Friday, December 15, 2006

Radiation, Free Radicals and Disease.

Radiation breaks down water in living cells into dangerously reactive free radicals which subject our bodies to a continual assault, attacking essential molecules of life such as DNA and proteins. Since radiation has been around for as long as the Earth has, we have fortunately evolved efficient defense systems called antioxidants, which generally intercept the radicals before they do too much damage. The energy spectrum of radiation spans the range from radio-waves, at fairly low energies, through the microwave, infra red, visible and ultra-violet wavelengths of light, and into the x-ray, gamma-ray and cosmic-ray regions. The latter constitute "ionising radiations" which are of relatively high energies, up to millions of electron volts. The disintegration of radioactive nuclei too, results in energetic particles which can also ionise molecules, such as beta-rays (high energy electrons) and alpha-particles along with gamma-rays. Indeed most nuclear disintegrations release gamma rays as the decay ("daughter") product nucleus is formed in an excited state and emits a gamma ray on returning to its state of lowest energy.
The word "radiation" refers to the process of emitting energy in the form of rays or particles, which are themselves often called "radiations". In 1895, Wilhelm Roentgen was the first to identify (though probably not discover as vacuum "Crookes" tubes had been around for several decades) x-rays, streaming from the "positive electrode" in such cathode ray tubes. Cathode rays are energetic electrons which "boil-off" from the surface of an electrically heated cathode, which on striking a (positive) electrode to which they are attracted by virtue of their own negative charge, excite atoms in the target, which emit energetic radiations known as x-rays. Within months of Roentgen's report, Antoine Henri Becquerel had identified natural radioactivity from uranium ore, making the discovery that the mineral could darken a photographic plate, even when the latter was wrapped in paper, and so the curious radiations had a peculiar power of penetration. In 1896, the first x-ray "photograph" was taken, in fact of Roentgen's wife's left hand - the bones are clearly visible, as indeed is her wedding ring, since the rays are stopped by denser material, thus permitting structural differentiation in living tissue. I wonder why Roentgen didn't x-ray his own hand, but left this privilege to his wife! Perhaps he wasn't entirely sure that x-rays were harmless and used her as a guinea-pig; but more likely, he did consider it a privilege, as radiations were to be revered for the next few decades as being possessed by almost miraculous properties. X-rays were put to generalised use in 1897 by the U.S. Army in the Spanish- American War to locate bullets and shrapnel in wounded soldiers.
In 1898, Marie Curie discovered that thorium too emitted "uranium radiation", and coined the term "radioactivity" to describe the phenomenon. In this same year, Marie and Pierre Curie manged to identify both the elements polonium (named after her native Poland) and radium. Polonium is a decay product of radium and both are members of the decay-chain leading down from uranium 238. The elements were "discovered" using spectroscopy, since both exhibited spectral lines unknown for any other elements. My casual annotation here trivialises the immensity of their accomplishment, which involved boiling, in 20 kilogram batches, 4 tonnes of uranium ore (pitchblende) in concentrated acids, and then separating out the constituent elements using probably the most laborious technique in classical chemistry: "fractional crystallisation". All the work was done in an unheated shed, which, as they came closer to their goal, was lit at night by the green glow from the radioactive salts in petri-dishes spread out over the simple wooden tables that were its furniture. Marie Curie described herself as "often physically exhausted" at the end of a day's work, no doubt as she, a slightly built woman, handled half-hundredweight quantities of materials, and stirred them with a heavy iron bar in cauldrons of boiling acid. It is likely too, that her strength was sapped by exposure to ionising radiation from these elements from which there was no protection at all, and which eventually took her life in the form of aplastic pernicious anemia (a form of leukemia). Yet she described those four years spent working "in the shed" with her husband as being "their happiest". I imagine an almost spiritual euphoria of belief, idealism, purpose and love, which only a precious few of us experience. Marie Curie was awarded the Nobel Prize for Physics, along with Pierre Curie and Becquerel, in 1903. In 1902, she isolated pure radium by electrolysing a solution of radium chloride (RaCl2) in water using a mercury cathode: the mercury was distilled-off, leaving 100 milligrams of metallic radium. This led to her being awarded a second Nobel Prize in 1910.
In 1899, Ernest Rutherford discovered "alpha-rays" and "beta-rays", as he termed them, differentiating between the two kinds by their differing penetrating power. Specifically, beta-rays (electrons) are stopped by a sheet of paper, but alpha-rays (helium nuclei and hence particles) require a sheet of aluminium to stop them. The lawyers were in quickly enough too, and also in 1899 the first malpractice suit award was made for x-ray "burns". Though the public "miracle" of radiation had inaugurated a huge industry, including "emanation-generators", devices which contained sufficient radium to produce a steady dose of "healthy radon" in the home, those working with radioactive materials and x-ray equipment had come to realise that there were serious health-effects attendant to radiation. As early as 1902, it was shown that a dose of x-rays could cause death in a mammalian foetus. Both the Curies and Becquerel received radiation "burns" from handling radium. The connection was made between exposure to radiation and the development of tumours. One particularly unfortunate pioneer was Clarence Dally, a fine experimentalist who was employed by the U.S. inventor Thomas Edison in making and experimenting with x-ray tubes. Dally suffered a steady contracting of tumours to both hands, which necessitated the amputation of his fingers, then hands and finally both arms. He finally died of generalised cancer aged just 39. Radiation induced tumours are a result of free radicals causing damage to DNA in cells, which mostly arise from the breakdown ("radiolysis") of water in the sheath surrounding the DNA double helix.
The symptoms of "radiation sickness" are well known (vomiting, hair-loss and in high doses, an ultimate liquefaction of internal organs as proteolytic enzymes are spilled from breached cell interfaces, then death). The lethal dose to a human is around 500 - 1000 Rems (5 - 10 Sieverts). Many animals have been irradiated in "radiation biology" experiments, and in the 1950's a connection was made between the effects of exposure to x-rays and "oxygen poisoning", which deep-sea divers may experience under inopportune circumstances (accelerated metabolism, coma and even death). It was proposed that oxygen free radicals may be involved in both cases. This led to the notion by Denham Harman in 1956 that the reason we age is that cells in the body are constantly attacked by free radicals formed from oxygen (which we breathe) and transition metals such as iron, and ultimately we die from accumulated wear and tear. In a similar manner to an old car, which rusts from exposure of oxygen radicals, so do we and eventually become "old bangers" and are finally shipped-off to the junk-yard!
As an extension of this "free radical theory of aging" is the notion that many diseases, including cancer, arthritis and cardiovascular disease, are the result of injury from oxygen free radicals. A huge industry has grown-up based around the concept of "antioxidants", and that taking supplements of antioxidants in the form of pills to some extent reduces the damage, and hence the likelihood of developing these illnesses. However, there is no conclusive evidence that antioxidant supplements do any good at all, whereas there is well documented data that taking too many or the wrong kinds can be positively harmful. In one trial of beta-carotene supplements in smokers in Finland, the intended three-year long trail was discontinued after just nine months because subjects began to show an elevation in levels of lung cancer by about 20%! Since beta-carotene is thought to protect against cancer, this is most alarming, but it just shows that Nature is more complex than we comprehend, and the only hard medical statistical evidence is that eating 5 - 8 portions of fruit and vegetables per day does seem to correspond with a reduced level of cancer, heart disease and arthritis. This is usually referred to as the "Mediterranean Diet", but I wonder to what extent the benefit actually is provided by the "Mediterranean Lifestyle", that people who are warmer, less stressed and happier are less prone to these diseases than are those of us living in the colder, more societally frenetic northern countries.

This text is based on a lecture "Radiation, Free Radicals and Disease" delivered by Professor Chris Rhodes at Kingston University, London on Wednesday, December the 13th (2006).


Unknown said...

I always enjoy your musings..
a couple links for you

A great book if you haven't read it

Lisa Blakesley said...

Are you aware of free radical exposure and a link with Parkinson's
Disease? I started working with radiation in 1971 at age 15 until
present, now age 53. Diagnoised with PD at age 47

Thank you

Professor Chris Rhodes said...

Hi Lisa,

sorry to hear you have PD, but yes, I had heard this, and for your interest here are a couple of links:

I am 49 and I have worked with radiation too, but so far I seem to be O.K. Coincidentally, one of my old professors has PD, which I think he became aware of when he was about 60 (he's 72 now). He certainly had some chemical/free radical? exposure during his career but as far as I know he never worked with radiation.

Now, my feeling is that although radicals may play a role in cell protein/DNA damage, it is more likely to be due to naturally caused radicals (through oxygen metabolism)rather than radiation since each cell in the body is assaulted by thousands of oxygen-radicals (from breathing oxygen) each day.

Low level radiation has been linked with various diseases (cancers) though, even at doses far less than would be thought harmful on the basis of how many radicals the corresponding amount of energy delivered might cause.

So, there are more subtle effects perhaps, for example cross-linking DNA chains through the thymine units.

We did of course evolve under conditions of background radiation and so there are protective mechanisms but some additional exposure may overload them.

Sorry to be vague but the jury is still out on much of this.



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