Nobel Prizefight

1. Noble Nobel?

2. Unraveling the dynamite prize

3. The biggest blunder

Oswald Theodore Avery (1877-1955) was a distinguished bacteriologist and research physician. In 1944, he figured out that DNA is involved in heredity. The discovery was certainly worth a Nobel, but no dice. Photo: NIH

Avery transferred DNA from donor bacteria to recipient bacteria. When the recipients divided, their daughters had traits (symbolized by the red body) from the donor. Avery was the first to realize that DNA carries heredity.

A very strong case
Serious, bespectacled man in black and white. Remember Oswald Avery? No? Well, don't look up the name of the researcher who linked DNA to heredity on any Nobel lists -- he didn't win The Big One. Still, it was Avery and his younger colleagues Maclyn McCarty and Colin MacLeod who set the groundwork for the biotechnological revolution by figuring out that it's not proteins that cause your hair to be blond, black, brown or blue, just like mom or dad.

Just kidding about the blue. But earlier in this century, as biologists started to envision the radical variations in the structure of various proteins, they naturally suspected proteins might carry heredity.

That applecart was overturned, in 1944, when Avery and colleagues:

1 Purified DNA from donor bacteria.

2 Exposed recipient bacteria to that DNA.

3 Allowed the recipient to divide, and saw that the daughter cells carried traits from the donors.

The conclusion was inescapable. DNA was carrying the information of inheritance. In other words, genes were made of DNA.

At the time, proteins had seized the imagination of scientists looking for a physical basis for evolution, says James Crow, a retired professor of genetics at the University of Wisconsin-Madison. "Avery was going against the stream somewhat. Almost everybody thought the gene was protein, because protein is very complicated, and the gene is complicated, and DNA seemed like a simple molecule."

diagram showing 1944 study of bacteria proving genes are DNA

Abundunce of a molecule?
Almost a decade before DNA's double-helix structure was described, DNA seemed like a boring molecule, about as interesting as a sentence written with four letters in fixed order: "abcdabcdabcdabcdabcdabcdabcdabcdabcdabcdabcdabcd."

Crow says that he learned of Avery's paper while a graduate student. "My own reaction was not to believe it was telling us anything about the gene, I thought there was some tricky selection process at work," that for some reason bacteria with traits like the DNA donor were being favored in daughter generations.

The conventional wisdom was that a trace of protein contamination had fooled Avery. But Joshua Lederberg, a geneticist who snagged a Nobel at age 33 for "discoveries concerning genetic recombination and the organization of the genetic material of bacteria," did take notice.

Fifty years after the fact, he wrote that he'd scrawled on Avery's paper:

"Unlimited in its implications"

"Direct demonstration of the multiplication of the transforming factor" [meaning that whatever was changing the recipient bacteria also affected the next generation]

"Viruses are gene-type compounds"

The Avery results hung in the air, only partly accepted, until 1953, when Watson and Crick shook biology by unraveling the curious double-helix structure of DNA -- work they might never have started had Avery and Co. not proved that you could change bacteria's genetics by adding DNA. (We're simplifying; other research in the interim also pointed to DNA as the molecule of heredity).

Avery never won a Nobel, partly because he died in 1955, and only the above-ground set gets prizes.

Still, Crow, says "It wasn't fully recognized at the time, but in retrospect he was a real hero." The research that grew from Avery's lab laid the groundwork for all of biotechnology and much of modern biology. "It was very profound," agrees University of Wisconsin-Madison professor of history and sociology J. Rogers Hollingsworth. DNA co-discoverer James Watson, he says, "was very much aware of the Avery paper" when he and Crick dove into the problem of DNA's structure.

As for Avery, "He was not bitter or unhappy," says Hollingsworth. "He was an amazing man, very remarkable. When he was awarded the Copley Medal (from the Royal Society in London), he didn't even go to London."

And yet to many, Avery represents the biggest booboo in Nobeldom. "He absolutely, there's no doubt in anyone's mind these days, should have been awarded the Nobel," says Hollingsworth. "This clearly was a major discovery, and one of the most important in biomedical science in the 20th century."

 Colorful, computerized image of DNA. All the refinements of DNA's complex structure rest on Watson and Crick's 1953 description of the double helix. And that rested on the findings of Oswald Avery, unsung siren of DNA. Photo: Lawrence Berkeley National Laboratory.

Still, he adds, the record of choices by Nobel committees is highly credible. "Certainly in the last half century, these Nobel committees really operate as though the whole world is watching them. I'm absolutely convinced that they take this as a very awesome responsibility; they spend years vetting some of these nominations, and consult with colleagues in these fields...."

Even though Nobel rules allow three awards for a particular discovery, and only two were given for the MRI in 2003, Hollingsworth generally gives the committee the benefit of the doubt on the current prizefight.. "I'm inclined to think, based on what I know about these committees, that there is a complex, fascinating story as to why the committee did not have Damadian share the prize. He had certainly done significant work in the area."

In 50 years, the Nobel archives for 2003 will be opened, and we can learn that reasoning.

In the meantime, you might make some discoveries in our bibliography.


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