Great Experiments: DYING GOATS, CANNIBALISM, And the central dogma

DYING GOATS, CANNIBALISM, And the central dogma

When 18,000 sheep in Scotland came down with a fatal neurodegenerative disease after receiving vaccinations, researchers were puzzled. The mystery became even greater when it was discovered that this disease, scrapie, was transmissible, and the infectious agent was in the formalin treated inoculum. After all, formalin should inactivate any infectious agent, since they all contain nucleic acids. This idea, that nucleic acids are the only mechanism by which heritable information is replicated, is known as the “central dogma” of biology.

So if 18,000 sheep dying of the mystery illness, scrapie, isn’t weird enough, let’s add in a cannibalistic tribe on a small island in the Pacific. The Fore people were dying of a strikingly similar illness, and it appeared to be transmitted through consumption of human flesh. The brains of affected people bore the same hole-ridden, spongey texture seen in biopsies of scrapie-affected sheep. What agent could be responsible for two infectious, neurodegenerative diseases? How could it be resistant to formalin?

Many hypotheses were offered, ranging from “slow virus” to “replicating polysaccharide”. However, it was work by Stanley Prusiner that lead to the unravelling of this mystery. Through tried and true reductionist biochemistry, Prusiner achieved the purest preparation of the scrapie agent yet. After quantitatively determining the amount of infectivity present in his preparation, he sought to determine what treatments would eliminate that infectivity. Through simple biochemical experiments, such as treatments with proteases and nucleases, Prusiner demonstrated that the scrapie agent was predominantly proteinaceous in nature. Prusiner also calculated the size of the agent, less than 50,000 Daltons, and inferred that this size did not allow for the presence of a replicating nucleic acid within the structure. And thus the term prion, or proteinaceous infectious agent, was coined by Prusiner. For his ability to follow his data and think beyond the central dogma, Prusiner was awarded the Nobel Prize, only 15 years later.

https://sci-hub.cc/http://science.sciencemag.org/content/216/4542/136.long

No comments:

Post a Comment

Note: Only a member of this blog may post a comment.

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