Poison and science

MANILA, Philippines — National Scientist Lourdes Cruz calls research not shared with fellow scientists, students and society as “useless.”

That’s a strong observation coming from a talented scientist whose work has led to the development of the world’s most powerful drug for chronic pain.

In the mid-1970s, Cruz published a seminal paper on the venom protein of Conus or sea snails shaped like cones. The publication was followed by a series of papers on the feeding and mating habits of the Conus geographus in captivity, assay of the toxin, toxin proteins of different marine snails and basic chemical and molecular make-up of the toxins and their effects on the nervous system.

In 1985, Cruz and co-researchers reported their findings in the prestigious journal Science that the venom of the marine snail called Conus geographus from the Philippine seas contains many peptides, or small proteins. The peptides affect the channels through which charged atoms or molecules called ions pass through membranes into receptors of the central nervous system. There were peptides that cause muscular paralysis, peptides that cause sleepiness or drowsiness and so on.

Because of limited research facilities here, Cruz had to work part-time at the laboratory of Baldomero Olivera, a Filipino scientist at the Department of Biology, University of Utah. She continued research at the College of Medicine, University of the Philippines Manila and the Marine Science Institute, UP Diliman. They led to the practical use of conotoxins (the toxins found in conus shells) and commercial applications in neuroscience and medicine.

The raw materials for research and development are abundant. There are about 500 known species of these predator snails that use harpoon-like teeth to inject venom and paralyze their prey. Marine cone snails are distributed throughout tropical and subtropical waters. The Conus geographus, the most poisonous of all cone snails, hunts fish in the central Indo-Pacific oceans.

The researches of Cruz on conotoxins have made clear the biochemical and molecular structure and properties of many types of conotoxins and their active mechanisms.

Talk of sharing knowledge: the findings were published as 81 research articles in renowned journals (including  Science, Proceedings of the National Academy of Science, Journal of Biological Chemistry, Biochemistry) and more than 20 chapters in books and proceedings.

After Cruz looked at their uses as tools to study brain activities, it led to the study by other scientists of other types of conotoxins. It is estimated that a Conus species has 100 to 200 conotoxins synthesized and secreted in the venom duct. Around 50 to 200 components are found in the venom of each species, according to the a 2017 publication of the World Register of Marine Species and Chemical Reviews, the journal of the American Chemical Society.

In 1978, a myotoxin or poison that destroys muscle cells, was purified from Conus geographus;  the myotoxin caused flaccid paralysis, respiratory failure and death in mice. In 1981, three highly toxic peptides from the same Conus species were found.

At the UP Manila laboratory and later at UP Diliman, Cruz continued the isolation, purification and characterization of the venom toxins of different species of the Conus such as C. magus, C. striatus and C. textile. Various enzymes and toxins were localized in the granules of the venom.

In 1985, Cruz and co-workers reported the discovery of the µ-conotoxins in C. geographus. By 2006, seven therapeutic products based on six different Conus venom peptides for pain, epilepsy and myocardial infarction, reached Phase 1 and preclinical trials that test drugs on non-humans subject.

Thirteen patents covering various conotoxins or conotoxin peptides and their applications have been granted to the group of Cruz and Olivera.

Today, Prialt (Ziconotide) is a powerful anti-pain drug sourced from the venom of the snail Conus magus and made by Jazz Pharmaceuticals in the United States. Injected intrathecally or into the spinal canal, Prialt is the only conotoxin approved by the US Food and Drug Administration. Conotoxins block the transmission of a chemical signal, in this case pain, between nerve cells. Prialt remains a last resort for the management of chronic pain because it is so powerful that it may induce hallucinations in humans.

Cruz’s work is a clear example of “useful” research shared with humanity. She shared knowledge to students as well, leading the MS and PhD biochemistry programs at UP Manila and UP Diliman, mentoring and graduating doctorate, masters and Bachelor of Science students.

In 2001, she established the Rural Livelihood Incubator in Morong, Bataan, which uses science and technology to generate livelihood, reduce poverty, improve health and preserve the cultural heritage of Aetas.

In November 2006, Cruz was conferred the order of National Scientist, the highest honor bestowed by the Republic of the Philippines on a Filipino scientist for outstanding achievements and contributions in science and technology.     

Formerly of Depthnews, the writer with pen name Balbakwa counts among his close and memorable encounters one with Edward Teller, the theoretical physicist who fathered the hydrogen bomb.