November 2012

From snail snatching to medical modulations

One man’s auspicious blend of past experience and present skills yields future success

Photo of Baldomero Olivera

Priceless explorations and explanations of DNA exonuclease processivity and the discovery of conotoxins make this man a valued contributor to both enzymology and neuroscience. However, he remarkably discovered the latter using little to no expensive laboratory equipment. Faced by lack of funding in the Philippines, where he returned home to work, he called on his own ingenuity to develop and complete what would be a monumental study. The subject of said study was a very simple and readily accessible resource in his part of the world: snail venom. This man is Baldomero Olivera, and two of his papers are now recognized as Journal of Biological Chemistry “Classics.”

Featured JBC Classic articles


 
Thomas K. R. & Olivera, B. M. Processivity of DNA exonucleases. J. Biol Chem. 253: 424–429 (1978).
 
Rivera J. et al. Neuronal calcium channel inhibitors. Synthesis of omega-conotoxin GVIA and effects on 45Ca uptake by synaptosomes. J. Biol Chem. 262: 1194–1198 (1987).
 

Olivera’s venom explorations proved fruitful when, after much hard work, he discovered conotoxins, the material discussed in one of the two articles highlighted in the JBC (1) and the material that would have a huge impact in the fields of neurology and medicine.

Remembering his pastime of collecting snails as a child, and having inside knowledge in the field of DNA enzymology, Olivera knew the potential value of carrying out a systematic study on the venom found in cone snails. Using his keen analytical, biophysical, enzymological and laboratory skills, as well as his aptitude for gathering gastropods, he successfully isolated and purified the active peptides in cone snail venom. He coined these venom peptides as conotoxins, and their discovery led to the creation of an entirely new field of research.

These toxins target sodium and calcium channels in the body. At the time of their discovery, little was known about voltage-gated calcium-channels, which are present in excitable cells such as muscle cells and neurons and which initiate a response such as contraction or excitation, respectively, upon the passage of calcium through the channels. One of Olivera’s peptides from cone snails, the Ω-conotoxin GVIA, functioned through inhibition of calcium uptake through binding to neuronal calcium channels. News of this discovery caused a boon of research in this field, yielding more than 2,000 studies, which utilized Olivera’s synthesized version of the Ω-GVIA peptide, active at concentrations of less than 1E-12M! Research in this field finally resulted in the purification of the neuronal calcium channel, which was subsequently named after Olivera’s peptide, “the conotoxin receptor.” In addition to the impact this discovery had in the field of neuroscience, a conotoxin peptide has been approved as a painkiller with strength exceeding that of morphine.

It should be noted to young scientists that these successes were not merely a chance happening. Olivera previously had performed significant work in the field of DNA exonuclease enzymology, using radioactive tagging of DNA to study the processivity of eight different enzymes. This work was published before restriction enzymes were used and far before genome sequencing took the stage. The second “Classic” presented in the JBC reports his discoveries in the field of DNA processivity in a time when this concept was unheard of (2).

Children radiate curiosity and the desire to discover the world around them. Many successful scientists such as Olivera never lose grip of that youthful curiosity and adventurous spirit, allowing them to draw on experiences and creative ventures in childhood to inspire their current research pursuits. Motivated by their successes, I’d like to encourage all aspiring scientists to nurture this childlike curiosity and to take Olivera’s example: Create continuity between your past and present self — the adventurous child inside and the professional adult you are working to become. You may discover that, with a youthful, exploratory attitude, you may break through obstacles and create and discover things you never dared to imagine.

References
  1. 1) Rivier, J. et al. J. Biol. Chem. 262, 1194–1198 (1987).
  2. 2) Thomas, K.R. & Olivera, B.M. J. of Biol. Chem. 253, 424–429 (1978).
     

 

Photo of Erica SharpeErica M. Sharpe (sharpeem@clarkson.edu) is a Ph.D. student in Chemistry at Clarkson University in Potsdam, N.Y.
 
 
 


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2 Comments

  • I enjoyed reading your article, Erica even though I didn't understand all the scientific terms. I especially liked the last paragraph urging aspiring scientists to hold on to their curiosity.

    Looking forward to seeing you in a few months. Love, Julian's Grandma

  • I liked your presentation of this subject Erica and the personalized warmth you added.

    You are a good writer, and scientist.

    Sincerely,

    Gerry Sharpe

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