Selected Student Papers
Janelle Pisarik
Paper #1
3 February 2005
Kuru, Prions, and Cannibalism:
An Interesting Link to Human
Genes’ Past
ABSTRACT: Prions are protein particles similar to viruses and they are easily spread from human to human. Kuru is an acquired prion disease found in the Fore tribe of Papua New Guinea. It is believed that Kuru was spread during ritualistic cannibalistic activities. After DNA analysis of members of the Fore tribe who participated in such activities, Dr. Simon Mead and his colleagues were able to draw conclusions about the human prion protein gene. Heterozygosity for a common polymorphism in this gene was shown to provide a resistance to prion diseases, while homozygosity proved susceptible to these diseases. Different forms of this polymorphism have been found all over the world, supporting the assumption that these genes evolved over time in their respective ethnic groups. While prion diseases can be transmitted through eating animals, the fact that gene variations are cultural and that cannibalism is an easier way to spread the disease and was practiced in many tribes, animal transmission is not considered a high possibility. With the beginning of the kuru epidemic, homozygotic individuals were selected against and thus a balancing occurred. With the lack of cannibalism, many younger generations are more genetically diverse. The author of the newspaper article did a very thorough job of explaining prions, kuru, and scientific conclusions. There was no slant in the article and the author was even able to include work from other, earlier studies to compare them with current findings.
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Anthropologists and scientists have long debated whether or not cannibalism was practiced throughout history, or whether it was only practiced in small, ritualistic communities and in times of starvation. New studies, however, may confirm that cannibalism was, at one time, common throughout much of the world. These studies deal with human DNA and the evolution of particular genes associated with certain diseases that transfer readily through the act of cannibalism.
The study originated in the early 1950s with Dr. D. Carleton Gajdusek’s observations of members of the Fore, a tribe from the eastern highlands of Papua New Guinea. Dr. Simon Mead and his colleagues continued research in to this subject in the early 21st century. Attention was drawn to the Fore in the mid-1950’s, when Australian authorities banned cannibalism, a ritual the Fore had been practicing since the end of the 19th century. The Fore were found to be suffering from a fatal neurodegenerative disease (a disease that slowly changes and deteriorates the nervous system including our spinal chords and brains) known as kuru. After the first noted case in 1920, the disease spread rapidly among the Fore, who had no direct contact with the outside world. While the disease spread rapidly, it seemed to mainly affect the tribe’s adult females and children of both sexes. (It is well known that adult Fore males participate little in the cannibalistic ritual.) Kuru killed 1% of the Fore population annually and it was found that young adult women were non-existent in some villages.
Kuru is a form of what is known as a prion disease. Prions are protein particles very similar to viruses and they are spread easily from one mammal to another through the act of eating the meat of an infected animal or human. It is believed that one human with a random mutation of a particular prion was consumed by members of the Fore. Yet not all members of the Fore contracted kuru. Why? Dr. Mead believes it has to do with human genes. In his experiment he sampled the DNA of 30 Fore women over the age of 50. All of these members had repeatedly participated in the mortuary feasts of the early 1900s, yet they were still living without symptoms of the disease. Dr. Mead noted that once an individual has consumed the prion, the prion proteins will begin to deform the person’s normal neural proteins (hence the name neurodegenerative), leading to the disease and eventually to death. While examining the DNA samples, Mead discovered that there were polymorphisms (variations of the same gene) at a specific spot on the human prion protein gene (PRNP). This specific spot, labeled codon 129, exists as two polymorphisms in Fore individuals. Twenty-three out of the thirty Fore women tested were found to contain a copy of each of the polymorphisms; they are thus considered to be heterozygotes for PRNP. However, other members of the tribe who contained two copies of either of the polymorphisms (also known as homozygotic individuals) died after partaking in the mortuary feasts. The combination of both polymorphisms seemed to inhibit or greatly reduce the protein to protein interaction that is needed to spread prion diseases, such as kuru in an individual. Individuals that were homozygotic had an onset of kuru at the average age of nineteen, while the heterozygotic individuals could harbor the prion for well over thirty years without showing any signs of the disease.
The study of the Fore led to a worldwide study of prions and codon 129 and a shocking discovery was brought to light. Different ethnic groups contained different polymorphisms of the human prion protein gene. Five polymorphisms were found in total, all of which were ethnically dispersed, with a greater quantity of different polymorphisms detected in African, South Asian, East Asian, Pacific, European, and South American cultures. Yet heterozygosity of each culture’s particular prion protein gene polymorphism at codon 129 was still shown to delay the onset of prion diseases such as kuru, Creutzfeldt-Jakob disease, and mad-cow disease. The hypothesis on heterozygosity was further confirmed by the fact that all of the people that contracted the human version of the prion mad-cow disease were homozygotic at codon 129. About half of Europe’s population today is heterozygotic for prion resistance, which would account for the low frequency of mad-cow patients.
The question that remains, however, is why do we have these polymorphisms to begin with? PRNP does not appear to scientists to be a rapidly changing and evolving gene. Europeans, Africans, and members of the Fore are all characterized by a very distinct version of the polymorphisms, thus suggesting that changes in codon 129 are ancient. Also, natural balancing selection of these polymorphisms has been seen. This means that while homozygosity for either of the polymorphisms in a population is unwanted, both polymorphisms are needed to insure heterozygosity. Those homozygotic individuals die, while those with both copies live and breed, passing on both polymorphisms. While researchers know that kuru began and was spread by cannibalistic acts in the Fore tribe, strong inferences can be made about cannibalism throughout the world. Prion diseases are only spread by eating meat of an affected individual or animal. One might suggest that these polymorphisms occurred due to the eating of affected animals, not humans. Yet if this was the case, many animals with the same prion would have to be consumed by most members of the population. The jump between animal and human strains of prion diseases is so large, that it would be virtually impossible for these diseases to be solely due to animal, and not human, ingestion. This can be further proved by the fact that only 134 people have contracted mad-cow disease out of the 50 million people that live in Europe. This minute number would not be enough to evolutionally shape our genes and select for or against a specific combination of polymorphisms in a population. While Dr. Mead could not rule animal consumption as the spreading of prion diseases out completely, he considers it highly unlikely, based on three things: how ethnically specific these polymorphisms are; how quickly a prion disease could be spread throughout a cannibalistic community, thus naturally selected for variations in the gene; and how unlikely it is that every member of a community would have eaten the same affected animals. Thus cannibalism seems a very likely solution to the origin of the human prion protein gene.
These conclusions by Dr. Mead and his colleagues give rise the authenticity of research reported by the popular press. One may ask how correct the article in The New York Times entitled “Gene Finds Cannibal Pattern” really is. In all actuality, the author did a very nice job presenting the process and conclusions of the Gajdusek and Mead experiments and explaining the concept of kuru and prions and how heterozygosity is beneficial. However, he oversimplified the concept of polymorphisms. As opposed to explaining that different ethnic groups contain different forms of the prion protein gene, he simply said that certain individuals have a protective gene signature and others do not. Overall, the article does not contain a slant, as the author simply presents the information and assumptions made by Dr. Mead as opposed to analyzing the information and producing his own conclusions.
In summary, prion diseases such as kuru are fatal neurodegenerative diseases spread by eating infected meat. Humans have evolved to contain polymorphisms of a prion protein gene at the codon 129. When someone with two copies of the same polymorphism eats infected meat, they contract the prion disease. However, if homozygotic individuals eat the same meat, they may not show signs of the diseases for years afterwards, and possibly never even know that they ate the prion. Different prions have evolved in different cultures, and the main reason for this seems to be that cannibalism was practiced by different cultures throughout the world. The article does a fine job of presenting a scientifically accurate representation of the concept and nature of the experiments preformed by Dr. Simon Mead.
Bibliography
Mead, Dr. Simon, et al. 2003. “Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics.” Science 300: 640-643.
Wade, Nicholas. “Gene Finds Cannibal Pattern.” New York Times, 11 April 2003.
Chan Jing Quan, Alex
BIOS 11108 – 26th February 2005
Biology Essay 2 – Study Discovers Genetic Link to Atherosclerosis
Researchers have long suspected atherosclerosis to be a genetically linked disease, since it has a higher tendency of affecting individuals who are related to patients already diagnosed with the condition. Up till now, the specific genes that may lead to a higher susceptibility to atherosclerosis in individuals have not been positively identified by scientific research. However, in a recently concluded study, a team of scientists might just have uncovered one such gene.
Atherosclerosis is a disease involving the inflammation and build-up of plaque along the walls of major arteries, making them narrow and hard. Diabetes, smoking, high blood pressure and high blood cholesterol levels may promote damage to the arterial linings, setting up an inflammatory response that results in plaque formation at these sites. It is this deposition of plaque (derived from cholesterol in the blood) that causes the walls of the arteries to become narrow and hard. This obstruction of blood-flow may eventually lead to potentially fatal incidences of heart attacks (loss of blood to the heart) and strokes (loss of blood to the brain). Thus atherosclerosis, if left untreated, is a life-threatening condition.
A paper published in the 1st January 2004 issue of the New England Journal of Medicine reports that a group of scientists from the University of Southern California and the University of California, Los Angeles, have uncovered a genetic link between a variation of the 5-lipoxygenase (ALOX5) gene and the onset of atherosclerosis. Researchers have discovered a positive correlation between the presence of this genetic variation in an individual’s deoxyribonucleic acid (DNA) sequence and his/her susceptibility to acquiring the disease.
DNA is a biological formation of specific sequences of nucleic acids that serve as our body’s blueprints. Within this sequence is information that pertains to how each part of our body is to be constructed and put together. Genes are selected sequences of DNA that are construction codes for specific amino acid sequences. These amino acids later combine to form proteins that make up the cells, tissues and organs of our body. Hence genes are essentially sub-sections of our body’s blueprint, each with a specific role to play in the proper functioning of the body.
More specifically, the genetic sequence in question is the ALOX5 gene, coding for the ALOX5 enzyme that plays a crucial role in the arterial lining’s inflammatory response. An enzyme is a protein that facilitates biological reactions within the body, and the ALOX5 enzyme aids in the formation of leukotrienes that react with a product of fatty acids in the blood to induce arterial inflammation.
Within the scope of this study, the objective was to determine the extent, if any, to which possessing a variation of the ALOX5 gene increases the chances that an individual develops atherosclerosis.
Headed by Professor James H. Dwyer, the team examined a randomly selected cohort of 470 healthy men and women from the Los Angeles Atherosclerosis Study between the ages of 40 and 60 who had not been previously diagnosed with cardiovascular disease. In attempting to establish a genetic link to the onset of atherosclerosis, the population of the test subjects was limited to a controlled demographic profile so as to minimize the negative effects that exogenous factors like location, culture and social circumstances might have on the accuracy of the study. Even though the researchers hypothesized that different individuals might be more or less genetically predisposed to acquiring atherosclerosis, it was important that all test subjects began the test healthy and “on a clean slate”, so that the onset of the condition can be tracked more accurately in relation to their diets and lifestyles. Atherosclerosis is considered a multi-variable disease, and the assessment of as many factors as possible will aid in the credibility of any conclusions drawn.
Researchers took ultrasounds to measure the open diameter of the subjects’ carotid artery (a major blood vessel in the neck), the thickness of which is known to be a marker for atherosclerosis. The narrower the open diameter of the carotid artery, the thicker and harder the arterial walls are thought to be, indicating the inflammation and build-up of plaque along this lining. Ultrasound, commonly used in pre-natal check-ups, is an ideal procedure in the examination of this critically important blood vessel because it is a non-invasive procedure, reducing the risk of any medical complications arising due to the study.
Furthermore, the team took DNA samples from subjects to determine their genotypes with respect to the ALOX5 gene: ascertaining whether they were heterozygous or homozygous for the common allele or variant allele. The alleles of a gene are basically different versions of the genetic sequence that occupy the same position, or locus, on a chromosome. The genetic material in human somatic (body) cells is split into twenty-three pairs of corresponding chromosomes and the ALOX5 gene is located on 10q11.2, which refers to a band (11.2) on the long arm (q) of the tenth chromosome (10). Since a normal individual has a pair of chromosome-ten’s, he/she can possess either a common or variant allele on each of the two chromosomes. A person who has two copies of the same allele has a homozygous genotype for that particular allele, while he/she is considered to be of heterozygous genotype if he/she has one copy of each allele.
In addition, since fatty acid consumption has been shown to affect the onset of atherosclerosis, researchers also sampled six 24-hour records of the subjects’ diet over a 1.5-year time span so that they could assess the subjects’ fatty acid consumption. A distinction was further made between the intake of arachidonic acid (a fatty acid found in non-marine meat) and marine fatty acids, since the former is thought to promote the build-up of plaque along the arterial walls while the latter discourages this development.
The team then used data collected from the above methods to determine how the different ALOX5 genotypes affected arterial width, and how these different genotypic groups responded to the consumption of different types of fatty acids.
Researchers found that 94% of subjects had at least one copy of the common ALOX5 allele (homozygous for the common allele or heterozygous). However, the team discovered that subjects who were homozygous for the variant ALOX5 allele had significantly thicker arterial walls than their peers, putting them at a greater risk of contracting atherosclerosis. The study further proposed that this increase in risk is similar in magnitude to those faced by diabetics but smaller than those experienced by smokers. Regarding the dietary effect, and taking into consideration the genotypes of the individual subjects, it was discovered that those who had at least one copy of the common ALOX5 allele showed little disparity in arterial diameter regardless of their diets. However, subjects who were homozygous for the variant allele benefited, in terms of having larger arterial diameters, from consuming more marine fatty acids and less arachidonic acid. The results indicate that the common ALOX5 allele may aid in regulating the inflammation of arterial linings and that consuming marine fatty acids, rather than arachidonic acids, may be a healthier choice for subjects who are homozygous for the variant allele, since it appears to inhibit the build-up of arterial plaque in the test group.