Andrew Bellesis Andrew Bellesis

The Carboniferous Rainforest Collapse: What We Can Learn from Ancient Trees that Sowed their Own Extinction

We live in an era of self-inflicted climate change, the direct effects of which are hard to ignore. Precipitation whipsaws between drought and flood, sunsets are turned blood red by the ash of forest fires, and extreme heat pushes our electrical grid to the breaking point. This historical moment easily inspires nihilism and despair- a sense that this crisis is immovable, cataclysmic, and unprecedented, and that we are powerless to change its outcome. However, we can contextualize our current situation by understanding the geological history of the Earth. The ecosystems of the deep past have a story to tell that serves as a warning about the effects of uncontrolled climate change, calling us to action. But they can also provide relief by demonstrating that in times of collapse and destruction, not all is lost. They show us how life reinvents itself and brings the world back into equilibrium. Earth’s history is pocked by climate crises and mass extinctions followed by periods of renewal and diversification. One such event, called the Carboniferous Rainforest Collapse, can help us understand the causes of climate change, how the global ecosystem responds, and it can even give insights into how and why we should fight climate change today.

Introduction

We live in an era of self-inflicted climate change, the direct effects of which are hard to ignore.  Precipitation whipsaws between drought and flood, sunsets are turned blood red by the ash of forest fires, and extreme heat pushes our electrical grid to the breaking point.  This historical moment easily inspires nihilism and despair- a sense that this crisis is immovable, cataclysmic, and unprecedented, and that we are powerless to change its outcome.  However, we can contextualize our current situation by understanding the geological history of the Earth.  The ecosystems of the deep past have a story to tell that serves as a warning about the effects of uncontrolled climate change, calling us to action.  But they can also provide relief by demonstrating that in times of collapse and destruction, not all is lost.  They show us how life reinvents itself and brings the world back into equilibrium.  Earth’s history is pocked by climate crises and mass extinctions followed by periods of renewal and diversification.  One such event, called the Carboniferous Rainforest Collapse, can help us understand the causes of climate change, how the global ecosystem responds, and it can even give insights into how and why we should fight climate change today.

 

Part 1: The Carboniferous World

The main characters in our story lived during the late Carboniferous Period, which ranged from approximately 323 to 299 million years ago.  Any time travelers waylaid in the Carboniferous would have found themselves on a seemingly alien world that is not well known in the popular imagination.  Much of the Earth was covered in immense swampland inhabited by massive tree-like plants known as arborescent lycopsids that have long since gone extinct.  The first dinosaurs would not appear for tens of millions of years, during the Triassic Period.  The first birds would not fly until 150 million years in the future.  The first flowers would not bloom for the next 170 million years, and only become common in 220 million years.  There were no fruits or vegetables to eat.  One would have been struck by the silence, only punctuated by pigeon-sized dragonflies with 70-centimeter wingspans buzzing overhead like toy quadcopters.  These insects were enabled to grow to enormous sizes due to the high-oxygen atmosphere.  Shockingly large millipedes called Arthropleura scuttled across the forest floor, attaining lengths of up to 2.6 meters. Yet this world would eventually give rise to the ecosystems that we know today.  The upheavals faced by the plants and animals in this distant past were necessary for the rise of our ancestors.

Although the planet was dominated by insects, vertebrates were beginning to colonize the land.  Tetrapods, which include all animals descended from the first fish to leave the water, had begun to establish themselves 70 million years prior in the Devonian Period.  They would eventually give rise to all reptiles, birds, and mammals.  However, during the Carboniferous, most tetrapods were amphibians that laid their eggs in water, like salamanders and frogs today.  The particularly moist climate suited their lifestyle well, and they evolved into diverse and occasionally large forms.  These included the needle-toothed, fish-eating Baphetidae, and the elongated, short-limbed Colosteidae.  Diplocaulus, a meter-long amphibian with horns and a boomerang-shaped skull, lurked at the bottom of lake beds, attacking small fish near the surface.  The earliest reptiles, which were less tethered to the water because they laid eggs with shells on land- a radical adaptation- began to diverge from their amphibian cousins at this time.

 The plants of the forests and swamps that played host to these animals were particularly fascinating, and extremely important in Earth’s history.  The vast swamps, covering millions of square kilometers near the equator, were dominated by a set of species known as arborescent lycopsids that are only distantly related to the trees we know and love today.  They lived in a huge, trackless wilderness that stretched from what is now the Midwestern USA, on to Eastern Canada, much of Europe, across Central Asia, and finally to China.  Our lost time traveler, knee-deep in water and peering up to the forest canopy, may have described the lycopsids as being trees, but something about them would have felt different.  They towered up to 50 meters high and had trunks up to two meters thick, but they supported their weight not through interior wood but with their tough exterior bark.  A lycopsid began its life as an unbranched, leaf-covered pole, cutting a figure closer to that of a young saguaro cactus than a tropical rainforest plant.  They grew in sunlit groves full of other young, unbranched lycopsids, quickly recolonizing environments that had been stripped of mature trees by floods or hurricanes.  As the trees reached their full height, they finally branched near the very top, creating a comically small crown for such a tall plant.  They perhaps most closely resembled the fictional Truffala trees dreamt up by Dr. Seuss in The Lorax.  Most lines of evidence suggest that the lycopsids lived fast and died young, surviving only 10-15 years, although there is ongoing debate in the scientific community about their lifespan.

 The lycopsids- the true masters of the Carboniferous- constituted over half of the biomass by volume of their habitats.  This enormous footprint meant that they had an important effect on not just the local, but global environment.  Their runaway growth was fueled by a voracious appetite for CO2, the key atmospheric component for photosynthesis.  The lycopsids gave the Carboniferous Period its name: during their reign, more carbon-rich coal was laid down than at any other time in Earth’s history.  The lycposids’ habitats have even been coined “coal swamps”.  During their lives, the lycopsids removed CO2 from the air to fuel their fast growth.  As they died, their bodies sank into the mire, first forming peat, which then became compacted into coal over millions of years.

 Calculating how much carbon the lycopsid forests put underground, and how quickly this happened is essential for understanding the devastating series of climate change events that followed.  Cleal and Thomas estimated that the lycopsid forests were prolific carbon sinks- they sequestered 65 to 234 tons of carbon per acre each year as part of their living biomass.  Any increase in plant biomass means that more carbon is removed from the atmosphere.  But what happens after plants die is critically important.  Today, when plant litter decays, the carbon is quickly released back into the atmosphere in the form of CO2.  However, during the Carboniferous Period, 70% of the carbon stored in plants remained in the ground when they died.  Decay rates were slow due to low levels of fungal activity and acidic soils.  Only 25% of carbon returned to the atmosphere from microbial activity, and another 5% returned via river runoff.  Hence, about 43 to 158 tons of carbon were permanently sequestered per year in an area the size of a football field.  Modern forests’ ability to sequester carbon pales in comparison, which permanently store only 0.8 to 4 tons of carbon per acre each year.  This number is jaw-dropping when viewed with a global perspective: These ancient forests removed 93 billion tons of carbon from the atmosphere annually, compared to only 7.6 billion tons removed by forests worldwide today.  Growing evidence suggests that the forests sucked so much CO2 out of the air that they had a destabilizing impact on the climate.  There is increasing scientific consensus that plants- particularly the ubiquitous lycopsids- played a central role in triggering climate change by decreasing the ratio of CO2 to oxygen in the air.   Feedback loops regulating surface temperatures, ocean ecology, and atmospheric composition amplified the effects that the lycopsids exerted on the ecosystem.  Hence, their prolific carbon usage was not without consequences- the late Carboniferous Period featured repeated, large-scale climate change events which eventually dried out the coal swamps and resulted in the extinction of the lycopsid forest and many of its inhabitants.

 

Part 2: Climate Change and the Downfall of the Lycopsids

The Late Paleozoic Ice Age, which spanned from 360 to 260 million years ago, was next level. It reached its zenith in the Carboniferous Period and featured the most extreme global cooling and glaciation of the last half billion years.  The Ice Age that our Stone Age ancestors survived tens of thousands of years ago was mild by comparison.  Glaciers menaced mountainous parts of the tropics and evidence suggests that they descended to elevations as low as 4,000 feet near the equator. CO2 levels fell below 200 parts per million (ppm) while oxygen levels skyrocketed- by comparison, today’s CO2 levels stand at 414 ppm, showing that small fluctuations in this trace gas yield disproportionate consequences.  Geological evidence from glaciers, plant fossils, and computer-based climate modeling converge to paint a picture of a world rocked by the formation of colossal glaciers interspersed with short intervals of rapid warming.  Sea levels rose and fell by many meters with the changing temperatures, quickly altering coastal ecology and causing shorelines to move by hundreds of kilometers in some places.

The rapidly changing, see-saw climate was difficult for global ecosystems to adapt to, although the full effects were not immediately apparent.  Just like climate change during the 20th century, it would have at first gone largely unnoticed as the rhythms of daily life unfolded.  Generations of lycopsids, giant dragonflies, and monstrous millipedes would have lived and died without ever knowing that a global catastrophe was beginning to develop.  The glaciers did not appear out of the blue, nor did they retreat in a single day.  But the lives of the plants and animals of the coal swamps were eventually interrupted by more frequent weather disasters - droughts, floods, fires, and unseasonable temperature swings would have occurred with increasing ferocity and regularity.  Eventually, the world hit a series of tipping points, changing the trajectory of history forever.  The extinction that followed was not the result of a single hammer-blow, like the asteroid that killed the dinosaurs.  Instead, the lycopsid forests and many of its denizens crept towards extinction, imperceptibly and over many generations.

The lycopsids, which had reigned supreme for 15 million years, suffered a series of stepwise collapses that first saw their territory diminish, fragment, and then vanish.  Glaciers expanded 317 million years ago, before retreating 6 million years later when CO2 levels rose.  While this did not destroy the forests, scientists have observed increased “turnover” of plant species where the composition of the forest changed rather subtly.  Only 3 million years later- a blink in geological time- a period of even more intense glaciation coincided with a sharp decline in the lycopsids, which were replaced by tree ferns.  The lycopsids needed a very wet climate year-round, but parts of the tropics began to experience distinct wet and dry seasons that favored drought-resistant species.  As time went by, and the climate rapidly bounced between global warming and cooling, lycopsid spores became less and less common in the fossil record.  The lycopsids received a final, crushing blow 2 million years later when the CO2 concentration plummeted to its lowest level, and glaciers continued to encroach as the ecosystem was pushed beyond a tipping point.

 It is important to consider that the iconic lycopsids were not the only life to dwell in the coal swamps, and the fates of countless species were intertwined.  There is abundant evidence that the Carboniferous Rainforest Collapse was also devastating for animal life.  Climate, vegetation, and food webs are all interconnected.  While many of the massive insects lived on for millions of years, amphibians did not fare as well.  They were the dominant land-dwelling vertebrates throughout the Carboniferous until the rainforest collapse.  At least nine families of amphibians went extinct in this short time span, and they never regained the prominence that they once had in the ecosystem.  Drier climates were particularly punishing for amphibians, which must lay their eggs in water, and many species relied on fish as their main food source.  But not all was lost. While ecosystem fragmentation is initially disastrous for life, populations that were isolated from one another quickly evolved new feeding strategies, and some animals benefitted from the drier climate.  A new world was born from the ashes of the lycopsid forests.   One obscure clade known as the amniotes benefitted enormously.  While at the time, amniotes did not appear to be that much different than amphibians, they would eventually give rise to all reptiles, birds, and mammals. We can count these early amniotes as our own distant ancestors.  Amniotes lay eggs that are protected by a membrane, and their young do not go through a larval stage, which liberated them from reproducing in the water.  Hence, there was an explosion in early reptile species following the downfall of the lycopsids.  Many new reptiles were not confined to eating just fish and insects- some became carnivores, eating amphibians and smaller reptiles.  Others became herbivores, a first for land-dwelling vertebrates. The resulting food web began to resemble the modern food web not long after the Carboniferous Rainforest Collapse.  This renaissance of reptiles shows that life can reinvent itself in new and profound ways after an ecological catastrophe, although this healing process takes millions of years and comes at a very high cost.

 

Part 3: What is to Be Done?

While the Carboniferous Period officially ended 299 million years ago, its legacy affects humankind every single day.  Humans have been using coal to keep warm and smelt metal for thousands of years, dating as far back as Bronze Age China and Roman Britain, but pre-industrial mining operations remained small and did not affect the global environment.  But large coal deposits dating to the Carboniferous have been used as a key energy source since the rise of capitalism, an economic system which, by its nature, demands the ever-increasing exploitation of resources.  During the Industrial Revolution, exponentially greater amounts of coal were needed to feed the steam engines powering the economies of Europe and the United States.  Today, nearly 8 billion metric tons of coal is extracted from the Earth each year, representing a disproportionately large fraction of our total carbon footprint.   The global carbon footprint mirrored the use of coal to power our ever-growing markets.  Yearly global CO2 emissions were estimated to be 10 million metric tonnes in 1750, increased to 100 million tonnes by 1836, a billion ton by 1886, and in 2021 stood at 36.3 billion tonnes, their highest level ever.  This represents a 3,600-fold increase in CO2 emissions from the onset of the Industrial Revolution until today.  This means that we are pumping CO­2 into the atmosphere almost as fast as the lycopsids were able to put it underground during their golden age.  The carbon that has been stored in the ground for the last 300 million years is now going back into the atmosphere, creating a perverse mirror image of the natural process that caused the most catastrophic climate change event in a half billion years.  In the last 60 years alone, human activity has increased CO2 in the air from 320 to 414 ppm, according to US government data.

 The lycopsids have pressing lessons to teach us about our place in the world and can give us insights about what to do in our age of climate crisis.  They show us that we are not the first dominant lifeform with the power to change the global climate.  And they illustrate that even the most abundant species can vanish after sowing the seeds of their own extinction.  They tell us, in no uncertain terms, that the world will move on, evolve, and reinvent itself, with or without us.  They warn us that if we seal our own fate for the wellbeing of the stock market, our legacy will be represented by a vanishingly thin layer of rock in the fossil record, our own remains trapped in the same strata as the plants and animals that we drove to extinction alongside us.

 But unlike the lycopsids, which could never have predicted or stopped their overuse of the world’s resources, we are capable of foresight and planning to avert disaster.  We must learn to take a long-term view of history, striving to build a better world not just for ourselves but for generations living thousands of years from now.  This involves fighting against the short-term thinking of our economic and political system.  The stability of our system relies on returning high quarterly profits for shareholders, no matter the cost to the environment or to humanity.  The environmental philosopher Edward Abbey aptly wrote that “growth for the sake of growth is the philosophy of the cancer cell.”  In other words, the infinite growth required to sustain capitalism will inevitably lead to our destruction, and we need to decisively break away from using a market-based economy for the sake of securing our collective future.  The invisible hand of the free market- driven solely by its own desires- does not know or care about climate change, just like the lycopsids.

 Switching to a green economy will require the mobilization of large swaths of society.  Scientists and science communicators must see climate activism as being a fundamental part of our work.  We should invest our time and energy into building a mass movement to stop climate change.  We need to fight the misinformation spewed by right wing media and the fossil fuel industry, both in our writing and as activists in our communities.  We must recognize that an effective movement will include a global coalition of Indigenous rights activists, trade unions, leftists, and young people in leading roles.  Furthermore, we should only fight for reforms that are not paid for by the working class and poor of the neocolonial world.  This stands in contrast to the popular “carbon credits” which were widely supported by large polluters at last year’s COP26 climate summit.  In this vein, we should not shy away from calling for far-reaching reforms, including taking extractive industries like fossil fuels into public ownership, so that the enormous revenue they generate can be used to quickly build green infrastructure and make them obsolete, rather than line the pockets of politicians and investors.  With coordinated and determined efforts, we will be able to keep the lycopsid’s carbon in the ground and achieve what they could not- a stabilized climate that never hits a disastrous ecological tipping point.

 

Bibliography

1             Berner, R. A. The long-term carbon cycle, fossil fuels and atmospheric composition. Nature 426, 323-326 (2003).

2             Cleal, B. A. T. a. C. J. Arborescent lycophyte growth in the late Carboniferous coal swamps. New Phytologist 218, 885-890 (2018).

3             DiMichele, C. K. B. a. W. A. Arborescent lycopsid productivity and lifespan: Constraining the possibilities. Review of Palaeobotany and Palynology 227, 97-110 (2016).

4             DiMichele, T. L. P. a. W. A. Comparative Ecology and Life-History Biology of Arborescent Lycopsids in Late Carboniferous Swamps of Euramerica. Annals of the Missouri Botanical Garden 79, 560-588 (1992).

5             Falcon-Lang, H. J., W. John Nelson, Philip H. Heckel, William A. DiMichele, and Scott D. Elrick. New insights on the stepwise collapse of the Carboniferous Coal Forests: evidence from cyclothems and coniferopsid tree-stumps near the Desmoinesian–Missourian boundary in Peoria County, Illinois, USA. Palaeogeography, Palaeoclimatology, Palaeoecology 490, 375-392 (2018).

6             Gerilyn S. Soreghan, D. E. S., and Nicholas G. Heavens. Upland Glaciation in Tropical Pangaea: Geologic Evidence and Implications for Late Paleozoic Climate Modeling. The Journal of Geology 122, 137-163 (2014).

7             Isabel P. Montañez, J. C. M., Christopher J. Poulsen, Joseph D. White, & William A. DiMichele, J. P. W., Galen Griggs and Michael T. Hren. Climate, pCO2 and terrestrial carbon cycle linkages during late Palaeozoic glacial–interglacial cycles. Nature Geoscience 9, 824-828 (2016).

8             John Dodson, X. L., Nan Sun, Pia Atahan, Xinying Zhoi, Hanbin Liu, Keliang Zhao, Songmei Hu, and Zemeng Yang. Use of coal in the Bronze Age in China. The Holocene 24, 525-530 (2014).

9             John H Calder, M. R. G., Andrew C Scott, Sarah J. Davies, Brian L. Hebert, S.F. Greb, and William A. DiMichele. A fossil lycopsid forest succession in the classic Joggins section of Nova Scotia: paleoecology of a disturbance-prone Pennsylvanian wetland. Special Papers-Geological Society of America 399, 169 (2006).

10           Jonathan P. Wilson, I. P. M., Joseph D. White,, William A. DiMichele, J. C. M., Christopher J. Poulsen and & Hren, M. T. Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate. New Phytologist 215, 1333–1353 (2017).

11           Nancy L. Harris, D. A. G., Alessandro Baccini, Richard A. Birdsey, Sytze de Bruin, Mary Farina, Lola Fatoyinbo, Matthew C. Hansen, Martin Herold, Richard A. Houghton, Peter V. Potapov, Daniela Requena Suarez, Rosa M. Roman-Cuesta, Sassan S. Saatchi, Christy M. Slay, Svetlana A. Turubanova and Alexandra Tyukavina Global maps of twenty-first century forest carbon fluxes. Nature Climate Change 11, 234–240 (2021).

12           Sarda Sahney, M. J. B. a. H. J. F.-L. Rainforest collapse triggered Carboniferous tetrapod diversification in Euramerica. Geology 38, 1063-1066 (2010).

13           Sues, H. D. & Reisz, R. R. Origins and early evolution of herbivory in tetrapods. Trends in ecology & evolution 13, 141-145, doi:10.1016/s0169-5347(97)01257-3 (1998).

14           Thomas, C. J. C. a. B. A. Palaeozoic tropical rainforests and their effect on global climates: is the past the key to the present? Geology 3, 13-31 (2005).

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Andrew Bellesis Andrew Bellesis

Participating in a Covid Vaccine Stage III Drug Trial: Scientific Prowess Meets Pandemic Politics

By the early summer of 2020, as new Covid cases surged passed 50,000 daily infections across the nation due to a hurried and botched reopening of the economy, the failure by political leaders to control the pandemic became apparent. With a further flood of cases expected to be ushered in with the cool weather in September, and political will to implement preventative measures fast eroding, I began to realize that the only path to returning to an approximation of normalcy would be the successful development and rollout of a vaccine. Hence, on listless evening at my apartment in Pittsburgh, PA, I looked up whether any clinical trials for Covid vaccines were available for local participants.

Part I: My Experience as a Vaccine Clinical Trial Participant

By the early summer of 2020, as new Covid cases surged passed 50,000 daily infections across the nation due to a hurried and botched reopening of the economy, the failure by political leaders to control the pandemic became apparent. With a further flood of cases expected to be ushered in with the cool weather in September, and political will to implement preventative measures fast eroding, I began to realize that the only path to returning to an approximation of normalcy would be the successful development and rollout of a vaccine. Hence, on listless evening at my apartment in Pittsburgh, PA, I looked up whether any clinical trials for Covid vaccines were available for local participants.

At that time, signups were buried within the Pitt+Me website, which is used to recruit volunteers for the plethora of medical studies that are unfolding at any one moment across the University of Pittsburgh and the healthcare conglomerate UPMC. Scrolling through the various studies being conducted served as a reminder that Pittsburgh has become a center of gravity for advanced biomedical research, providing some comfort that this is one of the better-equipped regions to reside during a pandemic. However, it took a considerable amount of time to denote that I was interested in signing up for a Covid vaccine trial, and I became worried that aspiring volunteers without internet access or with less experience searching the web could not find a way to submit their names, skewing the pool of applicants towards a younger and more affluent group. During the pandemic, far fewer workers would see the advertisements for medical studies that are often posted inside city buses. Nonetheless, I filled out the online form and waited to see if I could qualify as a participant. In the end, I signed up because I became curious about the vaccine development process, was interested in what the experience is like for volunteers, and because I missed my friends and family and just wanted to see them again. I hoped that by participating in a vaccine trial, I could vouch for the safety and efficacy of the development process and the diligence of the researchers. If a vaccine were to be approved, I hoped to be able to convince at least one other person that it is safe and worthwhile to be inoculated.

Between late June and mid-July, I completed additional online screenings to assess whether I could participate in a study. At this stage, I was asked to sign a consent form that described the ways in which my medical data would be used by the Pittsburgh Vaccine Clinical Trials Unit Registry for determining eligibility for participating in a study. Later that month, an email was sent to all potential participants that the university would begin enrolling hundreds of adults in the first of several stage III trials for different Covid vaccines. In late August, I received a call out of the blue from the vaccine registry. The coordinator explained that they were hurriedly trying to recruit the last of 250 volunteers for the first Phase III study to take place in the city. After assessing that my laboratory job put me at elevated risk for contracting the virus, I was invited to make an appointment to enroll in the trial.

The study took place in a cramped suite inside a nondescript medical office building on the leafy outskirts of the University of Pittsburgh campus. The atmosphere here was pleasantly different from the rest of the nearly deserted university. Medical workers of all stripes dressed in full PPE bustled through the warmly lit hallways, ushering participants into and out of rooms, filling out forms, carrying samples, and quietly conferring with one another. After being led to a standard examination room, I answered a litany of health questions and was given a brief physical.

A physician then coached me through a lengthy consent form, highlighting the various risks and benefits of being a clinical trial participant, and making sure that I understood the experimental design and objectives of the study. I was informed that I would either receive two doses of the Moderna mRNA-1273 vaccine or a placebo four weeks apart. Potential risks- which had been elucidated in previous rounds of research involving fewer participants- were quite small, even at this early stage. It was already known that participants receiving the vaccine could be prone to mild fever, pain or redness at the injection site, headache, muscle and joint aches, fatigue, chills, swollen glands, or nausea. However, these effects were more of an inconvenience than a threat to one’s overall wellbeing and resolved on their own within two days. Serious side effects had not been detected. I decided on the spot that such risks were a trivial price to pay if my participation could help get an effective vaccine approved. Importantly, this was a blinded study- until the initial results were known, neither I nor the researchers would know if I had received the vaccine or a placebo. This is an important measure to remove bias from the experimental design- this way, my expectations, the researchers’ expectations, observer bias, and confirmation bias are removed from the equation. In the words of the full, published experimental protocol: “The Blinded Phase of this study is a randomized, stratified, observer-blind, placebo-controlled evaluation of the efficacy, safety, and immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine compared to placebo in adults.” The goal of blinding is to turn the hopes and fears of participants, clinicians, and scientists into mere noise rather than bias.

Once I understood the basics of the experiment, I gave informed consent to continue my participation. I knew that I could drop out at any time, and that every step along the way was voluntary. A nurse then took seven tubes of blood to gather baseline information on my general health and SARS-CoV-2 antibody status, and then administered a nasal-pharyngeal swab to assess whether I had an asymptomatic infection. Lastly, a different nurse administered an injection into my arm, I waited a half hour in case any side effects quickly manifested, and then I was allowed to leave. Over the next few months, I reported regularly for additional blood work, nasal swabs, and physicals. Research staff asked a litany of health questions every time I returned. I completed an e-diary of my health once a week as well. Lastly, I was told to return to the clinic if I ever developed Covid-like symptoms so that the researchers could undertake further testing. I was compensated monetarily for each visit to pay for transportation costs and for the time I dedicated as a participant. It was not a luxurious amount of money- one visit to the clinic covered a week of groceries- but it was enough to encourage me to make it to every appointment and remain in the study. Importantly, I was asked to proceed with life as if I received the placebo and take full precautions against contracting Covid. Therefore, I continued to wear a mask indoors and avoid crowds. Now, it was a waiting game.

On November 25th, 2020, I was contacted by the research staff with the best possible news- an independent data safety and monitoring board had met the previous week and determined that the Moderna vaccine was safe and effective- no safety concerns were detected, and initial results showed a 94.5% efficacy rate. Of the over 30,000 participants in the study, 95 contracted Covid- of those, 90 were in the placebo group, and only 5 had been in the vaccinated group. The clinical trial was to continue while additional data were collected, emergency use authorization was submitted, and research protocols were updated to open the door to having the placebo group receive the vaccine. The emergency use authorization granted in December triggered the unblinding of the study- a necessary moral imperative to offer vaccines to those in the placebo group. The On January 8th, I returned to the clinic for a much-anticipated appointment to learn whether I had received a placebo or the vaccine. I was informed that I had been in the placebo group, and much to my relief, I was immediately given the opportunity to get vaccinated. I took the shot without hesitation, knowing that it would open the door to safely seeing friends and family for the first time in nearly a year. The rigor of the experimental design and professionalism of the researchers had convinced me that taking the vaccine was the safe, correct, and necessary decision.

 

Part II: The Science Behind Covid Vaccines

The development of no fewer than three Covid vaccines in the US in under a year should be considered one of the greatest technical achievements of the 21st century. However, a burst of progress of this magnitude did not occur in a vacuum. Political, economic, and historical factors made the design and rollout of these vaccines simultaneously achievable and imperfect. The decades of science that went into the successful formulation of safe and effective mRNA vaccines should be celebrated and understood to push back on misinformation that the process was rushed, untested, or unsafe. The political and economic factors that hobbled vaccine production, rollout, and uptake must be sharply critiqued.

Contrary to the popular narrative that mRNA vaccines were invented in only a few months, the necessary scientific knowledge that enabled their development began exactly 60 years ago with the discovery of mRNA and its function in 1961. Similarly, the lipid nanoparticles used to deliver mRNA into cells have been under investigation for decades. Some key milestones which are described in amazing detail by Hou et al. in a peer-reviewed paper are worth discussing.

mRNAs, or messenger RNAs, are delicate and transiently expressed molecules that our cells naturally produce every time they need to use a gene. Genes are segments of DNA that encode instructions on how to build a specific protein. Specialized proteins in the nucleus read genes and transcribe their DNA instructions into mRNA. The mRNA then leaves the nucleus and attaches to small structures known as ribosomes which then translate the mRNA into a protein which will serve one of thousands of distinct biological functions. Afterwards, the mRNA is broken down into its constituent parts and recycled. This process is akin to copying a paragraph out of a book and translating it into a different language that other people can understand and use. This process doesn’t change the content or meaning of the book- likewise, mRNA does not change the content of our genome. mRNA vaccines take advantage of this natural process. For infectious disease, mRNA corresponding to a viral gene is introduced into the cell and translated by the ribosomes. The immune system recognizes the resulting viral protein as a foreign invader, and makes antibodies against it, yielding protective immunity by preparing the body for a rapid response if it is exposed to the live virus. For example, the Moderna vaccine codes for the full-length SARS-CoV-2 spike protein, which mediates the attachment and entry of the virus into host cells, making it the perfect target for the immune response. The vaccine essentially shows the immune system Covid’s battle plan before it attacks, allowing the body to mount the ideal defense in the case of infection.

Extensive mRNA vaccine research has been conducted in animal models and in human clinical trials since the 1990s. In 1990, researchers at the University of Wisconsin injected mRNA into mouse muscle, eliciting the expression of desired proteins. Five years later, an mRNA-based cancer vaccine induced an immune response in mice. Scientists designed an mRNA influenza vaccine in 1993 that successfully triggered a virus-specific immune response in mice, demonstrating that mRNA vaccines can be used to fight infectious disease and paving the way for future research in humans. Currently, clinical trials in humans for mRNA vaccines against influenza, zika, cytomegalovirus, chikungunya virus, rabies, as well as a wide array of cancers and genetic disorders are underway. They carry enormous potential for answering previously insoluble threats to human health and represent the next generation of vaccine technology.

 

Part III: The Politics of a Pandemic

The haphazard and inequitable rollout of the Covid vaccines leaves less to celebrate. Years of austerity budgets and underinvestment in public health infrastructure caused even the wealthiest countries to struggle to manufacture and distribute vaccines quickly for general use. Growing nationalism has led wealthy countries such as the US to hoard vaccine doses, preventing countries in the Neocolonial world from beginning mass vaccination campaigns. At the current rate, low-income countries will need 57 years to finish vaccinating their populations. Profit motives play a large role in global vaccine inequality- for example Pfizer reaped hundreds of millions in profits during the first quarter of 2021, and Moderna, which received enormous public investments, will eventually garner billions in profits. Meanwhile, the fifty poorest nations have received only 2% of all vaccine doses. The profit-motivated US embargo on Cuba has compounded this problem by preventing the island nation’s public vaccine manufacturers from precuring basic equipment and blocking the eventual distribution of 100 million doses of its publicly developed, unpatented vaccines. Furthermore, large vaccine manufacturers have bought up more essential equipment than they could use, stockpiled it, and caused small manufacturers to shutter production lines. The cost of these overlapping problems is immense- inequality is causing the pandemic to drag on, allowing for new and deadly Covid strains to spring up, and resulting in untold human suffering across the globe. This starkly illustrates of the limits of a market-based, profit-driven economic system in fighting a pandemic.

Growing vaccine hesitancy has further complicated mass vaccination campaigns and prolonged the pandemic. To combat this phenomenon, we need to understand its complex historical, economic, and social roots. Deliberate right-wing misinformation campaigns need to be fought vigorously. Anti-vaccine politicians such as Gov. Ron DeSantis of Florida and Brazilian president Jair Bolsonaro need to be met with determined protests and a concerted mass movement to block their disastrous and politicized public health policies. Additionally, we need to win over the vaccine-hesitant to the reality that immunizations are safe and effective- wishing death on those who have been deliberately mislead by political leaders is both cruel and shortsighted. It is crucial that marginalized groups are persuaded rather than excluded and written off- for example, African Americans have been abused by medical institutions for decades and legitimate institutional distrust needs to be overcome. Uninsured Americans are also under-vaccinated due to continued inaccessibility of the vaccine and distrust in profit-seeking healthcare institutions that often do more to bankrupt them than to cure them. Fighting for racial equality in medicine, for universal healthcare, and for upgraded health infrastructure in poor and isolated communities is critical for long term improvements in public health.

The United States has nearly unlimited scientific talent, demonstrated clearly in the development and rigorous clinical testing of Covid vaccines that created a new paradigm in vaccine technology. The massive public investment pumped into vaccine research shows that we can prevent and treat diseases in ways that were impossible during the 20th century. It also shows the value in publicly funding the decades of science that got us to the jumping off point for the rapid development and testing of Covid vaccines. Realizing our full potential in the future will require continued and ramped up funding of biomedical research and a long term and determined fight to eliminate global and local inequalities within the medical system. We have the technology. The question is, how do we develop the political willpower?

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Andrew Bellesis Andrew Bellesis

On my Love of Science and Why I Left Graduate School

The first time that I set foot in a research lab as an 18-year old college freshman at Clark University, I knew that I was home and that I wanted to be a research scientist. That fall, I set to work synthesizing unusual and previously undescribed magnetic compounds from mixtures of copper ions and an assortment of organic molecules. I loved watching the chemical reactions in real time, the sound of the automatic stir bars whirring against the edges of my beakers. I loved the smell of the organic molecules hanging in the air and the quietude of the lab late at night. Afterwards, over a period of weeks or months, crystals of new compounds formed at the bottom of the beakers. They were beautiful- bright oranges, vibrant yellows, chartreuse and forest green. I relished being the first and only person with a supply of these new compounds. If the crystals reached a sufficiently large size- barely a millimeter across- I would scrape each crystal up into a vial and ship them off to collaborators a half a world away in New Zealand. There, scientists subjected my crystals to powerful x-ray radiation. The photons bounced off the electrons of each atom in the molecule, creating a unique diffraction pattern for each compound. They would then send the diffraction data back to our lab in Massachusetts where we would use it to solve the atomic-resolution structure of the novel compound for the first time. In parallel, I took magnetic measurements of crystals that had never been shipped to New Zealand. To do this, my professor and I cooled our compounds to nearly absolute zero, placed them in a magnetic field tens of thousands of times stronger than that of the Earth, and slowly raised the temperature to see how the electrons would align themselves. Learning the molecular structure and magnetic properties allowed us to glean insights into how subtle differences in molecular structure could lead to radically different magnetic properties. In the long term, this work builds scientific understanding of how to create superconducting magnets that could change the face of technology in ways both subtle and life changing.

The first time that I set foot in a research lab as an 18-year-old college freshman at Clark University, I knew that I was home and that I wanted to be a research scientist. That fall, I set to work synthesizing unusual and previously undescribed magnetic compounds from mixtures of copper ions and an assortment of organic molecules. I loved watching the chemical reactions in real time, the sound of the automatic stir bars whirring against the edges of my beakers. I loved the smell of the organic molecules hanging in the air and the quietude of the lab late at night. Afterwards, over a period of weeks or months, crystals of new compounds formed at the bottom of the beakers. They were beautiful- bright oranges, vibrant yellows, chartreuse and forest green. I relished being the first and only person with a supply of these new compounds.  If the crystals reached a sufficiently large size- barely a millimeter across- I would scrape each crystal up into a vial and ship them off to collaborators a half a world away in New Zealand. There, scientists subjected my crystals to powerful x-ray radiation. The photons bounced off the electrons of each atom in the molecule, creating a unique diffraction pattern for each compound. They would then send the diffraction data back to our lab in Massachusetts where we would use it to solve the atomic-resolution structure of the compound for the first time. In parallel, I took magnetic measurements of crystals that had never been shipped to New Zealand. To do this, my professor and I cooled our compounds to nearly absolute zero, placed them in a magnetic field tens of thousands of times stronger than that of the Earth, and slowly raised the temperature to see how the electrons would align themselves. Learning the molecular structure and magnetic properties allowed us to glean insights into how subtle differences in molecular structure could lead to radically different magnetic properties. In the long term, this work builds scientific understanding of how to create superconducting magnets that could change the face of technology in ways both subtle and life changing.

After three years, my imagination captured by x-ray crystallography and swimming with new knowledge of biochemistry, I decided to change direction in my research. Full of ambition and with my eye on combined MD/PhD programs, I drove across town and joined a lab at the University of Massachusetts Medical School which was laser-focused on uncovering the mysteries of a cancer-causing protein nicknamed CtBP. I quickly learned of our complicated relationship with CtBP, a protein that is both a savior and executioner. If an embryo suffers a mutation in their CtBP genes, the pregnancy is not viable and quickly ends in miscarriage. However, transcription of CtBP is rapidly shut off after early pregnancy, never to be turned on again. Unfortunately, in a subset of cancer patients, the body erroneously ramps up CtBP production. This in turn makes the cancer cells harder to kill and allows them to break away from existing tumors, and buoyed through the blood, land in distant tissues, colonizing more organs with a smattering of growing tumors. As of now, there is no treatment for this phenomenon. We had a singular objective: understand the structure and biochemistry of CtBP to make a drug that renders it inert in cancer patients.

As before, I quickly fell in love with the day-to-day research. I inoculated E. coli bacteria with synthetic variants of CtBP genes, and then while growing trillions of bacteria in large flasks of broth that smelled vaguely of chicken soup, I used a chemical to induce the bacteria to produce unnatural amounts of CtBP. Afterwards, I broke the cells open and purified the desired protein. In some experiments, I conducted batteries of biochemical tests to understand how individual CtBP molecules bind together in the hopes that we could design a drug to interrupt these interactions. In other experiments- my favorite experiments- I worked to crystallize the purified protein in a similar manner to the way I crystallized the magnetic compounds. I took microliter droplets of protein under varied chemical conditions, used a pipette to carefully transfer the droplet to a plastic microscope cover slip, and then flipped the coverslip upside down and sealed it off from the atmosphere and waited. Over the course of days and weeks, CtBP crystallized under a small range of precise conditions. The crystals were only visible under a microscope and were uniquely beautiful, gleaming like nearly translucent diamonds cut into a bipyramidal shape. While looking through the microscope, I added miniscule amounts of experimental drugs to the droplet and watched as the crystal cracked and then annealed when the drug bound. From there, I immediately scooped up the crystal with a tiny spatula and mounted it on a specialized x-ray machine. For hours thereafter, we took hundreds of x-rays of the crystal from different angles, slowly building the diffraction pattern needed to solve the atomic structure of the protein. In the following weeks, I poured over the x-ray data, slowly building an accurate structure of CtBP. Although I only solved three structures despite setting up over 3,000 protein droplets, the work was deeply gratifying. I decided that I wanted to spend the remainder of my career studying protein structure to advance medicine, abandoned my fantasy of going to medical school, and instead applied to PhD programs in biophysics and structural biology. I was at the peak of giddy confidence as I wrapped up my work at UMass with a master’s degree and a publication, ready to throw myself doggedly into the next stage of research.

I came to the University of Pittsburgh in the fall of 2017 in search of a new lab and a new scientific problem. The beginning of a PhD program yields the opportunity to reinvent oneself- to discover new ways of thinking about research, to deepen one’s existing knowledge, and learn new techniques. It gives one opportunity to try and fail, and to try again. At this juncture, I was infatuated with academia.

I approached my work with the usual zealotry, sometimes going months while working seven days a week. I lived on ramen, caffeine, and Chinese takeout. During the first eight months of my program, students rotate through three different labs in an effort to match with the right dissertation adviser. In my case, serendipity heavily shaped my decision. During my second semester, I was forced to drop out of a required computer programming course because I developed a mental block under the strain of the high workload. Panicking slightly and searching for alternatives, I asked my first-year adviser if I could rotate in her lab. She is a computational biophysicist, and all her students become adept programmers as they simulate proteins to understand how they fold into complex 3D shapes and build new software to simulate a vast array of chemical processes. Always better at research than classwork, I thought that hands-on experience with coding would get me back on track.

I immediately became fascinated with simulating proteins. I threw myself into the research, hungrily learning about this new approach to studying protein structure, and quickly made inroads into the intro-level problems that I was initially assigned to learn the techniques. I regained the confidence that I had lost when I dropped out of the programming class. After two months, I knew that I wanted to change directions in my research and study protein structure computationally.

I relayed this insight to my adviser, who then suggested a once-in-a-lifetime opportunity. She correctly intuited that I missed experimental work at some level and came up with the idea of a co-mentorship. The plan was simple: I would split the time between simulating proteins in her lab and working with proteins hands-on in a second lab under the tutelage of a renowned experimentalist and close collaborator. Towards the end of my PhD, I would tie these separate strands of research together into one momentous capstone project.

I knew that accepting this offer was a bit of a gamble- a co-mentorship is a particularly grueling track, especially since I was still a novice at simulation techniques. Nonetheless, I could not turn the offer down. Fueled by a mixture of equal parts curiosity and blind ambition, I delved readily into this unfamiliar situation. On the experimental side of my work, I began attempting to purify the HIV protein Vpr while it interacted with the human protein hHR23A. In my computational efforts, I began simulating protein unfolding mechanisms to gain fundamental insight into how proteins spontaneously lose their structure.

However, I quickly ran into problems in both labs in the summer of 2018. On the computational side, I was having difficulty learning the mechanics of programming beyond the introductory level. On the experimental side, I quickly came into conflict with the lab manager, who refused to provide a set of pipettes, insisting that they were needed for visiting undergraduate students, even though they are a central tool in any protein lab. I compounded this conflict when I borrowed his pipettes late one Saturday night and forgot to put them back in the right place. I was angrily confronted on the following Monday, and it was immediately clear that I had committed a serious taboo and that my standing in the lab was in trouble. I was ashamed and angry at myself for weeks. I had been the lab-equivalent of an inconsiderate roommate, or so I felt at the time.

Work intensified through the early fall when I began the last class required in the core curriculum. Here, we bounced between studying thermodynamics and statistical mechanics, solving problems with pen and paper, and undertaking lengthy coding projects with little oversight. Working close to 100 hours a week, I was reaching my breaking point. I was neglecting my family, my friends, and my soon-to-be fiancée who had just moved 600 miles from Massachusetts so we could start our life together. I was not taking care of my health. I was not so much as making progress but putting out fires. Everything came to a head in late September, after I asked a question in class which the professor couldn’t answer. Clearly annoyed, he assigned me the extra homework of answering this question and presenting it to the class. When I did not have time to complete this additional piece of work, he mocked me in front of my peers and told my classmates that it was my fault that this question was going to be on the exam. In this moment, I felt the fight go out of me. 

Rather than going back to work after class, I took a long walk to the public park, and while sitting on a bench atop a peaceful hillside, decided to leave science. In that moment, I felt the sharp, unremitting anxiety of the past months die away, while in its place grew a sense calm, if not serene, depression.

I emailed my advisers, explaining my situation and decision to leave. Alarmed, they called a direct meeting. To my surprise, this was not an exit interview. Instead, they offered six weeks of paid medical leave so that I could recoup my mental health. I could drop the class and make the credits up in the spring with a different professor. They explained that the school understands that a predictable fraction of PhD students will suffer a nervous breakdown, and that there is an informal institutional flexibility in place to accommodate for this. Stunned, I accepted the offer and decided not to look for jobs.

My time off allowed for an unprecedented period of reflection and quiet, and although I remained severely depressed, my anxiety eased, and I felt refreshed upon returning to lab after Thanksgiving. I was optimistic when I returned, and thankful to be back at work, I temporarily held myself to a sustainable pace.

However, in the new year, it became clear that this interlude did not solve some of my underlying weaknesses. My research progress in both labs stalled while I tried to split my time between projects. My programming had improved only marginally, which caused anxiety. I felt my colleagues growing impatient with my lack of progress. Furthermore, Vpr and hHR23A were proving recalcitrant to purification, and a viable path forward for the project was muddled at best. Meanwhile, the lab manager had taken to telling my colleagues that I was too stupid to work at the University of Pittsburgh. Frustrated and bitter, I again considered quitting, but instead doubled down on my efforts, and studied for and passed my comprehensive exams, which is a central milestone in a PhD program. This success provided a brief boost, which was augmented by the news that I had secured an NIH grant for my studies. Still, I saw the writing on the wall- I could not get through this PhD under the co-mentorship. Therefore, after careful consideration, I abandoned my experimental work to  solely focus on computation. I believed that I would be happier in my day-to-day work, away from the lab manager who undermined me, and that I would make faster progress in setting up simulations and writing programming scripts.

Initially, this decision paid off and I made rapid progress. However, by December 2019, I realized that no matter how hard I work, I will never be a PhD-level computationalist. To obtain a PhD, one must deeply understand their research, master the techniques, and develop a unique creative vision for the direction of their project. I was simply not able to make this come together. Therefore, I made the decision to write up the work that I had already completed and drop out of school with a master’s degree. Persisting in my studies would have been nothing more than a vanity project. After two and a half years, my dream of a PhD officially came to an end.

Accepting the unraveling of my degree has been a grieving process. At first, I was in denial, believing that a short break or switching labs would help. After this did not work, I experienced unremitting anger and self-hatred that lasted for months. I was rarely upset with the people around me. Instead, I felt as though I had failed everyone who was foolish enough to believe in my or show me any kindness, patience, or love. My sense of self worth was gutted. In academia, people will pay lip service and say that failure is not a referendum on your worth as a human being. However, when your research is a lifestyle that cannot be compartmentalized or shut away on weekends, when the pursuit of knowledge is your raison d’être, you realize that only those who are successful can make this claim without doubting the veracity of the sentiment.

As I worked through my anger and raw emotion, I have finally begun a journey of acceptance. I am at peace knowing that I will never become a professor or run my own lab. With failure came the opportunity to reinvent my career in a way that I had never thought possible. In retrospect, the worst part of this experience is how my PhD took my love for research and slowly turned me coldly indifferent so that I could survive day-to-day. I lost an important part of myself that I need to get back.

Shortly after leaving school, I was lucky enough to land a position as a research technician. I have never been more thankful that someone was willing to take a chance on me and that I now have the privilege of researching Alzheimer’s Disease. My hope is that by returning to the intellectually stimulating environment of a lab and contributing to a project, I will slowly regain my passion for research that I knew at Clark and UMass.  I can only achieve this revitalization in a job that can be compartmentalized, unlike a PhD. The rhythm of clocking in and out while still being in a research environment has given me a new toehold in science that I plan on sticking to for dear life.

While I am tempted to place all of the blame on myself for failing in my PhD, I realize that the reality is more nuanced. On one hand, my shortcomings- pure ambition, overzealousness, a tendency towards depression and anxiety, and a series of poor tactical choices that landed me in the wrong line of research- led to this outcome. However, there was also a wider programmatic failure that is present in many corners of academia. For instance, Pitt is flexible with students who experience a nervous breakdown because it knows this happens regularly. However, the administration is actively antagonistic to changing the work culture, improving employee benefits, and has litigated for years against graduate student unionizing efforts. A “survival of the fittest” attitude exists among many faculty and training staff. A very large power differential exists between students, professors, and the university. Poor behavior is very rarely reigned in and toxic work environments are frequently tolerated. Pay does not keep up with cost of living increases. There is no guaranteed vacation time or sick leave; this is up to the sole discretion of one’s adviser. I was lucky in that I had supportive advisers who encouraged me to make the right choices for my career rather than simply use my labor to win grant renewals. Their dedication is the reason why I do not want to leave science completely. Nonetheless, if the overall dynamics of higher education do not change, graduate students will continue to burn out at ever increasing rates. My story is by no means unique.

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