Magic Bullets: Chemistry vs. Cancer

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    Cancer Detectives
    A Class Simulation

    How can you study something that you cannot see? This is a major problem confronting many modern scientists. For chemists and biologists, the molecules being studied are so small that they cannot be seen directly. Even cells of the body are much too small to be seen easily. How then can scientists study them?

    This lab activity applies many of the skills teachers expect students to master in a science course. Some of them are listed in "Teacher Notes #5", below. The advanced preparation for this activity is relatively extensive, but the materials will last for years, since the activity is done using microscale quantities.

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    Safety
    Teacher Notes
    Advance Preparation
    Conducting the Activity
    Follow-up Discussion
    Answers to Questions/Conclusions
    Relevant National Science Education Standards
    Relevant New Jersey State Science Education Standards

    Safety

    General Safety Guidelines

    The following MSDS sheets are available on-line from Cornell University:

      Ammonium hydroxide
      Copper(II) sulfate pentahydrate
      Fluorescein sodium
      Iron(III) chloride hexahydrate
      Potassium ferrocyanide
      Potassium thiocyanate

    Teacher Notes

    1. In this exercise, cancer cells are distinguishable from normal cells by three properties:

      1. Cancer cells have a small extra mark in the nucleus of cell, as you can see below. The printable versions of the cells have this same discrepancy.

        normal and cancer cells

        Click on these links for printable versions of the normal cell and the cancer cell.

      2. A spot (that you place on each tested cancer cell) glows under ultraviolet light.
      3. A spot (that you place on each tested cancer cell) produces a color change when exposed to iron(III) chloride solution

    2. This activity can be completed in one 45-minute period.

    3. The exercise works best with students working in pairs (and larger groups) to promote cooperative learning. Eventually, though, the entire class must interact to reach consensus.

    4. Quantities given assume 12 lab groups of two students each. If adjustments must be made for the number of students in the class, try to keep the percentage of cancer cells close to 40%. This represents the approximate odds of a person being diagnosed with cancer in a lifetime in the United States. Assuming a life span of 70 years and an approximate U.S. population of 270 million, the percentage is closer to 30%, but published estimates are nearer 40%.

    5. This exercise is intended to simulate the general classic cancer detection processes. There should also be some emphasis on inquiry skills such as questioning, observing, classifying, collecting and managing data, hypothesizing, and concluding.

    6. The three conventional methods of detection of cancer cells are by feel or visual inspection, by imaging, or by biological or chemical test.

    Advanced Preparation

    Time required to photocopy, cut, and stain the cancer cells: ½ hour.

    Time required to make staining solutions: about 1 hour, but the solutions can be used from year to year.

    At least one day prior to this exercise, you will need to:

    1. Print the images of student "cells." For each set of 24 students you need to make five photocopies of the "cancer cell" and seven photocopies of the "normal cell." Click on these links for printable versions of the normal cell and the cancer cell.

    2. Note that the printable cell pages each have four images of the cell. If possible, photocopy the cells on to yellow paper (see #4, below). Cut the pages into four sections, one cell per section.

    3. Apply the fluorescent spot to the "cell": For the fluorescent dye, use a 0.1% solution of fluorescein (0.1 g of fluorescein in 100 g of water). Apply the same way you did for the chemical test above, except no developing is necessary; simply use an ultraviolet light source to make the fluorescein visible. Since fluorescein appears slightly yellow on the paper, you might want to photocopy the cell diagrams on yellow paper to mask the fluorescein stain somewhat. In any case, use only enough fluorescein to make it visible under the ultraviolet light. If it is too visible without the UV light and yellow paper is not an option, perhaps you could place the spot somewhere on the cell where there is more "noise" – more details and more printing – to camouflage the color somewhat. Be sure to place the fluorescein spot somewhere away from the chemical test spot; otherwise the UV spot may be masked by compounds placed on top of it.

    4. Apply the "color change" spot to the cancer "cell": Use a 0.1 M (approximate) aqueous solution of potassium thiocyanate [KSCN] (0.97 g of KSCN in 100 ml of water) for a dark red color, or potassium ferrocyanide [K4Fe(CN)6] (4.22 g of K4Fe(CN)6 in 100 ml of water) for a blue color. (Note: The blue color is the result of the hexacyanoferrato iron(III) ion [FeFe(CN)61-] and the red color is the result of the thiocyanato iron(III) ion [FeSCN2+].) Both of these original solutions are colorless, so students should not notice them on the diagram of the cell. Apply either one with the tip of a toothpick, putting down several layers. Alternatively, soak a cotton swab and use it to brush a light coating of the solution on the paper. In either case, try not to get the paper too wet with the solution. (Too much liquid will produce a wrinkled look on the paper.) Students will later develop the spot using a cotton swab wetted with a 0.1 M iron(III) chloride solution to produce the color. You should practice the toothpick or cotton swab application (and subsequent development) of the first solution on a blank piece of paper until you have a spot that meets the dual criteria: not showing up to the student's naked eye; becoming sufficiently visible to students when the iron(III) chloride solution is applied.

    5. Be sure to apply the fluorescent spot and the chemical test spot at different sites on the cell. It makes the most sense to place these two spots inside the nucleus, as that is the site of cell division that occurs uncontrollably in cancerous cells. Even if you do place both in the nucleus, separate them so that they don't interact in the chemical test. The fluorescent spot may be masked by the development of the color in the chemical test.

    6. Apply the spots the day prior to the exercise in class, to provide drying time.

    7. An alternative (slightly less visible) to the thiocyanate or ferrocyanide solution is to use a 1 M copper(II) sulfate [CuSO4] solution (25.0 g CuSO4.5H2O in 100 ml of water) as the applied spot. Then develop it with a swab of ammonium hydroxide solution, NH4OH. (Household ammonia works OK for this purpose, although the color deepens slightly with higher concentration. Weigh the better result against the greater hazard of student exposure to ammonia fumes.) A light blue color will appear due to the tetraaminocopper(II) [Cu(NH3)42+] complex ion.

    8. Place some of the iron(III) chloride solution in small labeled bottles or beakers for student use. Have these and cotton swabs at each lab station or table.

    9. Note: A somewhat more sophisticated level of class reasoning is required if you add one or both of these solutions (the fluorescent test and/or the chemical test) to one or two "normal" cell diagrams. This introduces conflicting evidence and requires that judgments be made about findings. Use this approach only if your class can handle the logic.

    10. Prepare three sets of cells, A, B, and U (for Unknown). In each of sets A and B, there should be 7 normal cells and 5 cancer cells. These are the two sets you will distribute in the first part of the experiment. In set U there should be 14 normal and 10 cancer cells. This will produce a class data table that approximates the United States data regarding cancer incidence in a person's lifetime. Remember to try to distribute the cancerous cells in such a way that each lab group gets one of these cells.

    11. Photocopy sufficient student pages of the Cancer Detetctives to give one to each student.

    12. Have available one ultraviolet light source for each lab group, if possible. The exercise can be done with just one UV light for the entire class, but it will take longer.

    13. It would be easy to correlate results if you had a scheme set up for the cancerous and noncancerous cells, e.g., a grid of cell letter and numbers that would correlate to the distributed cells. This would make grading student results much easier.

    Conducting the Activity

    1. The activity can be introduced in any way that fits prior work in your class. Emphasizing inquiry methods or the problems of detection (for scientists in general and for oncologists specifically) would be natural avenues to introduce the activity.

    2. Assign the students to read the Student version of this activity as homework the day before doing the activity.

    3. Print and distribute the student worksheet for the activity. If you wouild like to edit the worksheet, use the Microsoft® Word version of the worksheet.

    A. Visual (naked eye) Detection

    1. Distribute two cells to each person. Allow about 5 minutes for individual observations and inspection, and then another 5 minutes for lab group and larger group discussion. Encourage students to communicate with others around them so that they actually see what a "cancerous cell" looks like; otherwise they may flounder, not seeing any differences in their cells.

    2. You may wish to make an overhead transparency of a "normal" cell and keep it on the screen while students make their own visual inspections.

    3. As these observations wind down, do a cursory survey to determine approximate numbers of cancerous vs. noncancerous cells.

    4. Do a brief in-class discussion to generate class consensus regarding the hypothesis needed to test the new, unknown cell.

    5. Distribute the unknown cell to each student. Try to make sure that each lab group gets at least one cancerous cell and one normal cell, just so they have the experience of detecting the "cancerous cell" by noting differences between the two types.

    B. Radiation (ultraviolet fluorescence) Detection

    1. Ask students to go on to the radiation test, using the ultraviolet light. Each student will be responsible for testing all three of his or her cells and recording the results.

    2. You may need to help students recognize the fluorescence of their spots.

    3. Allow about 10 minutes for this step, including the time needed for intraclass discussion about the need to change the hypothesis. Ideally, each lab group would have an ultraviolet light source. More time will be needed if you have only one light source.

    C. Chemical (color change) Detection

    1. Make sure the bottles of iron(III) chloride solution and cotton swabs are available for each lab group.

    2. Check to see that students are "swabbing" in the correct place where you have prepared the spots, and that they are recording observations properly.

    Follow-up Discussion

    1. Collect class data in an efficient way.

    2. Discuss the results.

    3. Assign students to complete the "Questions/Conclusions" section.

    Answers to Questions/Conclusions

    1. What three methods are used to detect cancer cells in this exercise?

      Answer: Visual detection, radiation detection, and chemical testing.

    2. Which of the three methods appeared to be the most sensitive? The least sensitive?

      Answer: The chemical test should be the most sensitive, while the visual detection is the least reliable.

    3. How did the class hypothesis about cancer cells change with the results of each new experiment?

      Answer: Visual detection: The student simply looked for the telltale sign of difference between cancerous and normal cells, so the hypothesis consisted of a statement saying that cancerous cells are those that contain that sign or mark.

      Radiation detection: The student changed the hypothesis by saying that now cancerous cells are those that glow under the ultraviolet light.

      Chemical testing: Now the student should say that cancerous cells are those that produce a color change when tested with FeCl3 solution. Moreover, each previous hypothesis will be retained with each new test. Each new test merely uses a more sophisticated process to detect cancer cells, so each old hypothesis should still work.

    4. What new questions arise as a result of your work?

      Answer: Answers will vary. Examples might include the following: Is this why we ask doctors for second opinions? Are scientists ever wrong? What do they do when they are wrong? Is it really this easy to detect cancer? What do scientists do when they discover cancer?

    Relevant National Science Education Standards

      Unifying Concepts and Processes — The activity involves making a determination based on observable evidence.

      Science as Inquiry — The activity is inquiry-based.

      Science and Technology — The activity explores the technology of cancer detection.

      Science in Personal and Social Perspectives — The activity shows the involvement of science in facing a personal and community health challenge, specifically cancer.

      History and Nature of Science — The activity involves deteriming if a "cell" is cancerous by careful experimentation and observation, thus underscoring the nature of scientific knowledge.

    Relevant New Jersey State Science Education Standards

      5.1 The activity in inquiry based.
      5.4 The activity explores the application of scientific knowledge to the technology of cancer detection.

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