A young Canadian pays tribute to her older sibling, a nursing student who exemplifies STEM in service to others during the uncertainty of the COVID-19 pandemic.
Published February 28, 2022
By Roger Torda
Kelsey and Kaitlyn Holmquist
Sometimes superheroes can be found close to home. For Kelsey Holmquist, the best example of a Super Hero of STEM is her older sister, who “was a first year nursing student when the world began to fall apart at the start of 2020.”
Kelsey, a Canadian high school student, submitted the story of her sister, Kaitlyn, in the “Super Heroes of STEM” essay competition, sponsored by Johnson & Johnson and The New York Academy of Sciences. Kelsey’s entry, one of 74 from around the world, came in first place.
Kelsey wrote that her sister is her superhero because, in the midst of the COVID-19 pandemic, nurses “are the ones ensuring that victims of COVID-19 are given dignity in their recovery or final moments; they are the ones ensuring that humanity is not lost when patients are regarded as little more than a statistic.”
Kelsey is now in grade 12 in Edmonton, Alberta. She’s been accepted into a Bachelor of Commerce program at MacEwan University in Edmonton, the same university where her sister is studying nursing. Kelsey plans to major in legal studies and then pursue a law degree. “I am not entirely sure which specific branch of law I will pursue,” Kelsey told us. “But as of right now I am very interested in exploring the way law applies to those with mental illness, and how we can ensure it is applied justly.”
“The Unnoticed Hero”
Kelsey tells a compelling story in her essay, “The Unnoticed Hero,” about her sister’s decision to study nursing while pressured to become a doctor instead. She had excelled in math and sciences throughout high school, and she faced “backlash from teachers and peers alike aimed to guilt her into choosing a stereotypically more challenging and professionally esteemed program….”
But as Kelsey points out, registered nurses perform important – if sometimes unacknowledged – work, exercising independent thinking, catching errors in physicians’ instructions, and carrying out “life saving measures for the critical first two minutes before a code team can arrive.” Kelsey also writes that nurses are also scientists:
The image of a scientist has expanded throughout the years to include women, but it still remains entrenched in the idea that it must involve a dedicated laboratory and research team. Nurses defy this stereotype. With each patient Holmquist interacts with, she must identify the best approach. Similar to a high stakes hypothesis, she must quickly formulate a plan of action well supported by evidence and research.
Kelsey adds about her sister’s work as a health care aide during her first year in nursing school:
With each and every interaction Holmquist has been involved in, an impact has been made. One smile can make the difference in having an elderly patient get out of bed, which is one step closer to walking, and one step closer to playing with one’s grandchildren. There are no limits to the ripple effect of conviviality.
Omicron, Mandates, Prevention, and a Pancoronavirus Vaccine: Leading scientists and public health experts share stories of their work amid global questions about the Omicron COVID-19 variant.
Published December 17, 2021
By Roger Torda
Discovery; The Story from Southern Africa
The discovery of the Omicron variant in Southern Africa started with what experts call a “spike gene dropout.”
“It was identified by colleagues in Botswana and by our sequencers in South Africa,” explained Penny Moore, PhD. “We’d just been through a third wave in South Africa that was driven by the Delta variant. And what happened was a local diagnostic laboratory…started noticing an uptick in infections, and associated with that, they noticed that the diagnostic test that we routinely use was not performing optimally.”
Moore, a virologist at the University of the Witwatersrand, described the fast-moving sequence of events during a webinar hosted by The New York Academy of Sciences (the Academy) on December 14. She explained that the PCR diagnostic test looked for four genetic markers typically found on the COVID-19 coronavirus. The tests in early November showed a reduced sensitivity; they were not detecting one of the targets. “That’s something we’d previously seen, with the Alpha variant in the UK,” Moore continued. “It’s called a spike gene drop out, or spike gene target failure.” It was a red flag.
“So that’s what led us in South Africa to start sequencing very deeply,” Moore explained. “We have a really excellent, next-generation genomics consortium here in South Africa, and they moved very rapidly to target those specific diagnostic samples that were behaving differently in the diagnostic tests. And that…showed us that we were dealing with a variant that had many, many more mutations that we were used to seeing in Delta.”
“Deluged in Data”
Moore, and her colleagues, soon were “being deluged in data” as they tried to answer questions from around the world about Omicron’s properties, including transmission rates, efficacy of vaccines, and whether the new strain causes more or less severe disease than others. As Moore earlier told Nature, “We’re flying at warp speed.”
Moore was one of four prominent scientists and public health officials participating in the webinar, What You Need to Know About Omicron and Future Coronavirus Variants. The others were: Rick Bright, PhD, who heads the Rockefeller Foundation’s Pandemic Prevention Institute; Dave A. Chokshi, MD, MSc, the Commissioner of the New York City Department of Health and Mental Hygiene; and Drew Weissman, MD, PhD, a pioneer in mRNA vaccine research at the University of Pennsylvania. The program was moderated by the Academy’s Melanie Brickman Borchard, PhD, MSc.
Moore’s work, and that of her colleagues, has drawn praise from around the world. “Timing and speed is absolutely essential for getting in front of an outbreak and for saving lives,” Bright told the panelists. “And I believe the world owes a debt of gratitude to the researchers in Southern Africa for immediately sharing this virus sequence with the global GISAID community, and for rapidly notifying their government and the word of this variant.” (GISAID is a global initiative that promotes the rapid sharing of genetic sequence and epidemiological data associated with human viruses.)
New York City; Fighting Back with Multiple Responses, Exactly One Year Later
“I want to start by just recognizing that we are on, precisely, the one year anniversary of our vaccination campaign,” said Chokshi. “It was December 14 of last year when the first person in the United States, Sandra Lindsay, a nurse in Queens, was vaccinated.” The day of the webinar also marked an escalation in New York City’s measures to tamp down the pandemic. It was the first day of a vaccine mandate for children aged 5 to 11 who engage in indoor public activities.
“For New York City, we have about 160,000 children, five to 11, who are vaccinated with at least one dose so far,” Chokshi reported. “It’s a great start, but it’s only about a quarter of the total population.” He stressed that mask and vaccine mandates are only some of the tools at the city’s disposal: “We’re partnering with over 1,500 pediatrician offices. We’ve launched a school based vaccination clinic where we visited every single school that had children in that age range. And we have mobile vaccination units that are providing vaccination across the city.”
Yearning for Social Connection
Chokshi said the city would be working hard to support pediatric vaccination in the new year, including the vaccination of younger children, which he said he hoped would be approved in the first quarter. He also said that as a public health official and the father of a two-and-a-half year old daughter, he is closely following an early report out of South Africa of an increase in very young children hospitalized with COVID-19 infections.
While the Delta variant continues to circulate, and community spread of Omicron has begun in New York, Chokshi said he and his colleagues must address very human needs, as well as science.
“You know, as we are entering the holidays, people are yearning of the social connection that the holidays bring, particularly given the trials and tribulations that we’ve all been through over the past, almost two years,” Chokshi said. “And, I think as public health professionals, we have to recognize, that that is where our fellow New Yorkers, our fellow human beings, are. And so my job, and our job, is to provide the guidance and the tools to be able to facilitate people celebrating as safely as they possibly can.”
A Pancoronavirus Vaccine
Weissman, a pioneer in the development of a core technology that makes the mRNA vaccines possible, shared some background and a status report on his current efforts to create what he calls a “pancoronavirus variant vaccine”. “If you look at coronaviruses, there have been three epidemics in the past 20 years, Weissman said. “That tells us there will be more. And we can do what we did for COVID-19, which is rush and make a vaccine. But it still shuts down the world for a year and a half.” Weissman’s research focuses on another approach, creating a vaccine that prevents transmission of all coronaviruses and their variants.
Weisman said his lab’s challenge is to identify “conserved regions” of genetic sequences shared by all coronaviruses, and to direct the immune response against those targets. In the lab, Weissman said his vaccine has been effective against “all of the current variants that have appeared, and will likely work against any variants that appear in the future.” Plans are underway to begin clinical trials within about a year.
Vaccine Hesitancy
Moore described mistrust of vaccines in many communities in South Africa, including among people who work in hospitals who have a very high rate of exposure to Sars-CoV-2. “I think the barriers are in many cases the same barriers that have been faced across the rest of the world,” she said.
“There is a huge feeling of fear and helplessness in many of those communities and a lot of suspicion around vaccination…[T]here’s much talk in South Africa about the speed at which these vaccines have been developed. It’s something that we, as scientists, need to address very urgently. We need to explain that it may look like these vaccines have been develop really quickly, but it’s not true. You know, this comes out of decades and decades [of research]”
Concurrent Clinical Trials
Weissman spoke to the same issue:
“I joke with people about this because had we taken two years or three years to develop the vaccine, they would’ve yelled at us that we were too slow. What people have to understand is that RNA vaccines have been studied for 25 years. They’ve been in clinical trials for almost 20 years. This is not brand new technology,” he said.
“The nucleoside modified mRNA LMPs [lipid mRNA particles] that we’ve developed, they’ve been in clinical trials for over five years before COVID 19 hit. So even this exact platform isn’t new technology. What people have to understand is that no corners were cut in its development. What happened is the researchers, the pharmaceutical companies, the FDA, all got together and said, ‘how can we do these studies as fast as possible?’”
The answer, Weissman said, was to conduct Phase 1, 2, and 3 clinical trials concurrently, rather than serially, which would have taken several years. “So there were no corners cut,” Weissman added. “More people were studied for COVID 19 than just about any other vaccine. It was done quickly because we have an emergency.”
Testing, Testing, and Testing
Bright, who heads the Pandemic Prevention Institute at the Rockefeller Foundation, told the Academy audience that the emergency of Omicron could prompt necessary global, coordinated action—especially the expansion of testing—to control the pandemic.
“This virus has now taken hold of the human population,” Bright said, adding:
It is not going to go away on its own. We need to fight it with every tool that we have, vaccines, therapeutics, high quality masks, ventilation, air filtration, and implementing a robust testing strategy that can trigger effective contact tracing and rapid access to therapeutics. The question now for, for us, for me, is whether Omicron will remind the world of the urgency we face and drive us to real collaborative action.
The four experts all agreed a heightened focus on healthcare equity is necessary to control the pandemic. “Vaccine inequity is prolonging the COVID-19 pandemic and it’s jeopardizing all the progress that we’ve made to date,” Bright said, pointing out that people who are unvaccinated remain significantly more likely to get sick from COVID-19, to pass it on to others, and to facilitate the emergence of new variants.
Equity: An Important Factor
Chokshi said equity has been an important focus of efforts in New York City, especially in lowering barriers to access. This means bringing vaccines “into people’s communities, into their neighborhoods.” He cited as examples: “Partnering with federally-qualified health centers. Moving to a decentralized approach where we use mobile sites, and also using in-home vaccination which is now available to anyone 12 and up across New York City.”
Another part of New York City’s efforts, Chokshi said, is building trust:
“We worked on building vaccine confidence with our partners across New York City, knowing that government is one messenger, but that often it is not the most trusted messenger within communities. So we are partnering with faith leaders and community based organizations to build vaccine confidence.”
The Mission of the Academy
An important point that emerged in the December 14 discussion aligns closely with the mission of the Academy, that while science plays a central role in the global response to the pandemic, scientists must partner with members of many other communities, and with experts from many disciplines.
“We have to also realize that science alone can’t keep us safe,” Bright said. “We need to ensure that governments and companies and communities, and even individuals such as ourselves, are working together. We’re sharing information, we’re making decisions based on science…to stop this outbreak.”
This type of collaborative effort is a goal of an important new Academy initiative, the International Science Reserve (ISR). The project aims to mobilize scientists and critical resources in the face of future global crises, whether a new pandemic, a cyber attack, flooding, or a massive wildfire.
The Academy’s program on the Omicron variant was just the latest in a broad series starting early last year, all designed to help meet the need for unbiased, scientific information on Sar-CoV-2. Next in line is a symposium on March 30 and March 31, The Future of Vaccinology. The program will feature speakers from the Bill and Melinda Gates Research Institute, Pfizer, Novavax, and the Human Vaccines Project.
The Blavatnik Awards for Young Scientists in Israel is one of the largest prizes ever created for early-career researchers in Israel. Given annually to three outstanding, early-career faculty from Israeli universities in three categories—Life Sciences, Physical Sciences & Engineering, and Chemistry—the awards recognize extraordinary scientific achievements and promote excellence, originality, and innovation.
On August 2, 2021, the New York Academy of Sciences celebrated the 2020 and 2021 Laureates at the Israel Academy of Sciences and Humanities in Jerusalem, Israel. The multidisciplinary symposium, chaired by Israel Prize winners Adi Kimchi and Mordechai (Moti) Segev, featured a series of lectures on everything from a new class of RNA to self-assembling nanomaterials.
In this eBriefing, you’ll learn:
The secret life of bats, and how the brain shapes animal behavior
How genetic information in unchartered areas of the human genome—known as long noncoding RNA—could be used to develop treatments for cancer, brain injury, and epilepsy
Creative ways of generating light, X-rays, and other types of radiation for practical applications such as medical imaging and security scanners
The intricate choreography of protein assembly within cells, and how this dance may go awry in disease
Speakers
Yossi Yovel, PhD Tel Aviv University
Igor Ulitsky, PhD Weizmann Institute of Science
Emmanuel Levy, PhD Weizmann Institute of Science
Ido Kaminer, PhD Israel Institute of Technology
Life Sciences of Tomorrow
Speakers
Yossi Yovel, PhD Tel Aviv University
Igor Ulitsky, PhD Weizmann Institute of Science
From Bat Brains to Navigating Robots
Yossi Yovel, PhD, Tel Aviv University
In this presentation, Yossi Yovel describes his studies on bats and their use of echolocation to perceive and navigate through the world. To monitor bats behaving in their natural environment, he has developed miniaturized trackers—the smallest in the world—capable of simultaneously detecting location, ultrasonic sounds, movement, heart rate, brain activity, and body temperature changes.
By attaching these small sensors to many individual bats, Yovel is able to monitor large groups of free-flying bats—a task which would be almost impossible in other mammals. His current and future studies include applying bat echolocation theory to engineering acoustic control of autonomous vehicles.
Further Readings
Yovel
Moreno, K. R., Weinberg, M., Harten, L., Salinas Ramos, V. B., Herrera M, L. G., Czirják, G. Á., & Yovel, Y.
Igor Ulitsky outlines his investigation of the biology of a subtype of genetic material—long non-coding RNA (lncRNA)—an enigmatic class of RNA molecules. Similar to other classes of RNA molecules, lncRNAs are transcribed from DNA and have a single-strand structure; however, lncRNAs do not encode proteins. Even though non-coding regions of the genome comprise over 99% of our genetic material, little is actually known about how these regions function.
Ulitsky’s work has shown dynamic expression patterns across tissues and developmental stages, which appear to utilize diverse mechanisms of action that depend on their sub-cellular positions. These discoveries have unlocked the potential of using lncRNAs as both therapeutic agents and targets with promising leads for the treatment of diseases such as cancer, brain injury, and epilepsy.
Further Readings
Ulitsky
H. Hezroni, D. Koppstein, M.G. Schwartz, A. Avrutin, D.P. Bartel, I. Ulitsky.
Chemistry and Physical Sciences & Engineering of Tomorrow
Speakers
Emmanuel Levy, PhD Weizmann Institute of Science
Ido Kaminer, PhD Israel Institute of Technology
Playing LEGO with Proteins: Principles of Protein Assembly in Cells
Emmanuel Levy, PhD, Weizmann Institute of Science
In this presentation, Emmanuel Levy describes how defects in protein self-organization can lead to disease, and how protein self-organization can be exploited to create novel biomaterials. Levy has amassed a database of protein structural information that helps him to predict, browse, and curate the structural features—charged portions, hydrophobic and hydrophilic pockets, and point mutations—within a protein that govern the formation of quaternary structures. By combining this computational approach with experimental data Levy is able to uncover new mechanisms by which proteins operate within cells.
Further Readings
Levy
H. Garcia-Seisdedos, C. Empereur-Mot, N. Elad, E.D. Levy.
M. Meurer, Y. Duan, E. Sass, I. Kats, K. Herbst, B.C. Buchmuller, V. Dederer, F. Huber, D. Kirrmaier, M. Stefl, K. Van Laer, T.P. Dick, M.K. Lemberg, A. Khmelinskii, E.D. Levy, M. Knop.
Shining Light on the Quantum World with Ultrafast Electron Microscopy
Ido Kaminer, PhD, Israel Institute of Technology
Ido Kaminer discusses his research on light-matter interaction that spans a wide spectrum from fundamental physics to particle applications. Part of his presentation addressed the long-standing question in quantum theory over the predictability of motions quantum particles. He also demonstrated the first example of using free electrons to probe the motion of photons inside materials. Finally, he talked about the potential applications of tunable X-rays generated from the compact equipment in his lab, for biomedical imaging and other applications.
Further Readings
Kaminer
R. Dahan, S. Nehemia, M. Shentcis, et al., I. Kaminer.
This Year’s Blavatnik National Awards for Young Scientists Laureate in the Life Sciences is connecting the activity of cells and synapses to emotions and social behavior
Published October 21, 2021
By Roger Torda
Neuroscientist Kay Tye has challenged orthodoxy in her field by studying the connection between the brain and the mind. The work has led to breakthroughs in basic science. It also points to new approaches to mental illness, with significant potential impact.
Tye is a professor in the Systems Neurobiology Laboratory at the Salk Institute for Biological Studies. She and her research team work to identify the neural mechanism of emotional and social processing, in health and disease. Tye explained to the New York Academy of Sciences why this work is so important.
Impacts on Mental Health
“Mental health disorders have a prevalence of one in two. This is half the population. If we could understand how the brain gives rise to the mind, we could de-stigmatize mental health, and everyone would go and get the treatment that they need,” she says.
Current therapies for mental disorders are developed by trial-and-error, with drugs that have broad ranges of effects. Tye envisions a much different approach, with treatments that target specific mechanisms in the brain.
“Our insights could revolutionize our approach to mental health treatments, supporting individualized therapies that would be effective for everyone and have the precision to be free of side effects,” she says.
Tye is the daughter of two scientists—a biologist and a physicist—who met while travelling to the U.S. from Hong Kong to pursue their educations. From a young age, Tye says she was fascinated by subjective experiences, foreshadowing her studies on the connection between brain and mind.
“How do I feel the way I feel?” Tye recalls wondering as a child. “How can two people listen to the same song and one person loves it and one person hates it? What are emotions?”
Tye with her children
Tye went to MIT for her undergraduate degree and received her Ph.D. from the University of California, San Francisco. After a postdoctoral fellowship at Stanford, she opened her lab as an assistant professor at MIT in 2012. In 2019, she moved across the country again, to the Salk Institute.
As Tye gained confidence as a young scientist, she took on a difficult professional challenge as she sought to examine questions that had not traditionally been the purview of her field.
“As a neuroscientist, I’m often told I am not allowed to study how internal states like anxiety, or craving, or loneliness are represented by the brain,” she recalled in a TED Talk. “And so, I decided to set out and do exactly that.”
Research in Optogenetics
In her research, Tye uses technology called “optogenetics,” which transfers the light sensitivity of certain proteins found in some algae to specific neurons in the brains of lab animals. Researchers can then use light to control signaling by the neuron, and they can establish links between the neuron and specific behavior. Tye developed an approach using this tool called “projection-specific optogenetic manipulation.”
“This permits scientists to dissect the tangled mess of wires that is our brains to understand where each wire goes and what each wire does,” Tye said.
Kay Tye in the lab
Tye’s postdoctoral training was in the Stanford University lab of Karl Deisseroth, who had recently developed optogenetics. Many young neuroscientists wanted to be among the first to use optogenetics, and Tye was eager to use it to study behavior and emotion. Tye recalled that period.
“It was a very exciting time in neuroscience, and in 2009 I already felt like I had come late to the party, and knew I needed to push the field forward to make a new contribution,” Tye says. “I worked absurdly hard during my postdoc, fueled by the rapidly changing landscape of neuroscience, and feel like I did five years of work in that two-year period.”
Analyzing Neural Circuits
Tye’s research program initially focused on the neural circuits that process emotional valence, the degree to which the brain assigns positive or negative value to certain sensory information. Her lab has analyzed the neural circuits controlling valence processing in psychiatric and substance abuse disorders.
This work includes the discovery of a group of neurons connecting the cerebral cortex to the brainstem that can serve as a biomarker to predict whether an animal will develop compulsive alcohol drinking behavior. Recent research has focused on neurons activated when animals experience social isolation and enter “loneliness-like” states.
Kay Tye in the lab
Tye and her research team are also exploring how the brain represents “social homeostasis”— a new field of research which seeks to understand how individuals know their place within a social group and identify optimal amounts of social contact.
Kay Tye and her lab team
Pushing Boundaries in Her Field
Even after considerable success in her field, Tye says she still feels as though she is pushing boundaries of her discipline. In doing so, she is continuing to bring neuroscience rigor to the study of feelings and emotions. Referring to her recent work, Tye said:
We faced a lot of pushback with this line of research, just because “loneliness” isn’t a word that has been used in neuroscience until now. These types of processes, these psychological constructs didn’t belong in what people considered to be hardcore neuroscience.
We are now bringing rigorous neuroscience approaches to ideas that were purely conceptual before. And so we’re being quantitative. We are being mechanistic. We are creating biologically grounded, predictive dynamical models for these nebulous ideas like “feelings” and “emotions.” And this is something that I find extremely gratifying.
Evidence is mounting that psychedelics can be effective in treating patients experiencing depression, anxiety, addiction, and other mental health conditions. Therapy sessions in clinical trials can be very intense experiences, but volunteers are carefully supported and monitored closely.
Published August 12, 2021
By Roger Torda
What is it like to take psilocybin in a clinical trial? Roland Griffiths, PhD, a researcher who focuses on the effects of mood-altering drugs, recently described the course of a patient’s clinical trial experience with psilocybin, which is the active ingredient of psychedelic mushrooms. Speaking during a New York Academy of Sciences webinar, Dr. Griffiths explained that volunteers must first meet certain criteria. The experience can be intense, and researchers screen out people with certain psychological disorders. Scientists and therapists also look for people with whom they can establish a bond of trust, which can be especially important since the drug can bring about temporary disorientation or anxiety.
Dr. Griffiths is a professor of psychiatry and neuroscience at Johns Hopkins University School of Medicine and Director of the Center for Psychedelic and Consciousness Research. His studies include trials to evaluate the use of psilocybin for treatment of psychological distress in cancer patients, cigarette addiction, and major depression. The sessions are similar regardless of the therapeutic goal, but planning and follow up techniques vary depending on the psychological condition being addressed.
Therapy Requires Careful Execution
In all cases, the therapy takes careful execution. During the experience, volunteers are never left alone; two clinicians or therapists are always standing by. The day of drug treatment is long. And the dose of psilocybin is large. During the experience, volunteers are never left alone; two clinicians or therapists are always standing by.
Dr. Griffiths said eye shades and music help people turn their attention inward, and help them avoid being distracted by therapists who are in the room to monitor the process. This very inward-focus with psilocybin is different than therapy with some other psychedelics. In trials with MDMA, which is commonly known as Ecstasy, volunteers usually are more talkative while under the influence of the drug.
Sessions follow the treatment with psilocybin, when therapists help patients make sense of the experience.
Experiences can vary, but patients often exhibit emotionality and report visualizations and feelings of deep connection with “others”, including the divine. Dr. Griffiths said patients often rate the experiences as among the most personally meaningful of their lifetime.
While there are plenty of mysteries about the immediate impact of these drugs and their effects on consciousness, scientists are learning more about changes they bring about in brain chemistry. Scientists are also developing theories about how the drugs may lead to long-term changes and benefit, which volunteers report in many studies.
Scientists understand some of the short-term changes in the brain brought about by psychedelics. Many mysteries remain, however, about how the chemicals can bring persistent effects and may help treat psychological disorders such as PTSD.
Published August 12, 2021
By Roger Torda
hallucinogenic mushrooms close-up growing group psychedelic legally golden teacher psilocybe cubensis
Studies are showing psychedelics can be effective in treating depression and other psychological conditions. Results from a recent Phase 3 clinical trial, for example, show MDMA—often known as Ecstasy—can effectively treat Post Traumatic Stress Disorder (PTSD). Researchers and clinicians are excited about the results, for psychedelics may offer a new therapeutic avenue for several psychiatric disorders that have been difficult to treat.
But how do psychedelics work? Their long-term effects remain something of a mystery. Our knowledge is growing, however, about the short-term changes they bring about in our brains.
David E. Nichols, PhD, who is president and co-founder of the Hefftner Research Institute, explained during a webinar hosted by The New York Academy of Sciences (the Academy) that drugs known as “classical psychedelics”—including psilocybin, DMT, LSD, and mescaline—mimic serotonin, leading to changes in the dynamics of brain function.
Studies using brain imaging have shed light on how this activation of HT2 receptors impact a network of connections across the entire brain. Scientists don’t know how this leads to therapeutic efficacy, but research led by a group at Imperial College London suggests there may be something of a “reset” of key brain circuits that play a role in depression.
Roland Griffiths, PhD
Roland Griffiths, PhD, of the Johns Hopkins University School of Medicine, also spoke at the symposium. He explained that the immediate effects of psilocybin in the brain subside quickly, but some changes persist, even though it remains something of a mystery how this happens.
There is evidence to suggest the classical psychedelics, while creating connections across the brain, decrease organized activity in a something scientists call the “default mode network.” These changes may lead to a temporary weakening in our sense of ego or “self”, which may explain why the drugs seem to promote a heightened sense of connection with “others.”
Additional research suggests the drugs may affect how the brain uses new information to affect prior beliefs. The brain uses these “priors” to make predictions. New sensory data are normally used to update and correct the underlying beliefs. Psychedelics may interrupt this process, leading to changes in how an individual perceives the world.
Much research lies ahead, and Dr. Griffiths says scientists are humbled by what remains unknown about these processes.
During the webinar, Dr. Griffiths and Rachel Yehuda, PhD, of the Icahn School of Medicine, also took viewers behind-the-scenes of clinical trials with psychedelics.
Although advances made in health and safety have more than doubled life expectancy throughout much of the world since 1900, it hasn’t been without consequence. Disease, disability, and frailty have all impacted the quality of life associated with these later years. This unfortunate reality was recently illuminated by the COVID-19 pandemic, which severely affected this population, likely due to physiological changes and preexisting conditions. Fortunately, a primary goal of geroscience researchers is to attenuate age-related health issues so that older people not only enjoy an improved quality of life, but also maintain the resilience to survive severe diseases and infections.
While it’s irrefutable that we cannot avoid aging, it’s no longer within the realm of science fiction for us to temper and even reverse the aging process. On May 19, 2021, the New York Academy of Sciences hosted a virtual symposium that brought together geroscience experts spanning various disciplines, including genetics, endocrinology, gerontology, clinical psychology, and more. Speakers discussed targeting the key hallmarks of aging, developing biomarkers for geriatric therapies, and translating findings that extend healthspan and lifespan to the clinic.
Symposium Highlights
The Target Aging with Metformin study uses the FDA approved anti-diabetic metformin, which targets the hallmarks of aging, to investigate the prevention of age-related diseases.
Precluding the age-associated decline of chaperon-mediated autophagy restrains the aggregating effects of Alzheimer’s disease and extends lifespan in murine models.
Lower IGF-1 levels in older adults are associated with decreased cognitive impairment, age-related diseases, and mortality.
Epigenetic clocks can be applied to study biological aging differences, with accelerated epigenetic aging correlating with the prevalence and incidence of morbidity and mortality.
The metabolome is a powerful locus of opportunity to bridge the gap between genotype and age.
Alternative splicing is upregulated in response to declining mitochondrial function and increasing age.
Senescent cells upregulate pro-survival pathways, and their elimination alleviates diverse age-related conditions.
The mitochondrial-derived peptides humanin and MOTS-c are associated with increased longevity in animal models and humans.
Speakers
Nir Barzilai, MD Albert Einstein College of Medicine
Ana Maria Cuervo, MD, PhD Albert Einstein College of Medicine
Sofiya Milman, MD Albert Einstein College of Medicine
Morgan Levine, PhD Yale School of Medicine
Daniel Promislow, PhD University of Washington
Luigi Ferrucci, MD, PhD National Institute on Aging, National Institutes of Health
James Kirkland, MD, PhD Mayo Clinic
Pinchas Cohen, MD USC Leonard Davis School of Gerontology
Targetable Aging Processes
Speakers
Nir Barzilai, MD Albert Einstein College of Medicine
Ana Maria Cuervo, MD, PhD Albert Einstein College of Medicine
Keynote: Age Later: Translational Geroscience
Aging is the strongest risk factor for all age-related diseases, with diverse maladies accumulating during the later years of life. Hence, to abate or avert the relevant disorders, it’s critical to target the central driver—aging itself. Physician Nir Barzilai, the founding director of the Institute for Aging Research, investigates the genetics of longevity by studying centenarians and their offspring, interrogating the hypothesis that these individuals have genes that prolong aging and protect against age-related diseases.
Using Slow Off-Rate Modified Aptamer, Barzilai’s team assessed 5,000 proteins in a population of 1,000 individuals between the ages of 65-95, a period during which aging accelerates. Results demonstrated a significant change in the level of hundreds of proteins as a function of age. Among the top hits were proteins from collagen breakdown of tissue and cellular products, highlighting the pivotal role this process plays in aging, and suggesting that deterring disintegration may be a universal biomarker for geroprotection.
Metformin, a long-standing FDA approved anti-diabetic, targets the complement of aging indications.
A predominant challenge to translating advances made in geroscience from animal models to humans is the FDA, which currently doesn’t consider aging a disease indication or preventable condition. Barzilai and others are utilizing metformin, an FDA-approved anti-diabetic, to refute this contention. Various groups have shown that metformin has substantial effects on human healthspan, including delaying type-2 diabetes mellitus (T2DM). In this patient subset, metformin also impedes cardiovascular disease, cognitive decline, and Alzheimer’s and is associated with decreased cancer incidence, with population effects approaching 30% in all cases.
Barzilai’s team designed the Target Aging with Metformin, or TAME, study to investigate whether or not there’s a shift in the timeline of disease occurrence between a cohort receiving metformin versus a control cohort. Various biomarkers of aging and age-related diseases will be used to provide convergent evidence of broad, age-related effects, while also establishing a resource for innovation and discovery of emergent biomarkers.
“The most important thing for us is to develop biomarkers that will change when we use a gerotherapuetic,” Barzilai asserted, as this will expedite therapeutic prospects.
Targeting Selective Autophagy in Aging and Age-related Diseases
Physician-scientist Ana Maria Cuervo’s research seeks to understand the molecular basis of autophagy dysfunction with age and the contribution of defects in this cellular pathway to diseases such as neurodegeneration, metabolic disorders, and cancer. Autophagy belongs to the proteostasis network, which regulates protein content and quality control.
Chaperon-mediated autophagy (CMA) is a subset of the mammalian autophagy program that directly targets proteins to the lysosome for degradation. CMA has been shown to decrease with age in human and animal models. Cuervo’s lab developed a fluorescent murine reporter construct to visualize CMA and track the kinetics of its activity in different organs.
Blocking this pathway in neurons resulted in the aggregation of proteins like α-synuclein (α-syn), tau, and others that are causal in Alzheimer’s Disease (AD). Additionally, CMA reporter mice crossed with a mouse model of AD revealed that CMA activity dramatically decreases in the neurons of AD mice.
Leveraging these findings, Cuervo’s group generated a mouse model to restore CMA activity conditionally. Mice with preserved CMA exhibited an extended median and maximal lifespan compared to controls. Evaluation of the proteostasis network in mice with and without CMA restoration revealed major changes in the proteome. Mice in which CMA was preserved more closely resembled younger animals than their age-matched controls.
“By acting in one of these pathways, we can have an impact in the other hallmarks of aging… because of this interconnection among [them],” Cuervo emphasized.
A compound to selectively activate CMA was developed and tested in an AD model, with results illustrating a reduction in tau pathology and microglial activation in the presence of this agent.
Sofiya Milman, MD Albert Einstein College of Medicine
Morgan Levine, PhD Yale School of Medicine
Translational Geroscience: Role of IGF-1 in Human Healthspan and Lifespan
Physician Sofiya Milman conducts translational research to uncover the genomic mechanisms regulating the endocrine and metabolic pathways involved in age-related conditions like diabetes, cardiovascular disorders, and Alzheimer’s.
“The goal of geroscience is really to extend healthspan, and not necessarily lifespan,” Milman opened. “What we’re really trying to do is to compress the period of morbidity.”
To discover the biological pathways that allow humans to live long, healthy lives, Milman’s team focused on IGF-1: a reduction of this factor has been consistently shown to extend healthspan and lifespan in models. IGF-1 levels peak during the teenage years before gradually declining. If the reduction of IGF-1 protects from aging, Milman reasoned that lower IGF-1 levels would delay aging and prevent age-related diseases.
Examining a cohort of centenarians expressing lower levels of IGF-1 revealed a 50% reduction in cognitive impairment compared to higher IGF-1 level controls. Genetic studies demonstrated that centenarians were enriched for rare mutations in the IGF-1 receptor that diminished signaling. Additionally, individuals 65+ with low IGF-1 had less cognitive impairment, and delayed onset of cognitive impairment, multi-morbidities, and mortality.
Milman’s team also addressed the link between IGF-1 and age. Younger individuals with lower levels of IGF-1 were at an increased risk for mortality and age-related diseases compared to older individuals, while higher levels of IGF-1 in older adults were associated with increased risk. This suggests that the IGF-1 network aligns with the concept of antagonistic pleiotropy, wherein a factor that’s beneficial to individuals when they’re younger may become harmful when they’re older. It’s advantageous to maintain functionality of proteostasis and resilience as an individual gets older, but IFG-1 inhibits programs involved in these processes.
“So from this, we think it would be wise to maintain IGF-1 levels in youth, but to reduce them with aging,” Milman concluded.
Epigenetic Biomarker of Aging for Lifespan and Healthspan
Biological age is defined by changes or alterations in a living system that renders it more vulnerable to failure and is behind the age-related increase in susceptibility to chronic diseases. Unlike chronological age, it is very difficult to measure because it’s unobservable.
Morgan Levine integrates theories and methods from statistical genetics, computational biology, and mathematical demography to develop biomarkers of aging for humans and animal models. Among this work are efforts to establish systems-level outcome measures of aging to facilitate evaluation for gero-protective interventions.
“There’s some disagreement on how we actually quantify [biological age],” Levine started. “But I would argue that it’s really important to try and do so, because quantifying [this] will really help us in a number of endeavors in the field.”
Levin’s lab is particularly interested in epigenetic aging, as aging drastically remodels the DNA methylation landscape, with widespread increases and decreases as a function of age.
Senescent cells and cells with disrupted energy production show accelerated epigenetic aging.
Epigenetic clocks estimate DNA methylation across the genome and combine supervised machine-learning approaches to develop predictors of biological age.
“We think people who have a predicted [epigenetic] age that’s younger than their chronological age should be actually aging slower, whereas the opposite is true for people that have a genetic age that is predicted higher,” said Levine.
Applying these measures to diseased states yielded several pertinent findings. For example, individuals who have pathologically diagnosed Alzheimer’s post-mortem show accelerated epigenetic aging in their brain relative to their chronological age. Tissue differences were also captured, revealing that tissues seem to age asynchronously, with highly proliferative tissues and tumor cells having accelerated aging compared to slower aging brain tissue.
Levine’s group also evaluated cellular senescence and energy disruption, with results revealing that near senescent, HRAS oncogene induced senescent, and replicative stress senescent cells have an acceleration in epigenetic age compared to early parental control cells. Additionally, deletion of mitochondrial DNA accelerated epigenetic aging, while caloric restriction in mice stalled their epigenetic clocks.
Luigi Ferrucci National Institute on Aging, National Institutes of Health
Metabolomics in the Search for Biomarkers and Mechanisms of Aging
Daniel Promislow applies metabolomics and systems biology approaches to study aging, with a focus on understanding the evolutionary and molecular traits that shape fitness in the natural human population. Although genome-wide association studies have allowed researchers to identify thousands of polymorphisms associated with the complement of measurable traits, including aging, the disparities identified explain less than half of 1% of the phenotypic variations.
Many genes interacting with each other ultimately influence phenotypes, and the biological distance between the two is astronomical. To bridge this gap, researchers use endophenotypes—from the epigenome, transcriptome, proteome, metabolome, and microbiome—along with various omics approaches. Promislow’s lab focuses on the metabolome, which integrates information from the environment and genotype to ultimately affect aging.
Promislow’s team utilizes translational metabolomics in various insect and animal models to understand and translate aging patterns to human populations. Applying this approach to Drosophila demonstrated that the metabolome could predict stress resistance, completely separating groups of sensitive or resistant flies to a metabolic stressor by principal component analysis. These effects could not be recapitulated with a whole fly genome sequence dataset. Evaluating response to diet restriction (DR) also revealed changes in metabolite levels with age. Among nearly 200 different inbred strains, roughly 75% showed a benefit to DR.
“Interestingly, the effect of specific genetic variants on the lifespan response was very weak,” Promislow began. “But we did find genes that were associated with metabolites, which were associated with the lifespan response, reinforcing this idea…that the metabolite profile can be a kind of bridge between genotype and phenotype.”
Promislow’s group also demonstrated that the metabolome could serve as a biological clock, revealing that shorter-lived genotypes appeared to have a higher biological age than expected for their chronological age.
Translational Potential of the Biology of Aging
As individuals age, the incidence of chronic disease increase, and disease progression quickens. Physician-scientist Luigi Ferrucci aims to interrogate the causal pathways that lead to progressive physical and cognitive decline in aging.
Cellular damage is accumulated during a person’s life, eventually reaching a pathology threshold that becomes clinically relevant when the damage presents as a disorder. Conventionally, the disease is often only addressed once it reaches this stage. The problem with this approach is that the present disease is often a marker of a more profound and invasive disorder to come.
“[Instead], we need to measure the underlying force that determines the emergence of diseases and their consequences,” Ferrucci argued.
By interfering with the basic mechanisms of aging to curtail it, broader effects of abating multiple chronic disorders can be achieved.
Cellular damage is accumulated over the course of an individual’s lifetime, with disease presenting once the clinical threshold for a given disorder is reached.
The rate of biological aging can be defined by the ratio of cellular damage accumulation to repair capacity. If the rate of damage accretion is fast, but the repair capacity is high, there won’t be an accumulation of damage, and aging will be slowed. However, when damage outpaces repair, aging accelerates.
Repair pathways require energy to operate effectively, and mitochondrial function declines dramatically with age. Ferrucci’s team discovered that this decline is associated with an upregulation of alternative splicing of mitochondrial proteins. Delving deeper into this mechanism, they applied gene set enrichment analysis to 5,325 RNAs with at least one splice variant significantly altered in response to changing mitochondrial function, as measured by AMPK and aging.
Among the top hits were GLUT4, VEGFA, IRS2, mTOR, PI3K, ULK1, ACC1, NRF2, and PGC1-α. Of note, the splice A variant of the topmost hit, VEGFA, appeared to be geronic, while the B variant appeared to be anti-geronic, with the ratio of these variants declining with age. Thus, alternative splicing is a method by which the body copes with energy decline due to mitochondrial dysfunction.
Translational Research for Healthspan and Lifespan
Speakers
Pat Furlong, Panelist Parent Project Muscular Distrophy
Roman J. Giger University of Michigan School of Medicine
Senolytics: The Path to Translation
Physician-scientist James Kirkland studies the impact of cellular aging, specifically senescence, on age-related dysfunction and chronic diseases to develop methods for removing these cells and attenuating their deleterious effects. Senescent cells accumulate with aging and diseases, eliminating cells around them due to their senescence-associated secretory phenotype (SASP), which 30%-70% of senescent cells exhibit under most conditions.
Kirkland’s team applied a bioinformatics-based approach to analyze SASP proteomic databases, revealing that pro-survival networks are upregulated, with diverse senescent cells relying on different pathways. Several agents, termed senolytics, were identified that could target multiple nodes of these cascades.
“We’re moving away from the one drug, one target, one disease approach here,” said Kirkland, “to try and use agents that have multiple targets, or combinations of agents, to go after networks, and to go after senescent cells by doing this, and thereby improve…multiple conditions.”
Dasatinib (D), a SRC kinase inhibitor, preferentially killed senescent preadipocytes, which relied on survival pathways that signal through this kinase. Quercetin (Q) eliminated senescent human umbilical endothelial cells (HUVECs), which partly act through the Bcl-2 family and others that this cell type is susceptible to.
In an in vivo experiment, combining Dasatinib with Quercetin (D+Q) cleared transplanted luciferase-expressing senescent preadipocytes from mice, explicitly targeting those cells with a SASP. A single dose of senolytics also alleviated radiation-induced gait disturbance in mice, with the effects persisting long-term. Bi-weekly dosing reduced physical dysfunction in older mice, as measured by parameters of maximal speed, including treadmill and hanging endurance, grip strength, and daily activity, with D+Q significantly increasing performance across the board.
Many conditions have now been shown to be alleviated by various senolytics in a range of mouse models, with D+Q delaying death from all causes, and increasing healthspan and median lifespan.
Keynote: Mitochondrial-derived Peptides (MDPs) and the Regulation of Aging Processes
The discovery of mitochondrial peptides (MDPs), encoded from small genes less than 100 codons in length, established the birth and advancement of the microprotein subfield. Physician Pinchas Cohen works to understand mitochondrial biology and characterize MDPs, exploiting findings to target aging. MDPs are secreted from cells and circulate within the body.
“Overall, they serve as protective factors, or hormones if you will, that act in the brain, the heart, the liver, the muscle, and other organs,” Cohen stated.
Among these MDPs, Cohen’s lab identified humanin, encoded from the 16S region of mtDNA, and MOTS-c, encoded from the 12S region.
Humanin has a strong protective effect on neurons and against atherosclerosis, mitigates the side effects of chemotherapy while enhancing its benefit, and is related to longevity in model organisms and humans. Cohen’s lab employs mitochondrial-wide association studies (MiWAS) to link the dysfunction of MDPs to disease. MiWAS identified a single-nucleotide polymorphism (SNPs) in the humanin gene (rs2854128) associated with reduced levels and cognitive decline in humans and mice. Supplementing humanin in mice carrying this SNP improved their cognition.
MOTS-c is a novel exercise mimetic that has potential utility in numerous age-related diseases. Mice on a high fat diet receiving MOTS-c had dramatically lower weight compared to controls. MOTS-c treatment also improved exercise tolerance and performance in middle-aged and old mice, with older mice displaying the most dramatic improvement.
MOTS-c levels are diminished in older mice, and supplementation of MOTS-c in this cohort increases both median and maximum lifespan compared to controls.
Cohen’s group also identified a link between a SNP in MOTS-c–K14Q–which nullifies MOTS-c activity and the risk of diabetes in males of the Asian population. Evaluating Japanese males from three cohorts revealed a 50% increase in the risk of diabetes for carriers, with almost double the risk seen exclusively in men who were sedentary. Like other MDPs, MOTS-c is reduced with age, and its administration to mice significantly extends lifespan.
“I think that everything we do in the aging field can be reduced to trying to simulate the beneficial effects of a healthy lifestyle, particularly diet…and exercise,” Cohen said. “We think that…mitochondria are the main source of action [here] by inducing the production of peptides such as MOTS-c, humanin, and others.”
In this pilot episode of the webinar series STEM Supremes: Conversations with Women in Science, the Academy’s Chief Scientific Officer, Dr. Brooke Grindlinger, interviewed the ‘queen of telomeres,’ Australian-American scientist Dr. Elizabeth Blackburn. Light years on from her early work sequencing the DNA of the pond scum protozoan Tetrahymena, Blackburn unraveled our understanding of the function of telomeres—the protective caps on the ends of chromosomes—and the role they play in aging and diseases such as cancer. She has pioneered a path for women scientists, and received the pinnacle of scientific achievement—the Nobel Prize—for unlocking secrets about how we age at a fundamental level. The conversation spanned Blackburn’s teenage fascinations with science, the anxieties of transitioning from student to independent investigator, cultural and gender barriers she navigated along the way, and what excites her on the horizon of aging research.
In this eBriefing, You’ll Learn:
How sleep quality, exercise, diet, and chronic stress impact the length of human telomeres and, in turn, our genetic heritage
Studies underway to understand the effect of severe stress on how individuals will respond, long-term, to COVID-19 vaccination
Tactics for managing the transition from PhD student to post-doctoral fellow, and from post-doc to junior faculty member
Tangible actions academic leaders can take to better support parents, particularly women, as they navigate the competing demands of family and a research career
Goals of the Lindau Declaration 2020 on Sustainable Cooperative Open Science
Moderator
Brooke Grindlinger, PhD The New York Academy of Sciences
In Conversation with Elizabeth Blackburn
Speaker
Elizabeth Blackburn University of California San Francisco
A full transcript of this conversation is available for download here.
Elizabeth Blackburn, PhD
University of California San Francisco
Dr. Blackburn earned her BSc and MSc degrees from the University of Melbourne, and her PhD from the University of Cambridge in England. She was a postdoctoral fellow in the Molecular and Cellular Biology Department at Yale University, and later joined the faculty at the University of California at Berkeley in the Department of Molecular Biology. She was Chair of the Department of Microbiology and Immunology at UC San Francisco, and later served as the first female president of the Salk Institute for Biological Sciences. Among her many career honors, Blackburn shared the 2009 Nobel Prize in Physiology or Medicine with collaborators Carol Greider and Jack Szostak for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. Blackburn is currently Professor Emerita, Biochemistry and Biophysics, UC San Francisco.
Brooke Grindlinger, PhD
New York Academy of Sciences
Read more about Dr. Grindlinger, the Academy’s Chief Scientific Officer, here.
“… we can use those learnings to prepare a playbook for the next pandemic.”
Published June 1, 2021
By Nicholas B. Dirks
Nicholas Dirks
When I was first in discussions in early 2020 to take over the leadership of The New York Academy of Sciences from the retiring Ellis Rubinstein, we could still go out to dinner, attend meetings in person, and enjoy concerts and the theater in closed and crowded spaces. Masks were for surgeons in operating theaters and researchers working in labs. We could still enjoy networking at well attended conferences, traveling through crowded airports and train stations, and planning vacations and holiday family gatherings. Although for years I had always mentioned a pandemic as a primary example of a global challenge that would know no borders and require global cooperation, I also knew that the last such pandemic had happened 100 years ago. I confess I had assumed I was being largely rhetorical.
What a difference a year makes.
Now, more than a year after the lockdowns began across the world and in the U.S., we are at last seeing the light at the end of the tunnel. It will still require a leap of faith to predict when life will return to the way it was in 2019, but significant progress has been made during the past several months.
As with most life-altering events, much can be learned when we can take a hard, practical look at what we did wrong, what we did right, and how, with better planning, we might have changed the course of history. And if we’re smart about it, we can use those learnings to prepare a playbook for the next pandemic.
Accept that pandemics and other global catastrophes are here to stay and plan for them.
Much of the spread of COVID-19 in the U.S. can be traced to the lack of a cohesive national response. Poor communications also did not help. Mixed messages from public officials and health experts created confusion, and worse, disbelief that COVID-19 should be taken seriously. “It’s no worse than the flu” was one such frequent comment, along with “something that only old people get,” and the “cure or shutdowns cannot be worse than the problem.” Then there are the “hoax” believers, and the bizarre “treatments”—all fueled by misinformation and conspiracy theories running rampant on social media. We can’t predict what new crises are on the horizon, but it is incumbent upon all government officials to have emergency response plans ready for quick implementation. Aside from the obvious—i.e., having the necessary medical equipment and public health protocols already in place—understanding that social behavior needs to be addressed is just as important as medical intervention in meeting the crisis.
Look at challenges as opportunities for new ideas to blossom.
Like many other organizations whose core business is based on live in-person events, The New York Academy of Sciences had to quickly pivot to virtual forums when we could no longer host actual gatherings. But we have found that our online webinars and virtual conferences have broad appeal to our members—especially those who do not live within easy access of our physical conference location in downtown New York. At some point the in-person meetings will resume, but we will continue to offer the virtual options that will open up our programs to all our members and others across the globe.
Shutdowns have had some benefits.
The past year has been disastrous for many of us, with death and disease rampant both in the U.S. and globally, and with devastating economic effects on certain sectors and populations. At the same time, we learned what we can do with the technological tools on our laptops and in our phones, seen clear skies in polluted cities from Delhi to Beijing, as well as nature venturing out into the deserted streets. The YouTube video of a kangaroo hopping down an empty street in Adelaide was especially poignant. Of course, we cannot keep things shut down forever—we not only miss our social life, we depend on it. But as we consider not just the effects of a pandemic but the escalating threat of climate change, the past 12 months have provided a clear view of how our natural environment can quickly improve if we give it room to do so. We don’t all agree on everything, but we do all live on the same planet — and as the late Carl Sagan pointed out — “Like it or not, for the moment the Earth is where we make our stand.” It will serve humanity well in the future if we could use the lessons of the last year to develop much bolder plans to take on the significant global and planetary challenges before us.
As we look forward to life returning to normal, it is worth remembering that despite all our scientific and technological progress, we were blindsided by a microscopic virus that was exacerbated by polarized politics, and a lack of public understanding and trust in science. It is also clear that the massive disparities of our society and our economy have been magnified by this public health crisis. Scientists must work not only with each other but with social scientists, humanists, and many others, as we seek to find more effective ways to translate our knowledge into enlightened public policy that takes on the full complexity of the human condition.
Fortunately, for the past 200-plus years, The New York Academy of Sciences has been committed to working to bring the best and brightest minds together to develop solutions for our global challenges. It’s a mission I’m proud to embrace as the Academy’s president and CEO.
Currently the FDA categorizes psychedelics such as LSD and psilocybin as Schedule I drugs, indicating that these substances have no medical value. Despite this classification, a resurgence of research in approved labs has demonstrated therapeutic benefits of psychedelics for treatment of psychiatric disorders.
Of note, a recent trial on the effects of MDMA-assisted therapy for post-traumatic stress disorder (PTSD) showed a reduction in the severity of patient symptoms compared with the placebo arm of the trial, providing hope for the future approval of MDMA for therapeutic use. The exciting findings from this study as well as and investigations into other psychedelics are instigating a paradigm shift for treatment-resistant psychiatric conditions, along with increased public interest and efforts to legalize psychedelics for medicinal use.
The New York Academy of Sciences hosted a panel discussion bringing together leading scientists in the fields of pharmacology, neuroscience, and psychiatry to discuss how psychedelics work in the brain to produce therapeutic benefits for depression and other mood disorders. The conversation commenced a description of the socio-political context of psychedelics research, spanning the rise of psychedelics research in the 1950s, restrictions in the 1960s, renewed interest in the 1990s, and present day clinical trials for patients with depression and various other mood disorders.
The program continued by spotlighting the different types of classical and non-traditional psychedelics that are currently being investigated (e.g., psilocybin, MDMA, and ketamine) and how they work to produce therapeutic effects. Panelists concluded the conversation by sharing insights into the use of psychedelics in treatment settings, including explaining the process of facilitated treatment and the role of the therapist/guide during the psychedelic experience (including preparatory therapy, peak effects, and integration).
In this eBriefing, you will learn:
The socio-political history of psychedelic research for human health
The difference between classic and non-traditional psychedelics
The effects of psychedelics on the brain and targets
The role of the hallucinogenic experience
The role of psychological support during the psychedelic experience
Psychedelics for the Treatment of Depression and Psychiatric Disorders
Moderator
John Krystal, MD Yale School of Medicine
Speakers
Roland Griffiths, PhD Johns Hopkins University School of Medicine
David E. Nichols, PhD Heffter Research Institute
Rachel Yehuda, PhD Icahn School of Medicine at Mt. Sinai
John Krystal, MD Yale School of Medicine
Dr. John Krystal is the Robert L. McNeil, Jr., Professor of Translational Research; Professor of Psychiatry, Neuroscience, and Psychology; and Chair of the Department of Psychiatry at the Yale University. He is also Chief of Psychiatry and Behavioral Health at Yale-New Haven Hospital. He is a graduate of the University of Chicago, Yale University School of Medicine, and the Yale Psychiatry Residency Training Program.
Dr. Krystal has published extensively on the neurobiology and treatment of schizophrenia, alcoholism, PTSD, and depression. Notably, his laboratory discovered the rapid antidepressant effects of ketamine in humans. He is the Director of the NIAAA Center for the Translational Neuroscience of Alcoholism and the Clinical Neuroscience Division of the VA National Center for PTSD. Dr. Krystal is a member of the U.S. National Academy of Medicine and a Fellow of the American Association for the Advancement of Science. Currently, he is co-director of the Neuroscience Forum of the U.S. National Academies of Sciences, Engineering, and Medicine; and editor of Biological Psychiatry (IF=12.1).
He has chaired the NIMH Board of Scientific Counselors and served on the national advisory councils for both NIMH and NIAAA. Also, he is past president of the American College of Neuropsychopharmacology (ACNP) and International College of Neuropsychopharmacology (CINP).
Roland Griffiths, PhD Johns Hopkins University School of Medicine
Roland Griffiths is Professor in the Departments of Psychiatry and Neurosciences and Director of the Center for Psychedelic and Consciousness Research at the Johns Hopkins University School of Medicine. His principal research focus in both clinical and preclinical laboratories has been on the behavioral and subjective effects of mood-altering drugs and he is author of over 400 scientific publications. He has conducted extensive research with sedative-hypnotics, caffeine, and novel mood-altering drugs.
About 20 years ago, he initiated a research program at Johns Hopkins investigating effects of the classic psychedelic substance psilocybin, the active component in “magic mushrooms.” Remarkably, many research participants rate their experience of psilocybin as among the most personally meaningful of their lives, and they attribute enduring positive changes in moods, attitudes and behavior months to years after the experience. Completed and ongoing studies include those in healthy volunteers, in beginning and long-term meditators, and in religious leaders.
Therapeutic studies with psilocybin include treatment of psychological distress in cancer patients, major depressive disorder, nicotine addiction, anorexia nervosa, and various other psychiatric disorders. Related studies of brain imaging and drug interactions are examining pharmacological and neural mechanisms of action. His research group has also conducted a series of survey studies characterizing various naturally-occurring and psychedelic-occasioned transformative experiences including mystical experiences, entity and God-encounter experiences, Near Death experiences, and experiences claimed to reduce depression, anxiety, and substance use disorders.
David E. Nichols, PhD Heffter Research Institute
David E. Nichols previously held the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology and in addition was a Distinguished Professor of Medicinal Chemistry and Molecular Pharmacology at the Purdue University College of Pharmacy. He was continuously funded by the NIH for nearly three decades and served on numerous government review panels. His two principal research areas focused on drugs that affect serotonin and dopamine transmission in the CNS.
He began medicinal chemistry research on hallucinogens in 1969 and has been internationally recognized as a top expert on the medicinal chemistry of psychedelics (hallucinogens). He has published more than 300 scientific articles, book chapters, and monographs. In 1993 he founded the Heffter Research Institute, which has supported and funded clinical research with psilocybin and led the so-called “renaissance in psychedelic research.”
Rachel Yehuda, PhD Icahn School of Medicine at Mt. Sinai
Rachel Yehuda, Ph.D. is the Director of the Center for the Study of Psychedelic Psychotherapy and Trauma, Vice Chair for Veterans Affairs for the Psychiatry Department and a Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai as well as the Director of Mental Health at the Bronx Veterans Affairs Medical Center and the Director of the Traumatic Stress Studies Division.
Throughout her career her research has focused on the study of the enduring effects of trauma exposure, particularly PTSD, as well as associations between biological and psychological measures. She has investigated novel treatment approaches for PTSD and the biological factors that may contribute to differing treatment outcomes for the purpose of developing personalized medicine strategies for treatment matching in PTSD. This work has resulted in an approved US patent for a PTSD blood test.
Recently, Dr. Yehuda’s laboratory has used advances in stem cell technology to examine PTSD gene expression networks in induced neurons. The Center for Psychedelic Psychotherapy and Trauma integrates sophisticated brain imaging and molecular neuroscience in PTSD with clinical trials using MDMA assisted psychotherapy and other related medicines. She has authored more than 450 published papers, chapters, and books in the field of trauma and resilience, focusing on topics such as PTSD prevention and treatment, molecular biomarkers of stress vulnerability and resilience, and intergenerational effects of trauma and PTSD.
