Amplify Science Natural Selection Engineering Internship Chapter 1 Lesson 3

1. FIGHTING DRUG-RESISTANT MALARIA

2. Read the daily message and record notes of
important points and deliverables. (5 min)
Open your pinned Daily Message Notes
• Add the today’s date and the subject of the
message (Causes of Drug Resistance) at the
top of the note.
• Add (Copy/Paste) summary of deliverables
and/or important information under heading.
NSEI 1.3.1 WARM-UP

3. NSEI REVIEW NS IN PARASITES
Interns re-watch a video to review what you have learned about parasite populations and
antimalarial drugs. (5 min)

4. What have you learned about antimalarial drug resistance? Share with your table.
NSEI REVIEW NS IN PARASITES
Key Points:
• Antimalarial drugs act as a selection pressure on a population of malaria parasites.
• Every time a malaria parasite reproduces, a mutation that could lead to resistance to a
drug has a chance to occur.
• A mutation can result in a new trait that is adaptive or non-adaptive, or the mutation may
have no noticeable effect.
• Parasites with the adaptive trait of drug resistance will be more likely to survive the
exposure to that drug and be able to reproduce and pass this trait to their offspring.This
shifts the distribution of traits in that population, so that many more individual parasites
have resistance for that drug.
• In the presence of this selection pressure, the distribution of traits in a population of
malaria parasites may shift toward increased drug resistance.

5. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
Interns actively read from the Dossier to learn more about how single-drug and combination
treatments affect drug resistance. (25 min)
Open the Futura Biomedical Engineer’s Dossier.
Selecting the link in the Daily Message and use the
table of contents to navigate to Ch 4: “Antimalarial
Drug Resistance.”
• Today’s research connects what you have learned
about antimalarial drugs as a selection pressure to
how drug resistance develops in a diverse
population of parasites.
• You should make annotations that help answer the
question on the board: How do malaria treatments
influence drug resistance?

6. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
Read and annotate independently.
Actively read and annotate Ch.4
“Antimalarial Drug Resistance” of the
Dossier.
• Carefully review the diagrams and
captions, and to look at the glossary if
you need more support with
engineering and project terms.

7. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
Share and discuss your annotations
with your partner.
Talk about what you have learned from the
chapter.
What ideas do you have about how
antimalarial drugs influence drug resistance?

8. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
Let’s review the diagrams to check for understanding.
When the Red Drug was used,
the percentage of Red Drug-
resistant parasites increases.
What do you notice when the
Blue Drug is used on the same
population instead.
• The percent of individual
parasites that are resistant
to Blue Drug increases.

9. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
When a combination of
drugs is used, resistance
stays low.
Remember that an
individual parasite can
have more than one trait
for resistance—some
individuals are resistant to
more than one drug.

10. NSEI 1.3.2 READING
ANTIMALARIAL DRUG RESISTANCE
Summarizing key points
• Using a single-drug treatment results in a shift in the distribution of traits in a malaria
population toward having more resistance to the drug used in that treatment.
• Once there is resistance to a drug, that drug may no longer effectively treat malaria.
• Using a combination of drugs is preferable to a treatment with a single drug.

11. TESTING FOR RESISTANCE
USING ONE DRUG
Use the MalariaMed DesignTool to observe the effects of single-drug treatments and to
discuss the pros and cons of each drug type. (15 min)
Design Tool activity.
It is important to isolate the different drugs
to understand their effects on the malaria
population over the ten years of the
MalariaMed model.
Play and discuss the MalariaMed Design
Tool Demo video.

12. TESTING FOR RESISTANCE
USING ONE DRUG
You are working to address each of the criteria to a greater or lesser extent, but the
constraint of avoiding an increase in the malaria parasite population is something that
must be accomplished.
The Global Health Organization won’t even consider a treatment design that causes
an overall increase in the parasite population.
Before you can determine which malaria treatments are ideal for addressing the
project criteria and this constraint, you must better understand the drugs you have
available.
This is different from the
word criteria.
It is important to prevent an
increase in the total parasite
population.

13. TESTING FOR RESISTANCE
USING ONE DRUG
Analyzing Single-Drug Treatments
sheets
You will record the results of these tests to
help with your research.
We will run the first test together as a team.

14. TESTING FOR RESISTANCE
USING ONE DRUG
Open Futura MalariaMed and we will model building and recording a single-drug
treatment for Drug A.
Set up and test a 7-day treatment of Drug A at small doses.

15. TESTING FOR RESISTANCE
USING ONE DRUG
Run the test…
The results for Percentage of Parasite
Population with High Resistance at the end of
10 years.
Record these values in the first table on your
sheets.

16. TESTING FOR RESISTANCE
USING ONE DRUG
Record the result for Total Parasite Population
on your sheet.
This result compares the size of the total
parasite population from year 0 to year 10, so
there was roughly no difference in the number
of individuals in the sample population.
No change

17. TESTING FOR RESISTANCE
USING ONE DRUG
Record the results for Patient Side Effects and Cost on
your sheet.
These results are directly related to the project criteria
and the constraint you must consider so your
treatments do not result in an increase in malaria
parasites.
While you should be concerned with…it is also
important to try to reduce the malaria parasite
population.
• minimizing drug resistance,
• minimizing patient side effects, and
• keeping costs low,
The ways to reduce the malaria parasite population and
the ways to keep resistance low can sometimes conflict.
Mild side effects, $5,250.

18. TESTING FOR RESISTANCE
USING ONE DRUG
How to analyze test result histograms
The histogram bars in each graph reflect the same
population of malaria parasites at year 10.
What traits for drug resistance exist in the
population at year 10?
• Almost all the parasites have high resistance to
Drug A, most have no resistance to Drug B and
Drug C, but a small number have some
resistance to these drugs.

19. TESTING FOR RESISTANCE
USING ONE DRUG
Show the percentage by selecting the % button.
This helps you look at the population in a different way
(by displaying the percentage that the number of
parasites represents in each bar).
Note that for each graph the total should equal 100%
because each histogram represents the same total
parasite population.

20. TESTING FOR RESISTANCE
USING ONE DRUG
Compare this distribution of traits to the
population at the beginning.
Move the time slider to year 0.
What do you notice?
The population started with 90% of no resistance to
Drug A and 10% of some resistance to Drug A.
For Drug B, 40% had no resistance, 40% had some
resistance, and 20% already had high resistance.
For Drug C, 20% had no resistance and 80% had some
resistance.

21. TESTING FOR RESISTANCE
USING ONE DRUG
Let’s talk through the observations for the
effect of 7 days of Drug A at small doses.
As you move the time slider to each year, note that the
total parasite population decreased during the first 5
years.
Record that observation on your sheets.

22. TESTING FOR RESISTANCE
USING ONE DRUG
Focus on Resistance to Drug A histogram.
Note when the majority (over 50%) of parasites in the
population had the trait for high resistance to Drug A
57% by year 5.
Record this in the observations section of your sheets.

23. TESTING FOR RESISTANCE
USING ONE DRUG
Once most of the parasites in the population
have high resistance to Drug A, the population
begins to increase.
Record that observation on your sheets.
What does this observation suggest?
The malaria treatment, using only Drug A, isn’t working
anymore to kill the parasites, so the individuals with
traits for resistance are more likely to produce
offspring with that same trait.

24. TESTING FOR RESISTANCE
USING ONE DRUG
Predict what would happen if you continue to
use this same malaria treatment and could see
the results forYear 15?Year 20?
The population would continue to increase because
continuing to use Drug A acts as a selection pressure
on the population, so individuals with traits for
resistance tend to survive and the trait becomes more
common.

25. TESTING FOR RESISTANCE
USING ONE DRUG
By year 10, 99% had high resistance to Drug A
and 1% had some resistance to Drug A.
Record this observation on your sheets.

26. TESTING FOR RESISTANCE
USING ONE DRUG
Focus on Resistance to Drug B histogram.
Review the years again and note that by year 10,
parasites with high resistance to Drug B had decreased
from 20% to 0%, and parasites with some resistance to
Drug B decreased from 40% to 6%.
Record this observation on your sheets.
What does this observation suggest?
By not using Drug B, parasites with the trait for
resistance to Drug B can be killed by using a different
drug.

27. TESTING FOR RESISTANCE
USING ONE DRUG
Focus on Resistance to Drug C histogram.
Review the years again and note that by year 10, there
were still 0% of the parasites with high resistance to
Drug C and parasites with some resistance to Drug C
decreased from 80% to 16%.

28. TESTING FOR RESISTANCE
USING ONE DRUG
In pairs - complete the remaining two tests and
discuss pros and cons.
Each partner will select one drug (B or C), complete
the test, and record the results.
Which drug will result in the highest percentage of high
resistance or which one will reach 50% high resistance
in the fewest number of years.
Share and record the results from your partners so
everyone has a complete analysis.
Discuss and record the pros and cons among the three
different drugs, using the results of each test.

29. TESTING FOR RESISTANCE
USING ONE DRUG
Debrief the results and connect back to the Dossier reading.
In each case, we isolated variables so each test was the same except for one thing.
• Each test used drugs for 7 days.
• Each test used small doses.
• We only varied the drug type in each test.
What are the pros and cons of each single-drug test?
Try to consider other ways you could better understand the effects of a single-drug.
• Try larger doses,
• Try fewer days.

30. TESTING FOR RESISTANCE
USING ONE DRUG
Debrief the results and connect back to the Dossier reading.
Tomorrow you will wrap-up your research by isolating for other variables to better
understand how the drugs affect the traits for drug resistance in the malaria population.
You may wish to point out that, as you just saw in the Design Tool, the constraint of killing
malaria parasites can be at odds with the criterion of minimizing drug resistance.
The best way to minimize drug resistance is to not give any drugs at all.
One of the challenges of this engineering problem is finding a good solution that addresses the
three criteria within the constraint of killing malaria.

31. NSEI 1.3 HOMEWORK
After-Hours Work:
Revisit Chapter 4 in the Dossier and revise or add new annotations.