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Bennett Lewis
Bennett Lewis

The Human Animal: A Personal View Of The Human ...


Desmond Morris was born January 24, 1928 in Purton, North Wiltshire, United Kingdom. He is a British zoologist, ethologist, author, and surrealist painter. After Morris' military service, he attended the University of Birmingham and graduated in 1951 with a First Class Honours Degree in Zoology. In 1954, he received a D.Phil from Oxford University. After graduation, Morris was a Curator of Mammals at the London Zoo until 1966. Morris was a presenter of the ITV television program "Zoo Time" in the 1950s, but may be best-known for his 1967 best-selling book, The Naked Ape, which describes the evolution of human behavior from a zoological point-of-view. Morris has authored nearly fifty scientific publications.




The Human Animal: A Personal View of the Human ...


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Because of improved living conditions and increased access to medications, the proportion of human deaths caused by infectious diseases has trended downwards over the last centuries, giving way to degenerative and lifestyle diseases (7). However, history has previously witnessed spikes in morbidity and mortality, and this reduction may not be lasting. In Thailand, the number of deaths due to infections decreased to one-fifth from 1958 to 1997, after which it started increasing again, mainly due to the emergence of HIV (8). Burden of disease is not equally distributed. Infections, including parasitic diseases, contribute to more than 20% of the global burden of disease (9), but in Africa it is more than 70% (10).


To estimate the importance of diseases, different measures can be used, such as morbidity and mortality. To measure both the impact of mortality, disease, and long-term sequelae of human disease, disability adjusted life years (DALY), have been established (16, 17). The definition of one DALY is the loss of one healthy year of human life. In addition to these calculations, costs of illness for the public health sector, and losses to industry, tourism, and the agricultural sector can be estimated, although it may be more difficult to assess the costs of environmental impacts and loss of ecosystem services. To fully evaluate the economic and societal impact of a zoonotic disease, it is important to include all measurements (18). The combined impact of zoonotic diseases on human health, animal health, and livelihoods make them especially costly. The World Bank (19) estimates that direct costs of zoonotic outbreaks during the last century have exceeded US$20 billion, and US$200 billion in indirect costs.


Vector-borne diseases constitute around 23% of the infections considered emerging (20). Although arboviruses can be transmitted by a wide range of arthropods, mosquitoes are the most important from a veterinary and medical point of view and may have been parasitizing on mammalian blood for 100 million years (66). Disease from vector-borne pathogens often occurs as spillover events, as the pathogens generally circulate between reservoir hosts and the invertebrate vectors without causing apparent disease. However, many vectors are not specific in their requirements of their feeding hosts and may feed on other animals. These opportunistic, oligophilic vectors can thus transfer a pathogen from a reservoir host to animals or humans where disease occurs. Often these new incidental hosts are less capable of amplifying the pathogen and are epidemiological dead ends.


More industrialized animal keeping causes an increasing segregation of the animals and their vectors from humans. This has actually been one of the proposed explanations for the eradication of malaria in many developed countries (89). In Japan, the number of pigs produced has been increasing because of increased industrialized pig keeping, whereas there has been a decreasing number of pig farms. The incidence of JEV has not been following the increasing numbers of pigs, but instead has decreased with the number of pig farms (90).


Extensive animal keeping, backyard farming, and mixed production systems have also been associated with disease risks. The outbreaks of highly pathogenic avian influenza in Southeast Asia have been demonstrated to be dependent on rice production, duck densities, and human population density (91). In addition to the traditional backyard poultry keeping in poor rural or urban areas, there are increasing trends of keeping small flocks of poultry in middle- and high-income urban areas in many countries. In both cases, biosecurity measures and awareness of the importance thereof are often limited (35, 92).


As a key component of the HGP, it was wisely decided to sequence the smaller genomes of significant experimental model organisms such as yeast, a small flowering plant (Arabidopsis thaliana), worm and fruit fly before taking on the far more challenging human genome. The efforts of multiple centers were integrated to produce these reference genome sequences, fostering a culture of cooperation. There were originally 20 centers mapping and sequencing the human genome as part of an international consortium [18]; in the end five large centers (the Wellcome Trust Sanger Institute, the Broad Institute of MIT and Harvard, The Genome Institute of Washington University in St Louis, the Joint Genome Institute, and the Whole Genome Laboratory at Baylor College of Medicine) emerged from this effort, with these five centers continuing to provide genome sequence and technology development. The HGP also fostered the development of mathematical, computational and statistical tools for handling all the data it generated.


The HGP produced a curated and accurate reference sequence for each human chromosome, with only a small number of gaps, and excluding large heterochromatic regions [9]. In addition to providing a foundation for subsequent studies in human genomic variation, the reference sequence has proven essential for the development and subsequent widespread use of second-generation sequencing technologies, which began in the mid-2000s. Second-generation cyclic array sequencing platforms produce, in a single run, up to hundreds of millions of short reads (originally approximately 30 to 70 bases, now up to several hundred bases), which are typically mapped to a reference genome at highly redundant coverage [19]. A variety of cyclic array sequencing strategies (such as RNA-Seq, ChIP-Seq, bisulfite sequencing) have significantly advanced biological studies of transcription and gene regulation as well as genomics, progress for which the HGP paved the way.


Third, our understanding of evolution has been transformed. Since the completion of the HGP, over 4,000 finished or quality draft genome sequences have been produced, mostly from bacterial species but including 183 eukaryotes [31]. These genomes provide insights into how diverse organisms from microbes to human are connected on the genealogical tree of life - clearly demonstrating that all of the species that exist today descended from a single ancestor [32]. Questions of longstanding interest with implications for biology and medicine have become approachable. Where do new genes come from? What might be the role of stretches of sequence highly conserved across all metazoa? How much large-scale gene organization is conserved across species and what drives local and global genome reorganization? Which regions of the genome appear to be resistant (or particularly susceptible) to mutation or highly susceptible to recombination? How do regulatory networks evolve and alter patterns of gene expression [33]? The latter question is of particular interest now that the genomes of several primates and hominids have been or are being sequenced [34, 35] in hopes of shedding light on the evolution of distinctively human characteristics. The sequence of the Neanderthal genome [36] has had fascinating implications for human evolution; namely, that a few percent of Neanderthal DNA and hence the encoded genes are intermixed in the human genome, suggesting that there was some interbreeding while the two species were diverging [36, 37].


The HGP benefited biology and medicine by creating a sequence of the human genome; sequencing model organisms; developing high-throughput sequencing technologies; and examining the ethical and social issues implicit in such technologies. It was able to take advantage of economies of scale and the coordinated effort of an international consortium with a limited number of players, which rendered the endeavor vastly more efficient than would have been possible if the genome were sequenced on a gene-by-gene basis in small labs. It is also worth noting that one aspect that attracted governmental support to the HGP was its potential for economic benefits. The Battelle Institute published a report on the economic impact of the HGP [46]. For an initial investment of approximately $3.5 billion, the return, according to the report, has been about $800 billion - a staggering return on investment.


In fact, the application of systems approaches to disease has already begun to transform our understanding of human disease and the practice of healthcare and push us towards a medicine that is predictive, preventive, personalized and participatory: P4 medicine. A key assumption of P4 medicine is that in diseased tissues biological networks become perturbed - and change dynamically with the progression of the disease. Hence, knowing how the information encoded by disease-perturbed networks changes provides insights into disease mechanisms, new approaches to diagnosis and new strategies for therapeutics [58, 59]. 041b061a72


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