May 2009

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BIOASTRONAUTICS: A Training Program within HSTs Medical Engineering and Medical Physics (MEMP) PhD Program

May 2009

Introduction

Bioastronautics at the interface of biology, medicine, engineering and space research challenges the state of the art in human protection and integrative physiology. An astronaut who travels for long periods far from earth is affected by weightlessness, space radiation, and psychological stress, and is utterly dependent on artificial life-support. Bones and muscles, cardiovascular regulation and sensory-motor control depend on gravity on earth and require protection during space flight. The challenge of bioastronautics is to protect the astronaut during and following long flights, and to provide air, water, food, and telemedicine, while dealing with the scientific issues of gravitational biology. The new specialty, leading to a PhD in Medical Engineering and Medical Physics (MEMP) from the Harvard-MIT Division of Health Sciences and Technology (HST), will train leaders in bioastronautics for the 21st century. Established in 2006 and funded by the National Space Biomedical Research Institute (NSBRI), with support from NASA and its Johnson Space Center (JSC), the program adds to the basic training MEMP provides in biomedical and engineering disciplines. At the same time, it provides applications to human factors and space life sciences, and hands-on experience relating to human space flight operations. The Bioastronautics Training Program is open to MEMP students or other HST students pursuing a PhD at Harvard or MIT. Bioastronautics students must fulfill the MEMP requirements and take three foundation subjects with one additional subject chosen from a list of restricted electives (below). They attend specialized seminars throughout the academic year. They also spend a summer working in a setting of practical space activities--normally a months course at JSC, followed by an internship at NASA or at an industrial laboratory. Their clinical preceptorship (HST203) is taken at a NASA center or related laboratory, for example it may be combined with the Aerospace Medicine clerkship at JSC. Bioastronautics students normally pursue their thesis research with one of the Harvard or MIT faculty who are Principal Investigators of NSBRI or NASA Life Sciences grants. Applications to the program should be made at the time of application to MEMP and are due by December 15 of each year for the following September. Contact Catherine Modica (cmodica@mit.edu) for information about applying to MEMP or Prof. Laurence R. Young (lry@mit.edu), the Program Director, for information concerning the academic program.

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Descriptions of courses required for students in the Bioastroanautics Training Program beyond those required of all MEMP students

Please check MITs online subject listings and schedule at

http://student.mit.edu/catalog/index.cgi for updated schedule information.

Items in square brackets after course title indicate [Level / Units / Term (year indicates when next offered for alternate year course) / Prerequisites (P=Permission of the

instructor)]

Bioastronautics Foundations and SLS Seminar HST515J/16.423: Aerospace Biomedical and Life Support Engineering [H/ 3-1-8/ Spring/ 16.400, 16.06, 16.060 or P] (Newman) offers an advanced graduate curriculum in space life sciences and surveys the entire field. This subject will treat fluid regulation, the biological effects of stress, and microgravity countermeasures to the current emphasis on gravitational physiology.

16.453: Human Factors Engineering [H / 3-1-8 / Fall / 16.06 or 2.010] (Cummings and Young) covers human-systems integration with applications to aerospace vehicles and systems. It will teach anthropometrics, automation, human-computer interfaces and other topics relating to the human-vehicle interface. 16.89: Space Systems Engineering [H / 4-6-2 / Spring / 16.851, 16.892 or P] (Hoffman et al) focuses on the space system architectures and includes a preliminary spacecraft design. It will normally include aspects of human-induced constraints such as acceleration tolerance, communication requirements, radiation protection and EVA workload. (Earlier, this subject pursued a comprehensive Moon-Mars mission architecture study that led to a report "Paradigm Shift in Design for NASA's New Exploration Initiative" and to an MIT-Draper CE&R project.)

16:459: Bioengineering Journal Article Seminar [G / 0-2-0 / Fall, Spring / none] (Oman and Young): In addition to the HST Biomedical Engineering Seminar (HST 590) required of all MEMP students, the Bioastronautics students will participate in a specialized journal club format seminar series that provides a forum for review of Space Life Sciences journal articles and presentations of research by faculty and students. This seminar is offered each term and is intended to broaden the students view of the field. It links each month, by videoconference, to the University of Texas, Medical Branch (UTMB) Aerospace Medicine Grand Rounds.

Bioastronautics Restricted Electives Beyond the required Bioastronautics foundations subjects and the SLS Seminar, students in the program will choose at least one restricted elective from among the following subjects:

HST514J/16.430J: Sensory-Neural Systems: Spatial Orientation from End Organs to Behavior and Adaptation [H / 3-0-9 / Spring / Neurosciences, or Systems Engineering or P] (Young, Oman, Merfeld, and Wall) explores the sensorimotor system, especially in unusual environments. It will treat in depth the following topics in space

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physiology: sensory and balance system, motion sickness, sensory-motor adaptation, and countermeasureswith particular attention to artificial gravity.

HST560J/22.55J: Radiation Biophysics [H/ 3-0-9 / Spring / P] (Yanch) considers electromagnetic as well as passive shielding and the space radiation environment as it interacts with biological materials, cells and tissues.

HST922: Information Technology in the Health Care System of the Future [G/ 2-0-7/ Spring / None] (Locke et al) relates computer technology to delivery of care to patients, including telemedicine and special issues of astronaut treatment for medical and behavioral problems. It will include the topics of smart medical systems, sensor networks and monitors, safety, robotics and communication for human space missions.

HST971J/15.363J: Strategic Decision-Making in the Biomedical Business [G/ 3-0-6 / Spring / None] (Murray) is an introduction to some of the management issues associated with biomedical product development, as suggested by some of our industry associates. It covers a wide variety of activities at a range of company stages from start-up to mid-range to big pharmaceutical firms. Students wishing to study further may take more advanced subjects offered in the HST Biomedical Enterprises program.

16.895: Engineering Apollo: The Moon Project as a Complex System [H/ 3-0-9/ Spring / P] (Mindell and Young) offers a detailed technical and historical exploration of the Apollo project to fly humans to the moon. It relates the human space flight challenges of Apollo to the current Moon-Mars Vision.

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Detailed Course Descriptions (Based on Previous Offerings) HST 515J Aerospace Biomedical and Life Support Engineering offers an advanced graduate curriculum in space life sciences and surveys the bioastronautics field. This course was greatly enhanced through an NSBRI education grant (Newman) and includes 4 NSBRI PIs as lecturers. This course introduces students to a quantitative approach to the problems of physiological adaptation in altered environments, especially microgravity and partial- gravity environments. The course starts with an Introduction & Selected Topics, which provides background information on the physiological problems associated with human space flight, as well as a review of terminology and key engineering concepts. Modules on Bone Mechanics, Muscle Mechanics, Musculoskeletal Dynamics and Control, and the Cardiovascular System are then presented. These modules begin with qualitative and biological information about the system and its adaptation, and progress to a quantitative endpoint in which engineering methods are used to analyze specific problems and countermeasures. Part of the course curriculum focuses on interdisciplinary topics that may include extravehicular activity and life support. The final module consists of student term-project work. Students can choose to learn more about: neurovestibular physiology, creativity and visualization, leadership, engineering education, or to take an industry field trip. Learning Objectives 1. To apply engineering methods to the study of astronaut adaptation to reduced gravity environments. 2. To use analytical techniques, such as structural idealizations, control theory, electrical circuit and mechanical system analogs to model astronaut performance. 3. To enable quantitative assessment of the effectiveness of countermeasures. 4. To consider the socio-political implications for advanced technological R&D (e.g., space policy, health policy, international collaboration). 5. To teach, perform outreach, and demonstrate mastery of a chosen engineering concept. Measurable Outcomes and Assessment Students graduating from 16.423J/HST.515J will be able to: 1. Explain the short-term and long-term physiological consequences of space flight. 2. Use analytical techniques such as structural idealizations, control theory, electrical circuit and mechanical system analogs to model astronaut performance. 3. Calculate the stress and strain state in a human bone such as the proximal femur. 4. Use a mechanical model including springs, dashpots and concentrated masses to simulate muscle groups. 5. Derive and apply the equations of motion for a multibody dynamic system and understand applications of the theory.

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6. Select control laws and evaluate control parameters applied to space biomedical engineering. 7. Use a resistance-capacitance model to evaluate changes in the cardiovascular system. 8. Formulate multidisciplinary engineering-based models for physiological systems and identify the assumptions and limitations. 9. Communicate a scientific or technological research problem to policy/decision makers. 10. Teach younger students engineering concepts. Sessions: 1 Introduction 2 Term Project Ideas assignment posted 3 Humans in Space 4 Initial Self-Assessment assignment due 5 Exploration in Extreme Environments 6 Bone Changes in Space 7 Extreme Environments (continued) 8 Modeling Bone Space Flight Alterations 9 Muscle Mechanisms 10 Assignment 2: Bone assignment due 11 Muscle Mechanisms (continued) 12 Motor Control Optimization 13 Assignment 3: Muscle Modeling assignment due 14 Leadership: Apollo 13 Case Study 15 Quiz 1 16 Musculoskeletal Dynamics and Control 17 Dynamics and Demos 18 The control of hand equilibrium trajectories in multi-joint arm movements 19 Equilibrium point control hypothesis examined by measured arm stiffness. 21 Are complex control signals required for human arm movement? 22 Coriolis-force-induced trajectory and endpoint deviations in the reaching

movements of lab. 23 Team Project Day 24 Countermeasures and Artificial Gravity 25 An Overview of Artificial Gravity (optional) 26 Countermeasures and Artificial Gravity 27 Assignment 4: Dynamics assignment due 28 Team Project Day - Report to 26-414 at 9:30 29 Cardiovascular System, Prof. Roger Mark 30 Life Support and Performance Issues for Extravehicular Activity(EVA) 31 Extravehicular Activity (EVA) 32 An Investigation of Space Suit (Optional) 33 Cardiovascular Control, Prof. Roger Mark 34 Extravehicular Activity (EVA) 35 Cardiovascular Simulation, Dr. Thomas Heldt 36 An Episode of Ventricular Tachycardia During Long-Duration Spaceflight

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37 Venous Pressure in Man During Weightlessness (optional) 38 Cardiovascular function and basics of physiology in microgravity (optional) 39 EVA II: Research 40 Quiz #2 41 Student Term Presentations 42 Student Term Presentations 43 Teaching and Outreach 44 Teaching and Outreach

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16.453 Human Factors Engineering

Accidents associated with human error often reflect the failure to recognize human factors in the design stage. Interaction of humans with aircraft, spacecraft, and other complex machines. Manual control and human-computer interaction in semi-automated vehicles. Reviews sensory, motor, and cognitive performance characteristics and derives human engineering design criteria. Principles of displays, controls and ergonomics applied in various class design exercises. Meets with undergraduate 16.400, but assignments differ. A term project is required for Graduate credit.

Required Course Texts: Wiener, E. L., & Nagel, D. C. (Eds.). (1988). Human Factors in Aviation. San Diego:

Academic Press. (WN) Dismukes, R.K., Berman, B.A., & Loukopoulos, L.D (2007 ) Human Factors: The

Limits of Expertise. Rethinking Pilot Error and the Cause of Airline Accidents. Burlington, VT: Ashgate.

Wickens, C.D., & Hollands, J.G. (2000). Engineering Psychology and Human Performance. Upper Saddle River, NJ : Prentice Hall

M.S. Sanders and E. J. McCormick, (1993) Human Factors In Engineering and Design New York: McGraw-Hill. (SM)

Wiegmann, D.A., & Shappell, S.A., (2003) A Human Error Approach to Aviation Accident Analysis. Burlington, VT: Ashgate

Topic Primary Reading Case Study Notes

Intro SM1 Everglades L1011 Crash Example presentation

Human Senses in Flight WN4 SM 4 (91-100), 6 WS1 (G)

NTSB-AAR-74-3 (Delta - Boston, Bad FD)

Experimental Design I SM2 Website1

Air France Flight 3582 (Runway overrun)

Project #1, Due 28 SEP

Experimental Design II Website3 NTSB LAX05IA312 (LA JetBlue Nosewheel)

Information Processing WN5 SM3 WS2 (G)

NTSB: LAX02FA114 (LA - Helicopter CFIT)

Anthropometry & Cockpit Design

WN15 SM10, 13, 16

NTSB MIA02LA010 (MS - Gear-up Landing)

Spatial Orientation [1] SM 19

NTSB: NYC99MA178 (JFK Jr.) Project #2, Due 12 OCT

1 http://faculty.vassar.edu/lowry/webtext.html Chapters 1,2, 3(Parts 1 & 2), 7, 9, 10, 11, 12 2 http://en.wikipedia.org/wiki/Air_France_Flight_358 3 http://www.fao.org/docrep/W7295E/w7295e08.htm through section 6.4.4

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Workload & Situation Awareness

WN6, [2, 3]

BMI B737, 8JAN89, Leicestershire, UK4 (Engine shutdown error)

Displays I WN12 SM4, 5,10 WS3 (G)

20 JAN 92, A320 crash Strasbourg, France

Displays II SM6 MIA01FA028A (F-16/Cessna Midair)

Project #3 Due 31 OCT

Automobile Human Factors SM21

[4] Guest Lecturer: Dr. Andrew Liu

Quiz 1

Error WN9 SM20 WS4(G)

NTSB/AAR-88-05 (MI - Flaps on takeoff)

Automation WN13 SM22

American Airlines Flight 965, Cali5

Training & Aviator/Astronaut Selection

WN8 [5]

Long Duration Astronaut Selection6

Project #4, Due 14 NOV

Helicopter Human Factors WN18 NTSB SEA02FA008 (Alaska Helicopter)

Space HF I Casey Chapter [6]

Space HF II WS5 (G) [7]

Manual Control 1 [8] NTSB AAR-04/04 (NY - AA Tail Separation)

Manual Control 2 WN11 NTSB CHI95IA138 (DC - NWA PIO)

Manual Control 3 YF-22 crash 25 APR 92

Crew Resource Management WN7 WS6&7 (G)

NTSB NYC02LA013 (VA - Hard Landing)

Manual Control P-set Due

Review of Manual Control Homework & Round-up

Air Traffic Control WN19 Bashkirian Airlines Flight 29377 Guest Lecturer: Dr. Jing Xing, FAA CAMI

Quiz 2

Grad Student Presentations Grad final projects due

Student Case Study Presentations: Students will be assigned in groups no larger than 3 to present the case listed on a particular day. If a change of group assignment is needed, see the TA. Presentations should be 10-15 minutes long, cover the basic timeline and elements of the crash, and then analyze the human factors that shaped the incident. Pay particular attention to the topic of that days lecture as a guide to the human factor of interest. While all students should read the case summary prior to each class, presenters are expected to go beyond the provided web links to add additional information to their presentations. Important websites: 4 http://en.wikipedia.org/wiki/Kegworth_air_disaster 5 http://sunnyday.mit.edu/accidents/calirep.html 6 http://www.airspacemag.com/ASM/Mag/Index/1996/JJ/llda.html 7 http://en.wikipedia.org/wiki/Bashkirian_Airlines_Flight_2937

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NTSB search engine: http://www.ntsb.gov/ntsb/query.asp NTSB full reports from last 10 years: http://www.ntsb.gov/Publictn/A_Acc1.htm NTSB reports from 1968 1996 courtesy of Embry Riddle: http://amelia.db.erau.edu/reports/ntsb/aar/ Assignments:

Case Study Summaries: Those students not presenting a case study for a particular lecture will prepare a maximum one page summary of key human-factors issues in each case, and how they could be avoided in the future. This will be an individual effort and assignments will be turned in via the Stellar website (under Homework) prior to class.

Project assignments occur approximately every two weeks, and will be collaborative efforts with no more than 3 on a team. Individual project descriptions can be found on the Stellar website, and students will choose their own teammates.

Graduate Final Project: The final project for the 16.453 students will focus on the application of the Human Factors Analysis and Classification Scheme (HFACS) as outlined in the Wiegmann & Shappell text. Graduate students will select one of the topics from the list on Stellar, apply HFACS to each of the 3 cases both to draw conclusions as to the human factors involved in each of the individual cases as well as to perform a meta-analysis on the trends that embrace the 3 cases. This is an individual effort. It is expected that the reports will integrate topics covered throughout the semester throughout the model. All reports should conclude with a detailed evaluation of the HFACS methodology and its ability to provide accurate human factors analysis for individual cases as well as its ability to highlight systemic problems. On the final day of class, graduate students will give an oral presentation in class as well as hand in the written report, which should follow the format of a traditional research report. Grade Basis: Undergraduate Graduate Quiz #1 30% Quiz #1 25% Quiz #2 30% Quiz #2 25% Homework: 30% Homework: 10% Participation 10% Final Project 30% Total 100% Participation 10% Total 100% Reading References which can be found on the Stellar Site: [1] L. Young, " Spatial Orientation," in Principles and practice of aviation psychology. , P. S. Tsang

and M. A. Vidulich, Eds. Mahwah, NJ: Erlbaum, 2003, pp. 69-114. [2] N. R. Johnson and E. M. Rantanen, "Objective pilot performance measurement: A literature

review and taxonomy of metrics " presented at 13th International Symposium on Aviation Psychology,, Oklahoma City, 2005.

[3] M. Endsley, "Theoretical Underpinnings of Situation Awareness: A Critical Review," in Situation Awareness Analysis and Measurement, M. Endsley and D. J. Garland, Eds. Mahwah, NJ: Lawrence Erlbaum Associates, 2000, pp. 3-32.

[4] D. L. Strayer, F. A. Drews, and D. J. Crouch, "A Comparison of the Cell Phone Driver and the Drunk Driver," Human Factors, vol. 48, pp. 381391, 2006.

[5] T. R. Carretta, "Common Military Pilot Selection Practices," in Human Systems IAC Gateway, vol. XIII, H. S. I. A. Center, Ed.: U.S. Air Force, 2002, pp. 1-4.

[6] S. M. Casey, "Picture Window," in The Atomic Chef and Other True Tales of Design, Technology, and Human Error. Santa Barbara: Aegean, 2006.

[7] S. R. Ellis, "Collision in Space," Ergonomics in Design, vol. 8, pp. 4-9, 2000. [8] R. A. Hess, "Pilot Control " in Principles and practice of aviation psychology. , P. S. Tsang and

M. A. Vidulich, Eds. Mahwah, NJ: Erlbaum, 2003, pp. 265-309

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16.89J Space Systems Engineering Focuses on developing space system architectures. Examines interactions among subsystems in the context of designing a space system. Presents and applies to the project principles and processes of systems engineering, including developing space architectures, developing and writing requirements, and concepts of risks. The deliverable product at the end of the course is a conceptual design of a space system. Note: In recent years, this course has concentrated on human space systems, applicable to NASAs space exploration agenda. During the first part of the course, the faculty give lectures on various aspects of space systems engineering. The main part of the course consists of the students carrying out the space system design. Extensive use is made of the Aero/Astro computer design studio. This course is intended to give students actual experience in a team-based design process. Required text: Human Spaceflight Mission Analysis and Design, Wiley J. Larson and Linda K. Pranke, eds. McGraw Hill Space Technology Series Suggested texts: Space Mission Analysis and Design (3rd Edition); James R. Wertz and Wiley Larson, eds. McGraw Hill Space Technology Series Space Vehicle Design (2nd Edition) Michael D. Griffin and James R. French, AIAA Education Series The Lunar Base Handbook, Peter Eckart, McGraw Hill Space Technology Series Brief description of projects the students may be assigned. The most recent project was the design of a surface transportation system for lunar and Mars exploration. Topic for Spring 2008 will be a human mission to a near-Earth object (NEO).

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HST514 Sensory-Neural Systems: Spatial Orientation from End Organs to Behavior and Adaptation. Subject introduces sensory systems, and sensorimotor integration using spatial orientation and posture control systems as a model. Topics range from end organ dynamics to neural responses, to sensory integration, to behavior and adaptation, with particular application to balance, posture and locomotion under normal gravity and the conditions of space. Depending on the background and interests of the students, advanced term project topics might include: motion sickness; astronaut adaptation; artificial gravity; lunar surface locomotion and vestibulo-cardiovascular response; vestibular neural prostheses; or other topics of interest. Alternate-week student-team and weekly faculty presentations; term paper. The graduate-level bioastronautics subject was developed under a grant from the National Space Biomedical Research Institute. Student teams review 2-3 journal articles per week on alternate weeks. An individual term paper (20-30 pages) is required on a topic relevant to the course. Visits to Jenks Clinical Laboratory and Physiology Laboratory at Massachusetts Eye and Ear Infirmary. http://stellar.mit.edu/S/course/HST/sp06/HST.514J/

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HST560J Radiation Biophysics Objectives: The central theme of this course is the interaction of radiation with

biological material. The course is intended to provide a broad understanding of how different types of radiation deposit energy, including the creation and behavior of secondary radiations; of how radiation affects cells and why the different types of radiation have very different biological effects. Topics will include: the effects of radiation on biological systems including DNA damage; in vitro cell survival models; and in vivo mammalian systems. Covers radiation therapy, radiation syndromes in humans and carcinogenesis. Environmental radiation sources on earth and in space, and aspects of radiation protection are also discussed. Examples from the current literature are used to supplement lecture material.

Textbook: Radiobiology for the Radiologist (5th edition)

Hall, Eric J., Philadelphia, Lippincott Williams & Wilkins, 2000. Grading: There will be about 6 problem sets over the course of the semester. There

will be two exams. All students are required to write a term paper on a topic related to the subjects covered in this course. A list of possible topics will be provided, but students are free to choose their own topic. All students are required to give an oral presentation on their term paper topic. There will be no final exam.

Grading will be divided as follows: Problem sets, Exams, Term paper and presentation (30, 40, 30) %. Additional References

Atoms, Radiation, and Radiation Protection (2nd edition) Turner, J. E., New York, J. Wiley, 1995. Introduction to Radiobiology Tubiana, M., J. Dutreix, A. Wambersie, Taylor and Francis, London, New York, Philadephia, 1990. Radiation Biophysics (2nd edition) Alpen, Edward L., San Diego, Academic Press, 1998. Molecular Cell Biology (4th edition) Lodish, Berk, Zipursky, Matsudaira, Baltimore, Darnell, W.H. Freeman and Company, New York, 2000.

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16.895J Engineering Apollo: Moon Project as a Complex System

A detailed technical and historical exploration of the Apollo project to fly humans to the moon and return them safely to earth, as an example of a complex engineering system. Emphasis is on how the systems worked, the technical and social processes that produced them, mission operations, and historical significance. Topics include: historical antecedents, guidance and control, digital computing, systems engineering, project management, human-machine interface, propulsion and structures, space policy, industrial infrastructure, Cold War politics, American culture in the 1950s and 1960s, and future moon missions. Guest lectures by MIT-affiliated engineers and astronauts who contributed to and participated in the Apollo missions. Students work in teams on a final project analyzing an aspect of the historical project to articulate and synthesize ideas in engineering systems. Required Course Texts:

Chaikin, A Man on the Moon Kranz, Failure is not an Option Kraft, Flight : My Life in Mission Control Tom Kelly, Moon Lander Apollo 11: The NASA Mission Reports Cox and Murray, Apollo: The Race to the Moon

Topic Readings

Introduction and Overview

None

Apollo as a Complex System

Chaikin, A Man on the Moon, Prologue Cox & Murray, Apollo: Race to the Moon, Chapter 1

Historical/Technical Analysis of Engineering Systems

Vincenti, What Engineers Know and How they Know It (Chapter 1)

Systems Engineering & Atlas

Hughes, Rescuing Prometheus Chapters 1, 3 Johnson, The Secret of Apollo, Chapters 1&2

Organizing research from NACA to NASA

Bilstein, Orders of Magnitude, Chapters 1-2 Cox & Murray, Chapters 2, 6

Sputnik, Mercury and the Cold War

MacDougall, The Heavens and the Earth: A Political History of the Space Age Chapters 2, 7,8

Kennedys Decision: From Politics to Engineering Specs.

Reading: Launius, Apollo: A Retrospective Analysis Cox & Murray, Chapters 4 & 5

Comparison: The Soviet Moon Program

Gerovitch papers

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The LOR decision

Enchanted Rendezvous: John C. Houbolt and the Genesis of the Lunar-Orbit Rendezvous Concept Cox & Murray, Chapters 7, 8, 9

NASA Management and System Engineering

Reading: Managing Apollo (selections) Cox & Murray Chapter 11, 13, 21

Life support & Human Factors I

Pitts, The Human Factor (selections)

Life support & Human Factors II

TBD

Saturn: structure, propulsion, testing, control

Cox & Murray Chapter 10, Other TBD

The Apollo 1 Fire: accident investigation

Chaikin, Chapter 1 Cox & Murray, Chapter 14, 15, 16

System engineering: the LEM

Tom Kelley, Moon Lander Ch 2

Astronautical Guidance

Chaikin, Chapter 3 Battin, A Funny Thing Happened on the Way to the Moon

Ground Control and Tracking

Reading: Kranz, Failure is not an Option Kraft, Flight : My Life in Mission Control Cox & Murray, Chapters 18, 19, 20

Covering Apollo: The Role of the Press

Reading: Original Press Accounts

The Apollo Guidance Computer: Hardware

Reading: Hall, Journey to the Moon The History of the Apollo Guidance Computer, Chapters 4-7 (posted)

Apollo 16

Reading: Chaikin, Chapters 4,5,12 Beattie, Taking Science to the Moon pp. 235-42 (posted)

Apollo 13: accident investigation

Reading: Chaikin, Chapters 7 & 8

The Apollo Guidance Computer

Reading: Hall, Chapters 13-14 (posted)

Course Assignments and Grading: Attendance at course meetings is mandatory; failure to attend will be reflected in the final grade. In addition, there are three assignments for the course:

30% Participant Interview: in-depth interview with engineer, astronaut, or technician involved in the project, with write-up and analysis.

30% Quizzes: two or more unscheduled pop quizzes to check for reading assignments. If youve done the reading that week, the quizzes should be no problem.

40% Final team projects: Subsystem analysis and redesign. Detailed study of a single subsystem from Apollo, discussing specifications, engineering choices, performance, and

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problems. Redesign using todays technology, materials, and management techniques in support of CEV program using lessons derived from Apollo.

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HST.971 Strategic Decision-Making in Biomedical Enterprise Aim: Strategic Decision Making in the Life Sciences examines the key strategic decisions faced by managers, investors and scientists at each stage in the value chain of the life science industry. The course aims to develop your ability to understand and effectively assess these strategic challenges. It focuses mainly on the biotech sector, but includes examples from the pharmaceutical, and to a lesser extent, medical device sectors. It is intended for anyone interested in building a life science company or working in the life sciences industry as a manager, consultant, analyst or investor. It will also provide an analytical background to the industry for biological and biomedical scientists, engineers and physicians with an interest in understanding the commercial dynamics of the life sciences or the commercial potential of their research. Course Description: The course is structured around the life science industry value chain from early stage scientific ideas, through licensing, financing and valuation, to discovery, clinical trials, production and sales. The foundations of the course provide a thorough understanding of the economics, risks and competitive dynamics at each of these distinctive stages of the value chain. It also highlights the critical problems and current issues at each stage. Through a series of structured problem-solving exercises you will learn analytical tools for strategic decision-making and apply them to a wide range of problems confronting the life science industry. Some of the tools used in the course include value chain decision trees, pipeline valuation, alliance valuation, drug adoption and lifecycle predictions, market assessments, etc. We will consider problems at the level of a single idea/molecule but also examine decisions at a higher level of analysis including platforms and portfolios. Analyses include decisions regarding licensing, target markets, valuation, out-sourcing, and alliances. Course Organization: The course is held once a week on a Wednesday evening from 5:30pm 8:30pm in E51-149. Each week is organized into two periods often with an industry expert leading the analysis in the second period of the evening. There will be 12 sessions in total. Course Requirements: Like most Sloan School courses, much of the course centers on weekly reading and case preparation. In addition there will be a weekly analytical homework assignment that complements the cases and provides you with a chance to gain hands-on experience in using strategic decision-making methods. There will also be two short group projects that require a written analysis and an in-class presentation (one at the end of H1 and one at the end of H2). The homework and group projects are based on real life problems taken from life science firms, mainly biotechnology companies. Course Requirements & Grading The course is intended to be a seminar with a lot of interaction as is reflected in the grading schema. Grades will be strongly determined by your class participation which will depend upon thorough preparation including relevant homework assignments. The grading schema is as follows: a) Attendance & Class Participation (20%) This class follows a seminar format with the discussion often built around case study material. It will therefore be impossible to understand the material if you do not come to class and if you do not participate. Skipping class will affect your grade - and, more

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importantly, - your own and your classmates' experience in the class. If you miss more than two sessions during the semester it will severely impact your class participation grade. b) Homework Assignments (50%) A significant portion of the grade is awarded to a series of Homework Assignments which will include a mix of both qualitative and quantitative analysis. The homework is designed to build on the case studies that are being prepared for a particular week. Homework should be completed in groups of no more than three people and one copy of the homework submitted for each group. Groups must include at least one non-Sloan person (numbers permitting). The written analysis and spreadsheets are due by e-mail to the TA by 5:30pm on the day of class. c) Group Projects (H1 10% H2 20% - Overall 30%) There will be two short group projects each requiring a brief written analysis (4-5 pages for the mid-term and 15-20 for the final) and a short in-class presentation (approximately 15 minutes). These projects should be completed in groups of six. The H1 project focuses on an analysis of the milestones needed to build a business from a novel scientific idea. The H2 project will analyze the opportunities for competitive advantage in different parts of the biotech value chain in less developed nations teams can choose from a list of countries that will include China, India and Singapore. It is an opportunity to combine many of the tools and strategic analyses you have learned in the class and apply them to a real world challenge. COURSE READINGS Required Reading: All the required readings are included in the course packet (except for a few to be distributed in class). The course is built around a series of analytical case studies and related homework assignments. In addition there are relevant articles and commentary from a combination of academic journals, the press and industry publications. These are intended to provide more in-depth analysis as well as relevant commentary or debate. Background Reading: Werth, B., The Billion Dollar Molecule, (NY: Simon & Schuster, 1994). Bazell, R., Her-2: The Making of Herceptin, (Crown Publishers, Inc, 2001 Vasella, D. McElheny, V., Watson & DNA: Making a Scientific Revolution, (Basic Books, 2004) Primers: In addition to the material described above, at the end of the syllabus, I am providing a list of material for two primers the first for those of you who want a primer on the basics of drug discovery and the second on an introduction to business strategy and strategic decision making. All the material is available in electronic format through MIT Libraries VERA system virtual electronic resources by searching on VERA for the specific journal title (Harvard has similar access to these journals). They are also available in a binder in Dewey Library (E53). Again, these are not required reading but

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provide essential background for some of you in the class and cover those questions for which I am most frequently asked to provide in-depth reading material. COURSE OUTLINE (Based on previous offering.) Week TOPIC Class A (5:30 - 7) Class B (7 - 8:30) Assignment Due 1 Intro to the Biomedical Value Chain Class Introduction Discovery Value Chain Lecture (FM 1.5h) Life Sciences Competitive Advantage Class Discussion 2 Basic Biomedical Economics & Milestones Advanced Inhalation Research Case milestones (FM 1.5h) Business model analysis lecture (FM 1h) Drug delivery valuation analysis 3 Biomedical Opportunity assessment Cancer Therapeutics & Diagnostics - Opportunity analysis (FM 1.5h) Identifying biotech opportunities (Stan Lapidus, CEO Helicos Biosciences 1.5h) Cancer market analysis & opportunity memo 4 Core Elements Ideas Centagenetix Case - Licensing at the University Industry interface (FM 1.5 hrs) Biotech Licensing strategies (Dr. Liza Vertinsky, Wolf Greenberg 1.5h) Centagenetix licensing terms analysis 5 Core Elements People Intuitive Surgical Case team rewards (FM 1.5h) Assembling & compensating a biotech team (Laura Morse, Atlas Ventures 1.5h) Valuation & ownership assessment

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6 Core Elements Funding Direvo Biotech Case milestones & value step up (FM 1.5 h) Building Biotech Value (Dr. Kollol Pal, PureTech Ventures 1.5h) Valuation & milestone analysis 7 NO CLASS SIP PERIOD 8 Core Elements Summary Presentations - Building Financial, People & Technical Milestones Pre-clinical Development (Dr. Peter Elliott, SVP Combinatorx, 1.5h) H1 Project & Presentation 9 Value Chain Elements Clinical Trials Clinical Trials International Strategy Lecture (Dr. Robert Rubin, MGH) Clinical Trials VIOXX (with Dr. Howard Golub, CareStat) Clinical Trials VIOXX homework 10 Value Chain Elements Production Nucleon Case options for manufacturing (FM 1.5h) Production Strategy (Dr. Howard Levine, Bioprocess Consulting 1.5h) Nucleon production Decision Analysis 11 Value Chain Elements Marketing Heartport Case understanding market dynamics (FM 1.5h) Marketing lecture building a marketing/sales team (Tim Noyes, Trine Pharma 1.5h) Heartport adoption analysis 12 NO CLASS THANKSGIVING 13 Value Chain Strategy - Alliances Abgenix Case & Alliance strategies (FM 1.5h) Alliances Pharma perspective (Dr. Jeremy Levine, Novartis) Abgenix alliance decision analysis 14

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International Value Chain Presentations Biotech Competitive Advantage in Developing Regions Wrap Up Final Project & Presentation WEEKLY COURSE SCHEDULE Week 1 Introduction & Core Elements Value Chain Economics Class A: Course Introduction Class B: Understanding Competitive Advantage in the Life Sciences Readings: Drews, J., (2000). Drug Discovery: A Historical Perspective in Science, Vol. 287, pp.1960-1964. North Carolina Biotechnology CenterHistorical Timeline & Glossary Week 2 Basic Biomedical Economics & Milestones Class A: Advanced Inhalation Research Case Class B: Business Models Lecture Readings: Case: Advanced Inhalation Research HBS# 9-899-292 Dickson, M. & J.P. Gagnon (2004). Key Factors in the Rising Cost of New Drug Discovery Nature Reviews Drug Discovery 3, 417-429. Formela, J., (1998). Business models for the bio-entrepreneur, Nature Biotechnology, May 16, Vol. 16, Supplement p. 16. Van Brunt, J. (2003). From info to FIPCO, Signals Magazine, March 28, 2003. Week 3 Biomedical Opportunity Assessment Markets & Technologies Class A: Cancer Opportunities Class B: Opportunity Assessment Lecture Guest Speaker: Dr. Stan Lapidus, Helicos Corp. & Flagship Ventures Readings: Case: Material to be handed out before class Farmer, G. (2004). Targeted Lung Cancer Therapies, Nature Reviews Drug Discovery 3, 547-548. Week 4 Core Elements Ideas Class A: Centagenetix Case Class B: Licensing Lecture Guest Speaker: Dr. Liza Vertinsky, Wolf Greenberg Readings: Case: Centagenetix (A) #9-602-087 (B) to be handed out in class Webber, P. (2003). Protecting your Inventions: The Patent System, Nature Reviews Drug Discovery, Vol. 2, Oct. 2003, pp. 823-830.

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Edwards, M.G. et al. (2003). Value creation and sharing among universities, biotechnology and pharma, Nature Biotechnology, Vol. 21, No. 6, pp. 618-624. Additional Readings: Hay, P., (1999). How a Biotech Company Licenses Its Inventions, les Nouvelles, Dec. 1999, pp. 155-157. Gelijns, A.C. & S.O. Thier, (2002). Medical Innovation and Institutional Interdependence, in JAMA, vol. 287, no. 1., pp. 72-77. Week 5 Core Elements People Class A: Intuitive Surgical Case Class B: Assembling Teams Lecture Guest Speaker: Ms. Laura Morse, Atlas Ventures Readings: Case: Intuitive Surgical HBS# 9-202-094 Dubini, P. and H. Aldrich, (1991). Personal and Extended Networks Are Central to the Entrepreneurial Process, in Journal of Business Venturing, vol. 6, pp.305-313. Additional Readings: Cho, M.K. et. al. (2000). Policies on Faculty Conflicts of Interest at US Universities JAMA Vol. 284. The Right Connections summary of research by Monic Higgins and Ranjay Gulati, Harvard Business School Working Knowledge http://hbswk.hbs.edu/item.jhtml?id=1307&t=entrepreneurship Week 6 Core Elements Funding Class A: Direvo Biotech AG Class B: Financial Valuation, Milestones & StepUp Lecture Guest Speaker: Dr. Kollol Pal, PureTech Ventures Readings: Case: Direvo Biotech AG HBS# 9-804-017 Lytton, M. Snaring a venture capital investment: A Field Guide to Biotechnology Business Plan Writing Nature Biotechnology Bio-entrepreneur Supplement, Vol. 16 suppl., p. 54, May 1998. Dibner, M.D., et al., (2003). US venture capital for biotechnology, in Nature Biotechnology, Vol. 21, No. 6, pp. 613-617. Week 7 No Class SIP Week 8 Core Elements Summary Class A: Class presentations Class B: Pre-Clinical Milestones Lecture Guest Speaker: Dr. Peter Elliott, SVP Product Development, Combinatorix Readings:

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Pritchard, J. F. et al. (2002).Making Better Drugs: Decision Gates in Non-Clinical Drug Development, Nature Reviews Drug Discovery, Vol. 2, pp.542-553. Kenakin, T., (2003). Predicting Therapeutic Value in the Lead Optimization Phase of Drug Discovery, Nature Reviews Drug Discovery, Vol. 2, June 2003, pp. 429-438. Week 9 Value Chain ElementsClinical Trials Class A: TBD Class B: Clinical Trials lecture Guest Speaker: Dr. Howie Golub, Care Stat Group Readings: Case: VIOXX readings listed in the homework Additional Material: Feldman, S R. The design of clinical trials in psoriasis: lessons for clinical practice in Journal of the American Academy of Dermatology, Volume 49, Issue 2, Supplement 1, August 2003, Pages 62-65. Fransen, J. Are better endpoints and better design of clinical trials needed? in Best Practice & Research Clinical Rheumatology, Volume 18, Issue 1, February 2004, Pages 97-109. Piercey, L., (2003). Life in the Fast Lane, in Signals Magazine. Bazell, R., (2001). The First Life Saved, Chapter 6 in Her-2: The Making of Herceptin., pp. 77-155. Week 10 Value Chain ElementsProduction Strategy Class A: Nucleon Case Class B: Production lecture Guest Speaker: Dr. Howard Levine, Bioprocess Technology Consultants Readings: Case: Nucleon, Inc. HBS# 9-692-041 McCoy, M. Pharma Outsourcing Chemical & Engineering News, April 5, 2004, Vol. 82, No. 14; pg 33-46. Additional Material: Miller, G. Manufacturing role evolves with pharmaceutical business Pharmaceutical Technology. Cleveland: Jul 2003. Vol. 27, Iss. 7; pg. 20 Thompson, R.E. and H.L. Levine, (2002). Assessing the Benefits and Risks, American Pharmaceutical Outsourcing, Vol. 3, 7-15. Weintraub, A. and R. Sharpe, The Spoils of Success, Business Week, August 13, 2001, pp. 52-54. Week 11 Value Chain ElementsMarketing Strategy & Adoption Class A: Heartport Case Class B: Building a Marketing and Sales Force lecture Guest Speaker: Tim Noyce Readings: Case: Heartport, Inc. HBS# 9-600-020

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Changing Physician Behavior HBS Note #9-699-124 Additional Material: Cardiovascular disease, (2000). Nature Biotechnology, Vol. 18, Supplement 2000, pp. IT15-IT17. Smith, J.J. and J.A. Henderson, (2003). Clinical Introduction of Drug-Eluting Stents in the US: Regulatory and Legal Considerations, CIMIT Working Paper. Week 12 NO CLASS Thanksgiving Holiday Week 13 Dec. 1 Value Chain StrategyHow to Design the Biomedical Value Chain? Class A: Abgenix Case Class B: Pharmaceutical Deals and In-Licensing Guest Speaker: Dr. Jeremy Levin, Novartis Institutes Readings: Case: Abgenix and the XenoMouse #9-501-061 Arnold, K., et al. (2002). Value drivers in licensing deals, Nature Biotechnology 20, pp. 1085 - 1089 (2002). Kalamas J., G.S. Pinkus, & K. Sachs. (2002). The new math for drug licensing The McKinsey Quarterly, 2002 Number 4. Additional Material: Poile, S., and S. Elvidge, (2004). Early stage deals strategies and terms Pharmalicensing. (http://pharmalicensing.com/features/disp/1074083835_400537fb578f2) Malik, A., B. Zbar, & R.W. Zemmel. (2004). Making pharma alliances work The McKinsey Quarterly. 2004 Number 1. Edwards, M. and J. OC. Hamilton, (1998). Ten Deals that Changed Biotech, Signals Magazine Week 14 Value Chain Summary International Opportunities Class A: Final Project Presentations Class B: Final Project Presentations (cont.) Guest Speaker: Dr. Hannah Kettler, Gates Foundation BASICS OF DRUG DISCOVERY PRIMER This reading list is intended as a primer to provide you with a comprehensive background to many of the core technologies and techniques that are used in modern drug discovery. While it may be too technical in part for some of you, it is important to try and familiarize yourselves with the basic language, methods and their role in life sciences. Roses, A.D., (2002). Genome-Based Pharmacogenetics and the Pharmaceutical Industry, in Nature Reviews Drug Discovery, Vol. 1, July 2002, pp. 541-549. Butte, A., (2002). The Use and Analysis of Microarray Data, in Nature Reviews Drug Discovery, Vol. 1, Dec. 2002, pp. 951-660.

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Petricoin, E., et al., (2002). Clinical Proteomics: Translating Benchside Promise into Bedside Reality, in Nature Reviews Drug Discovery, Vol. 1, Sept. 2002, pp. 683-695. Bleicher, K., et al.,(2003). Hit and Lead Generation: Beyond High-Throughput Screening, in Nature Reviews Drug Discovery, Vol. 2, May 2002, pp. 369-378. Geysen, H. M., et al., (2003). Combinatorial Compound Libraries for Drug Discovery: An Ongoing Challenge, in Nature Reviews Drug Discovery, Vol. 2, March 2003, pp. 222-230. Walters, W. P. and M. Namchuk, (2003). Designing Screens: How to Make Your Hits a Hit, in Nature Reviews Drug Discovery, Vol. 2, April 2003, pp. 259-266. Zambrowicz, B. P. and A. T. Sands, (2003). Knockouts Model The 100 Best-Selling DrugsWill They Model The Next 100?, in Nature Reviews Drug Discovery, Vol.. 2, Jan. 2002, pp. 38-51. BASICS OF STRATEGIC DECISION-MAKING PRIMER The primer on strategic decision-making is intended mainly for those of you without a background of the MBA core and related courses. It is focused on a number of the tools that are useful in strategic decision-making. The first is the classic Porter Five Forces which is a basic technique for strategic analysis. The other two are basic analytical spreadsheet tools that allow you to undertake simple cash flow analysis, understand the meaning of Net Present Value and do simple decision trees which account for the probability of different outcomes and different paths over the life of a project. Please be sure to read at least the Porter article before the first class. Porter, M., (1979). How Competitive Forces Shape Strategy, Harvard Business Review, Reprint #79208. Cash Flow and the Time Value of Money, HBS #9-177-012. Decision Analysis, HBS #9-894-004.

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LABORATORIES ASSOCIATED WITH THE BIOASTRONAUTICS PROGRAM

Students can pursue thesis work in one of many associated laboratories at Harvard, MIT, and affiliated hospitals that have space life sciences related projects. Those listed below suggest the range of possibilities. Dr. Barger Laura Sleep deprivation laura_barger@hms.harvard.edu 617-732-7991 Dr. Bouxsein Mary Effects of Gravity on Bone mbouxsei@bidmc.harvard.edu 617-667-4594 Dr. Buckey Jay New Technology for Space

Medicine and Physiology: Decompression Sickness and Hearing Assessment jay.buckey@dartmouth.edu 603-646-2230

Dr. Bulyk Martha Genomic, proteomic, and computational studies of regulatory networks mlbulyk@receptor.med.harvard.edu 617-525-4725

Dr. Carter James Self-Guided Depression Treatment on Long-Duration Space Flights jacarter@caregroup.harvard.edu 617-667-1507

Dr. Cohen Richard Effects of Simulated Micro-g on CV Stability rjcohen@mit.edu 617-253-7430

Dr. Czeisler Charles Circadian Entrainment, Sleep-Wake Regulation During Extended-Duration Space Flight caczeisler@rics.bwh.harvard.edu 617-732-4013

Dr. Goldberg Alfred Muscle wasting and protein loss alfred_goldberg@hms.harvard.edu 617-432-1855 Dr. Hoffman Jeffrey Space Engineering and the Practice

of Astronautics jhoffma1@mit.edu 617-252-2353 Dr. Klerman Elizabeth Mathematical Modeling of

Circadian/Performance Countermeasures ebklerman@hms.harvard.edu 617-732-8145

Dr. Kosslyn Stephen Portable and Fast Assessment of Cognitive Functions smkosslyn@wjh.harvard.edu 617-495-3932

Dr. Lockley Steven Light Exposure to Facilitate Circadian Adaptation and Enhance Alertness slockley@hms.harvard.edu 617-732-4977

Dr. Mark Roger Computational Models of Cardiovascular Function; Clinical Decision Support Care rgmark@mit.edu 617-253-7818

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Dr. Merfeld Daniel Decoding of Graviceptor Cues, Including Adaptive Changes (NIH);

dan_merfeld@meei.harvard.edu 617-573-5595

Dr. Newman Dava Extra-Vehicular Activities; Bio-Suits; Micro-gravity

dnewman@mit.edu 617-258-8799

Dr. Oman Charles Visual Orientation, Navigation and Spatial Memory Countermeasures

coman@mit.edu

617-253-7508

Dr. Strangman Gary Neurobehavioral and Psychosocial Factors: Inflight depression strang@nmr.mgh.harvard.edu 617-724 0662

Dr. Summons Roger Geobiology, Astrobiology rsummons@mit.edu 617-452-2791 Dr. Wall Conrad Vestibular Function cwall@space.mit.edu 617-573-4160 Dr. Young Laurence Neurovestibular Aspects of Short-

Radius Artificial Gravity lry@mit.edu

617-253-7759