None of us has any control over the brilliance of the scientists who are conducting biotech research. We do not propose any overhaul of the FDA. What we know is that Members of Congress have control over the health care reform bill. BIO wants to support health care reform. We strongly support universal coverage. But, even more important, we want an opportunity to find cures and therapies for diseases like cancer. That is our goal and all we want is a fighting chance in the market place to achieve it. We look forward to working with the Technology Subcommittee to fashion a health care plan that encourages innovation. This is your jurisdiction, your expertise, and your issue. LIST OF ATTACHMENTS cle: "New Weapon in Gene Therapy May Be A Switch That Tells Cells When to Fight", 1 Street Journal, January 26, 1994. cle: "Biotech Firms Try to Block Clinton Price-Control Plan", Wall Street Journal, Jary 31, 1994. MEDICINE New Weapon in Gene Therapy May Be - Switch That Tells Cells When to Fight By JERRY E. BISHOP Staff Reporter of THE WALL STREET JOURNAL A biologist and a chemist may have found a way to install a biological “switch" in human cells that could turn genes on and off as needed. The discovery may open a new way to treat human ills with gene therapy. In existing gene therapy, a patient's cells are removed, implanted with a gene that tells cells to manufacture a protein that helps fight or resist disease and then reintroduced to the bloodstream. But now researchers are talking about a new era of "regulated gene therapy," in which one pill switches on a protein-making gene, and then a second pill turns it off. It may be possible, for example, for a diabetic to get an infusion of cells engineered with the gene switch and the insulin gene. Then, instead of taking several injections of insulin a day, the patient could take nontoxic pills to switch the insulin gene on and off as needed. Chemotherapy for cancer may someday be a matter of taking a pill to switch on poisonmaking genes in cells that have been ✔ned to home in on a tumor. st week, Arlad Pharmaceuticals Inc., a fledgling Boston biotechnology company, announced that it had licensed the technology. "It's the first time anyone has been able to regulate gene expression," says Ariad President Harvey Berger, who predicts that the first human experiments using the new technique might begin as early as next year. The invention - by chemist Stuart L. Schreiber of Harvard University and biologist Gerald R. Crabtree of Stanford University has been stirring enthusiasm among biologists, gene therapists and biotechnology researchers. Michael Blaese, chief of clinical gene therapy research at the new National Center for Human Genome Research in Bethesda, Md., notes that the problem with current gene therapy is that the implanted gene functions continuously, supplying, for instance, a child with a missing protein to avert mental retardation. "But many genes in the body, such as the one for insulin or for various hormones, work only intermittently," he explains. The new gene-switch technique "offers (gene therapy] a really unique set of tools." The researchers are even designing a "fail safe" switch that will cause the genetically engineered cells to self-destruct if they malfunction, cause unwanted side effects or have simply finished their job. The invention hinges on the workings of cell receptors - specialized proteins on or near the cell's surface. These receptors are designed to grab hold and react to chemical signals drifting by in the bloodstream. Each protein receptor reacts to one particular chemical signal and no other. When a receptor is tripped by a passing chemical, it launches a train of signals that reach into the nucleus of the cell where the genes reside. The signals tell the cell to start reading the "message" written in a particular gene: instructions to begin making a certain protein. For instance, a rising concentration of glucose in the blood trips a receptor that turns on the Insulin gene in certain cells in the pancreas gland. Drs. Schreiber and Crabtree created a synthetic receptor, derived from one found in white blood cells, called T-cells, that helps fight off invasions of foreign tissues. The T-cell receptor consists of several Identical but separate proteins that hang side by side just below the cell surface. The receptor lies dormant until some chemical permeates the cell and links two or more of the proteins together. This linking tells a gene in the T-cell to begin making proteins that launch an attack against, say, a transplanted kidney. What intrigued, the two scientists about this T-cell receptor was that a molecule of a Japanese drug, FK506, will bind to one of the receptor's proteins and prevent it from linking up to a neighboring protein. The drug thus blocks the receptor from turning on its gene, which explains why it is so effective in preventing the rejection of transplanted organs. The two scientists figured out how to use FK506 to activate the receptor and turn on the gene. They welded molecules of FK506 to opposite ends of a "linker" molecule to create a kind of dumbbell-shaped molecule, dubbed FK1012, Dr. Schreiber explains. When FK1012 seeps into a cell with the receptor, one end will bind to one receptor protein and the other end to a neighboring protein, thereby creating the link that activates the receptor and turns on the gene. The scientists can package the components needed to make the receptor into a gene cassette along with a "gene of inter est," which controls the relevant protein production. The cassette can then be spliced into whole cells such as T-cells. Whenever the researchers want to turn on the gene of interest they merely add a little FK1012. To turn it off, they add a modified version of FK506. The trick, says Dr. Schreiber, has worked in test tubes. "Next, we'll try to introduce the system in simple organisms like the fruit fly or a nematode," he says. "A little way down the road we'll put it into mice." * For their own basic research, Drs. Schreiber and Crabtree say they intend to insert a particular gene and the switch into mice and then turn the gene on or off at any stage of a mouse's development, from embryo to adulthood, to see what the gene does. For human therapy, Ariad envisions taking a patient's own T-cells and, in the test tube, Inserting the synthetic receptor and a gene of interest into the cells. The cells are returned to the patient who takes a pill of FK1012, or some similar drug whenever he needs to turn the gene on and a pill of FK506 to turn it off. The synthetic receptor would also give gene therapists a fail-safe switch. Nature has programmed all cells to die whenever their role in life is finished. The researchers hope to install a second synthetic receptor in the gene cassette. Then, when the cells have completed their gene ther apy or if something should go wrong, a simple pill could switch on the apoptosis signals and the cells would commit sui cide. THE WALL STREET JOURNAL WEDNESDAY, JANUARY 26, 1994 |