Case of HIV: War goes on

Before dwelling on HIV virus, it is important to know what it is and how it works. Simply speaking HIV virus is an enveloped RNA virus and belongs to Family Retroviridae. Two enzymes play key role in its replication. First enzyme is reverse transcriptase which transcribes its RNA into DNA within host cell and second enzyme is integrase which helps to integrate this newly transcribed DNA into the host cell DNA and then from onwards it replicates along with host DNA replication.

Its the same virus that leads to the condition of AIDS in which immune system finally fails leading to oppurtunistic infections and cancer and as result of weakened immune system, the patient finally succumbs to infections. The mode of HIV transmission is through body fluids contact. HIV after infection can remain latent for a long time and can become activated by the environment shift.The incubation period varies from few months to upto seven years and even in some cases HIV positive patient never contracts the disease.

Since the discovery of HIV virus back in 1984, the search for its cure or for its vaccine is a never ending struggle and is a constant riddle for the medical community. Scientists obviously have tried every possible method of vaccination but no method so far has bore fruit. The first vaccine that was developed to counter AIDS and was tested in humans was AIDSWAX which proved to be a failure. The vaccine was developed in hope that it will stimulate immune system to develop antibodies against viral envelope but it didn't work because of variable protein character of envelope.

Scientists next thought that they need a vaccine that can produce broadly neutralized antibodies so that it could block viral entry into the host cells. Simply put a type of vaccine that can produce variable type of antibodies in accordance to viral mutation. Though that type of vaccine is still a desirable goal of virologists, researchers settled on a less effective but still acceptable vaccine that might not prevent infection but keep viral count so low that could reduce the chance of getting sick or being able to transmit the disease. That type of vaccine would keep the virus levels very low by inducing Killer T cells that are meant to seek and destroy infected cells thus preventing viral levels to reach their peak which happens in early phase of infection. The maximum level to prevent infection is to keep viral population at 1700 or less viral copies /mm of blood.

Bearing this range in mind, researchers at Merck company developed a vaccine that used adenovirus type 5 as a vector to carry three HIV reserved genes (gag, pol and nef) into the host cells so that they could produce viral proteins and in a sense trick the immune system to produce antibodies against this virus. But this approach failed to produce any significant response in HIV patients. There is no pretending that Merck vaccine failure was a big blow to all active AIDS vaccination search. Scientists considered two probable causes for this vaccine failure. According to them either the choice of reserved genes or choice of virus itself was a wrong decision. The use of common cold virus was a wrong option because since we humans contract this disease on regular basis and have a innate immnue response to this virus in the form of antibodies against common cold. These common cold antibodies might had interfered with the HIV specific Tcell response and might had potentially reduced its effectiveness.

Whatever the reason the Merck vaccine failure caused a lot of pesimism in HIV researchers. Does this means that we have given up? No i guess not yet. So what we have learned so far? What our options are right now?

First precaution is that we have to use dead viruses for vaccination. Using attenuated viruses wiould be the last option because of the danger of viral recombination and also their chance of virulence reversal in viruses. And secondly we have to avoid making vaccines in response to viral envelpe becuse of its variable nature and concentrate on its reserved genome sequences or genes.

In the coming years scientists will concentrate on certain rare individuals which have innate immunity against HIV virus known as elite controllers. These individuals possess such type of genetic mutations that enable them to suppress viral population or don't allow their entry into Tcells. Some of these individuals possess immune cells that have either the greater number or have incresed funtionality. Also certain individuals posses variable CCR5 receptors that block the entry of viruses into WBCs. It is worth mentioning here that a team of German scientists treated a HIV positive person by carrying out a bone marrow transplant of a person by switching his immune cells by the donated bone immune cells of elite controller. The results were astonishing since it wiped out the virus in the HIV positive patient. The results were published in New England Journal of medicine. It is important to remember that HIV virus requires both receptors CD4 and CCR5 to gain entry into host cells. So this trick by nature works on them.
Also it is important to study immune response in monkeys to live attenuated SIV viruses which is a a very strong immune resonse and helps to control the virus. But using a live virus will be avoided in humans because of safety issues. Eventually ideal vaccine will be a broadly neutralising vaccine that could tackle all forms of virus which is still a dream. Details of vaccination research can be seen here.

So far from giving up, scientists are gearing up for yet another assault on this virus. This virus has proved to be tricky and resilient but so are the scientists who are also tenacious and patient. In the end we can hope that eventually we will be able to defeat this virus by our will to live and in time with the magic of Science.

Wonders of Biology: Stem cells

Stem cells are unspecialized cells that have the capacity to self replicate and to give rise to specialized cells. They are the building blocks of our body and are present at fetal development and also later on in some adult tissues. Stem cells give rise to every other cell in our body. The ability of stem cells to self renewal and to differentiate holds the key for their use. However there are certain obstacles in their use i.e the amount of stem cells that is needed, their feasibility, to produce the right kind and type of stem cells ,to ensure they reach their target and also their availability in short period of time and also ethical issues. It is due to number of these and many other reasons that progress in this field is very cautious and step by step.

Stem cell technology holds much more potential for the treatment of diseases than any other single treatment and that is one of the reason it has caught the eye of every other biologist.
Stem cell treatment is not a very new idea. It is already in use at limited scale such as blood-forming stem cells in bone marrow (called hematopoietic stem cells, or HSCs), are currently the only type of stem cell commonly used to treat leukemia, lymphoma and several inherited blood disorders. The clinical potential of adult stem cells has also been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer and also recently in case of HIV. However, these newer uses have involved studies with a very limited number of patients.

First main focus of biologists is to find the cure for neurodegenerative diseases using stem cell technique. Treating neuron disease is not an easy task. It is much more difficult to treat neurons than any other single body part. Main reason is due to the diverse types of neurons, their connectivity and their accurate circuit which is the biggest challenge to achieve. Scientists have started to treat neuron diseases that are easy to treat like those which involve replacement or transplant of few cell types. Examples include Parkinson, sensory disorders, glial diseases but diseases like motor system disorders, spinal cord injuries are complex and difficult to treat. Same is the case with the type of diseases that are not an easy target like Alzheimer’s disease because neuron damage is widespread and diffuse but still improvements can be made by using stem cell technique to studying them invitro and eventually the treatment of every type of disease can benefit from stem cell technology. Details can be seen here.

Another focus of stem cell research is to create enough blood cells to boost blood supply for blood transfusion. Researchers at Advanced Cell Technology in Worcester, Massachusetts, announced the breakthrough in stem cell technology by devising a method for making potentially unlimited supplies of synthetic blood from embryonic stem cells. Their findings are published in Blood, a scientific journal. Their research is in preliminary stages. They were able to create hematopoetic embryonic stem cells in lab but these cells were not quite the same as natural blood cells i.e the proteins in them are characteristic of fetal and embryonic cells rather than of mature erythrocytes and are known as erythroid rather than true erythrocytes. They have different globin molecule that carries oxygen and also they are larger, membrane differences from natural ones and also their half life and immunogenicity is another question mark. Another challenge is also to ensure to produce them on vast scale so as to meet the demands of blood transfusion since one pint of blood contains more than one trillion cells and scientists at Advanced dell tech have so far achieved to produce 10 billion to 100 billion red cells starting from a plate of human embryonic stem cells, much less even for one transfusion.

Still these new cells have no nucleus, which is a distinguishing feature of mature red blood cells and has the potential to carry the same amount of oxygen as natural blood cells have. These are the main two aspects that are encouraging to pursue this research further. Another positive aspect of this research on hESCs is that since RBCs are enucleated and short-lived, then in any case of mishap ( like tumor development) or failure, it will not harm the patient since RBCs will disappear after a while without causing any lasting harm. Scientist now are concentrating to convert these hESCs into adult stem cells and their main focus is to create O negative blood group cells (universal blood group).

Another arena for stem cell biologists is to cure heart diseases. So far the success in this field is in different directions but is encouraging. According to some reports, a team of scientists at Harefield heart Science centre, UK has succeeded in creating heart valves from embryonic stem cells that were extracted from bone marrow and have grown them on scaffolds of collagen (connective tissue material). The team will test these valves in animals first and is hopeful that similar valves could be fitted in humans within 5 years and estimated that whole human heart rebuild will require 10 years. Another team of Dutch scientists have created heart muscles from adult stem cells that they have retrieved during surgery. They cultured these cells and allow them to develop into mature heart muscle cells that were in perfect order and contract rhythmically and respond to both electrical activity and adrenalin. Scientists are hopeful that these cultured cells will enable scientists to study heart defects and test new medicines, and could one day be used to repair heart tissue which has been damaged during a heart attack. Another breakthrough in heart stem cell tech is done by the team of scientists at University of Minnesota who have created a beating heart in the laboratory for the first time which is hoped to increase the chances of successful transplantation. This research has so far been done only with rats and pigs and is highly experimental. It is unlikely to be applied to humans for years but will ultimately lead to humans. The principle involved is simple “decellularisation” in which powerful chemicals strip down the cells from the dead heart so that only the protein “skeleton” was left intact. Then the skeleton was seeded with live “progenitor” cells, which multiplied and grew back over it, eventually linking together into a new organ. Such cells are involved in the formative stages of specialized types of tissue such as those found in the heart. Similar procedure was performed by Professor Doris Taylor, director of the university’s centre for cardiovascular repair Taylor and her colleagues, in which they strip the cells from a dead animal heart and then reseeded the remaining protein skeleton with progenitor cells taken from the hearts of newborn animals and let them grow. Four days after seeding that observed that the cells started contracting, and after eight days the hearts started contracting. She is positive that same principle can be applied to humans to rebuild organs by using the skeleton of dead relative. She is hopeful that this will increase organ transplantation by 50% in the next 5 years.

Similar technique is used by British doctor Professor Paolo Macchiarini of Barcelona University, in case of a female patient whose trachea or windpipe was damaged and had a respiratory blockage. They extracted adult cells from that woman and grown them into six million cartilage cells invitro. Then they took windpipe of a deceased woman and removed the dead cells leaving only the collagen scaffold. Then those cartilage cells were grown on to the trachea skeleton, effectively making a windpipe in the lab. The windpipe was then cut into the right length and bent into shape and then was grafted in the patient. Now that patient is able to lead a normal healthy life. According to doctors this is just a start and they are hoping too use the similar technique to transplant other major organs. Details of the transplant were described in an early online edition of The Lancet medical journal.

So concluding my discussion, stem cell technique has started from treating some tissues replacement or transplant and eventually it will be able to create and transplant whole organs or organ systems, and will finally overcome the problem of tissue rejection for the times to come. So all in all we can say that stem cell tech has given us the right to expect miracles from Biology and a hope to end misery of humankind.

Darwin's day

Hi everyone! This is my first post. I would like to start my blog by reminding everyone that 12th Feb, 2009 is marked as the official day for celebrating Charles Darwin birthday as well as the 150th anniversary of the publication of his work "On the origin of species". This day is not celebrated as a national day by any single country but it's an international day of Science and humanity. This day is marked as the day to remember and honor the work of one of the greatest biologist who revolutionized the field of Biology and changed the way we look at life.

Charles Darwin, who is basically famous for his evolutionary theory via natural selection, has also done valuable contributions to other fields of Biology. His notable work includes "On the origin of species by means of natural selection(1859)", "The Descent of Man and selection in relation to sex", followed by "The expressions of the emotions in Man and Animals". His research on plants was published in a series of books including "The power of movement in plants" and in his final book "The formation of vegetable mould through the action of worms", he examined earthworms and their effect on soil. He is equally known for his work on coral atolls, barnacles and made valuable contributions to insect taxonomy. To check out the details about Darwin's day, click the link below:
http://www.darwinday.org/about/

Hello world!

Hi everyone! I am Mehreen. I am starting my own blog about Biology. As the name indicates the blog will strictly deal with biological issues. All the topics that I will discuss will reflect my personal thoughts, opinions and interests in Biology but every one is invited to comment on them. So without going into further details I launch BIODOMAINS.