Venom, M.D.: How Some of the World’s Deadliest Toxins Fight Cancer

Catalyst Volume 10

Nature, as mesmerizing as it can be, is undeniably hostile. There are endless hazards, both living and nonliving, scattered throughout all parts of the planet. At first glance, the world seems to be quite unwelcoming. Yet through science, humans find ways to survive nature and gain the ability to see its beauty. A fascinating way this is achieved involves taking one deadly element of nature and utilizing it to combat another. In labs and universities across the world today, scientists are fighting one of the world’s most devastating diseases, cancer, with a surprising weapon: animal toxins.

Various scientists around the globe are collecting venomous or poisonous animals and studying the biochemical weapons they synthesize. In their natural forms, these toxins could kill or cause devastating harm to the human body. However, by closely inspecting the chemical properties of these toxins, we have uncovered many potential ways they could help us understand, treat, and cure various diseases. These discoveries have shed a new light on many of the deadly animals we have here on Earth. Mankind may have gained new friends—ones that could be crucial to our survival against cancer and other illnesses.

Take the scorpion, for example. This arachnid exists in hundreds of forms across the globe. Although its stinger is primarily used for killing prey, it is often used for defense against other animals, including humans. Most cases of scorpion stings result in nothing more than pain, swelling, and numbness of the area. However, there are some species of scorpions that are capable of causing more severe symptoms, including death.¹ One such species, Leiurus quinquestriatus (more commonly known as the “deathstalker scorpion”), is said to contain some of the most potent venoms on the planet.² Yet despite its potency, deathstalker venom is a prime target for cancer research. One team of scientists from the University of Washington used the chlorotoxin in the venom to assist in gene therapy (the insertion of genes to fight disease) to combat glioma, a widespread and fatal brain cancer. Chlorotoxin has two important properties that make it effective against fighting glioma. First, it selectively binds to a surface protein found on many tumour cells. Second, chlorotoxin is able to inhibit the spread of tumours by disabling their metastatic ability. The scientists combined the toxin with nanoparticles in order to increase the effectiveness of gene therapy. ^{3 4}

Other scientists found a different way to treat glioma using deathstalker venom. Researchers at the Transmolecular Corporation in Cambridge, Massachusetts produced an artificial version of the venom and attached it to a radioactive form of iodine, I-131. The resultant compound was able to find and kill glioma cells by releasing radiation, most of which was absorbed by the cancerous cells. ⁵ There are instances of other scorpion species aiding in cancer research as well, such as the Centruroides tecomanus scorpion in Mexico. This species’ toxin contains peptides that have the ability to specifically target lymphoma cells and kill them by damaging their ion channels. The selective nature of the peptides makes them especially useful as a cancer treatment as they leave healthy cells untouched.⁶

Scorpions have demonstrated tremendous medical potential, but they are far from the only animals that could contribute to the fight against cancer. Another animal that may help us overcome this disease is the wasp. To most people, wasps are nothing more than annoying pests that disturb our outdoor life. Wasps are known for their painful stings, which they use both for defense and for hunting. Yet science has shown that the venom of these insects may have medicinal properties. Researchers from the Institute for Biomedical Research in Barcelona investigated a peptide found in wasp venom for its ability to treat breast cancer. The peptide is able to kill cancer cells by puncturing the cell’s outer wall. In order to make this peptide useful in treatment, it must be able to target cancer cells specifically. Scientists overcame the specificity problem by conjugating the venom peptide with a targeting peptide specific to cancer cells.⁷ Similar techniques were used in Brazil while scientists of São Paulo State University studied the species Polybia paulista, another organism from the wasp family. This animal’s venom contains MP1, which also serves as a destructive agent of the cell’s plasma membrane. When a cell is healthy, certain components of the membrane should be on the inner side of the membrane, facing the interior of the cell. However, in a cancerous cell, these components, (namely, the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) ) are on the outer side of the membrane. In a series of simulations, MP1 was observed to selectively and aggressively target membranes that had PS and PE on the outside of the cell. Evidently, using targeted administration of wasp toxins is a viable method to combat cancer.⁸

Amazingly enough, the list of cancer-fighting animals at our disposal does not end here. One of the most feared creatures on Earth, the snake, is also among the animals under scientific investigation for possible medical breakthroughs. One group of scientists discovered that a compound from the venom of the Southeast Asia pit viper (Calloselasma rhodastoma) binds to a platelet receptor protein called CLEC-2, causing clotting of the blood. A different molecule expressed by cancer cells, podoplanin, binds to CLEC-2 in a manner similar to the snake venom, also causing blood clotting. Why does this matter? In the case of cancer, tumors induce blood clots to protect themselves from the immune system, allowing them to grow freely. They also induce the formation of lymphatic vessels to assist their survival. The interaction between CLEC-2 and podoplanin is vital for for both the formation of these blood clots and lymphatic vessels, and is thus critical to the persistence of tumors. If a drug is developed to inhibit this interaction, it would be very effective in cancer treatment and prevention.⁹ Research surrounding the snake venom may help us develop such an inhibitor. .

Even though there may be deadly animals roaming the Earth, it is important to remember that they have done more for us than most people realize. So next time you see a scorpion crawling around or a wasp buzzing in the air, react with appreciation, rather than with fear. Looking at our world in this manner will make it seem like a much friendlier place to live.

References

1. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/scorpion-stings/home/ovc-20252158 (accessed Oct. 29, 2016).
2. Lucian K. Ross. Leiurus quinquestriatus (Ehrenberg, 1828). The Scorpion Files, 2008. http://www.ntnu.no/ub/scorpion-files/l_quinquestriatus_info.pdf (accessed Nov. 3, 2016).
3. Kievit F.M. et al. ACS Nano, 2010, 4, (8), 4587–4594.
4. University of Washington. "Scorpion Venom With Nanoparticles Slows Spread Of Brain Cancer." ScienceDaily. ScienceDaily, 17 April 2009. <www.sciencedaily.com/releases/2009/04/090416133816.htm>.
5. Health Physics Society. "Radioactive Scorpion Venom For Fighting Cancer." ScienceDaily. ScienceDaily, 27 June 2006. <www.sciencedaily.com/releases/2006/06/060627174755.htm>.
6. Investigación y Desarrollo. "Scorpion venom is toxic to cancer cells." ScienceDaily. ScienceDaily, 27 May 2015. <www.sciencedaily.com/releases/2015/05/150527091547.htm>.
7. Moreno M. et al. J Control Release, 2014, 182, 13-21.
8. Leite N.B. et al. Biophysical Journal, 2015, 109, (5), 936-947.
9. Suzuki-Inoue K. et al. Journal of Biological Chemistry, 2010, 285, 24494-24507.

Visualizing the Future of Medicine

Catalyst Volume 10

What do you do when you get sick? Most likely you schedule a doctor’s appointment, show up, and spend ten to fifteen minutes with the doctor. The physician quickly scans your chart, combines your narrative of your illness with your medical history and his or her observations so that you can leave with diagnosis and prescription in hand. While few give the seemingly routine process a second thought, the very way in which healthcare providers approach the doctor-patient experience is evolving. There is a growing interest in the medical humanities, a more interdisciplinary study of illness. According to Baylor College of Medicine, the aim of the medical humanities is “understanding the profound effects of illness and disease on patients, health professionals, and the social worlds in which they live and work.”¹ Yet medical humanities is somewhat of a catch all term. It encompasses disciplines including literature, anthropology, sociology, philosophy, the fine arts and even “science and technology studies.”¹ This nuanced approach to medicine is exactly what Dr. Kirsten Ostherr, one of the developers of Rice University’s medical humanities program, promotes.

Dr. Ostherr uses this interdisciplinary approach to study the intersection of technology and medicine. She has conducted research on historical medical visualizations through media such as art and film and its application to medicine today. Originally a PhD recipient of American Studies and Media Studies at Brown University, Dr. Ostherr’s interest in medicine and media was sparked while working at the Department of Public Health at Oregon Health Sciences University, where researchers were using the humanities as a lens through which they could analyze health data. “I noticed that the epidemiologists there used narrative to make sense of data, and that intrigued me,” she said. This inspired Dr. Ostherr to use her background in media and public health to explore how film and media in general have affected medicine and to predict where the future of medical media lies.

While the integration of medicine and media may seem revolutionary, it is not a new concept. In her book, Medical Visions, Dr. Ostherr says that “We know we have become a patient when we are subjected to a doctor’s clinical gaze,” a gaze that is powerfully humanizing and can “transform subjects into patients.”² With the integration of technology and medicine, this “gaze” has extended to include the visualizations vital to understanding the patient and decoding disease. Visualizations have been a part of the doctor-patient experience for longer than one might think, from X-rays in 1912 to the electronic medical records used by physicians today.³

In her book, Dr. Ostherr traces and analyzes a series of different types of medical visualizations throughout history. Her research begins with the study of scientific films of the early twentieth century, and their attempt to bridge the gap between scientific knowledge and the general public.² The use of film in medical education was also significant in the 20th century. These technical films helped facilitate the globalization of health and media in the postwar era. Another form of medical visualizations that emerged with the advent of medicine on television. At the intersection of entertainment and education, medical documentary evolved into “health information programming” in the 1980’s which in turn transitioned into the rise of medical reality television.² The history of this diverse and expanding media, she says, proves that the use of visualizations in healthcare and our daily lives has made medicine “a visual science.”

One of the main takeaways from Dr. Ostherr’s historical analysis of medical visualizations was the deep-rooted relationship between visualizations and their role in spreading medical knowledge to the average person. While skeptics may argue against this characterization, “this is a broad social change that is taking place,” Dr. Ostherr said, citing new scientific research emerging on human centered design and the use of visual arts in medical training. “It’s the future of medicine,” she said. There is already evidence that such a change is taking place: the method of recording patient information using health records has begun to change. In recent years there has been a movement to adopt electronic health records due to their potential to save the healthcare industry millions of dollars and improve efficiency.⁴ Yet recent studies show that the current systems in place are not as effective as predicted.⁵ Online patient portals allow patients to keep up with their health information, view test results and even communicate with their health care providers, but while these portals can involve patients as active participants in their care, they can also be quite technical.⁶ As a result, there is a push to develop electronic health records with more readily understandable language.

In order to conduct further research in the field including projects such as the development of better, easier to understand electronic health records, Dr. Ostherr co-founded and is the director of the Medical Futures Lab. The lab draws resources from Baylor College of Medicine, University of Texas Health Science Center, and Rice University and its diverse team ranges from humanist scholars to doctors to computer scientists.⁷ The use of technology in medicine has continued to develop rapidly alongside the increasing demand for personalized, humanizing care. While it seems like there is an inherent conflict between the two, Dr. Ostherr believes medicine needs the “right balance of high tech and high touch” which is what her team at the Medical Futures Lab (MFL) works to find. The MFL team works on projects heavily focused on deconstructing and reconstructing the role of the patient in education and diagnosis.⁷

The increasingly integrated humanistic and scientific approach to medicine is revolutionizing healthcare. As the Medical Futures Lab explores the relationship between personal care and technology, the world of healthcare is undergoing a broad cultural shift. Early on in their medical education, physicians are being taught the value of incorporating the humanities and social sciences into their training, and that science can only teach one so much about the doctor-patient relationship. For Dr. Ostherr, the question moving forward will be “what is it that is uniquely human about healing?” What are the limitations of technology in healing and what about healing process can be done exclusively by the human body? According to Dr. Ostherr, the histories of visualizations in medicine can serve as a roadmap and an inspiration for the evolution and implementation of new media and technology in transforming the medical subject into the patient.

References

1. Baylor University Medical Humanities. http://www.baylor.edu/medical_humanities/ (accessed Nov. 27, 2017).
2. Ostherr, K. Medical visions: producing the patient through film, television, and imaging technologies; Oxford University Press: Oxford, 2013.
3. History of Radiography. https://www.nde-ed.org/EducationResources/CommunityCollege/Radiography/Introduction/history.htm (accessed Jan. 2017).
4. Abelson, R.; Creswell, J. In Second Look, Few Savings From Digital Health Records. New York Times [Online], January 11, 2013. http://www.nytimes.com/2013/01/11/business/electronic-records-systems-have-not-reduced-health-costs-report-says.html (accessed Jan 2017).
5. Abrams, L. The Future of Medical Records. The Atlantic [Online], January 17, 2013 http://www.theatlantic.com/health/archive/2013/01/the-future-of-medical-records/267202/ (accessed Jan. 25, 2017).
6. Rosen, M. D. L. High Tech, High Touch: Why Technology Enhances Patient-Centered Care. Huffington Post [Online], December 13, 2012. http://www.huffingtonpost.com/lawrence-rosen-md/health-care-technology_b_2285712.html (accessed Jan 2017).
7. Medical Futures Lab. http://www.medicalfutureslab.org/ (accessed Dec 2017).