Week 1 — Principles & Practices

cover image cover image

This week lays the foundation for ethics, safety, and governance in biotechnology — and we get hands-on with lab basics.

Lecture (Tues, Feb 3)

Principles & Practices
(▶️Recording)
David Kong
George Church
Joe Jacobson

Recitation (Wed, Feb 4)

Principles, Ethics, Practices
(▶️Recording | 💻Slides)
Ronan Donovan
Suvin Sundararajan
Subastian Kamau
Greg Galperin

Lab (Thurs-Fri, Feb 5 - 6)


Lab: Pipetting


Homework — DUE BY START OF FEB 10 LECTURE

Documentation

Make sure to document every step of the in-silico and lab experiments. Make sketches, screenshots, notes, drawings - anything that helps you - and others understand the experiment.

Your Documentation should help you - and others - to understand the topic. Don’t be afraid to add things that don’t work. Show your failures - and how you overcame them. Your Documentation should be a description of the amazing journey you are on!

Overview

Ethics, safety, and security are essential considerations throughout (and beyond!) this class. We have therefore designed the Class Assignment this week to give you a strong foundation, and then will ask you to reflect each week and in the design of your final project.

Questions?

MIT / Harvard students: htgaa2026-TAs@media.mit.edu
Global students: htgaa2026-globalTAs@media.mit.edu

Class Assignment — DUE BY START OF FEB 10 LECTURE

Assignees for the following sections
MIT/Harvard studentsRequired
Committed ListenersRequired
  1. First, describe a biological engineering application or tool you want to develop and why. This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.
  2. Next, describe one or more governance/policy goals related to ensuring that this application or tool contributes to an “ethical” future, like ensuring non-malfeasance (preventing harm). Break big goals down into two or more specific sub-goals. Below is one example framework (developed in the context of synthetic genomics) you can choose to use or adapt, or you can develop your own. The example was developed to consider policy goals of ensuring safety and security, alongside other goals, like promoting constructive uses, but you could propose other goals for example, those relating to equity or autonomy.
  3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”). Try to outline a mix of actions (e.g. a new requirement/rule, incentive, or technical strategy) pursued by different “actors” (e.g. academic researchers, companies, federal regulators, law enforcement, etc). Draw upon your existing knowledge and a little additional digging, and feel free to use analogies to other domains (e.g. 3D printing, drones, financial systems, etc.).
    1. Purpose: What is done now and what changes are you proposing?
    2. Design: What is needed to make it “work”? (including the actor(s) involved - who must opt-in, fund, approve, or implement, etc)
    3. Assumptions: What could you have wrong (incorrect assumptions, uncertainties)?
    4. Risks of Failure & “Success”: How might this fail, including any unintended consequences of the “success” of your proposed actions?
  4. Next, score (from 1-3 with, 1 as the best, or n/a) each of your governance actions against your rubric of policy goals. The following is one framework but feel free to make your own:
Does the option:Option 1Option 2Option 3
Enhance Biosecurity
• By preventing incidents
• By helping respond
Foster Lab Safety
• By preventing incident
• By helping respond
Protect the environment
• By preventing incidents
• By helping respond
Other considerations
• Minimizing costs and burdens to stakeholders
• Feasibility?
• Not impede research
• Promote constructive applications
  1. Last, drawing upon this scoring, describe which governance option, or combination of options, you would prioritize, and why. Outline any trade-offs you considered as well as assumptions and uncertainties. For this, you can choose one or more relevant audiences for your recommendation, which could range from the very local (e.g. to MIT leadership or Cambridge Mayoral Office) to the national (e.g. to President Biden or the head of a Federal Agency) to the international (e.g. to the United Nations Office of the Secretary-General, or the leadership of a multinational firm or industry consortia). These could also be one of the “actor” groups in your matrix.

Reflecting on what you learned and did in class this week, outline any ethical concerns that arose, especially any that were new to you. Then propose any governance actions you think might be appropriate to address those issues. This should be included on your class page for this week.

Assignment (Final Project) – Due as part of your Final Project presentation (not Feb 10)

Assignees for the following sections
MIT/Harvard studentsRequired
Committed ListenersRequired

As part of your final project, design one or more strategies to ensure that your project, and what it enables, contributes to growing an ethical biological future.

Assignment (Lab Preparation) — DUE BY START OF FEB 10 LECTURE

Assignees for the following sections
MIT/Harvard studentsRequired
Committed Listeners(Not Applicable)

Lab Training (failure to complete this will jeopardize your acceptance into the course)

  • Complete Lab Specific Training in Person.
  • Complete Safety Training in Atlas
    • Navigate to atlas.mit.edu and on the right-hand side, click “Learning Center”
    • Head to the Course Catalog and find the following two courses:
      • General Biosafety for Researchers (EHS00260w)
      • Managing Hazardous Waste (EHS00501w)

Assignment (Week 2 Lecture Prep) — DUE BY START OF FEB 10 LECTURE

Assignees for the following sections
MIT/Harvard studentsRequired
Committed ListenersRequired

In preparation for Week 2’s lecture on “DNA Read, Write, and Edit," please review these materials:

  1. Lecture 2 slides as posted below.
  2. The associated papers that are referenced in those slides.

In addition, answer these questions in each faculty member’s section:

Homework Question from Professor Jacobson:

(To be added soon)

Homework Questions from Dr. LeProust: [Lecture 2 slides]

  1. What’s the most commonly used method for oligo synthesis currently?
  2. Why is it difficult to make oligos longer than 200nt via direct synthesis?
  3. Why can’t you make a 2000bp gene via direct oligo synthesis?

Homework Question from George Church: [Lecture 2 slides]

Choose ONE of the following three questions to answer; and please cite AI prompts or paper citations used, if any.

  1. [Using Google & Prof. Church’s slide #4]   What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?
  2. [Given slides #2 & 4 (AA:NA and NA:NA codes)]   What code would you suggest for AA:AA interactions?
  3. [(Advanced students)]   Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own:

Assignment (Your HTGAA Website) — DUE BY START OF FEB 10 LECTURE

Assignees for the following sections
MIT/Harvard studentsRequired
Committed ListenersRequired
  1. Begin personalizing your HTGAA website in in https://edit.htgaa.org/, starting with your homepage — fill in the template with information about yourself, or remove what’s there and make it your own. Be creative!
  2. As with all assignments in HTGAA, be sure to write up every part of this Homework on your HTGAA website in order to receive credit.

Reading & Resources (click to expand)

Lab-specific

Governance & ethics

Subsections of Week 1 (Feb 3)

Lab (Week 1) — Introduction to Pipetting and Dilutions

cover image cover image

Overview

Objective

Welcome to HTGAA! This is our very first lab, and in this lab we will introduce students to the foundational techniques of pipetting and serial dilutions, critical for precise liquid handling and solution preparation in biological and chemical experiments.

This is a one-day lab with two protocols covered on mixing colors and dilution. By the end of the lab, students will confidently use pipettes, prepare solutions with desired concentrations, and troubleshoot common errors in pipetting.

Concepts Learned & Skills Gained

Students will:

  • Understand Units and Conversions: moles (mol), molarity (M), and conversions between µL, mL, and L.
  • Perform Serial Dilutions: Learn the stepwise dilution process to achieve specific solution concentrations.
  • Gain Pipetting Proficiency: Operate P20, P200, and P1000 pipettes accurately for volume transfers.
  • Visualize Mixing Outcomes: Use colors and absorbance measurements to observe concentration gradients.

Pre-Lab

Reading

Key Definitions

Here are some key definitions we’d like you to know before you get started.

  • Moles (mol): A unit representing $6.022 \times 10^{23}$ particles (atoms, molecules, etc.).
  • Molarity (M): Concentration defined as moles of solute per liter of solution (mol/L).
  • Conversions:
    • 1 L = 1000 mL = 1,000,000 μL 1 M = 1000 mM = 1,000,000 μM

Planning Your Experiments

To calculate the volume of water needed for a dilution, use the formula: $$C_1 V_1 = C_2 V_2$$

Where:

  • $C_1$ : Initial concentration (stock concentration).
  • $V_1$ : Volume of stock solution needed.
  • $C_2$ : Final concentration (desired concentration).
  • $V_2$ : Final volume (total volume of the diluted solution).

Steps:

  1. Rearrange the formula to calculate $V_1$: $$ V_1 = \frac{C_2 V_2}{C_1} $$

  2. Calculate the volume of water (let’s call it $V_Water$) to add: $$ V_Water = V_2 - V_1 $$

Practice

Dilution Practice 1

  • Scenario: The stock concentration of a mystery substance (MS) is 5 M. Calculate how to dilute to 100 µM (0.1 mM):
    • Use sequential 1:499 and 1:99 dilution steps for accurate preparation.
      • Step 1: Dilute 5 M (5,000,000 µM) to 10,000 µM (500x dilution).
      • Step 2: Dilute 10,000 µM to 100 µM (100x dilution).

Dilution Practice 2

  1. The stock concentration of a mystery substance (MS) is 5 M.
    1. If the molar mass of MS is 532 g/mol, what’s the concentration of the stock concentration in g/mL? To make your life easier, you can use one of many online calculators.
  2. You will perform a serial dilution to get 100 uM of MS. Devise a plan to dilute a 5 M MS solution to 100 uM. How many dilution steps will we need? Which tubes should we use? Which pipettes?
  3. Fill out the following chart to prepare a final reaction with 60 uL reaction volume. Why did we make 100 uM MS if we actually need 40 uM MS? Why not prepare 40 uM in serial dilutions?
ReagentStock concentrationDesired concentrationVolume
Loading dye6X1X
MS100 uM40 uM
dH2On/an/a
Note

Please fill this out before coming to lab.

Additional resources

You must watch or be able to understand the following videos:

Protocol

Overview

Materials

Eppendorf Tube

Eppendorf Tube

PCR Tube Strip

PCR Tube Strip

  • Pipettes
    • P20: 1-20uL of liquid
    • P200: 20-200uL
    • P1000: 100-1000uL
    • Pipette tips: 10uL, 200uL, 1000uL
  • Tubes
    • Eppendorf tube (see image)
    • PCR tubes: (see image)
  • Tube holder
  • Stock reagents
    • dH2O
    • Mysterious substance (food coloring with water), henceforth: MS
      • Red, Blue and Yellow food coloring solutions
    • Gel loading dye (commonly used reagents for loading gels, strong purple color)

Part 1: Mixing Color

  1. Prepare tubes with red, yellow, and blue food coloring solutions OR watercolor
  2. Take ten tubes and mark them with numbers 1 to 6
  3. Tube 1, 2 and 3: add 500 uL each red, yellow, and blue solution to the tube.
  4. Tube 4: add 220 uL red solution to the tube, and add 220 uL yellow solution.
    1. Try adding this in 2 steps: add 200 uL first, and then 20 uL. Discard your tips after you add one color!
  5. Tube 5: add 525 uL yellow solution to the tube, and add 525 uL blue solution.
  6. Tube 6: add 155 uL red solution to the tube, and add 155 uL blue solution. Now you have a rainbow! You can try mixing other colors with the solutions.
  7. Try plating different volumes (e.g. 1uL, 2uL, 5uL, 10uL) on a petri plate to make some designs and build your intuitive understanding of these volumes.

Part 2: Performing Serial Dilution

  1. Perform serial dilutions to get 100 uM (0.1 mM) of MS.
    • Every time you mix in liquid, pipette up and down three or four times to ensure the two liquids are mixed thoroughly.
    • Mark each tube with its respective concentration using a pen.
  2. Prepare a final reaction of 60 uL based on your table in the pre-lab.
  3. Bonus: Take 20 uL from the final reaction and pipette it to a pre-prepared gel well. Wells are a bit trickier because they are thin and your pipette tip will puncture the gel if you’re not careful. Be gentle!

Lab Material for TAs/Nodes