Monday, April 13, 2020

Isotope Biogeochemistry of Viruses?

Maureen Coleman, Jake Waldbauer, Chris and Marilyn, Newsome's wedding 2008

“Viral infection drives microbial mortality and nutrient recycling in many ecosystems. Despite the importance of this process, little is known about how viruses obtain the resources they need to produce progeny.” Jake Waldbauer et al., Proceedings of the National Academy of Science, 2019.

I’ve often been asked what I think the next big thing in stable isotope biogeochemistry will be. I’m not very good at predicting the Big Trends. I think I do best with small, possibly important things that we don’t know much about. I’ll not have the time remaining in my active career to delve into this idea, so here goes some early ideas about studying the stable isotope patterns in viruses.

I was riding on the late night bus back to my hotel from the conference banquet of the International Meeting of Organic Geochemists (IMOG) in 2013 with a group of slightly inebriated fellow geochemists. The conference that year was held on the Canary Islands, remote volcanic islands off the coast of Africa. It was the typical blow out banquet with too much booze and never enough food. This wasn’t the super late bus with the out of control folks, but we were suitably loosened up. I found myself seated across the aisle from Jaap Sinninghe-Damste, ( ordinarily a bristly fellow who has been our field’s Young Turk for more than two decades. Earlier in the conference I received the Alfred Treibs Medal for my career in organic geochemistry. I was the first woman to receive the award. The normally cliquish community opened up to me, when I joined the elite, small group of 27 Treibs medalists.
Tenerife, site of IMOG 2013

Jaap leaned over in the bus and asked, “So what do you think the next big thing in Organic Geochemistry will be?”

I recognized this as an opportunity. “Let me think,” I answered. After a minute or two, I answered, “Viruses. We don’t know much about their biogeochemistry and nothing about their stable isotopes.”

He thought for a few seconds, “But they don't have lipids. What would we study?”

Lipids, essentially fats, are the molecules that last the longest in the fossil record—possibly even a billion years or so. Jaap’s career was built on finding new, novel, and rare lipid molecules in living organisms and ancient rocks. At Gordon conferences, small meetings held in rural New Hampshire, Jaap and his Dutch colleagues from NIOZ (Royal Netherlands Institute for Sea Research) often held court as young kings and princes of the field. With the exception of stable isotope God Jacob Bigeleisen, he’s the only one I’ve ever seen stand up in the middle of someone’s talk and essentially tell the speaker they were full of s*$%, such that the speaker ended his talk without finishing and sat down. One year when the IMOG meeting was held in the Netherlands, Jaap, a character personally as well as professionally, dressed in a white suit and disco danced imitating John Travolta in Saturday Night Fever.

Before the bus ride, I’d never had a serious conversation with Jaap. His persona was such that I didn’t necessarily want to get too close. But, I’d talked with many of the young people who had worked with him in his lab over the years. They gushed about what a good mentor he was. I was pleasantly surprised.

After telling him my thoughts on viruses, I asked him a question, “How do you guys identify all those complex lipid structures? I can barely figure out simple molecules.” “We have a manual,” he shot back. His lab group, easily 20 people at any one time, assembled a system for looking for diagnostic patterns. Everyone who worked there used the manual. It hadn’t occurred to me to do such a thing.
Marilyn and Kate Freeman, IMOG, Canary Islands, 2013

Viruses and their impact on ocean biogeochemistry are now a hot topic. Recently, friends and colleagues Jake Waldbauer ( and Maureen Coleman, University of Chicago, have been putting out some very intriguing papers on how viruses affect ecosystems at the very basic level. I’ve known Jake since he was in kindergarten. He worked in my lab as a college intern one winter, collecting fish and crabs in mangrove ecosystems with me and Mat Wooller. He’s gone up in the world since then and is a pioneer in using proteomics—the study of individual protein molecules—in geochemistry!

Viruses not only cause death and mayhem for humans—they may be controlling the most important processes in the ocean.

 Ecosystems are controlled by ‘bottom-up’ (resources) and ‘top-down’ (predation) forces. Viral infection is now recognized as a ubiquitous top-down control of microbial growth across ecosystems but, at the same time, cell death by viral predation influences, and is influenced by, resource availability…First, viral infection transforms host metabolism, in part through virus-encoded metabolic genes; the functions performed by these genes appear to alleviate energetic and biosynthetic bottlenecks to viral production. Second, viral infection depends on the physiological state of the host cell and on environmental conditions, which are challenging to replicate in the laboratory. Last, metabolic reprogramming of infected cells and viral lysis alter nutrient cycling and carbon export in the oceans, although the net impacts remain uncertain.” A. E. Zimmermann et al., Nature Review Microbiology, 2019.

Viruses are made up primarily of a protein outer “coat” with inner nucleic acids, either DNA or RNA. Animal viruses are more complex and often include an outer membrane built from fragments of the host’s cell membrane and a special type of protein that is linked to sugar molecules—glycoproteins. When a virus infects a cell, they coopt the cell’s biochemical machinery to make many copies of the protein coats. During this biochemical highjacking, the cell’s central metabolism is changed.

Changes in the fundamental biochemical pathways of living organisms cause major metabolic disorders. Think cancer, for example. The simple pathways all students learn in high school biology flow in different directions and at different speeds. When things like this happen, we know that the stable isotope patterns in amino acids, and maybe lipids, will be altered. For a brief, but fun period, I collaborated with Fabian Filipp and Christina Bradley on comparing melanoma (skin cancer) cell cultures with healthy human tissue. We found major differences in the isotope patterns of amino acids synthesized in the central pathways. There’s something to this work, but we weren’t able to follow up. I think it would be a very fruitful avenue of research.
Unpublished data of Bradley, Filipp and Marilyn

What if viruses ruled the amino acid biosignatures of organic matter in the ocean? Brian Popp, Hilary Close, and Matt McCarthy’s labs are devoting serious efforts at understanding what happens to organic matter once organisms die and sink to the bottom of the ocean. Perhaps viruses are playing a key role. Given their newfound importance, that very well might be.

What about in mammalian or animal tissues? Could the lipids in viral membranes survive in the fossil record? What if they could be found in some of Earth’s earlier rocks in the Cambrian?

And what if something like a virus, a primitive biogeochemical “secret agent,” might be a good model for searching for evidence of life on Mars or other icy moons? Many have thought about this including the first NASA Astrobiology Institute Director Barry Blumberg, who won a Nobel Prize for his work on hepatitis virus and its vaccine.

I think there’s some good geochemistry and biochemistry to do with viruses. If we were able to study the stable isotope patterns of those viruses that are causing major pandemics, could they reveal something about how they impact cell metabolism? Can those proteins and amino acids provide fodder for studying marine food webs?

I think it’s worth a closer look.


  1. The isotopic composition of Zinc in Human samples and its medical applications
    By Dr Osama Yousef Ali Ghidan
    ICPOES & ICPMS Technologiest-Central Analytical Research Facility (CARF)
    Queensland University of Technology (QUT)-Brisbane- Australia.

    Detecting variations in the Zinc isotopes composition in human samples have promising applications in medicine [1, 2]. Variations in the isotopic composition of Zn were confirmed to exist in Biological samples [1-6]. These variations are in the permil level and are theoretically attributed to many biogeochemical processes without a full understanding to the mechanism involved [1, 4, 5, 7]. The discovery of variations in the isotopic composition of Zn as a function of health disease human status have raised the need for a greater knowledge of the application of Zn Mass Spectrometry in the medical research. In particular; to investigate the relationship between the isotopic compositions of Zn in healthy- diseased human samples. These variations may become the new biomarker to the health disease status of human [1, 4].

    Using high accuracy mass spectrometric instrumentations like ICPMS, the purpose of this study is to identify an isotopic composition of Zn of healthy matrix that serves as a standard healthy matrix for future analyses. Moreover, the aim of this study is to measure variations in the isotopic composition of Zn of diseased samples relative to the healthy standard. Another aim of this study is to give an insight to the relationship between variations in the isotopic composition of Zn and health disease progress. Spiking a healthy matrix with a virus or bacteria will allow the variation in the isotopic composition of Zn to be measured as a function of time relative to the un spiked healthy matrix.

    The results will be used to assess the viability of using Zn to study disease progress, highlight the applications of the findings and make it applicable to medical profession where possible.


    1. Larner, F., et al., Zinc isotopic compositions of breast cancer tissue. Metallomics, 2015. 7(1): p. 107-112.
    2. Jaouen, K., M.-L. Pons, and V. Balter, Iron, copper and zinc isotopic fractionation up mammal trophic chains. Earth and Planetary Science Letters, 2013. 374(0): p. 164-172.
    3. Ghidan, O.Y. and R.D. Loss, Zinc isotope fractionation analyses by thermal ionization mass spectrometry and a double spiking technique. International Journal of Mass Spectrometry, 2012. 309(0): p. 79-87.
    4. Ghidan, O.Y., The isotopic composition of Zn in natural materials, in Department of Immaging and Applied Physics. 2008, Curtin University of Technology: Perth. p. 248.
    5. Pichat, S., Zinc in eastern equatorial Pacific sediments, O. Ghidan, Editor. 2007, Ghidan,O.: Perth.
    6. Pichat, S., C. Douchet, and F. Albaréde, Zinc isotope variations in deep-sea carbonates from the eastern equatorial Pacific over the last 175 ka. Earth and Planetary Science Letters, 2003. 210(1-2): p. 167-178.
    7. Tanimizu, M., Y. Asada, and T. Hirata, Absolute isotopic composition and atomic weight of commercial zinc using Inductively Coupled Plasma Mass Spectrometry. Anal. Chem., 2002. 74(22): p. 5814-5819.

  2. Dear Marilyn,
    I really enjoy reading your blog. Thank you for your thoughts and musings. It was a little hard reading for me today as those “young kings and princes” are my mentors and colleagues and hearing other people’s take on your family is never easy ��. I also have funny memories of that IMOG bus ride back from the dinner. I wonder whether Jaap had danced so hard that night that he had forgotten the ongoing work we were doing at that time regarding the role of viral infection in phytoplankton lipid dynamics. Or perhaps there was a misunderstanding somewhere. Either way here are the publications that arose from our collaboration with viral ecologists Douwe Maat and Corina Brussaard.
    Best wishes and thank you for the wonderful blog,
    Nicole Bale
    Increasing P limitation and viral infection impact lipid remodeling of the picophytoplankter Micromonas pusilla. D. S. Maat, N. J. Bale, E. C. Hopmans, J. S. Sinninghe Damsté, S. Schouten and C. P. D. Brussaard. Biogeosciences. 13, 1667-1676, 2016.
    Fatty acid dynamics during viral infection of Phaeocystis globosa. N. J. Bale, D. S. Maat, C. P. D. Brussaard, E. C. Hopmans, A. Mets, J. S. Sinninghe Damsté, S. Schouten. Aquatic Microbial Ecology. 74, 85–94. 2015
    Acquisition of intact polar lipids from the Prymnesiophyte Phaeocystis globosa by its lytic virus PgV-07T. D.S. Maat, N.J. Bale, E.C. Hopmans, A-C. Baudoux, J.S. Sinninghe Damsté, S. Schouten, and C.P.D. Brussaard. Biogeosciences. 11, 185-194. 2014

    1. Thanks Nicole! I'll look these up today. Marilyn

    2. Can I also recommend this cool virus and lipids paper that came out last year?


Rounding Third Base and Heading Home

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