|MadSci Network: Chemistry|
Angel, I’m glad that you asked this question. I am a medicinal chemist that works for a pharmaceutical company and I’d be happy to describe how chemists contribute to the development of new medicines.
Clinically useful medicines are usually developed through a lengthy and complex process. I’ll briefly describe this process and how chemists are involved in nearly every stage of it.
1. The first step is the discovery of a lead compound, or one that may be a good medicine. There are many approaches to this step. One is random screening which involves testing a wide variety of chemicals to see if they have a desired biological effect (such as reducing the inflammation that causes asthma, to use your example). Most major pharmaceutical companies have large “libraries” of unique chemicals which can sometimes number in the millions. Using robotic equipment, each of these chemicals is tested to see if it has the desired activity in a simple biological assay – if it does have the desired activity, it is considered a lead compound and taken on to the next step. At some point in the company’s history, a chemist prepared each of those individual compounds. Today, some specialized chemists use techniques called combinatorial chemistry to generate many compounds with diverse chemical structures in order to build larger and more useful libraries.
Another interesting approach to discovery of a lead compound involves studying traditional medicines. For example, the plant artemisia has been used for hundreds of years in traditional Chinese medicine to treat malaria. Recently, chemists investigated the numerous chemical constituents of the extract of this plant. They found that the anti- malarial activity could be attributed mainly to a single chemical that they named artemisinin. Artemisin has found to be a potent weapon against malaria, especially in areas where the malaria parasite has developed resistance to other drugs. Chemists are now exploring to see if even better anti-malarial compounds can be created using artemisinin as a lead. There are many other approaches to discovering a lead such as computer modeling, studying metabolites of known drugs, and clinical observation of unexpected pharmacological effects.
2. The next step is optimizing the lead. Once a chemical with the desired biological activity is found, chemists make small modifications to its molecular structure to see what effect this has on its activity. When beneficial modifications are found, chemists continue to make similar changes to continually improve the biological activity. The portions of the molecule that are necessary for activity are kept, and portions that are unnecessary can be removed to simplify the chemical structure. At the same time, these new leads are tested to see if they have unwanted side effects. More modifications are made to the chemical structure, this time trying to minimize unwanted biological effects (such as toxicity) without removing the desired pharmacological effects. By this iterative process, a new more active compound is developed.
3. The next step generally involves more rigorous biological and chemical testing to insure that the new compound has the potential to be a safe and effective new medicine. In this step analytical chemists are involved in examining many physical and chemical properties of the drug candidate. For example, they need to determine how well the compound dissolves in water (it usually needs to be water soluble in order to be distributed throughout the body by the bloodstream) and determine how stable the compound is in a biological environment.
4. Next, chemists need to develop a process for making the drug on large scale because significant quantities of the drug candidate will be needed for clinical trials where doctors test the drug in people. This often involves developing new efficient, cost-effective chemical reactions that use safe, non-hazardous reagents. Without a reasonably inexpensive manufacturing process that has a minimal environmental impact, it would not be practical to try to mass produce the drug to sell throughout the world.
5. The next step involves clinical trials. The drug candidate is tested in humans to see if it is safe and effective. Often it is compared to drugs that are currently on the market. Many specialized types of chemists, such as pharmacologists, are involved in this step, but most of the work is done by doctors and nurses.
6. The last step is regulatory approval in which a governmental agency determines whether or not the drug can be marketed and under what circumstances it can be used. The expertise of chemists is consulted to aid in making these final decisions.
As you can see, there is a tremendous amount of work that is put into discovering and developing a new medicine and bringing it to market and chemists are involved in nearly every stage. Chemists in the pharmaceutical industry work together with biologists, doctors, and many other scientists throughout the process. In my opinion, there are many exciting career paths for chemists who are interested in working in this industry and it can be very rewarding to see the impact that your work makes in contributing to people’s health and well being.
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