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The Immortal Cells: A True Story – In 1951, a black lady named Henrietta Lacks was admitted to John Hopkins Hospital. At the time of admission, she was pregnant but after delivering a child, she was diagnosed for cancer as doctors found tumor in her cervix. Doctors took a sample of that cancerous tumor without Henrietta Lacks’ permission. The code-named this sample as HeLa. Later, doctors realized that this wasn’t some ordinary sample. Unlike other samples where cells would die after some days, the cells of HeLa sample were alive and multiplying. Later cells of this sample were used for polio vaccine testing. To meet the growing demand for these cells to be used in various research, they were put on mass production.

To this day, HeLa cells are used in uncountable researches all over the world and are produced on mass scale. Development of many vaccines, many research results are based on the work conducted on HeLa cells. Henrietta Lacks died in 1951 because of this continuously growing cancerous tumor but this tumor is still alive and growing to this day. These cells are immortals and serving the mankind by saving many lives.

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NORMALLY we have this idea about cancer that it involves some kind of tumor which just doesn’t stop growing. Well, this idea is somewhat vague but it does give initial idea. For example, leukemia is a type of cancer which doesn’t involve any tumor and it affects bone marrow and blood. Uncontrolled cell proliferation is better definition of cancer. Again, leukemia is uncontrolled cell proliferation of white blood cells. One more word about tumors, though tumors are considered as symptoms for cancer, not all tumors are cancerous. As against to cancerous tumors, there are tumors which are benign in nature. They don’t grow indefinitely and don’t affect other cells. Very often, they can be removed.

Cancerous cells aren’t sick cells per se. They are perfectly healthy in themselves. But when viewed from the survival point of view of macroscopic body, they are threats. They are just selfish rebellions who don’t follow the established protocols anymore. They no more sacrifice their life for the sake of other. And all it takes one tiny cell out of 50 trillions cell to turn rebel to wreck havoc.

CELLULAR WORLD: Our body is a highly complex, condensed entity which ‘houses’ some 50 trillion (50,000,000,000,000) cells. Each cell have a life of its own. Each cell ‘knows’ what it is supposed to do and what it shouldn’t, when it is sick or when it has run a course of its life. It can also ‘see’ what is going on in its own surrounding. Similarly, each cell also knows its ‘friends’ and ‘enemies’. These cells live in perfect harmony. Of these, about 50-70 billion cells die everyday in a normal human adult.  In fact, it is rather more accurate to say that these cells ‘commit’ suicide and this process of committing suicide is known as ‘programmed cell death‘ or ‘Apoptosis‘. Many of these cells are perfectly healthy when they commit suicide. They commit suicide to serve bigger cause and to let other live. They are such selfless entities. They are ideal altruists. If you actually go in the details of cellular biology, you’d be astonished to see how detailed, complex and controlled is the functioning of life at the level of cell. You never wondered how a single cell zygote (fertilized egg) turns into a highly complex cluster of some 10 trillion cells which has the capability to think about God! (pause for comic effect.) A cell might get old. Or it might get damaged. May be it has served its utility and is no more needed and is still using precious resources. In each case, it has to die. Many times, when some foreign infectious agent (pathogen) gets into a cell, it kills itself and thereby kills that infectious agent also. So, a cell may also sacrifice its own life to save other cells and this phenomenon sometimes is called ‘altruistic death‘. And it is all programmed. Cell doesn’t ‘think’ the way we think. And this is not the end of the story. When a cell dies, what happens to remains of a dead cell? Well, there are scavenging agents which do all the cleaning. In absence of these agents, as you might guess, the remains of dead cell may affect the neighborhood adversely. You see, the cellular system is a perfect altruistic world where every cell is living for the sake of others and all cells live and die to serve a bigger cause of macroscopic life.

SO that was about apoptosis. Now is the turn to understand how those 10 trillions cells come into existence. The answer is cell division or Mitosis. If apoptosis is about cell death, mitosis is about cell birth or, to be precise, cell division because that is how we grow from zygote (a fertilized egg), which is essentially a single cell, to a complete human being consisting of some 50 trillion cells. For the time being, it is sufficient to know that mitosis is simply a process of cell enumeration by way of cell division. Remember how Amoeba divides itself which we studied in high school? That is what mitosis is. Each cell knows when to undergo mitosis, when it shouldn’t and when to stop. Wonder why our fingers are as long as they are? Or why we are as long as we are? It is all about controlled processes of mitosis and apoptosis which are regulated by genes. We look different from monkeys because we have different set of genes which controls mitosis and other fundamental processes in different manners. More on this sometime later. Maybe.

A- Mouse paw in early embryonic state. B - Mouse paw in later embryonic stage. This illustration shows both mitosis and apoptosis at work. In first image, fingers are not yet separated. The tissues which connect fingers undergo apoptosis at later stage thereby completing the process of fingers separation. (Image taken from Internet and doesn't belong to me.)

A- Mouse paw in early embryonic state. B – Mouse paw in later embryonic stage. This illustration shows both mitosis and apoptosis at work. In first image, fingers are not yet separated. The tissues which connect fingers undergo apoptosis at later stage thereby completing the process of fingers separation. (Image taken from Internet and doesn’t belong to me.)

Note: Loosely speaking, AIDS disease has something to do with uncontrolled apoptosis while cancer has its roots in uncontrolled mitosis and apoptosis. In fact, AIDS is directly connected with the uncontrolled Apoptosis in bone marrow. But that is a different story altogether.

EVOLUTIONARY ANGLE: Some cells may actually go rogue. Rogue in the sense that their growth become uncontrolled. Most of the times, these rogue cells are repaired or killed. But this doesn’t always happen. Some rogue cells do evade DNA repairing mechanism and immune system. Ditto for harmful viruses and bacterias. There is a never ending fight between our immune system and harmful agent, external or internal. Each outwits other. Both are continuously evolving. Both are struggling to survive. You may have heard that some anti-biotic medicine doesn’t work anymore because bacterias have become resistant to them. The reason is bacterias have evolved and are still evolving. They are not the same old bacterias anymore. Unlike bacterias which are actually foreign agents, cancer has its origin in our own cell. The original tissue where cancer has its origin is called primary tissue. These cancerous tissues can travel to other parts of body and thereby affecting them as well. In most cases, our immune system beat them but that is not always the case. Some times, cancer tissues do fool our immune system and are able to invade the other parts of body. This process is called Metastasis while these secondary settlement are called metastases and these metastases, rather than primary tumors, are responsible for most cancer related deaths. The journey of cancer from fully healthy tissue to fully malignant tissue involves multiple evolutionary stages (multiple mutations).

In fact, the entire cellular system and its working system have evolved to its present form to constrain cancer and other such undesired factors. There are multiple mechanisms to check cancer at cellular level. Apoptosis is there to check many undesired outcomes and cancer is one of them.  But evolution also works for cancer. Evolution is a key process for every living, be it a single cell bacteria or be it a much more complex species like human. In the eyes of nature, there is no difference between a cancerous cell or a healthy cell. The evolutionary survival methods of Natural Selection and mutations work for both of them.

Consider a normal mouse. A mouse living in the wild has life span of 1 year while it can have life span of 2-3 years in ideal lab conditions. A wild mouse has short life span as it is subjected to many unfavorable natural conditions such as hunting, disease or severe weather which ideal lab conditions avoid. What is interesting is the fact that cancer develops in mice when they are more than a year old. In the wild, a mouse doesn’t live long enough to face cancer. In this situation, mice ‘invest’ their ‘energy and efforts’ in reproduction during early part of life rather than in developing mechanism to fight cancer. When mice (or humans) are beyond their reproduction age, there may have been little reason for our body to develop mechanism to fight cancer. A living which produces more offspring has better chances of growth and survival. That is the key aspect of evolution. Somehow, evolution, when forced to make a choice, has preferred investment in reproduction rather than in long and healthy life. This principle applies to mice, bacterias, healthy cells or cancer cells. And that is one reason why mice are still around and that also hints why cancer is difficult to beat.

chromosomes_and_the_cellDNA & GENES:You might have some vague idea about DNA and genes. You know this has something to do with heredity and exists at cell level. In hundreds of movies, you saw how some tweakings in DNA structures have turned human into a Hulk or a vampire or some other strange creatures. We use these words quite frequently in various conversations. Corruption is in their genes. This or that company has ethics in its DNA. And so on.

cell5EVERY cell has an instruction manual called DNA (genome actually). This manual is written in an alphabet consisting of only four letters (bases) viz. A, T, C and G. Refer the image on the left side. Notice the double helix structure of DNA with rungs. Each rung is comprised of a base pair of two bases. Each cell has 6×10^9 base pairs. A always pairs with T while C always pairs with G. Each cell of our body has a copy of this manual, be it a liver cell, heart cell or neurons of our brain. Also, this manual has 23 chapters (chromosomes) which, in all, have some 22,000 manuals (genes). (Some cells, such as red blood cell doesn’t contain DNA but that is an exception.) Amazingly, each cell knows which part of a given chapter of this manual is to be referred and when to be referred. Simply speaking, a gene is that segment of DNA which code/s for one or more biological instructions (proteins, to be precise). So far, some 22,000 genes have been identified in the case of human and more are yet to be found.

THERE are similarities between a human and a monkey. It is because both of them have many similar genes. We have many dissimilarities because one of them has genes which other doesn’t have. In fact, gender of an embryo is decided by a gene called SRY. An embryo is, in a sense, a female until SRY gene comes into play which turns the embryo into male. You have got those blue eyes while someone else has black eyes. Well, genes are responsible for that. Thanks to your genes, you are what you are.

CANCER & GENES: It all starts with genes. As mentioned above, a gene is that segment of DNA which contains some instruction. If you refer the simplified schematic image of DNA on the right, you can notice that each strand of DNA has a sequence of bases (marked A, T, G & C). Now notice the left strand and read this sequence from bottom to top. The sequence would read as follows – CTGA and so on. All the genetic information and instructions are stored in the form of this sequence. When cell undergoes division, DNA also divides. While dividing, the information coded in the sequence is preserved. Sometimes, due to various reasons, this sequence gets changed. For example, the sequence CTGA may now reads as CTTA. This change in sequence also changes the information/instruction. This abnormal change in sequence is called mutation. If a apoptosis controlling gene undergoes mutation, it is possible it may no longer control apoptosis. This means a cell housing this mutated gene may continue to divide. (Such cancer causing genes are called oncogenes). That is simplest explanation of how a cell become cancerous.

GETTING OLD AND GETTING CANCER: Getting old and eventual death are some profound topics, both from philosophical and scientific points of view. So why do we get old? Well, we so far have only theories with some evidences. The most coherent theory is that our body has practically vast access to oxidizing agents. We eat foods which is processed for energy by our cells. As a result of this processing, many oxidants such as hydrogen peroxide are also formed as by products. These oxidants temper with the genes and thereby affect their functioning. Apart from food intake, radiation is also responsible for production of these oxidants. Similarly, mitochondria which are responsible for energy generation also produced oxidants as a result of energy generation. Smoking, sun  bathing, tobacco chewing are responsible for excessive and strong oxidant productions in our body. The thing is, these oxidants is responsible for mutations undergone by genes. In fact, some research shows that habit of eating less prolongs the life span. This, to an extent, validates the claim that less amount of oxidants in our body causes less number of damaged genes which in turn prolongs life span. The same principle work for cancer as well. And these very oxidants are the culprits.

Cancer

The point is: there are genes which control apoptosis and mitosis. There are genes which suppress tumors. Similarly, there are genes which do the repair works for damaged DNA. When these genes undergo successive changes (mutations) due to some environmental factors such as radiation or mutagens (agents which cause damages to DNA) such as tobacco, they malfunction or stop functioning. So, genes gets damaged/mutated in a way that it no more controls the growth of a cell. When such genes are activated, they make their parent cells proliferate. And that is how cancer happens. And DNA (therefore gene) is most susceptible to damage when it undergoes division during mitosis (cell division). Note that not every mutation causes cell to be cancerous and mutation in itself is a rarity. To have an idea of its rarity, for 6×10^9 base pares in a cell, only about 120 cases of mutations occur. And mutations causing cancer are even more rarer. To cause cancer, mutation has to happen at correct gene and at correct location on those genes. And if a cell still become cancerous, immune system is there to kill it. But, sometimes, cancerous cell does survive and thrive.

Side Note: You have probably read that humans are evolved from chimps. In response to this, a common confusion arises, that is, why chimps are still around if humans are evolved from chimps. The answer is mutations. Genes in some chimps, not in all chimps, underwent mutations. These mutated genes further underwent mutations. These successive mutations caused humans to evolve from chimps.

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mantis-shrimp-eyes

MANTIS shrimp is a highly unusual creature with some incredible abilities. Thus far, it was mostly known for its supersonic punches which can smash the aquarium glass with just one strike. They are known to have most elaborate, unique and complex vision system. Better than human. Better than any other animal. Unlike us, their two eyes can move and see things independently. Apart from this and other traits, they have one more incredible feature. They can see polarized and UV light which we human can’t. As it turned out now, mantis shrimps can ‘see’ cancer in a manner human invented machines couldn’t. As is known, cancerous tissue reflects polarized light differently when compared to healthy tissue. At present, cancerous lesions are recognized only after they grew big enough. Even then, imaging isn’t that good. Polarized imaging offers better and early results but developing such imaging system is something which is still in very early stage. The vision system of mantis shrimps now have provided a model for better imaging system. Nature is indeed full of wonders!

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