Could saving the natural world actually save us?

Animals have had an ever increasing importance when it comes to research and medicine. The inclusion of animals such as mice, goats, and rabbits within the lab space has allowed us to test novel drugs and therapies prior to running clinical trials. The incorporation of primates, such as cynomolgous monkeys, has made studying drug safety more elaborate, advanced, and applicable to humans.

Prior to Genentech’s revolutionary idea to treat diabetes with insulin created in bacterial cells, scientists would isolate the hormone from the pancreas of cows and pigs. Current recombinant DNA technologies have allowed us to genetically engineer proteins in almost any kind of living cell, with several of the currently best selling drugs being made in Chinese hamster ovary (CHO) cells.

‘Harnessing the Power of Nature’

Nonetheless, the real power of animals is not found in the way we use and incorporate them in the lab space, but in what we can learn from them and apply to ourselves. Through biomimicry (the imitation of natural biological designs and processes) and bioprospecting (the search for plant and animal species from which medicinal drugs and commercially valuable compounds can be obtained), we are now capable of harnessing the power of nature in order to improve and save human lives.

It has been noted that sharks tend to have a much lowerrate of cancer when compared to other animals. This low prevalence is primarily due to the shark’s advanced anti-cancer mechanism. Once a cell becomes cancerous, it will begin dividing and replicating uncontrollably. In order for a tumor to grow, it requires certain amounts of oxygen and nutrients. As a result the tumor will release a substance called an angiogenin factor, a molecule that promotes vascular growth towards and around the cancerous cells.

With enough resources, the tumor can now grow and even change location by metastasizing through the animal’s circulatory system. One of the world’s best-selling drugs, Avastin (bevacizumab), takes advantage of and mimics the shark’s anti-cancer mechanism byacting just like one of the shark’s hormones: an anti-angiogenin(an anti-VEGF, Vascular Endothelial Growth Factor, in our case). By preventing its vascularization, the tumor becomes deficient in terms of basic necessities, and as a result it will not be able to grow and expand.

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The Mystery of the p53 Gene

Scientists even look to elephants for cancer treatment. By definition, larger organisms have a greater chanceof contracting cancer (the fact that larger living things have more cells increases the probability that one of their cells will become cancerous), and yet it is not the case with elephants. Elephants benefit from having multiple copies of the gene p53 within their genome.

P53 is a known tumor suppressor gene that will signal to the cell to destroy itself (apoptosis) if it becomes cancerous. A mutation within this p53 gene means that the cell is no longer under this “safety” mechanism, and once mutated the cell has a much greater chance of dividing uncontrollably.

Compared to humans, who only have one copy, elephants benefit from multiple copies of the gene within their genome. This means that if a mutation were to take place in one of the copies of the p53 gene, then the elephant would have the other intact copies of the gene to compensate. This cancer prevention mechanism has intrigued scientists for years and they are now performing experiments to determine whether the addition of multiple copies of the p53 gene to our genomes through gene therapy could help ward off cancer.

‘The answer to our troubles might not lie within the most obvious of species’

Oncology might not be the only area in which the natural world can help us. Some researchers have turned to bears to improve organ transplants and transfers. As the bear hibernates throughout the long winter months, it goes into a deep slumber. Naturally, the heart rate and respiratory rate of the animal drop while it is asleep, and what has fascinated scientists is the fact that when the bear wakes up in the spring, its organs (which have been operating in a lower oxygen state for an extended period of time) appear intact. Acquiring a better understanding of the effect and mechanism of the bear’s hibernation hormones could improve the way doctors transfer organs between patients and among hospitals.

The answers to our troubles might not even lie within the most obvious of species either. A perfect example would be AstraZeneca’s Bydureon (exenatide) and Byetta (exenatide) which are used to treat Type 2 diabetes. Both drugs mimic exendin-4, an active protein found in the saliva of the Gila monster, a venomous lizard found in the southwestern United States. The protein analog can act in the same manner as the human glucagon-like peptide 1 (GLP-1), a hormone that is key in the regulation of the body’s insulin and glucagon levels.

Advances in genomic sequencing technology have revolutionized bioprospecting. Next generation sequencing methods are constantly improving, making sequencing processes both faster and cheaper. Scientists have recently started studying the venom of long-glanded blue coral snakes found in the jungles of Southeast Asia for pain medication, while research on the toxin of a Brazilian endemic species of wasps could hold the key to the next blockbuster oncology drug. It is only a matter of time before we begin seeing these products undergoing clinical trials.

Investing in Conservation Efforts could lead to the next Blockbuster Drug

But how long will all of this last? Trash dumping and overfishing have depleted our oceans of wildlife, while increasing desires for luxury items carved out of ivory have caused an increase in elephant poaching. Additionally, deforestation, habitat destruction,as well as global warming have all contributed to the reduction ofthe world’s Ursidaepopulations.

The removal of keystone species such as these can have catastrophicdownstream effects on multiple other species found within the same ecosystem. Numerous studies have been conducted in order to predict the probability of actually discovering a compound worthy of clinical investigation, but time is of the essence when it comes to biodiversity. By the time companies finally decide that a particular molecule from a specific animal could be worth their investment, several other species (both because and independently of humans) could have gone extinct.

A number of companies have been focusing on reducing their environmental impact by investing in green technology, such as solar panels and recycled materials. These actions could have a strong positive downstream factor on the flora and fauna worldwide, but only in the long run.

With new species discovered on a regular basis being counterbalanced by the number of different species worldwide depleting at an alarming and accelerated rate, time is running out.It would be in both the pharmaceutical and biotech industries’ best interests (not to mention the animals’ interests) to invest directly in conservation efforts. Some of the next blockbuster drugs are out there waiting to be discovered, and it will be up to the industry how much they are willing to protect the natural cornucopia of remedies and how quickly they are willing to invest in their discovery.

 

References:

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2) Callaway E. (2015). How Elephants Avoid Cancer. Nature doi:10.1038/nature.2015.18534

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4) Furman B. (2012). The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent.Toxicon, 59(4), 464-471. doi:10.1016/j.toxicon.2010.12.016

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7) Yang et al. (2016).The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophisbivirgatus). Toxins 2016, 8, 303; doi:10.3390/toxins8100303.