Science of small, unknown places

I submitted a shorter version of this article in a recent science writing competition among graduate students worldwide, arranged by the American technology manufacturer company Bio-Rad Laboratories. While it didn’t win any prizes- no surprise there- it was one of the five articles “highly commended” by the judges. I thought I would share the full version here.

For a moment, it sounded like the podcast I was listening to referenced my lab.

This had to be a mistake of some sort. The lab** I worked in was in a Bangladeshi research institute. I knew it had some international renown, but still, we’re talking about a developing country laboratory. It would take months for ordered reagents to reach us from overseas. Most of the micropipettes would leak. In terms of office space, my co-workers and I sat around a broken table in a tiny room, made even tinier by the fieldwork equipment stacked to one side. There weren’t even enough chairs to accommodate us all- some of us had to make do with cardboard boxes.

Of all places, why was research from this lab being referenced by these American scientists on the podcast?

I took a look at the episode again- the title was Microbiology papers for first year students. The scientists were discussing compelling articles to teach beginner microbiology students about the field, so the chosen papers were considered exceptional displays of research-in-action. And among the list of papers were…

Yep, there was no mistake. One of the papers was indeed based on work from our lab. I recognized some of the listed authors as well.

After my graduation, I had worked in this institute for two and a half years before leaving for my PhD abroad. In that period, this is a phenomenon I would encounter repeatedly- coming across compelling, insightful, widely cited research by scientists in my country that I had no idea existed.

I, in this case, was a Bangladeshi microbiology graduate — not exactly a layman.

These papers had never come up in class, much less picked up by the media to any great extent. I soon realized that there isn’t much of an operational science communication channel in Bangladesh. The country’s STEM students have no way of knowing about exemplary research conducted in domestic laboratories. Leaky pipettes and all.

We’ll have occasion to wax eloquent about systemic failures in our society. For now, let’s go back to the paper from the podcast.

The article was about an ancient, devastating disease, one visceral to my country’s experience. And yet, the disease as such doesn’t have a name in common Bangla- we simply knew it as the witch***. It’s not like my ancestors didn’t understand that diseases had natural causes. They did. And yet, the only way people could conceptualize this phenomenon — the ferocity with which it spread and laid waste to entire villages — was by appealing to the supernatural.

I’m talking, of course, about cholera. Absent medical intervention, the disease can flush out the body’s waters mere hours after being infected, leaving an empty husk behind. The advent of modern public health has indeed led to its decline — to a degree. Cholera is a particularly mighty beast to vanquish, for the simple reason that its germ lives in water. So until we find a way to sterilize the world’s oceans- the disease is here to stay.

One might think a relatively simple solution would be to avoid drinking contaminated surface water altogether, seeing this is how the germ spreads — but enforcing that runs into all sorts of problems. For example, there’s been a concerted push since the seventies to get my countrymen to extract water from underground aquifers, which is almost pristine in quality. This became an international scandal, however, when it was discovered that our groundwater is laced with arsenic — leading to a countrywide epidemic of skin and respiratory cancers that continues to this day. Don’t get me wrong, interventions aimed at improving water and sanitation are incredibly important, but a ham-handed implementation can leave a complicated legacy. In the groundwater case, said legacy happened to include “the largest mass poisoning of a population in history”****.

Scientific and news publications about the arsenic disaster in Bangladesh. Clockwise from top left: Undark, Nature, BMJ (British Medical Association), Human Rights Watch, WHO.

And so, the cholera problem persists. To a much lesser degree than it did before, but persist it does.

Our story begins in the eighties, with a group of scientists fidgeting with a question that sounds practically useless. Where does cholera live?

Well, we knew the answer to that one for a while. The germ that causes the disease lives in the water. But the scientists were asking something different: where does it live? As in, where in the water? The cholera germ, like many of its water-dwelling brethren, is more bug than fish: instead of swimming around freely in the water, it tends to stay attached to other aquatic organic matter like small plants or animals. This, then, is what our scientists were getting at: what does the germ attach to when it’s in the water?

From a “solving cholera” perspective, it seems as if their priorities couldn’t have been more skewed. We know it lives in water. The minute details of cholera ecology don’t really help the dying children.

Be that as it may, our scientists started hacking away at this “problem”. Their suspicions condensed around a tiny crustacean — the copepod, so named because of its shape resembling ancient Greek triremes.

Left: Copepods (Greek “Oar feet”) under the microscope. Right: Greek triremes

Since this plankton was so abundant in the water, it seemed reasonable that the germ would attach to it for protection against the elements. To test this hunch, the researchers set up an artificial pond in a flask with all the usual suspects present: the copepod, pond algae, and cholera germs. This experimental system, called a laboratory microcosm, is elegant in its simplicity — by observing these creatures in this simulated habitat, the scientists were hoping to catch the copepod-germ association “in the act”.

After a day and a half of our pond critters getting to know each other in the flask, this is indeed what came to pass. Under the powerful resolution of an electron microscope, copepod organs were found to be teeming with countless germs, while the surrounding water was surprisingly clear. The germs seemed to preferentially congregate on the copepods themselves, instead of floating freely in the water column. More bug than fish.

Thirty-six hours into the experiment: under an electron microscope, a copepod egg sac is seen covered with cholera germs (the white dots). The image is taken from the relevant research article, referenced below.

Ok, looks like our scientists solved their little puzzle. Cholera germs- at least sometimes- live on copepods.

Even with the benefit of hindsight, this conclusion and the investigation that led to it seem positively mundane. Which is why I can’t help but wonder- did the scientists anticipate that just two decades down the line, this piece of “meaningless” curiosity would end up saving lives in rural Bangladesh? Did they think quite in these terms when they were setting up the experiment, or looked at the micrograph?

This is where our paper comes in- the one referenced in the podcast.

How do we get people to stop drinking bad water—i.e., water contaminated with deadly germs? Again, this seems like a simple enough problem: get everyone to treat their water before drinking. On closer inspection however, none of the popular treatment options seem universally feasible. Boiling water is notoriously difficult for a rural family during the yearly floods, which is exactly when these diseases are most rampant; and groundwater boreholes often become submerged and inaccessible as well. Passing the water through a filter seems like a relatively hassle-free way of treating water, but filters to remove germs are extremely fine and quite expensive. Lest we forget, cholera is a disease that disproportionately affect the poor.

This is where our copepod scientists enter the scene once more, and cast a quizzical look at received wisdom.

Do we really need super fine, expensive filters to get cholera-free water? We would, if we wanted a filter fine enough to catch the microscopic germs. But is that really necessary? After all, hasn’t our previous research showed that the germs remain attached to copepods, leaving the surrounding water relatively germ-free? If that’s indeed the case- then all one must do to get rid of cholera germs in water is to remove their copepod hosts, and the attached bacteria would follow. Unlike their occupants, copepods are about a millimeter in length and can be seen with the naked eye. So in principle, they should be removable with coarse, inexpensive cloth filters as well.

After running filtration tests in the laboratory to test their idea, our scientists made their way to a cholera-prone area in Bangladesh for a robust demonstration. Their advice to the households under study was simple- when collecting water from the pond, cover the mouth of the container with a piece of cloth. As the pond water rushes inside the container, the cloth would catch the germ-carrying copepods, so the “filtered” water would be safer. Interestingly, this scientific advice itself had a distinct rural Bangladeshi flavor, because our researchers specifically advocated the use of old sarees as filter cloth. This item of clothing is universally worn by Bangladeshi rural women, and the fabric is fine enough to double as excellent copepod-filters. You had to fold the saree a few times to get there, but that was no trouble.

Women in rural Bangladesh collecting water with saree-covered pitchers. Image taken from The Borgen Project.

This story has an abrupt and decisive ending. After a year of observation, the rate of cholera among the households using the “saree filter” fell to half that of “control” ones.

At this point, it’s perhaps useful to think about where this story began, and where it now ends. The problem of cholera in Bangladesh- and waterborne diseases in developing countries more broadly- is complicated by factors that might seem nigh immutable: climate, geography, poverty, perhaps much else besides. And yet, somewhere within this complex, interlocking mess, there was a crack small enough for an incredibly simple but effective intervention to fit in. And that crack could only be accessed with a niche curiosity about microbial ecology — the whereabouts of a germ we can’t even see.

This is an example of how basic research- something with no apparent “practical” value- can lead to potentially life-saving innovations. This is not an instance of “big science” taking over the reins of a country’s public health. This is home-grown scientists, in collaboration with their international colleagues, working to repurpose existing interventions in a way that’s acceptable to prevailing cultural sensibilities.

All because they were stubborn enough to ask about weird planktons all those years ago.

There’s something strange about the science that comes out of small, unknown places. It can make a lot of noise outside its place of origin: where the science gets cited, the authors get renown, and it even gets picked up and spread around by pop media, like podcasts. But at its place of birth, it might pass away relatively unnoticed — until, of course, echoes are heard from abroad about how this science is really important and useful.

Perhaps, then, this is something our science educators should start taking seriously. Let’s start lifting up our research. Let’s give our students heroes and role models. All of this is way overdue.

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Notes

** This would be the Environmental Microbiology Laboratory — recently renamed Laboratory of Environmental Health.

*** The witch reference here is to ওলা বিবি. I know cholera has a Bangla name as well — ওলাওঠা — but I never heard it in common parlance.

**** This is in reference to a comment made by a WHO report, accessible here- https://www.who.int/bulletin/archives/78%289%291093.pdf

References

Huq, A., Small, E. B., West, P. A., Huq, M. I., Rahman, R., & Colwell, R. R. (1983). Ecological relationships between Vibrio cholerae and planktonic crustacean copepods. Applied and environmental microbiology, 45(1), 275–283.

Huq, A., Xu, B., Chowdhury, M. A., Islam, M. S., Montilla, R., & Colwell, R. R. (1996). A simple filtration method to remove plankton-associated Vibrio cholerae in raw water supplies in developing countries. Applied and environmental microbiology, 62(7), 2508–2512.

Colwell, R. R., Huq, A., Islam, M. S., Aziz, K. M. A., Yunus, M., Khan, N. H., … & Russek-Cohen, E. (2003). Reduction of cholera in Bangladeshi villages by simple filtration. Proceedings of the National Academy of Sciences, 100(3), 1051–1055.

Huq, A., Yunus, M., Sohel, S. S., Bhuiya, A., Emch, M., Luby, S. P., … & Colwell, R. R. (2010). Simple sari cloth filtration of water is sustainable and continues to protect villagers from cholera in Matlab, Bangladesh. MBio, 1(1), e00034–10.

Husband, biologist, philosophy enthusiast, nothing else much besides. In pursuit of happiness and understanding.