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Ann Thorac Surg 1995;60:497-498
© 1995 The Society of Thoracic Surgeons
Department of Surgery, Medical College of Virginia, Richmond, Virginia
In this issue of The Annals,Rowland and co-workers [1] call our attention to some of the strategies potentially useful for gene therapy. The concept of altering the control of cellular protein products through the process of gene manipulation is not new. The potential for clinical application of this strategy is, however, more realistic with every passing day.
Gene therapy is but one of the novel tools to emerge from the development of the branch of science termed molecular biology. Molecular biology is, in fact, a composite of two important pieces. The first of these is the collection of a series of biochemical techniques that facilitate understanding and manipulation of the genomic environment of the cell. The second component is conceptual. It changes our focus from primary manipulation of proteins by studying or manufacturing them exogenously and interacting with them (as with a monoclonal antibody), to an approach that manipulates cell proteins by using the nucleic acid base coding that is ultimately responsible for their production and degradation. In essence, this approach mimics ontogeny and has much greater flexibility and power.
To the surgeon who is just evolving an interest in this field, the information available must appear massive. Even so, the rate at which new information is being added is exponential and we must regard the entire field as still in relative infancy. Considering that there are about one hundred thousand genes in the human genome, each with its own transcriptional control parameters, many features of which are incorporated into the organization of base pairs preceding and sometimes remote from the gene itself, the magnitude of the science becomes apparent. On the other hand, some genes are far more important than others, and it is the manipulation of these genes that will receive initial attention. There is great excitement over the potential of gene therapy to introduce tumor suppressor genes, knock out genes that promote excessive growth in tumor cells, locate specific genes that control cell replication, introduce the genomic capacity to make critical proteins or polypeptides that are genetically deficient, inhibit the proliferative response to endothelial injury, transform scar tissue into contractile tissue or, in the terminology of the day, reengineer human physiology.
Oncologists have been working with strategies of gene manipulation longer than most other disciplines because it was recognized early that cancer was a problem of unregulated cell growth. Thus, it is not surprising that many of the studies approved for human trial are focused on patients with cancer. Surgeons should be encouraged and proud that pioneering studies approved by the National Institutes of Health were developed by surgeons [2]. Surgeons have a unique opportunity to gain access to tissues most affected by tumor growth. Early strategies may involve changing the physical environment of tumors to promote transfer of genomic material across cell membranes or specific cannulation of the vascular supply for tumor beds. Specific gene therapy may become a form of adjunctive chemotherapy, and there is much opportunity in this field.
On the other hand, diving into the literature of molecular biology is daunting, at a minimum. Surgeons are rightfully intimidated by attacking a literature written in a language that is difficult to understand. In fact, it is this language that keeps most surgeons from being more actively involved in reading about and using the tools of molecular biology in their practice. In distinction to the language, the concepts are remarkably simple to understand. Although many of the techniques are arcane and the detailed biochemistry very complex, liaison with fundamental scientists in cooperative ventures is not only possible but advisable. Surgeons should consider a couple of references that explain the concepts and critical language very well [3–5]. Surgeons working in academic institutions will find their colleagues in molecular biology enthusiastic and excited about the opportunity to collaborate. Most biologists do not possess the physiologic skills or knowledge to fully realize the potential of their work when applied to clinical environments, just as clinicians do not fully appreciate what molecular biologists can do to help with their scientific problems.
The article in this issue of The Annals is a good example of the potential strength of this alliance. Retroviral infection, chemical transduction, and inoculation of genetic material through the use of adenoviruses are all concepts easily understood. Yet the actual creation of viral vectors, the specific choice of virus, modification of the reproductive capacity of the virus, inclusion or exclusion of important promoter regions of genes, and substitution of generic promoters for specific base sequences all involve great technical skill. A cellular biologist can easily understand the concept of replacing a faulty heart valve while supporting the circulation. On the other hand, it would be imprudent for that person to attempt the procedure simply because it is understood. This is exactly the case for ventures into cell biology. The next several years should result in exciting applications of molecular biology to problems of great interest to thoracic surgeons, and we must be prepared to grasp the opportunities that lie before us. As when visiting any foreign territory, a knowledge of the language and customs will greatly enhance the adventure.
Footnotes
Address reprint requests to Dr Wechsler, Department of Surgery, Medical College of Virginia, Box 980645, Richmond, VA 23298-0645.
References
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  A. Basile-Borgia, J. H Abel, and H. Mahloogi Molecular advances in cardiac and cardiovascular disease Perfusion, March 1, 1999; 14(2): 89 - 99. [Abstract] [PDF]
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