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Daniel Dunaief

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Stony Brook University researchers Fusheng Wang and Dr. Richard Rosenthal

By Daniel Dunaief

Health care providers can use all the help they can get amid an ongoing opioid epidemic that claims the lives of 130 Americans each day.

In a cross-disciplinary effort that combines the computer science skills of Fusheng Wang and the clinical knowledge and experience of doctors including Dr. Richard Rosenthal, Stony Brook University is developing an artificial intelligence model that the collaborators hope will predict risk related to opioid use disorder and opioid overdose.

Fusheng Wang

Wang, a Professor in the Department of Biomedical Informatics and Computer Science at Stony Brook and Rosenthal, a Professor in the Department of Psychiatry and Behavioral Health in the Renaissance School of Medicine, received a $1.05 million, three-year contract from the independent funding organization Patient-Centered Outcomes Research Institute (PCORI).

“We have patients, clinical stakeholders, clinician scientists and community-based people within the system of care that have an interest at the table in the development cycle of this AI mechanism from day one,” Rosenthal said. The PCORI required that the scientists identify these stakeholders as a part of the research strategy.

The Stony Brook researchers are combining data from Cerner, a major electronic health record vendor under an institutional data usage agreement, with an awareness of the need to create a program that doctors can use and patients can understand.

Traditional public health studies rely on analyzing incidents that occurred. This approach, however, can be applied to population health management through early interventions, Wang explained.

With artificial intelligence, computer scientists typically plug enormous amounts of data into a model that searches through individual or combined factors and comes up with a prediction through a deep learning process.

The factors, which may be in the hundreds or even more, that contributed to the conclusion about a risk level aren’t always clear, which makes them difficult for doctors to explain and for patients to understand. Many of the factors may not be clinically intuitive.

Deep learning models can provide certain types of information about the prediction, such as a ranking of top factors. These factors, however, may not necessarily be clinically relevant, Wang explained.

To balance the need for data-driven analysis with the desire to create a product that people feel confident using, the scientists plan to become a part of the process.

“We are all going to educate each other,” said Rosenthal. “Patients will tell you what it means to be a patient, to be at the receiving end of some doctors telling them something they don’t know” while each group will share their lived experience.

Each participant will be a student and a teacher. Rosenthal believes this stakeholder in the loop approach will create a tool that is clinically relevant.

“There’s an opportunity to produce a highly accurate predictive mechanism that is highly acceptable based on transparency,” he said.

To be sure, people involved in this process could deemphasize a factor that doesn’t make sense to them, but that might otherwise increase the predictive accuracy of the developing model.

“This might come at the expense of the performance metric,” Rosenthal said.

Still, he doesn’t think any human correction or rebalancing of various factors will reduce the value of the program. At the same time, he believes the process will likely increase the chances that doctors and patients will react to its prognosis.

A program with a personal touch

Wang created the model the scientists are using and enhancing. He reached out to several physicians, including Director of the Primary Care Track in Internal Medicine Rachel Wong and later, Rosenthal, for his addiction research expertise.

Dr. Richard Rosenthal

Rosenthal started collaborating on grant proposals focused on big data and the opioid epidemic and attending Wang’s graduate student workgroup in 2018.

Wang recognized the value of the clinician’s experience when communicating about these tools.

“Studies show that patients have lots of skepticism about AI,” he explained. Designing a tool that will generate enough information and evidence that a patient can easily use is critical.

The kind of predictions and risk profiles these models forecast could help doctors as they seek the best way to prevent the development of an addiction that could destroy the quality and quantity of their patients’ lives.

“If we can identify early risk before the patient begins to get addicted, that will be extremely helpful,” Wang added.

If opioid use disorder has already started for a patient, the tool also could predict whether a patient has a high chance of ending treatment, which could create worse outcomes.

Refinements to the model will likely include local factors that residents might experience in one area that would be different for populations living in other regions.

Depending on what they learn, this could allow “us to frame our machine learning questions in a more context-dependent population, population-dependent domain,” Rosenthal said.

Opioid-related health problems in the northeast, in places like Long Island, is often tied to the use of cocaine. In the Southwest, the threat from opioids comes from mixing it with stimulants such as methamphetamines, Rosenthal added.

“Localization increases the accuracy and precision” in these models, he said.

Eventually, the model could include a risk dashboard that indicates what kind of preventive measures someone might need to take to protect themselves.

The scientists envision doctors and patients examining the dashboard together. A doctor can explain, using the model and the variable that it includes, how he or she is concerned about a patient, without declaring that the person will have a problem.

“Given these factors, that puts you at greater risk,” said Rosenthal. “We are not saying you’re going to have a problem” but that the potential for an opioid-related health crisis has increased.

Unless someone already has a certain diagnosis, doctors can only discuss probabilities and give sensible recommendations, Rosenthal explained.

They hope the tool they are developing will offer guidance through an understandable process.

“At the end of the day, the machine is never going to make the decision,” said Rosenthal. With the help of the patient, the clinician can and should develop a plan that protects the health of the patient.

“We’re aiming to improve the quality of care for patients,” he said.

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MetroCreative Photo

By Daniel Dunaief

Daniel Dunaief

My wife and I have been voting early for several years. We like the convenience of early voting and find that we don’t tend to have to wait too long through the potential long lines of Election Day.

This election day, in particular, seemed problematic to us, as talk of unofficial and party-trained monitors, some of whom are watching over the elections themselves while others are observing the actions of other monitors, are poised to pollute the process.

We drove to the early site, looking carefully from the road at the number of cars in the parking lot and the length of the line out of the building.

If the line exceeded a certain visual marker, we would have returned at another day and time. When we were sure the queue was shorter than our maximum, we pulled into the parking lot, where we immediately found a spot.

Standing outside in an organized, relaxed and respectful crowd, we opened our phones to take a last look at the backgrounds of some of the down ballot candidates and at the experiences of would-be officials who were unaffiliated with either major party.

An elderly black woman appeared behind us, holding a tiny bijou cream-colored dog inside her coat.

“I hope that dog has an official ID,” I offered, as she smiled at me. “Which way is she leaning this year?”

The woman shared a broad and welcoming grin and said her dog’s papers were up to date.

As other voters joined the line or exited the polling place, several people came over and chatted with her about her dog.

“I miss my dog so much,” a man said, as he asked if he could pet her puppy.

She said he was welcome to visit.

“I lost my dog a few months after I lost my wife,” the man said, barely holding back tears.

The rest of us offered sympathetic glances at the man, who, despite sharing a palpable and visible grief, had come out to vote.

The line continued to build, with a 30-something man in scrubs standing next to the woman with the dog.

As others waited for their turn behind us, almost everyone grinned at the dog whose calm demeanor and charm could easily have won him votes if he were running for office.

Once inside the building, the election official with a name tag that read Sarah asked a woman to dispose of an almost empty drink container in the nearby restroom. Sarah promised to hold the woman’s spot, while the voter deposited her trash.

When my wife and I got to the front, Sarah asked the woman behind us if her dog was a service dog. The woman hesitated and then said she had a bad ankle and would have to carry the dog all the way back to the car.

Sarah apologized and also planned to hold her spot. I walked to the open check in desk, handed over my driver’s license and was asked to pronounce my last name. I was directed to another line, where I waited until another official took me to a voting machine.

The woman who returned her dog to her car was standing at a desk. She said she had considered describing her dog as a service animal, but thought better of lying.

Once at a voting machine, I started making my choices.

“Kamala Harris, Kamala Harris, Kamala Harris,” a Black girl who was about 10 years old shouted in a loud crescendo as her mother stood in the machine next to mine.

“So sorry,” her mother sighed, smiling at me, as she tried to contain her daughter’s excitement.

This young girl clearly didn’t share any of the fear, name calling, or anger of this election. She read a name she knew and was overflowing with unbridled enthusiasm.

As a parent, I wished I had told that woman to videotape her daughter’s delight, not only for the historic nature of the moment, but also to capture the sound of an enthralled, youthful voice.

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By Daniel Dunaief

It’s back, bigger than ever, with an added Peter-and-the-Wolf style musical debut.

This year’s version of Science on Stage at Stony Brook University, which brings together the research and life experiences of three scientists with the artistic interpretation and creative talents of three playwrights, focuses on the theme of climate change.

Before the reading of the plays at the free October 28th event at the Staller Center’s Recital Hall, a group of eight high school students and two graduate students will perform an original piece of music composed by Professor Margaret Schedel called “Carnival of the Endangered Animals” (see accompanying story below).

Christine Gilbert with graduate student Emily Gelardi. Photo by Conor Harrigan

The event, which has a seating capacity of 379, which is almost triple the potential audience size from last year, and requires advance registration, is sponsored by the Collaborative for the Earth (C4E).

The organizers of Science on Stage “want people to be thinking about [climate change] from new ways or with new perspectives,” said Heather Lynch, inaugural director of the C4E and Endowed Chair for Ecology and Evolution at Stony Brook’s Institute for Advanced Computational Science and Professor in the Department of Ecology and Evolution.

In these performances, professional actors, directed by Logan Vaughn, share a dramatic reading of the scripts, titled “Ghost Forest,” “Counterfactual,” and “Resplendence.” After the performance, the scientists and playwrights will participate in a question and answer session led by Lecturer J.D. Allen, who is managing editor of NPR affiliate WSHU.

Provost Carl Lejuez, whose office provides funding for the C4E, celebrated the ongoing collaboration between the humanities and the sciences.

“Science on Stage is one of our true interdisciplinary gems,” Lejuez explained. “In a time of such misinformation, the arts provide such a powerful vehicle to communicate science in accessible and inspiring ways.”

Indeed, in addition to hearing an original piece of music and listening to a reading of the plays, audience members will have the opportunity to share their perspectives on climate science before and after the performance.

Christine Gilbert, who holds a joint appointment at the School of Communication and Journalism and the School of Marine and Atmospheric Sciences and is one of the participating scientists, is conducting a study of the effect of the experience with audience members.

Attendees can participate in a short mobile-based survey before the plays and immediately afterwards. A social scientist, Gilbert will follow up with those members who are willing to engage in individual interviews in the weeks after the performance.

Event organizers wanted to know “what is it that’s so magical in the intersection between science, humanity and art” that drew a crowd so large last year that the fire marshal had to turn people away, said Gilbert.

By polling the audience, Gilbert, who was one of the people who couldn’t watch the show last year, hopes to explore the effect of teaching complex science in this forum.

She also hopes to assess how audience members feel after hearing more about climate change and plans to share what she learns with Stony Brook and with the broader scientific community through a published paper.

Heavy and humorous

The scientists and the playwrights appreciated the opportunity to learn from each other and to engage in a creative effort designed to use science, or the life of scientists, to appeal to audiences.

Lynch, who participated in the Science on Stage effort last year, suggested that this year’s plays are powerful and evocative.

“These are deep, adult serious issues,” she said, cautioning that the language includes some cursing and that the themes include loss, parenthood and grief. “This is not Disney.”

To be sure, the plays blend a wide range of emotions.

“With short plays that deal with heavier topics, playwrights will gravitate towards humor,” said Ken Weitzman, Founder and Associate Professor of Theater at Stony Brook, who started Science on Stage virtually in 2020. “It’s how we engage” and commune with an audience.

Counterfactual

Playwright Mat Smart

Author of the play “The Agitators,” about a true narrative describing the 45-year friendship between suffragist Susan B. Anthony and abolitionist Frederick Douglass, Smart said he has taken long Uber rides with people whose views differ from his, leading to spirited conversations.

When Smart described his experiences to Reed, they discovered they had similar interactions.

While much of the script involves a combination of conversations and ideas, Smart explained that part of the dialogue in the play came from a discussion he and Reed had about food choices and climate change. 

The interaction about cheeseburgers is “based on something [Reed] said to me,” Smart said. Reed explained the high carbon footprint of a cheeseburger, although he urged Smart to cut back rather than eliminate them from his diet.

“The play is about two people who see things very differently who choose to have a dialogue and to have a tough conversation,” said Smart. “They’re both affected by it.”

Ghost forest

Playwright Gab Reisman

Elizabeth Watson, Associate Professor in the Department of Ecology & Evolution, teamed up with Gab Reisman, who wrote “Ghost Forest.”

In this play, a climate researcher’s subjects spring to life as she writes an important grant proposal.

While it doesn’t reflect how field research or grant writing typically goes, it does capture “some things that have happened to me,” Watson said.

Her field work has involved considerable challenges, including getting stuck in the mud, being covered in ticks, crawling across mudflats, and being abandoned on a raft in a lagoon.

Watson appreciates how the artistic effort allows her to connect with people who probably aren’t the same ones who would read a publication she wrote or come to a presentation.

She also added that the world has what it needs to deal with climate change and that people need to understand the kinds of partnerships and actions that make a difference.

Resplendence

Playwright Kareem Fahmy

After speaking with Gilbert, playwright Kareem Fahmy wrote “Resplendence,” which follows three generations of a family who try to save their island off the coast of Maine.

The New England State is an important setting for playwright and scientist. 

“Maine has such a special place in my heart,” said Gilbert, who has family in the state and attended college at the University of Maine. The pull of the “wild, eastern coast of Maine is so ubiquitous.”

Gilbert appreciated how Fahmy did a “great job of personalizing the context” of the state.

The challenge of preserving destinations, particularly those close to sea level, will likely persist.

“When you do any research about climate change, you have to be aware that this is not just a problem for people living today, but for people 200 years from now,” Gilbert said.

Weitzman said the play was an epic despite its short running time and thought it was “quite touching.”

Beyond the performance

Weitzman suggested that the plays can provide an educational component beyond the confines of the Staller Recital Hall. 

While people can’t produce the plays as part of paid entertainment, teachers can read and use them in the classroom. Actors Bill Heck, April Matthis, Tina Benko, Mandi Masden and Taylor Crousore will provide dramatic reading of the plays.

In a short time, the actors are “practically off the book,” as they embrace the opportunity to bring the words to life, Weitzman said.

He suggested the plays offer a glimpse into researchers’ lives. “Here is this person on the front lines. I’m surprised at the angles that are taken” in these plays.

Stony Brook University’s Staller Center for the Arts, 100 Nicolls Road, Stony Brook will present this year’s Science on Stage: Climate Edition on Monday, Oct. 28 at 4 p.m. Doors open at 3:30 p.m. The event is free and open to the public but reservations are strongly recommended.

To register, go to: https://bit.ly/4dcDtsi or click here.

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SBU’s Margaret Schedel brings endangered species to life through musi
Margaret Schedel discusses the ‘Carnival of the Endangered Animals’ with the band and conductor Justin Stolarik during rehearsal. Photo by Heather Lynch

Science on Stage at Stony Brook University added a new dimension to the performance this year, as Margaret Schedel, Associate Professor of Music, composed “Carnival of the Endangered Animals.” The original music, which will debut on Oct. 28 at 4 p.m. at the Staller Center’s Recital Hall, is a recreation of the sounds of a wide range of animals who are in danger of becoming extinct.

“It’s melodic, interrupted by moments of trying to translate” the calls from these animals, Schedel said.

Ken Weitzman, Founder and Associate Professor at Stony Brook, appreciates how quickly music can resonate for audiences.

“Music appeals to the emotions,” said Weitzman. “I’m jealous of how quickly music can do in 10 seconds what it takes me hours to do.”

The animals featured in the piece, along with the instrument that captures their sounds, are: the Atlantic Right Whale (Marimba); the A’kikiki bird, which is a Hawaiian honeycreeper (flute); Sumatran Tiger (trumpet); sage grouse (clarinet); Bajii, which is a Yangtze river dolphin; and the Jiangtun, which is a Yangtze finless porpoise (four-hand piano); gorilla (french horn); African bush elephant (trombone); Koala (bassoon); and the penguin (oboe).

Schedel plans to share information about each piece, which eight area high school students and two graduate students will perform, with the audience through a QR code, so they can connect the sounds with the message or visuals she was conveying.

Schedel tried to use a logical progression of the instruments, mixing up the woodwinds, percussion and brass.

Threatened by land development, the sage grouse includes high and low notes from the clarinet that gets covered up by the sounds of a flute and trumpet, imitating the sounds excavators make when they back up and develop McMansions.

Endangered by the spread of avian malaria carried by mosquitoes, the Hawaiian A’kikiki bird had been able to evade these insects by traveling higher up the mountain, where the colder temperatures kills the mosquitoes. That is not happening as much because global warming is enabling the blood sucking creatures to survive at higher elevation.

The sage grouse music starts with a melodic theme on the flute and as it goes higher, the theme becomes compressed. The buzzing brass, meanwhile, gets louder and louder as the mosquito pursues its meal, infecting the bird with a lethal parasite.

Reflecting the struggle for survival these creatures face, the Yangtze river dolphin, which had about 20 members when Schedel first started composing the music, may have become extinct by the time of the performance. That is, in part, why she combined the dolphin and the finless porpoise on the four hand piano.

As for the sounds of the elephant, Schedel recalled a safari she had experienced when she had been in South Africa. Elephants charged at Schedel and her group, who had come too close to the younger ones in the herd.

The elephants growled at Schedel and her companions.

“You can feel it in your chest, the sound waves moving,” she said. “Little by little, the younger ones put up their trunks and eventually a big momma elephant with a broken tusk put up her trunk, which is a symbol of, “we are calm,’” she said. With the trombone representing the elephant, the bass drum connotes its growling sounds.

When she was growing up, Schedel listened to the Leonard Bernstein version of “Peter and the Wolf” so many times that the recording is “nearly dead,” she laughed. She hopes people enjoy her piece with the same energy and excitement, connecting the sounds and the stories with the endangered animals. 

Schedel described the experience of creating the music as a “labor of love.”

 

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Eckart Wimmer. Photo by John Griffin/SBU
Jorge Benach. Photo from SBU
Carol Carter. Photo by Jeanne Neville/SBU
David Thanassi. Photo by Jeanne Neville/SBU

By Daniel Dunaief

The American Society for Microbiology named Stony Brook University’s Department of Microbiology and Immunology a “Milestone” program on Oct. 17th, recognizing the department’s historical research contributions in fields ranging from Lyme disease to polio virus, and infection and vaccines.

Stony Brook is the 20th program to receive this distinction from the ASM, joining Cold Spring Harbor Laboratory as the second such distinguished program on Long Island, and the fourth in the state.

It’s a “shared distinction among all the friends and colleagues from the department over the years” since its inception in 1972, said Carol Carter, Distinguished Professor in the department, and recent inductee into the National Academy of Sciences.

“It’s a family-community [honor],” she continued.

The Milestone recognition from the ASM raises the profile of the department and the university, as it recognizes its historical contribution to the field, and encourages and inspires the growing staff in a department in which basic research can lead to breakthrough discoveries.

“This is not an award or discovery for the last year or year before,” said Kevin Gardner, Vice President for Research and member of the Office of the President. “This is for historical levels of achievement over a really long period of time.”

Gardner planned to join department members, politicians including Assemblymember Edward Flood (R-Port Jefferson) and executives at ASM, as part of the recognition ceremony. The ASM, which was founded in 1899, and has over 32,000 members, is a “high-quality professional society and is about as good as they get,” Gardner added.

“It’s a tremendous honor.”

Theresa Koehler, president of ASM, will give a speech on the historic microbial science accomplishments at Stony Brook and designate the site officially a Milestone program.

Professor Emeritus, Nassau Community College/ University Medical Center and ASM Member, Lorraine Findlay, will also attend.

The ASM has been recognizing Milestones in Microbiology sites since 2002, when the first such honoree, Selman Waksam’s Laboratory at Rutgers University, received the honor.

“The program celebrates groundbreaking achievements that have shaped our understanding of microbiology and inspire future generations,” ASM Archivist Colleen Puterbaugh explained in an email.

The Stony Brook Department of Microbiology and Immunology has made the kind of fundamental discoveries regarding how cells work and how DNA and RNA and the different genetic building blocks come together that have led to treatments for diseases like polio, Gardner added.

“These types of recognition really help put the word out about what we’ve done and continue to do,” said David Thanassi, Chair of the Department of Microbiology and Immunology. “It helps build morale” and aids in recruiting additional faculty.

Last year, the department added four faculty members and is in the process of searching for another person to join.

In the wake of the COVID Pandemic, universities and research facilities have emphasized the importance of microbiology, immunology and virology, which are fields that could help provide the kind of basic science that leads to early diagnosis, prevention, and treatment.

“Other places want virologists, too, because there’s a greater awareness of the need for these types of researchers,” said Thanassi.

Compelling research

In the application Carter helped prepare to submit to the ASM, she focused on three specific basic research achievements that have had an important impact on human health.

Joseph Kates, Founding Chair of the department, discovered that viruses could package enzymes required to copy themselves. His research made it possible to target viral polymerases as a type of therapy.

“Up to that point, it really wasn’t known about the basics of how viruses replicate themselves,” said Carter. “Finding this enzyme that viruses have to carry in their coat meant humans could devise a strategy for countering their ability to replicate.”

When she was considering joining the young state university, Carter interviewed with Kates in 1975. Kates “was so impressive and so much fun,” said Carter, “it was difficult to envision why you wouldn’t come and work in his department.”

Additionally, the ASM considered the research of Jorge Benach, Willy Burgdorfer and scientists from the Rocky Mountain Laboratory, who identified the cause of Lyme disease, which is a particular problem on Long Island.

This work made it possible to create antibiotic therapies.

Benach was able to “isolate the spirochetes from patients and demonstrate that they were the causative agent of Lyme,” said Carter.

Benach also characterized the form of the infection that occurs in dogs. Meanwhile, Eckard Wimmer was the first to describe the chemical synthesis of a polio virus without using a natural template. He was also the co-discoverer, with Vincent Racaniello, of the human receptor for poliovirus.

Wimmer’s work started efforts to synthesize organisms in the absence of a natural template, making it possible to develop new strategies in virus vaccine development.

Two plaques

As a part of the ceremony, the ASM will award Stony Brook two plaques. One of them will be visible in the department itself, while the other will go up in the Renaissance School of Medicine’s lobby, near the dean’s office and the library.

Carter suggested that the department continues to conduct research that is globally important.

“These days, the [discoveries] are not low-hanging fruit,” Carter said.

“The answers don’t come easily. You do feel gratified, whether you or somebody else in your unit, provides some sort of understanding that we didn’t appreciate before,” she continued.

In addition to the principal investigators who conducted research that proved important for human health, Carter added that the students who gained experience and insights at the university have gone on to develop productive careers.

“We have had fabulous students.”

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SBU's Elizabeth Watson, second from right, and her team coring.

By Daniel Dunaief

Daniel Dunaief

I used to liken the process to sitting on a highway divider where the speed limit was 70 miles per hour, holding a notebook and trying to read and record as many license plates as I could, sometimes in the pouring rain, under a bright sun, or in thick fog.

Working for a wire service, with its 24-hour news feed and its endless space for stories, was exhilarating and exhausting. My editors sometimes called me at 4 a.m. to tell me about an important story that was breaking and to encourage me to come into the office to get to work.

Oh, and every three months, when the companies I covered reported earnings, I’d arrive at work for at least a week around 7 in the morning, wait for the numbers to come out, and then spend the day reading the reports, talking with analysts and investors, getting on media conference calls with top executives and watching the stock price of the company rise and fall.

My job was to search through all that information to anticipate how people would react to piles of electronic news.

It was a great opportunity to write on deadline and to experience the absurd. One day, I helped write a few headlines and then had to use the bathroom. As I pushed the door open, my editor, following uncomfortably closely behind me, hovered.

“Can I help you?” I asked, as I stopped and turned around.

“Yeah, how long are you going to be in here?” he asked in his usual staccato, urgent tone.

“As long as it takes,” I shrugged.

“Yeah, well, there’s a headline out there and you need to send out the first version of the story within 15 minutes,” he reminded me, as if I didn’t know our rules.

“I know,” I said, “and I’m sure my system will comply with the requirements.”

Those were tough days at the office.

I’m sure everyone has difficult days at work, whether it’s a police officer dealing with someone who is in an altered, drug-induced state who may be a danger to himself or others, a teacher helping a high-stress student prepare for a standardized test, a truck driver taking a long detour around a crash site, or any of the many other possible strains or obstacles between the start of the day and the workload.

Recently, I spoke with several climate scientists who are a part of the Science on Stage free celebration at Stony Brook University’s Staller Center, which is coming up on October 28th at 4 p.m. (see related story in the Arts & Lifestyles section).

These scientists endure everything from creature discomforts, to resistance to the work they’re doing, to their own deadlines and the need to conduct their studies, publish their results and apply for funding.

Indeed, Elizabeth Watson, Associate Professor in the Department of Ecology & Evolution at Stony Brook University, shared several challenging moments.

“I’ve gotten stuck in the mud, covered with ticks, I’ve gotten Lyme, crawled across mudflats, pushed boats across mudflats, had to row our power boat back to the launch ramp more than once, [and] got forgotten about on a raft in a lagoon,” Watson wrote in an email.

Each of those challenges could have become the focal point of action for a biopic about a scientist.

Heather Lynch, Professor in the Department of Ecology & Evolution, explained that her research on penguins in Antarctica requires considerable advanced planning.

“The main challenge of working in Antarctica is really the uncertainty imposed by the weather and logistics,” she explained in an email. “It’s not enough to have Plan B, it’s more like Plan B through Plan F and then some. Covid and now avian flu have made an already difficult situation even harder.”

Still, at their most challenging moments, waiting for the weather to change, hoping someone will remember to pick them up, or living without creature comforts, these researchers find joy and derive satisfaction in doing valuable and constructive work.

“I’m like a bricklayer, adding more bricks to an enormous wall of knowledge that was started long before I started working on penguins and will continue to be built long after,” Lynch wrote.

Or, to put it another way, Watson wrote that “I love my job! No regrets.”

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Shushan Toneyan and Peter Koo at Cold Spring Harbor Laboratory. Photo by Gina Motisi/CSHL

By Daniel Dunaief

The real and virtual world are filled with so-called “black boxes,” which are often impenetrable to light and contain mysteries, secrets, and information that is not available to the outside world.

Sometimes, people design these black boxes to keep concepts, ideas or tools outside the public realm. Other times, they are a part of a process, such as the thinking behind why we do certain things even when they cause us harm, that would benefit from an opening or a better understanding.

In the world of artificial intelligence, programs learn from a collection of information, often compiling and comparing enormous collections of data, to make a host of predictions.

Companies and programmers have written numerous types of code to analyze genetic data, trying to determine which specific mutations or genetic alterations might lead to conditions or diseases.

Left on their own, these programs develop associations and correlations in the data, without providing any insights into what they may have learned.

That’s where Peter Koo, Assistant Professor at Cold Spring Harbor Laboratory, and his former graduate student Shushan Toneyan come in.

The duo recently published a paper in Nature Genetics in which they explain a new AI-powered tool they designed called CREME, which explored the genetic analysis tool Enformer.

A collaboration between Deep Mind and Calico, which is a unit of Google owner Alphabet, Enformer takes DNA sequences and predicts gene expression, without explaining what and how it’s learning.

CREME is “a tool that performs like large-scale experiments in silico [through computer modeling] on a neural network model that’s already been trained,” said Koo. 

“There are a lot of these models already in existence, but it’s a mystery why they are making their predictions. CREME is bridging that gap.”

Award winning research

Indeed, for her work in Koo’s lab, including developing CREME, Toneyan recently was named a recipient of the International Birnstiel Award for Doctoral Research in Molecular Life Sciences.

“I was genuinely surprised and happy that they selected my thesis and I would get to represent CSHL and the Koo lab at the ceremony in Vienna,” Toneyan, who graduated from the School of Biological Sciences, explained. 

Toneyan, who grew up in Yerevan, Armenia, is currently a researcher in The Roche Postdoctoral Fellowship Programme in Zurich, Switzerland.

She said that the most challenging parts of designing this tool was to focus on the “interesting and impactful experiments and not getting sidetracked by more minor points more likely to lead to a dead end.”

She credits Koo with providing insights into the bigger picture.

New knowledge

Without taking DNA, running samples in a wet lab, or looking at the combination of base pairs that make up a genetic code from a live sample, CREME can serve as a way to uncover new biological knowledge.

CREME interrogates AI models that predict gene expression levels from DNA sequences.

“It essentially replicates biological or genetic experiments in silico through the lens of the model to answer targeted questions about genetic mechanisms,” Toneyan explained. “We mainly focused on analyzing the changes in models outputs depending on various perturbations to the input.”

By using computers, scientists can save considerable time and effort in the lab, enabling those who conduct these experiments to focus on the areas of the genome that are involved in various processes and, when corrupted, diseases.

If scientists conducted these experiments one mutation at a time, even a smaller length sequence would require many experiments to analyze.

The tool Koo and Toneyan created can deduce precise claims of what the model has learned.

CREME perturbs large chunks of input sequence to see how model predictions change. It interrogates the model by measuring how changes in the input affect model outputs.

“We need to interpret AI models to trust their deployment,” Toneyan said. “In the context of biological applications, we are also very interested in why they make a certain prediction so that we learn about the underlying biology.”

Using ineffective and untested predictive models will cause “more harm than good,” added Koo.  “You need to interpret [the AI model’s] programs to trust them for their reliable deployment” in the context of genetic studies

Enhancers

Named for Cis Regulatory Element Model Explanations, CREME can find on and off switches near genetic codes called enhancers or silencers, respectively.

It is not clear where these switches are, how many there are per gene and how they interact. CREME can help explore these questions, Toneyan suggested.

Cis regulatory elements are parts of non-coding DNA that regulate the transcription of nearby genes, altering whether these genes manufacture or stop producing proteins.

By combining an AI powered model such as Enformer with CREME, researchers can narrow down the possible list of enhancers that might play an important genetic role.

Additionally, a series of enhancers can sometimes contribute to transcription. A wet lab experiment that only knocked one out might not reveal the potential role of this genetic code if other nearby areas can rescue the genetic behavior.

Ideally, these models would mimic the processes in a cell. At this point, they are still going through improvements and are not in perfect agreement with each other or with live cells, Toneyan added.

Scientists can use the AI model to aid in the search for enhancers, but they can’t blindly trust them because of their black box nature.

Still, tools like CREME help design genetic perturbation experiments for more efficient discovery.

At this point, the program doesn’t have a graphical user interface. Researchers could use python scripts released as packages for different models.

In the longer term, Koo is hoping to build on the work he and Toneyan did to develop CREME.

“This is just opening the initial doors,” he said. “One could do it more efficiently in the future. We’re working on those methods.”

Koo is pleased with the contribution Toneyan made to his lab. The first graduate student who worked with him after he came to Cold Spring Harbor Laboratory, Koo suggested that Toneyan “shaped my lab into what it is.”

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METRO photo

By Daniel Dunaief

Daniel Dunaief

Back in the day when I covered Wall Street and spoke with power-broking bankers, mergers and acquisitions experts, and traders, I often chatted with people who had little to no time.

As often as I could, I’d catch someone in the midst of an exciting transaction. I pictured them standing at their desks, staring at papers, looking closely at the clock, and envisioning various life or community-altering transactions, such as multi-billion dollar mergers.

The information would be even better, of course, if other journalists hadn’t yet heard the news, giving me the chance to be first.

Some of my sources would share juicy tidbits, about a company, a strategic move, or a new hire. The cadence of their voice was often quick and clipped and the tone was close to a conspiratorial whisper, with the volume inversely proportional to the importance of the developing story.

They would often be eager to get off the phone so they could continue to rule the world, to collect multi-million dollar fees and to prepare to help other companies keep up with the fast-merging world by moving other pieces on the financial chess board.

A few seconds after sharing the final details, they would invariably use a two word signal that meant that the conversation, whether I liked it or not, was ending.

“Gotta hop!” they’d say. It was a universally understood code for, “I’m not hanging up on you, per se, but those are the last sounds you’ll hear from me on this call.”

During busy days on Wall Street, I’d picture investment bankers in expensive suits, hopping on one foot from building to building, keeping one leg in the air as they frantically finalized details and collected signatures.

Once they reached their destination, I imagined them putting the non-hopping leg down comfortably on the ground, while massaging the one that propelled them around the lower part of Manhattan.

Wall Street hasn’t cornered the market on signals that a conversation is coming to a close.

People in the Main Street world say they “gotta run.”

Sometimes, out of politeness, someone will indicate that he or she has another important call coming in that’s related to the topic at hand.

In more personal and familiar settings, my friends and family have various codes that suggest they are preparing to end a conversation.

An audible sigh is usually the equivalent of, “okay, let’s wrap things up here.”

Then, there’s the long, slow version of “alright,” which suggests that, fun as this conversation might have been, it’s time to end the call.

I appreciate the moment when people appear to want to be sensitive to me when they’re ready to disengage. That typically includes some version of, “I’m gonna let you get back to work or whatever it is you’re doing” when, more often than not, they have to return to something.

Of course, I have been on the other side of this disengagement effort, when someone who is on a long drive is not only eager for company but is also prepared to share, stream-of-consciousness style, everything they see and comment on the driving skills of everyone around them.

“What is that red car thinking?” they’ll ask. “Did you see that?”

“No, you see, the way the phone works, I can only hear your voice. I’m not looking through a body worn camera at the road ahead of you, but I’m sure the red car did something stupid and it’s great that you’re such a skilled defensive driver.”

I sometimes try to wrap up these calls with something like, “well, it’s been nice chatting with you.”

“Yes,” they’ll reply. “It’s nice chatting with you, too. So, what do you think of the presidential election?”

“Oh, um, I think it’s a good idea every four years or so. More often than that would become too hectic and stressful for the country.”

“No, I mean, what are your top 15 issues for the election this year.”

“I’d love to share them with you, but I have to hop and I want to give you a chance to get back to driving and someone is waiting to take a run with me, so, I’m gonna go.”

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Prateek Prasanna and Chao Chen at the NCI Informatics Technology for Cancer Research meeting in St. Louis in 2022.

By Daniel Dunaief

Cancer often involves numerous small changes before it become a full blown disease. Some of these alterations are structural, as otherwise healthy cells make subtle shifts that favor out of control growth that often defies the immune system and threatens the health of tissues, organs and the entire body.

Associate Professor Chao Chen and Assistant Professor Prateek Prasanna, both in the Department of Biomedical Informatics at Stony Brook University, recently received a four-year, $1.2 million grant from the National Cancer Institute to continue to develop an enhanced breast cancer imaging tool that could detect some of those changes.

Using advanced mathematical modeling and machine learning and working with clinical collaborators in radiology, radiation oncology, surgery and pathology, the researchers are developing a tool called TopoQuant. They hope they can provide a way to look at the changes in tissue architecture that occur during the growth and development of cancer and during radiation treatment.

Receiving the grant means “other researchers also think highly about the subject,” Chen explained. “This further boosts our confidence and is an approval for our effort so far.”

By combining two-dimensional and three-dimensional data, the Stony Brook researchers, including radiation oncologist Dr. Alexander Stessin, hope to provide an analytical tool that helps doctors and patients confronting cancer all the way from the early steps the disease takes to the ways it resists various treatments.

The researchers are using tomosynthesis and MRIs, both of which are three dimensional, and conventional mammographs, which are two dimensional.

Stessin will work closely to evaluate the efficacy of the TopoQuant framework to provide a predictive and useful interpretation of breast images.

The diagnostic and prognostic tool these scientists are developing has potential applications outside the world of breast cancer. The deep learning technique could help analyze images and information for other types of cancer as well as for various neurological challenges.

“In the tools we develop, a lot of the algorithms are domain agnostic,” said Prasanna.

The approach should work as long as the researchers can get structure-rich imaging data. To be sure, while this approach has had some promising early results, it has to proceed through numerous steps to help in the clinic.

In the meantime, the researchers plan to use the funds, which will support salaries and travel budgets for researchers, to continue to develop TopoQuant.

Chen and Prasanna envision providing physicians with an explanation of why artificial intelligence is guiding them towards a particular decision.

Doctors could “place more trust in a system like this,” Prasanna said. “It lends interpretability to an analysis that is typically more opaque.”

Healthy cells

When health care technicians gather information about breast cells, they often focus on developments in and around the cancer cells.

“The premise of the work” Chen and Prasanna are doing is to look at signals “even in the normal [healthy] areas of the breast, Prasanna said. “It’s important for physicians to look at these normal areas before they begin any treatment. What our tool lets them do is extract these signals.”

The process of developing this tool started about five years ago, as the scientists shared ideas and did preliminary studies. The work became more involved and detailed around 2020.

“The challenge is to have a harmonic combination between mathematical modeling and deep learning,” Chen explained. “Incorporating principled math modeling into deep learning is important yet not trivial.”

In their work, the researchers used phantom data called VICTRE from the Food and Drug Administration. They used simulated magnetic resonance images and validated that the method can extract the tissue structure faithfully across different breast density types. They are also using data from The Cancer Imaging Archive for initial model development.

At this point, the researchers have some evidence that the alpha version of the tool has been “promising” in the context of neoadjuvant chemotherapy, which they demonstrated in a paper they published in 2021.

The results from that study indicated different topological behavior of breast tissue characterized by patients who had different responses to therapy.

The researchers plan to continue to establish that the tools are properly characterizing what is happening. After that, they will validate the effort with a Stony Brook University Hospital cohort.

Clinicians from Rutgers are working with Chen and Prasanna and will do additional testing through external data sets.

Complementary skills

Chen and Prasanna, who have joint lab meetings and discuss their research every week, work in different parts of the campus. Chen’s lab is on the west campus, while Prasanna is in the east campus.

The researchers have combined their interests and skill sets to apply a computer science driven approach to medicine and the field of bioimaging analysis.

Chen does considerable work with topological information and machine learning. Prasanna, meanwhile, is also involved in the clinical world, combining his passions for engineering and medicine.

A native of Gansu Province in China, Chen lives near New York City and commutes to the university two or three times per week, working the other days from home and meeting with students and collaborators by Zoom.

When he first joined Stony Brook in 2018, Chen was concerned about jumping into a different department.

After visiting the department and speaking with Chair Joel Saltz and other faculty, he developed greater confidence when he learned of their passion for research, their research philosophy and the chemistry within the department.

Six years later, he thinks it was “the best career decision” he made.

A native of Cuttack, India, Prasanna and his wife Shubham Jain, who is in the faculty of Computer Science at Stony Brook, have worked together professionally.

The couple enjoys hiking and has been to 47 of the 63 national parks. One of their favorite parks is Katmai National Park and Preserve in Alaska.

Prasanna’s father’s family includes many physicians and his mother’s is involved in engineering. In his career, he has combined the professional focus from both sides of his family.

Early in his career, Prasanna worked on a project that used a smart phone to obtain fundus images of the eye to predict diabetic retinopathy.

At the time, he thought “this is where I want to be,” he recalled.

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Jillian Scully on the track. Courtesy Scully family

By Daniel Dunaief

Sometimes, Jillian Scully isn’t sure whether she’s dreaming that she’s practicing or she’s awake and on the field.

That’s because the Miller Place High School senior spends so much time honing her technique and trying to increase the distance she can throw a shot put and discus.

Jillian Scully

“I’ll have dreams where I’m practicing and it’s so vivid, I think I’m there,” said Scully. “I can feel the mud on my hands and the cold ball on my neck.”

The work has paid off, as Scully, who won the New York State Outdoor State Championship in shot put by over five feet in June, and set the school record in the shot put by over 12 feet, has been recruited by Division I track and field teams around the country, from UCLA to Arizona State, Colorado State University, and the University of Michigan, to name a few.

Two weeks ago, Scully and her parents James and Despina, (who goes by “Debbie,”) got up at 3 a.m. for a flight to Colorado, where they toured Colorado State University, and just last week, they visited the University of Michigan. On her college visits, coaches have given her tours of the campus and have outfitted her in university attire. Until she chooses a school, she can’t bring any of that clothing home.

“I’m expecting when I go to these schools that I’m going to have a gut feeling,” said Scully. I have a sense that I’ll know the best fit for me as soon as I step on [the right] campus.”

Scully, who is 6 feet, 1 inch tall, has found it tough to watch others train without being able to participate.

“It’s a little difficult seeing all the throwers getting to lift and throw and me being forced to watch,” Scully explained.

Scully explained that her favorite moment in a meet is when she takes her first step into the circle, which gives her a surge of confidence.

Each time she prepares to launch the ball or discus, things go “silent in my brain, the sound stops and I just throw,” she said.

A highly valued recruit, Scully started throwing shot put and discus in middle school. Ian Dowd, who coached track and field in middle school at Miller Place, recalled how Scully could sprint the fastest, jump the furthest and, as it turns out, throw a shot put remarkably far, without any training.

“She threw [the shot put] something crazy, like 25 or 26 feet, the first time she did,” said Dowd, who now coaches basketball in the Southampton School District.

Scully’s father James, who owns and runs the construction company JFS Contracting, dabbled in track when he was in high school, including throwing shot put.

“I never thought she’d have been that good,” Scully said. “I did it because I was bored and I wanted to do something.”

The younger Scully, however, who plans to study engineering when she’s not practicing or competing in Division 1 track meets, is focused and passionate about throwing the 8.8 pound shot put as well as the 2.2 pound discus.

While shorter than her 6’3” father, Scully is taller than her 5’8” mother, Debbie, who considers herself the “small one” in the house. Debbie has never tried either sport, but has picked up her daughter’s bag to move it in the house.

“It’s no wonder you’re so strong,” Scully told her daughter. “She’s walking around with a weighted vest all day long.”

Change of life

Before she discovered track and field, where she also runs the 4×100 relay, Scully, 17, was struggling.

Scully suggested that her mother gave her the “nudge” to try track.

Jillian Scully

“I was introduced to track at a certain point in my life when I was secluded from everybody,” said Scully, who was unreceptive to people and spent her free time playing video games or being unproductive.

“The person I was for however many years is not me,” Scully recalled. “I didn’t enjoy being that person.”

When she started competing in track, she felt the experience, including the camaraderie with her teammates, “clicked” and became “a part of me.” Spinning around in a small circle and throwing objects through the air became a necessary part of her mental health, and is a large part of her personality.

Hannah Kuemmel, the Athletic Trainer at Miller Place High School, has noticed the change in Scully.

“She is a lot more confident in who she is as a person and an athlete,” said Kuemmel, who also teaches a sports medicine class in which Scully sits front and center.

When she started competing in shot put and discus, she found a way to excel. “If I’m good, I might as well keep doing it,” she said. “I love it so much.”

Good isn’t the word Bill Hiney, her personal coach who has been working with her for over two years, and who has been in the field for 36 years, would use to describe her.

“I’ve often said she’s on another planet,” said Hiney, who is the Assistant Track and Field Coach during the winter and spring seasons for Southold High School.

A good female shot put thrower can reach the mid 30 feet. At 46 feet, 11 inches, Scully is throwing 10 feet further than the best female athlete Hiney has ever worked with, which puts her “in another dimension.”

Hiney describes her athletic student as the “icing on the cake in my long career. Coaches are lucky to have someone with athleticism, size and all the elements necessary to be extraordinary.”

Five squares

And, speaking of icing, the combination of her athletic training and metabolism make Scully a voracious eater, as she consumes five square meals a day.

She typically tops it off with a pint of Haagen Dazs mint chocolate chip ice cream in the evenings.

“She eats everything under the sun,” said her father, who adds that when he brings her 20 buffalo wings, she asks for another 20 so she can have a snack later.

These days, Scully, who coaches describe as tall and lean, puts her height to use in another sport, as she is an outside hitter for the varsity volleyball team, as well.

Scully’s parents appreciate how sports has given her the self-confidence and readiness to contribute to her team.

Even during track and field competitions, when she’s preparing to do her own throwing, Scully will speak with other athletes about their technique. “When Jillian was throwing against other girls, they asked her, ‘What can I do to throw better? What am I doing wrong?’” Jim Scully said. “She takes it upon herself to help all the other throwers,” and encourages them to improve.

Athletic trajectory

As well as Scully has performed in the shot put and discus, Hiney and the head coaches from universities around the country see continued growth ahead. Scully just started weight lifting this summer. “If it was karate, she’d be a white belt,” Hiney said. Well-known coaches in the field have come to watch her throw and have been impressed. Dowd believes Scully could reach an elite level if she keeps pushing herself, even climbing as far as the Olympics.

“I would love to see her with a US banner,” Dowd said. “That would be surreal.”

As for Scully’s thoughts on the matter, she would embrace an opportunity to represent her country at the Olympic games. She recalls sitting in class, and looking up how far Olympians, who competed in this past Paris Games, threw when they were her age.

“I’m trying to compare myself and set my goals,” she said. “That would be a dream for me, going to the Olympics and competing in these events.”

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

My Aunt Maxine had Down syndrome, which means she was mentally disabled.

In so many ways, Maxine and her life defied expectations and labels.

When Maxine was born, doctors told my grandparents that she wouldn’t likely live long, so they should consider putting her in an institution.

My grandparents couldn’t imagine being away from their daughter. They took Maxine home to the Upper East Side of Manhattan, where they raised and educated her.

As she grew up, Maxine was on the shorter side, at under five feet tall, and carried the youthful, round face of Down syndrome throughout her life.

She also had facial hair that my grandmother, mother and caregivers regularly trimmed.

My aunt lacked any self-consciousness about who she was, what she was, and how she related to the world. She figured everyone was as ready to love her and interact with her as she was with them.

More often than not, she smiled, offering an energetic and enthusiastic nod whenever anyone made eye contact. Plenty of people avoided looking at her in part because she was different and, in part, because she lived in New York and the rules of sidewalk engagement limited eye contact.

When people didn’t notice or engage with her, she kept walking, singing, talking to herself, chatting with her parents or the rest of us, or whistling, which she could do by inhaling and exhaling.

She lived at a higher decibel level. Her whisper was even louder than her normal speaking voice.

“What?” she’d whisper so loudly that it could be heard in the back row of a movie theater. “You want me to be quiet? Is that what you’re telling me?”

“Yes, shhhh.”

“Don’t shush me!” she’d say, her husky whisper, like her husky voice, becoming louder and indignant.

“Sorry, Macky,” I’d say. “People are trying to watch the movie. Can you watch it, too?”

“Oh, yes, yes, yes,” she’d say, nodding vigorously. “I’ll be quiet. I will. I’ll be quiet. If that’s what you want, I can be quiet. Sure, suuuuure!”

She was spectacularly funny and knew introductions were an opportunity for comedy.

“Who is this young lady?” she’d ask anyone who walked in the door in our house. The person could be anywhere from six to 96 and she’d ask the same thing.

“How old are you?” she’d ask.

No matter the answer, she’d suggest the person was a “lovely” young lady.

“What’s your name?” she’d ask.

When the person said her name, she’d say “what” several times and then ask the person to spell it. When she slowed our guest down repeatedly and asked her to say it again, the guest would shout.

“Hey, what are you yelling for? I can hear you. Not so loud. You’re hurting my ears.”

She’d squint and a smile would fill her face as she’d scan the room, knowing the old routine had hit the mark.

More than anything else, though, Maxine was compassionate, emotionally connected, loving and supportive.

She would sing the Star Spangled Banner when she listened to Robert Merrill on the radio before a Yankees game.

“It’s so beautiful,” she’d say, as she blew her nose and wiped her eyes.

I suspect many other Americans have an aunt, sibling, distant relative, friend or neighbor for whom labels mean even less than the totality of their lives, the winsome nature of their personality, and the triumphs that define their days.

Hearing anyone use the term “disabled” as a take down misses the point, particularly for those who seek to be the country’s leader.

Maxine required but also taught a level of patience. In exchange, our family and friends appreciated her joy of life and basked in her unconditioned positive regard. She wouldn’t have resented or hated others, wouldn’t have insulted individuals or a group and would have forgiven anyone who made a mistake.

Perhaps some day, those who use words like “mental disability” as a way to dismiss others or to cast others aside will think of the Maxines of the world. We can learn so much from others whose lives are different from ours and who aren’t trying to use words to project an image, to cut others down, or to suggest that someone is limited.

I can picture Maxine sitting in a chair next to me, tilting her head and looking at me from the side.

“You’re such a silly goose,” she’d laugh.

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