Inspired by @philipcball's question, here is a 🧵of some of the most beautiful #biology experiments (in my opinion)

Disclaimer: Not in order and no details (links provided)
1-Messelson-Stahl discovery of semi-conservative DNA replication (Okay that's obvious but bear with me)

Year: 1958

Side-note: notice how humble the paper title is.

Paper ➡️pnas.org/content/44/7/6…

Summaries ➡️
➡️
2-Hershey-Chase:

Viruses replicate by way of their nucleic acids (not proteins)

DNA is the origin of hereditary material

Year: 1952

Paper ➡️ rupress.org/jgp/article-pd…

Summary ➡️
3- Isolation of messenger RNA
Brenner, Jacob, Watson and colleagues

Papers ➡️ nature.com/articles/19057…
➡️nature.com/articles/19058…

Summary ➡️ bit.ly/CSHLsum

Brenner's story ➡️ bit.ly/BrennerYT
➡️bit.ly/Biochapter12
4- #Immunology (1)

Karl Landsteiner shows that antibodies can be generated against literally anything (with a lot of mechanistic analysis)

Year: 1937

➡️ amazon.com/dp/B00MAVFQ2Y?…
5- #Immunology (2)

Affinity maturation: antibody affinity increases over the course of an immune response

Herman Eisen & Siskin

Simply elegant.

Year: 1964
6- Luria-Delbrück fluctuation analysis:

"The mutational event precedes the selective pressure used to reveal it."

Year: 1943

Paper ➡️ bit.ly/LuriaDelbrück

Summary ➡️
7- Hayflick limit:

Year: 1961

Normal cells have limited capacity to divide (40 to 60 times)

Paper ➡️ bit.ly/Hayflicklimit

Summary from Hayflick ➡️
(Term coined by Frank Burnet)
8- Induction of pluripotency:

S. Yamanaka and co. (The Yamanaka factors)
4 factors make cells younger

Year: 2006

Paper ➡️ cell.com/cell/fulltext/…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…
9- #Immunology (3)
Induction of acquired immune tolerance

Medawar and colleagues: a SINGLE experiment that changed immunology

Year: 1953

Paper ➡️ nature.com/articles/17260…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…

Interesting slightly relevant ➡️
10- Protein Secretory pathway: Pulse-chase experiment

George Palade and colleagues Siekevitz and Jamieson

Year: 1967

Paper ➡️ doi.org/10.1083/jcb.34…

Really nice summary ➡️ molbiolcell.org/doi/10.1091/mb…

Modified from images by James Jamieson
11- Transposons: Jumping genes

Barbara McClintock

Year: 1950

Paper ➡️ pnas.org/content/36/6/3…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…

Summary ➡️
12- #Immunology (4): Inducible switching of antigen receptor specificity

Klaus Rajewsky and co.

Year: 2000
(also repeated in 2019 for a different question)

Paper ➡️ nature.com/articles/35036…
13- #Immunology (5) Discovery and imaging of meningeal Lymphatics

Kipnis and colleagues

Year: 2015

Paper ➡️ nature.com/articles/natur…

(Side-note: proposed by Paolo Mascagni 200 years ago)
14- #Immunology (6) Epigenetics (not gene expression) clearly distinguish memory and naive T cells

Love the heavy water multi-year tracking of T cells.

R. Akondy and Rafi Ahmed

Year: 2017

Paper ➡️ nature.com/articles/natur…

Lecture ➡️ videocast.nih.gov/watch=23509
15- #Immunology (7)

Discovery of mammalian Pattern Recognition pathway

Medzhitov & Janeway

Year: 1997

Paper ➡️ nature.com/articles/41131

Conceptualization ➡️
16- #Immunology (8)

Visualizing clonal burst and dominance in the germinal center

Victora and colleagues

Year: 2016

Paper ➡️ science.org/doi/full/10.11…
17- #Immunology (9)

Two tolerance checkpoints during B cell development

Hedda Wardemann & M. C. Nussenzweig

Year: 2003
18- #Immunology (10)

Some plasma cells live long. Labeling of plasma cells. Tracking of antibody

M Slifka & R. Ahmed (1998)
Manz & Radbruch (1997)
Amanna & Slifka (2010)

Papers ➡️ bit.ly/Slifka1998
nature.com/articles/40540
nejm.org/doi/full/10.10…
19- RNA ➡️ DNA

Reverse transcription: enzyme activity and inhibition assays

David Baltimore & Howard Temin (& Satoshi Mizutani)

Year: 1970

Papers: nature.com/articles/22612…
nature.com/articles/22612…

Conceptualization ➡️ nature.com/articles/22756…
20- Chemical synthesis of a virus

Eckard Wimmer and colleagues describe the synthesis of poliovirus in vitro (cell-free system)

Year: 2002

Paper ➡️ science.org/doi/abs/10.112…

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More from @Plasmacellguy

20 Oct 20
Our review on peripheral T cell tolerance is now online in @NatRevImmunol

Link rdcu.be/b8LRt

I want to state a few relevant points in this 🧵

#Science #Immunology #AcademicTwitter Image
Most studies and perspectives focus on one mechanism of tolerance and few have seriously considered all these together in the context of T cell differentiation.

We attempted to draw a conceptual framework for the known tolerance checkpoints at each stage of the T cell lifespan
In summary, we present 6 main tolerance hallmarks:
Quiescence
Ignorance
Anergy
Exhaustion
Senescence
Death
Read 9 tweets

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