Gastro-esophageal reflux disease (GERD) is among the most common chronic diseases in the Western world, affecting up to 30% of the general population in Europe and the US. It is a condition which develops when the acidic contents of the stomach flow backwards into the esophagus and cause what’s known as heartburn. While most patients respond well to the standard therapy of proton pump inhibitors which block acid-secreting cells in the stomach, we are still trying to understand the molecular reasons why 30-40% of reflux patients do not respond adequately to acid-suppressant therapy. Not only does GERD have a significant negative impact on health-related quality of life, but the over-subscription of ineffective drugs causes a significant economic burden on healthcare.

Heartburn is the most noticeable and troublesome symptom of GERD. From what we currently understand about the pathophysiology of the disease, we know that the reflux of acid evokes different types of pain, but the basic mechanisms and pathways by which this pain is generated is incompletely understood. The junction between the esophagus and stomach is structurally and functionally designed in a way to ensure that any acid secreted in the gastrointestinal tract flows towards the stomach, and not up onto the lining of the esophagus. This function is served by the muscle structure sitting at this junction, called the lower esophageal sphincter (LES), which ensures that the ingested food following a meal does not reflux. However, there are several factors which can make the LES’s job more difficult. One of the most obvious factors includes the excessive consumption of food, particularly during the later hours of the day. There is convincing evidence that 90% of reflux episodes occur post-prandially, due to minor elevations of intragastric pressure which causes the LES to relax and therefore allow the reflux of acid. In more advanced cases of reflux disease, acid pockets form at the gastroesophageal junction where unbuffered acid collects into a reservoir. When the LES fails in this setting, there is reflux of a higher volume of acid.

Focusing on the microscopic structure of the esophagus and stomach, we can see a minute yet essential difference between the linings of these two gastrointestinal organs. The esophagus has a stratified squamous epithelial lining, which acts as a tight protective barrier against food but is readily damaged when exposed to a chemical environment. On the other hand, the stomach is lined by tall columnar epithelium, which is designed to withstand very low pH and high levels of proteolytic activity. Our gastrointestinal tract (and the human body in its entirety) is perfectly designed to carry out the specific role of transporting food from the oral cavity from the esophagus to the stomach, where it is digested for our nourishment. It is oftentimes our greediness and overindulgence which disrupt the perfect order of our anatomy at a molecular level, resulting in the macroscopic changes we see at endoscopy and the symptomatic discomfort we feel from the painful circumstances of reflux. 

The stomach is our center of nourishment. Given that every food particle has the purpose of nourishing the cells of our body, why do we so commonly make the mistake of eating excessively, nocturnally, and quickly? Fatty foods influence the relaxation of the lower esophageal sphincter, along with alcohol, coffee, and acidic drinks. Large meals and rapid food intake distend the stomach, increase intragastric pressure and facilitating the reflux of acid from the stomach. Given these, it is plain to see that, in most cases, simple lifestyle changes can prevent the development of such chronic and discomforting diseases. The following verse in the Holy Qur’an offers a short but very effective prescription: “Eat and drink, but do not be wasteful” (7:31).

The philosopher and physician Ibn Sina (Avicenna) summarized the science of medicine as follows: “Eat little when you eat, and after eating do not eat again for a certain period of time; health lies in digestion. There is nothing heavier for the body to tolerate than putting food after food in the stomach.” Frugality in eating is also echoed in the teachings of Prophet Muhammad, peace be upon him, who famously said “There is no vessel which the son of Adam can fill more evil than his stomach, for it is sufficient for him to take a few mouthfuls in order to straighten his back; but if he must, then fill one-third with food, one-third with drink, and one-third with air” (Tirmidhi).

The lifestyle factors that are strongly associated with GERD are obesity and smoking. In the 30-40% of GERD patients who do not respond to acid-suppressant therapy, simple lifestyle changes such as cutting out acidic drinks and eating more slowly, and not after 7 pm have been effective alternative treatments. While our understanding of molecular pain mechanisms of the esophagus need further improvement, the simple act of making minor changes in our eating habits can ensure that the anatomy and function of our gastrointestinal tract remains optimal.

“Only when the last tree has died and the last river has been poisoned and the last fish has been caught will we realize we cannot eat money.” Cree Indian Proverb

The table I have under my laptop while writing this article, the materials used for my laptop, the cover case for my phone, the pen I have by my phone, the package for the mail I have received, the dividers I have in my notebook, the hair dryer I have for drying my samples before performing FT-IR on my samples, the FT-IR machine itself … They are all made up of plastics. I could go on and on, giving examples of what I observe in my immediate environment made of plastics. It would not be exaggerated to say that after the Stone Age, Bronze Age, and Iron Age, we are now living in the “Plastic Age” given the fact that the production of plastics has increased from 1.5 million tons per year in the 1950’s to 260 million tons per year in 2007.1 The majority of plastics we use in our daily life are petroleum-based plastics. What that means is, the starting materials of these plastics are chemicals derived from crude oil. There are some major concerns related with these petroleum based plastics – the Earth may run out of oil one day, or the questionable durability of how these plastics biologically degrade. Further environmental concerns exist, such as the toxic additives these plastics contain, including plasticizers like adipates and phthalate. Burning these plastics can release billions of tons of toxic pollutants every year; moreover, most plastic production reactions are done in toxic solvents, so the disposal of these solvents becomes a problem.2 Reflecting on it, it’s an incredible mercy that we have been able to get away with all the waste we have produced up to this point. But the question is: how much longer can we get away with such wasteful behavior?

One of Paulo Coelho’s passages from his book The Winner Stands Alone exactly describes my attitude and desire to “go green.” My heart pounds as I read the sentences that so touched me:

It seems now that-despite wars, famine in Africa, terrorism, the violation of human rights, and the arrogant attitude of certain developed countries-our main preoccupation is saving poor planet Earth from the many threats created by human society. “Ecology. Save the planet. How ridiculous.”

Hamid knows, however, that there’s no point in fighting the collective unconscious. The colors, the accessories, the fabrics, the so-called charity events attended by the Superclass, the books being published, the music being played on the radio, the documentaries made by ex-politicians, the new films, the material used to make shoes, the new bio-fuels, the petitions handed in to members of parliament and congressmen, the bonds being sold by the largest of the world banks, everything appears to focus on one thing: saving the planet. Fortunes are made overnight; large multinationals are given space in the press because of some completely irrelevant action they are taking; unscrupulous NGOs place advertisements on the major TV channels and receive hundreds of millions of dollars in donations because everyone seems obsessed with the fate of the Earth. Whenever he reads articles in newspapers or magazines written by politicians using global warming or the destruction of the environment as a platform for their electoral campaigns, he thinks:

“How can we be so arrogant? The planet is, was, and always will be stronger than us. We can’t destroy it; if we overstep the mark, the planet will simply erase us from its surface and carry on existing. Why don’t they start talking about not letting the planet destroy us? Because ‘saving the planet’ gives a sense of power, action, and nobility. Whereas ‘not letting the planet destroy us’ might lead to feelings of despair and impotence, and to a realization of just how very limited our capabilities are.” 3

On that note I would like to share some amazing facts I found while searching articles written on bacterial biopolymers, but first of all I would like to introduce some definitions on the concepts I will be writing about.

Plastics have many definitions, but usually, in a daily conversation, plastics mean “anything that can be molded or shaped.” Scientifically, a plastic is a sub category of a polymer. Poly- meaning “more than one” and -mer meaning “member of a particular group.”[4] Basically, a polymer is a naturally occurring or synthetic compound made of many relatively simple repeating units that are linked together in the same fashion, forming a carbon rich backbone in most cases. For example, PVC is a well known synthetic polymer, in which the monomer (the repeating unit) as seen in Figure 1 is repeated several times. A well known natural polymer is cellulose, in which the monomer as seen in Figure 2 is repeated several times.

Here it is important to note the difference between a polymer and a plastic. All plastics are polymers, as in the example of PVC, whereas not all polymers are plastics, as in the example of cellulose. The combination of the chemicals, and the type of bonds these chemicals are linked to each other by, determines the properties and applications of the polymers. The molecular weight of the polymer depends on how many times the monomer repeats itself. The molecular weight of polymers can be controlled during production with chemical techniques. One significant difference between natural vs. synthetic polymers is the molecular weight distribution. When the polymer is synthesized in the lab, the polymer product is a combination of different molecular weight chains. In other words, when a polymerization reaction takes place, lots of polymer chains are produced and one chain is never the same length or weight as another. Instead, there is a molecular weight distribution as seen in Figure 3, where most of the polymer chains in the solution have a molecular weight close to the value of Mw. So in the solution, we will have polymer chains that have molecular weights close to each other, and some extreme short or long polymer chains. It is impossible to synthesize a polymeric solution where all the polymer chains are of identical length and weight; therefore, we speak about the average molecular weight when the case is synthetic polymers. However, when we look at any polymer produced in nature, we see that the polymer chain length and molecular weight are the same every time the polymer is produced. So instead of a molecular weight distribution, natural polymers have a molecular weight value. This is important because the narrower the molecular weight distribution is, the better.

When talking about bio plastics, it is important to make the differentiation between bio-derived plastics and bio-based plastics. As Dr. R. Narayan explained in his talk at Johnson County Community College[5] , bio-derived plastics means that the plastic is isolated from a living organism, meaning that the living organism performs the polymerization reaction and then you extract the polymer from the organism.

On the other hand, bio-based plastics mean that the starting material of the plastic is derived from a living organism instead of a petroleum-based material, but it is polymerized into a plastic by humans. Therefore, not all bio-based plastics are biodegradable; however, the fact that the starting material is from a plant that can be replaced in a couple of years rather than a petroleum-based product which can only be replaced after a couple million years, drives motivation for their usage. There is the ethical concern that bio-based plastics are usually made from food sources, such as corn, however Dr. R. Narayan, who is one of the leaders in the field, argues that if the situation is handled appropriately, this should not be a problem. He argues that one up-side of the situation would be to increase values of crops and the prevention of mass migration to big cities. It’s your call to decide which side you favor more.

What is more interesting to me is the polymers being created in nature. A chemistry doctorate, Dr. Lon J. Mathias, writes that “We humans make nylons in tons per day in huge chemical plants where simple molecules are joined together in large quantities to give products that we need or want. Nature is much more careful and concise in how she does things. For a living organism to make an enzyme, another enzyme or active species must be involved. The synthesis always involves a template, or recording, of how the individual amino acids are to be joined together to give the final polymer. The enzyme adds a single amino acid, one at a time, as indicated by the mRNA. This is a slow and tedious process and takes a long time. Sometimes the enzyme gets frustrated, waiting for the right amino acid to come along, and slaps a wrong one on instead. To compensate for this, the enzyme is made to back up occasionally to check its work. If it has made a mistake, it has a process for clipping out the wrong amino acid and inserting the right one. We humans never do this. If we make a mistake, we simply grind it up and throw it away.”6

Dr. Mathias goes on, comparing the manufacturing conditions between nature’s form of polymerization and humanity’s. He says polypeptides in nature are synthesized in water, whereas we synthesize our polypeptides in toxic organic solvents. “This leads us to a problem: what do we do with the organic solvents when we’re through? Sometimes we burn them, but more commonly we try to recycle these materials, which not only are getting more expensive to buy in the first place (compared to cheap water, which is everywhere, or almost everywhere) but are also a responsibility for their recycling, purification, and final disposal. An example of how nature uses water in this way, and one which we still haven’t figured out, is the production of spider silk. Spiders spin their webs from solutions of polypeptides in water. These solutions are squeezed through the spider’s tiny spinneret and elongated quickly to form the spider webs which we’ve all seen and sometimes become tangled in. What’s really weird is that, once these spider webs form, they are no longer soluble in water. If we could just figure out how spiders first make spider silk in water and then spin their webs from it, we could make nylon the same way. This might save us a lot of waste disposal problems, and money.”6

Another spectacular creation in nature is polymers produced in bacteria which can be used as plastics once isolated from the bacteria. A wide range of biopolymers that are synthesized in bacteria serve diverse biological functions and have material properties suitable for numerous industrial and medical applications.7 Different carbon sources are efficiently converted into a diverse range of polymers with varying chemical and material properties.7 To be a little more specific, four major classes of polymers are produced by bacteria: polysaccharides, polyesters, polyamides and inorganic polyanhydrides (such as polyphosphates).7 These polymers serve various biological functions, for example, as reserve material or as part of a protective structure, and can provide a substantial advantage for bacteria under certain environmental conditions.7 Some of these biopolymers can be isolated from bacteria and can be used as plastic. Biopolymers are, by definition, biodegradable, and so their application as commodity products becomes increasingly attractive in view of the desire to avoid the use of recalcitrant oil based polymers that will accumulate in the environment.7 Biodegradable means that when exposed to the microbial flora present in a given environment (for example, in soil or water), biopolymers are fully degraded and mineralized to CO2 and H2O.5 The reason biopolymers are 100% degradable is, as they are produced in bacteria as storage material, they have sites where bacterial enzymes could attack to break them down when they search for nutrients. Whereas other polymers – even bio based polymers – will not have these enzymatic sites, so they are not always biodegradable.

One popular class of polymers produced by bacteria which can be used as plastics is called polyhydroxyalkanoates (PHA’s). PHA’s are a class of polymers produced in nature by the bacterial fermentation of sugar or lipids. They are produced by bacteria to store carbon and energy when there is a nutrient lacking from the environment. Many kinds of bacteria are able to produce PHA’s, such as soil inhabiting bacteria, and many bacteria in activated sludge, high seas, or extreme environments. 8 As we store fats in our bodies, the bacterium store PHA’s. In an environment that contains all of the necessary nutrients, bacteria grow and reproduce – in other words they produce biomass. However, when subjected to specific nutrient depletion (nutrients such as nitrogen or phosphorus) and excess amount of carbon resources, the bacterium starts storing PHA granules (Picture 3). The moment the missing nutrient is introduced back into the environment, the bacterium starts degrading the PHA granules and continues to produce biomass. Therefore, by manipulating the nutrient resources in the environment and providing optimum conditions, bacterium can be pushed to produce PHA’s.[9]

There are metabolic pathways involving various enzymes for the conversion of carbon sources to polymers. Scientists have been trying to genetically engineer bacteria for the increased production of these polymers. In some cases it is possible to over-express the key enzymes in the pathways to achieve increased production of PHA. However, this kind of research takes a lot of time and effort because altering biological activity is a very complicated process and in most cases, cells give unpredictable responses to alterations. By feeding the bacterium with different carbon sources at different conditions, it is also possible to alter the composition of the polymers. Moreover, different strains of bacterium produce different types of polymers; therefore, the range of biopolymer research is very wide. With over 150 different PHA monomers (the repeating unit of polymers) being reported, PHA with flexible thermal and mechanical properties have been developed. 7 Such diversity has allowed the development of various applications.

During his speech at the “2nd International PLASTiCE Conference Trends in Bioplastics” in Slovenia, 9 Dr. Martin Koller explained that there are two types of PHA’s that a microorganism produces. The first type are short length PHA’s (3-5 carbons in the backbone) and the second type are medium chain length PA’s (6-12 carbons in the backbone). While the medium chain length PHA’s can be used for biodiesel production, the short chain length PHA’s can be used as thermoplastics (plastics that can melt with heat, and can therefore be processed with the help of heat). These thermoplastics can be isolated from the organisms they are produced in by solvent extraction, mechanical disruption, or by using hypotonic media (having the lower osmotic pressure of two fluids) for cells that have high intracellular osmotic pressure.9 In the last case, the cells will explode due to the pressure difference and release the PHA’s; deionized water can be used as the hypotonic media. However, only specific strains can be treated with this method. At the moment, the most common technique used for extraction is solvent extraction. These solvents – such as chloroform or dichloromethane – are generally toxic, therefore creating a contradiction with the point of producing biopolymers.

Although not mainstream, some of these bacterial plastics are produced in the industrial world.8 The simplest and widest application for bacterial plastics is for packaging purposes. They can also be used in therapeutic applications, as they are generally biocompatible. Drugs can be incorporated into them, therefore as they biodegrade, they release the drug in a controlled time frame.9 For example, Dr. Martin Koller and his group have just finalized a project called “BRIC – BioResorbable Implants for Children,” funded by the Austrian Research Promotion Agency (FFG).10 Their purpose was to isolate a biocompatible polymer produced from bacterium which could be degraded and removed from the body within a certain time. The point of this project is based on the fact that in contrast to the traditional implants that need to be removed from the body after a certain amount of time, such as plates, screws or pins, the newly developed implants could be degraded and removed from the body naturally, preventing the need for a second surgery. This is a great advantage, especially for children, who would suffer greatly from additional surgeries.

Bacterial bioplastics have many other applications; however the biggest obstacle for their usage is the cost of production. During his speech, Dr. Keller stated the production of bacterial bioplastics is around five times more costly than petroleum based plastics. Most of the cost is related with the bioreactors needed to grow the bacterium and the solvents used to extract the polymers. The scientists are hoping to develop new techniques to reduce the cost of the polymers.

It is breathtaking that these creatures we cannot even see with the naked eye have been synthesizing polymers as well as we do, if not even better, and for a lot longer than us. The polymers they synthesize are completely biodegradable, have a constant molecular weight, and do not require toxic chemicals for their production, unlike the synthetic polymers we produce in the lab. They don’t harm nature as we do. And THAT is powerful.

References

1- Simon, Tristan (2007). “Experience Curves in the World Polymer Industry” Utrecht University, Netherlands.

2- Lei Pei, Markus Schmidt and Wei Wei (2011). “Conversion of Biomass into Bioplastics and Their Potential Environmental Impacts, Biotechnology of Biopolymers.” InTech.

3- Coelho Paulo(2008), “The Winner Stands Alone.” pg: 139.

4- http://dictionary.reference.com/

5- Narayan, Ramani (2013)”Bioplastics and Reducing Carbon Footprint.” JCCC Video. Johnson County Community College, USA.

6- Mathias, Lon J. (2005).”Natural Polymers.” Polymer Science Learning Center. The University of Southern Mississippi, USA.

7- Rehm, Bernd H.A.(2010). “Bacterial polymers: biosynthesis, modifications and applications” Nature Reviews Microbiology. Massey University, New Zealand.

8- Chen, Guo-Qiang (2010). “Plastics Completely Synthesized by Bacteria: Polyhydroxyalkanoates”. Plastics from Bacteria: Natural Functions and Applications, Microbiology Monographs, Springer. Tsinghua University, China.

9- Koller, Martin (2012). “Polyhydroxyalkanoates: Biodegradable polymeric materials from renewable resources” Plastice Project Video. 2nd International PLASTiCE Conference Trends in Bioplastics, Slovenia.

10- No name (2013).”Plastics from Renewable Raw Materials:Body automatically breaks down implants” Graz University of Technology, Austria.

11- Nishiyama, Yoshiharu; Langan, Paul; Chanzy, Henri (2002). “Crystal Structure and Hydrogen-Bonding System in Cellulose Iβ from Synchrotron X-ray and Neutron Fiber Diffraction”. J. Am. Chem.The University of Tokyo, Japan.

12- Ritter, Stephen(2005). “Green Success.” Science and Technology. pg: 40-43.

13- Waters Co. (2013). “GPC-Gel Permeation Chromatography”. Web.

They are tiny, and there are billions of them inside you. Tiny machines, one thousand times thinner than a hair strand but strong enough to carry all kinds of material within your cells. Yes, there is a complex army of tiny machines inside your body performing an amazing array of functions while you sit at home sipping your tea.

Your heart is beating. Its lifelong duty is to pump blood to tissues to deliver essential nutrients. Transportation of nutrients continues from blood vessels to cells and then into subcellular compartments. Inside of a cell, there is a need for sophisticated biomachines which are responsible for transport. Did you know that you were equipped with minuscule motors that transported cargos in your cells? Or about cellular highways where molecular cargos are transported?

There are various proteins called “motors” in the cell. They can convert chemical energy to mechanical energy to produce force and motion in the cellular highways.¹ Amazingly, molecular motors are much superior to man-made motors in terms of energetic efficiency by hydrolyzing ATP to fuel enzymatic reactions. These molecular motors include rotary motors, polymerization motors, nucleic acid motors and cytoskeletal motors.

Rotary motors

Bacterial flagellum, used for swimming, acts as a propeller and uses a rotary motor. It has been suggested that this motor is similar to Fo motor found in FoF1-ATP synthase. FoF1-ATP synthase takes part in the conversion of chemical energy in ATP to proton gradient, or vice versa. This chemical reaction involves mechanical rotation of parts of the complex.

Polymerization and nucleic acid motors

Polymerization motors take role in polymerizations and these polymerizations generate forces for repulsion (Actin or microtubule polymerization), or separation of clathrin buds from plasma membrane (Dynamin).

DNA and RNA synthesis also involves the use of molecular motors such as RNA polymerase (RNA synthesis from DNA), DNA polymerase (DNA synthesis), Helicases (separation of double stranded DNA prior to DNA or RNA synthesis), Topoisomerases (removal of supercoiling of DNA), RSC, SWI/SNF, and SMC proteins (Chromatin remodeling and chromosome condensation). Moreover, there are specific viral DNA packaging motors that pack tightly viral DNA into capsids. separation of double stranded DNA prior to DNA or RNA synthesis), Topoisomerases (removal of supercoiling of DNA), RSC, SWI/SNF, and SMC proteins (Chromatin remodeling and chromosome condensation). Moreover, there are specific viral DNA packaging motors that pack tightly viral DNA into capsids.

Cytoskeletal motors

Dyneins, kinesins and myosins denote the three major classes of molecular motor that moves along cytoskeletal structures. Myosin is among the most prominent of motor proteins that takes role in muscle contraction. Kinesin operates on microtubules (long tubes composed of dimers of the protein tubulin, arranged to form 13 parallel tracks) to move cargos inside the cells away from the nucleus (toward positive end of microtubules) and play essential roles in the formation of spindle apparatus and axonal transport. Dynein is also known to transport cargo but in the opposite direction to Kinesin, towards the cell nucleus (toward minus end of microtubules). In addition, dynein is required to beat cilia and flagella.

How molecular motors move

Myosin and kinesin are structurally similar in terms of being dimeric with two motor heads, two legs, and a common stalk. The head regions control the forward movement by binding itself to actin or microtubule filaments. Movement is facilitated by the consumption of ATP by ATPase sites. It is fascinating how these motors translate chemical energy into motion and still be different to the movement of cars. There are different proposals as to how molecular motors move, such as walking (hand-over-hand model), inchworm model, and biased diffusion model.

The-hand-over-hand model suggests that ATP binding induces a conformational change in the forward head movements and keeps fixed, thus leading to the movement of the rear head forward and vice versa. This model, which is also known as the walking model, is similar to upright walking where one foot moves forward while other stay fixed, and vice versa. On the other hand, the inchworm model suggests that only forward head movements use ATP and leads while the other head follows. Studies on the Myosin VI with shorter legs suggested a biased diffusion model. In the diffusion model, the motor moves randomly to the next binding site in a forward direction. In order to find out which mechanism used by molecular motors, scientists measured how much of the head moves following staining with a fluorescent dye. Since molecular motor movements are so small (5-10 nM), optical traps and cantilever probes (>100 μm) were not useful to watch head movements. By increasing both photostability and brightness of organic dyes, Dr. Yildiz at UC Berkeley was able to measure head movements down to 1.5nM scale.

Kinesin: A molecular motor that walks

Kinesins are among microtubule-based motors recently shown to walk like a mountain climber by swapping its two motor units (analogous to feet) in a hand-over-hand mechanism rather than an inchworm mechanism. This recent discovery sheds light on how kinesin moves its cargos such as membrane components, messenger RNA, signaling moleculers, and others along microtubules. In addition, as suggested by findings of Dr. Yildiz, kinesin demonstrates an asymmetric walking where motor heads alternate with slow and fast steps. Further studies using advanced microscopy techniques (called FIONA) which allow nano scale detection of movement down to 2nM resolution demonstrated delicately that processive kinesin motor takes about 8 nM steps (eight-billionths of a meter) for each ATP molecule consumption with alternating 16-nm and 0-nm steps. Furthermore, kinesin is attached to the microtubule while it waits for ATP between steps. Since kinesin is used for long distance cargo transport on relatively big highways of a cell, it elegantly demonstrates a processive motor that reliably travels in a coordinated manner. Of course, not all motors will be moving like kinesin.

Dynein moves through uncoordinated stepping of ring domains

Another motor protein involved in long distance cargo transport is dynein. Dynein is a staggering giant which is much bigger and complex than kinesin and myosin motors. There are about 15 types of dyneins known to take role in cilia and flagella movement and 2 cytoplasmic forms. Cytoplasmic dynein is a homodimeric AAA+ (ATPases associated with cellular activities) motor that transports toward the microtubule minus end, acting opposite to kinesin. FIONA assay demonstrated that the heads moving processively but independently. This mechanism is quite different from the hand-over-hand stepping of kinesin and myosin, for dynein’s steps are not strictly coordinated and highly variable. Most of the time, dynein heads move alternatively with variable head-to-head distance of about 5-50nM. Each head of dynein mostly does not pass each other.

Elegant design, efficiency in transportation and being part of the living system makes molecular motors in the cells superior to man-made motors. Molecular motors travel on cellular highways in the cellular microcosm in the manner of dutiful officials of a king traveling in his domain in security via the fastest modes of transportation and easily cross provincial boundaries, demonstrating more evidently that the Sovereignty of the Eternal King is limitless. Indeed, the signs of His Dominion are reflected by each and every entity from the microcosmic world to macrocosmic universe.

Note

1 Cellular highways are composed of microtubules, microfilaments and actin filaments. Myosin moves along microfilaments through interaction with actin, but dynein and kinesin move along microtubules through interaction with tubulin

References

• DeWitt MA et al. Cytoplasmic dynein moves through uncoordinated stepping of the AAA+ ring domains. Science. 2012 Jan 13;335(6065):221-5. Epub 2011 Dec 8.
• King SM. AAA domains and organization of the dynein motor unit. J Cell Sci. 2000 Jul;113 ( Pt 14):2521-6.
• Wilhelm J. Walter & Stefan Diez. A staggering giant. Nature. Vol 482. 2 February 2012.
• Molecular motors and Motor proteins. Retrieved from Wikipedia on 3/31/2012.
• Yildiz et al. Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging with 1.5-nm Localization. Science 27 June 2003:Vol. 300 no. 5628 pp. 2061-2065
• Yildiz et al. Kinesin Walks Hand-Over-Hand. Science 30 January 2004: Vol. 303 no. 5658 pp. 676-678

In the 21st century, we are plunging forward into a new era of technological power — one that offers enormous promise and danger.

What is nanotechnology?

In its most basic form, nanotechnology refers to the manipulation of materials at the atomic or molecular level. The name derives from the nanometer, a scientific measurement unit representing a billionth of a meter, three to four atoms wide. Scientists are learning how to connect atoms and molecules together to create nano-scale mechanisms that create switches or transistors, or even small machines that can perform complex tasks.

To use an oft-quoted comparison, a human hair is between 100,000 and 200,000 nanometers thick, while a typical virus can be just 100 nanometers wide. Atoms are typically between one-tenth and one-half of a nanometer wide. Due to the difficulties involved in working at this scale, manipulation of items as “large” as 100 nanometers is generally included in the concept of nanotechnology.

Nanotechnology enables scientists to create new materials atom by atom. With increasingly more powerful microscopes, scientists can see molecules that are mere nanometers (billionths of a meter) in size. To clarify this size, a pinhead is one million nanometers across. The field intertwines nearly all fields of science.

Most nanotechnology discussions deal with the futuristic concept of nanomachines or nanorobots: microscopic devices that carry out tasks at the atomic or subatomic level. Nanotechnology, also called molecular manufacturing, is “a branch of engineering that deals with the design and manufacture of extremely small electronic circuits and mechanical devices built at the molecular level of matter.” The goal of nanotechnology is to manipulate materials at the atomic level to build the smallest possible electromechanical devices, given the physical limitations of matter. Many of the mechanical systems that we know how to build will be transferred to the molecular level as some atomic analogy.

A typical vision of the twenty-first century: “Nanotechnologists will be building our cars one molecule at a time, invading our bloodstream to declog our arteries, and replicating themselves thousands of times over.”

Nanorobots (1)

A nanorobot is a computer-controlled robotic device constructed of nanometer-scale components to molecular precision, usually microscopic in size (often abbreviated as nanobot). This reminds one of the 1966 film Fantastic Voyage, in which a team of scientists (including Raquel Welch) are miniaturized, placed in a tiny submarine, and injected into a sick man’s bloodstream. Nanotechnology invariably involves work on a much smaller scale than the average blood cell.

Producing commercially viable nanomachines will be more challenging, since atomic manipulation, while not theoretically contrary to the laws of physics, is still extremely slow and costly. The most widely discussed long-term solution is to make the nanomachines self-replicating. Control mechanisms for such systems, mainly how a machine “knows” to copy itself and when to stop doing so, are still in their very early stages. Once again, theory is far ahead of practical reality.

Many of nanotechnology’s more recent practical applications have been in the area of material research. However, scientists believe that transistors eventually could be built in this way, paving the way for computational technologies that do not depend on silicon and that can pack even more circuitry into microscopic spaces.

Nanoshells (2)

Nanoshells, defined as tiny particles that can manipulate light, can be used to transform medical procedures, ranging from cancer therapy to medical testing and drug delivery. They are ideal for biotechnology applications because they are biocompatible, can be altered and modified, and absorb light easily in the near-infrared region, where human tissue is most transparent.

Nanoshells can be tagged and delivered specifically to tumor cells, thereby leaving healthy cells undamaged. In addition, they can reduce the amount of time needed to conduct medical tests from several days to a matter of seconds. When incorporated into temperature-sensitive polymers, nanoshells can be triggered to release a chemical using infrared light, thus enabling a patient to control the release of medicine that requires periodic dispensing.

A new bandage (3)

A new bandage that imitates natural healing process is used for injuries ranging from minor cuts to gunshot wounds. The bandage, a flannel-like material, stops bleeding immediately and eventually is absorbed by the body. This new material is developed by spinning a compound naturally found in the blood into a bandage that can minimize blood loss and be absorbed by the body, according to an article in the 12 Feb. 2003 issue of Nano Letters, a journal of the American Chemical Society. “We’ve taken an old technique — electrospinning — and applied it to natural fibers,” says Gary Bowlin, associate professor of biomedical engineering at Virginia Commonwealth University.

When a person bleeds from a cut or a wound, a blood clot forms and netting made of a substance called fibrin develops over the clot. According to researchers, fibrinogen, the compound in blood that comprises the “natural” bandage, is a fibrin precursor that can come from human, bovine, or genetically engineered bacterial sources. The goal is to pack the bandage like gauze so that it can be used to treat trauma patients, according to Bowlin.

Science fiction into reality (4)

Imagine a world in which cars can be assembled molecule-by-molecule, garbage can be disassembled and turned into beef steaks, and people can be operated on and healed by cell-sized robots. Sounds like science fiction? Well, with current semiconductor chip manufacturing encroaching upon the nanometer scale and the ability to move individual atoms at the IBM Almaden laboratory, we are fast approaching the technological ability to fabricate productive machines and devices that can manipulate objects at the atomic level. With this ability, we will be able to develop molecular-sized computers and robots that will give us unprecedented control over matter and the ability to shape the physical world as we see fit.

Nanofabrication techniques with applications in fiber optics, biotechnology, microelectromechanical systems (MEMS), and “tiny mechanical devices such as sensors, valves, gears, mirrors, and actuators embedded in semiconductor chips,” are of particular interest, as they are but a mere step away from the molecular machines envisioned by nanotechnology. MEMS are used in automobile airbag systems as accelerometers to detect collisions, and will become an increasing part of our everyday technology. In 1986, K. Eric Drexler, a researcher at MIT, foresaw the advent of molecular machines. In his Engines of Creation, he outlined the possibilities and consequences of this emerging field, which he called nanotechnology. Drexler has written numerous books on the subject, such as Unbounding the Future, and has founded the Foresight Institute, a nonprofit organization dedicated to the responsible development of nanotechnology. Today, nanotechnology research and development is widespread in numerous universities. The U.S. government has created an organization, the National Nanotechnology Initiative (NNI), to monitor and guide research and development in this field.

Potential benefits

It does not take much of a leap of imagination disassemblers dismantling garbage to be recycled at the molecular level, and then giving it to assemblers who will use it to build atomically perfect engines. Stretching this vision a bit, you can imagine a Star Trek type replicator that could reassemble matter in the form of a juicy steak, given the correct blueprints and organization of these nanomachines.

A laboratory-scale “in vivo nanoscope” could be capable of providing atomic resolution, real-time movies of happenings inside living cells in intact living animals. This nanoscope, a hybrid of conventional technology and early (pre-assembler) nanotechnology, is an enormous leap in the ability of biologists to understand the workings of cells and develop medical therapies.

Some of the more prominent benefits of nanotechnology would be precision manufacturing, material reuse, and miniaturization. Medical applications are pharmaceutical creation, disease treatment, and nanomachine-assisted surgery. Environmental applications lie in toxin cleanup, recycling, and resource consumption reduction.

Nanomedicine deals with the comprehensive monitoring, control, construction, repair, defense, and improvement of all human biological systems by working at the molecular level with engineered nanodevices and nanostructures; the science and technology of diagnosing, treating, and preventing disease and traumatic injury, as well as relieving pain and preserving and improving human health through the use of molecular tools and molecular knowledge of the human body; and the use of molecular machine systems to address medical problems and using molecular knowledge to maintain and improve human health at the molecular scale. Cosmetic nanosurgery carried out with simple nanomachines (no on-board computers, for example) could change hair color, cause hair to grow or not to grow in specific locations, keep teeth clean and skin smooth, and so on, all far more effectively than current treatments.

Looking somewhat further in the future at more radical modifications of the human body through nanotechnology, Edward Reifman describes dentistry with assembly-fabricated teeth, and even with the teeth and jaws being made of diamonds. “In the long term, we hope to be able to build small nanorobots which can search out and destroy cancerous tumors when they comprise just one or two cells” or “small drilling machines which dissolve clots.”

Viruses, which are natural nanomachines, could be fought more effectively, as the body’s own immune system has some handicaps: it tends to forget the shape of its enemies, cannot always successfully identify malignant cells, and suffers from a certain delay until the immune reaction is fully developed. Therefore, nanomachines could support the immune system. Nanomachines could rout bacteria, excise tumors, reconstruct damaged tissue, and even make a huge contribution to treating the process of aging.

Along with the obvious manufacturing benefits, there are many potential medical and environmental benefits. With nanomachines, we could better design and synthesize pharmaceuticals, directly treat such diseased cells as cancer, better monitor a patient’s life signs, and make microscopic repairs in hard-to-operate-on bodily areas. With regard to the environment, we could use nanomachines to clean up toxins or oil spills, recycle garbage, and eliminate landfills, thus reducing our natural resource consumption.

Potential dangers

The downside to these benefits is the possibility of using assemblers and disassemblers to create weapons, to be used as weapons themselves, or the possibility that they may run wild and wreak havoc. Other less invasive but equally perilous uses would be in electronic surveillance.

However, with nanotechnology, armies could develop disassemblers to attack physical structures or biological organisms at the molecular level. A similar hazard would be if general-purpose disassemblers escaped into the environment and started disassembling every molecule they encountered, the so-called “gray goo scenario.” Furthermore, if nanomachines were created to be self-replicating and, for some reason, had a problem with their limiting mechanism, they would multiply endlessly, like viruses.

Even without considering such extreme disaster scenarios, we can find plenty of potentially harmful uses for nanotechnology, such as the erosion of our freedom and privacy. For example, people could use molecular-sized microphones, cameras, and homing beacons to monitor and track others.

Ethical issues and analysis

Given the awesome potential dangers inherent in nanotechnology, we must analyze its potential consequences. Nanotechnology may never become as powerful and prolific as envisioned by its evangelists, but as with any potential near-horizon technology, we should formulate solutions to potential ethical issues before the technology is irreversibly adopted. We must examine the ethics of developing nanotechnology and create policies designed to assist its development while eliminating, or at least minimizing, its damaging effects.

Nanosensors(5)

A nanosensor is defined as a chemical or physical sensor constructed by using nanoscale components, usually microscopic or submicroscopic in size.

Nanotechnology brings science fiction into everyday life6 Nanotechnology’s more immediate future lies in its application in such sensors as electronic “noses” that can detect, for example, the presence of individual protein molecules in a blood sample. This involves a fingernail-sized chip with thousands of sensors, each set to detect a specific substance. It might even be possible to make these noses so small that they could fit on a needle. Then, there would be no need for a blood test, for a finger prick would be sufficient to allow a full blood analysis.

Nanosensors also will be of great value in producing new medicines, for they can effectively find active substances. So far, it has been possible to build this type of sensor one by one; the difficulty lies in integrating perhaps 100,000 of them on one chip.

Aging can be delayed by repairing human cells one by one. Unlimited computer power can be obtained by improved microchip performance. Global warming can be reduced by cleaning greenhouse gases out of the atmosphere with nanoparticles, and pesticides could kill insects without harmful byproducts. Creating artificial muscles and sensors, as well as nanocoating for metal, could increase power plant efficiency and potentially save millions of dollars a year for electricity generators. For example, we now have self-washing windows that repel dirt, thanks to their nanostructured surface.

Nanofluids (7)

On the medical front, researchers at Virginia Polytechnic Institute are developing magnetic nanofluids. They posit that magnetic particles attached to medicines, like those used in chemotherapy, can be concentrated on one part of the body by using external magnets on patients. 

Always clean clothing (8,9)

Imagine textiles that cannot be stained or wrinkled, that always maintain the look and feel of fabrics made from natural fibers. Imagine materials that are 100 times stronger than steel, but weigh only one-sixth as much. Nanofibers could be used in astronauts’ suits, moving with them as they work to give them greater flexibility in space, or to allow the disabled greater mobility by acting as extra muscles.

Imagine batteries that take up less than one cubic millimeter, but supply a medical implant with power. Imagine sensors, smaller than a pinpoint, that detect anything in extremely low concentrations, from specific antibodies to toxic chemicals.

A big splash of coffee leaves an unmistakable stain on an ordinary pair of trousers; on a pair of nanotextile trousers, it can be brushed off without leaving a trace. A titanium frying pan and the laser in a fairly modern CD player are both based on nanotechnology. By using nanotechnology, wall paint could automatically sterilize an operating theatre, filters could be used in water purifiers to automatically kill undesirable bacteria, and roofing tiles that convert solar light into household electricity could give way to reinforced self-repairing houses immune to all natural disasters “short of a large incoming meteor.(10)

Hence nano-technology is and will continue to become part of our everyday lives … sometimes without us even noticing.

Michael Crichton (11)

Crichton says “These organisms [self-reproducing tiny computers] will be created by nanotechnology, perhaps the most radical technology in human history: the quest to build man-made machines of extremely small size, on the order of 100 nanometers, or 100/billionths of a meter. Such machines would be 1,000 times smaller than the diameter of a human hair. Experts predict that these tiny machines will provide everything from miniaturized computer components to new medical treatments to new military weapons. In the 21st century, they will change our world totally.

“The potential benefits are spectacular: Tiny robots may crawl through your arteries, cutting away atherosclerotic plaque; powerful drugs will be delivered to individual cancer cells, leaving other cells undamaged; teeth will be self-repairing. Cosmetically, you will change your hair color with an injection of nanomachines that circulate through the body, moving melanocytes in hair follicles. Other nanomachines will lighten or darken skin color at will, removing blemishes, birthmarks and liver spots in the process; still others could cleanse the mouth and eliminate bad breath. Nonsurgical nanoprocesses could even perform liposuction and body reshaping. They will also repair knees and spines.

Living spaces will be transformed with self-cleaning dishes and carpets and permanently clean bathrooms. Windows will lighten or darken at will; programmable paint will change color. You can walk through the walls of your house, since they are composed of particle clouds. Your personal computer and your watch will be painted on your arm. Temperature-sensitive clothing will loosen when it gets hot, insulate when it gets cold.”

In the future, roving nanomachines will convert trash dumps to energy, solar nanomachines will be coated on the houses to generate electricity, and flexible nanomachines will provide earthquake protection. It may even be possible to move a house across the lawn on the backs of millions of nanomachines.

In 2003, nanotechnology is still very much in its infancy. However, such major corporations as IBM, Fujitsu, and Intel are funding this research. U.S. government investment has gone from virtually nothing only a few years ago to well over $600,000,000 per year in 2003.

At present, nonotechniques are being used to make sunscreens, stain-resistant fabrics, and composite materials for cars; soon, they will be used to make extremely small computers and storage devices. Pittsburgh based PPG Industries, Inc. is making self-cleaning window glass; the Westaim Corporation of Toronto is making nanocrystal wound dressings with antibiotic and anti-inflammatory properties. Currently, nanotechnology is principally a material technology.

Most experts predict that self-reproducing machines are only a decade away. Man-made, self-reproducing entities already have been released into the environment. The first of these, of course, were computer viruses. The first viruses were created as a game (“core wars”), a 1960s battle between mainframe programmers, each releasing a program into the other’s mainframe computer. Originally limited to specialists, hackers soon joined in. The growth of computer networking made rapid worldwide transmission possible. Computer viruses, worms on the Internet, have become an international threat to information and global business.

Scientists are witnessing some of the problems of self-replicating biotechnology agents. For example, a recent report indicates that modified maize genes are appearing in native maize in Mexico, despite laws against it and efforts to prevent it. This is only the start of probably a long journey to control this new technology. Laws have been passed to put hackers in jail; delinquent biotechnologists will soon join them. We need international controls to deal with self-reproducing technologies right now, whereas now there are essentially none.

Footnotes

(1) www.zdnet.com.au/newstech/enterprise/story/0,2000048640,20267134-2,00.htm

(2)www.rice.edu/projects/reno/Newsrel/2001/20010402_nanotechnology.shtml.

(3) www.smalltimes.com/document_display.cfm?document_id=5481.

(4) http://cseserv.engr.scu.edu/StudentWebPages/AChen/ResearchPaper.htm.

(5) www.nansosensors.com.

(6) Nino Simic, “Nano into Everyday Life.” www.oresundit.com/composite(1610).htm.

(7) Ryan Randazzo, Reno Gazette-Journal, 15 June 2002.

(8) www.agg.com/Practice/Nanotechnology_main.html.

(9) www.oresundit.com/composite(1610).htm.

(10) www.foresight.org.

(11) Michael Crichton, “Could Tiny Machines Rule the World?” Parade Magazine, 24 November 2002, pgs. 6-8.

Some nanotechnology links:

• www.about.com/nanotechnology (A search engine that compiles various sources and articles).
• www.jmtour.com (Professor Jim Tour’s research home page).
• www-ece.rice.edu/~halas (Professor Naomi Halas’ research home page).
• www.nano.gov (The National Science and Technology Council’s site for nanoscale technology, including information on federal initiatives). 

Before thinking about biology’s future, we should classify the most important developments made during the 1990s. The first one is cloning, most notably the sheep Dolly, a development that is still quite controversial. The problem here is twofold: religious, for some people say that scientists want to play God by “creating”; and ethical, for it could involve cloning human beings to harvest their organs. Technically, this latter issue is not a big deal.

Cloning

To deal with the first issue, we must understand the cloning process. Cloning is defined as the transfer of an ordinary cell nucleus to an egg with a depleted nucleus. Scientists have done this with frogs for years. But when they began to use mammals, people began to pay more attention.

Cloning is not creation, for it uses an existing genome encoded in an existing nucleus with a natural (but slightly modified) egg. So, the resulting organism is no more than a copy of the organism already created by the Creator.

In other words, cloning is like a copier: if you photocopy a book, you cannot claim that the copier wrote that book, even if there are some changes (e.g., lighter ink or different colors). Even if scientists one day change a portion of the genome prior to cloning so that the clone will have a different physical property, they still will be doing no more than making some small changes on a great piece of art already designed and created in a wonderful way.

The second issue, that of cloning people, is also important. The American government has already outlawed it. Why would someone want to clone himself or herself or someone else? There could be several reasons. First, to live forever, which is impossible. Even if everything were to work perfectly, the clone would be an entirely “new” person with a unique personality, for its environment would be an important factor in its development.

Second, to use the clone as an organ donor or for some other reason. A clone’s organs would not be rejected by the recipient’s immune system. However, cloning a human being just to harvest its organs is the same as killing someone for his or her organs. Although cloning now is a technically very painful and long process, advancements in biomedical technology probably will make it much easier in a few years, and available to those who can afford it.

Clearly, this process does not involve creating a new person. However, it does raise ethical complications, such as the ones mentioned above. To allay some of the public’s concerns, scientists should explain that “cloning” does not mean “creation.”

Genetic Manipulation

The second area that still needs a great deal of work is the manipulation, mainly in embryos, of an organism’s genetic code. This is already being done in many species, such as bacteria, viruses, yeast, frogs, chickens, pigs, monkeys, and mice. Researchers and scientists can change these organisms’ genes at the embryonic stage with great ease, so that the resulting organisms will have specific features. Through such manipulation, scientists strive to achieve a better understanding of various underlying biological and metabolism-related principals. This is not done extensively in human embryos, nor is it totally banned. For example, in vitro fertilization involves separating human eggs that are defective in their mitochondrial DNA from their mitochondria and replacing them with normal ones. Although the resulting embryo’s genomic DNA is unchanged, its mitochondrial DNA is replaced. This can be considered genetic manipulation to some extent. This leaves two questions: Will we allow the genetic manipulation of human embryos? Does this mean creation to some extent? Let’s assume that a couple cannot have a healthy child because of a serious illness. You can try to convince this family that they should forego having a baby, since the genetic manipulation of human embryos is banned. In the case of genetically inherited severe illnesses or some pre-birth vaccinations against AIDS, genetic manipulation of the eggs or the embryo can be a powerful method in the future. But there are consequences.

Consequences

First, right now we do not have the necessary technology to guarantee completely safe genetic manipulation. But since technology develops incredibly fast, we might be able to do so within the next decade. We should use this time to prepare answers to the ethical questions and developments that are sure to arise. Second, although this technology will be developed primarily for disease control and prevention, some will use it to manipulate an embryo’s physical or mental properties, such as increasing its mental power or changing its eye color. Of course, this technology will be available only to rich people first, which means that their children will be more skillful. This can be considered unethical, but is it really all that different from rich people using already existing specific drugs or surgical techniques that they can afford? Third, does this mean “creation” to some extent? It does not, for the scientist is only manipulating the existing genetic code so that it will assume another form in the other already-existing recipient. Even if these are new codes, they still coded by the same general principal that was created by the ultimate Creator.

Conclusion

As technology develops, it brings new ethical questions to the fore of the public consciousness, as well as new ways to increase our knowledge of how the universe works. Molecular biology and genetics are important branches of science that develop quicker than many others. All such developments, regardless of field, should be explained to the public clearly to avoid misunderstanding. We do not need to see a repeat of what happened after Dolly’s clone was introduced to the world.

References

• http://www.sciam.com/explorations/030397clone/030397/beardsbox.html.
• Lodish, Harvey et al. Molecular Cell Biology. New York: Scientific American Books, 1986.
• Lewin, Benjamin. Genes VI. New York: Oxford University Press, 1997.

At the end of the 1950s, Richard Feynman (1961, pp.282-96) described the possibility of building computers that were ‘sub-microscopic’. More recently, several people have advocated the realization of massively parallel computation using the techniques and chemistry of molecular biology.

At the end of 1994 Leonard Adleman published a paper on ‘Molecular Computation of Solutions of Combinatorial Problems’ (Science, vol.266, pp.1021 – 24). He explained how a problem could be set up by synthesizing DNA molecules with a particular sequence, and solved by letting the DNA molecules react in a test tube, producing a molecule whose sequence is the answer. In the same paper he recounted how he had put this theory into practice by solving a standard problem with a DNA reaction system. Adleman called his DNA computer the TT-100, for test tube filled with 100 microlitres of fluid, which is all it took for the reactions to occur.

Since then, many advances have been proposed to refine the protocol for programming a DNA computer to reduce the complexity of the operations and eliminate errors (see Lipton, n.d.; and Boneh and Lipton, nd.). Despite their respective complexities, biological and mathematical operations have some similarities:

The very complex structure of a living being is the result of applying simple operations to initial information encoded in a DNA sequence.

The result f(w) of applying a computable function to an argument can be obtained by applying a combination of basic simple functions to w.

For the same reasons that DNA was probably selected for living organisms as a genetic material, its stability and predictability in reactions, DNA strings can also be used to encode information for mathematical systems.

Conventional computers represent information in terms of 0’s and l’s, physically expressed in terms of the flow of electrons through logical circuits. Builders of DNA computers represent information in terms of the chemical units of DNA. Calculating with an ordinary computer is done with a program that instructs electrons to travel on particular paths; with a DNA computer, calculation requires synthesizing particular sequences of DNA and letting them react in a test tube. In a scheme devised by Lipton (n.d.), the logical command AND is performed by separating DNA strands according to their sequences, and the command OR is done by pouring together DNA solutions containing specific sequences.

‘It will fill a bathtub, not the universe,’ says Lipton, ‘and it will be incredibly cheap to build.’ A pound of DNA in 1,000 quarts of fluid, about three-feet square, will hold more memory than all the computers ever made. The chemicals are inexpensive; DNA runs virtually on its own power, and the soup, with a little splicing, can be re-used from one experiment to the next. Lipton estimates that a superparallel DNA computer, offering trillions of processors working simultaneously, could be built for $100,000.

The fastest supercomputers can currently perform 1000 million instructions per second (MIPS); a single DNA molecule requires approximately 1000 seconds to perform an instruction (.001 MIPS). Obviously, if you want to perform one calculation at a time (serial logic), DNA computers are not a viable option. However, if one wanted to perform many calculations simultaneously (parallel logic), a computer such as the one described above can easily perform 1014 MIPS. DNA computers also require less energy and space. While existing supercomputers operate 109 operations per joule, a DNA computer could perform 2 x 1019 operations per joule (many times more efficient). Data can be stored on DNA at a density of approximately 1 bit per cubic nm, while existing storage media require 1012 cubic nm to store 1 bit (Adleman, 1995).

Thus, the potential of molecular computation is impressive. However, it is too early for either great optimism or great pessimism. It is possible that DNA computers will become more common for solving very complex problems and DNA computers may also become automated. In addition to the direct benefits of using DNA computers for performing complex computations, some of the operations of DNA computers already have (Adleman, 1995), and more could be, used in molecular and biochemical research.

References

• Adleman,L.(1994).’Moleculer computation of solutions to combinatorial problems’,Science,vol.266,pp.1021-24.
• Adleman,L.(1995 ‘On constructing a moleculer computer’:ftp://usc.edu/pub/csinfo/papers/adleman/molecular_coputer.ps
• Boneh,D.&Lipton,R.J.’Making DNA computers error resitant’.(Unpublished manuscript.)
• Feynman,R.P. (1961)’Minaturization’,in D.H.Gilbert (ed.)Reinhold,New York.
• Lipton,R.J.(n.d.)’Speeding up computations via molecular biology’:ftp://ftp.cs.princeton.edu/pub/people/rjl/bio.ps

Cancer is a major cause of illness and death in developed countries. The risk of death from cancer has also been increasing in the less developed countries. As improvements in medical care have reduced deaths from infectious diseases and increased life expectancy, cancer has become the leading cause of death in many societies. For example, according to the American Cancer Society, about one in three people in the USA will develop cancer at some point in their life, and about one in four will die from it. Each year about 500,000 individuals die of cancer, a rate of about one death per minute, and more than one million new cases of cancer are diagnosed annually in the US. Currently more than 10 million individuals are receiving medical treatment for cancer in US hospitals and medical centres.

What are the causes of cancer?

Scientific evidence gathered over the last hundred years has dispelled the superstition, once prevalent, that cancer is a contagious disease. But, despite significant advances in the last decade, its underlying mechanisms are still a mystery.

The link between cancer and genetic mutation was shown early in this century: normal cells mutate into malignant ones because of changes in chromosome constitution.

There are four points which support the idea that cancer has a genetic origin:

1. More than 50 forms of cancer are known to be inherited to one degree or another
2. Some tests detecting mutations have shown that most environmental toxic agents which are called carcinogens are also mutagens.
3. Work with cancer-associated viruses has revealed the presence of some mutant genes, known as oncogenes, that promote and maintain tumour growth.
4. The chromosomal abnormalities found in particular forms of cancer, especially leukemia.
5. The environment and behaviour can also play a significant role in the genesis of cancer.

The existence of high rates of specific cancers in particular families has been known since early in the 19th century. Many explanations have been offered for this phenomenon, including multiple gene inheritance, environmental agents or even mere chance.

Hereditary forms of cancer

Recent advances in cancer research have provided some clues about the relationship between mutant genes and the cellular events that lead to tumour formation. Experimental evidence suggests that as few as two mutational events may be sufficient to cause a cell to become cancerous (see Figure I). In those forms of cancer that show a heritable predisposition, the first mutation is present in the germ cells and is transmitted genetically. The second mutations are acquired by somatic cells through spontaneous replication errors or exposure to environmental agents that cause genetic damage, resulting in cancer. On the other hand, not all individuals who inherit the first mutation will develop cancer.

If the second mutational event does not occur, then no tumour will develop. Research has focused particularly on two classes of genes in carcinogenesis: tumour suppressor genes which normally function to suppress cell division, and proto-oncogenes which normally promote cell division. 

Tumour suppressor genes

Tumour suppressors are detected in the form of chromosomal deletions (or other inactivating mutations) that are tumorigenic. The strongest evidence for their nature is provided by certain hereditary cancers. There is also now evidence that changes in these genes may be associated with the progression of a wide range of cancers. About 10 tumour suppressors are known at present. These genes act at certain points to inhibit cell division. These and or their gene products must be absent or inactive for normal cell division to take place. If tumour suppressor genes become deleted or inactivated by mutation, control over cell division is lost, and the cell can proliferate in unchecked fashion. The example of breast cancer illustrates how mutations in tumour suppressor genes are involved in the development of cancer:

The genetic link to breast cancer

In the USA, the ratio of women getting breast cancer is approximately 1 in 8. It is the most common form of cancer in women: 46,000 women die and 182,000 new cases are diagnosed each year. Epidemiological factors may also be involved in breast cancer, but geneticists have focused on the question – Is there a genetic predisposition to breast cancer? Their answer, for the present, is Yes: though involved in only about 5% of all eases, a particular gene has been identified and located on chromosome 17. It is responsible for susceptibility to a form of breast cancer that appears in the third and fourth decades of life. About one in 200 females inherits this gene, and 80% to 90% of these will develop breast cancer. Besides breast cancer, a gene has been found on chromosome 17 in sufferers from astrocitoma (brain tumours), colon, lung and bone cancers. This finding suggests that there is a mutation on this gene (called p53), and as a result the cells start growing abnormally.

The Future

Investigations into the tumour suppressor genes are an example of the recent progress in molecular aspects of cancer research. A better understanding of molecular carcinogenesis and molecular epidemiology will eventually decrease the quantitative and qualitative uncertainties associated with the current state of cancer risk assessment. It may be possible to immunize patients against their tumours by using these findings about genes-cancer relationships. Indeed, determination of the type and number of mutations in p53 and other cancer-related genes in tissues from ‘healthy’ individuals may allow the identification of those at increased cancer risk and their consequent protection by preventive measures.

Although there have been many and most welcome developments in the diagnosis and treatment of diseases, including cancer, there is a definite and reliably cure only for some of the infectious diseases. However, we firmly believe there are definite remedies for all diseases in the universe except death.

References

• HARRIS, ADRIAN L. (1990) ‘Mutant p53-The commonest genetic abnormality in Human Cancer?’ The Journal of Pathology.
• HARRIS, CURTIS C. (1993) ‘p53: At the Cross-roads of Molecular Carcinogenesis and Risk Assessment’, Science, 262.
• CUMMINGS, M. (1994) Human Heredity, West Publishing Company, St Paul. Lewm, B. (1994) Genes 5, Oxford University Press, New York.
• LEWIN, B. (1994) Genes 5, Oxford University Press, New York.

Denton, an Australian doctor and scientist, distinguishes a special (or micro) theory of evolution from the general theory. The former would claim only that closely related species can (and did in the past) evolve from others. But the general theory (the one that is widely accepted) claims to explain the origin and current diversity of all species as purely random mutations accompanied by natural selection over a very long period of time. While Denton accepts the special (micro) theory, he demonstrates so many flaws in the general theory that it must be rejected outright: its claims cannot be softened or modified in any way that could rescue the theory.

Chapter I traces the dramatic transformation of Darwin’s stance from a ‘fundamentalist’ acceptance of the Bible’s account of creation to outright rejection. Known facts about the geological age of the earth (the Bible implies 6000 years), fossil evidence of extinct species (Genesis states that all species were rescued from the flood), might justify a rejection of a literal reading of the Bible. But they do not justify a rejection of the concept of conscious design in the creation (implying a Creator). Yet, as Chapter 2 shows, this is just the position Darwin (and his followers) take: it is of the essential core of Darwin’s theory that natural selection is a blind process: ‘Darwin himself clearly stated that the mechanism responsible for … genetic variations [must] be entirely blind to the adaptive needs and requirements of the organism. Evolution by natural selection is therefore, in essence, strictly analogous to problem solving by trial and error, and it leads to the immense claim that all the design in the biosphere is ultimately the fortuitous outcome of entirely blind random processes – a giant lottery.’ This idea is frequently reflected in populist remarks like Carl Sagan’s: ‘given enough time, chance will work miracles’. But as anyone familiar with the relevant mathematics knows, ‘time in itself tells us nothing of the probability of achieving any sort of goal unless the complexity of the search can be qualified’. (Denton shows some of this complexity in Chapter 13, ‘Beyond the reach of chance’.) The universe simply isn’t old enough for even life, let alone life in all its diversity, to have arisen by chance.

Chapter 3 describes how Darwin’s theory turned into a general dogma largely because of the unacceptability as scientific theory of the alternative (conscious design implying a Creator). Yet, if stripped of the philosophical and metaphysical pretensions it so quickly assumed, the theory of evolution could be respectable as a ‘partial truth’. Denton explains in Chapter 4 that there is strong evidence (supporting the restricted claims of the special theory) for closely related animals or plants evolving from each other and forming distinct ‘species’, the term ‘species’ being understood as ‘a reproductively isolated population of organisms’.

According to Denton: ‘There are only two sorts of evidence for evolution which do not depend on actual observation of the process: finding a sequence of inter-grading forms leading unambiguously from one to another; or reconstructing them hypothetically by providing an entirely plausible genealogy including all the intermediate forms and thoroughly convincing explanation of how each stage of transformation came about.’ Example cases for the first sort of evidence are: the peppered moth, two species of European gull, and the droshopila species of Hawaii. Examples for the second sort of evidence include Mengels work on wood warblers of North America on Hawaiian honey-creepers by Amadon, and on small lizards of the Caribbean islands by Gorman and Atkins. How-ever, as Denton emphasizes, such evidence for special (micro) evolution in no way justifies the general theory. ‘However attractive the extrapolation, it does not necessarily follow that, because a certain degree of evolution has been shown to occur, therefore any degree is possible. There is obviously an enormous difference between the evolution of a colour change in a moth’s wing and the evolution of an organ like the human brain, and the differences among the fruit flies of Hawaii, for example, are utterly trivial compared with the differences between a mouse and an elephant, or an octopus and a bee.’

Denton gives good analogies and illustrative examples to argue the general principle that: ‘while sentences, machines and other sorts of complex systems can undergo a certain degree of gradual functional change, there is invariably a limit beyond which the system cannot undergo further gradual change. To cross as it were from one ‘type’ of system to another necessitates a relatively massive reorganization involving the redesign or respecification of all or almost all of the interacting component subsystems. Systems can undergo gradual micro-evolution through a succession of minor changes in their component structures but macro-evolution invariably involves a sudden ‘saltational’ change [i.e. non-gradual change by ‘leaps’]. Clearly, in all such cases, the extrapolation from micro- to macro-evolutionary change does not hold.’ Gradual random processes are incapable of producing ‘simultaneous highly specific correlated changes throughout [an] entire system’ which is precisely what they must be capable of if macro evolution is to work. (This argument is further elaborated in Chapter 13.)

Chapters 5 and 6 describe the ‘typological perception of nature which sees (and classifies) organisms as distinct groups separated by non-trivial, large gaps. There is abundant evidence for this approach and historically classification schemes were based on it. However, following widespread acceptance of the general theory of evolution, some felt the need to construct literally tree-like diagrams – many branches from a single trunk and root. Inevitably, such diagrams had many blanks, many wholly conjectural ‘branches’ needed to link known species through unknown transitionary species to alleged ancestors.

Chapter 7 discusses homology which, once thought to provide supportive evidence for evolution, turns out to be evidence destructive of the theory. 1-lomologous organs cannot be traced back to embryological development and there exist homologous limbs which, according to the theory, must have evolved from very different parts of the embryo. In short, homology does not imply common ancestry.

The subject of Chapter 8 is the key issue of fossil evidence. Darwin was expecting paleontological explorations to uncover the crucial missing ‘links’ predicted (and required) by his theory. However, as the evidence from fossil records has grown, so too has the untenability of Darwin’s theory.

To begin with, we need to know that fossils are a record only of skeletal remains: 99% of any organ ism is soft tissue which is not preserved in fossils. The coelacanth (a favourite with evolutionists) had been presented as a ‘link’ between fish and amphibians. Yet, its skeleton is identical to that preserved in aneien fossils which are as far from having been amphibians as are any other fish, The lesson is that conclusions based on skeleton forms alone do not count for much. Insects preserved in amber from hundreds of millions years ago, identical to modern insects, provide further examples of ‘living fossils’ which somehow evaded evolution.

Mother fossil record favourite with evolutionists is the horse series. Denton writes: ‘The difference between Fohippus and the modem horse is relatively trivial, yet the two forms are separated by sixty million years and at least ten genera and a great number of species. The horse series therefore tends to emphasize just how vast must have been the number of genera and species if all the diverse forms of life on earth had really evolved in the gradual way that Darwinian evolution implies. If the horse series is anything to go by, their numbers must have been indeed the infinitude’ that Darwin imagined. If ten genera separate Bohippus from the modern horse then think of the uncountable myriads there must have been linking such diverse forms as land mammals and whales or molluscs and arthropods. Yet all these myriads of life forms have vanished mysteriously, without leaving so much as a trace of their existence in the fossil record.’

The appeal by evolutionists to the incompleteness of the fossil record as an excuse for clinging to their theory might he worth attending to if the gaps, the incompleteness, were unsystematic or random. But the facts are otherwise: ‘The fundamental problem in explaining the gaps in … is their systematic character – the fact that there are fewer transitional species between the major divisions than between the minor. Between Eohippus and the modern horse(a minor division) we have dozens of transitional species, while between a primitive land mammal and a whale (a major division) we have none. And this rule applies universally throughout the living kingdom to all types of organisms, both those that are poor candidates for fossilization such as insects and those which are ideal, like molluscs. If the gaps really were lhe result of an insufficient search, or the result of the imperfection of the record, then we should expect to find more transitional forms between mouse and whale than between dog and cat.’

The hard evidence should make any objective inquirer ask, not whether we may one day fill the gaps in our record, hut whether gradual evolution ever occurred at all: ‘If the gaps cannot he adequately explained by appealing either to an insufficient search or the imperfection of the record, then this leaves a more or less saltational model of evolution as the only explanation of the gaps.’

In Chapter 9, Denton begins to draw the argument towards the conclusion that: Ultimately there is… absolutely no reason why functional organic systems should form the continuum that evolution by natural selection demands. In the world of physics and chemistry many phenomena are discontinuous. One cannot gradually convert one molecular species into another, neither can one convert gradually one type of atom into another. Between such entities there are jumps. Might not functional organic systems be similarly separated by discontinuities?’ He goes on: ‘It is possible to allude to a number of species and groups such as Archaeopteryx, or the rhipidistian fish, which appear to be to some extent intermediate. But even if such were intermediate to some degree, there is no evidence that they are any more intermediate than groups such as the living lung-fish or monotremes which… are not only tremendously isolated from their nearest cousins, hut which have individual organ systems that are not strictly transitional at all.’

The frustration at the failure to find intermediate forms and the difficulty of conceiving of gradual functional transitions led some scientists to an alternative to gradualism, namely ‘the concept of evolution by saltation, the idea that new organs and types emerge suddenly following some sort of massive macro-mutation.’ Advocates of the idea include the popular contemporary writer Stephen Jay Gould and his predecessor Goldschmidt who introduced the notion of the ‘hopethl monster’ in his the Material Basis of Evolution (1940) as a ‘means of getting from one type to another suddenly in one jump’.

The possibility of such a ‘hopeful monster’ had been likened to a ‘miracle’ by Darwin. The great majority of biologists have followed him in that judgement ever since. So-called freaks of nature do, of course, occur but they have little chance of reproductive survival given that they are horn into an environment where the non-freaks (the normal) survive to reproduce. Denton sums up by saying that: While it might he theoretically possible to avoid the impasse of gradualism by opting for saltation it seems unlikely that purely random processes would ever throw together suddenly adaptations like a feather or the avian lung or the amniotic egg.’

In Chapter 10, the process of DNA replication and protein synthesis is explained for readers unfamiliar with the subject. Equivalents of concepts like ‘universal Turing machine’ and ‘fault tolerant computing’ can be observed in perfectly economical design in the world of molecular genetics.

‘The Enigma of Life’s Origin’, the title of Chapter Il indicates the enormous conceptual and empirical difficulties evolution theory has faced in yet another once-promising area. It was hoped that as the nature of living organisms was more fully understood, the gap between them and inanimate forms would he narrowed. Exactly the opposite happened. The gap that separates the simplest living systems from inanimate systems seems unbridgeable: there is not a hint in inanimate systems of the DNA, messenger RNA, and the protein synthesis mechanism (implying self-replication), found in living forms.

Attempts to explain the origin of life through evolutionary means come up against two other major hurdles. The first is the so-called ‘oxygen-ultraviolet conundrum’. One has to assume that there was no oxygen in the early atmosphere because otherwise any organic compounds would rapidly oxidize. However, this assumption implies that there was no ozone to shield these compounds from deadly doses of solar radiation. In other words, this is a ‘catch 22: If we have oxygen we have no organic compounds, hut if we don’t have oxygen we have none either.’ The second hurdle is the shortage of time for the first life forms to evolve: ‘An Australian group reported the remains of a simple type of algae in rocks at least 3.5 billion years old… So life had to form between 3.9 and 3.5 billion years ago. Just a few hundred million years from nothing to organic compounds to the whole DNA, M-RNA, protein system.’

These and other apparently insoluble difficulties led the Nobel-prize winning scientist Crick to comment:

‘An honest man, armed with all the knowledge available to us now, could only state that in some sense, the origin of life appears at the moment to he almost a miracle, so many are the conditions which would have had to have been satisfied to get it going.’ The problem of the origin of life is an example of what Denton calls ‘the universal principle that complex systems cannot be approached gradually through functional intermediates because of the necessity of perfect co-adaptation of their components as pre-condition of function.’ Crick is also famous for running away from the problem by suggesting that life must have originated somewhere outside the galaxies known to us and been cast down amid cosmic dust as a ‘seed’ – his so-called panspermia’ theory.

The subject of Chapter 12 is the modern molecular biological techniques which have provided biologists with an entirely new way of comparing organisms at a biochemical level (as opposed to the classical anatomical comparisons). Again, the comparisons established that: ‘the pattern of diversity at a molecular level conforms to a highly ordered hierarchic system. Each class at a molecular level is unique, isolated and unlinked by intermediates. Thus molecules, like fossils, have failed to provide the elusive intermediates so long sought by evolutionary biology.’

The gaps in the ‘chain of being’ are seen at both empirical and theoretical level: wherever we find significant empirical discontinuities in nature we invariably face great, if not insurmountable, conceptual problems in envisaging how the gaps could have been bridged in terms of gradual random processes. We saw this in the fossil record, we saw it in the ease of the feather, in the case of the avian lung, and in the case of the wing of the hat. We saw it again in the ease of the origin of life and we see it here in this new area of comparative biochemistry.’

In Chapter 13 (‘Beyond the Reach of Chance’) Denton illustrates the impossibility of reaching functional complex systems via blind random processes.

In Chapter 14, we imagine ourselves in a cell magnified a thousand million times and try to grasp the wonderful reality of life. What we see is a system much more complex and perfect than any human artefact built so far. The elaborate Soviet lunar exploratory machine, the Lunakod, which moved on articulated legs, highlights by comparison the sheer ease of solutions provided in nature for such problems as self-location, stability and locomotion. The amazing storage capacity and efficiency (size and energy economy) of biological information storage and retrieval is another striking example of the ease of nature and the hardship’ humans face to match it even crudely by artifice.

Denton comments: ‘According to Paley, we would never infer in the case of a machine, such as a watch, that its design was due to natural processes such as the wind and rain; rather, we would be obliged to postulate a watch-maker. Living things are similar to machines, exhibiting the same sort of adaptive complexity and we must, therefore, infer by analogy that their adaptive complexity is also the result of intelligent activity.’ And he adds: ‘The conclusion may have religious implication but it does not depend on religious presuppositions.’

Chapter 15 (‘Priority of Paradigm’) gives Denton’s explanation of why the theory of evolution has been so pervasive in our age despite overwhelming contrary evidence.

It is a modern example of a scientific community defending a theory just as tong as ii holds sufficient intrinsic appeal.’ He likens it to the defence by medieval astronomers of the Ptolemaic theory of the heavens, and by the eighteenth-century chemists of the phlogiston theory of combustion.

There is not space here to argue at sufficient length against the widely held stance of modern scientists that the concept of a Creator-God is of no relevance to a properly scientific understanding of how the natural world is or how it operates, that, in brief, it cannot he a part of any scientific explanation or theory. We must insist, however, that scientific knowledge cannot exist (any more than its dominant theories can com -about) in some sort of vacuum, isolated from the complex of human knowledge, attitudes and relationships. The social implications of the ‘central claim of Darwinian theory that humanity was not born by the intentions of a Deity hut by a completely mindless trial and error selection of random molecular patterns…’ have been, in general, very had. A theory so certainly false should never have imprisoned scientific imagination for as tong as it has. Ii could not have done so if the aspiration to scientific knowledge had been tutored in the humility that comes with a serious, religious consideration of our status as creatures and servants of God. Only a religious perspective teaches that all human curiosity – its perceptive faculties, its intelligence and the instruments it devises to extend its powers – exists as the gift of the One All-Merciful God who created us and the intelligibility of the world so that we might draw nearer to Him. At least in the field of biology, the alternative to believing in a Creator did not, as is claimed, offer freedom from dogmatism: the lasting value of Denton’s hook is to have demonstrated that reality with clear argument and a large body of hard evidence.

Genetics is commonly taken to refer to a part of biology that concerns itself with the study of the transmission of hereditary characters. This fascinating science would have remained quite benign if this was all that it was. However, recombinant DNA technology with all the power it offers for biological control has changed all that. By making it possible to manipulate the reproductive potential of an organism, modern genetics has the power to alter the course of development of living organisms. Life can be changed, for good or ill; it can be enhanced or retarded or mutilated. Moreover, whatever molecular genetics can do to the biological world can in principle, be done to human beings. Molecular genetics poses a grave threat to our notions of human life, its intent and its meanings.

In his book Responsible Science (1986), Robert Nelson wrote: 

The challenge of molecular biology to traditional humanistic and religious concepts of human life needs to be taken very seriously. Not only the nature of life, but its purpose and worth are called into question by the rapidly growing knowledge of DNA and cellular development. If the human organism can ostensibly be reduced to an assortment of proteins and amino acids, hardly distinguishable at molecular levels from those of other organisms, where is the distinctiveness of human life to he found? And if found, how explained?

Biology, especially in the form of using genetics and evolution to explain social phenomena, has become a reductionist exercise. Reductionism means trying to explain the properties of complex wholes-molecules, say or societies-in terms of the units of which those wholes are composed. Scientists who are reductionists would argue, for example that the properties of a protein molecule could be uniquely determined and predicted in terms of the properties of the electrons, protons, etc., of which it atoms are composed. In a similar way, they could (and some do) argue that the properties of a human society are no more than the sum of the behaviours and tendencies of the individual humans of which that society is composed.

Genetics and evolution, as indicated above, have been used to explain social phenomena. This is the area of science called sociobiology. It is a discipline that passes moral judgement on many social issues because it presents biology as the human fate, an inescapable reality of nature. Since it is natural, the implication is that it is immutable.

Sociobiologists equate the social with the biological and maintain that differences of class, race, colour, gender and even economic status originate in individual biology. This type of thinking could lead to dangerous conclusions of a sort most of us would regard as immoral and unethical. It can lead, for instance, to the belief that some races are born ‘inferior’ to others; that women are inferior’ to men; IQ (Intelligence Quotient) is genetically determined; that social inequalities (wealth and poverty) are biological in origin. The big problem with this is that political leaders could use such arguments to assert that the current social order must prevail because it is the law of nature.

Sociobiology reached its peak when some biologists claimed to have discovered absolute evidence for genetic determinants of human behaviour. In his popular book The Selfish Gene (1976), Richard Dawkins wrote:

We, and all other animals, are machines created by our genes. Like successful Chicago gangsters, our genes have survived, in some cases for millions of years, in a highly competitive world. This entitles us to expect certain qualities in our genes. I shall argue that a predominant quality to be expected in a successful gene is ruthless selfishness… Much as we might wish to believe otherwise, universal love and the welfare of the species as a whole are concepts which simply do not make evolutionary sense … If you wish … to build a society in which individuals cooperate generously towards a common good; you can expect little help from biological nature.

The selfish gene thus operates to enhance its own selfish interests. The theory is based on the belief that genetic differences lead to behavioural differences, and that organisms are hosts to genes rather than the other way round. This provides the basis, as sociobiologists themselves claim, for the systematic study of the biological basis of all forms of social behavior, including sexual and parental behaviour, in all, kinds of organisms, including humans.

More and more human attributes are being subjected to a biological explanation. The Islamic view of human nature, however, does not consider biology as an inevitability. Human morality is the most important determinant, encompassing the spiritual dimension beautifully: The most honoured among you in the sight of God is the most righteous among you. And God has full knowledge and is well acquainted [with all things]. (Hujurat, 49.13)