Many students who study biochemistry in university subsequently gain employment in the pharmaceutical industry. A wide variety of career options are available to such individuals, with positions being available in pharmaceutical manufacturing, quality control, research and development as well as product registrations and marketing.
A job in the pharmaceutical industry has always been a popular career choice for a number of reasons. Salary and working conditions are usually good and many find the knowledge that the products they manufacture improve or prolong life or health fullfilling.. In the past most pharmaceuticals have been chemical in nature. Well-known examples of such drugs would include aspirin, as well as other painkillers, antidepressants, anaesthetics and steroids. Most of these drugs are manufactured by direct chemical synthesis in large chemical factories.
A wide variety of other chemicals which may be classified as pharmaceuticals are obtained from biological sources. Examples here include antibiotics, which are produced by certain micro-organisms, and drugs such as morphine, which are produced naturally by certain plants.
If a person develops a certain disease because the body fails to make a particular protein it seems logical that the disease could be treated by obtaining that protein from another source and injecting it into the affected individuals. In fact people with diseases such as haemophilia and diabetes can be successfully treated using such a strategy.
Most people donate blood at some stage of their lives. Such blood supplies can be used by doctors in a number of ways. They can be injected directly into other people who need blood - for example patients undergoing an operation. Quite a lot of blood is, however, used as a source of factor VIII which can be extracted or purified (by biochemists) from blood donations . Subsequently the factor VIII can be injected into haemophiliacs in order to give these people the ability to ‘clot blood’ if they get cut. Treating diabetes with insulin follows a similar approach. Insulin is produced naturally in the body by the pancreas. Unlike the situation regarding blood it is obviously impossible for healthy people to donate their pancreas! Insulin preparations used to treat diabetics normally has been extracted from the pancreas of slaughter-house animals, most notably pigs.
Insulin and factor VIII have been used to treat diabetes and haemophilia for many years now. Thus these were amongst the first proteins to be used as pharmaceuticals.
Another medical condition which can sometimes be treated using protein-based pharmaceuticals is that of infertility. The inability to have children can cause great distress to the affected people. While the medical problem can be with the male it is more usually associated with the female, due to the fact that her reproductive system is far more complex. During normal reproductive functioning in the female a single egg begins to grow and mature. If the female mates when the egg is fully ripe, she will normally become pregnant. If she does not mate at this time that egg will die away but another egg will begin to grow and mature, thus continuing the reproductive cycle. The growth and ripening of such egg cells in the body is caused by a particular protein hormone FSH (follicle stimulating hormone). Females whose body does not produce normal levels of this hormone are often infertile.
A strange fact is that FSH is found naturally in the urine of older women. This FSH can be extracted from the urine of such women and then injected into the infertile women. This promotes normal egg cell growth in such individuals, who then can become pregnant upon mating.
Sometimes quite high levels of FSH must be injected to induce egg cell growth. However, if the levels injected is much greater than the normal level found in a healthy body, the growth of several eggs at the same time (rather than just one) can occur. This is why some women who have been administered FSH as an infertility treatment can give birth to triplets or quadruplets. This principle is also often used in veterinary medicine, in particular within very valuable animals such as race horses.
In any one year such a horse can usually only give birth once. However, if you inject very high levels of FSH into the mare the growth of several eggs (rather than just one) will occur. The number of eggs that can grow at the one time can vary between two or three to two or three dozen! Obviously, no one horse could have two or three dozen foals together, therefore, after mating it is necessary to remove all the fertilized eggs from the horse. One such egg is then re-inserted into the horse - so that she will have one foal. The remainder of the eggs are then inserted into less valuable mares, who will each carry a foal to term. Each of these foals, of course, will contain the genetic characteristics of its valuable mother.
Such proteins could be of obvious benefit in treating some disease conditions. One exciting example of such a disease-fighting protein is interferon. The body actually produces naturally a number of different interferons, many of which have very similar biological actions. Interferons can have a variety of effects on the body but the main ones include:
Interferon is also used to treat some forms of cancer, as the interferon when it comes into contact with some cancer cells slows down their rate of growth. Most cells in the body divide only a few times before they die. Cancer occurs when some such cell, for some reason, becomes immortal. The cancer cell keeps on growing and dividing and all its daughter cells are also immortal. These cancer cells generally grow very quickly in a clump (called a tumour).
Interferon seems to be particularly good at slowing down the rate of some types of cancer, including leukaemia and cancer of the bowel, and hence may be used in treating such cancers. Many proteins which have pharmaceutical applications can be easily obtained in reasonably large quantities. Examples already discussed would include factor VIII obtained from donated blood and insulin obtained from the pancreas of pigs. However, many other proteins such as interferons are produced by the human (or animal) body in minute quantities. To obtain enough of many such proteins to make a single therapeutic doses might require the extraction of tons of animal tissue. This approach is obviously not feasible, and has limited the medical use of many such products in the past.
Modern laboratory techniques now allow biochemists to pin-point the gene which codes for any protein of interest. Furthermore they can remove that gene from one cell type and insert it into a different cell type. The recipient cell can now make the protein that the gene codes for. In this way an interferon gene can be removed from a human cell and can be put into a microbial cell. Micro-organisms cannot normally make interferon because they do not naturally contain the interferon gene. However, the micro-organism that the interferon gene has been transferred into can now make interferon.
This strategy is used to produce many protein pharmaceuticals (often called biopharmaceuticals) in micro-organisms. Micro-organisms are popular because they grow very quickly (they can divide in two as fast as once every twenty minutes). They are also easy to grow cheaply. In this way micro-organisms can produce very large quantities of any protein quickly and inexpensively.
Even proteins such as factor VIII, which are available in fairly large quantities from donated blood, are now being produced in micro-organisms by genetic engineering. This is mainly for safety reasons as certain diseases may be transmitted via contaminated blood. In fact many haemophiliacs contracted AIDS and/or Hepatitis B (i.e. from blood obtained from donors who had hepatitis B or AIDS) in this way. Producing the protein required in micro-organisms gets over this safety problem as no virus or infectious agents capable of causing human disease will be present. Overall, therefore, many of the most recent developments in fighting disease involves the use of protein- based pharmaceuticals. This is but one area which impinges directly on industrial biochemistry. Research into, and production of, proteins of potential pharmaceutical use will continue to offer exciting and rewarding careers to many of those who study biochemistry at university.
Gary Walsh is a Lecturer in Industrial Biochemistry at UL. He has formerly worked in the pharmaceutical industry and has interests in various aspects of protein research.
