*Names are altered for anonymity
As I entered the lab after lunch, Geeta,* a master's dissertation trainee, was being scolded by her mentor, Rakesh*, for not reading up when he told her to. Her ears had turned red, tears brimming her eyes. She left almost immediately as more people poured in. Although an average student, Geeta is sincere but rather meek. Her neglecting to read felt strange to me. Plus, Rakesh is known for his impatience and temper. Some nudging revealed that Geeta had read but couldn’t explain it to Rakesh. So he started shouting. And then she went blank.
Where I study, such scenes are common during the spring session with new doctoral aspirants and master's dissertation trainees abound. Fresh students grapple with the unstructured, scattered learning methods of real-life research and existing PhD scholars largely distance themselves from the role of a trainer/mentor. There is no formal “train-the-trainer” coaching, hardly even an informal discussion. There aren’t any “orientation sessions” to ease the newbies into the esoteric environment. Such unpreparedness leads trainees to doubt their capabilities and junior mentors to be clueless about what “picks up” their mentees. It sounds like a perfect recipe for disaster.
But we do not witness many disasters around us. Thanks to the autopilot. The emotion of autopilot has one aim - defense; to preserve our sense of self. This psychological tool called the “fight or flight response” derives from our primal instinct of surviving physical danger. It fulfills its goal very well but as a side-effect, it perpetuates an undercurrent of nervous energy that scans our environment for threatening events. In Geeta and Rakesh’s scenario, Geeta’s psyche will try to ‘flee’ such interactions through avoidance. If the same pattern reoccurs, her psyche will come up with ways to never interact with Rakesh. In case the interaction is necessary, her fears will play out in other ways. There’s very little chance that she’d actually learn anything in this process.
Being prepped up at all times to respond to a perceived threat can be draining and in the long run, it is counter-productive to stay on autopilot. There are two ways to break this stalemate - either Geeta has to ‘suck it up’ and deliver or Rakesh has to modify his training approach. Neither of them can be done while they’re both on autopilot. Here, we find ourselves staring at a problem - and it is not the autopilot. It is, in fact, a built-in response to the underlying problem(s).
Do all problems really have a solution like novelist, Alice Hoffman, says? The philosopher, John Dewey, said a problem well put is half solved. So let's begin there - defining the problem. We’ll have to take a couple of steps back to get to this one. Walk with me.
Flashback: College days are memorable for most of us. We’re young and everything seems possible. New friendships blossom, career opportunities abound. Academically, all we need to do is score reasonably well on tests. The syllabus is well-defined, lectures and classes help you learn. Umpteen sources are at your service. Sports and extracurricular activities take our minds away from academic demands from time to time, giving us breathing space. By design, we get much needed breaks. Students may sustain despite slacking on studies once in a while. In short, we are carefree for the most part.
Flash-forward: A research laboratory. In many ways, here, you are your own boss. You are solely responsible. This environment is a deep contrast to all previous educational settings. As opposed to timetables and syllabus, you will have a research aim and more or less nothing else. Not only do you have to create your own checklists (in a gently guided way, if you are lucky), you have to find ways to effectively complete them. That takes a serious amount of time devoted to self-learning. The linear ‘read-rote-repeat’ model fails miserably in this arena. If you have conceptual understanding in place of rote learning, you are fortunate. Still, you would need to cope with the lack of structure in your reading resource here. After all, to get good at pulling out useful research articles AND read them critically is an art. The motive is to read, understand, infer and then apply your understanding towards the project. Now this is a cyclic process, instead of the linear one you’re used to. Over that, seldom are there any check-ins as you follow this multistep process.
Application of knowledge boils down to experimentation - the technical part of research. Getting hands-on handling instruments, reagents, living material, etc for the first time means fertile ground for mistakes! There will be times when there’s no one around you to advise how to fix it, or tell whether it is even fixable (Your soul will be grateful for Google that day). Learning from failure and moving on like it was never a thing is the number one survival skill you’ll have to develop.
Copious amounts of literature might remain pending on your checklist as you set up that next experiment (or another trial at a failed one). You might have to execute a procedure when you aren’t completely sure of it. All the while, the clock is ticking. Unless you were always inherently great at it, time management becomes an overwhelming task. Time will be your most precious commodity because it feels as if it has shrunk.
Whether you are a fresh new researcher or mentor, taking a few steps towards each other will take us a long way. It’s never too late to make academia a better place. Shall we?
You order take-out at your favorite restaurant over the phone. You then drive to this restaurant, park your car, go inside and get your food. But haven't you wished that all restaurants had the option of a drive-through window? You save time, and it is indeed way more efficient.
Similarly, tiny cells in our body have their own version of drive-through windows, specialized structures known as 'porosomes.' However, unlike restaurants, every cell has several porosomes embedded on their outer covering, the cell membrane. The porosomes are tiny and cup-shaped, in the size range of nanometers, you could fit at least a 1000 porosomes on the tip of a single hair strand! The word 'porosome' literally translates to pore-forming bodies. They open and close, aiding in proficient cell secretion, just like a restaurant drive-through!
Wait…but what is secretion?...
To understand secretion, we need to know what cells are, and for that, we need to understand how animals are organized! Throwback to our school days, we learned that animals are made up of organs like the heart, brain, lungs, and many others. Each organ is made of tissues, and every tissue is built out of cells, so technically speaking, cells are the basic unit of life. Cells need to communicate with each other and their surroundings to keep an animal functional. They do so by releasing chemical messengers into their surroundings, and this process is known as 'secretion.'
Secretion is a universal phenomenon; almost all cells secrete at a basal level. But certain types of cells are specialized for secretion. These cells are critical for simple life processes such as thinking, digestion, building muscles, and energy production. Porosomes are thus present on cells that undergo secretion as their primary function. Furthermore, defective secretion by cells can lead to diseases; for example, Diabetes may be caused when β- cells of the pancreas fail to secrete the hormone, insulin.
So, how do porosomes know that a cell wants to secrete?
An extremely complex process turns on a switch within cells that causes them to secrete. Once the switch is on, it sets the 'secretory granules' in motion.Secretory granules are spherical bags within cells that carry chemical messengers such as insulin. During secretion, the secretory granules travel from the center of the cell towards the cell membrane, on which the porosomes are located.
The base of porosomes has a dedicated machinery that anchors secretory granules until they have released their contents. Once a granule latches on to a porosome, the porosome opens up, facilitating the release of chemical messengers. The porosomes, therefore, establish a connection between the granules and the cell exterior, similar to a drive-through window.
Cool! What else do we know about these porosomes?
Porosomes were discovered pretty recently in the early 1990s, and there is an interesting story to their discovery. Conventionally, it was believed that granules fuse to the cell membrane during secretion. But this couldn't explain some crucial observations made by scientists. Firstly, high-resolution microscopic images of cells after secretion show that granules still have chemical messengers left inside them. Secondly, imagine, if all the secretory granules fuse with the cell membrane, then cell size and volume must increase, which wasn't witnessed. Lastly and importantly, the secretory granules are very similar to soap bubbles. They are spherical, have a high surface tension, and pop as soon as they come in contact with a surface. Therefore, granules may find it difficult to merge with the cell membrane without exploding. So, a porosome structure was suggested and later discovered that prevents granule collapse.
Neurons of the brain, cells of lungs, and β- cells of the pancreas are all equipped with porosomes for secretion. Although similarly shaped, every cell type has porosomes that are distinct in size, make, and design. For instance, porosomes from brain cells may be unable to secrete insulin.
Recently, porosomes were fished out from β-cells of mouse pancreas and inserted into living cells of the same type. The newly engineered β- cells had extra sets of porosomes embedded on their cell membranes. These cells were able to release more insulin than usual. Although further research is required, this could be a potential therapy for mitigating, not just Diabetes but many other secretory diseases.
Another secretory disease is cystic fibrosis (CF), which occurs when lung cells have faulty fluid secretion due to the sub-optimal function of the CFTR protein. Interestingly, when separated from lung cells, CFTR was found attached to the porosome suggesting that reconstitution could be a potential treatment for CF patients too.
Porosomes, although tiny, have made a mighty shift in the way we now comprehend cell secretion.
On June 10th, I observed #ShutDownStem, a movement encouraging scientists to take a day away from science to educate themselves about racism. Prominent journals and institutions such as Nature, AAAS, and The Broad Institute tweeted out in support of #ShutDownStem and received angry tweets from troll bots and dissenters alike. The most common argument against the #ShutDownStem movement claimed that science is an objective enterprise and should not be politicized.
Scientists are humans. We are not intellectual superheroes. Please erase the vision of Sheldon Cooper and Dr. Fox from your head. We are not armed with eidetic memories and apathy that grant us immunity to societal influences. We are capable of ignorance, bias, arrogance, excessive-competitiveness, bullying, and you guessed it — racism.
Introspection is difficult. No one wants to admit they have tolerated or contributed to racism. For some, it is easier to ignore the ugliness and buy into the idea that science institutions are objective and based solely on meritocracy. In my reflection during #ShutDownStem, I decided to delve into the ugliness of racism in science and share what I learned.
Human Research Subjects
Due to disenfranchisement and undereducation, it has been easy to exploit African Americans in the name of science. An example of this is the Tuskegee Study of Untreated Syphilis in the Negro Male conducted by the Public Health Service and funded by the government. The motive of the study was to determine treatment strategies for syphilis. 600 black men enrolled in the study, 399 with syphilis, and the remainder without. The men were told they were being treated for an ailment, "bad blood." Instead, they received no treatment or diagnosis for their syphilis and the scientists observed their disease progression over many years. The study was terminated in 1972, and in 1974 a $10 million settlement was paid out to members of the study. But the damage was done. Men who participated in the study died, went blind, and succumbed to insanity. To this day, medical mistrust is propagated within the Black community due to the Tuskegee Study.
The Tuskegee Study does not stand alone in the narrative of Black people as research subjects. Dr. James Marion Sims, the "Father of Modern Gynecology," performed heinous experimental surgeries on black women slaves without anesthetic. Sims wasn't the best doctor, after killing his first two patients, he moved to Alabama and began tending to slaves. One of Sim's "patients" underwent 30 surgeries before he was able to repair her vaginal fistula. Sim's questionable experimentation is not only criticized by contemporary scientists but by many doctors of his time.
The scientific and medical communities owe a great deal of gratitude to Black Americans who enabled experimentation without their consent. Henrietta Lacks's story is well known due to a book and an HBO documentary detailing how her cells have contributed to billions of dollars' worth of biomedical science discoveries. Henrietta Lacks was a Black cervical cancer patient at John Hopkins University in the 1950s. A biopsy of her tumor was sent to a tissue culture lab, and scientists discovered Henrietta's cells were unique. They proliferated quickly and did not die like other cervical cancer samples. Henrietta's cells were named HeLa cells. They have been used to develop Polio and HPV vaccines and are widely utilized in biomedical research to this day. Knowledge about Henrietta's cells angered her sons. How could their mother's cells be bought and sold without their permission? Henrietta's family lived in poverty. Why had they seen no financial gain?
Think that racism in science is a thing of the past? Sadly, no. Today, clinical trials are often racially charged. A 2018 study found that health professionals were more likely to perform clinical trials that don't require consent, such as testing new CPR techniques and heart attack treatments, on Black patients. Also, minorities are frequently overlooked from potential life-saving cancer clinical trials.
Racial bias in research
The reference human genome blatantly favors Caucasian DNA sequences over other races. In 2001, George W. Bush halted the creation of new stem cell lines, limiting the ethnic diversity of stem cell research for eight years. In tech, face recognition software and self-driving cars perceive light skin with better accuracy. Science can absolutely be racially biased, and so can its funding. A major bias blunder that comes to mind in research funding is the inaction of the U.S. government during the AIDs epidemic. The disease, which mostly affected the gay and black communities, went largely ignored by the Regan administration. The federal government was slow to mount a response to the new virus, but when white children began contracting HIV through blood transfusions, financial support and prevention initiatives increased.
Racism in Academic Research
Racism in biomedical science is not exclusive to history. Black people and other minority groups are underrepresented in the sciences. Six percent of science Ph.D. holders are Black, a third of which hail from HBCUs. Academia, we can do better. We need to ask ourselves why this is. If we identify the routes of racism in science, we can fight it.
Firstly, we need more minority professors in higher education. I have earned a B.S., M.S., and am currently in my fourth year of my PhD, and I have yet to be taught by a Black science professor. Minority professors face a pay gap and are less likely to earn tenure. Secondly, higher education should cultivate a culture of inclusivity rather than striving to hit diversity quotas. It is not enough to get women and minorities into science; the academic environment must adapt to support their success. Lastly, if we want more scientists of color in America, we should provide the same quality of education to all children and erase the enormous disparities within our public-school system.
This post is by no means a comprehensive review of racism in STEM. As a multiracial woman who passes as white, I have not experienced discrimination due to my skin color. I cannot speak to the experiences of my Black friends and collogues, but I do stand with them. I believe racism is a beast that takes many forms. Regardless of your profession and field, you can stand against racism. I implore you to educate yourself and others about the reality of race in America, even if it is uncomfortable.
The barrier for science in higher education is high. The height of that barrier shrinks when you are privileged enough to have connections, early exposure to scientific opportunities, the ability to intern for free, and nepotism. As members of an esoteric practice, we can help shrink the barrier for the next generation. STEM education outreach programs, mentoring, and participating in science communication initiatives are all ways that you can help improve underrepresentation in science. Interested in STEM education outreach? There are many organizations devoted to increasing diversity in STEM:
Skype a Scientist
500 Women Scientists
National Society of Black Engineers (NBSE)
Can poop be used to help wildlife managers and biologists determine the health of a population?
The answer is, yes! That's right, poop. The taboo subject that still makes the child in us giggle. But how and why is it that fecal matter can matter to wildlife professionals? The fact is, we can learn a lot about an animal from its poop, from diet and immune health to even their stress levels. Here, we define stress as the complex physiological response to an ecological stressor (or stimuli) that can affect the internal stability of one's equilibrium. While acute - or short bursts - of stress can be ecologically beneficial to a species (such as the "fight or flight" response due to a predator), prolonged or chronic stress can have negative effects on an individual's ability to survive and reproduce. Since wildlife managers and biologists' goal is to have healthy wildlife populations, one can see how important the examination of stress can potentially be.
For example, let us examine Northern Bobwhite quail (Colinus virginianus). Bobwhite are considered a species of conservation importance to many wildlife managers and biologists due to decades of habitat loss and their popularity as a game species. Additionally, management efforts to help bobwhite populations and their habitats often help other species in that habitat, making bobwhite an essential species in many grassland communities.
Wildlife managers and biologists addressing bobwhite population survival and reproduction rates often observe them at a broad landscape level to determine the health of a specific population. While it is necessary in management to have these estimates, it does not necessarily address the underlying internal mechanism that may be driving these rates, such as stress.
How can we examine the stress response of a wild bobwhite population?
That's right, through their poop!
Traditionally, the most common way to examine stress in animals was through blood sampling. However, this can be very difficult in wild populations since one would first need to capture an individual, which may inherently increase its stress response. To overcome this limitation, several non-invasive sampling methods have become more prevalent in recent years, such as fecal sampling. This is noteworthy as it can allow managers and biologists to potentially address if there is a stress response that may be driving population effects, such as reduced population numbers.
However, before any wildlife manager or biologist can decide to use fecal sampling to examine stress in a population of their study species, it iscritical that they first validate — or prove — that the method works. Validation is required as several factors can influence stress levels in fecal samples. Some of thefactors that can influence these levels are:
How exactly does one go about validating the use of fecal sampling?
The goal of validation is to ensure that within every fecal sample of whatever species you are examining, you are able to detect biologically meaningful changes in their stress hormones. This is determined by two different tests:
It is crucial for managers and biologists to use both methods to validate the use of fecal sampling in their chosen species. It is especially important to biologically validate a method for sampling wild populations, as an event we believe may be stressful to a specific individual may not be. Additionally, managers and biologists dealing with wild populations are more concerned about how a species reacts to a natural stress event and not a pharmaceutical stress event.
How does one set up a validation study?
There are a number of ways one can set up a validation study. For example, to validate the use of fecal sampling in bobwhite, we took samples from 24 captive-reared bobwhite, of different ages and sexes, over seven days every four-hours across four different treatments. See treatment schedule below:
In order to determine if a stress response could be detected within the excessive amount of excrement (1,000 + samples) that were collected, each sample was extracted and run through radioimmunoassay (RIA) to determine stress hormone levels.
Were we able to validate the use of bobwhite fecal sampling?
Our results indicated that bobwhite had a stress response to the physiological validation, but not to the biological validation. The lack of a stress response from the biological treatment may have been due to:
To determine what may have caused the lack of a stress response during the biological validation, more validation is suggested before large-scale deployment of using fecal sampling as a method in bobwhite. These results reiterate the importance of using both physiological and biological methods to validate the use of fecal sampling in a species before deployment, as managers and biologists dealing with wild populations are concerned about how a species reacts to natural and not pharmaceutical stress events.
How could this method be potentially used?
As one can see, fecal matter can matter to wildlife professionals. For bobwhite, this method could be used as an additional tool to evaluate the health of a population and aid in conservation and management efforts. Integrating this technique with traditional population measurements (e.g. mortality and reproduction rates) could better inform managers and biologists of the physiological constraints imposed by different types of habitat or disturbances, leading to a deeper knowledge of the adaptive management needed for bobwhite.
Currently, there is still a large disconnect between wildlife management and disciplines, such as physiology. These fields should not be thought of as mutually exclusive, as each can provide unique information on the status and health of a population. Integrating different biological and ecological disciplines can allow for more progressive and effective wildlife management and conservation.
Want to learn more about this study? Read the research publication here:
Jessica L Mohlman, Kristen J Navara, Michael J Sheriff, Theron M Terhune, II, James A Martin, Validation of a non-invasive technique to quantify stress in northern bobwhite (Colinus virginianus), Conservation Physiology, Volume 8, Issue 1, 2020, coaa026, https://doi.org/10.1093/conphys/coaa026