Tuesday, December 27, 2011

A New and Promising Approach to the Treatment of Sickle Cell Disease

Sickle Cell Disease (SCD) is a serious genetic ailment that Impacts many individuals.  A patient with sickle cell anemia presents the following symptoms often beginning at 4 months old:

  • Painful episodes that can last hours or days
  • Attacks of abdominal pain
  • Bone pain
  • Breathlessness
  • Delayed growth and puberty
  • Fatigue
  • Fever
  • Jaundice
  • Paleness
  • Rapid heart rate
  • Ulcers on the lower legs (in adolescents and adults).

Other symptoms include:

  • Chest pain
  • Excessive thirst
  • Frequent urination
  • Painful and prolonged erection (priapism - occurs in 10 - 40% of men with the disease)
  • Poor eyesight/blindness
  • Strokes
  • Skin ulcers.

This disease was thought to have a genetic etiology based upon the epidemiological data which showed its prevalence among individuals of African descent (one in twelve African Americans are heterozygous for this trait).  Furthermore, these data also pointed to a recessive trait i.e. both alleles have to possess the altered gene for the symptoms to appear.

The disease presents with a singular characteristic – misshapen red blood cells.  This change in morphology from the normal disc-shaped cell to crescent-shaped is a direct result of the altered tertiary structure of the hemoglobin molecule (referred to as Hemoglobin S).  Normal hemoglobin has a globular - nearly spherical - structure.

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 may be effectively breached.   For examples severe combined immunodeficiency (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.

In addition, a new methodology in the approach to improving the health of individuals with SCD is being developed by Doctor Jian Xu and his colleagues from the Division of Hematology/Oncology at Children's Hospital, Boston.   This discovery is linked to the fact that in humans, there is a switch from a fetal form of hemoglobin (HBF) to the adult form.  It has been previously demonstrated that the persistence of HBF in adults lessens the severity of SCD.  Furthermore the silencing of HBF is under genetic control.

Xu and his team, working with the mouse as the preferred animal model, have shown the loss of a transcription factor – BCL11A – reverses HBF silencing and, therefore, substantially lessens the severity of SCD.  Although there are currently substantial barriers to translating these findings into therapies for this disease, this discovery offers new possibilities for real progress in this regard. 

Sunday, December 18, 2011

Regarding the Future of the Human Species

In my mind, the greatest challenge that faces the species in the 21st century is the issue of climate change.  It will prove to be the essential test as to whether the species is intelligent enough to recognize its culpability in endangering the life of the planet with the detritus of what is referred to as human progress; assume the appropriate responsibility for the consequences of its collective behavior, begin to seriously address the issue with the appropriate remedies in a timely fashion with the future in mind, or continue along its destructive path and suffer the undeniable fate.  If the past and present history of the species in regards to its capacity for stewardship of the planetary environment is any indicator than the real character of the future is sadly predictable.  With the optimism of Desmond Tutu in mind, what we need is a transfiguration on a global scale.  It is my fondest hope that such a monumental and unexpected change in human behavior occurs and radically alters human destiny.

Friday, December 2, 2011

Why Oil?

Once oil was discovered, it was inevitable that it would be used as a ubiquitous source of energy and, as a consequence, help drive the industrialization of the national economy ultimately creating our contemporary technology-based society.  The reason for this resides in the chemistry of oil, for it is a hydrocarbon and is readily combustible producing enough energy to drive the machines that have become a fundamental component of human life.  It is the utilization of machines that essentially transformed human existence and the course of human destiny. 

All of life is carbon-based and if one views life from the perspective of a biological machine, it is possible to see a parallel in that the overwhelming majority of life forms burn another carbon compound, glucose, for energy producing the same byproducts – carbon dioxide and water.

There is another application of oil that has become intrinsically bound up in the modern world and that is the manufacture of plastics and pharmaceuticals.  This is based on a fundamental property of carbon i.e. the intrinsic ability of this element to combine with itself to form long chains that have structural significance in the manufacture of plastics.  Since drugs by their nature interact with biological systems they, by necessity, are also made from carbon.

There are, therefore, some uses of oil that serve a very useful and not necessarily detrimental role for the whole of humanity.  I find it quite improbable that societies will willingly give up their reliance on the role of plastics in modern existence or the beneficial uses of pharmaceuticals in sustaining human health and extending life.  Plastics, of course, can be recycled and reused so that they do not necessarily contribute to toxic landfills or add carbon dioxide to the atmosphere and contribute to climate change.

The use of fossil fuels for energy and for powering automobiles for personal transportation is another matter entirely.   These uses are the overwhelming source of the production of greenhouses gases, and for this reason the curtailment of the use of fossil fuels for capturing energy is of the utmost importance.   Alternative sources of energy must be found and developed; this is an urgent issue.  National governments and global organizations must help mobilize research and development in the field of alternative energy production.  This cannot be done without an educated and enlightened population that appreciates the depth of the problem and demands a concerted effort towards its solution. 

The research that is proceeding in regards to alternative sources of energy such as solar, wind and water does not seem to be motivated by the appropriate sense of urgency that this global crisis requires.  In reality, the combined output of these sources will probably be insufficient to meet the energy needs of the future.  Nuclear fusion may eventually prove to be the final piece in the energy puzzle provided that a breakthrough is made in regards to the issue of the safe containment of the hydrogen fuel source at the extreme temperatures that are required to drive nuclear fusion - a process analogous to the mechanism that is responsible for the immense energy output of our sun.  

In summary, the discovery and use of oil served its purpose in powering the machinery of industrial-based societies, but its continues use as the primary source of energy for human societies on planet earth is unsustainable and must be supplanted by other more benign alternatives.  This, I believe, is the fundamental challenge of the twenty-first century.

Thursday, November 17, 2011

Bacterial Resistance to Antibiotics – How does it Occur?

Although the emergence of bacterial antibiotic resistance has concerned those involved in public health for many years, the mechanism for this resistance is still poorly understood.  The magnitude of this problem is compounded by the global spread of the infectious agents that cause such diseases as gonorrhea and tuberculosis and that have become resistance to a broad spectrum of antibiotics.

Dr. Qiucen Zhang from the Department of Physics at Princeton University in a collaborative effort with others at various institutions has attempted to define the variables and quantify the nature of the development of bacterial immunity to antibiotics.

In previous work, resistant mutations in bacterial populations have been isolated and their genetic makeup successfully analyzed.  However, Zhang and his colleagues sought to understand how such mutations actually occur and spread within a given bacterial population when it is first subjected to antibiotics.

In order to elucidate this process, it was important to simulate the micro-environment that is present in nature – within a host organism, for example.  The candidate organism that was chosen for this study was Escherichia coli, a ubiquitous bacterial species.  A device was constructed for this purpose was designed to mimic a normal bacterial niche.  The antibiotic that was chosen for this study was ciprofloxacin, often used in a clinical setting.  This substance inhibits DNA replication and cell division but does not kill the bacterial cell target.

The findings from these experiments were that resistance of Escherichia coli to ciprofloxacin occurred within a mere ten hours of the introduction of the drug, and with as few as 100 bacteria.  In addition, DNA analysis of the resistant strain showed four unique single-nucleotide polymorphisms (SNPs) that could account for the antibiotic resistance.

These results are of immense importance in that they help elucidate the often rapid appearance of antibiotic resistance with the body of mammals, including humans.  These data may also be of used in improving the understanding of the emergence of drug resistance in patients undergoing cancer chemotherapy.    

Thursday, November 10, 2011

Meteorites and Prebiotic Organic Matter

It has been long understood that in the early history of the earth before the appearance of life, there were present organic substances that were the precursors to the complex compounds that are the essential ingredients for all living things.  These molecular precursors are referred to as prebiotic organic matter.  In addition, the cosmological data has established that the earth along with all the other planetary bodies within our solar system were formed from material expelled from the sun during its formation – the so-called “protoplanetary disk.”

A fundamental question that arises from these known occurrences is the actual origin of prebiotic organic matter.  One of the possible answers to this question is that these materials may have been seeded as a result of collisions of meteorites on the earth’s surface.  This postulate is made even more plausible if one takes into account the fact that in the early history of the planet collisions with meteorites were exceeding common.
Of particular interest is a class of meteorites referred to as the carbonaceous chondrite meteors that are believed to be samples of primitive meteorites that contain the material that was part of the formation of planet earth some 4.6 billion years ago.  These generally consist of insoluble organic matter (IOM) and soluble organic matter ((SOM). 

Dr. Christopher D. K. Herd from the Department of Earth and Atmospheric Sciences at the University of Albert, Canada and his colleagues systematically analyzed the Tagish Lake – in the Southwest region of the Yukon in Canada - meteorite specimens that fell on the frozen lake and were harvested within a few days.  The freshness of the samples effectively ruled out the possibility of contamination from the local environment – an issue that is always of major concern in these types of studies.  The investigative group chose four samples for detailed evaluation. 

Their findings were of extreme interest, for they discovered that the water extracts from these samples were dominated by monocarboxylic acids (MCAs) including formic and acetic acids that play key and ubiquitous roles in the biochemical metabolism of life on the planet.  They isolated eleven different examples of this class of organic compound.  In addition to these, amino acids were also identified.  Amino acids are the basic building blocks from which all proteins are constructed.  The evidence that was accumulated in these studies supports an extraterrestrial origin for these compounds.

This conclusion, if true, is of immense value in understanding the evolution of life on planet earth as well as encouraging speculation as to the possibility of life on other worlds or so-called “exoplanets.”

Thursday, November 3, 2011

Snowpack Declines in North America

The levels of snowpack in the mountains in the Western United States have a substantial impact upon the local natural environment.   This is due to the fact that increased runoff impacts temperature due to the loss of capacity of snow and ice to reflect heat back into the atmosphere – the so-called "albedo feedback."  This in turn influences a wide range of ecosystem processes.

It has been reported that snowpack in the Western United States has experienced a noticeable decline in recent decades.  Weather projections predict that this decline will continue to increase in the twenty-first century.  In order to quantify these changes Dr. Gregory T. Pederson and his colleagues from the U.S Geological Survey (USGS) at the Northern Rocky Mountain Science Center in Bozeman, Montana have developed snowpack reconstructions for the headwaters of the Columbia, Missouri and Colorado Rivers.  These reconstructions examine levels of snowpack that span from five hundred to a thousand years.  These findings are based upon an "extensive network of tree-ring sites," and elucidate patterns of water management and snow accumulations over extended periods of time.  The study of tree-rings has long been utilized to reconstruct patterns in regard to precipitation, drought and temperature.  Previous studies have clearly demonstrated that the amount of water available to trees during their growing cycle is largely dependent on the amount of snowpack that accumulated during prior winter seasons.

As a result of the data accumulated during this investigation, the author concluded that, "Over the past millennium, late 20th century snowpack reductions are almost unprecedented in magnitude across the northern Rocky Mountains."   This is a matter of serious concern in that it may well be a harbinger of future conditions of drought and establishes further relationships between the accumulation of greenhouse gases in the atmosphere, temperature and the global water cycle. 

Monday, October 24, 2011

The Role of the Human Immune System in Obesity

Human immunity has developed, over evolutionary time, into a complex system that impacts a great deal of human biology.  It is for this reason that it often a key player in the cause of many ailments.  It has recently been implicated in human obesity, insulin resistance and type 2 diabetes – these three conditions constitute the so-called metabolic syndrome.  Immune responses are potent reactions to bodily insults and, therefore, must be tightly regulated.  These responses are activated and suppressed by a large family of small regulatory proteins referred to as interleukins.

The white blood cells (WBC) that are found circulating in human blood are, in fact, comprised of a complex mixture of cell types that all perform unique immunological roles.  Eosinophils are a particular WBC type that is classically involved in combating helminth (parasitic worm) infections and allergies.  In addition, macrophages are a subtype of WBC that is characterized by its large size and ability to respond to a wide range of human infections. 

Extensive studies of obesity using animal models led by Dr. Davina Wu at the Howard Hughes Medical Institute at the University of California in San Francisco have implicated Eosinophils and a particular subtype of macrophage referred to as alternatively activated macrophages (AAMs) in the maintenance of glucose balance in fat (Adipose) tissue.  It appears that the role of eosinophils in this process involves the secretion of a type of Interleukin called Interleukin-4 (IL-4).  When eosinophils are not present in adipose tissue, the level of glucose is no longer subject to regulation.

Doctor Wu and colleagues, working with the mouse model, have shown that the macrophages resident in the adipose tissue of obese subjects are actively involved in an inflammatory response while the macrophages in the adipose tissue of lean mice are not.

This study reinforces the established relationship between metabolism and immunity.  Furthermore, these findings support the connection between obesity and the enrichment of those genes involved in inflammatory and immune responses in humans – a strong indication of the health dangers posed by obesity. 

Saturday, October 1, 2011

A New Approach to Immunization Against the Flu Virus

Influenza – the flu – continues to infect millions of individuals each year and cause thousands of deaths.  In addition, the economic losses associated with this illness are considerable.  Although immunizations against this virus exist, their effectiveness is diminished by the fact that this virus mutates readily and produces a variety of strains that evade the immunization strategy.  These vaccines provide only limited protection against these strains.  In order to more fully understand the nature of the global health problems posed by the influenza virus, we will examine the nature of its action.


The influenza virus is essentially spherical in shape.  Its outer layer is, in fact, a lipid membrane that it has acquired from the host cell that it has previously infected.  Embedded in this outer layer are proteins that are characteristic of the strain of the virus.  It is these proteins that are potential targets for antibodies used in various vaccine regimens.   The virus – like all viruses – is essentially inert outside of living cells.  Once it effectively infects a target tissue – usually in the respiratory system –the virus delivers the infective material directly into the target cell.  The influenza virus belongs to a class of viruses called Ribonucleic acid (RNA) viruses; because, RNA is the infective agent.  Once the viral RNA enters the cell, it commandeers the cell machinery to produce more viruses and eventually kill the cell.  The dead cell releases its contents including many copies of the virus and each of these goes on to infect neighboring cells.

The strategy behind the development of vaccines against this virus is to discover an identifying protein on the virus' surface that persists (highly conserved) over a wide variety of subtypes.  This has proved to be a very elusive quest.   However, there has been a recent discovery of what is referred to as VH1-69 antibodies that knock out almost all type A Group 1 viruses.  This is an exciting development in its own right, since it is the type A virus that represents the most virulent strain.

One of the major surface proteins on the Influenza virus is Hemagglutinin (HA).   Antibodies that target HA, for example, bind with a unique part of the protein referred to as an antigenic determinant or epitope.  Doctor Damian C. Ekiert and his colleagues from the Department of Molecular Biology at the Scripps Research Institute in LaJolla California have isolated and characterized a human monoclonal antibody called CR8020 that has been shown to have broad reactivity to most group Type A 2 viruses.  It seems quite possible that a cocktail containing these two antibodies -  VH1-69  and CR8020 - may produce an effective universal flu vaccine.  This would be an exciting development from the global public health perspective.

Saturday, September 10, 2011

A Potentially New Therapy for Chagas Disease, a Parasitic Infection

Chagas disease is the result of an infection caused by the parasite, Trypanosoma cruzi.  The vector for this parasite is the so-called assassin bug or kissing bug that targets its hosts for blood, usually at night.  The parasite is usually transmitted through the insect's feces.  Millions of people in Latin America carry this parasite.  In addition, the United States and Spain have reported the highest incidences of this disease outside of Latin America.  Furthermore, the World Health Organization (WTO) has estimated that ten million people worldwide are infected with this parasite. 


The symptoms are somewhat benign at the early stages of infection.  Unfortunately, the parasite persists within the body for years or decades and can ultimately lead to serious damage to the heart, often resulting in death.


The current drugs available to treat this disease – nifurtimox and benznidazole - are outdated and of little value.  In addition to their serious side effects, their efficacy depends upon a 60 to 90 day course of treatment – this requirement makes their use highly impractical. 


In regards to the etiology of the disease, there is a crucial enzyme, cruzain, that is a necessary component in the life cycle of Trypanosoma cruzi.  Cruzain belongs to a class of enzymes referred to as proteases – enzymes that catalyze the degradation of proteins.  Doctor James McKerrow, a biochemist at the University of California, was in search of a suitable inhibitor of this enzyme.  He enlisted the help of his colleague Doctor Jim Palmer, a chemist who had synthesized a number of protease inhibitors when he was at Khepri Pharmaceuticals in San Francisco.  In response to this request, Palmer synthesized a potent version of an inhibitor that effectively led to the death of the parasites grown in the laboratory.


This is an exciting development that has captured the attention of the Food and Drug Administration (FDA) that has approved a phase I safety trial of the compound referred to as K777.

Friday, July 29, 2011

The Waste of Human Potential

Every day, within the human world, there is the regrettable and apparently inexorable waste of human potential.  Every day, countless numbers of individuals die from the starvation not because there is a scarcity of food, but because they do not have access to the abundance that does exist.  Everyday large numbers of humans die from diseases and conditions that are preventable, treatable and, in some cases, curable, only because they lack the resources to gain access to the wondrous medical advances that exist in the larger world.  Every day, tens of millions of children are denied access to meaningful educational resources; the net effect of this reality is that these children will never realize the wondrous gifts that they possess.  Instead, they will be relegated to a future in which their primary behavior will be directed towards survival in a world that apparently rejects their possible contributions to the larger society.  Every day, millions upon millions of human beings are without a place of shelter to which they can retreat from the relentless onslaught of their daily lives.  Every day, the natural environment worsens as human societies continue to pursue reckless and short-sided policies that suggest a grim future for the species.

Contemporary humans are living a tragedy that is wholly preventable.  There is no legitimate reason why any individual cannot have access to all the necessities required for a meaningful life.  There is no reasonable explanation for the barbaric conditions in which so many live.  There is no rational discourse that can abide the miserable fate of so many of the human kind other than the belief that only a few of us are deserving and the rest are the castoffs in the pursuit of wealth and power.

The pathetic aspect of the human condition is that we can be the architects of a very different world – a world that can not only sustain human life, but also enrich the lives of all of us, everywhere. 

Wednesday, July 27, 2011

An Entirely New Breed of Bacteria

It has been well established that the fundamental building blocks for life are proteins, fats, carbohydrates and nucleic acids (DNA and RNA).  The elements that are required to assemble these constituents are carbon, hydrogen, nitrogen, oxygen, sulfur and phosphorus.  In addition there are trace metallic elements that are required for metabolic activity through the agency of enzymes, oxygen transport and other biological functions; examples of these are iron, zinc and molybdenum.  These are usually present in trace amounts and function as necessary co-factors in a host of enzyme activities.  There have been many reported instances of substitutions in regard to these co-factors; examples include the substitution of tungsten for molybdenum and cadmium for zinc.  There has also been reported the substitution of copper for iron as an oxygen carrier in some arthropods and mollusks.
Doctor Felisa Wolfe-Simon and her colleagues at the NASA Astrobiology Institute have recently made quite an astounding discovery.  They discovered a bacterium, strain GFAJ-1, isolated from Mono Lake in California  that is capable of growing in the presence of Arsenic (As).  Furthermore, they were able to show in the laboratory that As was incorporated into the structure of nucleic acids and proteins. As is a chemical analog of phosphorus (P); it resides directly below P on the periodic table.  Its similarity to P in terms of its chemical properties explains why it is a deadly poison for complex multi-cellular organisms such as humans.
This is quite a significant discovery; it dramatizes just how adaptable living organisms can be.  Furthermore, it may broaden our perspective regarding the possibility of extra-terrestrial life.

Tuesday, July 12, 2011

New Hope for Those Suffering from Type 1 Diabetes

Unlike adult-onset diabetes, type 1 diabetes occurs early in life and is considered to be an autoimmune disease where the body's own immune system becomes mobilized against the insulin-producing cells that reside in the Islets of Langerhans in the pancreas.  This is an extremely devastating illness, since the resulting dramatic loss of insulin results in high levels of glucose in the blood – a condition known as hyperglycemia.  Although insulin treatments can control this condition, excess glucose circulating in the blood system reacts with tissues throughout the body and leads to devastating side effects over time including blindness, kidney dysfunction, heart disease and the enhanced likelihood of amputations on account of poor circulation.


There is, however, encouraging news on the horizon.  Results from a clinical trial conducted by Doctor Denise Faustman and her colleagues from the Immunology Laboratory at Massachusetts General Hospital indicate that a medication, bacillus Calmette-Guerin (BCG) used routinely as part of the treatment regimen for bladder cancer and as vaccination against tuberculosis could significantly improve the treatment for type 1 diabetes.  BCG is produced from a strain of the weakened live bovine tuberculosis bacillus.


In regards to the mode of action of this medication, it appears that it targets the immunoreactive cells responsible for the death of insulin-producing cells of the pancreas.  It seems that BCG stimulates the production of tumor necrosis factor produced used by certain cells in the immune system's repertoire to kill abnormal immune cells that invade healthy tissue.   In addition, those patients treated with high doses of BCG showed evidence of insulin production - a significant finding.  Faustman indicated that ,"Not only did we observe and measure the death of these self-targeting immune cells, but we also saw evidence of restoration of insulin production even in patients who've had type 1 diabetes for more than a decade."

Thursday, June 30, 2011

Climate Change Mirrors an Earlier Era in Planetary History

Doctor Lee R. Kump, a professor of geosciences at Pennsylvania State University, has illustrated some disturbing parallels between the changes in global climate of today with a well-studied era in the planet's past.  At that time, about fifty-six million years ago, temperatures worldwide rose some five degrees Celsius in the course of a few thousand years.  This period is referred to as the Paleocene-Eocene Thermal Maximum (PETM).  At that time in the planet's history the huge land mass known as Pangaea was in the final phase of breaking up into the current day continents.  This process led to the formation of the north-eastern Atlantic Ocean.  As a result, enormous volumes of molten rock were released producing intense heat.  Carbon-enriched sediments that were close to the surface were subsequently burned releasing greenhouse gases into the atmosphere, especially carbon dioxide and methane.   In addition, it is postulated that the concomitant warming of the ocean seabed led to the release of vast quantities of frozen methane.
The cumulative effects of these changes were the following:
  •          Marked increase in global temperatures (as noted above)
  •          Climate zones shifted towards the poles both on land and in the ocean propelling the migration of living things to accommodate this change
  •          Within the ocean depths, acidity increased and the supply of oxygen diminished killing of many organisms there.
These changes are striking similar to what is being reported currently.  In regard to the status of the oceans, an international workshop, sponsored by the International Programme on the State of the Ocean (IPSO), has recently met in Oxford, UK.  Their goal was to study the impact of human-made stressors including warming, acidification and overfishing on the overall health of the ocean.  The conclusions this international group of experts reached are quite alarming.  In essence, they have concluded that the stresses imposed on the world's oceans as a direct result of human activity may lead to "globally significant marine extinction."

In addition, Doctor Kump has determined from his studies that, in fact, "global temperature today is rising much more quickly than it did during PETM."  If the current rate of increase in atmospheric greenhouse gases continues unabated, it is estimated that global temperature will increase by eight degrees Celsius by the year 2400.  This kind of increase would profoundly and dramatically change the nature of life on the planet and drastically impact the possibility of continued human survival.  This kind of change can only be averted by a global commitment to dramatic changes in human behavior and expectations.  It should also be noted that it took some 200,000 years for the planet to cool down during PETM.  

Friday, June 17, 2011

Antibiotic Resistance – A Cause for Global Concern

Penicillin was discovered and developed as the first widely-used anti-microbial (antibiotic) agent in 1928.   Ever since that time, bacteria have developed resistance to a wide range of antibiotics as they have been introduced.  This capability can be explained based on two important properties of bacteria.  These organisms divide approximately every twenty minutes; therefore, through the course of a single twenty-four hour day, seventy-two generations have been produced.  If bacteria are in an environment permeated with antibiotic some of the progeny may develop a resistance due to a spontaneous mutation in their genetic material (DNA).  If this should happen, all the susceptible bacteria will die off leaving behind those that are resistant.  This process can be regarded as natural selection.  Since resistance is conferred by a change in the genetic makeup of the organism, resistance can then be passed on to all the progeny.  There has always been a potential public health risk in regard to this ability of microorganisms to become resistant to these agents.


Bacteria are classified into two distinct groups – gram-negative and gram-positive.  This classification was created based on their ability or inability to take up a particular stain.  A well known example of gram-positive bacteria that is disease producing (pathogenic) is Staphylococcus aureus that is of a particular concern in a hospital setting.  An antibiotic that has been traditionally used to combat this kind of infection is methicillin.  As a result of its universal application, a highly resistance form of this bacteria referred to as methicillin resistant Staphylococcus aureus (MRSA) has arisen.  This has created a serious public health dilemma.


From a public health perspective, a far more problematic issue is antibiotic resistance among gram-negative bacteria.  These bacteria possess a double cell wall that makes them more challenging to eliminate.  An example of a pernicious variety of this kind of bacteria is Klebsiella pneumoniae; this strain is particularly prevalent in hospitalized patients and is a major cause of pneumonia and bloodstream infections (sepsis).  The antibiotics that have been found to be effective against gram-negative bacteria are referred to as the carbapenems.  As one would suspect, Klebsiella has now been shown to possess resistant to the action of carbapenems.


Doctor Timothy Walsh and his colleagues from the Cardiff University, United Kingdom have examined the nature of this resistance and have found that the resistant strain produces an enzyme (NDM-1) that effectively inactivates carbapenems.  This is particularly disturbing since gram negative bacteria, Klebsiella as an example, also possess the capacity to transfer antibiotic resistance to other kinds of bacteria including the ubiquitous Escherichia coli that normally inhabits the large intestines of most mammals.


Given the seriousness of this issue, it is considerably disturbing that there are no new kinds of antibiotics against gram-negative bacteria currently being developed.  This reality holds an ominous prospect for the future in regards to global public health.  

Tuesday, June 7, 2011

Rheumatoid Arthritis – A Possible New Therapy

Rheumatoid arthritis (RA) is a chronic and debilitating illness.  It can strike at any age and seems to be more prevalent in women than men.  Although the specific etiology (cause) of RA is unknown it is categorized as an auto-immune disease – the body's immune system seems to mistakenly recognize normal tissue as foreign and attack it.  Other examples of autoimmune diseases are multiple sclerosis (MS) and Systemic lupus erythematosus (lupus).

The target for the autoimmune reaction in RA is primarily the joints on both sides of the body -wrists, fingers, knees, feet, etc.  The extent of the resulting disability can vary widely depending on other factors related to health.

In order to effectively treat RA, the underlying mechanism that leads to the disease needs to be better understood.  Recent evidence has implicated the so-called tumor necrosis factor α (TNFα) as a major component in the development of this illness.  TNFα is found on the cell surface of immune cells.  TNFα is a member of a group of substances referred to as cytokines.  Cytokines are small protein molecules that are secreted by both the nervous and immune systems.   They have been found to play critical roles in the modulation of the immune system.


Dr. Hao Wu and his colleagues from the Department of Biochemistry at the Weill Cornell Medical College in New York City have shown the disease-producing role of this substance using mouse models of inflammatory arthritis.  Furthermore, this investigative group has demonstrated that Progranulin (PGRN) slows the progression of arthritis in the mouse.  Progranulin is a naturally occurring growth factor for human fibroblasts – cells responsible for the production of collagen, an integral component of the body's connective tissue.  Progranulin seems to exert this inhibitory effect by binding to the receptor that normally binds TNFα, thereby inhibiting its role in the autoimmune process that results in RA.


These findings shed significant light on the immune process.  These data may ultimately contribute towards the treatment of this intractable disease.

Tuesday, May 24, 2011

Global Changes in Wind Speed and Wind Height

The changes precipitated by the accumulation of greenhouse gases within the global environment are not limited to change in temperature, but are, in fact, many and diverse.  The overarching range of effects that are a direct result of increased concentrations of greenhouse gases is referred to as climate change.  It appears that certain changes in the world's oceans are directly related to climate change.  We have already examined some of these influences including the rise in temperature and the increasing acidity of the world's oceans. 

In a recent report from the laboratory of Dr. I.R. Young and his colleagues from the Swinburne University of Technology at Melbourne, Victoria, Australia, it has been established that there is a trend towards increases in oceanic wind speed and wave height.  These findings are based on satellite-derived data using a variety of measuring devices including altimeters, sophisticated radar equipment, etc.  The advantage of using this type of instrumentation is that the scope of investigation is global in scale.

Oceanic wind speed and wave height are involved in the maintenance of the flow of energy from the atmosphere to the ocean and are involved in upper-ocean mixing.  In the analysis of the data, Young and his associates used a database that contained information collected over a twenty-three year interim.  The authors of this study caution that on account of the relatively brief interval of time encompassed by these data, they cannot determine if this trend will continue to increase or accelerate into the future.

On account of the importance of these changes in terms of their possible impact on the global climate system, it would be judicious to extend the lifetime of this kind of study into the future.

Wednesday, May 11, 2011

The Problem of Weight Control

It has been an oft-stated observation that obesity has become a major public health issue in the United States.  It is widely accepted that the reasons for this problem are multi-faceted, but a high fat diet together with insufficient exercise probably contributes significantly to this issue.  Since this problem has reached national attention, there are increased efforts on the part of scientists to more fully understand the biological processes that underlie weight control.

Ghrelin is a peptide – a peptide is a small protein – hormone found in the stomach that is known to stimulate weight gain in vertebrates.  Furthermore, it has been established that an enzyme, ghrelin-O-acyltransferase (GOAT) is necessary to activate ghrelin.  Doctor Brad P. Barnett and his colleagues from the Department of Pharmacology and Molecular Sciences at the John Hopkins University School of Medicine in Baltimore, Maryland have studied the process of ghrelin-mediated weight control in considerable detail using the mouse animal model.

Doctor Barnett and his team have successfully synthesized a peptide, GO-CoA-Tat, that is similar in structure to ghrelin and binds to GOAT; the result of this binding is the inhibition of the activity of the enzyme GOAT.  When mice were treated with this synthetic peptide, they became more tolerant of glucose and weight gain actually diminished.

This is an important finding for a number of reasons.  It helps elucidate the metabolic processes involved in weight control, and this approach may prove to be of therapeutic value, especially to those individuals whose obesity is difficult to treat by any other means.

Thursday, April 28, 2011

Patent Ductus Arteriosis – An abnormal Condition that can Occur in Newborns

The fetus does not depend on its lungs to deliver oxygen to the growing organism in the uterus; it derives its oxygen and nutrition through the mother's placenta.  Before birth, a blood vessel called the ductus arteriosis (DA) allows blood to circumvent the nonfunctional fetal lungs by connecting the pulmonary artery (that transports blood to the lungs) with the aorta that sends blood throughout the body.  This is a temporary measure and, normally, this vessel closes a day or two following birth so that the lungs may begin normal function.  If this vessel does not close, there is abnormal blood circulation between the heart and lungs.  The resulting condition is called patent ductus arteriosis (PDA).  Infants with this condition exhibit certain characteristic symptoms including, fast breathing, poor eating habits, shortness of breath, poor growth and heart murmur.

PDA is often found in premature infants and those individuals born with neonatal respiratory distress syndrome as well as babies with congenital disorders such as Down's syndrome and mothers who contracted German measles during pregnancy.

Studying newborn mice, Doctor Katrin Echtler and his colleagues from Munich discovered that circulating platelets (specialized cells that play an essential  role in blood clotting) were involved in the normal closing of the DA, and that if platelet production was disrupted, the DA failed to close completely.   Their findings were reported in the Journal of Natural Medicine.  This could prove to be an important finding with possible direct application to infants susceptible to PDA. 

Friday, April 22, 2011

Chemical Intervention in the Brain’s Natural Response to Stress

The human brain has a complex and reliable response to stressful and life threatening situations.  This mechanism, however, can have untoward consequences for the organism if it is triggered too frequently.  In contemporary living, humans are constantly exposed to stressors that engage this system.  In order to fully understand this process, the nature of the brain's natural "alarm system" is more fully described below.

When faced with what the brain regards as a dangerous situation, a well orchestrated sequence of chemical events is set in motion that can lead ultimately to a "flight or fight" response.  The chain of events begins when the brain signals the hypothalamus, situated deep within the brain, to secrete corticotrophin-releasing hormone (CRH) that signals the nearby pituitary gland to subsequently release adrenocorticotropin hormone (ACTH) into the bloodstream.  ACTH binds to specific receptors on the adrenal glands, located near the kidneys.  This binding triggers a cascade of chemical events within the cells of the adrenal gland that ultimately produce cortisol that is released into the bloodstream.  Cortisol is a hormone that elicits a wide range of responses throughout the body that heightens the organism's ability to respond to challenging situations.  But the persistent release of this hormone can result in lasting damage.

In order to mitigate the potency of this mechanism, the body has countermeasures at its disposal.  One of these, Neuropeptide Y dampens the effects of CRH in various regions of the brain.  Another is dehydoepiandosterone (DHEA) that counteracts the role of the hormone cortisol.    It is believed that certain drugs and psychotherapy might be effective in stimulating the release of these natural agents.  This ability to cope with stress is referred to as resilience.  From the above description, it becomes quite evident that resilience is important in the maintenance of good health.

 in H


Sunday, April 10, 2011

Continued loss of Greenland and Antarctic Ice Sheets

Dr. Rignot and his colleagues from the University of California, Urvine have been measuring changes in the mass of the land-based ice sheets in Greenland and the Antarctic.  They have reported their findings in the scientific publication Nature Geoscience.

The current understanding of the process of climate warming in Greenland and the Antarctic suggests that snowfall may increase in the continents' interiors and, at the same time, accelerate melting on the coasts on account of the warmer air and ocean temperatures.  To further elucidate this mechanism, the team utilized highly sophisticated satellite radar observations between the years 1992 and 2006 covering 85% of Greenland's and Antarctica's coastlines to estimate the total mass movement of melt water into the ocean. 

Collecting this kind of information was once an extremely daunting task due to limitations in the ability to measure such intricate changes.  The technological advances over the past decades, however, have made it possible to measure trends on a monthly basis.  The results of such continuous observations demonstrate that the rate of the combined loss of the ice sheet has indeed increased and accelerated over the last eighteen years by a total of 36.3 Gigatons (Gt) per year.  A Gt is equivalent to 1 billion tons.   This rate is some three times faster than rate of ice melting in mountain glaciers and at the polar ice caps.  Should this rate of loss of land-bound ice continue unabated, it would prove to be the largest contributor to the ineluctable rise in the sea level by the end of this century.  This is not taking into account the distinct possibility that the rate of increase in atmospheric greenhouse gases as a result of human activity will increase over the coming decades.  According to Dr. Rignot, "Changes in glacier flow therefore have a significant, if not dominant impact on ice sheet mass balance."

This is a significant and troubling finding that adds yet another dimension to the disturbing prospects posed by the ever escalating concentration of greenhouse gases in the earth's environment.  Hopefully, the human community will use these kinds of data to implement policies that will ensure a tangible decrease in the actual use of fossil fuels to propel national economies.

Sunday, March 27, 2011

Cancers Caused by Infectious Agents

We do not generally regard cancer as being contagious.  Although this is generally t rue, there are a growing number of cancers that have been shown to be caused by contagious agents, especially by specific viruses.  In the table below, the kinds of cancers caused by such agents are shown along with the microorganism implicated and their prevalence by location.


Causative Agent

Stomach (Gastric) Cancer

H. Pylori - Bacterium

Cervical Cancer

Human Papilloma Virus (HPV)

T-Cell Leukemia

HTLV-1 – related to the AIDS virus

Burkitt's Lymphoma

Epstein Barr Virus (EBV)

Kaposi's Sarcoma

HTLV-3 – AIDS Virus

Primary  Liver Cancer

Hepatitis B Virus (HBV)


In regards to the data listed in the table above, there is additional information associated with them:

  •          H.Pylori is a highly specialized and fairly ubiquitous bacterium that can survive in the harsh acidic environment of the stomach; it is found in the mucus layer on the inside of the stomach within those individuals who are infected.  For this reason, it is particularly difficult to treat with antibiotics.  It is found in about 2/3 of the world's population.  It has also been implicated in the onset of chronic gastritis and peptic ulcers.
  •          HPV has recently been implicated as the causative agent for cervical cancer.  Cervical Cancer is prevalent in sexually active women.  A vaccine against this virus has recently been developed.  It has been shown to be highly effective in preventing the onset of this cancer in young women. 
  •          EBV, the virus that causes Burkitt's lymphoma found predominantly in Africa, is the same virus that causes mononucleosis in individuals in the West.  The reason for this distinct difference in disease outcomes is poorly understood, but a genetic basis for this difference is likely.
  •          The AIDS virus is not directly responsible for the onset of Kaposi's sarcoma.  The disease is manifested in AIDS patients on account of their highly suppressed immune system due to infection with the AIDS virus that make AIDS patients especially susceptible to this cancer.
  •          Once an individual is infected with HBV as a result of close human contact with an infected individual, the virus can infect the liver without any noticeable symptoms.  This can be the case for many years before the onset of Liver cancer.   HBV is believed to account for 80% of primary liver cancer (cancer that originates in the liver).  It is a deadly cancer.  Fortunately, there is a vaccine against HBV infection, but there is currently no vaccine to prevent infection by the Hepatitis C Virus (HCV) that is also known to cause primary liver cancer. 

Monday, March 14, 2011

Disease-in-a-Dish – Another Application of Stem Cell Research

Stem cells have the capacity to be transformed into any specialized body cells under the right conditions.  This may seem very surprising, but there is an explanation that has at its roots in the nature of the genetic structure of living cells.  All cells in the human body, regardless of their structure and function, have the identical set of genes (genome).  If the genes determine the structure and function of cells, what, therefore, establishes the various unique and diverse tissue cell types such as liver, kidney, skin, etc.  The answer lies in what genes are expressed, turned on and what genes are not expressed, turned off.  The process of selectively turning genes on or off to produce specialized cell types is referred to as differentiation.  Stem cells are pluripotent – they are capable of becoming any specialized cell type under the appropriate conditions.

A considerable controversy erupted over the use of stem cells due to the fact that the source of these cells was from human embryos – so-called embryonic stem cells.  However, a new class of stem cells has been developed that are derived from the use of ordinary tissue cells treated with a cocktail of specific initializing factors that transform these cells to stem cells, so-called induced pluripotent stem cells (iPS) that have been shown to exhibit the same capacity as embryo-derived cells.

The following is a description of a direct application that utilizes iPS in a very interesting and potentially useful way.  Doctor K. Eggan and his colleagues from the Harvard Stem Cell Institute (HSCI) collected skin cells from two patients suffering from amyotrophic lateral sclerosis (ALS).  ALS is a degenerative disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement also known as Lou Gehrig's disease.  These fibroblast cells were subsequently grown in culture and treated with the appropriate regulator genes to reprogram the cells to become iPS cells and thereby pluripotent  in behavior.  These iPS cells tend to clump into what is referred to as "embryoid bodies" and to these clumps were added retinoic acid and a compound that is known to accelerate cell division.  The result of the addition of these added factors was to successfully transform these embryoid bodies into motor neurons.

Since these newly derived nerve cells originated from patients with ALS, they retain all of the genetic properties and characteristics of the disease.  This affords an excellent opportunity to test these cells with drugs that may have potential therapeutic value for ALS patients. 

This  approach as outlined above is referred to as "disease-in-a-dish" and is an expansion of the pioneering efforts of Doctor Yamanaka from Japan.   It offers great promise in the study of such intractable diseases as ALS.

Wednesday, February 23, 2011

The Biology of Obesity

Obesity in the United States has reached staggering proportions where 34% of the population is considered to be obese. The measure of obesity is the so-called “body mass index (BMI) that represents the ratio between a person’s weight in pounds multiplied by 703 (a constant) over the height in inches taken to the second power – Weight (in pounds) X 703/ (height in inches) 2. For example an individual weighing 190 pounds and with a height of 66 inches would have a BMI of (190 * 703)/ (66 inches) 2 which is equal to 30.6. A BMI greater than 30 is defined as obese and a value of over 25 is considered overweight.

The BMI was originally developed by the Belgium statistician Adolphe Quetelet (1796-1874). It is important to note that this value does not measure body fat directly, but it is a useful indicator of obesity that is recognized throughout the world.

There are many factors that contribute to obesity in the American culture. This is, however, beyond the scope of this overview. We will examine, instead, what is currently understood regarding the biology of obesity. Current understanding seems to point to three different systems of the human body that contribute to obesity – namely, the nervous system –the brain, metabolism and the genetics. We will examine these in turn.

It has long been known that the areas of the brain including the hypothalamus and the brain stem are involved in regulating the feelings of hunger and fullness. In addition, current data provided by functional magnetic resonance imaging (FMRI) that allows an investigator to visualize metabolically active parts of the human brain have also implicated the so-called pleasure reward centers of the limbic system and the prefrontal cortex. It seems that overeating, in effect, mimics drug addiction. This understanding may eventually prove useful in the treatment of obesity.

It seems that some adult men and women have retained stores of brown fat from childhood. Unlike white fat, brown fat is associated with leanness and its main function seems to be the generation of heat; whereas, white fat is involved primarily in storing energy. In some ways brown fat seems to be closely related to muscle. It remains to be seen what the factors are that predispose certain individuals to retain brown fat.

Variations in twenty separate genes have been implicated in regards to obesity; however, their cumulative contribution would be too small to account for the marked prevalence of obesity in the general population. This does not preclude the contribution of environmental factors in activating or suppressing certain genes and contributing to obesity in this way. Such genetic switches have been discovered in mice, suggesting that analogous mechanisms operate in humans.

Understanding the biology of obesity is an essential step in determining the best ways to treat this growing epidemic that has become strongly associated with modern life and culture.

Wednesday, February 16, 2011

The Negative Impact of Loneliness on Human Health

Loneliness is a common experience in human life.  It may arise from the ordinary vicissitudes of living.  Loneliness, on occasion, confronts all individuals in all walks of life and at all stages of life.  It is a quite normal and natural phenomenon. 

However, a condition of chronic loneliness has been shown to have more serious implications.  John Cacioppo, a social psychologist from the University of Chicago, has been engaged in protracted studies regarding the biological effects of a chronic state of aloneness.  As a result of his numerous investigations, he, with the help of his collaborators, has discovered changes that occur in the cardiovascular, immune and nervous systems in chronically lonely individuals.  In fact, it has been well established that individuals suffering loneliness have increased mortality.

Cacioppo has been involved in the study of the human brain's role in social behavior and is, in fact, credited with being a founder of the discipline of social neuroscience.   As a result of his extensive studies into loneliness, he has come up with some very important findings.

It is the perception of loneliness that seems to be more important than the number of social contacts a person may have.  This perception has definitive physiological impacts that adversely affect health.  It seems that lonely people have an activated sympathetic nervous system; this system is involved with the flight or fight response.  The neuro-transmitters that are produced as a result of this response, epinephrine and cortisol, lead to the constricting of blood vessels that increase blood pressure and put added stress on the heart.  In addition, the subjective feeling of loneliness impacts the immune system, resulting in an increase in the inflammatory response – implicated in heart disease – and a decrease in the capability of the body to fight viral infections.   It has also been reported that the area of the brain, the ventral striatum, implicated in the brain's reward circuitry has been shown to have decreased activity in lonely people as compared to "normal" controls.  Some genetic susceptibility to this state of mind has also been shown.

These data strongly suggest that loneliness has an adverse impact on the quality of life and the general health of those who suffer from it.  It is somewhat troubling that modern life seems to make individuals even lonelier.  The current estimate – as compiled by the U.S.  Census Bureau - is that 29% of the population lives alone; this represents a 30% increase from 1980.

Monday, February 7, 2011

Global Impact of the Rising Sea

There are many complex and interrelated facets to the consequences that result from the increasing level of Carbon Dioxide (CO2) in the earth’s atmosphere. A common misconception is that the apparent increases in the severity of winter in many parts of the United States refute the urgent need to introduce public policy that would seriously control CO2 emissions. Quite to the contrary, dramatic changes in climate that are evidenced throughout the world reinforce the serious nature of the impact of the accelerated release of green house gases into the atmosphere on global climate.

One of the more disturbing consequences of climate change is the potential for a significant rise in the sea level. Of particular interest are the consequences an increase in the sea level would have on the inhabitants of the Mekong Delta in Vietnam. This area is inhabited by 18 million people - a number that represents 22 percent of the entire Vietnamese population and accounts for 40 percent of the country’s cultivated land. In this fertile region, food production accounts for more than half the rice, 60% of the fish and shrimp and 80% of the fruit crop for the entire nation.

This area is especially vulnerable to sea level rise. Periodic flooding has played a significant role in the life of the peoples of the Mekong Delta. As a matter of fact, flood depths from a half a meter to three meters represent what is considered to be within the normal range. Such a level of flooding is referred to “nice floods” by those living in the area. However, more severe flooding can have a dramatic impact on the ability of the residents to cope.

In fact, both the frequency and magnitude of the flooding that exceeds four meters have increased. As a consequence, Individuals and families from this region are making the decision to seek another livelihood, preferably in the cities.

Using computer modeling, it has been estimated that one meter rise in sea level would impact seven million people living on the delta and a two meter rise would adversely affect fourteen million people – 50 percent of the delta population. Although current models for sea level rise do not anticipate such dramatic increases, unforeseen possibilities such as the accelerated melting of land-locked on Greenland and West Antarctic could dramatically change these predictions.

Given this information, it would be advisable for governments throughout the world to formulate policies with the purpose of curtailing the outpouring of CO2 into the atmosphere.

Wednesday, January 5, 2011

Asymptomatic HIV Positive Individuals – How are they different?

AIDS is a horrific disease characterized by a severely compromised immune system. Without a competent immune system, the body is unable to combat infectious diseases and non-infectious ailments such as cancer. It has, of course, been well established that AIDS is a result of an infection caused by HIV-1, a retrovirus that preferentially attacks Helper T cells (CD4+) – cells that are primary players in a functioning immune system. The symptoms characteristic of AIDS ordinarily show themselves once the number of circulating CD4+ cells reaches a dangerously low level. There is a direct correlation between the number of viral particles circulating in the blood – the so-called “viral load” – and the onset of symptoms. Most infected individuals demonstrate a viral load exceeding 10,000 viral copies/ml of blood. The new life-saving therapeutic drugs are able to decrease this viral load substantially.

There are a small number of HIV-1+ individuals, however, who have depressed viral loads without the use of drugs. These individuals are collectively referred to as HIV Controllers. They show stable and normal levels of CD4+ cells, do not show signs of disease and are less likely to be infectious.

It would, therefore, invaluable to understand what makes HIV Controllers different. There is for this reason a large study underway to unravel this mystery. This study is referred to as The International HIV Controllers Study with literally hundreds of contributing scientists from around the world. One of the goals of this study is to discover the genetic basis for this apparent advantage shared by HIV Controllers. To do this, genomic DNA – the full complement of DNA within an individual – was sampled from Controllers and Progressors – those HIV-1 -infected individuals who progress to full blown disease - and subsequently compared between these two groups. The results reported in the December 10, 2010 edition of the renowned scientific journal Science showed that there were over 300 single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC). The MHC region in the human genome has been shown to have strong genetic associations with infection and inflammatory diseases.

To quote the authors, “Altogether, these results link the major genetic impact of host control of HIV-1 to specific amino acids – the chemical building blocks of protein - involved in the presentation of viral peptides – small protein molecules - on infected cells. This represents a significant finding that helps elucidate the nature of the protection that Controllers naturally possess and may eventually prove useful in devising therapies against AIDS.