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Biochemistry

Let Marine Microbes Be Thy Medicine

The deep ocean is probably the last place you’d think to look for ways to combat viruses like the novel coronavirus.  Yet the test used to diagnose COVID-19 was developed with the help of a microscopic organism found in the deep sea—and the key to a vaccine may also be found under the watery depths.

A type of red algae living among coral reefs produces a compound potent against the MERS coronavirus. Source: Aquaviews

We have witnessed a coronavirus outbreak every decade this century: SARS in 2002, MERS in 2012, and now coronavirus disease 2019 (COVID-19).  As of May 9th, nearly four million people worldwide have been infected with the newest coronavirus.  The United States alone accounts for over a quarter of these cases.  In a last-ditch effort to stop the spread, cities across the globe have shut down, putting 20% of the global population under lockdown.

One question is on everyone’s minds: When will this end?  It is becoming painfully clear that the virus is not magically “going to disappear”, as President Trump claimed in February, nor will the arrival of summer stop the growth of the virus.  More than likely, we will have to wait for the development of a vaccine for SARS-CoV-2, the novel virus that causes COVID-19.  Such a vaccine will take 18 to 24 months to produce.  This is not to say that life will be on deep freeze until then.  If we can get a better grasp on who is currently sick and who has already had the virus, then we can start to relax current social-distancing rules—for example, letting those who are immune return to work.  The only way we can obtain this information is through coronavirus tests—and lots of them.

 

A Testing Time

There are two types of coronavirus tests: one that flags an active infection (molecular test), and one that checks for antibodies in the blood (serology test).  Both are important—while the molecular test diagnoses who currently has the virus, the serology test indicates if a person was previously infected and as a result may have developed immunity.

The molecular test is the one you would receive if you suspect you have the coronavirus.  These tests are administered by collecting a swab from the nose and throat of a patient, and then analyzing the sample for signs of the virus using a technique called polymerase chain reaction (PCR).

How PCR Testing Works
PCR is a technique that takes tiny amounts of DNA and multiplies it into large enough quantities so that scientists can detect it.  The process requires an enzyme called DNA polymerase (which assembles the building blocks of DNA) and in the case of COVID-19 testing, enzymes isolated from the coronavirus.  (Enzymes are proteins present in every cell—if you think of a cell as a little chemical factory, then enzymes are the machines that allow chemical reactions to take place.)  This DNA cocktail is subjected to multiple cycles of heating and cooling.  With each cycle, the number of DNA strands doubles, until after about 40 cycles there are roughly 100 billion copies of the original DNA sample.  After this process is complete, scientists can measure how much viral DNA is present—and determine whether the patient is positive or negative for coronavirus.

While the wait for a coronavirus test result usually takes a few days, the PCR analysis itself only takes a few hours.  This was not always the case.  Only a few decades ago, PCR was “super laborious, it took forever”, according to Julie Huber, an oceanographer at Woods Hole Oceanographic Institution.  During the heating cycles, the high temperatures would damage the DNA polymerase, so scientists had to manually add fresh enzyme after each cycle.  In those days, PCR could be likened to having to copy a document by hand, over and over and over again, to analyze a single sample.

 

Small But Mighty

Unique life forms thrive at deep sea hydrothermal vents. Source: Oregon State University / CC BY-SA 2.0.

A revolution in the PCR technique came at the hands of an unlikely source: microbes that live in hot springs and deep sea hydrothermal vents.  Heated by the earth’s interior, these sizzling waters were thought to be inhospitable to life.  So it was with great surprise that scientists first discovered the bacterium Thermus aquaticus in the hot springs of Yellowstone National Park during the 1960s.  Since then, similar heat-loving microbes have been found in hydrothermal vents up to 5,000 meters (16,400 feet) deep in the ocean, where vent fluids can exceed 400oC (750oF).  Their secret to surviving these boiling-hot environments?  Unusual, heat-resistant enzymes.

The serendipitous discovery of these enzymes sparked interest from biochemists who had been on the hunt for heat-stable compounds.  By the 1980s, scientists had incorporated the enzyme into the PCR technique, speeding up and automating the procedure.  This upgrade transformed PCR from a slow, manual process into a high-speed, DNA photocopying machine.

In the modern era of epidemics, using PCR technology to help diagnose viral diseases is saving lives.  By enabling (relatively) quick testing for diseases like AIDS, SARS, and now COVID-19, PCR allows us to track infections—and help slow their spread.

 

Coronavirus: Endgame

While widespread coronavirus testing is essential for slowing the spread of the disease, it is not sufficient to completely stop the pandemic.  As Ed Yong maps out in The Atlantic, worldwide synchronous control of the virus is no longer on the table, and attempting to achieve herd immunity would come at too great a cost.  Therefore, the only viable endgame for the pandemic is to develop a vaccine.  At this moment, scientists worldwide are hunting for a safe and effective vaccine.  One place they might look is the ocean.

Looking to nature for medicinal cures might seem a little like quackery, but the ocean has already proven extremely valuable to modern medicine.  For example, various marine sponges produce compounds that scientists have used to develop the anti-HIV drug AZT, as well as medications to treat advanced breast cancer, herpes, and leukemia.  An ocean bacteria contains a protein with anti-malaria and anti-tuberculosis properties.  And scientists are currently investigating the potential of venom from cone snails as a non-addictive painkiller that could replace opioids.

A compound extracted from the red algae Griffithsia found around coral reefs even proved promising for fighting the coronavirus that caused MERS.  But ultimately, small cases numbers for MERS, and the complete (and somewhat mysterious) disappearance of SARS, meant that efforts to develop vaccines for these coronaviruses fizzled out.

The ocean is potentially a vast repository of disease-fighting compounds, which we can access only by valuing exploration over exploitation. Source: Wired

Despite our recent brushes with coronavirus outbreaks—and that an imminent pandemic was inevitable (as Bill Gates, among others, warned us in his 2015 TED Talk)—we were caught flat-footed by the novel coronavirus.  So what can we learn from this experience?  In order to be better prepared for the infectious viruses that will surely plague us in the future, we need to proactively develop a repository of chemical compounds from nature that exhibit anti-viral properties.

Given the unique biology of marine organisms, many of these compounds will come from the ocean.  These organisms have evolved in order to survive unthinkably harsh conditions underwater (think extreme pressures, temperatures, and chemical environments), and their genetic codes represent a treasure trove of unusual and useful properties.  Yet we know shockingly little about ocean—less than 0.05% has been explored—even as we increasingly exploit its depths.  By identifying marine life forms, particularly deep sea microbes, that are potent against viruses, we can accelerate vaccine development—and have a better fighting chance when the next pandemic hits us.

 

First, Do No Harm

Despite our reliance on the ocean, we continue to conduct activities that threaten it.  From climate change to deep sea mining, we are irrevocably altering natural areas and harming marine life—even the tiniest microbes will not emerge unscathed.  A warming world delivers a double whammy: an increase in infectious diseases concurrent with the loss of natural resources we can draw on to fight them.  Indeed, at the start of 2020 the World Health Organization declared that the “climate crisis is a health crisis”.

Perhaps the pandemic can provide a wakeup call: We need to value ocean exploration over exploitation.  Marine resources that can alleviate human suffering and save lives are worth their weight in gold.  By probing the depths of our blue planet, we can identify compounds to combat infectious disease—and perhaps unearth the key to a vaccine or cure for future coronaviruses.

After all, if a virus could bring the world to its knees, who’s to say an ocean microbe can’t save it?  ■

The author would like to thank fellow Oceanbites writer Ashley Marranzino for going above and beyond the call of duty while editing this post.

 

Sources:

Degnarain, N. (2020, March 16). Will ocean seabed mining delay the discovery of potential coronavirus vaccines? Forbes.

Hugus, E. (2020, March 19). Finding answers in the ocean. Woods Hole Oceanographic Institution.

Wei-Haas, M. (2020, March 31). Key ingredient in coronavirus tests comes from Yellowstone’s lakes. National Geographic.

I am a Ph.D. candidate at Boston University where I am developing an underwater instrument to study the coastal ocean.  I have a multi-disciplinary background in physics and oceanography (and some engineering), and my academic interests lie in using novel sensors and deployment platforms to study the ocean.  Outside of my scholarly life, I enjoy keeping active through Thai boxing and cycling around Boston.

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