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Sharp discusses basic reasearch and industry in the life sciences

(Following is the text of remarks delivered by Professor Phillip A. Sharp, head of the Department of Biology and 1993 Nobel laureate, at last week's colloquium on Science in the National Interest: A Shared Commitment.)

The title of this afternoon's session is "Basic Research and Industry" and I am charged with addressing this topic from the perspective of life sciences. This I am pleased to do as the topic provides an opportunity to stress the importance of continuous and vigorous support of research in the life sciences.

However, I do not want to dissect out basic research from the whole fabric of research in this area. It is extraordinarily difficult to establish what is basic versus applied research in the life sciences.

Is the discovery of the first oncogene, which is a mutant form of a natural gene that causes the growth of a human cancer, applied or basic research? It is certainly applied in the sense that it has helped us define the problem of cancer at a new genetic level and this has led to new treatments. It is also basic in that the discovery fundamentally advanced our understanding of the basic processes controlling cell division. To a physicist, this is all applied research because no fundamental laws of physics are being explored. To a clinician, who wants to develop new treatments, it is all basic research because the results do not immediately help in curing the sick. Thus we should discuss research as it relates to the national interest, particularly in the life sciences.

The case for supporting such research is very strong. The future holds great challenges for the nation in maintaining the health of its citizens, in promotion of a growing economy, and in maintaining an attractive and clean environment. Each of these challenges is directly related to life processes. Thus, building the science and technology bases in the life sciences is critical for a successful future. I will try to make these points more explicit in a few moments but first I want to emphasize the ignorance that still prevails in our knowledge of the most basic and fundamental aspects of life sciences.

We have seriously studied the most fundamental nature of biological systems for only a little more than 40 years. The structure of DNA, the genetic material, was reported in 1953. The recombinant DNA era began 20 years ago and for the first time we could isolate and manipulate genes. Until this revolution, the biochemical realm of human cells was largely unexplored.

Today we are still in the process of discovering new genes and protein structures. However, we know very little about how these cellular components interact and how they execute their chemical functions. This integration step is not commonly possible and limits the impact of specific knowledge. Let me mention some explicit examples of things we do not yet understand. These include questions as basic as the process by which a protein folds into its native structure. How many genes are important for the formation and maintenance of a human? Are there 30,000, 50,000 or 100,000 genes in the human chromosomes? Finally, we know very little about how the brain works or, for that matter, how it stores information in memory. All of these and many more questions remain to be explored.

The development of recombinant DNA technology also generated the biotechnology movement. Many novel therapies have emerged from biotechnology and currently almost 100,000 people are employed in this sector. It is still a growing area of technology which is becoming more diverse with new discoveries and new societal needs.


In fact, the rate of change of technology and science in the realm of biotechnology is staggering. Who would have suspected a few decades ago that the nation would be focused on DNA fingerprinting in a murder case, or struggling with an epidemic caused by a new human virus, HIV, and planning the sequencing of the total human genome? Biotechnology depends upon new discoveries and new applications.

Among the societal concerns mentioned above are the quality of future health care and the containment of rising costs of health care. There are two primary opportunities to improve health care and to reduce costs simultaneously. The first of these is prevention. In most cases preventing disease whenever possible is cheaper and better than curing it. However, most diseases cannot be simply prevented. The second opportunity is the development of more effective treatments through research. Better treatments depend primarily on the discovery of better drugs that reduce damage due to disease, or drugs that cure a disease. More importantly, better treatment or diagnostic protocols offer the hope of improvement in the quality of health care. Thus the quality of health care in an environment of constrained costs depends upon critical research and innovation.

For example, the most successful biotechnology-produced product to date is Epogen, a drug developed by Amgen, which stimulates the generation of red blood cells. This protein and similar blood factors may make it possible to do bone marrow transfer on an outpatient basis. Thus, probably a growing number of cancer patients can be treated more effectively at lower hospitalization costs.

The process of development of new pharmaceutical agents is beginning to change rapidly because of advances in basic science. At one time, large pharmaceutical companies almost exclusively developed new drugs by screening natural products for activity. This worked reasonably well but it did not provide a learning curve to make the development of future drug candidates easier. The era of modern biological sciences is beginning to change this tradition. The inner workings of human cells, the nature of mutations which cause disease, and the ability to design model animal systems emulating human diseases are revolutionary approaches to pharmaceutical discoveries.

We are only at the beginning. These advances in cell biology are complementary to advances made both in chemistry, such as combinational libraries which allow the sampling of large numbers -billions-of different chemical structures at the same time, and in structural biology, where methods have advanced the rapid determination of the atomic structure of macromolecules. As all of these technologies-and others not mentioned here-are melded into pharmaceutical research, new drugs and treatments will emerge.


Perhaps there is no area of life sciences that offers more opportunity for research to advance public health than that of neuroscience. It is commonly agreed that about half of all health care costs are related to mental disease. With a large aging population, these costs will only increase. Dementias such as Alzheimer's disease are not yet understood and therefore there are no effective treatments available. The same can be said for most mental health problems. The science of the brain and its processes can now be approached with a vast array of new methodologies. These include powerful methods to identify genetic changes causing disease, new methods to manipulate mice to study the workings of their nervous systems and a recently developed appreciation of cellular processes important in nerve cells. Advances in research here will underpin future advances in health care.

In my comments I have tried to stress the riches of opportunities that lie before us in research in life sciences. This research is in the national interest because it directly provides the basis for an increase in the quality of health care and for future uses of biological systems to produce new materials and agricultural products. In addition to these opportunities for new products, the environment, impacted by our technology, is largely a biologically driven issue. Thus, biological sciences have much to offer to the nation. Perhaps this is the primary reason that a few years ago MIT decided that all of its students would be required to take a course in modern biology. MIT's students will be prepared for this future.

A version of this article appeared in MIT Tech Talk on February 15, 1995.

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