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.