Genetics and human malleability.

Genetics and Human Malleability Just how much can, and should we change human nature ... by genetic engineering? Our response to that hinges on the answers to three further questions: (1) What can we do now? Or more precisely, what are we doing now in the area of human genetic engineering? (2) What will we be able to do? In other words, what technical advances are we likely to achieve over the next five to ten years? (3) What should we do? I will argue that a line can be drawn and should be drawn to use gene transfer only for the treatment of serious disease, and not for any other purpose. Gene transfer should never be undertaken in an attempt to enhance or "improve" human beings. What Can We Do? In 1980 John Fletcher and I published a paper in the New England Journal of Medicine in which we delineated what would be necessary before it would be ethical to carry out human gene therapy. [1] As with any other new therapeutic procedure, the fundamental principle is that it should be determined in advance that the probable benefits outweigh the probable risks. We analyzed the risk/benefit determination for somatic cell gene therapy and proposed three questions that need to have been answered from prior animal experimentation: Can the new gene be inserted stably into the correct target cells? Will the new gene be expressed (that is, function) in the cells at an appropriate level? Will the new gene harm the cell or the animal? These criteria are very similar to those required before use of any new therapeutic procedure, surgical operation, or drug. They simply require that the new treatment should get to the area of disease, correct it, and do more good than harm. A great deal of scientific progress has occurred in the nine years since that paper was published. The technology does now exist for inserting genes into some types of target cells. [2] The procedure being used is called "retroviral-mediated gene transfer." In brief, a disabled murine retrovirus serves as a delivery vehicle for transporting a gene into a population of cells that have been removed from a patient. The gene-engineered cells are then returned to the patient. The first clinical application of this procedure was approved by the National Institutes of Health and the Food and Drug Administration on January 19, 1989. [3] Our protocol received the most thorough prior review of any clinical protocol in history: It was approved only after being reviewed fifteen times by seven different regulatory bodies. In the end it received unanimous approval from every one of those committees. But the simple fact that the NIH and FDA, as well as the public, felt that the protocol needed such extensive review demonstrates that the concept of gene therapy raises serious concerns. We can answer our initial question, "What can we do now in the area of human genetic engineering?," by examining this approved clinical protocol. Gene transfer is used to mark cancer-fighting cells in the body as a way of better understanding a new form of cancer therapy. The cancer-fighting cells are called TIL (tumor-infiltrating-lymphocytes), and are isolated from a patient's own tumor, grown up to a large number, and then given back to the patient along with one of the body's immune growth factors, a molecule called interleukin 2 (IL-2). The procedure, developed by Steven Rosenberg of the NIH, is known to help about half the patients treated. [4] The difficulty is that there is at present no way to study the TIL once they are returned to the patient to determine why they work when they do work (that is, kill cancer cells), and why they do not work when they do not work. The goal of the gene transfer protocol was to put a label on the infused TIL, that is, to mark these cells so that they could be studied in blood and tumor specimens from the patient over time. The TIL were marked with a vector (called N2) containing a bacterial gene that could be easily identified through recombinant DNA techniques. …