Thursday, November 14, 2013

Radiation, Free Radicals and Disease.

This text is based on a lecture, "Radiation, Free Radicals and Disease," first delivered by Professor Chris Rhodes at Kingston University, London on Wednesday, November the 27th, 2013, and which he gave subsequently at the Slovak Technical University in Bratislava (24th June, 2014), and the University of Constantine the Philosopher in Nitra, Slovakia in 2014 (25th June, 2014).

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, and 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. Indeed, some tens of thousands of "radium emanators" were sold and installed the houses mostly of Americans, so they could "invigorate" drinking water and thus receive the "beneficial" consequences of "radium emanation", i.e. what we now call Radon and try to protect ourselves from at all costs. Remarkably, radium suppositories were also sold, with the intention of re-invigorating the flagging manhood.

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 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 "healthy radon" industry, those working with radioactive materials and x-ray equipment had come to realise that there were serious adverse 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 (80%) arise from the breakdown ("radiolysis") of water in the sheath surrounding the DNA double helix, while the remaining 20% is from direct damage to the DNA molecules by ionising radiation.

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. It is likely that the human body has been adapted by evolution to adjust the balance between ROS and antioxidants so finely that the intake of additional antioxidants has but a minor influence, and so the degree of oxidative damage is little reduced. In a way, it is reminiscent of the concept of ‘inbuilt obsolescence,’ that we cannot live forever and are designed not to.

To whit, the degree of protein oxidation (according to the infra-red C=O bond absorption intensity) in samples taken from species of vastly differential longevity (rats, rabbits, flies and humans) has been plotted as a function of lifespan fraction, and remarkably in all cases, all is fairly constant (well protected) until around the half-way point - i.e. around the age of 40 or so in the case of humans - whereupon a relentless upsurge occurs, as we progress toward its conclusion. In all probability, we are protected by Nature until we have passed our reproductive years, and then the segment of the code reads-through to conclude this brief ride on Spaceship Earth, making way for the next  and fresher generation.

1 comment:

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