Proteins, large organic compounds made of amino acids, provide many of the most basic units of function in living systems. They make up about half of the dry mass of animals and humans. There may be as many as 1 million different types of proteins in the human body (it is estimated that the human proteome is comprised of an average of 5-7 protein isoforms per open reading frame in the human genome and a further 600 000-odd immunoglobulins present in serum at any given moment) - nobody really knows. The word protein comes from the Greek prota, meaning 'of primary importance', and they actually may become of great importance in nanoscale fabrication as well. Proteins have an amazing number of functions inside our bodies: Enzymes serve as catalysts to break down food into various components; transport proteins such as hemoglobin transport molecules (e.g. oxygen); storage proteins store molecules (e.g. iron is stored in the liver as a complex with the protein ferritin); structural proteins such as keratin or collagen are needed for mechanical support in tissues like cartilage and skin but also hair and nails; proteins are the major component of muscles and for instance actin or myosin are key to contracting muscle fibers; hormones control the growth of cells and their differentiation; antibody proteins are needed for immune protection; and toxins are, well, toxic, but in minute amounts could have beneficial medical properties. Scientists believe that this variety of natural protein functions - actuation, catalysis, structural transport and molecular sequestering - could serve as valuable and versatile building blocks for synthesis of functional materials. Researchers now have found that nanometer-scale changes in protein conformation can be translated into macroscopic changes in material properties. The result is a new class of dynamic, protein-based materials.
Cancer is an enormous socio-economic problem. According to the National Cancer Institute (NCI), it is estimated that in 2007 there will be over 1.4 million new cases of cancer (of any type) and over 550,000 deaths from cancer in the United States (you can download a detailed Cancer Statistics 2007 Presentation; ppt download, 808 KB) from the American Cancer Society. This makes cancer the second deadliest disease category, after heart diseases. But while the mortality rates for heart diseases have dropped by more than half from 1950 to 2004, and other major disease categories show similar trends, cancer death rates have stayed pretty much the same. Shocking but true, if you are a male living in the U.S., your lifetime probability of developing some type of cancer is 1 in 2. If you are female, your probability is 1 in 3. Equally dismal are the economic cost associated with this disease: The amount of direct cancer-related costs (treatment, care and rehabilitation) have reached $74 billion in the U.S. in 2005, and growing fast, while the overall economic costs (including loss of economic output due to days off and premature death) are estimated to be over $200 billion per year (2005 data). This Spotlight will discuss existing and new approaches to fight cancer and their limitations. The goal is to stimulate readers to support and participate in interdisciplinary research and teaching efforts toward relieving suffering and death due to cancer. Fighting cancer involves three phases: (i) detection, (ii) treatment, and (iii) monitoring. Success depends on matching science to the actual practical needs. We'll take a look at - in particular nanotechnology - efforts underway in the direction of these three phases and comment on some of the practical problems encountered fighting cancer. We also speculate about some unconventional research that might be successful fighting cancer in the future.
Nanotechnology enabled synthetic biology could one day lead to an artificial construct that operates like a living cell. That day might be a considerable distance off, given the difficulties scientists are still having in even understandiing the organizing principles and workings of a cell, not to mention being able to duplicate cell components and assembling them into a working whole. The large discrepancy between the functional density (i.e., the number of components or interconnection of components per unit volume) of cells and engineered systems highlights the inherent challenges posed by such a task. Just take 'simple' bacteria like Escherichia coli (which has an approx. 2 square micrometer cross-sectional area). The E. coli cell has some 4.6-million base-pair chromosome (the equivalent of a 9.2 megabit memory) that codes for as many as 4,300 different polypeptides under the inducible control of several hundred different promoters. The most advanced silicon chips will be able in a few years time to come close to this performance (on the other hand, you have several trillion E. coli in your gut; you would need to swallow a lot of computer chips to match this combined 'computing' power). Another way to look at the synthetic cell challenge is to regard the cellular environment as a highly complex synthetic medium, in which numerous multistep reactions take place simultaneously with an efficiency and specificity that scientists are not capable of duplicating at this scale. Researchers in The Netherlands have now succeeded in constructing nanoreactors that can be used to perform one-pot multistep reactions - another step towards the goal of artificial cell-like devices, but more promising in the short term for screening and diagnostic applications.
What do humans have in common with the pinky-sized tropical zebrafish that zip around in many hobbyists' home aquariums? Well, surprising as it may be, quite a lot actually. Zebrafish share the same set of genes as humans and have similar drug target sites for treating human diseases. For this reason, scientists, when turning to a model-organism to help answer genetic questions that cannot be easily addressed in humans, often chose the zebrafish (Danio rerio) - and save a few mice in the process. Zebrafish are small, easy to maintain, and well-suited for whole animal studies. Furthermore, its early embryonic development is completed rapidly within five days with well-characterized developmental stages. The embryos are transparent and develop outside of their mothers, permitting direct visual detection of pathological embryonic death, mal-development phenotypes, and study of real-time transport and effects of nanoparticles in vivo. Therefore, zebrafish embryos offer a unique opportunity to investigate the effects of nanoparticles upon intact cellular systems that communicate with each other to orchestrate the events of early embryonic development. In a new study, researchers explore the potential of nanoparticles as in vivo imaging and therapeutic agents and develop an effective and inexpensive in vivo zebrafish model system to screen biocompatibility and toxicity of nanomaterials. Such real-time studies of the transport and biocompatibility of single nanoparticles in the early development of embryos will provide new insights into molecular transport mechanisms and the structure of developing embryos at nanometer spatial resolution in vivo, as well as assessing the biocompatibility of single-nanoparticle probes in vivo.
In old movies, saying "the rabbit died," was a popular way for a woman to reveal she was pregnant. The belief was that the doctor would inject the woman's urine into a rabbit. If the rabbit died, she was pregnant. The rabbit test actually originated with the discovery that the urine of a pregnant woman - which contains the hormone Human chorionic gonadotropin (hCG) - would cause corpora hemorrhagica in the ovaries of the rabbit. These swollen masses on the ovaries could only be detected by killing the rabbit in order to exam its ovaries. So, in reality, every rabbit died whether the woman was pregnant or not. Fortunately (for rabbits in particular), immunoassays - which can detect hormones (such as hCG), antibodies and antigens in the blood - were developed in the 1950s. Radioimmunoassays were first used to detect insulin in blood, but were later used for a variety of diagnostic tests. The technique is extremely sensitive and specific, but the necessary radioactive substances make it risky and expensive. In the 1960s, immunoassay technology was greatly enhanced by replacing radioisotopes with enzymes for color generation, which eliminated the risk and a great deal of expense. Today, most immunoassays are Enzyme-Linked ImmunoSorbent Assay, or ELISA. Because it can evaluate the presence of antigen or antibody in a sample, ELISA is commonly used to test for HIV, Hepatitis B, and West Nile Virus. ELISA has also been used in the food industry to detect potential food allergens such as milk, nuts, and eggs. Although there are numerous variations of ELISA, the test basically involves an antigen attached to a solid surface. When the antibody is washed over the surface, it will bind to the antigen. The antibody is then linked to an enzyme - usually a peroxidase (enzyme that causes oxidation) - which reacts with certain substrates, resulting in a change in color that serves a signal. The evolution of immunoassays has continued with developments such as fluorimetric immunoassay (which has replaced the rabbits in pregnancy tests.) Now, scientists at the Chinese Academy of Science have discovered a way to improve the process even more by eliminating one of the steps in certain immunoassays.
A quantum dot (QD), also called a nanocrystal, is a semiconductor nanostructure that can be as small as 2 to 10 nm. The usefulness of quantum dots comes from their peak emission frequency's extreme sensitivity - quantum mechanical in nature - to both the dot's size and composition. QDs have been touted as possible replacements for organic dyes in the imaging of biological systems, due to their excellent fluorescent properties, good chemical stability, broad excitation ranges and high photobleaching thresholds. By contrast, conventional organic dyes cannot be easily synthesized to emit different colors and have narrow excitation spectra and broad emission spectra that often cross into the red wavelengths, making it difficult to use these dyes for multiplexing. QDs hold increasing potential for cellular imaging both in vitro and in vivo. Researchers have now used QDs for in vivo imaging of embryonic stem cells in mice. This opens up the possibility of using QDs for fast and accurate imaging applications in stem cell therapy.
Medicine is big business. The big pharma companies have traditionally enjoyed enormous profits that would make the eyes of other companies' CEOs water (apart from big oil companies, of course). The combined annual net income for the top 10 pharma companies (ranked by market capitalization) currently is about $73 billion. Pfizer alone has a net income of approximately $19 billion. The recipe for success? Patent protection and intellectual property rights (IPRs). The core of Big Pharma's business model relies on patent protection for their blockbuster drugs, which allows them to sell these drugs at extraordinarily high profit margins that they wouldn't be able to generate in a competitive market. Point in case: Lipitor, the cholesterol-lowering drug that accounts for nearly $13 billion of Pfizer's revenues and over 40% of its profits. Another key part of the pharma business model is heavy spending on sales and marketing. Novartis, for instance, is spending around 33% of sales on promotion, compared with about 19% on R&D, although the cost of bringing a new drug to market could well exceed $1 billion (and that is also the argument pharma companies use to justify their profits). However, pharmaceutical companies are faced with the expiration of the patent protection on their main profit generators, they have relatively few new products in the pipeline, and they need to come to terms with the emerging nanomedicine landscape. While nanomedicine potentially offers promising new value propositions and revenue streams, for instance in diagnostics, it also could completely displace certain classes of drugs such as current chemotherapy agents with novel nanoparticle reformulations. In what looks like more of the same though, it seems that the future of nanomedicine business will also depend on patents and IPRs, potentially even more so than today.
Nature is truly a brilliant nano engineer and has been so for billions of years. There is an abundance of 'smart' biological materials with hierarchical nanostructures - built from proteins - that are capable of adapting to new tasks, are self-healing, and can self-assemble autonomously simply out of a solution of building blocks. The performance and capability of these natural materials is something engineers can only dream of today. But by unlocking nature's secrets tiny step by tiny step, one day we will be able to not only duplicate but surpass the performance of natural materials. Only in recent years have scientists begun to understand the underlying principles and mechanisms of these materials - Why is spider silk stronger than steel? Why can cells be stretched reversibly several times of their original length? What kinds of molecular flaws lead to malfunctions in cells and tissues, as it occurs in Alzheimer's, rapid ageing disease progeria or muscle dystrophies, diseases in which the cell or tissue fails mechanically? Scientists at MIT have, for the first time, revealed the fundamental fracture and deformation mechanisms of biological protein materials, clarifying some long-standing issues about the deformation behavior of cells and Alzheimer's pathogens. The researchers report that the fracture mechanisms of two abundant nanoscopic building blocks of many proteins and protein materials exhibit two distinct fracture modes, depending on the speed of deformation. This is a surprising observation with far-reaching implications for the development of novel self-assembled protein materials and possibly the cure of certain genetic diseases