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Entries in double helix (3)


Photograph 51: Rosalind Franklin and the DNA Double Helix, Part 2

My last post introduces Rosalind Franklin.  She’s the unsung heroine whose name should go right along with “Watson & Crick.”  We should be saying “Franklin, Watson, and Crick.”  But alas, Franklin’s contribution to the discovery of DNA”s structure came at a time when women weren’t even considered in any professional work, even if their accomplishments were outstanding. 

         Also, Franklin died young, and Nobel Prizes are never awarded posthumously, so Crick and Watson and, of all people, Franklin’s nemesis Maurice Wilkins, received the Nobel for DNA.  (Barbara McClintock suffered from this same lack of considerations, but fortunately, she outlived it, and received the Nobel Prize at the age of 81.)

         Franklin earned her doctorate in chemistry from Cambridge University during WWII, went on to make important discoveries about carbon, then learned X-ray crystallography in Paris.

         X-ray crystallography is a technique for figuring out the structure of a molecule.  The substance in question must first be crystallized.  Then a miniscule sample of the crystallized material is mounted on a pin, and an X-ray beam is aimed at the crystal; behind the crystal is a piece of photographic film.  Most of the X-rays pass right through the empty space within the crystal and expose the film.  But when an X-ray hits the nucleus of one of the atoms in the crystal, the ray gets deflected.  The pattern of deflections shows dark on the photographic film after it is developed.  This pattern gives strong clues about the three-dimensional positions of the atoms in the molecule.

         After her work in Paris, Franklin went to King’s College in London to figure out the structure of the DNA molecule.  At King’s, Wilkins had been unable to get a clear X-ray photograph of DNA. 

         The first thing Franklin did at King’s was to figure out that Wilkins’ DNA crystals weren’t pure.  There were actually two crystalline forms of DNA, and Wilkins had been trying to X-ray a mixture of these, so of course he had been unsuccessful at finding the DNA structure.

         The plot thickens.  More about this in my next post; stay tuned.



Photograph 51: Rosalind Franklin and the DNA Double Helix, Part 1

Rosalind Franklin was the superb X-ray crystallographer who figured out the molecular structure of the DNA double helix.  Her accomplishment was almost completely hidden in 1953 when Francis Crick and James Watson announced that they had solved the structure of DNA.

         Rosalind Franklin died young, of ovarian cancer, possibly caused by years of exposure to the X-rays she used in her work.  But since her death, the women’s movement, and the increasing number of women in science, have brought her story to public attention.  Books, such as Rosalind Franklin: The Dark Lady of DNA, by Brenda Maddox, and articles about Franklin tell a far different story from the one in James Watson’s The Double Helix.

         Now Anna Ziegler has written a play about Rosalind Franklin, called Photograph 51 after Franklin’s famous X-ray diffraction photo that led directly to the discovery of the double helix.  I’ll have more to say about Rosalind Franklin in my next post.  Meanwhile, here is some film about the new play.



What we didn't expect from the Human Genome Project

The history of DNA research is a tale of patient researchers laboring day after day on myriad tiny problems.  It is a tale of myriad answers leading at last to profound insights.

    This is what happened with the Human Genome Project.  The question the HGP set out to answer was:

• What are all the genes in a human being?

    Before the Project began, geneticists had learned a lot.  They knew that genes work by manufacturing proteins.  They knew that genes do this indirectly:  Enzymes in the cell nucleus unroll and unzip the DNA double helix and copy a target gene into messenger RNA.  The messenger RNA carries the gene’s code to cell parts outside the nucleus to direct protein manufacture.  Finally, geneticists knew that humans have around 100,000 proteins in their bodies.  So researchers expected the HGP to take years and to turn up about 100,000 genes.

    But the geneticists working on the Project, devised new, speedier techniques for decoding DNA.  A lot sooner than anticipated, the whole human genome was known.  And there weren’t 100,000 genes—there were only about 30,000!  Or maybe only 25,000!  A humbling conundrum.

• How do the 100,000 proteins come from only 25,000 genes?

    Before the Human Genome Project, something else had come to light:  When a messenger RNA gets copied from one of our genes, it gets “edited.”  Molecules called spliceosomes cut the RNA message into fragments, remove some of the fragments, and splice the rest back together again.  The spliced message is what actually gets translated into a protein.  But the spliced message isn’t always the same.  The set of fragments that get spliced together can differ.  So that alternative proteins result from the same messenger RNA and therefore from the same gene!

    Is this how 25,000 genes make 100,000 proteins?  How did this incredible system evolve?   Some biologists think the first active catalytic molecules of life were RNA, while others think they were protein.  Intriguingly, spliceosomes have some of both.  Could alternative splicing be connected to the earliest molecules of life?  When we investigate this editing of RNA, are we seeing far back into life’s beginnings, just as we see far back into the beginnings of the universe when we investigate the oldest light we can find with the Hubble Telescope?