Hormesis - A little radiation may be a good thing

Last Thursday, my wife and I gave a presentation to the new students in the Honors College at WSU on the common reading book, Physics for Future Presidents. One large chunk of the book discusses nuclear power and its risks. When extrapolating to low dose, the author is careful to always state "assuming the linear hypothesis."

This got me thinking about an article in Scientific American that I read back in 2003 on the topic of Hormesis. The idea is that toxins might actually be beneficial when taken in low doses. As an example of Hormesis, exercise wreaks all sorts of havoc on the cellular level, but is healthy in moderation. The explanation is that the body's response in repairing the damage does some good that goes beyond the status quo. At higher levels of exposure, the body cannot keep up with the damage, and toxic effects become - well, toxic.

The red curve in the figure shows the linear hypothesis; the toxicity of a toxin, quantified in terms of the death rate, increases with dose. Hormesis, shown in green, yields a benefit at low exposure levels. Serious scientific studies are finding a hormesis response in many toxicological studies.

Hormesis may describe the effect of ionizing radiation on living creatures such as humans (see the references below). Karl Grossman furiously protests on the anti-Nuke website NuclearFREEPlanet.org. He sees these studies as an obvious ploy by nuclear scientists to pollute the planet, "These scientists don't just want to minimize or even flatly deny the deadly impacts of radioactivity - they want people to think it's healthy." What if it is actually healthy?

Our presentation to the students of the Honors college focused on the notion that decisions that are made based on the facts have better outcomes when not clouded by ideology. We should not bash science just because its conclusions weaken those arguments that support our beliefs.

My point in using this example is not to be an advocate for nuclear energy, nor is it to support the hormesis hypothesis. Rather, it is to illustrate the pitfalls of clinging to an ideology. If the best evidence shows that low levels of radiation is safe and potentially beneficial, then why not loosen standards to reflect the best science?

Some readers may find these arguments reminiscent of the homeopathy hypothesis, that ingesting toxins at levels of zero concentration can cure various ailments. There is absolutely no evidence for homeopathic effects. Wikipedia devotes a page to Jacques Benveniste, who purported to observe such effects (published in the prestigious journal Nature), but whose work has been discredited many times since (blue dot in the figure). A site visit by a team assembled by the editors of Nature at the time of the report in 1988 found serious procedural problems that explained the spurious result.

Sadly, homeopathic remedies are found on the shelves of my local pharmacy and are even covered by the health plans of many countries. I would venture a guess that there is a large overlap between people who use homeopathic remedies and those who deny hormesis based on their anti-nuke sentiments. If so, they may be wrong on two counts.

At the risk of accusations of being pro nuclear, I will post some interesting statistics on radiation, and a comparison of the dangers of various energy sources including nuclear power. Until then, I encourage you to read the informative links in this post. For someone with a more serious interest, I recommend the articles in the reference list, which appear in hard-core scientific journals. If you are left with a desire to dig deeper, there are several hundred more articles on the topic. But, stay away from ideological websites, unless your aim is to feed your ideology rather than learning the truth.

Buon Pomeriggio!

References

Title: Hormesis: The dose-response revolution
Author(s): Calabrese EJ; Baldwin LA
Source: ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY Volume: 43 Pages: 175-197 DOI: 10.1146/annurev.pharmtox.43.100901.140223 Published: 2003

Title: The frequency of U-shaped dose responses in the toxicological literature
Author(s): Calabrese EJ; Baldwin LA
Source: TOXICOLOGICAL SCIENCES Volume: 62 Issue: 2 Pages: 330-338 DOI: 10.1093/toxsci/62.2.330 Published: AUG 2001

Title: Hormesis: A highly generalizable and reproducible phenomenon with important implications for risk assessment
Author(s): Calabrese EJ; Baldwin LA; Holland CD
Source: RISK ANALYSIS Volume: 19 Issue: 2 Pages: 261-281 DOI: 10.1111/j.1539-6924.1999.tb00404.x Published: APR 1999

Title: Evidence for beneficial low level radiation effects and radiation hormesis
Author(s): Feinendegen LE
Source: BRITISH JOURNAL OF RADIOLOGY Volume: 78 Issue: 925 Pages: 3-7 DOI: 10.1259/bjr/63353075 Published: JAN 2005

Title: Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity
Author(s): Cypser JR; Johnson TE
Source: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Volume: 57 Issue: 3 Pages: B109-B114 Published: MAR 200

Title: RADIATION HORMESIS - ITS EXPRESSION IN THE IMMUNE-SYSTEM
Author(s): SHU ZL; LIU WH; SUN JB
Source: HEALTH PHYSICS Volume: 52 Issue: 5 Pages: 579-583 Published: MAY 1987

Title: Exercise and hormesis: oxidative stress-related adaptation for successful aging
Author(s): Radak Z; Chung HY; Goto S
Source: BIOGERONTOLOGY Volume: 6 Issue: 1 Pages: 71-75 DOI: 10.1007/s10522-004-7386-7 Published: JAN 2005

Title: Effect of a continuous gamma irradiation at a very low dose on the life span of mice
Author(s): Caratero A; Courtade M; Bonnet L; et al.
Source: GERONTOLOGY Volume: 44 Issue: 5 Pages: 272-276 DOI: 10.1159/000022024 Published: SEP-OCT 1998

Research summary on COMPLEX MOLECULES MADE SIMPLE

A review of our work that will appear in Physical Review

COMPLEX MOLECULES MADE SIMPLE

Organic molecules are versatile and can be custom tailored for a large variety of applications that span such diverse fields as cell microscopy, cancer therapy, computing technology, or high speed communications, to cite just a few. With this high degree of flexibility comes complications. Even when a system can be reasonably approximated by two excited states, at least 7 parameters are required to predict important properties such as the nonlinear-optical response. In the present work, a combination of sum rules and symmetry constraints has been shown to allow the problem to be reduced to 3 parameters, which can be determined using two simple measurements -- the linear absorption spectrum and a measurement of the hyperpolarizability at just one one wavelength using hyper Rayleigh Scattering. This approach has been applied to the complex molecule AF455, and shown to accurately predict not only the correct shape of the two-photon absorption spectrum, but also its absolute magnitude. Here is a rare instance where two simple measurements accurately predict all the linear and nonlinear optical properties of a molecule. With complexity simplified, new paradigms for making better materials may follow.

My voice from the past

A while ago, David Bradly, a reporter from ScienceBase had contacted me about a paper from my group on self healing in a molecule called AF455. He wrote a short news piece on our work. After the piece was posted, he contacted me with additional questions. In response, I shot him an email, which he posted in its entirety. This was back in April of 2007, more than 4 years into my past.

Just 5 minutes ago, I was searching for articles related to our research and ran across my email. I tend to write emails from the top of my head, without much editing, so it was eerie to see myself in an unguarded moment. In effect, it was my own voice form the past, real and uncensored. When writing for the public, as I do in papers and proposals - and even in this blog, I choose my wording carefully, though often not with good results. While you may not notice the tone, reading this email rekindles in me the excitement of discovery that I was feeling at that time. It is better than any diary entry.

I am glad that David Bradley posted this email, which is truly a window into my past. It is reproduced below. As you may have guessed, he asked me about applications of our work.

Dear David,

The molecule AF455 is indeed complex, and that is what makes its irreversibility so puzzling. The DO11 dye, which we previously studied for reversibility is a relatively small molecule; and, the mechanisms for the recovery is the breaking up of dimers that form in the degradation process. This requires the molecules to be able to move around a bit. AF455 clearly can not move around easily, so another mechanism must be responsible.

Any device that operates at high intensity, such as lasers, displays, and all-optical switches and logic, suffer from photodegradation. Solid state lasers, for example, live longer than ion lasers and dye lasers; but, dye lasers have much more flexibility is the range of colors that are available. Polymer displays, on the other hand can be mechanically flexible and can be used to host all sorts of organic molecules. The general theme is that organic molecules have a much broader pallet of what they can do, but, they are not as stable.

So in our work, we are not so much interested in targeting specific applications. Rather, we want to understand the mechanisms for recovery since most materials degrade irreversibly. And here we have two very different molecules that behave the same way. There is one similarity. We discovered this property by accident!

If a material absorbs light strongly, it will damage when the absorbed optical power reaches the material's damage threshold. In applications where the material is transparent, light can be absorbed through a two-photon absorption process. Not as much light is absorbed in the process, but, over long-enough periods of time, cumulative effects cause the material to degrade.

Bright light can cause all sorts of things to happen in a material. If it induces a chemical reaction that causes a molecule to break apart into pieces, that process is irreversible. On the other hand, if the light causes the molecules to change shape into a form that no longer absorbs light or perhaps causes some charge to jump from one side of the molecule to the other, this change is reversible. The trick is to find materials that are not killed by the zap of laser, but that prefer to take a nap.

Another intriguing observation is that when such molecules wear out, rest, then recover many times, they seem to degrade more slowly and recover to a higher level of efficiency upon further cycling. It's like a weight lifter that gets stronger after each workout. So, it may be possible to make our molecules more buff by giving them a good workout. We observed this kind of response in the DO11 dye, but have not seen it in the AF455 dye.

So, while we see two-photon absorption (TPA) as a universal nuisance that destroys materials, and that's the motivation for our studies, there are many important applications. Two-photon absorption is strongest where the light intensity is the highest, and is ideal in applications where a chemical reaction in a material operates above a certain threshold power. The important consideration is that for absorption to occur, two photons must participate.

Cancer therapies are one such application. The patient drinks a cocktail of molecules that like to stick to a particular type of tumor cell. Also, these molecules are tailored to be strong two-photon absorbers to a color of light to which cells and flesh are transparent. Then, just aim a laser beam at the tumor right through the skin. In this way, only the tumor cells are zapped. Since the skin is not perfectly transparent, it will also absorb some of this light, causing a bit of damage. Ideally, you want to make the strength of two-photon absorption as high as possible so that the amount of damage to the tumor is as big as possible relative to the damage to healthy cells. You want the special molecules to live as long as possible so that they can be repeatedly zapped without the patient having to ingest more of the cocktail, which could have side effects.

Since TPA is a process where two photons are simultaneously absorbed, it can be used to drive chemical reactions at the intersection point of two beams of light. As an example, a liquid can be made to turn solid (i.e. polymerize) at the crossing points. In this way, a three-dimensional object can be made piece by piece inside the liquid, such as gears, shafts, and other nano-scale parts. So, it's like having the ultimate nanolab.

So, TPA is something that is simultaneously very useful in important applications; but, can be a nuisance in all applications that require the use of light. We are thinking more about ways to make a molecule snooze to help it recover rather than find more ways to put it to work. Happy dreams!

Mark

Another paper accepted, but in record time

In a recent post, I mentioned a paper that took about 4 years to get published. In contrast, we did some work that took about 3 months to complete, and today, the manuscript was accepted for publication in JOSA B.

The topic:

Testing the diffusion hypothesis as a mechanism of self-healing in Disperse orange 11 doped in PMMA

This is an important piece of work that get's us one step closer to understanding self healing in dye-doped polymers, a phenomena that was discovered in our lab a decade ago. The first comment I always get when introducing our work at scientific meetings is that the laser is heating the material, causing the dye molecules to diffuse away from the beam. When the laser is turned off, the dye molecules diffuse back. So, rather than the molecules breaking apart and then reassembling themselves, they are just moving out then into the beam - a much less sexy phenomena.

The report of one of the reviewers summarizes our results best:

This manuscript describes a combined experimental and theoretical study on the recovery of absorption in dye-doped polymer samples exposed to high light intensities. There are several possible mechanisms for such a self-healing effect and it is of significant interest to understand which one(s) contribute. The paper presents a set of experimental data on the dynamics and spatial profile of the optical properties of the damage region. It then presents a thorough and detailed model of what is expected if diffusion of undamaged dye molecules into the damaged region is responsible for all or part of the recovery. The difference between the broadened profile of the concentration predicted by the diffusion model and the constant profile shape observed experimentally is persuasive in demonstrating that diffusion is not a significant contributor to the self-healing. The manuscript is well-presented, thorough, and sound. It warrants publication in JOSA B.

Congratulations to Shiva and Nathan for a job well done!

Finally, after 4 years!

During my summer stay at the University of Leuven in 2006, I was working with my colleagues on interpreting data from new experiments using the intrinsic hyperpolarizability as a guide. That was when we discovered that modulation of conjugation was a new approach for making molecules with larger nonlinearities. It was an exciting time that eventually led to a paper that hit the internet in January 2007.

It caused quite a sensation. The morning that it appeared, I had a pile of emails in my inbox from reporters. My collaborator was even interviewed on Belgian TV. The Inquirer, a British publication, called us boffins (at first I thought it was a derogatory term). CBC News, ScienceBase, Materials World, Nature, and many others also covered the story.

In the midst of all this mayhem, we were working on another project. Who would have guessed that it would be 4 years from the initial idea until the work was finally published. I mentioned this work a while back in a post as being finally done, but as it turns out, it wasn't. We kept on finding mistakes.

While this work will most likely not get as much attention as our paper from 2007, it is perhaps a much better piece of work because it carefully shows how a combination of sum rules and symmetry can be used to reduce a complex problem into a simple one. With all of the complexity removed, it becomes easier to build an understanding of the physics underlying the phenomena that we observe. This is another paper that I rank in my top ten. I predict that this paper will get less citations than my top-40 cited papers, but those statistics are unimportant to me.

The title of the paper is Experimental verification of a self-consistent theory of the first-, second-, and third-order (non)linear optical response, by Javier Perez-Moreno, Sheng-Ting Hung, Mark G. Kuzyk, Juefei Zhou, Shiva K. Ramini, and Koen Clays. It is slated to appear in Physics Review A -- a journal I consider to be top notch. No glitz, no fancy photos, just hard core Physics.

Xavi must have been thrilled when he got the letter:

Dear Dr. Perez-Moreno,

We are pleased to inform you that your manuscript has been accepted
for publication as a Regular Article in Physical Review A.

His email to his coauthors tells it all:

After 3.5 years of revisions, I think we learned a lot about AF455 and octupoles in general, group theory, fluorescence, quantum yields; but, it has paid off. I feel very proud of this paper!

Xavi

I agree!

The scientific method and discourse

Since the announcement of a possible merger between the college of sciences (COS) and the college of liberal arts (CLA), many faculty members at our university on both sides of the divide could be heard complaining. In a mixed-party conversation, a CLA colleague vocalized concern that in a merged college, liberal arts would be strong-armed by the sciences, philistines who might not be aware of other ways of knowing.

I was curious about this seeming paradox of alternatives to the scientific method, so I asked to be enlightened. "Discourse" was offered as an example of another way of knowing. This got me thinking about scenarios where this approach might be appropriate. Perhaps an autobiography that describes the suffering of a minority could strike a cord with others who experience the same pain. Similarly, such a narrative could convey the meaning of oppression to outsiders. While the scientific method might be appropriate for studying the brain chemistry underlying emotions, it is not applicable in the human activity of communicating emotions. There is no hypothesis that is being testing, so I am fine with this concept.

Immediately after vocalizing my thoughts, my moment of clarity was yanked away by the accusation that the scientific method is clearly not always appropriate in science. Data can be misinterpreted, protocols changed after the fact, and falsity propagated by stubborn scientists who are too arrogant to change their minds. No scientist would ever claim infallibility. I felt that the accusations were extreme and did not ring true.

I was then lectured on how eastern holistic medicine such as acupuncture, long ignored or belittled by science, was now becoming accepted by western medicine, as was therapeutic touch. I was flabbergasted by this misinformation. It just ain't so! Since I could see the fruitlessness in an appeal to reason, I remained silent and changed the subject.

Sadly, health insurance companies are being strong-armed by patients who are demanding that alternative medicine be covered. When an insurance company caves, it implicitly implies that there is validity to alternative approaches when in fact, these treatments have been shown by double blind experiments to be ineffective. In the end, we all suffer as precious resources are squandered on worthless treatments.

Then there are politicians such as Senator Tom Harkin of Iowa, who have a special interest in alternative medicine and who have used their power to create a government-funded clearinghouse for Complementary and Alternative Medicine (CAM) research. As a result, The National Center for Complementary and Alternative Medicine was established, and now garners a yearly budget of $130 million. While there is a need for studies of alternative approaches that are not potentially lucrative enough for pharmaceuticals to foot the bill, the research is heavily biased by true believers who control the funding, rehashing treatments that have be shown over and over again to be ineffective.

The downside of this "research" is that it bestows the air of legitimacy. As a result, there is growing support for alternative medicine.

If this is what our comrades in CLA generally mean by other ways of knowing, then it does not belong in academics. While all new ideas deserve to be heard, ones that have been shown to be false and counterproductive need to be put to rest as a historical curiosity - a lesson in how the mind can be fooled and how we can avoid making similar errors in the future. We need to learn the difference between a closed mind and letting go of notions that are known to be false unless reliable new evidence is brought to light.

While I have been generally in support of government involvement in healthcare to insure universal coverage for all, the fact that centralization gives politicians the power to decide what is science gives me cause to reconsider my position. One may protest that government is not so capricious; but, consider that the French healthcare system covers homeopathy, an idea that is utter nonsense both in its inefficacy as established in scientific studies, as well as in the fact that its basis runs contrary to all that we know. Sadly, even private insurers are covering alternative medicine; so, both government and the private sector have failed us in optimizing health outcomes.

Once again, I am too exhausted to fight a war that long ago has been won on the battlefield of reason. For further reading, I recommend the report prepared by the Center for Inquiry, which describes the history and science of acupuncture; and Robert Park's excellent piece on alternative medicine.

Facebook censorship

I recently tried to post a photo and the quote (below) on Facebook. My post was flagged as offensive and it was immediately removed. The image appears on the right and the quote is:

"When fascism comes to America, it will be wrapped in a flag and carrying a cross” -- Sinclair Lewis

Can anyone explain to me why this is offensive?

I appealed Facebook's decision. I'll keep you posted about their reply.

Wasting time, in a good way

Today my morning started early; responding to emails at 6:30 am and an 8:00 am search committee meeting. Various other administrative tasks delayed my arrival in the lab until about 9:45am. After doing the rounds in the lab, and then signing some more paperwork in the Physics office, I made it to my desk, where I spent the rest of the morning answering emails - with a short diversion to chat with the guys fixing our sprinkler system.

After lunch, I finally got back to the task of working on Nathan's cascading paper, which incidentally, I worked on a bit last night. As I was revising text in response to the reviewer's comments, I had a stroke of genius which I imagined would make a significant impact on the world of physics.

Without going into details, cascading is a process by which two molecules cooperate by exchanging a real photon. My insight provided the means for making the exchanged photon virtual. As a consequence, this photon's energy would not need to be conserved as long as the process were fast enough not to violate the uncertainty principle. This made the problem richly beautiful; and more importantly, it meant that a large area of nonlinear optics was flawed. I couldn't resist thinking about this problem with my full attention, so I placed my long "to do" list on the back burner.

I drew Feynman diagrams of the process and immediately realized that if the virtual photon did not conserve energy, it forced the cascading process to also not conserve energy. Thus, the photon must be real and my line of reasoning flawed. I am no genius after all!

However, by taking this detour, I found myself thinking about various cases where virtual processes contribute. To cut to the chase, my understanding of nonlinear interactions took a quantum leap. It made me appreciate the clever minds of great physicists such as Feynman, whose work embodies incredibly deep reasoning.

While most detours on the road waste time and make drivers frustrated, this kind was enjoyable and fulfilling. As I sit at my desk plowing through my work, I remain permeated with a calm happiness.

Until next time...