The rules of the game are similar to the popular game “Mastermind”.  The teacher plays the role of the biologist conducting an assay and also fills the role of the “Mastermind”: the person who knows the answer to the puzzle.  The students will try to solve the puzzle by playing the role of medicinal chemists.

  • The chemist/student assembles a molecule by attaching “molecular fragments” to the Velcro attachment points on the “scaffold”.  An assembled molecule is presented to the biologist/teacher for evaluation in the assay.
  • The biologist/teacher tells the chemist/student how many of the “molecular fragments” in the molecule are correct and how many are in the correct Velcro space on the scaffold.  (The biologist/teacher does not tell the chemist which pieces are correct or which pieces are in the correct place.)   For example the biologist will say “The assay indicates that your molecule has two correct pieces but only one is in the correct place.”  This is the only feedback given to the student/chemist.  The chemist/student must use that knowledge (plus his or her skills of logic) to prepare a second guess.
  • Each piece can be used more than once in the puzzle.  Therefore, it is important that each student have access to sufficient copies of each molecular fragment to fill all of the Velcro spots on the scaffold.
  • Each time the student makes a guess, he/she must pay $100 of the play money.  It is explained that drug discovery requires a significant investment.  For example, chemicals to synthesize the compounds must be purchased, reagents and robotic instruments are required for the biological assay, laboratory space requires rent payments, and the scientists must be paid.
  • Game play continues in an interactive fashion with the chemists paying $100 per guess, guessing by presenting their designed molecule, and receiving feedback from the biologist until the student logically deduces the correct structure.
  • Each chemist who discovers the drug is rewarded with a $500 payout for his/her discovery and asked to sit quietly until the others finish.  Play continues until all the students have the satisfaction of “discovering the drug”.

This demonstration has been conducted in a room with ten to fifteen “chemists” (students) and three “biologists” (the teacher with a few student volunteers).  In larger classrooms of up to thirty students, the game has been played with students paired into teams of two or three.


An example of the game is provided below.  In this example, the students are told their goal is to synthesize a treatment for allergy.  The molecule they will discover is fexofenadine, sold under the commonly known trade name Allegra.  At the start of the game, the students are provided with a black-colored core scaffold and three each of  green (piperonyl), red (4-(2-carboxypropan-2-yl)phenyl), and blue (phenyl) molecular fragments.

The chemist’s initial guess places a red piece in scaffold slot 1, a green piece in scaffold slot 2, and a blue piece in scaffold slot 3:
Guess #1

The biologist’s response is that the chemist has selected two of the correct pieces but none of the pieces are in the correct place.

In the second guess, the student rearranges the blue and green pieces:

Guess #2

The biologist responds by pointing out that still two of the pieces are correct, but now one is in the right place.

In the third guess, the student has changed the red piece for another green piece:

Guess #3

The biologist responds that now only one piece is correct.  Also, one piece is in the correct place.  Logically, this information will inform the student that the green piece is not used in the solution.  The student/chemist has also confirmed the blue piece is in the correct location.

In guess 4, the student has replaced the green pieces with red pieces:

Guess #4

This triggers the response from the biologist that two pieces are correct and they are in the right locations.

In the fifth guess, the student has correctly deduced that scaffold slot 1 should also contain a blue phenyl piece:

Guess #5

The biologist responds that the compound has the correct properties to be an allergy treatment and the puzzle is solved. The final structure is the allergy medication Allegra.

To make each of the guesses, the chemist paid $100 of the play money.  In this example the student guessed five times and therefore spent $500.  The reward of $500 for discovering the drug covered the cost of the drug discovery effort and the student broke even.