1 Quick Reference Summary

🎨 Creative Exploration

Goal: Generate diverse, creative ideas

AI Role: Creative brainstorming partner

Key Tactic: Ask for multiple, varied, “weird” ideas

Risk if Skipped: Right answers to uninspired questions

🔬 Targeted Training

Goal: Achieve precise, correct result

AI Role: Meticulous step-by-step calculator

Key Tactic: Demand step-by-step work, definitions, unit checks

Risk if Skipped: Creative ideas without rigorous support

🔍 Sanity Checks

Goal: Identify flaws and hidden assumptions

AI Role: Skeptical peer reviewer

Key Tactic: Ask “What’s wrong?” and “What if…?”

Risk if Skipped: Critical errors go unnoticed

2 The Problem and Solution

AI tools like ChatGPT solve textbook problems well but struggle with creative research. However, if you give them worked examples they can become more reliable and predictable. If you do not traine them, it is likely the stryggle with creative endeavours and become sloppy.

In general, I have found that we can AI differently for different research phases. One phase is exploring broadly, as if you had a canvas for brainstorming. The other phase it is like having a scalpel for precise work, that you can use for sanity checks based on your expertise and sources of knowledge that are reliable.

Canvas mode, adopting now this terminology, can increase idea variety, making it better for discovery. However, it might be risky when you need precision. The scalpel mode reduces idea variability through step-by-step reasoning, giving you reliability but possibly locking you into familiar approaches, and knowledge. Finally, sanity checks help you probe assumptions that both other modes miss. This is where you exercise your critical thinking and skepticism.

3 Examples

3.1 Canvas Examples

3.1.1 Idea Farm

Generate 8 different explanations for why heritability estimates vary between populations. 
For each one:
- State the core mechanism in one sentence
- Give two testable predictions  
- Describe the single most decisive observation that would falsify it
- Rate how likely it is (low/medium/high) and why

Include at least 3 weird but biologically plausible ideas.

3.1.2 Cross-Pollination

How would a control engineer think about gene regulation? An economist about 
population dynamics? A physicist about protein folding? For each perspective, 
what tools or principles could we steal for biology?

3.1.3 Challenging Assumptions

Everyone assumes linkage disequilibrium decays exponentially. What if we 
dropped that assumption? What alternatives are there, and what would each 
predict about patterns in real populations?

3.1.4 Adopting Expert Personas

Act as [famous scientist] with their theoretical perspective, but with access 
to modern knowledge. From that viewpoint, generate 5 unconventional hypotheses 
for [your problem]. Focus on concepts that [scientist] would emphasise.

Examples:
- "Act as Sewall Wright in the 1940s, but with modern genomics knowledge..."
- "Take the perspective of Lynn Margulis and her focus on symbiosis..."
- "Channel Mary-Claire King's approach to genetics and human disease..."

3.2 Domain-Specific Examples

3.2.1 Quantitative Genetics

Quantitative Genetics Canvas Prompt

List 10 reasons why a selection experiment might give weird results that don't 
match the breeder's equation. Include some exotic possibilities like epigenetic 
effects, maternal environments, or developmental noise. For each one, what would 
it predict about the pattern of response over time?

3.2.2 Network Biology

Network Biology Canvas Prompt

Why might feed-forward loops evolve in gene regulatory networks? Think beyond 
the standard 'noise filtering' explanation. Consider development, evolvability, 
robustness to mutation, metabolic costs, etc. For each idea, give me a prediction 
and a way to test it.

3.3 Scalpel Examples

Now you can pick one promising idea from your brainstorming and work through it carefully. This is where you want AI to be systematic and show all its work.

Bounds to Always Check:

  • Heritability: \(0 \leq h^2 \leq 1\)
  • Variance components: all \(\geq 0\)
  • Probabilities: sum to 1, each between 0-1
  • Population sizes: positive integers
  • Units: consistent throughout calculations

3.3.1 Example of a Template

Scalpel Template: Step-by-Step

Solve this step-by-step:

1) Define all variables and state your assumptions clearly
2) Write down the relevant equations or logical steps
3) State the key limitations or conditions under which this model fails
4) Plug in numbers and work through the calculation
5) Check your units and whether the result makes biological sense
6) Give me your final answer in one clear sentence

3.3.2 Worked Example

Q: A plant population has mean height 100 cm, total variance 25 cm², and genetic variance 10 cm². After selecting the tallest 20%, the mean is 105 cm. What’s the predicted response?

Step-by-step solution:

  1. Variables: \(h^2 = \frac{\sigma_G^2}{\sigma_P^2} = \frac{10}{25} = 0.4\); \(S = 105 - 100 = 5\) cm
  2. Equation: Response \(R = h^2 \times S\)
  3. Model limitations: This assumes no epistasis, no linkage to deleterious alleles, no GĂ—E interactions, constant heritability under selection, and large population size (no drift effects)
  4. Calculate: \(R = 0.4 \times 5 = 2\) cm
  5. Units check: cm âś“; Bounds check: \(0 < h^2 < 1\) âś“; Magnitude: reasonable âś“
  6. Answer: The population should increase by 2 cm on average

New population mean = \(100 + 2 = 102\) cm

3.3.3 Making AI Show Its Work

Always demand:

  • Explicit assumptions (“I’m assuming linkage equilibrium…”)
  • Step-by-step calculations (not just final answers)
  • Units and sanity checks (“Does a 50% increase make biological sense?”)
  • Clear final statements (“Therefore, the effective population size is…”)

3.4 Sanity Check Examples

If you believe you got a reasonable and clean answer. it is time to break it. This catches errors and reveals hidden assumptions that th eother two modes might have missed.

3.4.1 Attack the Questions

Reality Check Template: Attack Questions

I just calculated [your result]. What's the biggest flaw in this reasoning? 
What assumptions am I making that might be wrong? In what situations would 
this completely fail?

3.4.2 Constraint Checking

Reality Check Template: Constraint Checking

Check if my answer violates any biological constraints. For instance:
- Is heritability between 0 and 1?
- Are population sizes positive?
- Do probabilities sum to 1?
- Are growth rates reasonable?

3.4.3 Alternative Explanations

Reality Check Template: Alternative Explanations

What's the strongest alternative explanation for this result? How would I design 
an experiment to distinguish between my explanation and the alternative?

3.5 Templates that might be useful

Here are ready-to-use templates you can customise for your research:

3.5.1 Canvas Templates

The Idea Farm (click to expand)
Generate [number] distinct explanations for [your phenomenon].
For each one:
- State the core mechanism in one sentence
- Give two testable predictions  
- Describe what evidence would prove it wrong
- Rate how likely it is (low/medium/high) and why
Include at least 3 weird but biologically plausible ideas.
Cross-Domain Thinking (click to expand)
How would researchers from these 5 fields approach [your problem]: control theory, 
economics, physics, computer science, and ecology? For each perspective, what tools 
or principles could we borrow? What new predictions would that generate?
Assumption Challenge (click to expand)
Everyone in my field assumes [standard assumption]. What if we dropped that? 
What alternatives exist, and what would each predict about [your system]?

3.5.2 Scalpel Templates

Step-by-Step Problem Solving (click to expand)
Solve this step-by-step:
1) Define all variables and state your assumptions clearly
2) Write down the relevant equations or logical steps
3) Plug in numbers and work through the calculation
4) Check your units and whether the result makes biological sense
5) Give me your final answer in one clear sentence
Method Verification (click to expand)
I'm using [method] to analyse [type of data]. Walk me through:
1) What assumptions this method makes
2) How to check if my data meets these assumptions  
3) What the results mean biologically
4) What could go wrong and how I'd know

3.5.3 Sanity Check Templates

Attack Your Result (click to expand)
I just calculated [your result]. What's the biggest flaw in this reasoning? 
What assumptions am I making that might be wrong? In what situations would 
this completely fail?
Alternative Explanations (click to expand)
My data shows [pattern]. I think it's due to [your explanation]. What's the 
strongest alternative explanation? How would I design an experiment to 
distinguish between these possibilities?

4 Research Examples

4.1 Selection Response Problem

Canvas Phase: “Why might selection response be weaker than predicted? Generate 6 mechanisms including some unusual ones.”

Results might include: linkage drag, maternal effects, developmental constraints, inbreeding depression, environmental correlation, epigenetic inheritance.

Scalpel Phase: Pick “linkage drag” and model how linked deleterious alleles reduce response.

Reality Check: “What would prove linkage drag wrong? How could I test this experimentally?”

Falsifier: Response increases after breaking up linkage through recombination.

4.2 Network Evolution Problem

Canvas Phase:
“Propose 8 evolutionary explanations for why incoherent feed-forward loops are common in regulatory networks.”

Possible mechanisms: - Gene duplication-divergence: One copy retains activation, other evolves repression - Falsifier: No paralogue age differences between activating and repressing arms - Cis-regulatory co-option: Recruitment from stress response circuits
- Falsifier: No shared regulatory motifs with stress response genes - Post-transcriptional delay: MicroRNA-mediated repression creates temporal lag - Falsifier: Loss of transient dynamics when miRNA biogenesis is disrupted

Scalpel Phase: Model population genetics of how gene duplication could create this pattern.

Reality Check: “What phylogenetic patterns would I expect if duplication-divergence is correct? What would falsify it?”

4.3 Population Genetics Project

Canvas Phase: “I’m studying why genetic diversity varies so much between island populations. Generate 8 different mechanisms.”

Results: founder effects, ongoing migration, population bottlenecks, selection differences, mating system variation, mutation rate differences, genetic drift, population structure.

Scalpel Phase: Calculate expected \(F_{ST}\) values under the island model: \(F_{ST} = \frac{1}{1 + 4N_em}\)

With \(N_e = 1000\), \(m = 0.01\): \(F_{ST} = \frac{1}{1 + 40} = 0.024\)

Units check: Dimensionless âś“; Bounds check: \(0 \leq F_{ST} \leq 1\) âś“

Reality Check: “What would prove migration wrong? Design controls for drift effects.”

Falsifier: If \(F_{ST}\) values don’t correlate with geographic distance, ongoing migration model fails.

5 Practical Tips for PhD Students

5.1 When to Use Each Phase

5.1.1 Canvas for:

  • Starting new projects
  • When you’re stuck
  • Literature reviews (finding new angles)
  • Proposal writing
  • When everyone agrees on something (challenge the consensus)

5.1.2 Scalpel for:

  • Homework problems
  • Data analysis
  • Method development
  • Checking calculations
  • Writing methods sections

5.1.3 Reality Check for:

  • Before submitting anything
  • Peer review preparation
  • When results seem too good to be true
  • Experimental design

5.2 Getting Better Results

5.2.1 In Canvas Phase:

  • Ask for specific numbers of ideas (forces variety)
  • Demand weird but plausible options
  • Ask “What would [famous scientist] think about this?”
  • Request testable predictions for each idea

5.2.2 In Scalpel Phase:

  • Always ask to see intermediate steps
  • Request unit checking
  • Ask for biological interpretation of mathematical results
  • Demand explicit assumptions

5.2.3 In Sanity Check:

  • Play devil’s advocate with your own work
  • Ask about edge cases and failure modes
  • Request the cheapest experiments to test key assumptions
  • Be willing to discard your idea. After rigorously working through the maths (Scalpel), you might feel invested in your result. This is the sunk cost fallacy. A key scientific skill is killing your own darlings. If Reality Check reveals a fatal flaw, celebrate! You’ve saved weeks or months on a dead end. Start fresh Canvas phase with what you’ve learned.

5.3 Chat Hygiene: When to Start Fresh

Good lab practice means knowing when to clean your workspace. AI conversations degrade over time: Answers get vaguer, errors compound, and the AI gets stuck repeating itself.

5.3.1 Start a new chat when:

  • Switching from Canvas to Scalpel phases (different goals need fresh context)
  • AI gives repetitive or increasingly vague answers
  • You’ve had more than 20-30 exchanges
  • Moving to a completely different topic
  • AI contradicts something it said earlier
  • Answers stop including requested detail

5.3.2 Warning signs of a degraded chat:

  • AI says “as I mentioned earlier” but didn’t mention it clearly
  • Mathematical work becomes sloppier or skips steps
  • Responses get shorter and more generic
  • More hedging (“this might be…” instead of clear statements)

5.3.3 Pro tip:

Copy key results into a notes file before starting fresh. Build on previous work without carrying conversational baggage.

5.4 Common Mistakes to Avoid

  1. Using only Scalpel mode - Right answers to wrong questions
  2. Using only Canvas mode - Ideas without rigorous follow-through
  3. Mixing the modes - Asking for creative ideas while demanding mathematical precision
  4. Trusting first answers - AI often improves with follow-up questions
  5. Not checking units - Mathematical errors are common and often obvious
  6. Marathoning one chat - Long conversations degrade performance and accumulate errors

6 Bottom Line for Scientists

AI can be powerful for research, but you need strategy. Don’t expect it to replace your scientific thinking. Use it to enhance your natural research process.

Canvas phase helps you think more broadly than you would alone.

Scalpel phase helps you work through complex problems without arithmetic errors.

Reality check helps you catch mistakes and strengthen arguments.

The key insight: different research phases need different AI interactions. Match your prompting strategy to your research needs.

Most importantly: you’re still the scientist. AI is a sophisticated tool, like a microscope or statistical software. It amplifies your capabilities but doesn’t replace your judgement, creativity, or domain expertise.