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Magic of nanomedicine Research goals Update on the effects of atomic radiation
THIS UNIVERSE |
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Magic of nanomedicine Let us imagine having bones woven with fabric such that one could fall out of a building and walk away. Imagine that in the event of a fire, microscopic vessels just 10 billionth of a metre wide, pressurised with 1000 atmospheres of pure oxygen could sense oxygen levels in the blood and provide hours of respiratory requirement for the body. Imagine medical nanites being injected into the blood stream, consuming atherosclerotic plaques in the walls of the blood vessels or doctors could search out and destroy the very first cancer cells that would otherwise have caused a tumor to develop in the body. All these sound like something from a science fiction movie, but these are the long term goals of nanomedicine that we anticipate will yield medical benefits as early as 10 years from now. Despite advances in modern medicine over the last century, the state of current medicine has been limited both by its understanding and by its tools and in many ways is still more of an art than a science. Only within the last 50 years has medical science begun to examine disease pathology on a molecular level, thus from a molecular viewpoint, modern medicine remains crude. For example, today’s drug is essentially a single molecule with an often sophisticated but always limited repertoire. With nanomedicine, tomorrow’s “Smart Pharmaceuticals” could essentially be programmable machines with a range of “sensory”, “decision-making”, and “effector” capabilities. They can avoid side effects and allergic reactions by coming in generic, biocompatible housings, becoming active only upon reaching their ultimate destinations, and attaining almost complete specificity of action. They can check for overdosage before becoming active, thus preventing accidental or intentional poisoning. They may work in concert with 3 of 4 “sister” agents that together produce versatility unattainable by one agent alone. Despite, the vast increase in complexity over present day drugs, such agents via nanomedicine can be expected to be totally “pure” and predictable in their behaviour. Safety and efficacy may be inherent in the designs of such “drugs” in which case regulatory issues could be simplified rather than complicated. So what exactly is nanomedicine? Nanomedicine may be defined as the monitoring, repair, construction and control of human biological system at the molecular level, using engineered nanodevices and nanostructures. Basic nanostructural materials, engineered enzymes and the many products of biotechnology will be enormously useful in near term medical applications. However, the full promise of nanomedicine is unlikely to arrive until after the development of precisely controlled or programmable medical nanomachines and nanorobots. Basic principle of nanomedicine is three — dimensional positional control of molecular structure to create materials and devices to molecular precision. The human body is comprised of molecules, hence the availability of molecular nanotechnology will permit dramatic progress in human medical services. More than just an extension of “molecular medicine”, nanomedicine will employ molecular machine systems to address medical problems, and will use molecular knowledge to maintain and improve human health at the molecular scale. Nanomedicine will have extraordinary and far-reaching implications for the medical profession, for the definition of disease, for the diagnosis and treatment of medicine conditions, including aging and ultimately for the improvement and extension of natural human biological structure and function. Thus nanomedicine is the preservation and improvement of human health using molecular tools and molecular knowledge of human body. Technically, it is the application of nanotechnology i.e. engineering of tiny machines; to the prevention and treatment of disease in the human body. In other words, nanomedicine is highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle or nerve. A nanometer is one-billionth of a meter, too small to be seen with a conventional lab microscope. It is at this size scale about 100 nanometer or less that biological molecules and structures inside living Nanotechnology involves the creation and use of materials and devices at the level of molecules and atoms. Research in nanotechnology began with applications outside of medicine and is based on discoveries in physics and chemistry. This is because it is essential to understand the physical and chemical properties of molecule or complexes of molecules in order to control them. The same holds true for the molecules and structures inside living tissues. Researchers have developed powerful tools to extensively categorise the parts of cells in vivid details and we know a great deal about how these intracellular structures operate. Yet, scientists have still not been able to answer questions such as, “How many?”, “How big?” and “How fast?” These questions must be addressed in order to build “nano” structures or “nano” machines that are compatible with living tissues and can safely operate inside the body. Once these questions are answered, we will design better diagnostic tools and engineer structures for more specific treatment of diseases and repair of tissues. More specifically, it is the use of engineered nanodevices and nanostructures to monitor, repair, construct and control the human biological system on a molecular level. The most elementary of nanomedical devices will be used in the diagnosis of illnesses. Chemical tests exist for this purpose. These could be employed to monitor the internal chemistry of the body. Mobile nanorobots, equipped with wireless transmitters might circulate in the blood and lymph system and send out warnings when chemical imbalances occur or worsens. Similar fixed nanomachines could be planted in the nervous system to monitor pulse, brain-wave activity and other functions. A more advanced use of nanotechnology might involve implanted devices to dispense drugs or hormones as needed in people with chronic imbalance or deficiency states. Heart defibrillators and pacemakers have been around for some time. But nanodevice carries this to the next level down in terms of physical dimensions, with the potential to effect the behaviour of individuals cells. Ultimately, artificial antibodies, artificial white and red blood cells and antiviral nanorobots might be devised. The most advanced nanomedicine involves the use of nanorobots as miniature surgeons. Such machines might repair damaged cells,or get inside cells and replace or assist damaged intracellular structures. At the extreme, nanomedicines might replicate themselves, or correct genetic deficiencies by altering or replacing DNA i.e. deoxyribonucleic acid molecules.
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In India, with the convergence of human gene sequencing and advances in nanotechnological engineering and a deepening understanding of the function of cellular system, nanotechnologists believe it will be possible to design medically active microscopic machines to fight disease and affect physiological repairs at the cellular level. Invading bacteria will automatically be destroyed, since they do not “fit” within the physiological blue print encoded in the nanorobot patrolling the body. Diagnosis of disease will no longer rely upon patient history and the results of laboratory tests, but will result from an ongoing internal examination of deviations from the encoded molecular blueprint and programmed repair functions designed to correct anomalies at the molecular level. Cell damage attributed to aging will be repaired from the inside out. The potential benefits of medical applications of nanotechnology is nanomedicine are read more like science fiction than science fact. In 1997, a group of health scientists concluded that if a breakthrough to a molecular assembler occurs within 10 to 15 years, an entirely new field of nanomedicine will emerge by 2020. These scientists postulated that initial applications would be focused outside the body in diagnostic and pharmaceutical manufacturing, but the most powerful uses would be within the body. Some of the applications they discussed included cell-herding machines to stimulate rapid healing and tissues reconstruction and cell repair machines to perform genetic surgery. Many of these research goals may take 20 or more years to achieve. Till now researchers have been able to move molecules and even construct nanomotors. There are some technical challenges in the field of nanomedicine. The problems with nanotechnology begin with assembly. As we are aware that nanotechnology is molecular manufacturing-building things, one atom or molecule at time with programmed nanoscopic robotic arms. Atoms don’t simply let themesleves be pushed around. They are constantly moving, jiggling, combining, and reacting, always ready to confound the would be molecular architect. A design that might seem perfectly reasonable to an engineer in the nanoscopic world might, on a nanoscale, fold instantly into a ball of goop. Imagine anyway, that we have a robot hand that can assemble nanomachines, that we have managed to build a stable structure containing ten atoms and we now want to add another piece to it. We would need to grab another atom or molecule, at time making sure that none of the positions of the neighbouring atoms are altered. Each atom’s position is specified in three dimensions, so we would have a 3 dimensional problem at least, if the fourth dimension i.e. timing is not a factor. This is not easy to calculate. The difficulties continue. Because the robot handles one atom at a time, it has to work fast, and with speed come mistakes. A free radical, a highly reactive molecule can clip off a single atom, and thereby undo all that the robot has contrived. The robot would have to detect and correct errors as they appeared, not only as it assembled a device, but also afterwards, in order to maintain its integrity. Another problem is scalability. Unlike the technology for sequencing genes, which began small and only later moved to mass production, carbon nanotubes have been produced by the thousands from the very start. Unfortunately, thousands are not good enough if the goal is to knit the nanotubes into organs, limbs or other cellular structure. For that tons of nanotubes are required with no currently suitable means of mass production. However, on the bright side, the same things were said about combinatorial chemistry, recombinant DNA, decoding the human genome and landing to the moon. Nanomedicine development centers are being established which will serve as the intellectual and technological centerpiece. These centers will be staffed by highly multidisciplinary scientific teams including biologists, physicians, mathematicians, engineers and computer scientists. Research conducted over the first few years will be directed towards gathering extensive information about the physical properties of intracellular structures that will inform us about how biology’s molecular machines are built. As this catalogue of the interactions between molecules and larger structures develops, patterns will emerge, and we will have a greater understanding of the intricate operations of molecular structures, processes, and networks inside living cells.
—RS
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Update on the effects of atomic radiation The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) in its much awaited latest review published on August 5, 2008, concluded that radiation is not riskier than what was stated in earlier reports. Regulatory agencies can breathe easy as they need not alter the dose limits they prescribed to radiation workers and public The report (Volume I) consists of the main text and two of the five annexes: “Epidemiological studies of radiation and cancer” and “Epidemiological evaluation of cardiovascular disease and other non-cancer diseases following radiation exposure”. UNSCEAR may publish the remaining annexes before the end of 2008. UNSCEAR’s assessment of the risk of radiation depended heavily on the study of A-bomb survivors. The new analysis using the radiation doses recently re-estimated by the Radiation Effects Research Foundation, showed that the cancer risk factors may be lower. The committee considered cancer incidence and mortality due to cancers in 20 organs and tissues among A-bomb survivors; these were eight more than those in the earlier study. Nearly half of the survivors are still alive. Those exposed in childhood are now reaching the age at which larger numbers of cancers would be expected to arise spontaneously. There is compelling need to continue the study of A-bomb survivors for their entire life span. The UNSCEAR observed that the cancer risks obtained in new findings from the study of nuclear workers in 15 countries, studies of persons living near Techa river in the Russian Federation who were exposed due to radioactive discharges from Mayak plant and a study of persons exposed to fallout from the nuclear test site in Kazakhstan are generally more than those obtained from the study of A-bomb survivors. However, there are concerns about bias in
these studies. The committee found significant associations between radiation exposure and cardiovascular diseases and other non-cancer diseases. Such associations can occur at doses below those hitherto
considered as thresholds for other effects. Specialists consider that the harmful effects of irradiation originate in the irradiated cells. But there is evidence that non-irradiated cells may show effects such as “genomic instability” (cells surviving irradiation may produce daughter cells that over generations show changes though daughter cells themselves were not irradiated), “bystander effects” (the ability of exposed cells to convey damage to neighbouring cells not directly irradiated) and other effects. The committee concluded that the available data provide some disease associations but not for causation. It recommended future research designing studies that emphasize reproducibility, low dose responses and causal associations with health effects. High doses of radiation may suppress immunity mainly due to cell destruction. Low dose irradiation may suppress the immune system or stimulate it. The immune system may remove aberrant cells which have potential to form tumours. A-bomb survivors show perturbations to stable immune systems. In the final document, the Committee proposed methods to estimate risk from radon, a well established carcinogen, present
in dwellings. To determine radiation risk at typical doses to workers, we need low dose studies. But most low dose studies have inadequate statistical power. The UNSCEAR completed the report in 2005. The Committee acknowledged that resource crunch was the cause for the delay in publishing the report which is now called UNSCEAR 2006. According to a UN specialist, financial restrictions and-sometimes benign neglect- has slowed down the Committee’s work. UNSCEAR reports provide the scientific basis to arrive at dose limits (safe levels of radiation to radiation workers and members of the public). Set up in 1956, the UNSCEAR published 17 documents. The first two reports UNSCEAR 1958 and 1962 paved the way for prohibition of atmospheric weapon testing
in 1963. India has been a member of the UNSCEAR from its very inception. Traditionally, the Chairman of UNSCEAR is from a non-nuclear weapons’ state. V.R. Khanolkar, a pioneer in pathology from India was Vice-Chairman in years 1958-1959; A.Gopal Ayengar a geneticist and the first research scientist Homi Bhabha recruited into the Department of Atomic Energy was Vice-Chairman in 1964-1965 and Chairman in 1966-1967. Let us hope that UNSCEAR will continue to function effectively in spite of various limitations. The writer is former Secretary, Atomic Energy Regulatory Board |
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THIS UNIVERSE It is an admitted fact that water flows from higher to lower level. It is also a fact that 2/3rd of the earth is covered by water. Then how is it that ocean water on the northern hemisphere does not flow down to southern hemisphere and it remains stuck to the place where it is almost evenly distributed. Does gravitational pull play any role in this? You have to understand that on the earth ‘up’ is the direction away from the centre of the earth and ‘down’ is towards the centre. In this respect the northern and southern oceans are at the same ‘height’. Merely because in our maps northern part is shown towards the top of the page, does not mean that it is higher in altitude. Yes, the gravitational pull is the only determinant.
Acceleration due to gravity (g) decreases as we move upwards. Then why does a body gain weight when it is raised from the surface of the earth. Is it because of height? But don’t we use the height for measuring potential energy of the body (P.E =mgh).If energy raised the mass of the body then according to Einstein’s equation this increase in mass should be negligible and thus increase in weight should be negligible. But in reality on a weighing pan I don’t find so. When you raise a mass away from the centre of the earth you are working against the gravitational force. I agree that the force required to raise the mass through a meter would decrease as you go higher because the gravity goes on decreasing. None the less this the total work becomes potential energy. But the body does not gain mass. On the other hand if we were to weigh the body at that height its weight would be less than it was on the ground, precisely because the value of g is less there. Just remember that the rest mass of a proton or any other particle, or thing, remains the same whether it is on earth, on the moon, in orbit or on the Sun. The weight of course would be different. |
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Imagine if a broken part of a cell could be removed and replaced with a miniature biological machine. Think of pumping the size of molecules could be implanted to deliver life saving medicines precisely when and where they are needed or nanomouthwashes that could eliminate gum diseases and tooth decay — nanomachine acting as security guard and attacking any foreign entity in the body.