The Hole Story:
Drugs and Sunlight
Methods of Study
The various breakdown products which are formed from the drugs have to be identified along with the particular way in which they react with materials that are found in the normal human body, such as proteins, DNA and cell membranes. “Basically what we are doing is studying the drug substances,” says Moore. “Our research is involved purely at the test tube level. It does not involve the use of animals or anything like that. We are simply looking at the fundamental chemical mechanisms.”
Moore and his researchers take the chemicals and irradiates them with UV light (filtered to simulate sunlight) and observe what happens when they are mixed with materials found in the human body. They also look at the effect of oxygen since oxygen, of course, is plentiful in the environment and many of the reactions depend on oxygen reacting with the molecule.
Obviously what is happening in the body is very complicated but Moore is trying to do the work in fairly simple systems. At this stage he is looking at the building blocks of biological systems. The work that he has done so far has tended to involve a wide variety of different drugs. In future research he intends to go further towards the biological component by looking at the actual breakdown of biological molecules such as the breakdown of DNA.
Because of the limitations of the available resources he has had to stay with the simpler systems so far. However this is also good training for the students in many of the analytical techniques which are used to determine the structure of new compounds and their properties. In this sense Moore’s research is also fulfilling a training role and that is important because most of the students have relatively unsophisticated abilities. The simpler systems are a useful introduction for them.
What has been found from these experiments so far is that the drug molecules react, in a photochemical sense, in these relatively simple chemical systems. He can then compare how much they react with what has been found in a biological system by others who have experimented on animals. There is also clinical evidence in the form of information collected by the Department of Health listing those drugs which are highly reactive in photosensitivity responses. So far there seems to be a pretty good correlation between the chemical results and the animal and human results. So simply studying the chemicals in the test tube seems to be a fairly good predictor of what they are going to be like in the human body in terms of responses to sunlight.
If a data base can be firmly established which shows the types of compounds and relates their chemical structures to the way they may react with in the biological system, then it will be much easier to make predictions about new compounds and might avoid a lot of animal testing. This is one of the selling points that Moore likes to use for his work. He foresees a situation where the ability to predict serious effects will replace much of the animal testing that is currently undertaken.
One of the techniques he uses is called chromotography. It is used to separate the individual components of a mixture of chemicals. In the chromotography technique a substance passes down a column within which a material has been packed that has a certain attraction that varies for different compounds. With a manipulation of the conditions it is then possible to effect a separation whereby some of the compounds stay in the column longer than others. The compounds then come out in a particular order which is determined by their attraction or lack of attraction for the material that is packed in the column.
The chromotography technique, in its very many different forms, is one of the major analytical techniques used in drug research. The technique is widely used to study the distribution of drugs in the body. It is also used in an area of research related to Moore’s research which studies what happens to drugs in the body. When a patient takes a drug the drug may undergo chemical change in their body. This process is called metabolism. The enzymes within the body act upon the drug attempting to change its chemical structure so that it can be excreted from the body more quickly.
The other major piece of equipment being used is an artificial light source which gives a strong band of UV irradiation. But he has to be careful working with it because it can cause sunburn and so he has to protect himself from it with the appropriate filters and screens and so forth. But the risk is not a significant problem because, generally speaking, in a laboratory situation it is easy to control by having everything behind the appropriate shields and it is only switched on when the system is all set up and ready to go.
“We’re using sources which are stronger than sunlight,” he says. “That is simply to accelerate the reaction because otherwise we would be waiting around too long to get sufficient amounts to be able to handle it satisfactorily. But we also do some comparisons with sunlight. We will put samples out to be exposed to sunlight and we will make sure that the same sorts of reactions take place there as we see in the laboratory.”
“Oxidation and the production of free radicals are the main concerns with drugs reacting to sunlight,” says Moore. “Free radicals are parts of molecules. As the molecule falls apart it forms very reactive fragments which cause further damaging reactions. You may have heard about free radicals. In popular medical literature you will hear these days about preventative therapies involving mega doses of vitamins. Vitamin C and Vitamin E are molecules which are claimed to be good for you because they are able to react with free radicals and prevent them from doing harm,”
Many useful as well as detrimental biological reactions occur via the free radical process. Therefore, there are species in the body capable of mopping them up. The idea with preventative medicine is that you keep up the supplement. The sorts of things that Moore’s research has found go very much hand in hand with this approach in that the drugs, which are the most reactive clinically, are also the ones which are the most readily able to form free radicals and also to combine with oxygen.
Some of these effects have been used by doctors beneficially. There is one very serious skin condition, for instance, called psoriasis which can be treated by the use of drugs and exposure to UV light. If this treatment is not overdone it can lead to a remission of the psoriasis. The same principle is used to find and treat cancerous tumours in the brain. A drug is given that is capable of absorbing light. It makes its way to the tumour and then an optical fibre is used to direct a red laser light to the site of the tumour. The photochemical reaction that then takes place will kill the cancer cells by breaking down the cell membrane and the amino acids and lipids.
Previously in this chapter: