GILBERT LING & HAROLD HILLMAN
Gilbert Ling was a biologist and biochemist who developed a so called controversial theory of cell function in the 20th century. His theories are known as the "association-induction hypothesis" or AI hypothesis, and they are controversial because they dissent with the held theories.
According to the AI hypothesis, the structure and function of cell membranes are maintained by the association of proteins and lipids in a specific way. Ling suggested that cell membranes are not composed of a lipid bilayer (see notes on Harold Hillman later) as commonly believed, but rather a network of proteins and lipids that interact with each other through weak, non-covalent bonds.
Ling also proposed that the properties of water (see works by Gerald H. Pollack for more justification on this subject) play a crucial role in cellular function. He argued that the water molecules inside cells are structured in a way that allows them to interact with proteins and other cellular components in a specific manner, influencing cellular function.
Ling's theories were controversial because they challenged the widely accepted “model” of the cell membrane and were not supported by “experimental” evidence. However, some scientists have since revisited and reevaluated his ideas, suggesting that they may have merit and could provide new insights into the workings of cells.
Despite the controversy surrounding Ling's theories, his work continues to influence the study of cell biology and biochemistry.
Ling provided multiple evidences of his work and continually proved his theories, yet while Gilbert Ling's theories are considered influential, they were also highly controversial within the scientific community. While Ling provided evidence to support his ideas, many scientists have continually criticised his work and questioned the validity of his methods and conclusions, this has been done rather than proving him wrong via experimental data.
Ling's use of a technique called "microspectrophotometry" to study cell membranes has been heavily criticised. This technique involves shining light on a sample of cells and measuring how much light is absorbed by different molecules within the cells. Ling used this method to argue that the cell membrane was not composed of a lipid bilayer, but rather a network of proteins and lipids.
The sodium pump hypothesis is a widely accepted “theory" of cellular function that proposes that cells use an enzyme called the sodium-potassium ATPase to pump sodium ions out of the cell and potassium ions into the cell. This process is thought to be crucial for maintaining the electrochemical gradient across the cell membrane and enabling a wide range of cellular functions.
Gilbert Ling was a prominent critic of the sodium pump hypothesis. He argued that the process of pumping ions across the cell membrane was not sufficient to explain the full range of cellular functions, and that there were other factors at play that were not being adequately considered.
One of Ling's main criticisms of the sodium pump hypothesis was that it relied on the concept of a lipid bilayer membrane, which he argued was an oversimplified model of the cell membrane. Ling believed that the cell membrane was much more complex and dynamic than the simple lipid bilayer model, and that its properties were determined by the interaction of proteins and lipids in a specific way.
Ling also argued that the sodium pump hypothesis did not adequately account for the role of water in cellular function. He believed that the properties of water were crucial for enabling cellular functions such as protein folding, and that the sodium pump hypothesis did not adequately consider the role of water in these processes.
Overall, Gilbert Ling's critique of the sodium pump hypothesis was part of his broader effort to develop a more nuanced and comprehensive understanding of cellular function. While his ideas remain controversial, they have sparked new lines of research and inquiry into the nature of the cell membrane and the role of water in cellular processes.
The sodium-potassium ATPase, also known as the sodium pump, is an enzyme that uses energy in the form of ATP to transport sodium ions out of the cell and potassium ions into the cell, maintaining the electrochemical gradient across the cell membrane. The energy required for the sodium pump to work has been extensively studied and is estimated to be around 20-30% of the total energy consumption of the cell.
Ling criticised the mathematical calculations used to estimate the energy required for the sodium pump to function. In particular, he argued that the models used to estimate the number of sodium pumps in a typical cell were based on oversimplified assumptions that did not adequately account for the complex structure and function of the cell membrane.
Ling also argued that the assumptions used in these calculations did not adequately consider the role of water in cellular function. He believed that the properties of water were crucial for enabling cellular functions such as protein folding, and that the mathematical models used to estimate the energy requirements of the sodium pump did not adequately consider the role of water in these processes.
However, while Ling's criticisms of the mathematical models used to estimate the energy requirements of the sodium pump have been influential, the overall concept of the sodium pump remains a key focus of research in cellular biology and biochemistry, and its energy requirements continue to be studied and refined over time.
Sodium pumps, gates, and channels are all molecular structures that are apparently too small to be directly imaged using conventional optical microscopes, such as those used in photography. These structures are typically only a few nanometers in size, which is much smaller than the resolution limit of most optical microscopes.
To study these molecular structures, scientists use a range of different techniques that allow them to indirectly observe their properties and behaviour. One commonly used technique is X-ray crystallography, which involves crystallising the molecular structure and then using X-rays to create a diffraction pattern that can be used to reconstruct the structure.
Other techniques, such as electron microscopy and nuclear magnetic resonance spectroscopy, can also be used to study the structure and function of these molecular structures. These techniques allow scientists to indirectly observe the behaviour of sodium pumps, gates, and channels in a variety of different contexts, from living cells to isolated proteins.
While we do not have photographic images of these molecular structures, the indirect observations made using these techniques have provided valuable insights into the mechanisms by which they function, and have paved the way for the development of new drugs and therapies that supposedly target these structures in the treatment of diseases.
Given that electron microscopy and nuclear magnetic resonance spectroscopy are able to collect digital images, isn't is odd that we don't have images to use in academic texts and have to rely upon trusting that they exist?
While electron microscopy and nuclear magnetic resonance spectroscopy can produce digital images of molecular structures, the images produced by these techniques are not like the photographic images that we are used to seeing in textbooks and other publications.
The images produced by these techniques are typically complex, three-dimensional representations of the molecular structure, and may not have the same level of clarity and detail as a photograph. Additionally, these images may require extensive processing and interpretation by scientists in order to accurately depict the structure and function of the molecular structure being studied.
Furthermore, the study of molecular structures is an ongoing area of research, and the precise details of these structures are still being refined and revised over time. As a result, it can be difficult to produce definitive images of these structures that accurately reflect the current state of scientific understanding.
The images produced by techniques such as electron microscopy and nuclear magnetic resonance spectroscopy are created using sophisticated data analysis techniques, rather than being direct images of the molecular structures being studied.
For example, in electron microscopy, a beam of electrons is used to interact with the sample being studied, and the resulting data is used to reconstruct a three-dimensional image of the sample. Similarly, in nuclear magnetic resonance spectroscopy, radio waves are used to excite the nuclei of the atoms in the sample, and the resulting signals are used to create a detailed image of the molecular structure.
These techniques require careful data analysis and processing in order to produce an accurate representation of the molecular structure being studied.
Technology is adequate to collect photographic images, it is more likely that these do not exist and Ling is correct.
While it is true that advances in technology have made it possible to collect high-resolution images of very small structures, such as molecules and molecular complexes, it is important to note that the collection and interpretation of these images is not always straightforward.
Collecting high-quality images of molecular structures requires not only sophisticated technology, but also careful sample preparation, imaging protocols, and data analysis. Even with the most advanced imaging techniques, it can still be challenging to obtain clear and accurate images of molecular structures.
Furthermore, while Gilbert Ling's criticisms of the sodium pump hypothesis are respected by some scientists, his ideas are not widely accepted within the scientific community. The vast majority of experimental evidence supports the idea that the sodium pump plays a critical role in cellular function, and the energy requirements of the sodium pump have been extensively studied using a variety of experimental approaches.
Many drugs apparently act by binding to specific receptors on the surface of cells, triggering a series of downstream signalling events that ultimately lead to the drug's therapeutic effects. Examples of drugs that act by binding to receptors include:
Beta blockers: These drugs bind to beta-adrenergic receptors on the surface of heart cells and block the effects of adrenaline and other stress hormones, reducing heart rate and blood pressure.
Opioids: These drugs bind to opioid receptors in the brain and other parts of the body, reducing pain and producing feelings of euphoria and relaxation.
Antihistamines: These drugs bind to histamine receptors, blocking the effects of histamine and reducing symptoms of allergies and inflammation.
Anti-anxiety medications: These drugs, such as benzodiazepines, bind to GABA receptors in the brain, enhancing the effects of the neurotransmitter GABA and reducing anxiety and muscle tension.
Antidepressants: These drugs, such as selective serotonin reuptake inhibitors (SSRIs), bind to serotonin receptors in the brain, increasing levels of the neurotransmitter serotonin and reducing symptoms of depression and anxiety.
Can we view these receptors on a cells surface?
Receptors on a cell's surface can be visualised using various techniques, including immunofluorescence microscopy and live-cell imaging.
Immunofluorescence microscopy is a technique that uses fluorescently labeled antibodies to specifically bind to and visualise the location and distribution of specific receptors on the surface of cells. This technique involves labelling the receptors with fluorescently labeled antibodies, which can then be detected using a fluorescence microscope.
Live-cell imaging involves visualising the behaviour and activity of receptors in real-time using microscopy techniques. This can involve labelling the receptors with fluorescently labeled ligands or other molecules that allow the receptors to be tracked and monitored over time.
Overall, the ability to visualise receptors on a cell's surface depends on the specific receptors and the techniques used to label and visualise them. Some receptors may be more difficult to visualise than others, depending on factors such as their expression level, localisation, and interactions with other molecules in the cell.
The images of receptors on the surface of cells that are produced using microscopy techniques are usually created rather than direct images taken of a cell. That is, the images are generated through a process of labelling the receptors with fluorescently labeled antibodies or other molecules, and then using a fluorescence microscope or other imaging techniques to visualise the labeled receptors.
This means that the images are not exactly direct photographs of the cell or the receptors themselves, but rather representations of the location and distribution of the labeled receptors within the cell.
Harold Hillman was a biologist who was critical of many of the commonly used techniques and assumptions in the field of biology. He argued that many of the techniques used in biology, such as fixation and staining of cells and tissues, could alter the natural structure and behaviour of the cells being studied, leading to inaccurate or misleading results.
Hillman also criticised the use of electron microscopy, which he argued could damage or destroy the structures being studied and could produce artefacts that did not accurately reflect the natural state of the cells or tissues. He proposed alternative techniques for studying biological structures, such as using live-cell imaging and observation of natural behaviour.
Hillman also questioned many of the underlying assumptions and theories in biology, such as the idea that cells are composed of discrete, membrane-bound compartments, arguing that this view was based on outdated models and did not accurately reflect the complex and dynamic nature of cells.
Overall, Hillman's critiques of biology techniques were aimed at encouraging researchers to take a more critical and holistic approach to studying biological systems, and to avoid making assumptions based on outdated models or techniques that could produce misleading results. To-date, and given the last few years of lack of scientific scrutiny, we seem to be ignoring a great deal of question in order to maintain the current order.
