You might have heard about the molecular imaging technique cryo-electron microscopy (cryo-EM) because of the 2017 Nobel Prize in Physics. This WiSE Wednesday we’d like to tell you another story involving a Nobel Prize and electron microscopy (though not the cryo kind). In many ways, this story has striking resemblance to a more well-known story of a woman being denied a share of a Nobel Prize for her work. You might know the story of how Rosalind Franklin got the “pictures” of DNA used to solve its structure that earned James Watson and Francis Crick the Nobel Prize. But did you know that Louise Chow took the images that led to her collaborator, Richard Roberts winning the Nobel Prize in Physiology of Medicine in 1993 for the discovery of RNA splicing?
Louise Chow was born in Hunan Province, China and got an undergraduate degree in Agricultural Chemistry from National Taiwan University before moving to the United States to pursue a graduate degree in Chemistry from the California Institute of Technology. Her thesis work involved developing techniques to use electron microscopy to visualize gene organization in bacteria and bacteriophages (you might remember “phages” from last week’s profile of Martha Chase).
After graduating, she took a post-doctoral position at the University of California, San Francisco (UCSF), and then joined Cold Spring Harbor Laboratory (CSHL) in 1975 with her husband and fellow scientist Thomas Broker. It was here at CSHL that she performed the groundbreaking work that undoubtedly was crucial to “Robert’s” discovery of splicing, and for which many people believe she deserved a share of the Nobel Prize.
In order to make a protein, the DNA in genes is first copied into an RNA intermediary called messenger RNA (mRNA). Initially, this RNA contains “extra segments” called introns between the “exons” that actually code for the protein. RNA splicing is the process by which the introns are removed to make mature mRNA that can be translated into functional protein. Chow and Roberts working at CSHL and Phillip Sharp and his team working at MIT independently discovered this process in 1977. Using electron microscopy methods she’d been perfecting for years, Chow set up the experiments and took images that directly showed splicing taking place.
The finding was revolutionary and an eventual Nobel Prize was almost a given. But whom to award it to? It was agreed that Roberts & Sharp would share pieces, and many people felt that Chow also deserved a share. But, the argument went, if they gave Chow a piece, wouldn’t they have to give Susan Berget, the electron microscopist working with Sharp, a share? And you can’t split a Nobel 4-way, so the men deciding whom to nominate decided to exclude Chow rather than incite controversy over why they chose to award one woman but not the other (1).
Chow and her husband (and vocal advocate) Thomas Broker left CSHL in 1984, continuing their collaborative work on human papillomaviruses (HPV) at the University of Rochester School of Medicine in 1984 and later (1993) at the University of Alabama at Birmingham (UAB). One of Chow’s major breakthroughs in this HPV research was developing a way to produce large amounts of the virus in the lab and study its replication process in tissue cultures. In addition to her work in the lab, she is an Associate Editor of Virology and a member of an NIH advisory committee that reviews gene therapy protocols. She was elected to the National Academy of Sciences in 2012.
I had the great privilege of hearing Chow talk when she came to CSHL for a meeting honoring the 40th anniversary of the splicing discovery. I can’t give her the Nobel Prize she deserves, but I award her this WiSE Wednesday profile.
 Anthony Flint (5 November 1993) "Behind Nobel, A Struggle for Recognition Some Scientists Say Colleague of Beverly Researcher Deserved A Share of Medical Prize". Archived from the original on June 6, 2004. Retrieved 2018-03-18. , Boston Globe.
photo: the University of Alabama at Birmingham (UAB)