Summarize evidence that DNA is the genetic material (Griffith, Avery, Hershey-Chase)

The 3 Classic Experiments

1. Griffith (1928) — Transformation

WHAT he used: Two strains of Streptococcus pneumoniae (bacteria that cause pneumonia in mice):

S strain (Smooth): has a polysaccharide capsule → virulent (kills mice).
R strain (Rough): no capsule → harmless (mouse lives).

HOW the experiment ran (4 injections into mice):

Injection	Result	Why?
Live R	Mouse lives	harmless
Live S	Mouse dies	virulent
Heat-killed S	Mouse lives	dead bacteria can't infect
Heat-killed S + live R	Mouse DIES 😱	the surprise!

Why this step matters: In the last injection, neither ingredient alone kills. Yet the mouse dies, and Griffith recovered living S bacteria from it.

2. Avery, MacLeod & McCarty (1944) — What is the transforming principle?

HOW:

Enzyme added	Destroys	Transformation still happens?
Protease	proteins	✅ Yes
RNase	RNA	✅ Yes
DNase	DNA	❌ No

Why this is the key: Only destroying DNA stopped R→S transformation. Therefore the transforming principle = DNA.

3. Hershey & Chase (1952) — Radioactive labeling

HOW (the steps):

Grow two phage batches: one with $^{35}S$ (hot protein), one with $^{32}P$ (hot DNA).
Let each infect E. coli.
Blend (shake off the empty phage coats stuck outside) → "Why this step?" to separate what entered the cell from what stayed outside.
Centrifuge: heavy bacteria form a pellet at the bottom; light phage coats stay in the supernatant liquid.
Measure where the radioactivity is.

Label	Found in pellet (inside cells)?	Conclusion
$^{35}S$ (protein)	mostly in supernatant	protein stayed OUTSIDE
$^{32}P$ (DNA)	mostly in pellet	DNA went INSIDE

Why this proves it: The molecule that enters the bacterium and directs production of new phage = the genetic material. That molecule was DNA.

Figure — Summarize evidence that DNA is the genetic material (Griffith, Avery, Hershey-Chase)

Worked "Forecast-then-Verify" examples

Recall Feynman: explain to a 12-year-old

Imagine you want to know which ingredient in a cake makes it taste sweet: flour, eggs, or sugar. Griffith mixed a "dead sweet cake" with a "plain cake" and the plain one magically became sweet — so something sweet jumped across. Avery then removed one ingredient at a time; only when he removed the sugar did sweetness disappear — so sugar (DNA) is the sweet-maker. Hershey-Chase painted the sugar one color and the flour another, baked the cake, and saw that only the sugar's color ended up inside the new cakes. So DNA is the "recipe" that gets passed on, not protein.

Active Recall

What did Griffith's experiment demonstrate?

That a heritable "transforming principle" can pass from dead virulent (S) bacteria to live harmless (R) bacteria, making them virulent.

Why did Griffith NOT identify DNA as the genetic material?

He only showed something transferred; he had no method to identify which molecule it was.

What is "transformation" in bacteria?

Uptake of free external DNA that permanently changes a cell's inherited traits.

In Avery's experiment, which enzyme abolished transformation?

DNase (which destroys DNA), proving DNA was the transforming principle.

Why were people skeptical of Avery's conclusion?

They feared trace protein contamination, and DNA's 4 bases seemed too simple to store genetic information.

What two molecules make up a bacteriophage?

A protein coat and DNA — nothing else.

Which radioactive isotope labeled protein in Hershey-Chase, and why?

^{35}S

, because protein contains sulfur but DNA does not.

Which isotope labeled DNA, and why?

^{32}P

, because DNA contains phosphorus but protein does not.

Why is the blending step needed in Hershey-Chase?

To shake the empty phage coats off the bacterial surface so we can tell what actually entered the cell.

After centrifugation, where were bacteria vs phage coats?

Bacteria (heavy) in the pellet; phage coats (light) in the supernatant.

What was found in the pellet in Hershey-Chase?

^{32}P

(DNA) — showing DNA entered the bacteria and is the genetic material.

Why is Hershey-Chase considered more convincing than Avery?

A phage contains only protein + DNA, removing the "contaminating third molecule" loophole.

Connections

DNA Structure — once DNA was proven genetic, scientists rushed to find its structure (Watson-Crick).
DNA Replication — explains how this genetic material is copied.
Bacterial Transformation in Biotech — Griffith's discovery underlies modern gene cloning.
Central Dogma — DNA → RNA → Protein; this note establishes DNA as the start.
Chargaff's Rules — base-pairing evidence supporting DNA's information role.

Concept Map

Hinglish (regional understanding)

Intuition Hinglish mein samjho

Socho 1950 se pehle scientists ko pata tha ki genes hote hain, lekin yeh kis molecule mein store hote hain — protein ya DNA? Sab log sochte the protein hi hoga, kyunki protein ke 20 amino acids hote hain (zyada "complex"), aur DNA mein sirf 4 bases — bohot simple lagta tha. Yeh teen experiments dheere-dheere prove karte hain ki boring DNA hi asli genetic material hai.

Griffith ne mice mein bacteria inject kiye. Live R (harmless) se chuha zinda, live S (virulent) se mar gaya. Heat-killed S akela kuch nahi karta — par jab heat-killed S ko live R ke saath mix kiya, chuha mar gaya! Matlab kuch heritable cheez dead S se live R mein jump kar gayi — isko "transforming principle" kaha, par Griffith ko nahi pata tha yeh DNA hai.

Avery ne smartly ek-ek karke molecules destroy kiye. Protease se protein toda — transformation phir bhi hua. RNase se RNA — phir bhi hua. Par DNase se DNA toda — transformation band ho gaya. Toh transforming principle = DNA. Lekin log shak karte the ki thoda protein contamination ho sakta hai.

Hershey-Chase ne phage (virus jisme sirf protein coat + DNA hota hai) use kiya. Protein ko $^{35}S$ se aur DNA ko $^{32}P$ se label kiya (kyunki protein mein sulfur, DNA mein phosphorus). Phage ne bacteria infect kiya, fir blender se hilaya aur centrifuge kiya. Result: $^{32}P$ (DNA) bacteria ke andar (pellet) mila, $^{35}S$ (protein) bahar reh gaya. Final proof: DNA hi andar jaata hai aur genetic material hai. Yaad rakho: DNA Pays ( $^{32}$ P), Protein has Sulfur ( $^{35}$ S).

Test yourself — DNA Structure & Replication

Connections