Why You Should Care If A Python Has A Cold
There’s a lab in San Francisco doing what science might call silly things a few years ago. As recently as 2010, the work they’re doing would have been too slow, expensive, and outlandish to consider as a diagnostic technique. Not today though.
Joseph DeRisi runs the DeRisi Lab at UCSF. There, researchers are making waves with a new approach to disease diagnosis. They’ve turned heads with their research into Zika, West Nile, and brain-eating amoebas, but their best story is about snakes. Really big snakes.
Dr. DeRisi regaled Adam Savage of the story on his podcast, Still Untitled: The Adam Savage Project. It all started when the lab received a letter about a sick snake. DeRisi didn’t follow up for a while, but finally decided to do some investigating. Through a series of steps that included him receiving a cooler full of python heads from Florida (it’s always Florida), DeRisi eventually had a few samples of snakes with the particular disease that he was ready to test.
This is where the lab gets silly. The DeRisi lab is most famous for its use of a technique called Metagenomic Sequencing. It’s a method of DNA sequencing that looks deep, much deeper than we’ve been able to look at DNA in the past. When complete genomic sequencing was first invented, it cost $2.7 billion to identify the details of one genome. That’s almost $1 per base pair, the tiny pairs of letters that make up DNA. Today, the DeRisi lab pays about $1,000 dollars for Metagenomic Sequencing, an even more complex method of searching through DNA.
What do they use it for? All kinds of stuff.
The DeRisi lab specializes in disease. They use their awesome sequencer to analyze and identify all the DNA from a sample and figure out what the “bad guy” is that’s causing the infection. They call it “hypothesis-free testing.” Why’s that? You may wonder. Well, it comes down to how medical tests are usually done.
Most often, if you’re sick, a doctor will take down information about your symptoms and use her knowledge and background to make a hypothesis about what your disease could be. They usually come up with a few different options in what they call and differential diagnosis. They’ll then carry out a series of tests to determine which of these diseases or infections you probably have.
The DeRisi lab does things differently. Instead of coming up with ideas and ruling some out, they sequence all the DNA they can find, compare it to the DNA of a healthy representative from the species they’re working with, and look for any outliers. All animals, humans included, share more than 99% of their DNA with every other being from their species. There are a few minor differences between individuals, but, overall, any python’s or human’s DNA is pretty much the same as any other human or python. But bacterial and viral DNA, those baddies we usually just categorize as germs, that looks quite different.
When the techs at DeRisi lab analyze the DNA, it’s easy to spot these differently coded strands, they just don’t match up. It’s like spotting some lines of Spanish text in the middle of a book written in English. They stand out like a sore thumb even though they’re written with the same letters, anyone can spot them. The lab then compares the DNA they found to a huge database of bacterial and viral DNA so they can identify exactly what type of germ they’ve found. They can then pass those results on to a doctor or veterinarian who now knows exactly which disease to treat.
So how does this all relate back to pythons?
To answer that, we have to go back to Joe’s letter.
Joe had received the letter from someone who was concerned that their python was “stargazing”, a condition that occurs in pythons and boa constrictors that causes them to wave their heads about and stare up at the ceiling. It’s not unlike what Kaa does in the Jungle Book, but with a little more death than hypnosis. Actually, a lot more death. This condition all but inevitably leads to death, rather quickly at that. Still, no one knew too much about what caused it.
Joe left this letter laying on his desk for a while before he followed up with a veterinarian friend of his. The vet taught him a bit more about stargazing and told him that no one really had the answer as to why this occurred. This piqued Joe’s interest and he asked the vet to give him some samples from snakes who had this condition so he could analyze them with his metagenomics back at the lab.
The vet passed this information on to others in their field and pretty soon the DeRisi lab had a collection of python samples. At one point he even received a cooler full of python heads in the mail from an ambitious hunter in the Everglades. Since these snakes are considered an invasive species there, Florida has a bounty out for snakes and this hunter thought they could be used for science too. Unfortunately, there was no way to know if these pythons had previously been stargazing and the lab was unable to use them.
Eventually, the lab had enough pythons to test. They took the DNA and ran it through their machine to identify any viral or bacterial DNA that may be hiding in their samples. It turns out, there was some, quite a bit actually. It all came from a specific species of virus called arenavirus. This information was described in a paper in the Journal of Microbiology written by professor of microbiology Mark Stenglein, Joseph DeRisi, and other authors who assisted on the paper.
Still though, why should we care?
It’s not a bad question, but it comes with a great answer. We should care because this specific arenavirus (reptarenavirus) has a very interesting grandparent.
As DeRisi told Adam Savage on his show, reptarenavirus is a hemorrhagic fever virus. That is, it will give you a fever and make you bleed. Fun. More than that though, reptarenavirus is a close relative of a much more famous hemorrhagic fever virus, ebola.
Ebola, that hemorrhagic fever virus we’ve all come to know and loathe, shares a “skin” with reptarenavirus. The “skin” of viruses is a protein coat. It’s a bundle of small molecules on the surface of the virus that help it with many functions. This skin is an essential part of how viruses work and is inherited from previous generations of virus. It’s a trait that gets passed down from generation to generation. Just like you have a nose similar to your mother’s, a virus will have a protein coat similar to its.
The protein coat of reptarenavirus is similar enough to ebola that scientists can see that they’re related. This is weird though, because the arenavirus family (arenaviridae) and the ebola virus family (filoviridae) weren’t known to comingle before. So we’ve discovered a virus related to ebola that may give us more information about its makeup and history. We’ve also revealed some interesting facts about filoviridae’s sex life that I’m sure it’s not happy to have out in the public sphere.
But there’s more! Much more. The lab discovered information that could change our approach to stopping ebola outbreaks altogether.
All viruses need a reservoir. They need some species to grow in that they don’t kill off. To be effective, viruses need to have a reservoir to grow, mature, and propagate in before they move on to infect another species and kill off the host.
Why a reservoir? If an infected host grows sick and dies, the virus can’t live on and spread to other hosts. It dies too. Viruses need living hosts that they don’t kill so that they can continue to grow in number and spread those numbers to other species. The viruses that leave the reservoir may eventually die when their host is killed, but the overall population continues to live on in the reservoir.
As Stenglein points out in his 2012 paper, reptiles may be that host for ebola or similar viruses. To this day, we don’t know what the reservoir species for ebola is. There was some speculation that the source was fruit bats, and they are clearly a carrier of the disease, but ebola can infect them as well. It can harm and even kill them, and this makes them a bad option as a host species. What species can ebola grow in without infecting? Snakes.
We don’t yet know if Central African snakes are indeed the reservoir species for ebola and similar diseases, but the work by Stenglein and those at the DeRisi lab show that it’s possible that this is the case. This brings us one step closer to identifying the source of ebola outbreaks and gives us another tool to prevent them in the first place. If we can definitively identify the reservoir, we can be more proactive in disease prevention and keep many more people safe.
All of this sprung from a chance letter and metagenomic research into python disease. Wow.
There’s new information hiding out there, waiting to be found by curious researchers with the right tools. The DeRisi lab is doing that work right now and doing an incredible job, finding sources of disease and giving us new diagnostic avenues and tools. The DNA revolution has brought us much more than ancestry tests, it’s bringing us one step closer to stopping terrible diseases like ebola. Who knows what else the lab will find as they keep digging into all the DNA that’s out there? We’ll just have to keep an eye out.
