Monday, December 4, 2006

Killer Chemistry

I can't believe that's the best title I can come up with. Anyway...

This post is no longer timely, but I will finish what I started some time ago.

I conceived this blog with the intention of devoting at least half of it to science, but apparently I am much more interested in politics after all. In any case, there has been much ado over Polonium-210 recently, because of the poisoning of a former KGB operative.

First, the "-210" after polonium denotes its atomic mass, or the total number of protons and neutrons in its nucleus. Polonium, like all elements, is defined by the number of protons in its nucleus, so this extra number (indicating that it is a particular isotope) basically denotes how many neutrons it has. Polonium has 84 protons, so Po-210 has 126 neutrons. Many elements have only one isotope, and most that have more than one isotope have only a few. Polonium has many, but here I will talk only about Po-210, the isotope used to poison Litvinenko.

By the way, you may have noticed that the mass numbers used to describe isotopes of scary radioactive elements are almost always above 200. There is a good reason for this, and it has to do with the nature of radioactivity itself. Within the nucleus of an atom there is tension between the nuclear strong force, which binds protons and neutrons together, and the electrostatic repulsion of positively charged protons. The strong force is dominant at short distances, which is why small nuclei tend to stay bound together very tightly. However, as the distance between protons increases, the repulsion caused by their like charges becomes more salient than the attraction of the strong force. Consequently, when a nucleus attains a certain mass, the repulsive forces predominate and it becomes unstable. It can increase its stability (which is the same as lowering its energy) by emitting certain particles in order to achieve a better balance between attractive and repulsive forces. In addition to explaining radioactivity, this balance of forces is also the concept behind nuclear fusion. Nuclei with few protons, like helium, have very little repulsion between them, and thus the addition of more protons does not destabilize the atom. In fact, the atom is more stable with more nucleons, because the strong force binding it tightly together is not strongly opposed by proton repulsion. This is why heavy nuclei like U-235 are used for nuclear fission and hydrogen is used in fusion; if you want to release energy, you split large nuclei or combine small ones.

Back to Po-210. Polonium was discovered by Marie Curie, who did a great deal of the seminal work on radioactivity, and named for her native Poland. It can be produced a few ways from other radioactive nuclides, but Curie probably discovered it as the last (radioactive) product of the radon-222 decay chain, which is ultimately a part of the uranium-238 decay chain. It decays by alpha emission to lead-206, which is stable (i.e. not radioactive). More on what that means shortly.

Interestingly, while Curie did her famous work in her adopted France, Francium was later discovered by another woman, Marguerite Perey, at the Curie Institute in Paris. Apparently, Cheeseeatingsurrendermonkium was taken. Also, it would be difficult to distinguish such an element's abbreviation from that of Cesium (Cs), its close chemical cousin. A lazy element with no known applications and a peculiar odor, Francium is disliked by the other alkali metals for its haughty disdainfulness and effeminate cigarette holder-thingies.

Po-210 has a number of advantages as a poison. As mentioned above, it decays by emission of alpha particles. An alpha particle is essentially a helium-4 nucleus: 2 protons and 2 neutrons. This is a very large particle, as these things go. Typically when we think of radiation, the concern is neutrons (1/4th the mass of an alpha particle) and/or high energy photons, like gamma-rays, which are even smaller. This is important because at the the scale of these particles, almost everything is empty space. The bulk of the volume comprising a single atom is actually just the unoccupied space between the nucleus and the electron shell, so a subatomic particle can easily pass through loosely packed atoms and molecules (like air) without colliding with anything. And the size of the particle determines the likelihood that it will collide with a nucleus; larger particles will collide more often. Thus alpha particles cannot travel far, even through air, before smashing into something and coming to rest as plain-old helium. This means that a pure alpha emitter like Po-210 can be safely handled with very little shielding (paper is sufficient) or even none, because the particles will not penetrate the epidermis into tissues where they can really do damage. This also accounts for radiation screeners' inability to detect Po-210; if the particles don't reach the detector, it can't detect them! (In investigating the case, they have been able to track Po-210 contamination. I'm not sure if they have detectors that are capable of directly detecting alpha emission, but I know that alpha particles can precipitate the emission of neutrons from other elements. In fact, Po-210 is often used as a neutron source to initiate a chain reaction like those in nuclear weapons. So I suspect a better way to detect it is by introducing beryllium or some other metal from which Po can liberate neutrons, and then using conventional detection technology to look for those.)

While Po-210 is fairly easy to handle safely, that doesn't mean it's not dangerous. It simply needs to be introduced to the body by inhalation or ingestion, for example, and will then wreak havoc on the unprotected tissues. There are a few mechanisms by which it causes damage to tissue. First, remember that it is a 2-proton nucleus. This means that it will strip away 2 electrons from other molecules in order to balance its charge. This kind of ionization is usually a bad thing in tissues; it is the formation of the free radicals we have all heard of as potent carcinogenics. Free radicals are associated with the negative effects of aging and the carcinogenic effects of cigarettes. The anti-oxidants we always hear about in healthy and often brightly-colored foods like tomatoes and berries putatively confer their health benefits by neutralizing these radicals. This type of damage may be the greatest concern in chronic and/or low-level exposures.

The other source of damage is the physical collisions of the alpha particles with parts of the cell. This is most harmful in the nucleus, where particles are likely to collide with dense coils of DNA. It's never good when something messes with your DNA, but not all types of damage are equal. Your cells have remarkable mechanisms for repairing DNA, but alpha particles are capable of severing both strands of DNA. Double-stranded breaks are tough to repair; you don't have the other strand to use as a template, or you have very little of it if the ends overhang slightly. Still, our repair mechanism for double-stranded breaks (non-homologous recombinational repair, sometimes called non-homologous end joining) works pretty well with isolated breaks of the kind that may occur naturally in a cell. The problem is that if you have lots of these breaks simultaneously, as with high doses of UV light or other ionizing radiation, the ends of non-matching fragments can get joined. These transpositions can cause lots of problems and eventually lead to, you guessed it, cancer.

In Litvinenko's case, he would have accumulated so many of these damaged and swapped DNA fragments so quickly that they would have immediately begun to affect his cells. You would expect the effect to be most prominent in cells that are highly active and rapidly dividing (which entails replicating their DNA), and this is exactly what happened. His rapidly dividing epithethial cells died or malfunctioned, causing his hair to fall out, and most probably some serious problems with his skin and the lining of his digestive tract. Some people may have noticed that his symptoms were reminiscent of a chemotherapy patient; that's exactly right. Chemotherapy fights out-of-control replication of cancer cells by inhibiting DNA synthesis, and unfortunately this inhibition cannot be contained only within cancerous tissue. Also, chemotherapy is usually accompanied by radiation therapy, which seeks to induce enough mutations in the DNA of cancer cells that they can no longer reproduce viable cells. This is why a substantial percentage of people who overcome their cancer with this treatment will later develop leukemia; the radiation induces the same carcinogenic mutations discussed above in other, previously healthy tissues. In both treatments, the goal is to halt DNA synthesis, either by inducing mutations that are lethal to the cell, or by chemically blocking the process. Litvinenko's death was, in effect, similar to a massive overdose of chemo/radiotherapy, in that it was caused by the prevention of DNA synthesis in cells that must replicate for the body to function.

A few more interesting links: