Scientific Foundations Syllabus

Goals of Course

Modern medicine is built upon our understanding of how the human body works, fails and responds to treatment. Biomedical science is the tool that has allowed us to expand our knowledge of the human body and design treatments and cures for diseases. This course provides you the content and critical thinking skills to develop your own foundational understanding of biomedical science and medicine.

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, Epidemiology and Public Health, Pathology, Physiology, and Pharmacology. Each of these threads will continue throughout the pre-clerkship curriculum, so Scientific Foundations will present the core concepts and introduce the modes of thinking that are essential for each thread.

Instead of presenting each thread in its own silo, the content from most of the threads has been integrated into themes:

  • Building a Body
  • Fluids and Gradients
  • Gene Expression
  • Cell Energy
  • Cell Communication
  • Life and Death of a Cell
  • Population Health

Themes

Building a Body

Life depends upon interactions. Chemicals interact to form molecules. Different molecules join to form macromolecules, such as DNA, RNA, protein, lipid and carbohydrate. These macromolecules coalesce to form living units called cells. Cells and external macromolecules organize into functional structures called tissues. Tissues contribute to the structure and function of the all of the organs in our bodies, and the organs generate the physiological activities that give us life. This chain of interactions that links molecules to tissues and organs means that events at the molecular and cellular level drive the activities of tissues and organs.

This theme will describe the connections that lead from molecules to macromolecules to cells to tissues and how the properties of individual components at each level affect structure and activity of the next level. We start with the structure and properties of the four major macromolecules and how each is assembled from smaller molecular subunits. We then turn our attention to how these macromolecules interact to form the primary structural units of cells, including cell membrane and cytoskeleton. Next, we examine how individual cells interact with each other and an external matrix of macromolecules to form the tissues in our bodies. Lastly, we explore how these interactions mediate the development of a fertilize egg into an embryo. Along the way, we describe diseases which arise due to small changes at the macromolecular level compromising the function of tissues and organs.

Fluids and Gradients

Although we are land-based animals, all of the living cells in our body exist in an aqueous environment. The inside of cells is also aqueous, meaning that any water-soluble molecule or macromolecule can freely diffuse into or out of a cell. In Building a Body, we'll explain how the cell membrane restricts diffusion of material into and out of cells. Fluids and Gradients will reveal that the ionic composition of the fluid inside cells is very different from the fluid surrounding cells, creating ion gradients across the cell membrane. The theme will explain the biological significance of the ion gradients and how cells expend energy to maintain the gradients. Lastly, the theme will detail how disruptions in the gradients lead to disease and how physicians use measurements of ionic composition of the bodies fluids to diagnose disease.

Gene Expression

Although the cells in our bodies are composed of four 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 briefly cover the events of protein production but delve deeper into the mechanisms that regulate the rate of protein production.

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 too much 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

Life requires energy. In our bodies and cells, the main currency of energy is ATP but other molecules are also used. This theme describes how cells convert macromolecules we obtain from food into ATP and other key molecules. 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.

Our body stores energy which is released when the demands for energy exceed the readily accessible supply or when resources are limited. The theme will describe how cells convert molecules we obtain from digestion of food into macromolecules, such as carbohydrate and lipid, instead of ATP.

Having shown how cells store energy and generate ATP, the theme will describe how cells use energy and ATP to build the molecules, such as nucleotides amino acids, that are required to assemble the macromolecules which are essential for life.

Lastly, the theme will point out mutations that affect the activity of enzymes in the pathways that produce and store energy and how those mutations lead to disease.

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.

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

We constantly lose cells everyday to natural processes. Continuous loss of cells without replenishment would compromise the activities of our tissues and organs. Cell division gives rise to new cells that can replace old or dead cells. The rate of cell division in a tissue or organ must closely match the rate at which cells are lost. Too much cell division leads to overgrowth of cells and potential formation of a tumor.

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 the 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.

Population Health

In medicine, each scale of analysis brings with it a distinctive set of principles, concepts, and dynamics. This is as true for populations as it is for macromolecules, cells, or individuals. In Scientific Foundations, the Epidemiology and Public Health Thread will explore foundational issues in population health that can be revisited in more sophisticated and clinically relevant forms later on.

On the epidemiological side this includes understanding the metrics of disease in populations - incidence and prevalence - and the various ways these measurements are used. This is followed by an exploration of causation, a concept at the very center of medical science. The remaining sessions focus on the range of study designs that are used in both public health and clinical epidemiology. Two particular challenges are emphasized: the relationship between the nature of the investigation and the selection of an appropriate study design, and the vulnerability of such designs to bias and confounding.

Epidemiological analysis is taught in the context of specific public health challenges. We begin by exploring the importance of prevention and examine differences between moderating the impact of disease on individuals and developing programs to prevent illness in populations. We take up the problem of medical errors, but in Scientific Foundations the public health topics also emphasize the health consequences of social influences that may not be under the control of medicine. These include social disparities in health, disasters and emergency preparedness, and incarceration.

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
  • Epidemiology and Public Health: PH
  • 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.

Epidemiology and Public Health Workshops

Goals and Format

The workshop is the primary teaching vehicle for the Thread and provides a forum for epidemiology Case Studies and journal article discussions. These discussions also address clinical recommendations, ethical considerations, and public health policies. Following introductions at the first session, students will each select (using a lottery system) a public health Thread topic to present, based on a peer-reviewed journal article. For each workshop session, epidemiological techniques and concepts have been placed in association with a field of public health and are organized in a logical sequence. The idea is to make the epidemiology relevant to the public health area under discussion, and progressively add depth to students' ability to assess the professional literature.

Student presentations are made in pairs, and student leaders may choose any of the articles listed at the end of the Lesson Plan for that session. The articles have been selected based on 1) their relevance to the public health topic of the week, 2) the methods used and the epidemiologic issues raised by the research (always the same as the epidemiologic technique/concepts covered in that week's Case Study), and 3) the articles' potential to stimulate critical discussion. The student-led workshop discussions should take 40-50 minutes.

Student Preparation

Epidemiology Lesson Plans: There is a Lesson Plan associated with each week's topic. The Lesson Plans include a brief introduction to the public health topic; the week's learning objectives in both public health and epidemiology; the assigned and recommended readings; an outline of the epidemiology topics for which you are responsible; the lecturer and lecture title.

Epidemiology Case Studies: Workshops begin with Case Studies, which focus on key epidemiologic points highlighted in the learning objectives in the week's Lesson Plan. Background material necessary for completing the Case Studies is found in the assigned epidemiology reading, also listed on the week's Lesson Plan. The Case Studies draw from both peer-reviewed articles and hypothetical scenarios. Please read the Case Studies ahead of the session and be prepared to respond to the questions in workshop.

Assigned Readings: There are articles and/or chapters assigned each week, and these are listed on the Lesson Plans. To improve the accessibility of the material and to assist in learning key concepts in the reading material, an outline of the week's public health and epidemiology topics are provided in each Lesson Plan. It will be helpful to read the outlines before tackling the assigned readings. The readings serve as introductions to the public health topic and cover an epidemiologic technique or concept associated with that topic. The assigned readings are designed to take less than two hours per week. You are asked to read the articles before workshop and to be prepared to discuss them.

Recommended Readings: These articles have also been included in the Lesson Plans for students who would like to explore the topic in greater depth. The articles are readily available via links on Blue Dogs and through the iPads; students are encouraged to look through these articles, as time and interest allows.

Organizing Your Journal Article Presentation: Students should contact their workshop leader one to two weeks ahead of time regarding their choice of journal article and discuss their approach to the material. S/he will also be available to help guide you, refine the questions to be addressed, review drafts of slides, and if requested, refer you to expert faculty.

Faculty workshop leaders may ask to see an outline of the presentation prior to the session - this is requested only to provide helpful suggestions or feedback.

  1. It is recommended that presenters use 7-10 PowerPoint slides. The slides may be of various kinds: reproductions of tables or figures from the article; summary slides the presenters feel will be helpful to the discussion; slides drawn from other material connected to the topic. Please refrain from using extended audio or video material as part of the presentation.
  2. Please begin your presentation by stating the question that the investigators have chosen to address. The remaining discussion can help situate the journal article in the context of the public health field, explore the strengths and weaknesses of the methods, evaluate the importance of the intervention under study, or consider what might be successful "next steps" in the research agenda. It is also appropriate to raise questions about the clinical, policy, or bioethical implications of the article.
  3. Please choose to emphasize two or three of the above elements rather than offer an encyclopedic amount of material. This will enhance your presentation and place a personal stamp on the discussion. That is, it is better to go deeply into a few points than to skim over many issues. Discussions are intended to be analytic rather than strictly informational.
  4. Student leaders are asked to consider how best to draw classmates into the conversation. This can be done, in part, by framing the presentation as a story or narrative to show how the investigators approached their research question. Please feel free to challenge classmates as to how they would have organized the study, which techniques they would have used as methodology, or what they would have anticipated the results would show. Material from the article can then be incorporated or summarized as necessary.

The following article offers an introduction to journal article presentation.

Atzema C. Presenting at Journal Club: A Guide. Ann. Emergency Med. 2004; 44(2): 169-74. (http://www.sciencedirect.com/science/article/pii/S0196064404003361#)

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

There are two types of labs in Scientific Foundations. Histology labs focus on teaching you the structure function relationship of cells and tissues and helping you develop the skill of identifying cells and tissues based on their appearance in histological slides.

The histology labs will employ a flipped curriculum to allow you to learn content and engage in active learning and application of knowledge. Each lab will have a video and reading that will teach you the essential content for the lab. You should complete one or both of these before coming to the lab. In the lab, you will work on you own and in a team to answer questions and solve problems.

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

Team-based Learning (TBL) is a teaching method that delivers content and allows students to apply what they've learned to solve real-world problems. TBL employs a flipped curriculum in which you learn content before coming to class and then use in-class time for active learning and problem-solving. As the name suggests, you will work in a team to answer questions and solve problems. For more information, please Read More

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:

  1. How Drugs are Discovered
  2. Consideration for Testing a Drug on Humans
  3. How Investigational Drugs are Tested in Humans
  4. Regulatory Review Process for New Drugs
  5. Post-Approval Activities

The modules can be accessed via this link: http://curriculum.med.yale.edu/pharm/merck/ In Scientific Foundation, we ask that you complete the first two modules before September 22. 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.

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. The course will also offer weekly quizzes that address the content presented that week. These quizzes are optional.