Fibril shape is the basis of prion strains and cross-species prion infection

New research on prions, the infectious proteins behind “mad cow” disease and Creutzfeld-Jakob disease in humans, suggests that the ability of prions in one species to infect other species depends on the shape of the toxic threadlike fibers produced by the prion. Two studies on the topic appear in the 8 April issue of the journal Cell. Although research suggests that prions from one species rarely infect other species, some scientists believe the species barrier was breached when a new version of Creutzfeld-Jakob disease appeared in humans after several recent epidemics of bovine spongiform encephalopathy or “mad cow” disease. Since then, barriers to the transmission of prion diseases between species “have emerged as a major public health issue,” according to Eric Jones and Witold Surewicz of Case Western Reserve University.

Prion diseases are caused by misfolded variants of the normal prion protein, which aggregate into fibrous tangles called amyloid fibrils and cause fatal wasting of brain tissue. The abnormally folded protein itself appears to act as an infectious agent, transmitting disease without a DNA or RNA genome such as in a virus. Although disease prions seem to infect normal prions by binding to them and forcing them to take on the abnormal configuration, researchers remain uncertain about the exact molecular details of infection.

Earlier studies identified many “strains” of disease prions across mammalian and yeast species. Researchers thought these strains could be defined by differences in the underlying amino acid sequences of the prions. Under this scenario, disease transmission would be more likely between species with similar prion amino acid sequences. But a few mysteries stood in the way: Some individuals harbored several different prion strains that caused different disease outcomes, even though all the prions shared the same amino acid sequence. In some cases, a single amino acid change in one species could completely change its ability to infect a previously “off-limits” species, Surewicz and colleagues found.

In a study published last year in the journal Molecular Cell, Surewuicz and colleagues also demonstrated that a “preseeding” process between animals with different prion amino acid sequences could overcome species barriers. For instance, mouse prion fibrils normally infect humans but not hamsters. But when mouse prions were brought into contact with hamster prion amyloid fibrils, a new strain of mouse fibrils emerged with the ability to infect hamsters but not humans. The new mouse strain had the same amino acid sequence as the original mouse strain but completely different infectious capabilities.

With the help of atomic-level microscopic observation of prions in humans, mice, and hamsters, Jones and Surewicz discovered that it is the specific shape of the amyloid fibrils, and not the amino acid sequences, that may allow prions from one species to infect another. In a second Cell study, Jonathan Weissman and colleagues at the University of California, San Francisco came to the same conclusion in their experiments with yeast. They too discovered that the particular shape of a prion amyloid fibril was the determining factor in whether one species of yeast could infect another yeast species. Just as in the case with the preseeded mice fibrils, a particular fibril shape in Saccharomyces cerevisiae yeast allowed prion transmission to Candida albicans yeast. The transmission event led to a new strain of Candida prion fibrils that could in turn infect Saccharomyces.

Although fibril shape appears to be the deciding infective factor, amino acid sequence is still important because it defines a set of possible preferred fibril shapes that prions can adopt, Weissman says. Species with similar amino acids sequences share an overlapping set of shapes, which helps explain why species with shared sequences have the ability to infect each other. Surewicz says the next step in their research will be to examine fibril shape differences at much higher resolution. Their experiments also used a shortened version of the mammalian prion protein, so they hope to test the fibril factor in a full-length protein soon.

Jones and Surewicz also note that the new findings offer “the unsettling possibility” that repeated cross-species transmission events might eventually create prion fibril strains that can bridge the infection gap between previously separate animals like humans and elk and deer, which suffer from a prion disease called chronic wasting disease. Surewicz stresses, however, prion infection between species is still rare. “Fortunately, transmission by eating is very ineffective. There have been hundreds of thousands of bovine spongiform encephalopathy cases, for example, and lots of people exposed to tainted beef products, but very few cases of variant Creutzfeld-Jakob.” He says there “must be protective mechanisms working there, but we don’t know what they are.”

Source: Cell Press
April 26, 2005

Original web page at


Gene-editing technique cuts out diseased DNA

A gene-editing process that corrects mutations without weaving foreign genetic material into the chromosome has been demonstrated in diseased human cells for the first time. It could provide a less risky and more efficient alternative to gene therapy, which has resulted in leukaemia in some patients.

A team led by scientists at Sangamo Biosciences in Richmond, California, US, say they have corrected the single gene mutation that causes the fatal X-chromosome-linked severe combined immune deficiency (X-SCID) – or “bubble boy” disease – in human T-cells. They treated the cells in test tubes with the company’s proprietary type of “zinc finger nucleases” (ZFNs) and have published their results in Nature.

ZFNs are proteins made up of “fingers” of around 30 amino acids and stabilised by a zinc atom. Each finger binds to a specific combination of DNA bases and is attached to a DNA-cutting enzyme called a nuclease. By using different combinations of amino acids, they can be designed to latch on to DNA at exactly the place where the mutated gene lies and cut it. This triggers the body’s natural repair process, called homologous recombination, which corrects the gene where the DNA was cut, The researchers provided the cells with a copy of the correct gene as a template.

Boys with X-SCID have a faulty gene on their X chromosome which renders their immune systems highly deficient. In 2000 Alain Fischer at the Necker Hospital in Paris, France, treated 10 boys with X-SCID using a mouse retrovirus to add a healthy copy of the gene. Although the treatment worked, at least two of the boys developed leukaemia as a result and one died. This was because the position of insertion of the new gene cannot be controlled and in these cases ended up being inserted near another gene called Lmo2. This helps control cell growth and can contribute to cancer if turned on at the wrong time. In contrast, ZFNs are highly specific. “ZFN-induced gene targeting places the normal gene at its normal chromosomal location, where it should have no untoward genetic consequences,” explains Dana Carroll, a biochemist at the University of Utah in Salt Lake City, US, who has used ZFN to correct genes in fruit flies. But Carroll warns that side effects cannot be ruled out: “There is still the possibility that some alternative reactions may occur.” For example, some cancers are thought to be caused by chromosomes that are broken and then stuck back together incorrectly.

Matthew Porteus at the University of Texas Southwestern Medical Center in Dallas, US, an author of the Nature paper, established in 2003 that ZFNs can stimulate homologous recombination in human cells. But he corrected “model” genes, rather than disease-causing ones. Furthermore, both Porteus and Carroll only managed to correct a few per cent of treated cells.

In the latest work, the gene was corrected in 18% of the cells treated, enough to finally make the method therapeutically viable. “The Sangamo group has achieved truly remarkable efficiencies,” says Carroll. The researchers say the advance was achieved thanks to the specificity of a pair of two-fingered ZFNs, which bind to six base pairs each, to home in precisely on the target. “They used more complex ZFN combinations than had previously been used,” says Carroll. “This is a very satisfying demonstration of the power of the basic ZFN technology.”

Sangamo’s primary aim is to take blood from patients, correct the genetic errors and then infuse it back into them. As well as X-SCID, it says it will be targeting other genetic diseases caused by single gene mutations, including sickle cell anaemia and beta thalassemia. And it suggests that immune cells could perhaps be altered to prevent infection with HIV.

Journal reference: Nature

New Scientist
April 26, 2005

Original web page at New Scientist


Lessons in senescence

The cells stop dividing; the studies keep multiplying.
Exogenous expression of the ras oncogene triggers senescence in human fibroblasts. Staining with DAPI reveals the gradual appearance of senescence-associated heterochromatin foci, transcriptionally silent regions of DNA. Four days after cells are infected with a ras-containing retrovirus, nuclei also show a marked colocalization between heterochromatin protein 1ß and promyelocytic leukemia protein; ten days after infection, colocalization decreases. When aging and damaged cells undergo apoptosis or malignant transformation, their lives reach a dramatic dénouement: suicide or cancer. But when they undergo senescence, their destiny seems drab in comparison. They irreversibly exit the cell cycle, linger indefinitely, and die of undetermined causes. Senescent fibroblasts, in particular, “get big and flat, and they look ugly,” resembling fried eggs, notes Scott W. Lowe, a professor at Cold Spring Harbor Laboratory on Long Island.

For decades, senescent human cells were found only in culture. But since the 1990s, investigators have detected senescence in T lymphocytes extracted from HIV-infected people and in tumors exposed to cancer treatments. Persistent doubts about the phenomenon’s relevance in vivo should have softened. Yet the senescent cell remained a cytological ugly duckling. Not as scientifically glamorous, as revealing, or as well defined as the apoptotic or transformed cell, it received far less attention.

Lately, however, that ugly duckling has matured into a more formidable bird. Accumulating evidence suggests that even if few senescent cells normally exist in vivo, their secretions promote diseases and aging, says Felipe Sierra, director of the cell structure and function program at the US National Institute on Aging (NIA). As a result, he senses a modest resurgence in the senescence field after what he calls “a very dark period a few years ago.” Last January, an NIA-sponsored workshop explored possible interactions between senescent cells and the extracellular matrix. The meeting, held at the Buck Institute for Age Research in Novato, Calif., was intended as a wake-up call to its 18 participants to “start worrying” about the physiological effects of these interactions, says Sierra.

Another boost to senescence studies comes from new findings on intracellular mechanisms. Earlier research established that the p53 and Rb tumor-suppressor pathways are vital to the process, and the cyclin-dependent kinase inhibitors p16 and p21 also play roles. Yet senescence is far from fully characterized on the molecular level. One recent paper identifies proteins and mechanisms in a novel pathway, and another report implicates an enzyme not previously linked to senescence.

A deeper understanding of tumorigenesis is the likeliest outcome of these in vitro advances. René Bernards, a professor at the Netherlands Cancer Institute in Amsterdam, acknowledges that cell-culture senescence could be an experimental artifact. But Bernards, who conducts RNA interference screens for senescence-related genes, contends, “It’s a useful artifact because it involves many of the players that are normally deregulated in cancer.”
Links between senescence and the organism-wide aging process, on the other hand, are more tenuous and their therapeutic lessons more problematic. Efforts to reduce senescence in aging tissues “might end up promoting cancer,” cautions Peter D. Adams, a biologist at Fox Chase Cancer Center in Philadelphia.

Scientists originally induced senescence by serially passaging cells in culture. After a cell line has replicated several dozen times, telomeric erosion leads to mitotic arrest. In the past decade, studies have established that activated oncogenes, DNA damage, or oxidative stress can also trigger senescence. Different experimental protocols and culture conditions yield subtly different types of senescence. Moreover, its manifestations vary between cell types and even within a broad class of cells such as the fibroblasts.

Researchers agree nevertheless that all senescent cells probably undergo chromatin remodeling that permanently prevents their reentry into the mitotic cycle. Estela E. Medrano, a biology and dermatology professor at Baylor College of Medicine in Houston, studies histone acetylation and deacetylation, chromatin changes that respectively enhance and repress gene transcription. Her specialty is the melanocyte whose senescence might cause aging human skin to become mottled, and whose inability to senesce could foster melanomas.

Medrano postulates that senescence is mediated by a competition between histone acetyltransferases (HATs) and histone deacetylases (HDACs) to bind to promoters of cell-cycle genes. Excessive HAT or HDAC levels can each trigger senescence, she maintains. Her lab is investigating cellular complexes that sense these levels. “We want to know how and when the complex formations occur when the cells are aging in culture,” says Medrano.

In 2003, Lowe’s lab reported a striking chromatin development in some senescent fibroblasts. After DNA staining, their nuclei displayed many small, distinct spots containing heterochromatin, which is transcriptionally inactive. In contrast, DNA staining and heterochromatin markers were more uniformly distributed both in quiescent cells, which temporarily forgo mitosis under low-serum conditions, and in senescent fibroblasts that Lowe now hypothesizes lack a robust p16 response.

Formation of these small spots, which Lowe called senescence-associated heterochromatic foci (SAHF), was linked to repression of genes targeted by the transcription factor E2F; these genes encode mitogenic proteins. Lowe recognizes that SAHF might merely be a consequence, not a cause, of senescence. Yet he plans to explore “how these genes get silenced” and particularly how p16 and Rb contribute to the process.

Adams has already uncovered a pathway to SAHF that he says might operate parallel to the Rb pathway. By his own admission, Adams is not a senescence expert. But he recalls wondering, in reaction to Lowe’s paper, whether SAHF creation and exit from the cell cycle might be promoted by human homologs of certain yeast proteins; other researchers had found that the yeast proteins contribute to gene-silencing by helping form heterochromatin. Adams’ group subsequently uncovered several landmark events in a SAHF pathway. Participants include a histone H2A variant and nuclear bodies containing promyelocytic leukemia protein, a tumor suppressor.

Adams views his task now as filling in the gaps between these events. “It’s like digging a tunnel from England to France,” he explains. “You dig from England and you dig from France. And, hopefully at some point, you meet in the middle.” Lowe says that follow-up experiments should test whether manipulations to the molecules in Adams’ model would, in the long term, make cells resistant to senescence or, if not, would enable senescent cells to proliferate again.

Heterochromatin represses gene activity, but many genes in senescent cells actually display higher expression levels. The repression of repressors could account for some of this increased activity. Senescence experts insist, however, that euchromatin, which facilitates gene transcription, must also be involved. Data from a cDNA microarray study provide tentative support for this contention. Hong Zhang, a postdoc working with genetics professor Stanley N. Cohen at Stanford University School of Medicine, examined the gene-expression profiles of human fibroblasts and mammary epithelial cells. By filtering out genes upregulated in quiescence, the study identified transcriptional fingerprints unique to senescence, not those merely correlated with cell-cycle arrest. It also found that upregulated senescence-specific genes were physically clustered, an arrangement consistent with euchromatin formation.

“The clustering is sort of an in silico experiment,” notes Zhang. “You do it computationally, and it’s very exciting. But I think the first thing I need to do is to confirm it experimentally, to see whether there is a chromatin-structure alteration that occurs during senescence.” One possible approach, he adds, is a so-called “ChIP-Chip” experiment. Antibodies that bind, for example, to acetylated histones could be used to immunoprecipitate euchromatin-associated genomic regions, which then would be fragmented and identified on a genomic microarray.

Instead, Zhang has focused on smurf2, a ubiquitin ligase whose gene is upregulated in senescent cells. He and Cohen induced high levels of smurf2 expression in early-passage human fibroblasts, whose telomeres presumably were not exhausted. Showing no stress response or detectable DNA damage, the cells entered senescence if their p53 or Rb pathway was functioning. Intriguingly, the smurf2-induced senescence did not appear to depend on the enzyme’s ubiquitin ligase activity.

Protein upregulation, not as a cause but as an effect of senescence, is the bailiwick of Judith Campisi, a senior scientist at Lawrence Berkeley National Laboratory in Berkeley, Calif. A theory that she and others have touted is that senescent cells, far from being physiologically inert, secrete proteins that stimulate tissue aging and tumorigenesis. These secretions include degradative enzymes, inflammatory cytokines, and growth factors.
Campisi estimates that 30 to 40 proteins are involved.

In a study published in February, lab members irradiated human fibroblasts, causing them to senesce. The researchers injected these cells into mice together with immortal but nontumorigenic mouse mammary epithelial (MME) cells, and the murine cells formed malignant tumors. Further experiments suggested that this tumorigenic conversion was partly mediated by matrix metalloproteinase-3, an enzyme secreted by the senescent cells. In other experiments, the senescent fibroblasts were cultured with another nontumorigenic MME cell line. The MME cells formed abnormal alveolar structures and produced twofold less of a major milk protein.

Campisi draws two lessons from the study. The first is that senescent cells in vitro can disrupt a normal tissue’s function and structure, a process that she suggests might similarly occur during aging. The second is that, as experiments increasingly reveal which secreted factors yield particular outcomes, “we might be able to modify the senescent phenotype in a tissue-specific and situation-specific manner” so as “to intervene in an intelligent way.”

Chromatin remodeling is thought to mediate senescence in human melanocytes. According to one hypothesis, the histone acetyltransferase p300 is removed from promoters of certain cell-cycle regulatory genes, and histone deacetylases (HDACs) are added. The resulting repression of those genes leads to a halt in mitosis. Investigations of senescence in vivo are also continuing. Rita B. Effros, a pathology and laboratory medicine professor at the University of California, Los Angeles, has long taken a leading role in characterizing senescence in CD8+ T lymphocytes. In 1996, she and colleagues reported that, in HIV-infected people, some of these so-called cytotoxic or killer T cells displayed short telomeres and could no longer proliferate. To combat the virus, which infects CD4+ helper T cells, these HIV-targeted CD8+ cells presumably divided so much that they became senescent. A similar phenomenon occurs in elderly people harboring cytomegalovirus, another latent virus.

Senescent T cells, which resist apoptosis, accumulate over time. The immune response eventually suffers, according to Effros, possibly because the cells secrete certain cytokines or because their overwhelming presence depresses the generation of T cells that target other antigens. In a recent study, Effros’ lab inserted a gene encoding human telomerase into a culture of HIV-targeted killer T cells taken from people infected with the virus. This manipulation kept the cells from senescing but failed to improve their cytotoxic efficiency. Acknowledging the impracticality, if not danger, of gene therapy, Effros says she is collaborating with Geron Corporation, of Menlo Park, Calif., to test the effects of a telomerase-activating compound on immune cells. The goal, she adds, is a “pharmacologic way of manipulating telomerase that would selectively affect normal T cells and improve their function.”

While Effros is trying to prevent senescence, Igor B. Roninson, director of the cancer center at Ordway Research Institute in Albany, NY, hopes to impose a safe form of senescence on the wildly proliferating cells of malignant tumors. In the 1990s, Roninson’s lab discovered that various chemotherapeutic drugs could induce terminal proliferation arrest in different human tumor cell lines. This effect, which also occurs after radiation treatment, was later detected in breast carcinomas excised from patients who underwent chemotherapy.

Cancer treatments appear to cause cellular senescence, Roninson explains, by damaging DNA and thereby activating various signal-transduction pathways. He observes that the process is often not immediate; video microscopy indicates that some senescing cells first pass through a state called mitotic catastrophe. Induction of senescence is also not without its hazards. A cDNA microarray study by Roninson’s lab showed that senescent cancer cells upregulate genes that encode tumor-promoting, as well as tumor-suppressive, secreted factors.

Roninson’s newly formed company, Senex Biotechnology, also in Albany, is seeking drugs that stimulate the beneficial side of this process. One class of compounds would “induce senescence with minimal cytotoxicity and with preferential expression of growth-inhibitory genes over tumor-promoting genes,” he says. Retinoids belong to this class, but Roninson notes that their utility is limited because many tumor cells lose their retinoid receptors. Another class of compounds would prevent the induction of tumor-promoting genes in cells that have senesced as a result of other treatments. Roninson reports that such activity is faintly displayed by nonsteroidal anti-inflammatory drugs that inhibit the transcription factor NF-ĸB. Senex is developing more efficient compounds, he adds.

Some researchers have qualms about fighting cancer by promoting senescence. Given the many factors secreted by senescent cells, Campisi observes, “If I had a tumor and I was being treated by chemo, I would want those tumor cells to die.” And noting that cultured senescent cells can be genetically tweaked to reengage in mitosis, Bernards asserts, “The only good tumor cell is a dead tumor cell, as they say.”

Roninson responds that cytostatic drugs would avoid the cytotoxicity that “is the principal cause of the negative side effects” experienced by cancer patients. Stressing scientists’ longstanding quest for such drugs, he says that he is “not in the minority” in his goal of forcing tumor cells to undergo permanent growth arrest, rather than only apoptosis. Instead, he maintains, “it’s the aficionados of apoptosis who are in the minority by denying this as a goal.”

The Scientist
April 12, 2005

Original web page at The Scientist


Life Sciences in the 21st Century

Jörg Ladwig Peer M. Schatz is CEO of Qiagen, a supplier of life science research tools and employer of 1,400 people in 12 countries. Schatz has a Master’s degree in finance from the University of St. Gall, Switzerland, and an MBA in finance from the University of Chicago. He is also a member of the Advisory Board of the Frankfurt Stock Exchange. In many ways the laboratory tools we use today may remind us of computers in the late 1970s. In those days, systems were mostly incompatible and were dedicated to specific tasks. When the first personal computers emerged, these systems were integrated: “Cut and paste” became ubiquitous, and it became possible to share and compare data over multiple and geographically dispersed platforms. A main driver for development was the standardization of the interfaces and communication protocols were standardized. The more complex and interrelated the applications, the more important it becomes that as much analytical risk as possible is removed, allowing various data contents to be compared and exchanged.

This is comparable to what we are seeing in the life sciences. Systems biology is a key development in academic and industrial research. In systems biology, the knowledge taken from different disciplines, including genomics, proteomics, glycomics, metabolomics, and others is brought together to help unveil the regulatory network of a biological system. Scientists, often dispersed in networks, are increasingly combining the analytical results of various analytes to understand basic biological principles and interactions on a cellular level. This makes it an exciting time to be serving the life sciences industry. Our customers are entering into new areas of research at a rapid pace, and the demands of the community are changing as well. Systems biology and the trend towards standardization of tools are some of the most significant changes taking place in science in the early 21st century.

Analyses are often linked, compared, and performed with various analyte formats such as DNA genotyping, expression analysis on RNA and protein analysis. We and other companies have invested significantly to address this trend in the life sciences. For example, Qiagen offers a deep and broad range of preanalytical tools for nucleic acid analysis. These can be used alongside a large and advanced protein fractionation product portfolio, which prepares various analytes simultaneously from the same sample. In all applications, the processing (both automated and manual) is designed to be as similar as possible, regardless of what analyte is prepared.

While the value of long-term standardization of platform tools is often questioned, the standardization of interfaces can dramatically enhance the flow of information and therefore of innovation. Anyone who has traveled the world can recall the frustrating array of phone and power plugs that can be found, with each country requiring a different adaptor. Computers in the 1970s were similar, and the emergence of interface standards such as the USB port significantly increased the number of products and value of PCs. Preanalytical tools for the collection, stabilization, purification, and handling of laboratory samples are comparable to an interface. They allow samples to be transformed into standardized formats, which make downstream analysis start with the same material, every time, and in every sample. Standardization therefore increases the value of information and ultimately, innovation.

In academia, we are seeing an increase in networked research and a greater demand for accelerating preclinical research. Preanalytical processing is a major influence on the quality of analytical results. This influence increases exponentially when the research results from different laboratories drive joint research efforts in networks. Roadmaps and regulatory frameworks increasingly reach into pre-clinical research. This trend leaves no room for uncertainty; full regulatory compliance of any tool is therefore critical. At Qiagen, we try to ensure the removal not only of quality risk in sample processing, but also all uncertainty as to compliance with regulations, frameworks, or roadmaps.

This trend towards making research comparable across analyses and geographic boundaries also confirms the need to be present in all major countries, to have the highest quality standards, to meet all regulatory requirements, and most importantly, to have a total commitment to focus. Almost 25% of Qiagen’s sales are generated from clinical diagnostics, and Qiagen has a range of products that are compliant with key regulatory frameworks in the United States or Europe. In addition to the diagnosis of infectious diseases and disease susceptibility, the market is facing another area of increasing importance: the screening of patients for clinical trials of targeted drugs, and ultimately for personalized medicine.

Astra Zeneca’s lung-tumor drug, Iressa, according to results published in April 2004, showed a significantly higher-than-normal response rate in patients with a certain enzyme pattern. In July 2004, NitroMed announced that the Phase III clinical trial of its heart failure treatment, BiDil, had been stopped early because of the significant survival benefit seen in African-American heart-failure patients. On the other hand, in late September 2004, Merck had to withdraw its COX-2 inhibitor drug, Vioxx, because data compiled by Kaiser Permanente suggested that patients who took Vioxx had a higher cardiovascular risk than those who did not take the drug.

In November 2003, the US Food and Drug Administration published the draft of new guidelines accelerating the use of molecular biology in clinical research, and the preselection of patients to increase clinical trial safety. The FDA recommended genotyping and gene expression profiling of patients in clinical trials to allow for the selection of specific patients for trial enrollment, and to help in determining the correct dose. In addition, the FDA expects further detailed information on specific drug metabolisms (pharmacogenomics), pharmacokinetics, and subject stratification, to support scientific arguments and the validation of biomarkers.

The proven ability to seamlessly integrate sample collection, stabilization, and purification and handling technologies into complex diagnostic workflows has become increasingly important as patient samples are used for larger numbers of tests and in more diversified settings. Integrated technologies such as PreAnalytiX’s PAXgene (a joint venture between Qiagen and Becton Dickinson), allow consistent and easy blood collection, stabilization, and purification of nucleic acids for large-scale analyses. Such products have become essential standards for the further development of these markets and will ensure that survey data from pharmacogenomic trials and Phase I-III clinical trials are not biased. The use of universally available, standardized tools in clinical research allows greater speed and flexibility as well as a diagnostic perspective. This streamlines and increases the reliability of clinical assay development and drug-development programs.

Consistent or standardized processes are also the bedrock for the commercialization of molecular biology technologies in molecular diagnostics, which stands to benefit in a very significant way from the advancements and successes in molecular biology-related research. Molecular biological methods are already an integral part of everyday laboratory routine, including genetic identification in forensics and in paternity testing. They are also today’s standard in the diagnosis of infectious diseases such as HIV, hepatitis B and C, as well as human papillomavirus (HVP). In addition, molecular diagnostics companies have been successful in developing specific standardized tests for predisposition to cancers of the lung, intestine, prostate, pancreas, liver, stomach, and skin. The list of such predisposition tests is getting longer every day.

With an ever increasing number of samples and the dissemination of molecular biology approaches in the life sciences and health care, we observe a very significant need for consistent and comparable solutions that have highest performance but are also simple. The pharmaceutical and diagnostics industries are demanding less complex analytical platforms to increase the ease of use and decentralize the analytical work between different laboratories and hospitals.

The breadth of sample types that can be analyzed is increasing both in research and in diagnostics and now includes more “live” sample material such as various tissue formats and whole blood. This significantly increases the scope of available sample quality. At the same time, the sensitivity and cost of downstream analysis has increased. Samples that need processing are often limited in amount or partially degraded. Tool providers must cover a wide spectrum of different products and technologies to meet all the different requirements in these markets and to find the best solution for future needs. This can be done only with a commitment and focus. By delivering innovative technologies and solutions, tool providers continue to advance standards and enable researchers in academic and industrial environments to achieve breakthroughs in healthcare. This leads to an improvement in living conditions, which will contribute to improving people’s lives.

Science has achieved such incredible successes in the last few years, and the advancements seem to be accelerating. It was very fitting that the scientific world started the new millennium with the successful completion of the greatest scientific challenges of recent years: the publication of the sequence of the human genome. While in itself a dramatic and hugely significant event, it stands for the spectacular speed at which science overall is advancing.

The Scientist Daily
March 15, 2005

Original web page at The Scientist