Researchers are getting closer to identifying a way to design safer gene therapy techniques, which in turn could lead to the development of safer diagnostics. A research team at the National Human Genome Research Institute's (NHGRI; Bethesda, Maryland) division of intramural research released a report in a June issue of the journal Science touting a discovery about how a genetically engineered virus can disrupt a gene's normal function. "Gene therapy is a promising field that offers fundamentally new ways of curing human illness," said NHGRI director Francis Collins, MD, in describing the report. "A decade of clinical studies has demonstrated the complexity of the biology behind gene therapy and the technical problems researchers have experienced. This study provides insight into one of the most serious, current technical hurdles," he added.

The discovery has widespread implications, especially for federally funded gene therapy research, the researchers believe. In January, the FDA halted 27 current gene therapy studies after two children treated by French researchers developed a leukemia-related condition. The children have a form of severe combined immunodeficiency disease. Current methodology involves curing a genetic illness by inserting normal, functional copies of a gene into target cells of the body. Different types of viruses can be genetically engineered by researchers so that the target cells are "invaded" by the normal cells, and the normal genes are integrated into the chromosomes. The most widely used virus in gene therapy studies Moloney murine leukemia virus (MoMuLV) is actually a mouse retrovirus, but it can infect human cells.

The children in the French study, NHGRI researchers believe, developed leukemia because the MoMuLV inserted therapeutic genes next to a gene that promotes blood cancer. "Provided this new insight, researchers can now aim to improve the design of gene therapy techniques that can insert genes in less risky areas of the genome," explained NHGRI scientific director Eric Green, MD. Green is director of the division of intramural research and chief of the Genome Technology Branch, where the discovery was made. "The viruses used therapeutically can be altered in various ways and now tested in the lab to see if they insert curative genes more safely," he added.

The belief is that MoMuLV randomly integrated into target cells had not been challenged because scientists weren't able to study the integration patterns in a large-scale method. NHGRI scientists developed a technique to rapidly sort through the genome of hundreds of individual cells to see where the MoMuLV inserts itself. The researchers were able to identify the insertion site by capturing and sequencing a small sample of the human genome immediately adjacent to where the retrovirus inserted. The researchers looked at the computerized databases of the finished copy of the human genome. They compared the sample sequence to the sequence of the 30 base pairs of the subunits that make up the human genome.

"Without the success of the Human Genome Project, knowing precisely where the retroviruses inserted would have been nearly impossible," Collins noted. "These are the kinds of laboratory applications for which the finished genome sequence was intended, applications that will end up improving the practice of medicine."

Digital mammography not superior to film

A study released in June by the Michigan Cancer Consortium (MCC; Lansing, Michigan) has concluded that there is "insufficient data" to demonstrate that digital mammography is superior to standard screen film mammography for the early detection of breast cancer. The study, which reviewed a variety of evidence concerning digital mammography, was requested by member organizations of the MCC, according to Vicki Rakowski, co-chair of the MCC and executive vice president of medical affairs for the American Cancer Society's (Atlanta, Georgia) Great Lakes Division. The study was conducted by 12 members of MCC, described as experts in the field of breast cancer.

Rakowski said, "since January 2000, when the FDA approved digital mammography for clinical use, it has been a topic of controversy and confusion among consumers, the healthcare providers who advise them and health facilities considering the purchase of the technology." She added: "We now have a current, succinct summary about the issue."

Reviewing the findings of the study, Max Wicha, MD, also a co-chair of MCC and director of the University of Michigan's (Ann Arbor, Michigan) Comprehensive Cancer Center , said that "until such time that digital screening is shown to be superior in the early detection of breast cancer, screen film mammography will remain the method of choice for breast cancer screening." He said, however, that the MCC's position on the issue could change "when and if additional evidence emerges."

In a summary of the study's findings, various similarities were reported for the two modalities as well as a list of advantages and disadvantages for digital screening. Similarities listed included comparable sensitivity, comparable training requirements, the same compression of the breast required and similar screening intervals.

The advantages of digital screening included:

Greater speed in acquiring images and more efficiency in storing and transmitting collected electronic data.

Improved ability to manipulate the images and decreased need to recall the patient for additional images.

Greater contrast resolution to enhance detection of subtle differences between normal background tissue and tumors.

Potentially lower biopsy rates.

The listed disadvantages included:

Better spatial resolution for traditional film and the potential for increased manipulation of digital images for their optimal interpretation.

Higher digital radiation dosage "for women with large breasts that may need more than one exposure to image the entire breast."

Higher cost "as high as $500,000 [for digital equipment], compared to $75,000 for screen film equipment."

Rakowski noted that the National Cancer Institute (Bethesda, Maryland) is currently conducting a large research effort, called the Digital Mammographic Imaging Screening Trial, which will track nearly 50,000 women and evaluate the available digital mammography systems. That study is designed "to provide additional insight into the issue," she said, but she noted that its results will not be available until next year or 2005. "Until those data are analyzed, we will not know if there is additional benefit to women from digital screenings or an improvement in the accuracy of breast cancer detection," she said.

Lifetime risk to increase for diabetes in U.S.

One in three Americans who were born in 2000 will develop diabetes, according to a Centers for Disease Control and Prevention (CDC; Atlanta, Georgia) report presented at the American Diabetes Association's (Alexandria, Virginia) 63rd annual scientific sessions held in New Orleans, Louisiana, in mid-June. "The estimated lifetime risk of developing diabetes for persons born in 2000 was 33% for males and 39% for females, based on data from the National Health Interview Survey, U.S. Census Bureau and other sources," said K.M. Venkat Narayan, MD, chief of the diabetes epidemiology section in the division of diabetes translation at the CDC. The highest estimated lifetime risks were among Hispanics 45% for males and 53% for females.

"Primary prevention of diabetes is thus an important priority for the nation," said Narayan, "because diabetes is one of the most prevalent and costly chronic diseases in the U.S." And James Gavin III, MD, PhD, chair of the National Diabetes Education Program (NDEP), jointly sponsored by the National Institutes of Health (NIH; Bethesda, Maryland) and the CDC, emphasized that "Prevention is imperative. The healthcare delivery system must dramatically scale up preventive efforts to stem the rising tide of Type 2 diabetes." Gavin went on to describe an effort of the NDEP to help prevent Type 2 diabetes. The campaign, "Small Steps, Big Rewards. Prevent Type 2 Diabetes," emphasizes that modest lifestyle changes including healthier diets and physical activity can prevent the onset of Type 2 diabetes, the less serious and most common form of the disease. Nationally, diabetes has increased nearly 50% in the past 10 years alone, according to CDC estimates, and the incidence of the disease is expected to grow another 165% by 2050 under current trends.

"The Diabetes Prevention Program (DPP) and other international clinical trials have shown that Type 2 diabetes can be prevented or delayed through modest changes in lifestyle," said Gavin. In the DPP, people with pre-diabetes those whose blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes were able to cut their risk of developing Type 2 diabetes by more than half by losing 5% to 7% of their body weight through moderate changes, including a lower-fat diet and increased exercise, such as a 30-minute brisk walk five times per week. These lifestyle changes worked for people of every ethnic or racial group who participated in the study, and they were especially successful for people over age 65.

Heart valves to get 'virtual' modeling

A pair of researchers at Atlanta, Georgia, universities are attempting to integrate disparate approaches in tackling the problem of blood surging through artificial mechanical heart valves, with the hope that they can bring better design to those devices and then extend their work to even more complicated issues of heart repair. Focused on what he calls the "virtual" side of the problem is Fotis Sotiropoulos, associate professor in the School of Civil and Environmental Engineering at the Georgia Institute of Technology (Georgia Tech) and an expert in computational fluid mechanics. Focused on what is the more traditionally real or "experimental" side, is Ajit Yoganathan, regents professor in the Wallace H. Coulter School of Biomedical Engineering at Georgia Tech and Emory University, and internationally known for his work in fluid mechanics research and, in particular, artificial heart valves. The two have received a four-year, $1.4 million grant from the NIH to merge their separate approaches to design mechanical heart valves that will provide longer life to those implanted with these devices.