If bitten by a Mojave rattlesnake, you would experience immediate shortness of breath, weakness or paralysis of the lower limbs, double vision, inability to speak or swallow, and involuntary tremors of the facial muscles. Chances are within 10 minutes of the bite, you would be dead. But can such deadly venom also prolong life?
SJSU Biology Professor Julio Soto thinks so.
Soto and his team of students are investigating possible medical uses for rattlesnake venom. Their research suggests that the venom's toxin, when cloned and mutated, could limit and potentially destroy cancer cells.
"These venoms are complex mixtures of proteins," says Soto. "Some are hemotoxic, affecting blood and other tissues, while others are neurotoxic, attacking the nervous system. But all venoms have tiny molecules called 'disintegrins.'"
Some disintegrins bind specifically to blood platelets, explains Soto, while others can bind to cancer cells, which induces cell death (apoptosis) and blocks migration ( metastasis) and cell proliferation.
"Due to these properties, disintegrins make excellent candidates for the development of anti-cancer therapies," Soto explains.
Over the course of two years, Soto's team of students and fellow faculty researchers successfully extracted and cloned a disintegrin gene from a Mojave rattlesnake that binds to blood platelets as well as to cancer cells.
Then, they mutated it. Sounds like science fiction, but Soto says reassuringly, "it's only molecular biology with a lot of chemistry thrown into it."
Once created, the mutant genes were sent to the Natural Toxins Center at Texas A&M University to be tested. "The lab found that none of the mutants inhibited blood coagulation," reports Soto.
This was a huge step forward. In developing chemotherapies, "you don't want to inject something that is going to prevent blood clotting," he explains. Next, Soto is testing how these mutants can help inhibit cell migration. "Death from cancer is often due to metastasis or migration of cancer cells from one part of the body to another," says Soto. By preventing that spread, the disease remains localized and, therefore, more receptive to targeted drugs.
Soto is also using the mutant toxin to induce apoptosis in cancer cells. "Apoptosis is a natural thing," he explains. "During development some cells, including neurons, commit suicide. Abnormal cells, like cancer cells, can also go through the same process when a receptor in their membrane is activated. We're looking at helping the cancer cells to commit suicide."
Chemotherapy drugs on the market today target all dividing cells, not just cancer cells. "That's why people lose hair during treatment," Soto says. "We're trying to create an anti-cancer therapy that leaves the healthy cells alone."
Soto thinks there can't be only one way of looking at cancer treatment. "Our approach is not conventional," he says. "There might be someone with brain cancer who cannot be operated upon because it's too dangerous. So, what do you do? This is where our research comes in. We want to develop something that will stop the growth by either killing the cancer cells or by inhibiting them from multiplying or by preventing them from migrating. We want to create treatment options for doctors and patients."
While actual drug production remains far down the line, Soto is proud of the fact that at least the first phase of the process -- the research -- has begun.
"It is a never-ending game in pursuit of the perfect solution," he says. "We're just taking baby steps in this lab right now and trying to find something that might be potentially interesting to a company."
Before mapping out any research project, scientists like Soto must determine what has been done already. "You don't want to repeat somebody else's work," stresses Soto. "And you don't want to compete on something that's already in the works, because someone with a bigger, better, more expensive lab will beat you to it. You have to know that you can't target everything and understand your limitations."
At San José State, Soto initially focused his research on cell death because of the instruments available to him. Testing for cell migration had to be done in collaboration with Texas A&M.
Even so, "the process of making the mutations was very challenging," says Soto. "You have to have research funds to run that process."
Between paying students, investing his time in the lab, and buying reagents, he has spent approximately $50,000 so far.
And unlike corporate researchers, Soto has to make his research findings public in order to get grants. "Anybody can purchase venom and run all the tests we have," says Soto. "In a sense I am not worried about competing with anyone, because we have created these mutants with a novel reagent (a chemical compound used to initiate a reaction). At the same time, I know that once I publish the data, I will have to make the reagent available to whoever asks for it."
Working in a National Science Foundation-funded state university lab is very different from working at a high-end, well-endowed corporate facility. However, Soto finds his current role more rewarding.
"In a company, it doesn't matter how you perform research -- it just needs to be done in six months," he says. "Time is money for them. Companies invest a lot of money and they need to have products in the market by a certain deadline. Here, we also have deadlines, but the focus is on learning and teaching the research process."
The best part of working at a university, in Soto's opinion, is the ability to help produce a new generation of inquisitive researchers. "I give students a whole gamut of projects to work on," he says.
The snake venom project, in particular, has provided excellent training for students interested in pursuing employment at biomedical companies.
"In this project they have worked with DNA and proteins -- that is a huge transition," he reveals. "By cloning something and then working to mass produce it, they learn cell biology, molecular biology and biochemistry all in the purview of a single project -- that's a lot of perspective and skills to compete with in the industry."
Four students are currently working on Soto's snake venom project. "We're now looking at new species of snakes to see if we can find something that has not been studied before and doesn't resemble anything that we already have," says Soto.
Interning in Soto's lab this past summer, Chris Petro, a biotechnology major from California State Polytechnic University, Pomona, discovered two new toxins in a snake venom that hadn't been studied previously.
Talking of his experiences in the lab, Petro says: "It's one thing to work for experience or money and quite another to work for something that could save people's lives. It makes you feel your work is truly important."
- Mansi Bhatia
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