HIV Treatment – A Promising Approach to Prevention

The use of antiretroviral drugs (ARVs) by patients infected by HIV, the causative agent of AIDS, has prolonged the lives of many individuals.  When several of these drugs are used in combination, typically three or four, this protocol is referred to as Highly Active Antiretroviral Therapy (HAART).  The application of HAART has been found to consistently lower the viral load – the number of viral particles in circulation in the bloodstream – resulting in preserving the integrity of the immune system with the resulting increase in the quality of life and longevity of AIDS patients.

Since this therapeutic approach lowers the viral burden, it might be assumed that it would also dramatically lower transmission of the disease.  Although this is a very appealing idea, the efficacy of ARVs in diminishing the spread of AIDS through sexual contact with infected individuals required further study.

Such a study was, in fact, conducted; it was referred to as the 052 clinical trial conducted by the HIV Prevention Trials Network.  Results of this study were finally reported in May on 2011 – ARVs effectively reduced heterosexual transmission of HIV by 96%.

Inspired by these encouraging data, Doctor Anthony Fauci, Director of the U.S. National Institute of Allergy and Infectious Diseases, stated that, "The idea of the tension between treatment and prevention, we should just forget about it and just put it behind us, because treatment is prevention."  On account of the profound implications of this result, the prestigious scientific publication, Science, has proclaimed this the scientific breakthrough of 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. 

Regarding the Future of the Human Species

In my mind, the greatest challenge that faces the species in the 21^st 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.

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.

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.    

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.”

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 20^th 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.