Scientific Foundations Syllabus

Contact Information

Scientific Foundations

Director - Dr. Pete Takizawa

Threads

Important Dates

  • Self-Assessment: Friday, September 6 through Sunday, September 8
  • Qualifier: Wednesday, September 18 through Sunday, September 22

Assessment

The course offers three types of assessment. There will be one qualifier at the end of the course and a self-assessment midway through the course; both are required but only the qualifier requires you to achieve a minimum score. If your score falls below the minimum score, please contact the Course Director to set up remediation. The course will also offer weekly quizzes that address the content presented that week. These quizzes are optional.

Where to Get Help

It is not uncommon for students to struggle in this course or other courses. If you encounter difficulty learning the material, you can contact the Course Director to set up a meeting to find ways to help you navigate the course. Another resource is Student Helping Students which is a student-run group that reviews material covered in courses and presents the material in a way that previous students have found helpful. To get personalized help, Student Affairs can arrange for a tutor for a part of a course or an entire course.

Course Goals

Scientific Foundations aims to instill in students a firm understanding of the basic principles in molecular biology, cell biology, physiology and pharmacology that will serve as a foundation for your subsequent education and development as physician-scientists.

Course Learning Objectives

  • Students should be able to define the volumes and composition of the fluid compartments in the body and the mechanisms by which cells generate and use membrane potential.
  • Students should be able to diagram the pathways through which ligands and drugs alter cell behavior and calculate the availability, distribution, clearance and efficacy of drugs in patients.
  • Students should be able to describe the molecular connections and functional organization of macromolecules, cells and tissue.
  • Students should be able to describe the regulation of gene expression at the levels of transcription and translation and the mechanisms of protein folding, localization and degradation.
  • Students should be able to list the pathways and major enzymes that allow cells to generate molecules of energy currency (ATP, NADH, NADPH), generate the building blocks of macromolecules (amino acids, nucleotides and fatty acids), and metabolize macromolecules.
  • Students should be able to describe the basic pathways and mechanisms that regulate cell division and the responses of cells to injury.
  • Students should begin to identify biases in the way medical knowledge is generated or interpreted and how these biases affect patient care.
  • Students should begin to identify biases in the way medical knowledge is generated or interpreted and how these biases affect patient care.

    • Why study the basic sciences

    Before committing to learn new information and develop new skills, one should always consider what they will get from their new knowledge and skill set. Most people reading this syllabus hope to one day become a physician of some type. So, it’s reasonable for you to ask what benefit does learning the basic sciences offer to those who are on a pathway to becoming a physician.

    The primary benefit of a knowledge of the basic sciences to medicine is that it allows one to identify probable biological causes of disease. In addition to knowing the clinical symptoms of a disease, an understanding of basic science can help one develop a description of events at the molecular, cellular and physiological levels that have lead to a patient’s symptoms. What is the benefit to knowing these details?

    One benefit is to help you become a better diagnostician. An essential skill for most physicians is to consider information gathered from a patient’s history, physical exam, current complaint and perhaps a few initial test results and come up with a list of likely reasons for the patient’s current condition. This skill is called clinical reasoning and involves the process of developing a differential diagnosis. Most of you who have watched experienced physicians interact with patients probably marvel at how these physicians can effortlessly identify the reason for a patient’s ailment based on a few seemingly disparate pieces of information. Often, these physicians appear to use little information from the basic sciences to make their diagnosis.

    Thus, it is fair to ask what role, if any, does knowledge of basic science play in a physician’s process of diagnosing disease? This question has been studied experimentally, and the results suggest that physicians can usually rely on clinical information and use pattern recognition to diagnose simple or straightforward cases. However, when confronted with a challenging and complex case physicians will turn to their understanding of physiology and biomedical science to reason through the case.

    The same research study found benefits of biomedical knowledge to medical students. First, students who have learned the biomedical causes of disease retain for longer the ability to diagnose that disease compared to students who only learn the clinical features of the disease. Second, students who have learned the biomedical causes of diseases are better able to diagnose complex cases (e.g. cases with a lot of extraneous detail) which are a more accurate reflection of real-world cases. Thus, for both the novice and experienced diagnostician, biomedical knowledge has an important role in helping them diagnose disease in patients.

    Another benefit of biomedical knowledge is that physician-scientists can it to develop new diagnostic tests for disease and more effective and safer treatments for disease. Identifying the mechanisms and molecular players in disease processes creates opportunities to design methods to detect the development of a disease before it negatively impacts someone’s life. For example, knowing the role serum LDL plays in development of coronary heart disease has allowed us to identify patients who are at risk for coronary heart disease and implement treatments to reduce that risk. We can also target key molecular components of disease with drugs to slow or stop disease processes.

    Biomedical science seeks to understand health by learning about the parts.
    Biomedical science seeks to understand health by learning about the parts.

    How the Course is Organized

    Scientific Foundations presents the foundational material from several disciplines that are the pillars of biomedical science and medicine. These include Biochemistry, Cell Biology/Histology, Pathology, Physiology, and Pharmacology. Each of these disciplines will continue throughout the pre-clerkship curriculum where they are called threads because of the way their content is woven into the courses across the pre-clerkship curriculum. Scientific Foundations will present the core concepts and introduce the modes of thinking that are essential for each of these threads.

    Scientific Foundations will present the core concepts for longitudinal threads.
    Scientific Foundations will present the core concepts for longitudinal threads.

    When you draw on your biomedical knowledge to analyze a case, the relevant information doesn’t usually come from only one discipline. Instead, you will often integrate information from several disciplines. For this reason and others, the content from the threads covered in this course has been integrated into themes that reflect important biomedical processes:

    • Building a Body
    • Fluids and Gradients
    • Gene Expression
    • Cell Energy
    • Cell Communication
    • Life and Death of a Cell
    Scientific Foundations takes the core content from several disciplines and integrates it into themes.
    Scientific Foundations takes the core content from several disciplines and integrates it into themes.

    Each of these themes is composed of several subtopics.

    The themes in Scientific Foundations ground students in the principles of modern medicine.
    The themes in Scientific Foundations ground students in the principles of modern medicine.

    Themes

    Many of the themes in the the course are centered around cells and their roles in supporting critical life processes and development of disease. We are multicellular organisms that have evolved a developmental program (which will be described in Genes and Development) that creates structures - our organs and tissues - that perform specific functions to increase our chances of survival and reproduction. Disease often arises when one or more of our organs alters its normal behavior or fails to perform one of its evolved functions. To understand why organs and tissues stop working properly, we turn to biomedical science. Biomedical science operates under the paradigm that to understand the whole we must learn how the individual parts work and interact with each other. Thus, to understand how organs and tissues work and occasionally fail to work, we need to study their structural and functional parts. All organs and tissues are composed of cells and material produced by cells, which work in concert to generate the life-supporting functions of each organ and tissue. Thus, cells are the fundamental units of life and understanding how they work in tissues and organs is key to learning the biological causes of disease.

    Building a Body

    Building a Body describes the interactions that generate functional cells and allow cells to assemble into tissues and organs. Building a Body will first look at the component parts of cells, such as DNA, RNA, protein, lipid and carbohydrate, and then show how these macromolecules are organized to form cells. Next, we will examine how cells and the external macromolecules produced by cells assemble into functional structures called tissues. The body contains four types of tissues: epithelia, muscle, nervous and connective. Organs are composed of a mix of these tissues (and other types of cells) that generate a structure capable of performing several functions. Thus, Building a Body will trace the chain of interactions from molecules to cells to tissues and organs. Along the way, we describe diseases which arise due to small changes at the macromolecular level and compromise the function of tissues and organs.

    Building a Body diagrams interactions from molecules to macromolecules to cells to tissues.
    Building a Body diagrams interactions from molecules to macromolecules to cells to tissues.

    Fluids and Gradients

    Although we are land-based animals, all of the living cells in our body exist in an aqueous environment. The aqueous environment solubilizes critical biological molecules and driven by thermal energy allows them to diffuse and mix. As a result, enzymes find substrates to drive reactions; proteins bump into each other and adhere to create structures; nutrients move into cells while waste products leave cells. All this rapid movement of molecules and macromolecules, such as proteins, requires cells to have a barrier to prevent material they need to survive from simply diffusing away into the surrounding aqueous environment.

    The cell membrane defines this barrier and creates within our bodies two large reservoirs of fluid: intracellular and extracellular. Extracellular fluid is further subdivided into fluid that surrounds cells and fluid within the circulatory system. The types and amounts of solutes in these fluid compartments differs and is tightly regulated. For example, cells must balance the concentration of solutes inside their cell membranes with the concentration of solutes outside their cel membranes. An imbalance between concentrations generates an osmotic gradient which can cause cells to swell or shrink. Cells also generate chemical gradients of specific ions across their cell membranes. These gradients will allows cells to take up specific nutrients, undergo rapid changes in shape or biochemical activity and communicate with neighbors. When cells lose the ability to control these ion gradients, it often leads to death and a decrease in the functionality of the cells’ tissue or organ.

    Fluids and Gradients describes the content of body fluids and transport across membranes.
    Fluids and Gradients describes the content of body fluids and transport across membranes.

    Gene Expression

    Although the cells in our bodies are composed of four different types of macromolecules, proteins and to a lesser extent RNA drive most of the reactions that are critical to the function and survival of cells. The concentration and location of proteins within cells determines the rates of these reactions and whether the cell is normal, dying or dangerous. This theme will cover the events that produce a protein from a gene and describe the mechanisms that regulate the rate of protein production.

    Gene expression traces protein production and the perils of unfolded protein.
    Gene expression traces protein production and the perils of unfolded protein.

    Once a protein is synthesized its ability to catalyze a reaction depends upon whether it folds into a correct three-dimensional structure and finds its reactants. The theme will describe the basic process of protein folding and how cells target proteins to the specific organelles or regions of the cell.

    Lastly, given the large amount of protein produced by cells, they are always at risk of accumulating unfolded protein. Build up of unfolded protein in cells can lead to cell death and a reduction in a specific physiological activity. The theme will describe how cells detect and respond to unfolded protein.

    Cell Energy

    Many reactions and molecular events require an input of energy to proceed. Our cells obtain energy from the chemical bonds in the molecules that compose the food we eat. Because of the diversity of molecules in our food and the large number of different enzymes that require energy for their reactions, cells have evolved to use a common currency to exchange energy between food molecules and enzymes: ATP. This theme describes how cells convert macromolecules in food into ATP. The theme reveals how the pathways that lead from macromolecule to ATP are regulated and the benefits to cells of using one pathway versus another.

    Because cells in the different organs and tissues vary in their energy needs, our bodies need a global energy policy to maintain a sufficient distribution of energy-rich molecules throughout our body and to create an adequate reserve supply of energy when demand increases. Several homeostatic mechanisms control the concentration of energy-rich molecules in the circulatory system and the storage of energy as fat and carbohydrate. Breakdown of these mechanisms can lead to chronic diseases such as diabetes and cardiovascular disease.

    Cell Energy explores the integrated pathways of energy production and synthesis of key molecules.
    Cell Energy explores the integrated pathways of energy production and synthesis of key molecules.

    In addition to energy, our cells need an ample supply of macromolecules, such as amino acids, nucleotides, sugars and lipids, that are the building blocks of essential large molecules and structures. While some of these building blocks are obtained through our diet, our cells can also synthesize many to ensure they have an adequate supply. Occasionally, cells are face with the opposite challenge of having too much of a particular molecule and need a way to dispose of the excess. This theme will outline the anabolic and catabolic pathways that regulate the concentration of the different molecular building blocks.

    The importance of these biochemical pathways to medicine can be seen in the numerous genetic mutations that result in metabolic disease. Many of these mutations manifest themselves in newborns and are called in-born errors in metabolism. This theme will highlight these mutations, their medical impact and potential treatments.

    Cell Communication

    We are multicellular organisms composed of trillions and trillions of cells. There are over 200 different types of human cells and these are organized into tissues and organs that are distributed throughout our bodies. To produce a functioning organism, the cells in the different tissues and organs must work in a coordinated fashion. Coordination requires communication and this theme will explore how cells communicate with each other, often from different parts of the body.

    Cell Communication translates the language of small molecules and how cells listen to each other.
    Cell Communication translates the language of small molecules and how cells listen to each other.

    The theme will first describe the language of small molecules that cells use to communicate and show how cells detect and differentiate between different small molecules. Next, the theme will diagram the events that occur when a cell detects a specific small molecule and how a particular sequence of events triggers a change in cell behavior.

    With an understanding of how cell communication works, the theme will reveal how science and medicine have developed small molecules or drugs to manipulate the activity of cells either to treat a disease or reduce its symptoms. The basic mechanisms of action of drugs will be described as well as the way the body processes those drugs.

    Life and Death of a Cell

    All cells have a limited life span which is often determined by their exposure to the environment. As multicellular organisms, we need a way to replace dying cells so that our organs and tissues continue to function properly. In many organs and tissues, stem cells differentiate and divide to generate new cells that can replace old or dead cells. Importantly, the rate of cell division in a tissue or organ must closely match the rate at which cells are lost. If the rate of cell division is too fast, it leads to overgrowth of cells and can compromise the structure and function of a tissue or organ. Rapid cell division is also increases the risk of development of a tumor.

    Life and Death of a Cell reveals how and when cells divide and how and when they die.
    Life and Death of a Cell reveals how and when cells divide and how and when they die.

    This theme will describe the mechanics of cell division and then list the pathways and regulatory elements that control the rate of cell division. The theme will also introduce how mutations in regulatory factors lead to the development of tumors.

    Cells are also occasionally subjected to physical, chemical and even electrical trauma that causes damage. How they respond to these injuries determines whether cell survives, dies or becomes pathologic. The second part of this theme will show how cells respond to injury and try to repair themselves. The theme will also discuss what happens to a cell when the damage is too much to repair and how cells can die without causing damage to surrounding cells. Lastly, the theme will demonstrate the pathological effects of large scale damage to cells and tissues.

    Bias in Biomedical Research

    Using the scientific method (i.e. hypothesis-tested research) has increased our understanding of nature and allowed us to identify disease processes and intervene to slow and even stop those processes. The increase in expected life span over the last 100 years is due in large part to knowledge generated by biomedical research. Despite its successes, biomedical research is a human endeavor and affected by the biases of the humans who perform, oversee and use the research.

    Scientific Foundations will explore an important bias in biomedical research which is how do we decide which questions or problems to investigate. We lack knowledge about many diseases and even some basic biological processes, but have limited resources to fund studies to explore these areas. The course will provide examples of how the ways we view the world have influenced the choices we’ve made on what to research. You will have an opportunity to discuss these biases and identify additional biases.

    Teaching Methods

    Scientific Foundations uses lectures, small-group sessions, labs and team-based learning to deliver content and develop your critical-thinking skills.

    Lectures

    Lectures will present the essential concepts and illustrate the how these concepts inform medicine and our ability to diagnose and treat disease. Although the lectures will be recorded for you to review, I encourage you to attend lectures because it will give you the opportunity to interact socially and intellectually with your classmates, ask questions and hear questions from classmates, and get to know the faculty.

    If you have to miss a lecture, please try to watch the podcast of the lecture the same day it was given. Many of the small-group sessions assume that you are familiar with the content presented in the preceding lectures, and if you haven’t attended or watched a lecture, you will not be able to contribute to the discussion in small group and fully develop your critical-thinking skills.

    Small Group Sessions

    Scientific Foundations contains three different types of small group sessions from the Biochemistry thread, Physiology thread and Epidemiology and Public Health thread. These sessions from each thread will be indicated in your schedules by a two letter code:

    • Biochemistry: BC
    • Physiology: PY

    The different small groups will use different types of teaching methods and ask you to prepare differently before each session.

    Biochemistry Conferences

    Goals

    These conferences are designed to relate “textbook” biochemistry to the practice of medicine. Each conference is focused on a particular medical topic of biochemical relevance---emerging infections, new ways of looking at old diseases, and therapeutics. In each case, though disease is highlighted, it is the molecular aspects of the topic that will be emphasized. Our goal is to stimulate discussion on the underlying biochemistry, to provoke curiosity and to promote brainstorming on new approaches to medical problems.

    Format

    With the exception of the first biochemistry conference, which is led by the conference leader, each biochemistry conference will be led by the students. At the first conference each student will sign up to lead 2 discussions of their choice, working paired with another student. Their responsibility will be to summarize (5-10 minutes—good practice for ward rounds) the topic of the day, focusing on the articles included in the conference book, drawing from other sources when necessary.

    Student Preparation

    The student presenters must have read all the materials, must understand the figures and must be able to explain unfamiliar words. Handouts or writing on the board is preferred to Powerpoint for audiovisual aids.

    Each conference is accompanied by questions that will bring forth some important points for discussion, and the students will also lead the class in answering these questions. Discussion should not be limited to these questions, however, and other provocative questions are encouraged.

    The responsibilities of the students in the room who are not presenting are to read the conference materials and to come to class with new questions for discussion.

    All reading materials for the conferences will be available on BlueDogs.

    Students are expected to stay in their randomly assigned conference section unless they switch between levels. The learning that we hope to accomplish in the biochemistry conference sections is truly the “Yale System” at its best---students can pursue topics that catch their interest as far as that interest leads them.

    Role of Conference Leader

    The conference leader will be there to monitor the discussion, to answer additional questions and to serve as a resource for the student presenters.

    The conference leader is a discussion facilitator, and is there to make sure that there is a good discussion with participation from all members of the section. He or she will strive to make sure that the discussion is inclusive of everyone.

    Physiology Case Conferences

    Goals and Format

    The physiology case conferences use a clinical scenario to demonstrate involvement of physiological systems in whole body homeostasis. The goals are for students to identify and describe the involved physiological system(s), explain how a derangement or malfunctioning of the system correlates with the clinical presentation and explain how the proposed therapeutic approach compensates for and/or corrects the derangement or malfunction. Achieving these goals requires that students can identify relevant and irrelevant pieces of clinical data, i.e., critical thinking, and apply reasoning skills to explain the interactions of the physiological processes that are responsible for and/or compensate for the malfunction.

    The case conference leaders have flexibility in the teaching method they would like to use, but most have individual students answer a question, followed by embellishment and/or correction of the answer by fellow students and/or the faculty leaders. The individual cases typically have 8-12 questions, giving most, if not all students the opportunity to take the lead on answering a question in every case

    Student Preparation

    As the success of the sessions depends on participation by all students in the group, it is imperative that prior to the case conference session every student have: a) a good understanding of all lecture and assigned reading materials relevant to the physiological systems involved in the clinical scenario and b) drafted responses to each question in the case to the best of the knowledge and ability. Students should understand that it is not expected that they will provide the best and a thorough answer to every question, but it is expected that students will have drafted responses that demonstrate the use of their knowledge and understanding of the physiological systems

    It is also imperative that students do NOT use WebMD, Up-to-Date and similar online resources in drafting their responses. It is often clear to the faculty when such has been done as the responses are “shallow”, sometimes wrong and the student has very little knowledge beyond what was learned from these resources

    Role of Faculty

    The faculty leaders have two main roles. 1) To assist the group in fully answering the questions. 2) To mentor students having difficulty in providing thoughtful and complete answers to the questions or to challenge students with a better grasp of the content to provide a more in-depth answer

    Labs

    Scientific Foundations also has one pathology lab that introduces some of the essential concepts and skills in pathology that you will use throughout medical school. The labs are highly interactive and use active learning to teach content and develop critical thinking.

    Team-based Learning and Interactive Sessions

    Team-based Learning (TBL) and Interactive Sessions (IS) are a teaching methods that deliver content and allow students to apply what they’ve learned to solve real-world problems. Both employ a flipped curriculum in which you learn content before coming to class and then use in-class time for active learning and problem-solving. In class, you will work in a team to answer questions and solve problems. For more information on TBL, please Read More. Interactive Sessions differ from TBL by having a less defined format.

    Prep Time

    Scattered throughout the course are sessions called prep time. These have been inserted into the schedule for you to use to prepare for team-based learning sessions or interactive sessions by watching videos or reading notes or textbooks. Students are expected to devote up 20 hours each week to prepare for sessions in their courses and activities in their clinical experiences (ILCE and Clinical Skills). Sessions that have prep time require you to devote extra time to learning material and to accommodate this increased time, we have set aside time for what would have been a lecture in the course for you to finish the preparatory material.

    Online Pharmacology Module

    The Pharmacology Thread has developed an online curriculum that describes how new drugs are discovered, tested and then reviewed. The online curriculum was developed in collaboration with Merck Pharmaceuticals and is the divided into five modules:

    • How Drugs are Discovered
    • Consideration for Testing a Drug on Humans
    • How Investigational Drugs are Tested in Humans
    • Regulatory Review Process for New Drugs
    • Post-Approval Activities
    • Principles of Vaccine Development and Clinical Vaccinology

    In Scientific Foundation, we ask that you complete the first two modules before September 17. On that date, there will be an in-class discussion of the content in the first two modules. If you have any questions about the online Pharmacology modules, please contact Dr. Mike DiGiovanna at michael.digiovanna@yale.edu.