Understanding common themes in experimental passages

MCAT
By Neetij

MCAT experimental passages can be among the most enigmatic things you encounter as a pre-medical student. Usually, you’re given an excerpt of an actual scientific paper published some years ago. Reading and understanding a paper is no small task. 

Biologists tend to draw from the same pool of concepts and strategies when designing experiments. What we have here today is a small collection of principles I’ve found useful to know for the MCAT. 

“Teams” 

We’ll begin with the concept of “teams,” which you might find useful when you’re analyzing a regulatory system. If a multiple genes/proteins are working at the same time, group them into teams based on passage information. What do I mean here? 

Let’s say a passage involves certain genes that either promote or suppress cancer. You might encounter proteins like p53, c-myc, src, p21, Rb, and Akt. 

You find out the following from the passage: p53, Rb, and p21 are tumor suppressors, meaning they can act against the growth of cancer. 

c-myc, src, and Akt are proto-oncogenes, meaning they can act to promote cancer growth. 

We have two teams here: Team Cancer and Team Anti-Cancer. 

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It might be helpful for you to jot down a little table like this to keep track of the proteins while thinking about the questions. 

Let’s look at an example question: 

“Which of the following changes would reduce uncontrolled cell growth?” 

a. Inhibiting c-myc

b. Activating src

c. Inhibiting Rb

d. Activating Akt

Using our table, we can add some more information to this question that might make it easier. 

“Which would reduce uncontrolled cell growth?” (aka Anti Cancer) 

  • Inhibiting c-myc (hurt the pro-cancer team)
  • Activating src (help the pro-cancer team) 
  • Inhibiting Rb (hurt the not-cancer team)
  • Activating Akt (help the pro-cancer team)

 

The question asks about something that will help the Anti-Cancer team, or in other words, hurt the Pro-Cancer team. This leaves us with the correct answer, (a). 

Necessary vs. Sufficient 

One of the most important concepts you’ll encounter on the MCAT is the difference between “Necessary” and “Sufficient”. It’s a universal and significant part of understanding biological processes. 

What does each of these words mean? 

If we were to say… 

A is necessary for B to occur, that would imply if you take A away, B DOES NOT OCCUR

A is the only direct cause of B.

If we were to say… 

A is sufficient for B to occur, that would imply if you add A and nothing else, B DOES OCCUR

A always causes B.

Some examples: 

  • Necessary AND sufficient: A particular gene mutation is the only cause of, and always causes, Tay-Sachs disease
    • No one without the mutation gets the disease (necessary)
    • If you have the mutation, you will get the disease (sufficient). 
  • Necessary but NOT sufficient: Being infected with HIV is the only cause of AIDS. 
    • No uninfected person gets AIDS (necessary). 
    • You can get infected, but you might not get AIDS (NOT sufficient).
  • Sufficient but NOT necessary: Decapitation is not the only cause of death, but it pretty much always causes death. 
    • Not all deaths are caused by decapitation. (NOT necessary) 
    • A person who is decapitated is basically dead. (sufficient)
  • Neither necessary NOR sufficient: A number being odd is neither necessary nor sufficient for the number being a multiple of 5. 
    • If a number isn’t odd, it can still be a multiple of 5 [10, 20, 30] (not necessary).
    • A number can be odd but not be a multiple of 5 [3, 7, 9] (not sufficient). 

Genes: Knockout and Knock-in 

Another motif you will likely encounter in science passages is gene knockouts and “knock-ins”. A gene knockout, as you might know, occurs when a researcher artificially deletes an entire gene from the genome, thus preventing the cell or organism from producing whatever that gene codes for. For example, a particular gene produces Factor VIII, an important component in blood clotting. If we were to knock out the Factor VIII gene in a mouse, we would almost certainly observe poor clotting in the mouse. You might see this abbreviated as “ΔFactorVIII”, where the ‘Δ’ indicates a deletion or knockout. 

Screen Shot 2024-07-27 at 9.38.27 AM

A knock-in, in contrast, is when you add something to the genome that wasn’t there before. Let’s consider the mouse with poor clotting. Say you have a gene for Factor VIII that has a few mutations in it – the Factor VIII it produces doesn’t work quite as well as the wild-type (i.e., “normal”) Factor VIII, but it does work. If we were to “knock-in” this mutant Factor VIII into the mouse, we’d observe intermediate clotting, since the mutant protein would be able to fulfill part, if not all, of the function of the normal protein.  

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Interfering with DNA -> mRNA -> Protein 

Lastly, let’s go over what happens when a scientist interferes in some way with transcription, translation, and protein function. 

One way of manipulating gene function is a simple gene knockout. Since we already discussed gene knockouts, I won’t belabor the point – in short, knocking out a gene prevents the cell from producing any mRNA or protein from that gene, and its associated function does not occur. This change is often permanent, unless a “knock-in” experiment is also conducted. 

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Another way of manipulating gene/protein function is gene silencing. The gene is not eliminated – it remains perfectly intact and is transcribed normally to produce mRNA. Instead, a gene can be silenced with the addition of microRNA (miRNA) or small interfering RNA (siRNA) molecules. One of these molecules binds to the mRNA and marks it for destruction before it can be translated. This silencing is often temporary, and once the miRNA or siRNA is degraded, the protein is produced once again.

Screen Shot 2024-07-27 at 9.40.17 AM

Lastly, a final way of manipulating gene/protein function is via direct inhibition of the protein. The gene remains intact, the mRNA is properly transcribed, and the protein is produced. However, the addition of (for example) a small molecule inhibitor might bind to the protein and prevent it from performing its function. This inhibition is often temporary as well. 

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Together, these concepts represent a handful of useful principles for analyzing scientific passages on the MCAT. 

Neetij graduated from St. Olaf College with a major in Biology and a minor in Biochemistry. He developed a love of research as an NIH IRTA fellow and as a scholar within the Fulbright US Student program, and he is now pursuing an MD at the Washington University School of Medicine in St. Louis.

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