reduced in intensity over time.

Why was there a radiation environment?
Why exactly! Perhaps radiation was actually necessary for life!

What do you mean?
During this early time, it has been postulated that organisms developed powerful defense mechanisms against adverse radiation-related health effects, such as mutations and malignant changes - effects originating in the cell nucleus, where DNA is their primary target.

So our bodies are capable of coping with low levels of ionizing radiation exposure?
Absolutely.

Okay, but how realistic is this postulate?
Bear with me now. According to one researcher, exposures to natural radiation sources, which you know by now can vary substantially in magnitude all over the world, results in as much as 1000 DNA damaging "events" in each cell per year. However, he goes on to say that by comparison, every mammalian cell suffers about 70 million spontaneous DNA damages per year, caused by non-radiation events such as aggressive "free radicals" formed by the metabolism of oxygen.

So?
Proponents of hormesis claim that the defense system mentioned above is required in order to permit a living organism the ability to survive a high rate of DNA damage. To continue the argument, the fact that evolution proceeded for so long is proof, in their view, of the effectiveness of living things' defenses against spontaneous DNA damages - and also against natural doses of radiation.

And what is the conclusion?
Low-dose radiation stimulates this defense system, resulting in fewer metabolic mutations, less cancers, and increased longevity. This stimulation is radiation hormesis. The defense system maintains the integrity of organisms not only during its lifetime, but for thousands of generations. If this system were absent, we all would die of cancer in the first few months of life, or be crippled by hereditary changes . . . or so the theory goes.

So how does hormesis impact cancer rates?
Epidemiological evidence that radiation hormesis decreases cancer incidence and mortality originates from several sources, including Hiroshima and Nagasaki A-bomb survivor studies, inhabitants of regions with high natural radiation, and from studies involving the effects of/from: residential radon, medical exposures, occupational radiation exposures, and the inhabitants near the Techa river, in the Ural Mountains where there was significant radiological contamination as a result of the Soviet Union's nuclear weapon's legacy.

Well, that's interesting. Are there any others?
An interesting one is the Department of Energy study entitled"Health effects of low-level radiation in shipyard workers" by Professor G.M. Matanoski of the Johns Hopkins School of Public Health in Baltimore, Md. Professor Matanoski's report indicated that nuclear shipyard workers had a significantly lower cancer death rate than non-nuclear workers and much better general health. The death rate from all causes for the nuclear worker population was much lower than the death rate from all causes for non-nuclear workers. This improved health is hypothesized to have been due to stimulation of the immune system by the increased radiation.

Wow. Is that all?
No its not. Scientific evidence for improved health from high natural radiation was also shown in a recent study published in the Health Physics Journal entitled "Natural Background Radiation and Cancer Death in Rocky Mountain and Gulf Coast States". In brief, the cancer death rates in three mountain states with high natural radiation exposure rates were compared to the cancer death rates in three gulf states with only one-third of those rates. The authors found that the cancer death rate was about 25 percent lower in the mountain states. Once again, the implication is that the increased cancer death rate in the gulf states is due to a radiation "deficiency".

Well, that certainly makes a good case for hormesis, doesn't it?
Well, we need to be careful here before jumping completely on the hormesis bandwagon. Each of the studies we just talked about may well have scientific merits. But the data and the accompanying findings are still being subject to scientific scrutiny by proponents and detractors of hormesis alike - as well they should be. We should also point out that evaluating epidemiological data can be tedious and difficult, at best. The findings of these studies are always subject to interpretation! Accordingly, there are individuals in the scientific community who might reach an entirely different conclusion by making very minor and seemingly inconsequential modifications to the evaluation parameters.

Is there a super-star in the hormesis research business?
I don't know if I would call him a super-star, but if we were to choose one individual, it would have to be a gentleman by the name of T.D. Luckey. This researcher is credited with making radiation hormesis a very well known term. As a professor at the University of Missouri, Columbia for many years, Dr. Luckey researched and documented stimulatory effects over an 80-year period in plants, as well as in an incredibly diverse collection of aquatic and terrestrial animals.

He sounds like quite a guy.
He is. In fact, the May, 1987 edition of the Health Physics Journal was devoted to a "Special Issue on Radiation Hormesis". One of the papers, "Radiation Hormesis in Plants", described enhanced plant growth through radiation stimulation. Included were references to Dr. Luckey and a host of examples from his work, along with approximately 200 additional studies.

Okay, that is for plants. What about for animal populations?
In December of 1982, in another Health Physics Journal article, Dr. Luckey described a variety of stimulatory effects involving growth and development, fecundity (ability to produce offspring), health, and increased lifespans for animals. Specific improvements included neurological function, growth rate, survival of young, wound healing, immune competence, and resistance to infection, radiation morbidity (radiation sickness), and tumor induction and growth.

And do you have a favorite example?
As a matter of fact, I do. An IEM staff member, while conducting his graduate research on the "The Effects of Acute Ionizing Radiation on the Hormetic Response in Daphnia Magna", made some interesting observations. However, to our knowledge, Dr. Luckey is not aware of the work of this struggling student!

Maybe he should be. What was the experiment about?
Let me give you some background information first. Daphnia magna is an aquatic animal whose population consists almost entirely of females. Interestingly, males are not required for reproduction. Females produce eggs in a transparent pouch found on the top of their bodies. The eggs develop into young and are released from the mother approximately every three days. In the study, females were irradiated with gamma rays from a Cobalt-60 source, to total doses of 250, 500, 1000, 2000, and 5000 rads. Each brood of young was watched carefully so that the effects of the radiation exposure could be determined and documented.

What did the IEM staffer find out?
Relative to the "control" population, which received no radiation dose other than that from the ambient background, increased lifespan, reproduction, and survival were noted in all of the dose groups except for those irradiated to 2000 and 5000 rads. At those higher doses, detrimental effects began to appear including reduced lifespan and aborted young.

Wow. Its great to hear about a first-hand experience. Where can I find additional information on hormesis?
There are in fact many avenues to pursue on this interesting and really timely topic. For starters, check out some of the Health Physics Journal articles we just talked about, but pay particular attention to the references. And don't forget to check out that special edition of the Journal devoted entirely to the topic of radiation hormesis. It is in Volume 52, Number 5, published in May, 1987.

What about on-line resources?
There are a number of them as well. For example, the website http://www.stockton-press.co.uk/het/ contains several very worthwhile articles taken from the January, 2000 issue of Human & Experimental Toxicology Journal. This was a special issue on chemical and radiation hormesis. In fact, if you click on the "Free Online Sample Copy" link, all of the articles can be downloaded in PDF format. There is also the Biological Effects of Low-Level Exposure (BELLE) website at http://www.belleonline.com/, where there are several newsletters devoted to hormesis.

What if I want to know more about Dr. Luckey's work?
Then you definitely need to read his book, Radiation Hormesis, published by the CRC Press in 1981. In addition, be sure to review two of his papers: "Hormesis from ionizing radiation," in the 1984 edition of the Health Physics Journal, and "Physiological benefits from ionizing radiation" that appeared in the 1982 edition of the Journal.

You bet I will. Do you have any final thoughts?
I guess when it comes to hormesis, there are few "fence straddlers". There are strong advocates for and against it. At the moment, those in favor are in the minority, but that doesn't stop them from letting you know how they feel! While not a common occurrence by any means, you may even happen along an article or two in your local newspaper. For example, Dr. John Cameron had an article in the January 28, 2000 edition of the Georgia Morning News entitled"Low-level radiation is healthy". In that article, Dr. Cameron stated that "Radiation is an essential trace energy for improved health". Definitely a strong stand on the topic!

It sure sounds like he doesn't pull any punches.
No he doesn't. However, gradually accepting, let alone "embracing" the hormetic response requires an "open mind" for those not acquainted with the possibility that radiation may actually have beneficial aspects to it. You already know that it does, because you have read other chapters in this "Radioactivity Basics" section of the IEM web page and you are aware of the fact that, at least in the medical arena, radiation and radioactivity is helping us win the war against cancer.

You're right. There are number of beneficial and life-saving uses of radiation that you have told me about. Its too bad we can't be more open to the possibility of hormesis.
Perhaps Dr. Leonard Sagan, a noted scientist and active supporter and a contributor to that special edition of the Health Physics Journal stated it best. Hormesis, according to Dr. Sagan, is not presently accepted because it does not fit the widely held beliefs that 1) radiation exposure is harmful; 2) radiation exposure is harmful at all levels; and 3) there are no effects at low doses which cannot be predicted from effects noted at high-dose levels. Until we climb these hurdles, radiation hormesis will not factor into the way in which we design and implement radiation protection programs.

I see what you mean. Thanks for the information.
You're welcome. You might want to re-visit the other two "Radioactivity Basics" sections on the ALARA concept and the LNT hypothesis, in light of what you now know about hormesis. And stay tuned for new developments in this fascinating yet controversial radiation-related concept.

I can't wait.
Neither can I!

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