Elizabeth Sajdel-Sulkowska was simply three months previous when Nazi troopers set fireplace to her household’s residence within the midst of the Warsaw Rebellion of August 1944, because the Polish resistance tried to grab management of town from the Germans. When that revolt finally failed, town was razed, and there was no time to seize diapers and milk because the household rushed from the burning constructing. Sajdel-Sulkowska’s dad and mom have been taken to Dulag 121, a transitional camp from which they have been to be despatched to a focus camp. They escaped that destiny solely as a result of her mom gave the camp’s milkman her jewellery to ship a letter to Sajdel-Sulkowska’s godfather, who paid the Germans in cost to launch them.
Though her dad and mom’ lives have been spared, her father, a biology professor, died of most cancers three years later. When her mom, a chemist, obtained a job as head of a meals high quality laboratory in Łódź, she ultimately needed to place Elizabeth within the care of nuns within the countryside, 11 miles away. From ages six via 9, she lived with about 30 different half-orphans and orphans, with out working water or electrical energy or private consideration, taking an hour-long practice experience to see her mom on weekends.
It was a childhood, she says, of “great stress.”
So maybe it’s no accident that as an grownup, Sajdel-Sulkowska was drawn to the research of stress—whether or not attributable to burns, altered gravity, chemical pollution, or bacterial an infection—and its impact on mind growth. In the midst of her 57-year profession, she has printed greater than 100 papers, chronicling her analysis in cells, in animal fashions, and with postmortem human mind tissue. She has studied the interactions between neurons and the glial cells that defend and help them, the adjustments in RNA transcription throughout mind growth and in Alzheimer’s illness, and the function of the thyroid hormone in mind growth, and printed literature evaluations on the function of the intestine microbiome and gut-brain axis in autism and covid.
As a baby, Sajdel-Sulkowska would inform anybody who requested that when she grew up, she needed to be a professor like her father. At 10, she returned from the orphanage to reside together with her mom, who had remarried, and he or she ultimately attended an all-girls highschool in Łódź. When her metallurgist cousin Witold Vatha Kosicki, SM ’29, realized of her curiosity in science, he invited her to go to the US so she might interview at MIT, a college she’d by no means heard of. Getting accepted to Warsaw College’s extremely aggressive division of arithmetic and physics helped her qualify for a visa to the US—and satisfied MIT that she was certified to attend the Institute. After arriving within the US in 1962 and finishing a six-week English course (“I barely handed it,” she confesses), she began on the Institute within the spring semester of 1963.
At MIT, Sajdel-Sulkowska deliberate to check nuclear physics till she took a course on DNA and RNA with Gene Brown, a professor of biochemistry and a pioneer within the discipline of metabolism. The fabric was so new there wasn’t even a textbook. However Brown’s lecture on the invention of the double helix impressed her to modify to biology. “It was fascinating,” she says. “The lectures have been so unimaginable—I knew I wasn’t going again to physics.”
Sajdel-Sulkowska’s cousin had offered cash for her to attend MIT for one semester. “The remainder of it needed to be sort of patched,” she says. So she washed dishes within the chemistry division, plotted soil stress on graph paper within the mechanical engineering division, collected animal urine samples, and for one yr labored as an au pair.
Throughout most of her time at MIT, Sajdel-Sulkowska lived together with her mom, who had come together with her to the US and labored as a technician in a medical lab on Ames Avenue. They initially lived on Beacon Avenue in Boston, in a basement room with uncovered pipes and wires, sharing a rest room with different households. However her advisor, Margaret Freeman of the Russian research division, visited someday and was so appalled on the circumstances that she invited Sajdel-Sulkowska and her mom to remain at her residence in Belmont. Then, halfway via her undergraduate profession, she spent a yr in McCormick Corridor, which had opened in 1963.
Sajdel-Sulkowska’s time in McCormick was a “turning level,” she says. When she lived off campus, she studied and labored on her downside units alone and assumed everybody else was doing the identical. Her isolation was exacerbated by the language barrier, and he or she felt much more alone within the face of male friends brimming with confidence, family suggesting she swap to secretarial college, and an teacher who informed her, after a nasty expertise with a rat in an animal laboratory class, that MIT was not the place for her. At McCormick, she says, she realized that “not everyone is aware of every thing” and that “there are folks serving to you—that you simply don’t need to do all of it your self.”
Her first paper on stress was printed in 1969, 16 years after the double-helix construction of DNA was found. On the time, the discovering that stress might alter the physique at a mobile degree was a revelation.
Sajdel-Sulkowska began her profession at a time when there have been only a few ladies in science. Although MIT started formally accepting ladies in 1882, she was one in all solely two or three ladies incomes a bachelor’s diploma in biology in 1967; her total class of greater than 900 had solely 20 to 30 ladies.
Being a kind of few ladies was not straightforward. Within the 1960s and ’70s, when she continued at MIT for graduate college, the sector of biology had a tradition of what she calls “unchecked harassment.” There was no method to complain with out retribution. “That sort of tradition created intimidation,” she says. “In case you undergo incidents of harassment, you turn into extra vigilant.” Male colleagues needed to be handled as male colleagues, not as colleagues. Nonetheless, she says, there have been “quite a lot of useful folks.”
Lots of these useful folks have been these she encountered within the Margaret Cheney Room, a Constructing three sanctuary for feminine college students full with a bed room, bathe, and phone cubicles. “That was a haven,” she says—a spot the place she made lifelong mates. It was additionally there that she wrote her doctoral thesis—longhand, together with her husky, Amis, at her facet, over the course of three months. She would write for 3 hours, sleep for 20 minutes, and repeat.
Sajdel-Sulkowska earned an SM in diet and meals science (or, as she calls it, “eukaryotic biology in disguise”) and an ScD in the identical topic with a minor in neuroendocrinology. Her graduate work could be her first foray into the research of stress as she examined DNA-dependent RNA polymerase II, an enzyme that copies DNA into RNA, and its regulation by cortisol, the stress hormone. By means of research in rat liver cells after which, after a nudge from her committee, in reside rats, she discovered that there’s a physiological response to emphasize via regulation of RNA transcription. Her analysis confirmed that synthetic cortisol injected into rats altered the RNA polymerase enzymes that synthesize the RNA element of ribosomes. These ribosomes in flip synthesize the proteins that perform features within the cell.
Her first paper on this work was printed in 1969, 16 years after the doublehelix construction of DNA was found; a second paper adopted in 1971. On the time, the discovering that stress might alter the physique at a mobile degree was a revelation.
It was an exhilarating time to be learning biology, says Sajdel-Sulkowska; whereas she was engaged on her doctorate, researchers at MIT, Caltech, and the College of Wisconsin, Madison, found reverse transcriptase, the enzyme that copies RNA into DNA (the counterpart to the RNA polymerases she studied), for which they might later earn a Nobel Prize. “I used to be working within the laboratory, I used to be in a terrific group, issues have been occurring—it was thrilling!” she says.
Reflecting on her time at MIT, Sajdel-Sulkowska says she cherished the environment (“I preferred the truth that you can work late within the night”) and the power. The challenges she needed to overcome to succeed on the Institute have been price it, she says: “I needed to do it, and I did it.”
After incomes her ScD in 1972, she interviewed for a college place at Northwestern College and was supplied the job. However she had just lately met Adam Sulkowski, a psychiatrist and postdoctoral fellow, who had simply arrived from Poland through France on a visa sponsored by Boston College and couldn’t relocate. She returned to Boston, they married that October, and he or she grew to become a postdoctoral fellow at Brandeis, the place she continued to check RNA polymerase in yeast. Two years later, the primary of their 4 sons was born.
Sajdel-Sulkowska carved out a profession that was each broad and deep at a time when combining scientific work and motherhood was extraordinarily uncommon and lodging for US working moms virtually nonexistent. When her oldest son was born, in 1974, her three-month maternity depart was unpaid. After her second son arrived whereas she was finishing one other postdoc, at Shriners Burn Institute at Harvard Medical Faculty (HMS), the price of day care for 2 kids exceeded her wage. So with no day care, her husband watched the 2 boys within the morning, and he or she discovered herself beneath a “great quantity of stress.”
And at Shriners, stress was once more the topic of her work. In guinea pigs which have suffered extreme burns, she found, a rise in cortisol inhibits DNA synthesis within the thymus, which performs a key function in immune perform. Her analysis revealed that eradicating burned tissue as quickly as potential results in a sooner return to regular thymus perform and a sooner restoration from burns.
In 1980 she grew to become a lecturer within the HMS division of psychiatry with an appointment at McLean Hospital, and he or she was named an assistant professor six years later. Over the subsequent twenty years, she would work on a variety of matters, together with the connection between mercury and autism, the mechanisms of Alzheimer’s illness, and the function of the thyroid hormone in mind growth. She balanced work and motherhood with the assistance of her mom and her husband, who was supportive and happy with her. “The place there’s a will, there’s a approach,” she says.
In 1989, Sajdel-Sulkowska spent a sabbatical within the lab of Nobel laureate Walter Gilbert at Harvard, gaining expertise in cloning, sequencing, and polymerase chain response (PCR)—a time she sees as one other turning level in her profession. Within the Gilbert lab, which she describes as a big, vibrant group of younger and older scientists, everybody’s work and opinion mattered. “We often met as a gaggle and will freely talk about our experiments,” she says. The expertise gave her confidence. “At that time I felt that I might be able to begin one thing on my own,” she says.
As soon as again at HMS, she strove to create the identical kind of environment in her lab and commenced pursuing grants to fund extra impartial work. When inspiration struck for an particularly formidable analysis challenge a number of years later, in 1998, Sajdel-Sulkowska embraced the problem. She’d been watching Star Trek together with her sons when she got here up with the thought for an experiment analyzing the impact of one more sort of stress: altered gravity. In latest NASA mind analysis on pregnant rats on the house shuttle Columbia, greater than half of the rat pups had died. She wrote a grant proposal to work with NASA’s Ames Analysis Middle to check altered gravity’s influence on rats’ mind growth. For her research, she positioned pregnant rats in cages at completely different factors on a 24-foot centrifuge, exposing them and their growing pups to various ranges of greater-than-Earth gravity for 42 days, via being pregnant and lactation. Then she measured the size of time the rat pups have been in a position to keep on high of a motorized rotating cylinder (what’s often called a rotarod take a look at) and found that hypergravity decreased motor perform. Rat pups that developed at 1.65 occasions Earth gravity might solely keep on the spinning wheel for as little as 10 seconds earlier than falling off, whereas the pups that developed at Earth gravity have been in a position to keep on for nearly a minute.
Her analysis steered that this can be as a result of the upper gravity will increase oxidative stress (an extra accumulation of free radicals that may injury the physique’s cells) or suppresses thyroid exercise, an issue that she had beforehand discovered to lower the mass of the growing cerebellum.She additionally confirmed that hypergravity decreases the variety of a vital sort of neurons in that area of the mind, which is chargeable for motion, amongst different features.Curiously, she discovered that male growing brains have been extra delicate to hypergravity than their feminine counterparts. On the finish of the experiment, the cerebellums of the male pups have been visibly smaller than regular.
As her hypergravity analysis was underway, Sajdel-Sulkowska additionally examined the impact on mind growth of one other environmental stressor that had turn into pervasive: polychlorinated biphenyls, or PCBs, a gaggle of poisonous artificial chemical substances used so broadly from the 1930s via the 1970s that they contaminated the air, water, and soil. She subjected rat pups that had been uncovered to PCBs from earlier than start to rotarod checks and located that their efficiency decreased as nicely. So did the mass of their cerebellums, and as with hypergravity, the impact was better in males than in females.
In 2010 Sajdel-Sulkowska, who had misplaced her husband to most cancers in 2002, was devastated when her youngest son died on the age of 23 as he was recovering from an accident. Work would show to be a lifeline. She moved again to Poland, the place diving into new analysis “helped me survive,” she says. First as a visiting professor in veterinary drugs on the Warsaw College of Life Sciences after which educating and doing analysis on the Medical College of Warsaw, she had a chance to work with many younger scientists. Her analysis collaboration with Katarzyna Czarzasta, who’s now an assistant professor on the Medical College of Warsaw, was notably fruitful—and continues as we speak. “She is an excellent mentor,” says Czarzasta, who provides that she handled her college students as equals.
Whereas educating in Poland, Sajdel-Sulkowska encountered many college students who suffered from melancholy. “I additionally noticed nice stigma related to psychiatric problems in Poland, particularly with melancholy throughout being pregnant,” she says. That obtained her enthusiastic about latest analysis on the usage of probiotics—that are available within the grocery retailer—as a substitute remedy for melancholy. And that led to a number of initiatives on perinatal melancholy that she hoped would lay the groundwork for a research on probiotics as a remedy for it.
The variations in stress response between men and women are a minimum of partly as a result of intercourse hormones. Testosterone will increase cortisol ranges, so the stress response is larger in males.
In a single, she utilized power delicate stress to rats simply earlier than being pregnant to mannequin perinatal melancholy, which she verified by measuring cortisol ranges and time spent grooming. Then she studied their pups and documented damaging results on their neurodevelopment and cardiac growth. The consequences differed in female and male offspring, and the sex-dependent cardiovascular results in females endured as they aged, doubtlessly affecting the next era as nicely. The research added to the rising physique of analysis displaying that the influence of setting and conduct—also referred to as epigenetic results—will be handed alongside to offspring.
Previously, Sajdel-Sulkowska says, experimental work, together with analysis on melancholy, was carried out solely on males, in order that researchers wouldn’t have to manage for ladies’s month-to-month hormone fluctuations. However thanks partially to pioneering research like hers, scientists are starting to acknowledge the significance of learning the sexes individually.
The variations in stress response between men and women are a minimum of partly as a result of intercourse hormones, says Sajdel-Sulkowska. Testosterone will increase cortisol ranges, so the stress response is larger in males; the consequences of stressors on the thyroid hormone, too, are completely different. However past that, she factors out that every intercourse has completely different points in relation to well being normally: completely different microbiota, completely different illness dangers, and completely different illness progressions and mortality charges. Because of this, remedies for a lot of illnesses could must be tailor-made particularly for males or females to be efficient. (See “Melancholy is completely different for ladies. One-size-fits-all medicine aren’t serving to.”) And even as soon as each environmental elements and intercourse variations are thought of, particular person variations, corresponding to an individual’s distinctive microbiome, are more likely to matter too. Sajdel-Sulkowska foresees a day when synthetic intelligence will make it potential to correlate the variations in people’ microbiomes with illness, finally resulting in individualized probiotic remedies for quite a lot of circumstances—maybe together with melancholy.
Sajdel-Sulkowska would stay in Poland for a full decade, returning to the US in September of 2020. A yr later, after 35 years as an assistant professor, she was compelled to retire from HMS when Harvard didn’t renew her college appointment. Having targeted on analysis with out giving a lot thought to development, she was instantly with out a tutorial residence. In 2022, she joined the Nationwide Coalition of Unbiased Students (NCIS) so she might proceed her work with out being affiliated with a specific college.
Sajdel-Sulkowska by no means had the safety of a tenured place and estimates that over the course of her profession, her common wage was $35,000 a yr. (“I by no means realized that I might title my compensation,” she says.) However she was by no means in it for the cash; she was pushed by the work itself. And in her residence nation, she acquired a number of the recognition that eluded her at Harvard. Throughout her decade of analysis and educating in Poland, she was awarded the nation’s highest educational honor when she was named a Presidential Professor by Polish president Andrzej Duda.
Upon returning to the US throughout the pandemic, Sajdel-Sulkowska tackled a literature evaluation to search for connections between covid, the microbiome, and the gut-brain axis, the bodily and biochemical indicators that shuttle between the digestive system and the central nervous system (see sidebar). However the theme of stress continued to intrigue her; she printed a paper on maternal stress in rats in 2021 and has one other in progress. This latest analysis closes the circle opened together with her doctoral thesis at MIT, she says: “I did my PhD thesis on stress—and I’m ending my profession with [studying] stress.”
Sajdel-Sulkowska sees how her present work would possibly apply to her personal life. Her mom endured excessive stress throughout World Struggle II, and he or she skilled excessive stress herself as a baby born simply earlier than the Warsaw Rebellion. Now, she wonders how that may have an effect on her personal kids—in people, the epigenetic impact of stress is understood to stretch for a number of generations.
Her final yr in Poland, she and her oldest son mapped the routes her aunt and mom took after the home the place she was born was razed by the Nazis. They visited the transitional camp that her dad and mom have been taken to. And on her method to the presidential palace in 2016 to just accept her educational honor, she handed by the location of her dad and mom’ burned residence. She remembered telling folks she needed to develop as much as turn into a professor, like her father.
“Wow,” she thought. “What a protracted method to come and expertise that.”
Analysis snapshot
Highlights from Sajdel-Sulkowska’s lengthy and different analysis profession
Past her research of stress, Elizabeth Sajdel-Sulkowska has delved into many different areas all through her lengthy profession. Right here’s a sampling of what else she has studied:
The impact of thimerosal on mind growth
Individuals had lengthy speculated that thimerosal, a mercury-based preservative nonetheless utilized in small quantities in some vaccines and medicines, is likely to be linked to autism. Beginning in 2006, with help from two autism organizations, Sajdel-Sulkowska discovered that exposing rat pups to thimerosal throughout the perinatal interval ends in motor impairment, elevated oxidative stress within the cerebellum, and a lower in an enzyme referred to as deiodinase 2, which is concerned in regulation of the thyroid hormone—and that the consequences have been extra pronounced in males. postmortem human brains, she discovered that oxidative stress markers have been elevated within the cerebellum in folks with autism, and that their thyroid hormone ranges and thyroid-hormone-dependent gene expression have been disrupted as nicely. Nevertheless, she didn’t observe completely different mercury ranges in postmortem brains of individuals with and with out autism. Though the small quantity of thimerosal utilized in vaccines has not been implicated in autism, in 1999 public well being departments and the American Academy of Pediatrics beneficial limiting its use as a precautionary measure. Thimerosal has since been eradicated from almost all childhood vaccines and decreased or eradicated in different vaccines.
The influence of perinatal bacterial an infection on the growing mind
In 2008-’09, throughout a fellowship in Japan, she studied the impact of frequent perinatal infections on mind growth by exposing rats to a lipopolysaccharide, or LPS, a sort of molecule discovered within the outer membrane of sure micro organism. She discovered that, much like rats uncovered to thimerosal, LPS-exposed rats had elevated oxidative stress, a lower in deiodinase 2, a lower in thyroid hormone, and decreased gene expression within the cerebellum. Their motor studying, as measured by the rotarod take a look at, was additionally impaired.
The connection between covid, the microbiome, and the gut-brain axis
In the course of the pandemic, Sajdel-Sulkowska reviewed the printed literature on all three matters to search for connections. Others had discovered that the virus SARS-CoV-2 enters the physique by binding to the receptor for a human protein often called angiotensin-converting enzyme 2, or ACE2—a receptor discovered on cells within the lungs but in addition within the intestine, amongst different locations. And researchers had realized that the virus occupies and blocks websites via which some vitamins usually enter the intestine, resulting in a deficiency of these vitamins and decreased manufacturing of short-chain fatty acids for which they’re required. Sajdel-Sulkowska hypothesized that the deficiency in short-chain fatty acids, which lower irritation and in addition contribute to regular mind perform, could play a job within the “mind fog” and neuropsychiatric problems some covid sufferers expertise. These results, she predicts, might doubtlessly be combated with probiotics. She performed an identical literature evaluation of the connection between autism and the intestine microbiome.
