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.