Thursday, December 30, 2010

Asthma and Bacteria – A Possible Link

Asthma remains a baffling disease that impacts a growing number of individuals, especially children. Asthma is characterized by a constriction and swelling of the airways. The symptoms include the production of mucus and more importantly coughing, wheezing and a shortness of breath. Currently there is no cure for this condition but medications can be used to control it. The severity of this disease varies widely; it can be vary from a nuisance to a life threatening condition.

Recent evidence suggests that there is a strong connection between asthma and the kinds of bacteria that the body ordinarily harbors. Some years ago, Dr. Gary Huffnagle, an immunologist from the University of Michigan, subjected experimental mice to yeast introduced into their intestines; mold spores placed in their noses and an antibiotic drug. These animals began showing signs of asthma and blood tests indicated immune system dysfunction.

In addition, studies have indicated that children raised on farms are much less prone to suffer from diseases of the lung, including asthma, and Dr. William Cookson, a respiratory physician from the Imperial College of London, suggests that exposure to a diverse bacterial environment in childhood may play a protective role. Additionally, children born via the sterile environment of a cesarean section are more prone to suffering from asthma than those that have passed through the birth canal, and children that have had multiple courses of antibiotics are more likely to have asthma than their counterparts.

The relationship between asthma and the bacteria that ordinarily reside within the body is an exceedingly complex one. Yet, it has become clear that children who are stricken by asthma have different bacteria within their bodies and often a less diverse population than non-asthmatic children. The findings of these studies reinforce what has long been suspected regarding asthma,

Tuesday, December 14, 2010

Deepwater Horizon Blowout - Existence of Undersea Plumes of Oil

The environmental catastrophe caused by the blowout of the Deepwater Horizon at the Macondo well site resulted in the largest offshore oil spill in history. Although much of the surface oil contamination has been significantly mitigated, there remains an issue regarding the existence of undersea hydrocarbon plumes.

These plumes have been tracked by Dr. Richard Camilli and his colleagues from the department of Applied Ocean Physics and Engineering at the Woods Hole Oceanographic Institution. As a result of the blowout, more than 4 million barrels of oil were released into the Gulf of Mexico. Since the source of the spill was some 1500 meters beneath the surface, this resulted in the formation of undersea plumes of oil. On account of the complex variables that are involved in plume formation – the interplay of gas and oil in multiphase flow and the solubility of each of the constituents in the complex mixture - , it is exceedingly difficult to derive models that can reliably predict the behavior of hydrocarbons under such conditions.

In spite of the daunting problems associated with this catastrophe, the investigators were able to detect and measure the hydrocarbon plumes. They discovered the presence of a continuous plume of oil more than 35 kilometers in length at an approximate depth of 1100 meters. This plume persisted for months without signs of significant biodegradation.

Further studies by other investigators, however, have shown that the presence of the plume stimulated the growth of bacteria that are known to degrade hydrocarbons. The encouraging aspect of their findings is that, “the potential exists for intrinsic bioremediation of the oil plume in the deep-water column without substantial oxygen drawdown.”

The existence of undersea hydrocarbon plumes in the Gulf of Mexico has inspired scientific investigators to study their properties. The results of their work may lead to strategies designed to counter the ill effects of similar human catastrophes should they happen in the future.

Sunday, October 31, 2010

Virus Discovered as a Causative Agent in a Disease Prevalent in Central China

There have been many reported cases of a deadly fever outbreak in Central China. Numerous instances have been reported for the last three summers. The inexplicable illness is characterized by high fever and gastrointestinal distress (GI). Many of the individuals impacted by this illness bled severely, and, most alarmingly, as many as 30% of the victims have died. At first, scientists at the Chinese Center for Disease Control and Prevention (CDC) postulated that the disease was a form of human granulocytic anaplasmosis (HGA) a bacterial infection spread through tick bites.

Xue-jue Yu, a visiting scientist studying this illness at the Chinese CDC’s National Institute of Communicable Disease Control and Prevention (NICDC), was skeptical of this explanation. According to him, the mortality was too high, and, more conclusively, examination of blood samples did not reveal the presence of Anaplasma phagocytophilum - the bacterial agent that is responsible for HGA. Pursuing this problem, his team finally discovered a new type of bunyavirus as the culprit. Members of this family of viruses include the hantavirus and the Rift Valley fever virus. Hantavirus is responsible for a serious illness referred to as hantavirus pulmonary syndrome (HPC) spread by infected rats to humans. Yu’s results were subsequently reported in the New England Journal of Medicine (NEJM).

This is a rather disturbing finding and may point to the emergence of a new virus with a potentially deadly outcome for those infected. It is certainly worth increased attention on the part of public health professionals throughout the world.

Tuesday, September 28, 2010

Uncovering the Mode of Action of H. pylori Known to Cause Stomach Cancer and Gastric Ulcers

There are a number of cancers that have been linked definitively to infectious agents. T-cell leukemia has been shown to be caused by HTLV1, a retrovirus very similar to the virus that causes AIDS. The human papillomavirus (HPV) has been implicated in cervical cancer, and primary liver cancer has been shown to be caused by the Hepatitis B virus.

There is now clear evidence that a bacterial infection commonly found in the stomach caused by Helicobacter pylori (H. pylori) is responsible for stomach ulcers and cancer of the stomach. It has been found in 70% of those individuals with stomach cancer and is carried by 50% of the world’s people. This bacterium has a characteristic corkscrew morphology – shape. It has been proposed that the H. pylori pathogen is protected from the harsh acidic conditions of the stomach by its ability to bore into the protective gastric mucosal lining. It has also been established that H. pylori infection may lead to chronic inflammation that can trigger either gastric ulcers or cancer.

Dr. Nina Salama and her team at the Fred Hutchinson Cancer Research Center in Seattle successfully created genetically modified H. pylori that lacked four essential shape-forming proteins and as a result the organism lost its corkscrew morphology. As a consequence, these modified bacteria became less effective in attacking gastric tissue. H. pylori has a shape that is shared by other virulent bacteria including Vibrio cholerae that causes cholera and Campylobacter jejuni that is responsible for bacterial diarrhea.

Currently H. pylori is resistant to treatment with traditional antibiotics. However, discoveries such as the ones made by Dr. Salama offer hope that a more complete understanding of the mechanism of infection may eventually prove useful in treating the infection and preventing gastric ulcers and cancer in the future.

Thursday, September 16, 2010

Kidney Disease as a Consequence of Genetic Resistance to a Parasite

It has been well established that carriers of the sickle cell trait – predominantly found in sub-Saharan African populations - have an innate resistance to malaria. There is now evidence of an analogous relationship between a genetically-determined resistance against an infective agent and disease - in this case involving kidney disease.

Research results coming out of the laboratory of Martin Pollak, a nephrologist and human geneticist from the Harvard Medical School in Boston, have established a link between certain renal (kidney) conditions and a parasite called Trypanosoma brucei that is spread in African populations by a tsetse fly vector and causes African sleeping sickness. The kidney diseases studied were focal segmental glomerulosclerosis and end stage kidney disease; both of these maladies are four or five times more prevalent in African American populations than those of European origins.

As a result of exhaustive genetic analysis, Pollak and his team identified two variants in the so-called APOL1 gene that strongly correlates with kidney illness. The variants were referred to as G1 and G2. G1 turned up in 52% of glomerulosclerosis patients as compared to 18% of controls, and the G2 variant was found to be 50% more common with either kidney disease. Furthermore, they went on to determine that if both of the APOL1 genes (genes normally exist in pairs – one residing on each member of a chromosome pair) carried one of the disease-bearing variants, the probability of expressing kidney disease would increase seven fold.

The APOL1 gene is responsible for the production of apolipoprotein L-1. It has been demonstrated that the apolipoprotein L-1 promotes degradation of the trypanosome parasite by forming pores in its membrane. Pollak and his colleagues discovered that individuals, who carried either G1 or G2 in their blood plasma, effectively killed a subspecies of parasite T. brucei rhodesiense that is resistant to the normal gene product as did the synthetic versions of the variant proteins.

These are very interesting findings that point to the complex relationship between parasites and the hosts they infect. In addition, the fact that the man-made variants G1 and G2 proved efficacious in killing the parasite may prove to be clinically useful.

Tuesday, August 17, 2010

Genetic Basis of Tibetans’ Adaptation to High Altitude

The ability of native Tibetans to tolerate high altitude is, of course, legendary. Tibetans living on the Tibetan plateau at elevations that exceed 4000 meters are exposed to an atmosphere that has oxygen concentrations that are approximately 40% lower than that which is available at sea level. From a biological perspective it is of interest to know how this has been achieved.

From the evidence accumulated by Jian Wang and his associates from the University of California at Berkeley, Tibetans have acquired a number of inherited adaptations to this extreme environment, including – higher birth weight, higher hemoglobin – the protein found in red blood cells that binds oxygen - levels, higher oxygen saturation in the blood of infants and adults following exercise when compared with a control group of Han Chinese who moved to Tibet and are genetically distinct. Tibetans have occupied the Tibetan Plateau for over 25,000 years, possibly enough time to accumulate genetic adaptations through natural selection.

In an attempt to delineate the genetic characteristics of these adaptations, the investigators analyzed the DNA from both Tibetans and the control group. There results demonstrated, in fact, a single-nucleotide polymorphism (SNP) – a single point variation in the DNA studied – from a gene that encodes for the EPAS1 protein. This protein has been shown to be involved in the body’s response to hypoxia – low oxygen environment. This change occurred at a much higher frequency in native Tibetans than in the control group of Han Chinese.

These results represent a very important finding in regards to the fact that this beneficial genetic modification occurred over a very brief interval of time as compared to previously studied human genetic adaptations.

Saturday, August 7, 2010

An Argument for a Dramatic Improvement in the Science Education of Our Children

The technological wonders of the modern age are quite spectacular. One of the most profound of these is the Hubble telescope. Many human lives are saved and horrific diseases are averted daily due to the great strides made in the arena of health and medicine. The additional examples that could be cited are too numerous to mention here. Technological improvements are a direct outcome of the application of scientific enquiry and discovery.

The human world is beset with many problems that demand solution – the most urgent of these being climate change. There is a growing body of scientific evidence that supports this contention, including:

•Record setting high temperatures during the last ten years
•Erratic, severe and unusual weather conditions
•Increase in the frequency and severity of forest fires
•Increased acidity in the world’s oceans that has impacted the health of coral, phytoplankton and shelled creatures especially oyster larvae
•Melting and receding of glaciers worldwide
•Melting of the ice in the Arctic Ocean during the summer months.

The science that has established the relationship between the increased concentration of carbon dioxide and methane, the so-called greenhouse gases, resulting from human activity is clear and irrefutable.

In spite of these data, there is a marked resistance in this country to accept not only the obvious implication of these observations, but the meaningfulness of the observations themselves. This, to me, is extremely disturbing, for inaction or lack of sufficient resolve to confront this issue will inevitably result in disastrous consequences for future generations.

This inability to grasp the urgency of the issues that confront us is a direct result of the failure to educate our children in the realm of science. Science has some essential characteristics that make it exceedingly well suited for problem solving. It is cooperative effort; scientific advances are a direct result of strides made by investigators in the past as well as the present. Science depends on a growing body of knowledge; it builds upon all that has been already discovered. In addition, the scientific process is open-minded; any hypothesis or law must fit the data that is accumulated through observation. If new data does not fit the interpretation then the conclusions need to be modified to accommodate the newly acquired facts. Science requires a rigorous thought process that relies on higher-order functions in the human brain.

In my judgment, it is not possible to meet the challenges we face in this technologically-driven world without a sufficiently adequate education in the sciences. We have failed abysmally in this regard in the United States. Ignorance is not bliss by any stretch of the imagination. Ignorance will inevitably lead to erroneous conclusions and ultimate disaster.

Wednesday, August 4, 2010

Dangers of Increased Acidity in the World’s Oceans as a Direct Result of Human Activity

The effect of increased carbon dioxide resulting from human activity on the oceans is quite clear. There is a direct relationship between increasing levels of carbon dioxide in the atmosphere and the increasing acidification of the oceans. The chemistry has been well documented. Carbon dioxide (CO2) when dissolved in water (H2O) forms carbonic acid (H2CO3). This acidification has been implicated in the destruction of coral. Recent evidence has also demonstrated that increased acidity in the oceans also has a deleterious impact on oyster larvae as well.

As I have reported earlier, it has been shown that increased acidity in the oceans has placed increased stress on phytoplankton, an organism that is a fundamental part of the food web in the world’s oceans. They account for one-half of all oxygen production as a result of photosynthesis on the planet.

In this article we will review the impact increased acidity is having on the world’s oceans in greater detail. Currently, human societies are collectively depositing gigatons of carbon dioxide per year into the earth’s atmosphere - a gigaton is equivalent to one billion tons. According to Lee Kump, a geochemist at Pennsylvania State University, this kind of growth in the level of carbon dioxide emissions as a direct result of human activity on the earth may be considered, “as one of the most notable, if not cataclysmic events in the history of the planet.”

It is estimated that there has been a drop of 0.1 pH unit in the global ocean since the beginnings of the industrial revolution with a .026 drop within the last fifteen years. These are disturbing data. Computer modeling predicts that if this trend continues the pH will have dropped to 7.8 from the 8.2 value in the pre-industrial age, where pH is a logarithmic measure of the concentration of hydrogen ions – a solution having a pH below 7.0 is considered to be acidic. By way of comparison, the pH of the stomach is around 2.0.

According to Richard A. Kerr in an article published in the June 18 2010 Science, decreasing pH impacts species that build shells or skeletons of calcium carbonate in the following way, “These organisms include tropical corals, echinoderms, mollusks, microscopic foraminifera floating in surface waters and certain algae. When the hydrogen ion concentration of seawater gets high enough, the calcium carbonate in these organisms begins to dissolve.”

The oceans provide much of the world’s supply of food. These data taken together with the warming effect on the earth’s oceans as a result of increased carbon dioxide in the earth’s atmosphere and its resulting effect on weather patterns, paints an alarming picture in regards to the changing natural environment and the future of humanity.

Tuesday, July 20, 2010

The Fight Against Malaria – Some Encouraging News

Malaria continues to be a scourge in many parts of the world. The problem is particularly acute in Africa. Malaria is a pervasive illness characterized by high fevers, shaking chills, flu-like symptoms, and anemia. It is caused by a parasite referred to as Plasmodium falciparum (the Asian variety is Plasmodium vivax and not as virulent). Plasmodium is carried by the Anopheles mosquito prevalent in the tropics.

The plasmodium parasite exhibits a number of stages in its life cycle. The disease progresses in the following way. Once an individual is infected, sporozoites migrate to the liver where they develop into merozoites. From there they enter the bloodstream and attack red blood cells. Within 48 to 72 hours the infected red blood cells breakdown releasing more parasites into the bloodstream.

Chloroquine is a commonly used drug against Malaria. However some strains of the anopheles mosquito have developed an immunity to this drug. In this case, quinidine or quinine plus doxycycline, tetracycline, or clindamycin; or atovaquone plus proguanil (Malarone); or mefloquine or artesunate; or the combination of pyrimethamine and sulfadoxine, are given instead.

Malaria is so pervasive that it is estimated that 300 to 500 million individuals contract the disease each year resulting in approximately 1 million deaths. This is a wholly unacceptable situation from a world health perspective.

In spite of this daunting reality, significant inroads have been made, especially in the area of prevention. Thanks in part to the mass infusion of resources from the Bill and Melinda Gates Foundation, insecticide-treated bed nets, indoor spraying of insecticides and a category of powerful drugs called artemisinin-based combination therapies (ACTs) have shown remarkably positive results in pilot studies. In addition, although many attempts at making a completely effective vaccine have failed, a vaccine that seems to be 50% effective in offering protection for the first 8 months is now under development. These efforts, taken together, offer significant hope that the spread of this horrific disease may be curtailed in not eventually eliminated.

Wednesday, July 7, 2010

Impact of Climate Change on Phytoplankton

There is an unambiguous relationship between increasing levels of carbon dioxide in the atmosphere as a direct result of human activity and the increasing acidification of the oceans. This results from a well known chemical principle that carbonic dioxide (CO2) when dissolved in water (H2O) forms carbonic acid (H2CO3). This acidification has been implicated in the destruction of coral.

In a recent report in the journal Science, Doctor D. Shi from the Department of Geosciences at Princeton University has established a correlation between increasing acidity in the oceans and increased stress on phytoplankton. Phytoplankton is a fundamental part of the food web in the world’s oceans and, therefore, plays a key role in the life of the oceans. In addition they account for one-half of all oxygen production as a result of photosynthesis on the planet.

Doctor Shi and his colleagues have shown that acidification of the ocean places stress on phytoplankton populations by impacting the bioavailability of Iron. Iron plays a pivotal role in the metabolism of these organisms. This particular consequence of the ever increasing level of atmospheric carbon dioxide is certainly a cause for concern.

Tuesday, June 29, 2010

New Frontiers in the Treatment of Alzheimer’s

Alzheimer’s is a devastating disease of the human brain that ordinarily displays symptoms in old age. It is an ailment that is characterized by progressive dementia that totally incapacitates the patient and ultimately ends in death.

Alzheimer’s is characterized by a gradual build up of protein fragments referred to as amyloid-beta peptides. These fragments accumulate in the intercellular spaces within the brain. The disease process ultimately leads to profound cell death. Anti-amyloid drugs and a vaccine have been developed to combat this disease. These novel therapies have so far been disappointing.
As a result of extensive research into the disease process, there is now a new understanding of disease progression. The buildup of the amyloid-beta peptides begins from 5-20 years before diagnosis. In addition a protein called, TAU that normally functions to maintain the infrastructure within nerve cells (neurons) is modified leading to disruption of normal cell function. This seems to occur 1-5 years prior to the appearance of symptoms, and finally, brain shrinkage becomes noticeable as a result of significant cell death 1-3 years before diagnosis.

On account of these findings, the current understanding is that the failure of new therapies to effect a beneficial change may be due to the fact that when treatments are initiated the brain damage is already too advanced to yield beneficial results.

In the town of Medellin, Columbia there are approximately 5000 members of 25 extended families who develop early-onset Alzheimer’s. This is a result of dominant gene that is found in less than one percent of 27 million Alzheimer’s cases worldwide (2006). Individuals of these families, therefore, allow an ideal setting to test this hypothesis. The planned trial is referred to as the Alzheimer’s Prevention Initiative (API). The overall approach is to have appropriate candidates – apparently healthy with the deleterious gene – who are around the age of forty treated with the anti-myeloid therapies as previously discussed.

If this approach yields promising results, - the treatments delay or stop the inexorable progression of the disease - this would be exciting news, especially since the U.S. population is aging.

Wednesday, June 16, 2010

Regarding Platelets

Platelets are cell-like bodies that represent an essential component of circulating blood. The role of platelets in blood clotting has long been understood. Since platelets, like red blood cells do not have nuclei and the DNA that is essential for life, it was assumed that blood-clotting was the only role for platelets.

In recent years, platelets have been shown to possess diverse functions. They have been found to release growth factors and other factors that help in the repair of damaged tissues. In addition, they help initiate the inflammatory response, alert immune cells and they have even been implicated in the attack of invading microbes in the midst of a bacterial infection. They also function as carriers, delivering serotonin to the liver which aids in the regeneration of the liver following a traumatic injury. Platelets also participate in the development of the circulatory system in newborns.

It is interesting to note that Doctor Weyrich and his colleagues from the Human Biology and Genetics Program at the University of Utah have demonstrated that platelets reproduce in spite of the fact that they lack a cell nucleus. They send out a strand with one or more bead-like bulges that eventually separate producing new platelets.

This new understanding of how platelets function will ultimately open the door to new kinds of therapies and treatment for diseases in which they are apparently implicated.

Pathways Toward Increasing Human Lifespan

The target of the drug rapamycin is TOR, an enzyme. An enzyme is a protein that serves as a biological catalyst in living systems. TOR has been shown to play a key role in cell growth and the metabolic pathways that maintain homeostasis on both the cellular and organismal levels. Insulin and insulin-like growth factors are activators of TOR. Additionally, caloric restriction (CR) triggers a biochemical signal that inhibits TOR activation acting as negative feedback.

Persistent activation of TOR has been clearly shown to be involved in various diseases including cancer, cardiac performance and obesity-related ailments. Conversely, the inhibition of TOR has been shown to prolong life span. The positive effect of CR on longevity has been demonstrated in many animal species. CR may exert its effect through the inhibition of TOR.

Sestrins (Sesns) are proteins that are highly conserved in nature – found in many mammalian species across the evolutionary spectrum. They increase within cells that are exposed to stress such as CR. There is evidence that they also may function as antioxidants. Sesns are, in fact, feedback inhibitors of TOR.

There is mounting evidence that Sesns are involved in preventing age-related disease and, therefore, prolonging life. This kind of understanding of the aging process may find some future application.

Monday, June 7, 2010

Advances in the Delivery of Anti-Cancer Drugs

One of the major obstacles to the effective treatment of cancer patients with potent anti-cancer medications is the successful delivery of the drug(s) to the entire tumor mass. Investigators led by Dr. Kazuki N. Sugahara at the Vascular Mapping Laboratory at the Center for Nanomedicine, Stanford-Burnham Medical Research Institute at the University of California at Santa Barbara have devised an approach to overcome this limitation.

Using the mouse as the animal model, they have utilized a tumor-penetrating peptide (a small protein) called iRGD to effectively increase the access of anti-cancer drugs to cancerous tumors and, thereby, increase the therapeutic potency of these medications.
The peptide iRGD penetrates into an actively proliferating tumor mass by specifically binding to the av integrins – proteins that are uniquely found on the endothelium (the cells that line the interior wall of blood vessels) of tumor blood vessels. In fact, when iRGD was co-injected with an albumin – albumin is a common protein found in circulating blood - binding dye used as a marker, the dye was found to successfully accumulate in five different tumor models including breast, prostate and pancreatic cancers.

In addition, the scientists involved in this research found that iRGD when co-injected with the anti-cancer drug Doxorubicin (DOX) resulted in a sevenfold increase in accumulation of DOX in prostate cancer tumors in the animals studies.

These results are especially encouraging given the fact that many anti-cancer drugs like DOX have significant side effects at high doses. This serious limitation can be sidestepped if the drug gains access to tumor cells at more manageable doses.

The Successful Synthesis of a Bacterial Chromosome

A major breakthrough in molecular biology has recently been reported from the laboratories of Dr. J. Craig Venter at the J. Craig Venter Institute in Rockville Maryland and San Diego California. The investigators in this ten year project have successfully synthesized a bacterial chromosome using the DNA sequence data from a species of microorganism called M. mycoides and subsequently introduced this product into a different bacterial species, M. capricolum replacing its DNA with the synthetic variety. This wholly modified organism grew and divided with the characteristics of the donor species.

The technique that was utilized is outlined below:
• A copy of the chromosome of M. mycoides was made by using yeast cells to assemble the DNA in stages. This was an arduous and time-consuming project that required much trial and error.
• The fully synthetic copy was then placed into the recipient microbial species M. capricolum. In order to show that the synthetic chromosome was successfully introduced, the investigators purposefully incorporated into the synthetic product DNA sequences that spelled out in genetic code the e-mail addresses and the names of many of the people involved in the project. In addition, a gene was introduced into the synthetic DNA with the information to produce a blue gene product that would make bacterial colonies visible.

After months of thwarted attempts, blue bacterial colonies were found growing, indicating success. It should be made clear that this breakthrough does not constitute the creation of a synthetic life form, since the bacterial cell machinery was already pre-existing. However, it does demonstrate that the transformation of one bacterial species to another is feasible through the technique that is outlined above, and that it may be possible to introduce synthetic genes capable of producing novel gene products into synthetic bacterial chromosomes and produce organisms with new capabilities such as producing pharmaceuticals or neutralizing chemical pollutants, etc. In addition, this technology also brings with it serious ethical considerations that need to be addressed as well.

Tuesday, June 1, 2010

Neanderthal DNA

An international team of scientists from the Department of Evolutionary Genetics at the Max-Planck Institute for Evolutionary Anthropology at Leipzig, Germany, reported a draft sequence of the Neanderthal Genome – the full complement of genes. Neanderthals lived in Europe some 30,000 to 45,000 years ago and in the Middle East some 80,000 years ago. This species did, in fact coexist with modern humans.

The Neanderthal DNA that was analyzed was harvested from three female Neanderthals that lived in Croatia approximately 38,000 years ago. Although an extraordinary amount of DNA has been successfully defined, about one-third of the genome remains ambiguous. The investigators, however, devised a novel technique to fill in these “gaps.” The scientists involved in this extensive undertaking then compared the Neanderthal-derived data to the DNA obtained from five individuals from distinct parts of the world. The results of these studies yielded some surprising conclusions.

They found that the Neanderthal and modern human genomes are 99.84% identical to each other, and that those regions of the DNA that are different represent those genes that have been modified since the human species diverged from Neanderthals estimated to have occurred between 270,000 and 444,000 years ago. Furthermore, the genetic areas that differ seem to involve genes that play a role in skin, metabolism, the skeleton and the development of higher order brain function.

The most surprising result of all was the discovery that both Europeans and Asians share from 1% to 4% of their DNA with Neanderthal DNA, whereas Africans do not. This result is strongly suggestive of interbreeding between modern humans after they emerged from Africa and Neanderthals.

These data shed some new interesting light on human evolution. It has become increasingly clear that the analysis of DNA of humans and other species is an important and often essential tool in the study of the evolutionary process.

Monday, May 24, 2010

Gulf Oil Spill - An Ecological Disaster

According to Doctor Samantha B. Joye, from the Department of Marine Sciences at the University of Georgia, involved in gathering data from the Gulf oil spill, “There’s a shocking amount of oil in the deep water, relative to what you see in the surface water.” She went on to say that, “There’s a tremendous amount of oil in multiple layers, three or four or five layers deep in the water column.” These plumes were discovered by scientific investigators from a number of universities working from aboard the Pelican, a research vessel.

The controversial chemical dispersants that have been used by British Petroleum (BP) to break the oil down into small droplets may have contributed to the creation of these plumes. The naturally occurring oil-eating bacteria “feeding” on this oil are depleting the oxygen dissolved in the gulf, for as they rapidly grow and divide they are consuming oxygen. Doctor Joye said the oxygen had already dropped 30 percent near some of the plumes in the month that the broken oil well had been flowing and, “If you keep those kinds of rates up, you could draw the oxygen down to very low levels that are dangerous to animals in a couple of months. That is alarming.” In addition, the natural rate of replenishment of oxygen in deep water from the surface is a slow process.

In my estimation this oil spill will prove to be an ecological disaster of immense proportions if the flow of oil is not stopped in a timely fashion. The fowling of the gulf with oil will add an additional insult to the acidification of the oceans that is a direct result of the ever-increasing concentration of carbon dioxide in the atmosphere.

Thursday, May 20, 2010

How Cancerous Tumors Can Avoid the Immune System

The danger that cancer poses to the patient is the ability of cancerous cells to metastasize – spread throughout the body. This is referred to as a malignancy. Cancers can arise in any tissue i.e. from lung, liver, brain, stomach etc. Cancerous cells are characterized by their capacity to divide out of control, their primitive function and their ability to metastasize. The body’s natural defense against malignant tumors is afforded by the immune system through the production of so-called effector T cells or cytotoxic T lymphocytes that circulate throughout the body, and attack cells that have become malignant.

In response, cancerous cells have been shown to be able to suppress the immune system’s effectiveness. One of the mechanisms that they employ is to reduce the expression of certain proteins on their cell surface that can alert the immune system to their presence; substances that trigger immune responses are referred to as antigens. A common example of an antigen is the proteins in ragweed pollen that elicit an allergic response in some individuals. Another method of evasion has been shown to occur, namely that certain tumors can secrete proteins that inhibit effector T cell responses and promote regulatory T cells that can inhibit immune responses.

As a result of the elegant studies of Doctor Jacqueline D. Shields from the Institute of Bioengineering in Switzerland, yet another mechanism of circumventing the immune system has been discovered. It was found that certain melanomas – an aggressive form of skin cancer – can reorganize their cellular environment (stromal microenvironment) into structures that are similar to the lymphoid tissue of the immune system. This reconstruction results in fooling the immune system to the extent that it recruits regulatory T cells that actually promote tolerance and enhance tumor progression.

Studies of this kind shed significant light on the progression of Cancers, and reinforce the important role that immune surveillance plays in the body’s natural defense mechanisms. By elucidating the actual manner in which tumors can thwart these defenses, the possibility of developing effective therapies is appreciably enhanced.

Sunday, May 16, 2010

Atrazine – A Potentially Dangerous Herbicide

Atrazine (1-chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine) is a widely used herbicide in the United States. Atrazine is in a class of compounds that is known to mimic steroid hormones in a variety of animal species. Atrazine is used to stop pre- and post-emergence broadleaf and grassy weeds in major crops. Approximately 36 million kilograms of this substance are applied on U.S. farms yearly. It has been estimated that 225,000 kilograms of the herbicide become airborne and fall with rainfall as far as 1,000 kilometers from its source.

In a study under the direction of Dr. Tyrone Hayes of the Department of Integrative Biology at the University of California Berkeley, 40 male African clawed frogs were exposed to atrazine at a level of 2.5 parts per billion (ppb) in drinking water. This is at a level lower than the 3 ppb allowed in drinking water by the Environmental Protection Agency (EPA). As a result 30 of the frogs were chemically castrated. Interestingly enough, four of the treated frogs turned female and produced viable eggs despite being genetically male. Only six of the frogs resisted atrazine and displayed normal sexual function. This result was confirmed by additional studies. A possible candidate for the apparent sex change effect is the enzyme aromatase that triggers the production of the female hormone, estrogen causing male gonads to become ovaries.

On account of these disturbing data, the European Union has prohibited its use. The rationale for the continued use in the stated by the Environmental Protection Agency (EPA) is, "The total or national economic impact resulting from the loss of atrazine to control grass and broadleaf weeds in corn, sorghum and sugar cane would be in excess of $2 billion per year if atrazine were unavailable to growers." In the same report, it added the "yield loss plus increased herbicide cost may result in an average estimated loss of $28 per acre" if atrazine were unavailable to corn farmers”

In summary, Atrazine is a common agricultural herbicide whose primary effects are reproductive and developmental. The study cited above indicates that for the organism studied, the frog, profound reproductive harm occurred at levels below what is currently allowed in drinking water. This is cause for concern especially in regard to the fact that atrazine is often found far from its original site of application.

Thursday, April 29, 2010

Cancer Vaccine – A New Hope for Patients with Prostate Cancer

For those patients with aggressive prostate cancer there are a number of available therapies, including prostate gland removal, radioactive seed implants, and androgen deprivation therapy. Each of these has significant drawbacks. There is a vaccine, however, that has been developed for prostate cancer that may provide yet another modality to the treatment of this disease.
The first vaccine that directly treats cancer could be available soon if Seattle’s biotech company, Dendreon Corporation secures U.S. approval of its product called Provenge. The mechanism of action of this vaccine employs what is referred to as immunotherapy – the recruitment of the patient’s own immune system to preferentially destroy cancer cells. This approach has been used in the past to fight cancer with limited success. This particular application may prove to be more fruitful.

Dendritic cells which are found in the bloodstream play a key role in the immune response. They are referred to as Antigen Presenting Cells (APC). These cells interact with antigens – substances that induce the immune response – and by presenting these antigens to immunological T cells, trigger them to divide and find and destroy those cells carrying the antigen. For prostate cancer, the antigen is prostatic acid phosphatase (PAP). PAP is found predominantly on prostate cancer cells, and, therefore, would be the antigen of choice.

With this information in mind, the strategy used to produce the vaccine is the following:
•The patient’s Dendritic cells are harvested and stimulated to divide in the laboratory
•These APCs are then exposed to PAP, and bind to it
•These APCs armed with the antigen are then injected back into the patient.

Hopefully, these cells will then trigger the appropriate T Cells in the body to multiply, find and ultimately destroy the cancer cells carrying PAP. Initial clinical trials of this vaccine have proven quite promising. If successful, this would be very exciting news, for it would represent an essentially non-invasive technique to cure prostate cancer without any real risk to the patient, since it is the patient’s own cells that are used in the treatment.

Monday, April 26, 2010

Obesity , Inflammation and the Human Gut

Obesity is a condition that has reached epidemic proportions not only in the United States but a good portion of the developed world. A number of factors contribute to this condition; predominant among these are high daily caloric intake accompanied by an increasingly sedentary lifestyle for many. A more alarming trend is the extent to which this is being seen in children.

One of the more serious side effects that are directly related to obesity are Type II Diabetes – a condition that results in the inability of cells in the body, especially those of the muscle and the liver, to properly absorb glucose – a major component of cellular metabolism. As a result, the level of glucose in the blood increases significantly. This condition has serious implications for the health of the diabetic including heart disease, blindness, an increased likelihood of amputation and other consequences.

Scientists have spent considerable effort trying to understand the underlying processes that can more thoroughly explain the condition of obesity. The term that is used to describe the complex interaction that lies at the heart of obesity is referred to as the Metabolic Syndrome. Low-grade inflammation has been implicated in this syndrome, and the gut may play an important role. It has been established that obesity is associated with increased immune system activity.

The human gut harbors a large spectrum of bacteria that are beneficial. If there is an impairment of the body’s first line of defense, the innate part of the immune system, this might impact the bacterial population in the gut and trigger an inflammatory response. As a result of the studies done by Dr. Vijay-Kumar and his colleagues from the Department of Biology at Emory University in Atlanta, Georgia, this hypothesis has been shown to have validity in the mouse, an animal model often used in immunological research. In his studies, the obesity of mice with this dysfunction was exacerbated when fed a high caloric diet.

This kind of study demonstrates that obesity is a complex problem and, therefore, needs to be addressed from a variety of different perspectives.

Wednesday, April 14, 2010

Concerning a Theory of Human Emotions

Humans are endowed with a life of the mind that encompasses the unique ability to reason and a diverse range of emotions. It is the emotions that provide the drive and motivation to act in the world as well as imbue an individual existence with both color and spirit. Emotions project the individual’s reaction to personal experience. They are felt internally and are an external manifestation of a person’s response to external conditions.

I believe it is reasonable to assume that the emotions have a neurological basis; it has been well established that the area of the brain referred to as the amygdala, located within the limbic system, is the site where neurological activity associated with the emotions is found. Over the millions of years of human evolution, the neuronal infrastructure of this section of the brain was assembled in order to improve the survivability of the species in an essentially hostile environment.

In my mind, the panorama of the emotions can be conceptually divided into two distinct categories. Within one subset, I place those emotions that are elicited in response to a perceived and imminent threat to the safety and integrity of the individual or group. These emotions include fear, anger, hatred and rage.

Humans are gregarious by nature and have a natural affinity towards others. This socially-oriented proclivity has immense ramifications in regards to the fate of human populations. There exists in all of us what is perceived as a need for a sense of “connectedness” that drives this movement towards others. It is the state of health of this connectedness that is the source of the emotions I place in the second category. The sense of belonging can either be enhanced or diminished. The emotions that reflect this enhancement are love, joy, delight, happiness and elation. Those emotions that are elicited as a result of the feeling of diminishment of belonging are grief, sadness, sorrow, depression and despair.

This innate need for feeling connected not only applies to others in the human family but to the natural world as well. This reality is reflected in the richly textured myths of early human societies. Native American populations viewed themselves in a context of connection to all that surrounded them including the inanimate world. Life in the modern technological era has deprived us of this sense of belonging to the greater world. I have concluded that it is this schism that is at the heart of anxiety that drives so many to distraction.

The internal and overwhelming sense of isolation that is the hallmark of the modern world has diverted humans from their true nature. Collectively, humans are neurologically wired to be an integral part of all that surrounds them. This desire for “oneness” lies at the heart of so many of the world’s religions. It is this state of harmonious relationship that so many seek, especially in form and texture of their god(s).

We are essentially a tribal species. It is this need for fully participating within the fabric of a social environment that is so often thwarted by the hard-edged structures that are imposed by the exigencies of modern life.

I am convinced that it is possible to retain the benefits of technological progress while seeking to soften our rigid social structures and permit a greater sense of openness and inclusion. The significant threat that human activity poses to the health of the natural environment may provide an impetus for a change in the way we have come to perceive others and the natural world. We should seek to enhance and not curtail the internal desire for wholeness, while utilizing and maintaining our higher faculties as well.

HIV Vaccine – A Promising Development

The human immunodeficiency virus (HIV) is responsible for the complex of symptoms that characterize acquired immunodeficiency disease syndrome (AIDS). The devastating impact of this disease resides with the fact that HIV targets a particular subset of cells that play a critical role in the human immune system. These cells are called Helper T cells that carry a particular protein marker (CD4) on their cell surfaces. When an individual, infected with the HIV reaches a certain threshold in viral load, the number of CD4+ cells, circulating in the bloodstream, drops dramatically. Under these circumstances, the infected person is prone to infections of all kinds, especially opportunistic infections – infections that result from bacteria, fungi or viruses that the general population is protected against with a healthy immune system.

This disease had a devastating and profound impact on the millions of lives throughout the world and has resulted in orphaning many children in the developing world. As a direct result of the intense research into the nature of HIV, there is now a “cocktail” of medicines that greatly reduces the viral load in AIDS patients; however, these drugs are prohibitively expensive. The application of safe sex practices can reduce the probability of becoming infected in sexually active individuals, but real the hope lies in the development of an effective vaccine.
HIV is a member of a class of viruses called retroviruses. These viruses are particularly troublesome for two reasons:
•They are capable of integrating into the host’s DNA and can repeatedly re-emerge and, therefore, re-infect
•They can produce many variants through minor changes in their genetic makeup.
This latter characteristic has proved problematic in developing an effective vaccine. There has been a modicum of hope and interest, however, in phase III of the trial of a vaccine that recently enrolled more than 16,000 participants in Thailand. Although analysis of the results of this trial showed an effectiveness of only 26.4%, it seems to have provided some encouragement on the part of investigators. Jerome Kim of the Walter Reed Army Institute of Research remarked that, “We’ve taken a small step. It’s not a home run, but it opens the door to future work.”

The development of a truly effective vaccine would have enormous implications for the world in general and the millions that are at risk in particular. It would also put an abrupt halt to the spread of this horrendous disease.

Tuesday, April 13, 2010

Mental Illness - a New Frontier

There is currently a considerable effort being undertaken to revise the Diagnostic and Statistical Manual of Mental Disorders (DSM). This endeavor has been inspired by the significant strides that have been achieved in understanding the nature of mental imbalances made possible by breakthroughs in the areas of neuroscience and neurobiology. As we have noted previously, many disorders including Chronic Depression and Obsessive Compulsive Disorder (OCD) have been shown to result from a dysfunction in particular neural circuits in the brain.

In spite of these findings, there remains much to be discovered in regards to the biological basis of mental disorders – what causes these disruptions in the brain’s circuitry. For this reason, the DSM will remain focused on symptoms for the various disorders.

There is a new initiative that has been launched by the U.S. National Institute of Mental Health (NIMH) to fund the pure scientific research that is required to uncover the root causes of mental disorders. According to Bruce Cuthbert, an NIMH scientist, “What we are doing is trying to develop new ways to classify disorders that are based on identifiable neural circuits.”

To date the draft DSM has outlined five domains of mental function that correlate with specific regions of the brain or particular chemical signaling pathways or both. The road to completion of the DSM will be a long and arduous one, but well worth the effort, especially in regards to improved treatments for those unfortunate enough to be plagued by mental illness.

Tuesday, April 6, 2010

The Beginning of Cellular Life - An Hypothesis

A necessary first step in examining the evolution of cellular-based life from the pre-biotic world is to discern what constitutes the makeup of cells in the broadest possible terms. In deconstructing cell structure from the viewpoint of prokaryotes, I have come up with the following:

•Cell Membrane to delineate the cell and protect it from the local environment
•Cell infrastructure composed of the most basic structural components including actin, myosin, etc.
•Source of readily available energy
•Proteins especially enzymes involved in catabolic and anabolic activities
•Signal transduction pathways that allow for both intracellular and extra-cellular communication.
•Nucleic Acids: DNA and RNA to serve as information stores for the cell.
•Mechanisms for DNA and cellular replication.

Any Attempt to propose a mechanism by which primordial cell-like structures evolved into the complex cells that exist today, strongly suggests a gradual stepwise process that took eons to accomplish. It also suggests, in my mind, that the process would involve steps in which cellular organization would grow in complexity from the level of simple molecules (substrates) through proteins and finally through protein-nucleic acid interaction to the encoding of the genetic material. In this way, selection pressures and processes would enhance each succeeding step.

Elements of Hypothesis:

•There existed in an aqueous environment (possibly shallow ponds or along coastal regions or possibly the sea floor) where there was an abundance of nucleotides, fatty acids, amino acids, peptides and polypeptides. It is possible that some of this organic material may have been seeded by meteorites.
•In these organic-enriched regions, conditions were appropriate for the spontaneous formation of cell-like structures.
•These cell-like structures developed semi-permeable membranes formed from the spontaneous assembly of proteins and lipids (probably a more primitive structure than found in present day cells) and highly permeable to dissolved organic matter in the local environment.
•The local environment was such that amino acids, nucleotides, fatty acids and carbohydrates could readily penetrate the cell membranes of these primordial cells and concentrate there.
•Ambient conditions including oxygen concentration, temperature, abundance of ammonia and methane made the spontaneous synthesis of proteins and nucleic acids not only possible but highly likely.
•Assuming that spontaneous formation of tRNAs were a likely scenario, these tRNAs could bind to their appropriate amino acids. These amino acid carriers collided with each other and result in the formation of random polypeptide chains. Subsequently, Polypeptides that were capable of binding to carbon sources such as glucose stabilized these small proteins and gave them a competitive advantage over more non-specific proteins. Since the metabolic pathway for glucose metabolism is universal to all life, one must assume that glucose was abundant in pre-biotic times. This same argument can be applied to the presence of ADP/ATP, since this molecule is the essential ingredient for all energy sustaining life activities.
•Some of these selected proteins also possessed catalytic capabilities and were able to breakdown carbon rich substrates and ultimately capture energy in ATP molecules. This energy may have been used in accelerating the synthesis of more complex molecules and intra-cellular structures, the precursors of cellular organelles.
•There is mounting evidence that strongly suggests that RNA may have played a pivotal role in information storage in the early evolution of cellular life. As I have postulated above, tRNAs may have been abundant. Additionally, evidence for the role of RNA in information storage includes:
oThe discovery of RNA that possesses catalytic activity referred to as ribozymes. There is a ribozyme that has been found in the core of Ribosomes.
oThe discovery of small pieces of RNA that can readily bind to a variety of organic molecules and that are found on the ends of mRNA in prokaryotes. These pieces function as switches that can turn translation on or off and are referred to as riboswitches.
oDouble-stranded RNA that can silence gene transcription in a complex referred to as RISC.
•What is now referred to as the anti-codon region of tRNA may have been used to make mRNA possibly happening spontaneously utilizing an environment rich in small pieces of RNA or assisted by a ribozyme. These nascent mRNAs served as templates for the further synthesis of specific and biologically valuable proteins. Whether or not such associations are possible today in conditions that simulate the pre-biotic environment would need to be tested. It is possible that “ancient” RNA had a different structure than the current form. This early mechanism was probably inefficient and prone to error.
•These early cells were infiltrated by competing entity that gradually assumed a symbiotic relationship and was to become what is now referred to as ribosomes. These structures contributed a much more efficient mechanism for the synthesis of proteins.
•Messenger RNAs were no longer able to sustain the growing complexity of cell life as embodied in metabolism and energy transfer mechanisms. A more highly conserved store of information was required. The appearance of an enzyme capable of using mRNA as a template to make highly stable double-stranded DNA encouraged the further development of cellular complexity and evolution. This transition was necessitated by the fact the extra-cellular environment was no longer as rich in nutrients and building materials as was previously the case. It has become clear that large portions of the genome of humans and other complex organisms are made up of retrotransposons. There are relatively small pieces of DNA that code for reverse transcriptases that allow for copying of these segments and ultimately inserting them in other places in the genome. These were originally discovered by McClintock and referred to as so-called “jumping genes.” Integration of these pieces in the promoter or structural regions of active genes can have profound impacts on gene expression. Certain diseases have been associated with this process. Furthermore, there are retrotransposons that have been conserved among and between organisms. This suggests that the increasing complexity of the genome as seen in evolution may be in large due to retrotransposons. In addition, retrotransposons have many characteristics similar to retroviruses suggesting that retroviruses may have played a significant role in delivering novel genetic material to the genome.
•Gradually the repertoire of catalytic and structural proteins and genes grew in complexity leading ultimately to modern DNA and cell replication and both anabolic and catabolic pathways.
•At some point in this process cells became “alive”: able to do work against the forces of entropy, grow in complexity and produce more of themselves in a chaotic environment.

Functional Heart Muscle Made from Embryonic Stem Cells in the Mouse

Currently, the demand for organs for transplant far exceeds the number of organs harvested from human cadavers. As a result many seriously ill individuals die from diseased essential organs such as the heart, liver and lungs. This is a dilemma that plagues modern medicine
The work of Ibrahim J. Domian from the Cardiovascular Research Center in Boston Massachusetts suggests an alternative to the reliance on intact organs for transplantation. Dr. Domian and his colleagues have successfully grown functional mouse heart muscle from mouse embryonic stem cells (ESC) in a laboratory (in vitro).

The process by which an embryonic stem cell becomes a cell with a specialized function such as a muscle cell is referred to as differentiation. This group has discovered a progenitor cell capable of in vitro expansion, differentiation and assembly into functional muscle tissue. This work is preliminary in nature. However, the implications are far reaching. One can envision a time in the future when ESC are engineered to produce an intact organ in the laboratory. Such a development would potentially save innumerable lives.

Sunday, April 4, 2010

Multiple Sclerosis – Prevalence in the Pacific Northwest

Multiple Sclerosis (MS) is a characterized as an autoimmune disease – the body’s immune system attacks its own tissue. It is a chronic, disabling disease of the central nervous system (brain and spinal cord). The disease causes inflammation, destruction, and scarring of the sheath that covers nerve fibers, called myelin, in the brain and spinal cord. As a result, electrical signals from the brain are impaired and disrupt muscular activity throughout the body. The onset of this disease generally occurs between the ages of 20 and 40; women are twice as likely to develop MS as men.

In MS, the target of the immune system is the myelin that covers the axons of nerves (neurons) of the central and peripheral nervous system. Myelin is a complex substance made up of 80% lipid (fat) and 20% protein. One of the primary functions of myelin is to serve as insulation for the neurons. These neurons transmit signals from the central nervous system to the muscle; these signals are essentially electrical in nature. Without the proper insulation provided by the myelin, these signals degrade and impact muscular activity. Destruction and deterioration of the myelin has a dramatic and deleterious impact on the peripheral nervous system. The MS patient experiences periodic and acute episodes in which proper function of the muscles is impaired and can be crippling. These episodes eventually subside but generally leave behind some residual impairment. MS is a chronic disease whose cause is unknown and remains incurable; its impact can range from mild to severe. There are, however, some promising therapies that have been perfected to help with the symptoms and hopefully retard the disease’s progress. These approaches will be discussed in a subsequent article.

MS has been shown to be particularly prevalent in the northern latitudes; residents of the Pacific Northwest are particularly susceptible. The reason(s) for this phenomenon is poorly understood and is the subject of intense investigation. A possible explanation may relate to the climate and the fact that many of the inhabitants of the Pacific Northwest are from Northern Europe whose people have an increased susceptibility to the disease. In regards to the impact of climate on the prevalence of MS, there has been some evidence that the lack of Vitamin D, whose production in the human body is triggered by sunlight, may play a role.

MS is a disease that is under intense investigation. The hope remains that its cause and eventual cure will be discovered.

Thursday, April 1, 2010

The Crisis in Antibiotic Resistance and One Possible Solution

There is a looming public health crisis in regard to the growing incidences of infectious diseases that have become resistance to the usual repertoire of antibiotics. Insidious examples of this are the troublesome occurrence of Methicillin-resistant Staphylococcus aureus (MRSA), especially in hospital settings, and antibiotic-resistance strains of such communicable diseases as Tuberculosis and Gonorrhea found throughout the United States and other parts of the world.

On account of this problem, there is an urgent need to discover new families of antibiotics that possess novel mechanisms for their action. Promising results have recently come from the laboratory of Dr. John A. Robinson from the Chemistry Department of the University of Zurich in Switzerland. Dr. Robinson and his colleagues have synthesized a new class of antibiotics they refer to as peptidomimetic antibiotics. This class of compounds is based on the naturally occurring antimicrobial peptide (a peptide is a small protein) called protegrin 1 (PG-1).

This group demonstrated that this type of antibiotic was particularly effective against Pseudomonas aeruginosa (PA). This particular organism is ubiquitous and is particularly threatening to those individuals who have a compromised immune system, or suffer from a wound as a result of injury. If these bacteria infect the lungs, kidneys or the urinary tract, the results can be fatal.

These investigators clearly demonstrated that peptdiomimetic antibiotics protects against lethal infections in whole animal studies. Although, the particular antibiotic tested had no appreciable effect on other types of bacteria, it may have use against so-called nosocomial infections - infections that appear as a result of a prolonged stay in hospital - and lung infections in patients suffering from cystic fibrosis, who are especially susceptible to drug-resistant strains of PA.

Monday, March 29, 2010

Ardipithecus ramidus – Newest member of the Human Family

Ardipithecus ramidus – Newest member of the human family
There are a number of traits possessed by humans that set apart members of the species Homo sapiens from all other primates. The most notable are the ability to walk upright, the opposable thumb and the size of the brain that allows higher order thought processes and the ability to communicate through the use of language.

Current evidence suggests that some five to eight million years ago, there lived the common ancestor of both humans and chimpanzees. The discovery of Lucy in 1974 represented the first relatively intact fossil remains of the earliest known hominin - the family that includes humans and our true human ancestors. Lucy lived some 3.2 million years ago, walked upright and had a brain roughly the size of a chimpanzee. The species to which she belonged was given the name Australopithecus afarensis.

In 1994, the relatively intact fossil remains of a hominin that was discovered to have lived 4.4 million was found in Ethiopia. It took a team of investigators some 15 years to excavate the fossil referred to as Ardi, and it was in October of this year that the skeleton was unveiled. Ardi is more primitive than Lucy and has been placed within a species defined as Ardipithecus ramidus. The base of Ardi’s skull is short from front to back and the upper blades of pelvis are shorter and broader than living apes. This lowers the center of gravity and permits balancing on one leg that is an absolute requirement for walking upright.

The sediments in which Ardi was found indicate that these ancient creatures lived on an ancient floodplain, covered with woodlands. Ardi probably coexisted with fig and palm trees, monkeys, kudu antelopes and peafowl.

Although the conclusions reached by the team that found these remains have been met with some skepticism, this discovery is a significant one and takes us closer to a more complete understanding of the evolution of our species on our wondrous planet.

Friday, March 26, 2010

Bisphenol A – Is it a Significant Threat to Human Health?

Plastics are ubiquitous in our daily lives. Chemically, plastics are referred to as polymers – they are made up of repeating subunits or building blocks bonded to each other much like beads on a string. Recently Bisphenol A (BPA) has come under increasing scrutiny by the Environmental Protection Agency (EPA) for its possible harmful effects on human health.

BPA is used to make polycarbonate plastic and epoxy resins for use in digital media, electronic equipment, automobiles, sports safety equipment, reusable food and drink containers, circuit boards composites, paints and adhesives and numerous other products. It terms of scale of production, approximately 2.8 million tons of BPA was produced in 2002. Concern for the safety of this compound has been heightened because the recent finding that plastic caps of infant feeding bottles that have been scratched or cracked can leach BPA into infant formula even in the cold. BPA is so prevalent that it has been estimated that 90% of Americans have it in their urine.

BPA belongs to a class of compounds known as xenoestrogens – foreign man-made substances that mimic estrogen, the female sex hormone. Because of its structural similarity, BPA can bind to tissues in the body that are biologically designed to interact with estrogen. Since estrogen exerts such a wide ranging impact on human body, it would be reasonable to assume that BPA could, therefore, interfere with normal estrogen-related activity and have a deleterious impact on human health.

This hypothesis seems to be supported by extensive scientific data. A 2007 review of the literature determined that low doses of BPA during development exert a significant impact on brain structure, function and concomitant behavior in rats and mice. Furthermore, a study by the Yale School of Medicine conducted in 2008 demonstrated that neurological effects occurred in non-human primates when regularly exposed to doses of BPA that were equal to the EPA-determined maximum safe dose. And most importantly, a major study of the health effects of exposure to BPA, conducted by Iain Lang and his associates, was reported in the prestigious Journal of the American Medical Association (JAMA). The data collected from a study of 1500 participants showed a significant association of exposure with heart disease, diabetes and abnormal liver function. Although these data did not show an unambiguous cause and effect relationship, the preponderance of data from animal studies strongly support such a relationship.

New Insights into Mental Illness

Many residents of the Pacific Northwest are plagued with mental illness. These individuals have long endured the stigma that has been associated with it. Many of the misconceptions surrounding this category of disease come from a lack of understanding as to the root causes of these ailments. Thanks to the remarkable strides made in the area of neurobiology, a much clearer picture is emerging regarding the underlying causes for these mental conditions.

The picture that is currently emerging in regards to a number of mental disorders including major depressive disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) is that there is dysfunction within particular brain circuits. The case regarding major depressive disorder will be discussed in further detail below.

Major depressive disorder impacts 16% of the entire national population – a significant number of individuals. The symptoms of this devastating illness include profound feelings of despair and helplessness. In addition, there is also a host of physical symptoms including loss of appetite, sleep disturbances, constipation and fatigue. Depression has been shown to impact the immune system and, therefore, places the sufferer at additional risk for infectious disease and cancer. Despite its wide-ranging effects, this disease is essentially a brain disorder.

Current evidence clearly implicates an area of the brain referred to as the prefrontal cortex (PFC) within an area called 25 – which functions as a hub for the neuronal circuit that underlies the manifestation of clinical depression. Area 25 got its name from Korbinian Brodmann, a German neurobiologist, in 1909. Dr. Helen Mayberg from Emory University has conclusively demonstrated that this area is overly active in depression, and that when patients are successfully treated, this activity diminishes regardless of the methods employed. Furthermore, area 25 is rich in the substances that transport serotonin, a major neurotransmitter found in the brain. Many anti-depressant medicines react directly with these transporters. A gene responsible for the production of an essential transporter has also been implicated with major depressive disorder – a conclusion that is consistent with the known association of depression with inheritance.

This new scientific understanding of the origins of many of the common mental illnesses will, hopefully, help to shatter the out-dated mystique around mental illness and accelerate the development of new and highly efficacious treatments.

Thursday, March 25, 2010

A Major Breakthrough for Gene Therapy

There are host of diseases that are a direct result of a mutation in a single gene. Examples of this kind of disease are many including sickle cell anemia, severe combined immunodeficiency disease (SCID) and many others. The world famous Nobel prize-winning chemist, Linus Pauling (1901-1994) coined the term Molecular Disease to refer to this type of illness.

In the past, this type of illness has been impervious to the possibility of a cure, since its origin resides in the very makeup of an individual’s heredity as expressed through the genes. Recent advances in molecular biology and gene therapy have demonstrated that this daunting limitation can be effectively breached. SCID is a particularly devastating and ultimately fatal disease in which the affected child has no defense against infections. Through the ground breaking work of Dr. Alessandro Aiuti, ten patients suffering from SCID are still alive. The mutated gene in this condition is the ADA gene. The laboratory of Dr. Aiuti from the San Raffaele Institute for Gene Therapy in Milan. Italy successfully used the following procedure: bone marrow cells from the patients involved were incubated with a specially engineered virus containing the normal ADA gene. These engineered cells were reintroduced into the patients. Positive results were seen almost immediately following treatment. A similar approach has been used in the treatment of a disease characterized by a congenital degeneration of the retina. In this study four of six patients had a notable improvement of vision.

The latest advance has been made with Adrenoleukodystophy (ALD), a disease linked to the X chromosome. This is a severe neurodegenerative disease that leads to destruction of myelin, the outer membrane of nerve cells, in the brain and severe nervous system dysfunction. This disease is caused by a mutation in the ABCD1 gene. The first successful clinical test using gene therapy for ALD has recently been reported by Dr. Nathalie Cartier and his colleagues from the University of Paris-Descartes in Paris, France. The approach used was to take hematopoietic stem cells (HCS) from two young male patients and incubate their cells with a virus that was engineered to carry the normal ABCD1 gene. These modified cells were then reintroduced to the patients. Eventually, blood cells with the normal gene were found distributed throughout each patient’s body. Within 14 to 16 months post treatment, cerebral demyelination was arrested and neurological and cognitive functions remained stable. The patients’ own cells were used in this procedure; this avoids any need for a donor and obviates any concern of possible rejection. This is an extraordinary result and has profound implications for the future of gene therapy in medicine.

Prions - The killer proteins

The agents of disease, pathogens, are known to be either viral or bacterial in origin. It is only relatively recently that proteins have been implicated in disease. In 1976 Daniel Carleton Gajdusek won the Nobel Prize in physiology or medicine for his work on kuru. Kuru is a neurological disease that is extremely prevalent among the Fore people of Papua, New Guinea. The disease spreads in a way that is suggestive of being infectious, yet the victims show no signs of fever or immune response. Dr. Gajdusek won the Nobel Prize in part for the fact that he explained the method of transmission – cannibalism as practiced during funeral rites among the Fore. But the causative agent remained a mystery; treatment of brain tissue with agents that ordinarily kill viruses or bacteria had no effect. It was not until the early 1980s that Stanley Prusiner of the University of California proposed that proteins were the culprits.

His explanation called the Prison hypothesis won him the Nobel Prize. According to this model, the protein culprit is abnormally shaped or folded and that it serves as a model for other proteins in the nervous system to misfold and aggregate forming plaques. Eventually this process causes nerve cells to stop functioning properly, ultimately leading to death.
His explanation has since been proven to be correct. As a matter of fact, other neurological disorders have been shown to be caused by prions, including scrapie, mad cow disease and Creutzfeldt-Jakob disease. A recent spate of publications suggests that an analogous mechanism may be involved in two dreaded illnesses that appear in old age – Alzheimer’s and Parkinson’s disease. These diseases are not contagious, however, as is the case with true prion diseases. What they do seem to share in common is the fact that they spread through the nervous system in a similar way. To support this hypothesis, a team of investigators injected extracts taken from the brains of Alzheimer’s patients into mice with a susceptibility to the disease. Within a few months, the mice developed wide spread plaques. This work was reported in The Journal of Neuroscience in 2000. This finding suggests that there is a substance in the diseased brain that can “seed” plaque formation.

This is an important finding, for if, in fact, diseases like Alzheimer’s or Parkinson’s develop in this manner, than it may be possible to abort the spread of the affected proteins with specific antibodies or small molecules designed to interact with the suspected agents.