Reflections on Molecular Biology

 

What is Molecular Biology?

Reflections by Professor Gerald Stubbs, Director of Undergraduate Studies in Molecular Biology at Vanderbilt from 1989 to 2002.

Molecular biology is really two very similar but different things: the study of biological processes in terms of the molecules whose properties affect those processes, and the study of the molecules themselves.

An example of the first might be the search for a defective gene that causes some metabolic disease such as diabetes or some forms of cancer. The diseases are biological processes. Like all biological processes, their characteristics are determined by the properties of molecules. One type of molecular biologist begins with a biological phenomenon: it might be a disease, or it might be a fundamental biological process such as the dividing of cells during growth, the signalling by one organ in the human body to induce a response in another organ, or the capturing of light energy by plant cells for the manufacture and storage of fuel molecules such as sugars. This type of molecular biologist would probably be primarily interested in the biological process, and would try to explain the process by determining what molecules are responsible for it, discovering the properties of those molecules, finding out how those properties explain the phenomena we observe, and perhaps even developing ways to alter (as, for example, in plant breeding) or stop (as, for example, in disease control) the process. As an example of this type of molecular biology from a familiar area, you might consider the following question (now quite well answered): what sort of molecules do we use to digest the food we eat, and how can they break down the biological molecules in our food without breaking down the very similar molecules in our own bodies?

Another type of molecular biologist might be primarily interested in a particular class of biological molecules. What are they made of? How are they made? How do they interact with other molecules? How do they change under different biological conditions? The digestive molecules of the preceding paragraph are in fact members of the molecular class of proteins; so are the molecules that carry oxygen from our lungs to our tissues, some of the molecules (hormones) that travel through our bloodstream from various glands to stimulate activity in distant tissues, and the molecules in our muscles that make them contract and exert force. Proteins are long, chain-like molecules, folded up in distinctive ways. The folding of a protein is very complex and essential for its correct function. What makes proteins fold correctly? If they unfold can they fold again? What happens to them if they fold incorrectly? Why is folding necessary anyway? These questions are among the most popular current topics of molecular biological research today, because they have so much bearing on the way in which living organisms work.

As you can see, there is not a very sharp line between the two types of molecular biology. No molecular biologist is strictly confined to one of them. To give an example from my own experience, I began as a chemist, excited by viruses because I thought of them as the biggest and most challenging molecules that one could find out about. But as I learned more of what others had discovered about viruses, and as I added to that store of knowledge myself, I became intrigued by the way in which those molecular properties affected the life-cycle of the viruses. Today, two of my interests are the defenses that hosts set up to combat viruses, and the means by which viruses travel from an infected cell to cells throughout the host. These are biological processes, well-studied long before anyone had any idea of their molecular bases. So I have found myself moving from one type of molecular biology to the other. Of course, I still retain my interest in the fundamental molecular properties of viruses, so figuratively speaking, I never set foot in the laboratory today without both of my hats firmly on my head.

Sometimes people use the term "molecular biology" to mean only the study of genes and methods of manipulating genes. But it is much more than that. Molecular genetics is, of course, a major area of molecular biology. Another important area is biochemistry: the study of the chemical properties of biological molecules. Yet another is molecular cell biology: the study of the different parts of living cells, and how they use particular molecules to interact with each other and carry out their specialized functions. Other fields of molecular biology combine all of these areas: the study of development (e.g. Why do two identical cells later become a red blood cell, specialized for carrying oxygen through the body, and a macrophage, specialized for finding and destroying invaders such as bacteria?) is an excellent example of a field requiring input from cell biology, biochemistry, and molecular genetics.

In this department, we want to ensure that all of our Molecular and Cellular Biology majors are exposed to the broad spectrum of molecular biology. Indeed, even if you take only our introductory courses, we will introduce you to the basics of molecular genetics, biochemistry, and cell biology. We will even touch on a few more specialized areas, such as biophysics and neurobiology. An essential part of our philosophy is that the biological sciences should be taken as a whole, and that all aspects of biology bear upon each other in important and interesting ways.
Careers in Molecular Biology
(and other uses for a Molecular Biology degree)
Reflections by Professor Gerald Stubbs, Director of Undergraduate Studies in Molecular Biology at Vanderbilt from 1989 to 2002.
Last revised January 11, 2002

In an article in the leading science news journal ten years ago (Science, 24 May, 1991), ten fields were categorized as the "hottest" scientific fields of the nineties. These were Materials Science, Computational Science, Complex Systems, Optical Physics, Molecular Biology (by which they meant the study of the three-dimensional atomic structures of biological molecules), Genetics (meaning molecular genetics and genetic engineering), Immunology, Cellular Differentiation and Development, Neuroscience, and Earth Systems Science. Not only were five of these ten fields best entered by means of a molecular biology degree, but two others (computational science and complex systems) owe much of their success to their applications in molecular biology. Two quotes from that article are typical: "I think the 21st century will be the century of biology in the way that the 20th century has been the century of physics and chemistry" (Professor Wayne Hendrickson, Columbia University) and "I used to think of genetics as a subspeciality of medicine. Now I think of medicine as a subspeciality of genetics" (maybe that one is a bit over-enthusiastic! Professor Fred Bieber, Harvard Medical School).

Traditionally, graduates from Vanderbilt majoring in molecular and cellular biology have gone to medical school or graduate school. There are, however, quite a number of other possibilities, some of which I will list here (in alphabetical order). I expect that the largest areas of employment for our graduates in the next ten years will be biotechnology, biomedical research, and medicine, but I would not care to guess in what order.

Biomedical research: By biomedical research we mean most of the research that has eventual significance for our understanding of human biology or medicine. It is usually carried out in major research universities (less than 5% of all degree-granting institutions in the United States would qualify for this description; Vanderbilt would be fairly typical of the top tier of these), in state and federal government research laboratories such as the National Institutes of Health, and increasingly in industrial laboratories. This traditional area can be entered at many levels. With a bachelor's degree in molecular biology, most available positions are as technicians. Either experience or a master's degree leads to increased independence, responsibility and rewards. The head of a biomedical research laboratory will usually have a Ph.D., or occasionally an M.D., but a significant minority of young researchers enter the field as technicians, and decide after a year or two about going on to graduate school.

Biotechnology: A rapidly expanding field, overlapping in places with biomedical research. A lot of publicity has been given to drug design; very briefly, if a disease depends on a particular protein, we can (in theory) use molecular genetics to clone the gene for the protein and obtain large quantities for study, crystallography to learn the three-dimensional structure of the protein, and biochemistry to design a drug that will modify the behavior of the protein. This type of research is the reason that protein crystallographers, in particular, have been absorbed en masse from the job market in the last ten years, to take jobs in drug companies. A similar explosion had taken place ten years earlier when the drug companies hired all the molecular geneticists that they could lay hands on, and perhaps thirty years earlier (so that wave is retiring to make room now!) for biochemists. But biotechnology has also led to a wide variety of other products, ranging from environmental toxin diagnostic kits and other agriculturally useful products, to the enzymes that some washing powders claim will give you a brighter, cleaner wash (and so they will, but the fact that most of them are unstable above 70°F is keeping quite a few molecular biologists occupied right now!) Most companies fall into one of two categories: the large, established company, often with a major investment in pharmaceuticals or other chemicals and recognizing that the time has come to invest in the new biological approaches to molecular design and synthesis, and the small, innovative company, usually taking a high risk with a small number of potential products. Positions vacant, and especially periodic advertising supplements, in the weekly journal Science give an idea of some of the opportunities.

Within biotechnology, some of you may be interested in the very specialized area of bioinformatics. The vast array of information produced by molecular biology is difficult to manage, and a whole field has arisen, devoted to organizing, searching, and using this information. Typical qualifications are a Master's (sometimes a Ph.D.) degree in molecular biology, with a strong background in computing. At present there is a shortage of people trained in this area. Of course, supply and demand fluctuate, and the shortage may not exist five or ten years from now. But the field is growing, and students interested in both molecular biology and information technology may find it to be a very attractive option.

Business: Obviously, a biotechnology company whose executives understand the product has a certain advantage over one in which they do not. The smaller biotechnology companies in particular tend to feature scientifically trained management.

Law: When I came to Vanderbilt in 1983, none of our majors was planning a career in law. Since then, several of my advisees have taken that direction. The reason is simple, and is the same as the reason for two of the preceding paragraphs: biotechnology. Most lawyers do not need a degree in molecular biology. But certain areas of the law depend so heavily on molecular biology, that the opportunities for the rare lawyer with such a first degree are excellent. Of particular interest are patent law (for example, involving many of the products of genetic engineering), company law (biotechnology, see above), and forensics (identification based on DNA fingerprinting has led to some major legal problems in the last decade). Patent lawyers specializing in molecular biology usually have some postgraduate training in molecular biology, either at the Master's or doctoral level, since they need to be familiar with research.

Medicine: The advantages of a degree in molecular biology for entry into medicine should be obvious. Medicine is a discipline with a strongly scientific element, and in modern medicine, that science is largely molecular biology, given the broad definition of molecular biology that we have always used in this department. Most of our former students (and a glance at the MCAT Topics in Biological Sciences and Chemistry!) particularly emphasize the value of the introductory courses and Biochemistry.

Public Health (also Nutrition, and other fields related to medicine): In recent years, these areas have become much more molecular, and molecular biology is now an excellent preparation for them. They are usually entered through a Master's program; there are a number of excellent programs in both public and private universities in this region and throughout the country.

Teaching: Listed last only for alphabetical reasons. You will have read for yourselves how desperately this country needs to improve its scientific education. Areas to consider include public and private high schools, small colleges (where the faculty spend more time teaching, perhaps doing research in the summer), and major universities (usually with a much lighter teaching load, and an expectation of significant research effort). From my own experience, I can strongly recommend teaching as a rewarding career. Personally, I have preferred to combine it with research. Not everybody does, and your choice of type of school should be based on what mix of teaching and research, and what age-group of students, will give you the most satisfaction. One word of warning - like all worthwhile careers, teaching is not a nine-to-five job! But you have a choice: you can be bored for forty hours a week, or you can have an exciting job that stays with you all the time. We still manage to have homes, families and vacations!

M.D., Ph.D. or M.D./Ph.D.? Some students think of a Ph.D. as something to try for if they cannot get into medical school. You should understand from the beginning that the M.D. and Ph.D. degrees represent different types of training, and that very few people are suited to both. Ph.D. courses do not emphasize absorption of vast tracts of material as M.D. courses do, but that does not mean that they are easier. In fact, they are, on the whole, more difficult, because of the requirement that you produce original research. If you cannot get into medical school, you will probably not get into a good Ph.D. program, and you will almost certainly not get through one successfully. Your decision should be made on the basis of one simple question: do you want to be a physician, or do you want to be a researcher?

If you want to be a researcher, there is a further question: do you want to do clinical research? If so, you should go to medical school. If you can get into an M.D./Ph.D. program, that is all the better, but many clinical researchers do not have Ph.D.s; they get their research training as post-doctoral fellows, after the completion of their medical studies. If you want to do non-clinical research (and most medical research is non-clinical), then the years spent getting an M.D. may not be a wise investment. In the Vanderbilt medical school departments of Biochemistry, Cell Biology, Microbiology, Physiology, and Pharmacology (pre-clinical departments, where virtually all the non-clinical research is carried out), a recent survey showed that 85% of the faculty had Ph.D.s, 10% M.D.s, and 5% both.

You may wish to note that medical schools emphasize MCATs and overall GPA, while graduate schools require you to take GREs, and like to see a high GPA in the sciences, but are less concerned about your other subjects. Graduate schools also like to see research experience. Reference letters, of course, are important for both, but perhaps more so for graduate school. One final, non-trivial point: although most people know that Ph.D.s do not earn as much money as M.D.s, many do not know that virtually all science Ph.D. students in reputable schools receive both tuition and stipend support from the school or a professor's research grant, so financial considerations are not as critical as you might expect.

Information on graduate programs is posted outside the Biological Sciences Office. A number of publications rank graduate schools in different fields. Always be cautious about these rankings, and consult professors here about the graduate schools to which you plan to apply. Nevertheless, a widely consulted ranking is the well-known US News and World Report list, at www.usnews.com.

Opportunities for BS and MS graduates: There are many opportunities in molecular biology that do not require a Ph.D. or an M.D. An interesting source of information is the Advertising Supplement Career Opportunities and Graduate Programs for BS / MS Scientists, published around August or September (e.g. 24 September 2004) in the journal Science. The journal is available in the library.


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