Premedical MCAT Preparatory Course Using Evolutionary Medicine

EvMed Premed Synthetic Course: Premedical MCAT Preparatory Course Using Evolutionary Medicine Noel T. Boaz, Ph.D., M.D.

The basic medical sciences are a disparate array of disciplines whose integration defies the intellectual efforts of average and even the above-average premedical and medical student. Failing to understand why they are required to learn the myriad and apparently unrelated facts in the basic science premedical and medical school curricula they resort to the time-honored strategy of rote “memorization without understanding” (Regan-Smith et al. 1994). Although there is a place for rote learning in the procedural phases of medical education (Kwan and Mafe 2016), assimilating in this way the torrent of facts in the eclectic mix of the medical basic sciences unconnected except by their perceived application to curing disease or treating patients, is not conducive to retention of information, does not facilitate translation of scientific concepts into medical practice, and ultimately does not serve to advance medical care and improve patient outcomes. There is a better way.

An overarching paradigm now unites disciplines in the biomedical sciences. It is the Synthetic Theory of Evolution by Natural Selection (Darwin 1859, Simpson 1944, Mayr 1982), and it has given rise to the new field of Evolutionary Medicine (Eaton, et al. 1988, Nesse and Williams 1999, Boaz 2002, Gluckman et al.

2016, Stearns and Medzhitov 2016). Evolutionary Medicine incorporates the biopsychosocial model of standard Biomedicine but seeks to supersede its limitations replete with inferential disease associations, syndromes with causally unrelated signs and symptoms, and wide tolerance of idiopathic diagnoses.

Rather, drawing upon a multidisciplinary array of cross-verifying scientific disciplines that include genomics, evolutionary and developmental (“evo-devo”) biology, astrobiology, onto-phylogenetic anatomy, biomedical anthropology, comparative physiology, and evolutionary neuroscience, Evolutionary Medicine seeks to understand the origins and phylogenetic development of human adaptations. It thereby aims to uncover the root causes of disease, illness, and congenital malformations. The promise of this new field of medicine is the more precise targeting of the etiologies of pathology, thereby improving therapeutic efficacy and thus avoiding many of the undesirable side effects of overly broad pharmaceutical regimes, preventing unnecessary surgical interventions, fostering more effective mental health treatments, and embracing preventive medicine as a primary modality of medical care. In the present context of premedical education, Evolutionary Medicine offers the distinct advantage of offering the “why” answers by providing narrative hypotheses that integrate the disparate views of the many disciplines that play into modern scientific medicine. Whereas traditional medicine can be viewed as much the same as the 12 blind sages of ancient India describing an elephant by reference to only those part that they could individually perceive, Evolutionary Medicine offers a synthetic overview of the whole animal.

Course Schedule Classes

Content

Assessments and Activities 1

Module 1 Natural Selection and Evolutionary Medicine

Medicine is applied human biology, and all biology is evolutionary biology. General foundation in human and organismic biology as part of Medicine; Human relatedness to other living creatures, why and how we age, how the immune system works, how genetic diseases fit in, the role of nutrition and lifestyle in health, including heart disease, basic neurobiology and endocrinology, the hormonal biology of stress, and human reproduction, including early development and sexual differentiation.

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Module 2 Elemental and Molecular Organization

The abiotic environment of physical and chemical laws and molecular organization were the stage on which the first self-replicating nucleic acid molecules and proto-cells evolved.

Astrobiology shows that deep sea hydrothermal vents during a lengthy “snowball-earth” phase were a formative pre-sunlight and oxygenless crucible in which the first cells were formed.

These were the beginnings of biochemical and cellular mechanisms underlying normal and disease processes. Etiologies of metabolic diseases and structural biochemical abnormalities are investigated, emphasizing integration with anatomical structure and physiological function.

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Module 3 Cellular Life: Prokaryotes and the RNA World

Basic biology of bacteria, with particular emphasis on cellular processes and structures which are determinants of pathogenicity, characteristics used for detection and identification, and targets of antimicrobial chemotherapy; virology, pathogenic organisms, and infectious disease; pathogenic microorganisms and the diagnosis, treatment, and prevention of human infectious diseases.

Laboratory teaches standard microbiological techniques and illustrates key principles.

Module 4

Structural organization of cells, tissues, and organ systems at the microscopic level, emphasizing the 2

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Lecture Lecturio videos and questions

Cellular Life: Eukaryotes, DNA, and the Nucleus

dynamic relationships between structure and function. Students directly observe microanatomical structure in the laboratory, and begin using their knowledge of normal structure and function in clinical problem solving. DNA replication and repair, transcription, protein synthesis, and new “-omics” disciplines. Topics include how mutations result in disease processes; the molecular nature of specific genetic disorders, classic Mendelian inheritance and complex forms of inheritance, the impact of genetic disease on the family and society, diagnostic, prenatal, pre-symptomatic testing, and genetic screening and gene therapy.

Module 5 Opisthokonts and Origins of the Reproductive System

The fertilized egg (zygote) is the totipotential first cell in an individual’s body and all other cells differentiate from it; undifferentiated pluripotential stem cells are retained in the adult gonads, comprising the core of the reproductive system.

Unicellular opisthokonts, akin to living choanoflagellate organisms, were our distant ancestors from whom we inherit our flagellated cells. Lack of normal cell motility in sperm (Kartagener’s Syndrome) and dysfunction of uterine tube cilia are major causes of infertility.

Module 6 Cnidarians and the Evolution of the Endocrine System

Before there were somatic nerves there were hormones. Cells live, reproduce, metabolize, and communicate intracellularly and with other cells first through various chemicals; These chemicals diffuse through intracellular (interstitial) spaces to bind to membrane receptors on other cells, thereby communicating with them and changing their chemistry; These paracrine functions are important in embryonic development of tissues and in functions of adult organs as well; Distant chemical communications evolved in tandem with the evolving circulatory system and hormonal functions become organized in the adult within the endocrine system. Extant species of cnidarians, a group of organisms that that contains jellyfish, are

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Draw-It-to-Know-It Concept Mapping with LucidChart

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

representative of this group of our ancient deuterostome ancestors.

Module 7 The Cardiovascular System Evolves to Supply an Elongated and Bilaterally Symmetrical Body

The heart is the first organ system to become functional and begins to contract at Day 10 of embryogenesis; by providing an effective delivery of nutrients and a removal system for metabolites the vasculature is an adaptation that now allows body length to increase and other systems to develop; The model extant organism of this stage of our evolutionary history is the nematode worm, Caenorhabditis elegans, similar to early members of the Bilateria. These animals evolved larger size by adding segments onto their tail ends, resembling millipedes and centipedes in this respect; Humans retain this basic segmental (“metameric”) structure throughout their bodies, although it is most obviously retained in the vertebral column and thoracic cage.

Module 8 Chordate Organization and the Gastrointestinal System

A central organizing mesodermally-derived cartilaginous notochord divides the bilaterian body plan; pharyngeal gills evolve as a feeding adaptation and re-organize the head region; muscles evolve that bend the notochord to form swimming movements; Metabolism at a multi-system level starts when the gut tube forms at embryonic Day 16, allowing ingestion and digestion, and forming the definitive body cavity (coelom) around which other organs will develop.

Module 9 Vertebrates and the Evolution of the Urinary System

The kidneys develop behind the gut tube and fulfill the function of excretion of metabolic wastes; a segmented glomerular filtration system (mesonephros) is connected by the cardiovascular system to the rest of the body; the metanephric kidney evolves to maintain isotonic balance in fresh water, thus our kidneys function initially to filter out excess water from the environment; resorption of water evolves for life on land through adaptations of kidney tubules, the Loop of Henle, and collecting ducts; the kidneys become essential in maintaining acid-base balance and electrolyte levels in the blood to ensure physiological homeostasis; Kidney function becomes closely correlated with 4

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

maintaining stable blood volume; its dysregulation can lead to high blood pressure (hypertension) and is treated medically with diuretics that increase urine output.

Module 10 Evolution of the Immune System

Cells originally with a digestive function specialize to recognize and engulf invading cells from outside the body; the lymphatics develop alongside veins to connect to lymph nodes and specialized organs such as the thymus develop with immune function.

Module 11 Nervous System

The neural tube forms by Day 25 of embryonic development and becomes segmented throughout its length; nerves develop to send and receive impulses to and from body segments more rapidly; increasingly effective sensory modalities and an integrating brain develop; neural crest cells migrate widely in the body and form the adrenal medulla, head-and-neck mesenchyme, and peripheral nerves throughout the body. A simplified view of the human brain is that it “triune,” organized with structures and pathways evolved at the reptilian, mammalian, and advanced primate levels.

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Module 12 Musculoskeletal System

Blocky segments of mesoderm develop into the somites which differentiate to form skeletal muscles and the bony skeleton by the fifth week of embryonic development; the skull, pharyngeal arches, limbs, and tail develop each with their own set of skeletal elements and associated muscles; Patterns of nerve supply to the muscles and skin follow the primitive segmental arrangements of dermomyotomes, a pattern of structural organization that finds many clinical applications in medicine. Much of the musculoskeletal system is adapted to moving the body through space (locomotion) and feeding.

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Module 13 Respiratory System

Lungs are among the last of the major systems to develop, forming from the gut tube and maturing only within the last month of fetal life; significant changes in the blood, heart, pharyngeal arches, and 5

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Lecture Lecturio videos and questions

Module 14 Mammalian Adaptations

Module 15 Primate Organization

Module 16 The Human Condition – Brain and Behavior

kidneys occur to enable effective functioning of the air-breathing lungs.

Draw-It-to-Know-It Concept Mapping with LucidChart

Skin, hair, and nails form from the ectoderm and become progressively more impervious to fluids, light, trauma, and pathogens as development proceeds, creating with the immune system the body’s most important defense to infection. The placenta evolves to provide for fetal development inside the mother’s body and post-partum lactation nurtures the young; homeothermy and testis descent.

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

Binocular stereoscopic vision, grasping hands, and a vegetarian-omnivorous diet evolved among primates; higher primates evolved a new biochemical pathway using ascorbate, predisposing them to Vitamin C deficiency and scurvy; Human sexual selection, mating, social behavior, play, and learning are primate patterns.

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The hominid body plan is altered by bipedalism and the brain enlarges greatly; the cerebral cortex mediates all human behavior but underlying brain structures and neurotransmitters still operate; significant postnatal brain maturation occurs. The learned system that controls human social behavior, culture, is key to human survival and adaptability; Epidemiological transitions have occurred as human population densities have increased, with balancing selection conferring fitness benefits in response to infectious and parasitic diseases; “Diseases of Civilization.”

Lecture Lecturio videos and questions Draw-It-to-Know-It Concept Mapping with LucidChart

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Learning Modalities Lectures Each module in the course will have a stage-setting narrative lecture based on the 17-stage onto-phylogenetic model published by Boaz (2002) (Figure 1).

Fig. 1. Onto-phylogenetic stages of the human organism from Boaz (2002). This evolutionary approach elaborates organismal biology from 1) early to late geological time, 2) simple to complex structure and function, 3) microscopic to macroscopic scales, and 4) regional anatomical systems based on key morphophysiological adaptations. Human pathologies from this view of Evolutionary Medicine can be understood as disruptions or dysfunctions of one or more of these adaptational plateaus.

Lectures will be built around the evolutionary nodes of human phylogeny as referenced to the Time Tree of Life Project (www.timetree.org), which integrates genomic, paleontological, and geochronological data (Figure 2). LUCA refers to the Last Universal Common Ancestor which lived some 4.3 billion years ago. This empirical framework underlies the evolutionary narrative illustrated in Figure 1. The figure lists early major steps in the evolution of the integument, one of the eleven systems of the body.

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Fig. 2. Phylogram of human evolution from the Last Universal Common Ancestor to modern hominins. Inferred geological ages for taxonomic nodal points are indicated. Extant comparative or model organisms are listed along the top row.

Lectures will highlight Evolutionary Medicine as a robust field of ongoing research, as indicated in Figure 3. Although essentially retrodictive and historical in its narrative elements, evolutionary medicine draws on numerous independent paradigms and scientific disciplines to falsify hypotheses. Those hypotheses which defy disproof are incorporated into the synthesis. This synthetic nature of Evolutionary Medicine is the glue that binds the many disparate fields of scientific medicine together and enables a coherent picture of human health and pathology to emerge.

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Fig. 3. A matrix of hypotheses (narrative elements) in Evolutionary Medicine on the Y-axis and scientific disciplines (paradigmatic tools) used to test them on the X-axis. Only those narrative elements that survive multiple empirical cross-checks are retained as working hypotheses.

Lecturio Videos and Question Banks As part of this review course students will have access to Lecturio. Of the many premedical, postbaccalaureate, and medical student review course platforms now available, Lecturio was found to offer the best fit with this curriculum, with which it will be closely integrated. Video lectures (Figure 4) by medical school faculty are professionally produced and are cross-referenced to the most commonly used textbooks, which will be referenced in this course. These lectures and the associated references will be the primary sources of basic science content utilized in the evolutionary narratives.

Fig. 4. A Lecturio lecture on amino acid metabolism.

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Lecturio offers a wide range of premedical (MCAT) and medical student (USMLE) questions for review and practice (Figure 5). These questions are adaptive in that they remember past mistakes by the student and repeat these questions for closer review and reinforcement. There is an emphasis on clinical vignette questions that are now emphasized on medical board examinations.

Fig. 5. A USMLE-type review vignette question in Lecturio. The question is first read aloud, the answer options given, and the steps needed to answer the question are reviewed. In this instance the question is identified as a cardiovascular system question. It is a second-order question, i.e. one that needs two steps to answer. And lastly, it is a question in which the information in the stem (the main narrative) is required to answer the question. If the student answers correctly, he or she goes on to the next question. If not, there is a detailed answer that pops up to explain why that selection is incorrect, and the student has another chance to answer. The system remembers incorrect answers and will re-present a missed question in a future review session.

DRAW-IT-TO-KNOW-IT Active learning is a central element of effective didactic practice, even in on-line courses. Draw-It-ToKnow-It is a medical education learning platform that presents videos that lead a student though drawing a structure, flowchart, or process. Figure 6 shows three successive stages of a lesson from Draw-It-To-Know-It on kidney structure and its relationship to the clinical entity of nephrotic syndrome.

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Figure 6. Three stages of completing and labelling a drawing of nephrotic syndrome. The top panel shows the initial drawing that a student makes of the kidney’s glomerulus and the pathological damage that underlies nephrotic syndrome. The middle panel shows the main clinical manifestations of and treatments for the disease. The third panel shows the addition of a second column of specific disorders that make up nephrotic syndrome.

LucidChart Concept Mapping Experience shows that many students have enough knowledge to pare down the number of potential answers in a multiple choice question to two, but choosing between those two becomes a toss-up. 5050 are not good odds for getting into medical school or passing one’s licensure examination. Concept mapping is an active-learning modality developed by Dr. John Pelley, a professor of biochemistry at Texas Tech University School of Medicine to aid medical students who had failed to pass the USMLE Step

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One examination. It is a laborious and time-consuming process but for students who are committed to drilling down to the right answer, it is a tried and true method of success. An example of a simple concept map is illustrated in Figure 7.

Constructing a concept map

1. Select the topic to be studied. Since it is going to be subdivided, the size of the topic is not critical. It can be part of a lecture or material that is covered in several lectures.

2. Identify by listing on a notepad or highlighting the major concepts from the text, and especially material from the lecture notes that was especially emphasized.

3. Rank the concepts (and facts) from most general to most specific.

4. Arrange the concept map with the most general concept at the top. Link it to the less inclusive concepts and enclose the text with circles or other shapes. Label lines with linking words that explain the relationship, if needed. Arrowheads can show direction, cause-and-effect, etc.

5. Try to branch out at each level of the hierarchy with more than one link.

6. Identify and draw cross-links between related concepts. This is a powerful step in developing integrative thinking.

7. Alternative patterns: A “spider” or cluster pattern can be constructed from the center outward, but this will not be seen as readily by sensing types.

8. Leave white space to grow your map for further development, explanations, action items.

9. Expand the map over time (right up to an exam if necessary!)

10. Compare your maps with others; different groupings or overall organization can teach insight.

Figure 7. An example of a concept map of caffeine used to begin mapping its pharmacological effects on the body (from J.W. Pelley, Ph.D. https://www.ttuhsc.edu/medicine/medical-education/successtypes/documents/conceptmappingmedschool.pdf ).

A flexible and user-friendly software program that can be used on mobile phones, tablets, laptops, or desk-top computers is LucidChart, which will be provided to students in this course. Comparison of student-generated concept maps of a problem or question provides an excellent basis for a small-group learning session.

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References Cited Boaz, N. T. 2002 Evolving Health. New York: John Wiley Darwin, C.R. 1859 Origin of the Species. London: Murray.

Eaton, S.B., M. Shostack, and M. Konner 1986 The Paleolithic Prescription. New York: Harper and Row Kwan R, Mafe C. 2016 Rote learning: a necessary evil. Adv Med Educ Pract. Aug 2;7:429-32. doi: 10.2147/AMEP.S115838. PMID: 27536167; PMCID: PMC4976761.

Gluckman, P. D., Beedle, A., Buklijas, T., Low, F., & Hanson, M. A. 2016 Principles of Evolutionary medicine (Second edition). Oxford: Oxford University Press.

Mayr, E. 1982 The Growth of Biological Thought. Cambridge MA: Belknap.

Nesse, R., and G. Williams 1999 Why We Get Sick. New York: Vantage.

Regan-Smith MG. Obenshain SS, Zeitz H, Richards B, Wood- ward C, Small PA. 1994 Rote learning in medical school. JAMA, 01 Nov 1994, 272(17):1380-1381.

Simpson, G. G. 1944 Tempo and Mode in Evolution. New York: Columbia Univ. Press.

Stearns, S. C., & Medzhitov, R. 2016 Evolutionary medicine. Sunderland, Massachusetts: Sinauer.

Trevathan, W., E.O. Smith, and J. McKenna (eds.) 2007 Evolutionary Medicine and Health. 2nd ed. New York: Oxford University Press

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