Biotechnology offers great promise for new medicine
By: Molly Bloom
The recent mapping of the human genome and other developments in biotechnology have great promise for the future of medicine. Yet this opportunity is still very much a promise, not a reality, according to Dr. John Baumann, president of the medical and dental staff at The Medical Center at Princeton.
Dr. Baumann will be one of the speakers at a seminar Nov. 1 on the opportunities for new medicine based on genetics research. "We’re standing on the edge of what will be, looking into the future of what it may be possible to do," said Dr. Baumann. "The rapidly-growing library of genetic research gives scientists a new way to look at disease."
Usually doctors look at diseases in terms of their symptoms, said Dr. Baumann, who is also director of the J. Seward Johnson Sr. Radiation Oncology Center. In this approach, doctors try to cure the disease by treating its symptoms. But now doctors can take a different approach to treating disease. Because they know more about the genetic basis of disease, they can zoom in and attack the disease at the cellular level, Dr. Baumann said.
Doctors can look at disease not just a collection of symptoms, but as a result of biochemical abnormalities, he said. Since the genome codes everything about a person, many diseases are the result of a "defective" gene.
Adenosine deaminase (ADA) deficiency, for example, is a severe combined immune deficiency also known as the "Boy in the Bubble disease." It is a result of inheriting two defective copies of the gene that codes for ADA gene. ADA is used by the body to convert a potentially toxic cellular waste product into a benign compound. When a person does not have a correct copy of the ADA gene, his body is unable to perform this conversion.
"Gene therapy offers a very promising new kind of pharmaceutical," said Shirley Tilghman, Howard A. Prior professor of life sciences at Princeton University, in an e-mail. One of the most talked-about new treatments involves replacing "bad" genes with "good" ones.
A common approach to this replacement involves inserting the correct DNA sequence into a retrovirus, a type of virus that normally infects cells by copying part of their genetic material into the genetic material of a host cell. The harmful parts of the retrovirus genome are replaced with a specific gene sequence.
The virus transfers this sequence into the host cell and replaces the defective gene with a brand new correct copy of it. In an early gene therapy experiment, researchers inserted a functioning ADA gene into a retrovirus’s genome. The retrovirus delivered the new gene to a target cell. The target cell incorporated the gene into its DNA.
The newly modified cells were reintroduced into ADA patients. Because they could then produce ADA, their ability to function normally was greatly improved. But because the target cells had a relatively short life span, the treatment needed to be repeated every six months.
"But to date there is not a single FDA approved therapy in which genes are introduced into people," said Dr. Tilghman, founding director of Princeton University’s Lewis-Sigler Institute for Integrative Genomics. Fixing the genome bit-by-bit may be common in hospitals of the future, but for now it is still in the labs.
Doctors are already using their expanded knowledge of the genome to treat patients. "Certainly there are patients who could benefit from genetic counseling," said Dr. Baumann.
A patient can be tested for genes known to cause an increased risk for a disease. While it may not yet be possible to cure the disease, the new knowledge of their risk factors can help patients choose among treatment options or modify their behavior to decrease their risk of eventually getting the disease.
For breast cancer patients, this knowledge can mean the difference between choosing surgery or another treatment option, he said. Knowledge is power. And with this great power to look into someone’s genetic makeup and medical future comes the possibility of abuse of power.
Dr. Baumann is concerned that, without proper regulations, insurance companies could use information about a patient’s genetic tests to discriminate against them, refusing to insure them or to provide expensive treatments. "There has to be a serious effort to maintain privacy," he said.
The shield of privacy should be comprehensive. "Once there’s a chink in that armor, that can affect you and your entire family," said Dr. Baumann.
Researchers and other concerned parties must also ensure that clinical trials of gene therapies are safe, Dr. Tilghman said. "The tragic events at Penn last fall [in which an 18-year-old died after receiving an experimental gene therapy at the University of Pennsylvania for an inherited liver disease] highlight the critical importance of good solid basic and pre-clinical research to ensure that when genes are introduced into people, there is a minimal risk."
"As you can imagine," Dr. Tilghman continued, "gene therapy research will be watched very very carefully from now on, to ensure that patients in clinical trials are properly protected."
This type of new research is "too new" for there to be special scientific guidelines for it, said Dr. Baumann. Clinical trials of gene therapies generally follow the same model as those for conventional treatments, he said.
"I don’t see any reason why genetic research should be handled differently from other kinds of clinical research," Dr. Tilghman wrote in an e-mail interview. "Gene therapy will be monitored very closely because it is entirely new, not because there is something fundamentally different."
According to Dr. Elliott Sigal, senior vice president, early discovery and applied technology at Bristol-Myers Squibb, genomics is offering major medical opportunities for the pharmaceutical industry. The pharmaceutical research and development process is typically quite long before drugs make it to market. Genomic technologies offer the promise of a large influx of novel discovery targets and improved processes for drug discovery and development.
Dr. Sigal’s responsibilities encompass genomics, pharmacogenomics, high-throughput screening, combinatorial chemistry, structural biology, biopharmaceuticals and external biotechnology alliances. He joined Bristol-Myers Squibb in 1997 as vice president for the then new department of applied genomics.
One of the most exciting opportunities in clinical development is the potential to use an individual’s genetic information to select the right drug for the right patient, according to Dr. Sigal, who also will speak at the Nov. 1 seminar. Theoretically this offers the ability to develop tailored medicines with both higher efficacy and better safety profiles.
The talk will be moderated by Richard Preston, author of "The Hot Zone," a non-fiction account of the spread of the ebola virus, and "The Cobra Event," a novel about biological terrorism.
Mr. Preston received a doctorate in English from Princeton University in 1983. He is a regular contributor to "The New Yorker" and has written numerous magazine and journal articles on current issues in science and technology.