Great Experiments: Selection does not induce mutations: it reveals them(discussed Oct 12)

Selection does not induce mutations: it reveals them
(discussed Oct 12)

In the early 1900s, scientists discovered the existence of bacteria-killing viruses and soon after, observed singularities of resistant bacteria within cultures. This led to the description of bacteriophage as “dissociating agents,” yet no one could present evidence as to the mechanism of acquired resistance, what characteristic of bacteria was “dissociated” by bacteriophage. In 1943, Salvador Luria and Max Delbruck used logical deduction to simplify the problem and formulated two hypotheses: either the bacteria acquired heritable resistance in the presence of virus (adaptive) or the bacteria accrued mutations conferring resistance prior to viral exposure (spontaneous). They developed the theoretical distributions of resistant bacteria expected for each hypothesis and then experimentally observed that the actual distribution supports the mutation hypothesis. This simple logic puzzle not only answered a question in the minds of bacterial biologists; it demonstrated that mutations (beneficial or not) occur in the absence of selection. Selection simply reveals them.

Paper: Luria and Delbruck. 1943. Genetics 28.

Extra tidbits:

1. In addition to demonstrating that random, selection-independent mutations were the source of resistance in the bacterial cells, Luria and Delbruck also went so far as to formulate a mathematical model for estimating the mutation rate in a given culture. Their archaic method is one of a few models still used today.

2. The molecular basis of bacterial resistance has since been attributed to mutations in the fhuA gene, which encodes for a protein FhuA that acts as a phage receptor, among other functions. Read more here.

3. In his 1984 autobiography entitled A Slot Machine, A Broken Test Tube: An Autobiography, Salvador Luria wrote:

Everyone knows that in research there are no final answers, only insights that allow one to formulate new questions.

This work initiated the field of "modern" bacterial research and with it an unending cycle of new insights and new questions.

4. Six years later, Howard Newcombe published similar results in Nature.

(image source: Wikipedia)

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FOR COURSE PARTICIPANTS:

Our goal: to learn about important, beautifully designed experiments from across the biological and biomedical sciences.

In the course, you'll gain experience in reading classic papers and explaining key experiments from your own fields of interest to colleagues in other fields.

Students propose papers to discuss in the form of short written posts on this site. Papers to discuss are selected by class vote each week.

This course should strengthen your communication skills and your understanding of diverse fields of biology–and importantly, it should inspire creative thinking about your own research.

Writing your posts

Each person should contribute at least 4 posts about their favorite experiments by 1 month before the end of the semester (by the end of October). Please propose your own schedule for 4 posts in an email to Bob.

Please post about experiments that you consider to be (1) fundamental to an area of science and (2) beautifully designed. Experiments that changed or founded a field and also made you hit your head and say, "damn, why didn't I think of that?!" are great choices.

Posts should be 150 words or fewer, plus a picture or movie with an appropriate image credit included. Please do not exceed 150 words. This is an exercise in clear, concise writing.

Your post should be written for an intelligent audience who understands biology but knows little to nothing about the field you're writing about. Avoid confusing jargon. Informal wording is fine. Your post's title should capture what's interesting and fundamental about the work, for example the central question addressed by the work.

Please provide a link to the one paper you chose, bullet-pointed so that there's no confusion about which one this is. If you like, below the one bullet-pointed link you can also provide a link to a companion paper or two that can help put the main paper into context.

It's considered very bad form to cut and paste text from programs like Microsoft Word for your post, because hidden formatting comes along and can cause headaches. It makes me sad. A tip: copying your text from Word into a Google search bar, and then copying that text from the search bar, eliminates the formatting.

You can modify your posts at any time. It's okay to rewrite your dusty old posts to try to re-invigorate interest.

Voting

Voting will take place each Friday until 5pm on a poll that will be sent to you. Each poll will generally include all posts that are up by that Friday at 8am.

Please vote every week. Please don't vote for your own selections. The voting will decide which paper we'll read for the following week's meeting. Posts that are getting few or no votes will be removed periodically.

Meetings

We'll meet each Thursday at 12:30pm in GSB3101. Each week, we'll discuss the winning paper. The person who chose it will present it along with anything else that seems relevant, with everyone's help, tolerating constant interruptions for some interesting discussion.

An important part of the course: Everyone else should plan to present one other thing briefly and informally to everyone–a related paper, some historical background, or anything at all you chose to explore because you found it interesting and relevant. Come prepared to answer questions, since we're all curious.

If you don't have time to do the readings one week, please skip the meeting that week. This way, everyone who comes will be full participants. No one will be badgered for missing just 1 or 2 meetings, I swear.

-Bob Goldstein