Diagnosing Alzheimer’s Earlier
Researchers at the Mayo Clinic may have found a way to cast light on the difficult problem of diagnosing Alzheimer’s disease. At this time, the only way to definitively diagnose Alzheimer’s disease is at autopsy, when the characteristic amyloid b-protein plaques and neurofibrillary tangles can be seen directly. However, Joseph F. Poduslo and colleagues at the Rochester, Minn, healthcare facility report in the August issue of Nature Biotechnology (2000;18:868–872.) that they have found a way to radiolabel the neuritic-type plaques deposited by the amyloid b-protein in the living brain.
Using a transgenic mouse model of Alzheimer’s, Dr Poduslo intravenously administered a synthetic form of the amyloid b-protein that was radiolabeled with iodine-125. The radiolabeled material crossed the blood-brain barrier and bound to the diseased plaques. Thus, the plaques were labeled with the radioactive material.
Although the results are promising, Dr Poduslo said he must increase labeling efficiency to label more of the plaques throughout the brain—a feat that may be achieved with another isotope.
Patenting Life’s Instructions
When and what to patent was the topic of a July 13, 2000 hearing on “Gene Patents and Other Genomic Inventions” before the House Judiciary Subcommittee on Courts and Intellectual Property.
Although members of the subcommittee said the subject is difficult for nonscientists to understand and that they doubted legislation on the issue would be introduced this session, they said it will doubtless come up in future sessions of Congress. The hearing was also called to determine the validity of proposed patent guidelines from the Patent and Trademark Office. Those new rules should be in final form by the fall.
The hearing exposed committee members to diverse testimony from patient advocacy groups, the federal government, and industry. With different constituencies, the groups provided differing points of view about the need for patents on the discovery of genes or other entities involved in genomes.
The issue of patenting genes and DNA sequences came to attention during discussions of the Human Genome Project and amid fears that a private company might end up owning significant parts of the genetic blueprint of life. Although everyone agrees that at some point in molecular genetics a patent is necessary, the point at which patenting should occur is in dispute.
“No one would begin the expensive process of drug development without intellectual property protection. The development of cures for uncured diseases, such as kidney cancer, will come out of the human genome project only if commercial development can take place,” said Carl Dixon, the President and Executive Director of the Kidney Cancer Association, a voluntary patient organization. “This development can take place only if commercial enterprises are able to commit substantial amounts of capital to research and development.”
Testifying on behalf of the government, Q. Todd Dickinson, Undersecretary of Commerce for Intellectual Property and Patent and Trademark Office Commissioner, said a balance must be achieved between encouraging new innovation while still providing research incentives.
“Research tools like gene patents are particularly deserving of patent protection,” said Randal W. Scott, MD, president and chief scientific officer at Incyte Genomics. His company’s future depends on gene patenting.
“Critics of gene patents often argue that they are merely research tools and, as such, should not be eligible for patent protection to avoid the risk of making research more expensive,” Dr Scott told the committee. Dr Scott disagrees with this argument and said that under current law, inventions that “enable further scientific progress are particularly deserving of protection.” Nothing in the history of patent law or in court decisions interpreting this law supports the distinction between unpatentable “research tools” and other patentable inventions.
Former National Institutes of Health Director Harold Varmus, MD, said he is “troubled by widespread tendencies to seek protection for intellectual property increasingly early in a process that ultimately leads to products of obvious commercial value, because such practices can have detrimental effects on science and its delivery of health benefits.” Speaking as president of the Memorial Sloan-Kettering Institute in New York City, Dr Varmus said the patenting of basic techniques in molecular biology and similar actions changed the conduct of biomedical science “in some ways that are not always consistent with the best interests of science. It has promoted the creation of sometimes aggressive and usually expensive offices at many academic institutions to protect intellectual property and to regulate the exchange of biological materials that would at one time have been freely shared among academic colleagues.” He is most concerned that these changes have reduced the exchange of ideas among academic scientists—a factor that has delayed the progress of science. Without restructuring patent rules, progress could be retarded even further.
Varmus noted that “Efforts to seek intellectual property protection for cloned genes, gene variants, portions of genes, DNA copies of messenger RNA, and the proteins encoded by genetic information have presented an especially perplexing problem because the traditional standards for patenting, especially non-obviousness and utility, have been difficult to define fairly in this context. As a result, some of the gene patents issued to date do not display the traditional balance between the exclusionary right granted by the patent to the inventor and the disclosure to the public of a new, useful, and non-obvious invention that might otherwise have been maintained as a secret. Such patents appear to reward excessively the preliminary and frankly obvious work of determining DNA sequence and to diminish the prospect of financial return from the innovative scientific work required to determine gene function and utility.”
“Furthermore, some of the issued patents have seemed very broad in their claims. For example, some grant rights to many other functionally related genes solely on the basis that their sequences resemble the submitted one; such apparently extensive rights might well discourage others from studying members of such gene families to achieve practical goals,” Varmus said.
“Contemporary biologists are privileged to work at a time of unprecedented excitement. But overly enthusiastic protection of intellectual property too early in the process of product development can impede the delivery of public health benefits from discoveries in many important fields, including genomics,” Varmus concluded.
Gene for Familial Primary Pulmonary Hypertension Identified
Scientists from the College of Physicians and Surgeons at Columbia University in New York and the International Primary Pulmonary Hypertension Consortium have identified the gene mutation responsible for familial pulmonary hypertension, a rare inherited disease. In the September issue of The American Journal of Human Genetics, James A. Knowles, MD, and colleagues of Columbia reported on their studies of families carrying the disease, which helped uncover the genetic alteration. The other report is slated for the September issue of Nature Genetics (2000;26:1–4). Both reports were released early on the respective journals’ websites.
Knowles and colleagues said that mutations in the gene for bone morphogenetic protein receptor-II are the cause of the disease. The gene is located on chromosome 2, an area of hot research among scientists looking for the cause of this disease. Dr Knowles and members of his laboratory examined the DNA of people from 35 families in which the disease was passed down through the generations. Narrowing the possibilities, they found a mutation in 9 families that might interfere with the action of the protein made at the command of the gene. Claude Lenfant, MD, director of the National Heart, Lung, and Blood Institute called the finding a major breakthrough. “The identification of a gene that is associated with the inherited form of the disease takes us one step closer to understanding its causes and provides essential information that should lead to the design of more effective therapies for this devastating condition.”
- Copyright © 2000 by American Heart Association