Terence Allen > Quotes

“Long before the idea of scanning specimens with a small spot of light produced confocal light microscopy, the idea of using a small spot of electrons to scan surfaces had been around for as long as electron microscopy itself. A surface demarcates the boundary of a solid, and is the site of interaction with the surrounding environment, from a ball bearing to a living cell. In the mechanical world, adhesion, friction, wear, and corrosion are all dependent upon surface properties. The smooth surface of a ball bearing is crucial in the reduction of friction, but its efficiency may well be compromised by wear or corrosion.”
― Terence Allen, Microscopy: A Very Short Introduction

“In our own bodies, only the liver is capable of limited regeneration, but chop a limb off a starfish or a salamander, and it will grow a new one. We are starting to understand the molecular signals that are used by these species to regenerate limbs in adult life. Mammals seem to only use this signalling pathway during the growth of the early embryo but it is a pathway that may well have the potential to be reactivated. Following surgical removal, the wings can grow back in embryonic chickens when the production of a protein called wnt is switched on. Frog limb regeneration can also take place later in the life cycle when wnt protein is expressed. Tadpoles have this ability but it is normally lost when they metamorphose into frogs. The expression of wnt signalling protein around an injury is thought to cause a reprogramming or transdifferentiation of mature cells into stem cells capable of producing the cell types needed for the limb. Very young children have been known to re-grow severed fingertips, and so there are intriguing possibilities for human tissue regeneration.”
― Terence Allen, The Cell: A Very Short Introduction

“The actual mechanics of cell division, according to Dick McIntosh at the University of Denver, require significantly more instructions than it takes to build a moon rocket or supercomputer. First of all, the cell needs to duplicate all of its molecules, that is DNA, RNA, proteins, lipids, etc. At the organelle level, several hundred mitochondria, large areas of ER, new Golgi bodies, cytoskeletal structures, and ribosomes by the million all need to be duplicated so that the daughter cells have enough resources to grow and, in turn, divide themselves. All these processes make up the ‘cell cycle’. Some cells will divide on a daily basis, others live for decades without dividing. The cell cycle is divided into phases, starting with interphase, the period between cell divisions (about 23 hours), and mitosis (M phase), the actual process of separating the original into two daughter cells (about 1 hour). Interphase is further split into three distinct periods: gap 1 (G1, 4–6 hours), a synthesis phase (S, 12 hours), and gap 2 (G2, 4–6 hours). Generally, cells continue to grow throughout interphase, but DNA replication is restricted to the S phase. At the end of G1 there is a checkpoint. If nutrient and energy levels are insufficient for DNA synthesis, the cell is diverted into a phase called G0. In 2001 Tim Hunt, Paul Nurse, and Leeland Hartwell received the Nobel Prize for their work in discovering how the cell cycle is controlled. Tim Hunt found a set of proteins called cyclins, which accumulate during specific stages of the cell cycle. Once the right level is reached, the cell is ‘allowed’ to progress to the next stage and the cyclins are destroyed. Cyclins then start to build up again, keeping a score of the progress at each point of the cycle, and only allowing progression to the next stage if the correct cyclin level has been reached.”
― Terence Allen, The Cell: A Very Short Introduction

“The advent of low temperature scanning EM led to a study by Bill Wergin and colleagues from NASA in which they collected samples from different types of snow cover found in the prairies, taiga (snow forest), and alpine environments. With snow depths up to a metre, various layers occurred in which the crystals underwent a change in their microscopic shape from the original freshly fallen crystals, to the development of flat faces and sharp edges. It is this metamorphosis of lying snow that determines the likelihood of avalanches, which can be predicted from the crystal structures at various depths. Although scanning EM (electron microscopy) is hardly available as a routine assay in distant mountain regions, this work helped in the use of microwave radiology investigation of the snow water equivalent in the snow pack, as large snow crystals scatter passive microwave more than small crystals. Smaller and more rounded crystals of snow do not interlock, and can slide more easily over each other, increasing the risk of avalanches.”
― Terence Allen, Microscopy: A Very Short Introduction

“Our best ability to see detail with the eye is to perceive two strands of human hair that are separated by a hair’s width. This is the limit of our resolution—the ability to see detail, measured by the distance at which two points are still distinct. Magnification without increased resolution merely produces a larger image with no increase in detail. Amazing as our own eyes are, they are poor compared with those of an eagle, where the resolution is eight times as good, enabling it to spot a rabbit at a distance of two miles.”
― Terence Allen, Microscopy: A Very Short Introduction

“So how does a cell go about ending its own existence? The actual mechanism of ‘cell suicide’ depends upon mitochondria, termed the ‘angels of death’ by Nick Lane in his book, Power, Sex and Suicide: Mitochondria and the Meaning of Life . The first change occurs in the mitochondrial inner membrane, which becomes damaged by aberrant biochemical activity, leading to the formation of pores in the mitochondrial membrane (Figure 12b, d). At this point, the mitochondrion becomes committed to trigger apoptosis, and releases cytochrome c (a protein crucial to its normal function of energy production) which exits through the newly formed pores. This information came to light as a result of some neat experiments in which apoptotic mitochondria were introduced into perfectly healthy cells, resulting in apoptosis. The released cytochrome c binds to several other proteins in the cytoplasm to form a complex called the apoptosome which, in turn, activates a cascade of ‘executioner enzymes’ which not only kill the cell but cause fragmentation of the nucleus and cytoplasm into bite-size pieces ready to be phagocytosed by neighbouring cells.”
― Terence Allen, The Cell: A Very Short Introduction

“With the advent of nanotechnology, microfabrication has produced novel manmade constructs called metamaterials which exhibit entirely new properties in terms of their effect on light, effects which are not found in conventional materials, or even in nature itself. Early in the 21st century, a chance observation showed that an ultrathin layer of silver on a flat sheet of glass would act like a lens, and from this point, the development of the ‘perfect’ or ‘superlens’ began, with the theoretical possibility to image details such as viruses in living cells with a light microscope, bypassing Abbe’s diffraction limit. Metamaterials have been produced that make this possible, as they have a property previously unimagined in optics, and not found in nature, which is a negative refractive index.”
― Terence Allen, Microscopy: A Very Short Introduction

“So far we have considered the effects of varying the type of illumination, so at this point we can sum up how one specimen can be imaged in four separate ways. In a conventional microscope with bright field illumination, contrast comes from absorbance of light by the sample (Figure 7a). Using dark field illumination, contrast is generated by light scattered from the sample (Figure 7b). In phase contrast, interference between different path lengths produces contrast (Figure 7c), and in polarizing microscopy it is the rotation of polarized light produced by the specimen between polarizer and analyser (Figure 7d). This is ‘converted’ into an image that has colour and a three dimensional appearance by the use of Wollaston prisms in differential interference microscopy. For virtually any specimen, hard or soft, isotropic or anisotropic, organic or inorganic, biological, metallurgical, or manufactured, there will be a variety of imaging modes that will produce complementary information. Some of the types of light microscopy we have looked at above have direct parallels in electron microscopy (Chapter 4).”
― Terence Allen, Microscopy: A Very Short Introduction

“Pulsed lasers produce incredibly short bursts of electromagnetic energy. For example, a pulsed femtosecond laser produces a flash of light that lasts for femtoseconds to a picosecond (a picosecond is one trillionth of a second, a femtosecond is one thousandth of a picosecond), instantly followed by another (and so on). These lasers brought about the possibility of exciting fluorophores with two photons of only half the necessary energy, but they need to arrive almost simultaneously to generate the ejection of a photon. Infrared pulsed lasers penetrate living tissue more effectively, with the advantage that fluorescence is achieved from much deeper in the tissue than normal fluorescence, where the depth of penetration is limited by multiple light scattering events. Multiphoton microscopy (mainly two photon in practice, but also feasible as three or more photons) allows imaging from as deep as a millimetre (one thousand micrometres), an improvement of several hundred micrometres over fluorescence confocal microscopy. A second advantage of two photon excitation is that it forms as a single spot in the axial plane (z axis) without the ‘hourglass’ spread of out of focus light (the point spread function) that happens with single photon excitation. This is because the actual two photon excitation will only occur at the highest concentration of photons, which is limited to the focal plane itself. Because there is no out of focus light, there is no need for a confocal pinhole, allowing more signal to reach the detector. Combined with the increased depth of penetration, and reduced light induced damage (phototoxicity) to living tissue, two photon microscopy has added a new dimension to the imaging of living tissue in whole animals. At the surface of a living brain, remarkable images of the paths of whole neurons over several hundred micrometres can be reconstructed as a 3D z section from an image stack imaged through a thinned area of the skull in an experimental animal. Endoscopes have been developed which incorporate a miniaturized two photon microscope, allowing deep imaging of intestinal epithelium, with potential to provide new information on intestinal diseases, as most of the cellular lining throughout our gut is thin enough to be imaged in this way. So far a whole range of conditions including virtually all the cancers of the digestive tract as well as inflammatory bowel disease have been investigated, reducing the need for biopsies and providing new insights as to the nature of these conditions.”
― Terence Allen, Microscopy: A Very Short Introduction

“It has been estimated that a career electron microscopist who spends his working days preparing, sectioning and staining, observing, and recording biological material will get through the equivalent of one cubic millimetre of tissue in a forty-year working lifetime.”
― Terence Allen, Microscopy: A Very Short Introduction

“Although the nucleus might have been recognized by Antonie van Leeuwenhoek in the late 17th century, it was not until 1831 that it was reported as a specific structure in orchid epidermal cells by a Scottish botanist, Robert Brown (better known for recognizing ‘Brownian movement’ of pollen grains in water). In 1879, Walther Flemming observed that the nucleus broke down into small fragments at cell division, followed by re-formation of the fragments called chromosomes to make new nuclei in the daughter cells. It was not until 1902 that Walter Sutton and Theodor Boveri independently linked chromosomes directly to mammalian inheritance. Thomas Morgan’s work with fruit flies (Drosophila) at the start of the 20th century showed specific characters positioned along the length of the chromosomes, followed by the realization by Oswald Avery in 1944 that the genetic material was DNA. Some nine years later, James Watson and Francis Crick showed the structure of DNA to be a double helix, for which they shared the Nobel Prize in 1962 with Maurice Wilkins, whose laboratory had provided the evidence that led to the discovery. Rosalind Franklin, whose X-ray diffraction images of DNA from the Wilkins lab had been the key to DNA structure, died of cancer aged 37 in 1958, and Nobel Prizes are not awarded posthumously. Watson and Crick published the classic double helix model in 1953. The final piece in the jigsaw of DNA structure was produced by Watson with the realization that the pairing of the nucleotide bases, adenine with thymine and guanine with cytosine, not only provided the rungs holding the twisting ladder of DNA together, but also provided a code for accurate replication and a template for protein assembly. Crick continued to study and elucidate the base pairing required for coding proteins, and this led to the fundamental ‘dogma’ that ‘DNA makes RNA and RNA makes protein’. The discovery of DNA structure marked an enormous advance in biology, probably the most significant since Darwin’s publication of On the Origin of Species .”
― Terence Allen, The Cell: A Very Short Introduction

“From its earliest days, scanning EM proved to be a source of images that everybody could relate to, regardless of a microscopic or indeed even a scientific background. From early images showing great detail of everyday objects and animals, for example the edge of a scalpel or razor blade or the multiple compound eyes of a spider, the extra information provided by the high magnification was instantly apparent, grasping the attention of the general public in a way that transmission EM images did not (Figure 19). Today, images of bacteria, stem cells, and tumour cells are a regular sight in TV news, documentaries, newspapers, and magazines, usually brightly coloured. False or pseudo-colouring of scanning EM images is useful for highlighting specific features, as well as increasing the overall impact, which can sometimes be a little on the garish side.”
― Terence Allen, Microscopy: A Very Short Introduction

“At one end of the scale, astronomers search the heavens for new information about the universe, whilst at the other end, microscopists chase atoms and molecules to study defects in crystals or the basic processes of life. These investigations may be separated by more than twentyfold orders of magnitude, but are nevertheless driven by the same insatiable curiosity of the human psyche to explore beyond the vision of our own eyes.”
― Terence Allen, Microscopy: A Very Short Introduction

“Modern scanning probe instruments will often provide several different modes within the same instrument, including aspects of light microscopy such as near field optical scanning microscopy (NOSM) and micro tools for nanofabrication such as micro-writing devices (nanolithography), indentation probes providing exact positioning and force control, all in a specimen chamber in which both the temperature and gaseous environment can be precisely controlled. This type of scanning probe microscopy has made it possible to investigate a surface phenomenon termed surface plasmon polaritons (SPPs for short), which are surface electromagnetic waves that propagate between the interface of a metal and a dielectric (insulator). More explanation of SPPs would require a VSI on surface physics, but suffice it to say, the scanning plasmon near field microscope has made it possible to work towards practical exploitation in the applications of SPPs (which make it possible to ‘package’ light in smaller quantities than ever before) in optics, data storage, solar cells, chemical cells, and biosensors.”
― Terence Allen, Microscopy: A Very Short Introduction