Jellyfish, Biophysics and Surgery

03-03-2010

I just returned from the annual meeting of the Biophysical Society in rainy San Francisco. The Society is the first scientific society I joined - 34 years ago! Oh, you didn’t know that they accepted high school students as members? - heh heh heh.

The meeting was filled with the usual things that biophysicists think about: protein structure and function, lipid membranes, molecular modeling … all that neat stuff. I presented a poster on a strange phenomenon Ewa Nurowska and I observed about the chloride conductance in glycine receptor channels. Not to worry, I’m not going to describe that here.

What I really want to talk about is surgery! Yes, surgery had a prominent place at a meeting of biophysicists. The occasion was the National Lecture, presented by Roger Tsien - one of a trio who shared the Nobel Prize for Chemistry in 2008. You may not recognize Roger’s name, but you probably have seen his work in one form or another. If you have ever seen an image of a cell glowing green - that’s due to Roger’s discovery and the development of green fluorescent protein. GFP was isolated from a type of jellyfish. Roger’s group modified the GFP gene to make it more efficient. He subsequently developed variants of GFP that absorb ultraviolet light and then fluoresce at visible wavelengths that cover the whole rainbow. The colorful pictures allow researchers to determine, for example, what cells are expressing what proteins. It has become an indispensable tool in many fields of biological research.

Roger went on to describe how he is now developing probes for use in MRI and electron microscopy, but also that he wanted to determine whether optical dyes could have medical application. The way to get GFP into cells, however, is to incorporate it into the genome - and that’s neither practical nor ethical with humans. Also, GFP is fine for single cells but the emitted light would be absorbed by the tissue and fat of an intact person.

To overcome these problems, he started with one of his red dyes, Cy5, (long wavelengths penetrate tissue better) and linked it to a carrier polypeptide. The carrier molecule is positively charged and will stick to cell membranes. But, it becomes sticky only after being partially degraded by a protease that is excreted from many tumor cells. So, when the dye-polypeptide complex is externally applied to a surgical field containing normal and cancerous tissue, only the tumor cells are labeled. Now, you may ask, what good is a red dye in a bloody surgical field? Well, the dye emits a specific red wavelength, so a digitized image can highlight what the human eye cannot. The surgeon can view a false-color image of the tumor in the surgical field. Roger’s videos showed several examples with mice. The most impressive video was one in which two dyes were used. The surgeon observed a lime green tumor, cyan blue nerves (both false colors) and the usual surgical field. She excised the cancer, carefully avoiding the branch of the nerve that was surrounded by the tumor. Way cool!

You might have thought that advances in cancer treatment would be based on chemo or radiation therapy. But don’t discount the possibility of a more colorful operating room.

You can read more about Roger’s work in the March 2, 2010 issue of PNAS (Nguyen et al, "Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival", PNAS 107:4317).