Authors Posts by Daniel Dunaief

Daniel Dunaief

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Journalists need to embrace Detective Sgt. Joe Friday’s line from “Dragnet,” “Just the facts, ma’am.”

Caught up in intense public passions, journalists can either throw their opinions at the inflamed cacophony or they can seize an opportunity to do something that has escaped most politicians: Represent broader interests.

We live in a world of spin, where claims and counterclaims come out so rapidly that reality has become a blur. The challenges in sifting through fact and fiction have increased as officials of all stripes shout their truths from the rooftops, even if they have an obstructed view of the world down below.

When I was in journalism school more than two decades ago, a good friend from Bulgaria, who was one of the few people who could pronounce my name correctly when she read it in my mailbox, shared her writing with me.

I noticed a flaw in the way she recorded dialogue. The quotes in her story often lacked the syntax and vocabulary that native English speakers possess. When I asked if she only spoke with other Bulgarians, she playfully punched my shoulder and said she needed to hear better.

That was an unintentional consequence of the way someone who spoke three languages translated the world.

The chasm today between what people say and what others hear, even those who speak the same language, has gotten wider. Editors and reporters return to their desks or take out their laptops, ready to share quotes, events and facts.

These fellow members of the media may find themselves seeing what they want to see, much like the parent of an athlete on a field or a coach who has become an advocate or cheerleader. In editorials, where we’re clearly sharing an opinion, that works, but in news reports we should share the facts, offer context — and increase the value of fact-based reporting.

With facts under regular assault, the search for them, and the ability to verify them, becomes even more important.

A divided nation needs balanced, fair, accurate and defensible reporting. In their publications, scientists share materials and methods sections, which should allow other researchers to conduct the same experiments and, presumably, find the same results. Far too often, opinions disguised as news urge people to trust the writer. Why? Readers should be able to pull together the same raw materials and decide for themselves.

I know government officials don’t always deal in facts. I also know numbers can be repackaged to suit an agenda, turning any conclusion into a specious mix of farce and mental acrobatics. To wit, he’s the best left-handed hitter every Tuesday there’s a full moon below the Mason-Dixon line. Just because it’s presented as a fact doesn’t mean we have to report it or even mock it. If it’s meaningless, then leave it alone. The argument that other journalists are doing it doesn’t make it acceptable.

Several years ago, someone called to berate me for what he considered errors in my story. Rather than shout him down, I gave him the chance to offer his perspective. Eventually he calmed down and we had a measured, detailed discussion. This became the first of numerous conversations and interactions in which he provided important perspectives and shared details I might not otherwise have known.

Reporters face a public acutely aware of its own anger. Almost by definition in a country where the two major political parties struggle to find common ground, some group of readers disagrees with our coverage. We shouldn’t try to please everyone. In fact, we should try to please no one — we should merely work harder. It’s time to allow facts to speak for themselves.

It’s become an Abbott and Costello comedy routine, except in the nation’s capital. Let’s take a look:

Trump: “Strange as it may seen, they give ball players nowadays very peculiar names.”

Costello: “Funny names?”

Trump: “Nicknames, nicknames. Now, on the Washington team, we have who’s on first, what’s on second, I don’t know is on third.”

Costello: “That’s what I want to find out. I want you to tell me the names of the fellows on the Washington team.”

Trump: “I’m telling you. Who’s on first, what’s on second, I don’t know is on third.”

Costello: “You know the fellows’ names?”

Trump: “Yes.”

Costello: “Well, who’s playing first?”

Trump: “Who was playing first, but I fired him.”

Costello: “You fired him? Who did you fire?”

Trump: “Yes. I most certainly did. It was time for a new first baseman. We’ve got a better one coming in to play first.”

Costello: “Oh yeah? Who is that?”

Trump: “No, who was on first.”

Costello: “What are you asking me for?”

Trump: “I’m not asking you, I’m telling you. Who was on first.”

Costello: “I’m asking you, who’s on first?”

Trump: “I already told you, not anymore.”

Costello: “Not anymore is on first?”

Trump: “Yes.”

Costello: “You won’t tell me the name of the fellow on first base?”

Trump: “Yes, not anymore.”

Costello: “OK, so not anymore is playing first?”

Trump: “He was, but he just left, too, so now I have no one.”

Costello: “You don’t have a first baseman?”

Trump: “Yes, I do, no one.”

Costello: “How can no one play first?”

Trump: “He’s very talented. He’s one of the best players I’ve ever seen at the position. He’ll win games for us.”

Costello: “When you pay the first baseman every month, who gets the money?”

Trump: “He did, but no one gets it now.”

Costello: “So, you’re not paying anyone?”

Trump: “No, we’re paying no one. Sometimes his wife comes down and collects his paycheck.”

Costello: “No one’s wife?”

Trump: “Yes. After all, the man earns it.”

Costello: “No one does?”

Trump: “Absolutely.”

Costello: “Washington has a good outfield?”

Trump: “Oh, it’s great again.”

Costello: “The left fielder’s name?”

Trump: “Why.”

Costello: “I don’t know, I just thought I’d ask.”

Trump: “I just thought I’d tell you.”

Costello: “Then tell me who’s playing left field?”

Trump: “No, who was playing first, but he was fired.”

Costello: “Stay out of the infield! The left fielder’s name?”

Trump: “Why.”

Costello: “Why?”

Trump: “I’m thinking of moving why to center field after he did such a great job in left.”

Costello: “Who did a great job in left field?”

Trump: “No, who only plays first and he’s not on the team anymore, so I don’t want to talk about him.”

Costello: “You got a pitcher.”

Trump: “Wouldn’t this be a fine team without a pitcher?”

Costello: “Tell me the pitcher’s name.”

Trump: “Tomorrow.”

Costello: “Why not now?”

Trump: “No, why is in left field. He never pitches, but he might play center field.”

Costello: “Now when the guy at bat bunts the ball against tomorrow — me being a good catcher — I want to throw the guy out at first base, so I pick up the ball and throw it to no one.”

Trump: “Now, that’s the first thing you’ve said right.”

Costello: “I don’t even know what I’m talking about.”

Above, Alesi, the skull of the new extinct ape species Nyanzapithecus alesi. Photo by Fred Spoor

By Daniel Dunaief

They were in a terrible mood. They had spent an entire day searching for clues about creatures that walked the Earth millions of years ago and had come up empty.

“We were not finding even a single bone, nothing,” recalled Isaiah Nengo, who will be an associate director of the Turkana Basin Institute and an assistant research professor at Stony Brook University this fall.

Alesi after attached sandstone rock was partially removed at the Turkana Basin Institute, near Lodwar, Kenya. Photo by Christopher Kiarie

One of the fossil hunters in the group, John Ekusi, started rolling a cigarette. Nengo told him to move away from them so that they didn’t inhale second-hand smoke. Walking ahead, Ekusi made a spectacular discovery that Nengo called a “freak of a fossil.” Ekusi pointed out a bone sticking out of the ground that looked like the femur of a large animal. When they got closer, they could see that it had brow ridges. Pushing aside dirt, they saw the outline of a primate skull.

“We knew we had found something unique and we started celebrating right there,” Nengo said. “We were dancing and high-fiving. The thrill was unimaginable.”

Nengo and his team discovered the fossil on Sept. 4, 2014, in northern Kenya. This week, a team of researchers from the United States, France and England are unveiling three years worth of research into this remarkable find in the prestigious research journal Nature.

For starters, the researchers had to confirm the date of their fossil, which was about the size of a lemon. Rutgers University geologists Craig Feibel and Sara Mana studied the matrix around the fossil and the area around it.

Akai Ekes and John Ekusi watch as Isaiah Nengo lifts the sandstone block with Alesi after six hours of excavation. Photo from ​Isaiah Nengo

“There was no doubt that [the fossil] came from this deposit and hadn’t rolled in or washed in” during some later period, explained Ellen Miller, a professor of physical anthropology at Wake Forest University.

Next, they had to figure out what kind of primate they had: It could have been an ape or a monkey. Fred Spoor, a paleontologist at University College London, did an initial CT reading using a medical scanner. He found intact molars that were characteristic of apes.

The researchers wanted to do a more thorough analysis of the three-dimensional shape of the skull, so they called Paul Tafforeau, a paleoanthropologist specialist of X-ray imaging who works as a beamline scientist at the European Synchrotron Radiation Facility in Grenoble, France. Typically, such research centers require scientists to wait a year or more.

As soon as Tafforeau saw the photos, Nengo recalls, he said, “You can bring it in anytime.” Tafforeau used a technique called propagation phase contrast–X-ray synchrotron microtomography. In an email, Tafforeau described it as being close to a medical scanner, but 1,000 times more precise and sensitive.

Over the course of three or four days, Tafforeau analyzed the teeth that hadn’t erupted from this young primate, which indicated that this individual died when it was only 16 months old. The teeth also demonstrated that the toddler, whose gender is difficult to determine because of its age, belonged to a new species, called Nyanzapithecus alesi. The name Alesi comes from the Turkana word “ales,” which means ancestor.

Tafforeau said the thickness of the tooth enamel suggest a classic hominoid diet, which would be similar to that of a modern gibbon, and would consist mostly of fruits and leaves. Researchers estimate that an adult of this species would weigh about 20 pounds.

Turning their attention to the fantastic creature’s ears, the researchers found that it didn’t have a balance organ. That means it couldn’t move as rapidly through trees as a gibbon. The ears of this primate, however, did have fully developed bony ear tubes. These ear structures “absolutely confirmed that these were apes,” said Miller. “We had no specimens between 15 million and 10 million years ago.”

Field crew of the​ Stony Brook University-affiliated​ Turkana Basin Institute​ when Alesi​ ​was discovered​ ​at​ Napudet​ in September 2014. From​ ​left, Abdala Ekuon, John Ekus​i, Isaiah Nengo,​ ​Bernard Ewoi, Akai Ekes and Cyprian Nyete.​ Photo from Isaiah​ ​​​Nengo.

Scientists generally believe apes and humans diverged in their evolution about 7 million years ago. That means this toddler ape belongs to a species that is likely a common ancestor for other apes and humans.

Anthropologist Meave Leakey, a research professor in the Department of Anthropology and the Turkana Basin Institute, suggested that this fossil “gives us a picture for the first time of what the ancestor of apes and humans looked like 13 million years ago. It also suggests,” she continued in an email, “that the nyanzapiehecines were close to the origin of all living apes and humans.”

Leakey described the fossil as one of the most complete skulls of an ape ever found anywhere and indicated it was of an age that is poorly represented in the African fossil record.

The three years between the discovery of the fossil and its unveiling to the world in the Nature article is “actually very quick,” Leakey explained. The images captured through the synchrotron provide detailed pictures of structures that would otherwise be hidden by bone.

Gathering and interpreting these images meant traveling to Grenoble, which, she explained, “takes considerable time.”

Researchers involved in this study said this is just the beginning of the work they will conduct on this rare and detailed fossil. Nengo said they had already collected two terabytes worth of data from their scans. Much of the further study of this ape will involve a closer examination of all of that data.

“A paper coming out in Nature makes it seem like the end of the process,” Miller said. “This is just the beginning.” He is intrigued to learn more about the organization of the brain.

Nengo hopes to bring together researchers for a two- or three-day workshop in September or October at Stony Brook University to tackle the next phase of analysis for Alesi.

As it turns out, September will likely become an important anniversary for Nengo, as he recalls the memory of a day three years ago that didn’t start out particularly well, but that ended with a rare and thrilling fossil find.

Nengo recalled how excited he was to return to the Turkana Basin Institute to show Richard Leakey, the founder of the site, Meave Leakey and Lawrence Martin, the director of TBI. “I had photos on my iPad and they were absolutely thrilled,” said Nengo. “Everybody was beginning the guesswork of wondering what it is.”

Organizers of the 3rd annual Genome Engineering: The CRISPR-Cas Revolution event, from left, Maria Jasin, Jonathan Weissman, Jennifer Doudna and Stanley Qi. Photo courtesy of CSHL

By Daniel Dunaief

One day, the tool 375 people from 29 countries came to discuss in late July at Cold Spring Harbor Laboratory may help eradicate malaria, develop treatments for cancer and help understand the role various proteins play in turning on and off genes.

Eager to interact with colleagues about the technical advances and challenges, medical applications and model organisms, the participants in Cold Spring Harbor Laboratory’s third meeting on the CRISPR-Cas9 gene editing system filled the seats at Grace Auditorium.

Jason Sheltzer. Photo from CSHL

“It’s amazing all the ways that people are pushing the envelope with CRISPR-Cas9 technology,” said Jason Sheltzer, an independent fellow from Cold Spring Harbor Laboratory who presented his research on a breast cancer treatment.

The technology comes from a close study of the battle between bacteria and viruses. Constantly under assault from viruses bent on commandeering their genetic machinery, bacteria figured out a way of developing a memory of viruses, sending out enzymes that recognize and destroy familiar invaders.

By tapping into this evolutionary machinery, scientists have found that this system not only recognizes genes but can also be used to slice out and replace an errant code.

“This is a rapidly evolving field and we continue to see new research such as how Cas1 and Cas2 recognize their target, which opens the door for modification of the proteins themselves, and the recent discovery of anti-CRISPR proteins that decrease off-target effects by as much as a factor of four,” explained Jennifer Doudna, professor of chemistry and molecular and cell biology at the University of California at Berkeley and a meeting organizer for the last three years, in an email.

Austin Burt, a professor of evolutionary genetics at the Imperial College in London, has been working on ways to alter the genes of malaria-carrying mosquitoes, which cause over 430,000 deaths each year, primarily in Africa.

“To wipe out malaria would be a huge deal,” Bruce Conklin, a professor and senior investigator at the Gladstone Institute of Cardiovascular Disease at the University of California in San Francisco and a presenter at the conference, said in an interview. “It’s killed millions of people.”

Carolyn Brokowski. Photo by Eugene Brokowski

This approach is a part of an international effort called Target Malaria, which received support from the Bill and Melinda Gates Foundation.

To be sure, this effort needs considerable testing before scientists bring it to the field. “It is a promising approach but we must be mindful of the unintended consequences of altering species and impacting ecosystems,” Doudna cautioned.

In an email, Burt suggested that deploying CRISPR in mosquitoes across a country was “at least 10 years” away.

CSHL’s Sheltzer, meanwhile, used CRISPR to show that a drug treatment for breast cancer isn’t working as scientists had thought. Researchers believed a drug that inhibited the function of a protein called maternal embryonic leucine zipper kinase, or MELK, was halting the spread of cancer. When Sheltzer knocked out the gene for MELK, however, he discovered that breast cancer continued to grow or divide. While this doesn’t invalidate a drug that may be effective in halting cancer, it suggests that the mechanism researchers believed was involved was inaccurate.

Researchers recognize an array of unanswered questions. “It’s premature to tell just how predictable genome modification might be at certain levels in development and in certain kinds of diseases,” said Carolyn Brokowski, a bioethicist who will begin a position as research associate in the Emergency Medicine Department at the Yale School of Medicine next week. “In many cases, there is considerable uncertainty about the causal relationship between gene expression and modification.”

Brokowski suggested that policy makers need to appreciate the “serious reasons to consider limitations on nontherapeutic uses for CRISPR.”

Like so many other technologies, CRISPR presents opportunities to benefit mankind and to cause destruction. “We can’t be blind to the conditions in which we live,” said Brokowski.

Indeed, Doudna recently was one of seven recipients of a $65 million Defense Advanced Research Projects Agency award to improve the safety and accuracy of gene editing.

The funding, which is for $65 million over four years, supports a greater understanding of how gene editing technologies work and monitors health and security concerns for their intentional or accidental misuse. Doudna, who is credited with co-creating the CRISPR-Cas9 system with Emmanuelle Charpentier a scientific member and director of the Max Planck Institute for Infection Biology in Berlin, will explore safe gene editing tools to use in animal models and will specifically target Zika and Ebola viruses.

“Like most misunderstood disruptive technologies, CRISPR outpaced the necessary policy and regulatory discussions,” Doudna explained. The scientific community, however, “continued to advance the technology in a transparent manner, helping to build public awareness, trust and dialogue. As a result, CRISPR is becoming a mainstream topic and the public understanding that it can be a beneficial tool to help solve some of our most important challenges continues to grow.”

Visitors enjoyed a wine and cheese party on the Airslie lawn during the event. Photo from CSHL

Cold Spring Harbor Laboratory plans to host its fourth CRISPR meeting next August, when many of the same scientists hope to return. “It’s great that you can see how the field and scientific community as a whole is evolving,” Sheltzer said.

Doudna appreciates the history of Cold Spring Harbor Laboratory, including her own experiences. As a graduate student in 1987, Doudna came across an unassuming woman walking the campus in a tee-shirt: Nobel Prize winner Barbara McClintock. “I thought, ‘Oh my gosh, this is someone I revere,” Doudna recalled. “That’s what life is like” at the lab.

Brokowski also plans to attend the conference next year. “I’m very interested in learning about all the promises CRISPR will offer,” she said. She is curious to see “whether there might be more discussion about ethical and regulatory aspects of this technology.”

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I wanted Dustin Fowler to succeed next year. In case you missed it, he’s the kid who came up from the New York Yankees minor league baseball system who ran into a low wall at Chicago White Sox and hurt his knee, ending his season and, as it turns out, his Yankees career before it began.

Fowler was slated to lead off the second inning of his first major league game, but, instead, was carted from the field to receive emergency medical attention.

It’s somewhere between incredibly difficult and impossible to make the major leagues and yet Fowler was good enough to be on the field.

And then, like the real person Archibald “Moonlight” Graham, who was featured in the Kevin Costner movie “Field of Dreams,” Fowler got within inches of holding a bat and facing major league pitching, when the season ended for him.

Fowler hasn’t left baseball but, as of this week, he’s no longer on the team he imagined joining. In need of starting pitching for this stretch run from now until October, the Yankees traded him as a part of a package to get Sonny Gray from the Oakland A’s.

Now, I want the Yankees to win and Fowler was a chip the team could trade to get a talent who could pitch more than five innings, and who might win important games in October.

And yet when Fowler left the Chicago field, I’m sure I wasn’t the only fan who hoped to support him a second time if and when he got another opportunity — and the Yankees needed him.

He still may get his chance with Oakland. After all, if he was good enough before his injury, he may ride the same determination and skill on the long road back to the majors.

Over before it started, Fowler’s Yankee career will feel like an unopened or undelivered present, shipped somewhere else.

Fowler was our boy. He was drafted in the 18th round in 2013 and had worked his way up to the Yankees’ Triple-A affiliate, Scranton/Wilkes-Barre RailRiders. In the statistics for his career, there is a “1” next to the number of games he played in 2017 with the Yankees, along with “zeros” all the way through every other column. No doubles, triples, home runs or runs batted in for this Yankee apparition.

This is the time of year when baseball general managers have to decide between the present and the future. What are they willing to give up in an uncertain future for a present that may be less of an unknown?

Will the A’s and now Yankees pitcher Gray be worth the price of sentiment if he wins important games down the stretch and into the playoffs?

Derek Jeter used to remain unflappable as teammates wandered on and off his team, often shrugging off questions while indicating he knew it was a business.

If that business does well, do we care that some kid who may or may not have amounted to much for our team is now playing for someone else after bouncing back from adversity?

Fowler will be the one who made it to the team, only to have a freak type of baseball interference prevent him from fulfilling his rise from Yankees prospect to Yankees player.

The A’s and their fans will now pick up the Fowler narrative, making him a part of their lore and history. No matter how things pan out, Yankee fans can wish him the best even as we wonder what that might have been as a part of the New York narrative.

Michael Airola. Photo from SBU

By Daniel Dunaief

Numerous trucks arrive at a construction site, each doing their part to make a blueprint for a building into a reality. In a destructive way, molecules also come together in cancer to change cells that cause damage and can ultimately kill.

Researchers often know the participants in the cancer process, although the structure of each molecule can be a mystery. Determining how the parts of an enzyme work could allow scientists and, eventually, doctors to slow those cancer players down or inactivate them, stopping their cell-damaging or destroying processes.

Recently, Michael Airola, who started his own lab at Stony Brook University early this year and is an assistant professor of biochemistry and cell biology, published a paper in the Proceedings of the National Academy of Sciences in which he showed the structure of an important enzyme that contributes to cell growth regulation in cancer and other diseases, including Alzheimer’s disease.

Called neutral sphingomyelinase, this enzyme produces ceramide, which allows cancer cells to become metastatic. Finding the structure of an enzyme can enable scientists to figure out the way it operates, which can point to pharmacological agents that can inhibit or deactivate the enzyme.

“We are trying to understand the link between structure and function to try to get the first sort of snapshots or pictures of what these enzymes look like” in the on and off states, said Airola. In his research, he showed what this enzyme looked like in its off or inactive state.

Airola joined Stony Brook Cancer Center Director Yusuf Hannun’s lab as a postdoctoral researcher in 2010, when Hannun was working in Charleston, South Carolina, at the Medical University of South Carolina. When Hannun moved to SBU in March of 2012, Airola joined him, continuing his postdoctoral research.

Michael Airola in April in New Orleans aboard the steamboat Natchez on the Mississippi River with his family, wife Krystal Airola, four-year-old Harper and two-year-old Grady. Photo from Michael Airola

Airola conducted his research at Stony Brook and Brookhaven National Laboratory, where he used a technique called X-ray crystallography, which shows the structure of crystallized molecules. Getting this enzyme to crystallize took considerable effort, especially because it has what Airola described as a floppy segment between two rigid structures.

Those floppy pieces, which Airola said aren’t the active sites of the enzyme, can interfere with the structural analysis. To see the important regions, Airola had to cut those flexible parts out, while fusing the rest of the enzyme into a single structure.

The crystallization took almost three years and was a “very difficult process,” Airola recounted. “To get proteins to crystallize, you need to get them to pack together in an ordered fashion.” He said he needed to develop some biochemical tricks to delete a large part in the middle of the protein. “Once we found the right trick and the right region to delete, we were able to crystallize the protein in about three months.”

Airola said he took considerable care to make sure removing the floppy or flexible region didn’t disrupt the function of the enzyme. Hannun and Airola are co-mentoring Prajna Shanbhogue, a graduate student who is in the process of discovering molecules that activate and inhibit the enzyme.

Hannun was pleased with the work Airola did in his lab, which he suggested was a “challenging type of research. Getting to a structure of a protein or enzyme (a specific type of protein) can take several years and is never guaranteed of success, but the rewards can be tremendous,” Hannun explained in an email, adding that Airola was a “critical contributor” and introduced structural biology to his group.

While Airola will continue to work on this enzyme, he is exploring another enzyme, in a collaboration with Hannun and John Haley at Stony Brook, that is involved in colon cancer.

Airola, two graduate students and three undergraduates in his lab are focusing considerable energy on an enzyme involved in the production of triglycerides.

Airola recently received a three-year, $231,000 grant from the American Heart Association to study lipins, a class of enzyme that plays a role both in heart disease and in diabetes. As he did with the enzyme that makes ceramide, Airola is developing a way to understand the structure and function of the triglyceride enzyme. He’d like to find out how this enzyme is regulated. “We’re trying to see if we can inhibit that enzyme, too,” he said.

Airola has “some creative ideas about using information from lipin proteins in plants and fungi, which have a less complex protein structure than mammalian lipins but catalyze the same biochemical reaction,” Karen Reue, a professor in the Department of Human Genetics, David Geffen School of Medicine at UCLA and a collaborator with Airola, explained in an email.

Reue’s lab will complement Airola’s work by conducting physiological analyses of the various “minimal” lipin proteins in processes that the mammalian proteins perform, including triglyceride biosynthesis.

While lipin proteins are necessary for metabolic homeostasis, Reue said a reasonable but still challenging goal might be to modulate the enzyme’s activity for partial inhibition in areas such as adipose tissue, while allowing the triglycerides to perform other important tasks.

Airola lives in East Setauket with his wife Krystal Airola, who is doing her residency in radiology at SBU, and their two children, four-year-old Harper and two-year-old Grady. The couple, who is expecting a third child next month, enjoy living in East Setauket, where they appreciate that they have a forest in their backyard and they can enjoy the water in Port Jefferson and West Meadow Beach.

When Airola’s postdoctoral position ended, he did a broad, national search for his next position and was delighted that he could remain at Stony Brook. “We love the area,” he said. “The research and science here are fantastic.” Airola’s collaborators are optimistic about the prospects for his research.

He is an “up and coming structural biologist that has already made important contributions to the field of lipid biology” Reue said and is a “creative and rigorous scientist with a bright future.”

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We worry about infections regularly. The last thing people want is a cold right before they go on a summer vacation, before they see a newborn, or before they are about to give a presentation half way around the world to a group of people who might approve their work for the next three years.

And, yet, there are some types of infections, or infectious behavior, that have the opposite effect, making us stronger, purging our system of toxins and giving us the extra energy to work harder, to be more patient with traffic around us and to smile when someone accidentally insults us.

Laughter fits that bill. TV producers certainly understand this when they add laugh tracks to their shows. It allows people to feel as if they are not alone, as they laugh with others they can’t see, even if they are alone in front of their TV.

A late family friend used to become so caught up in funny stories that his quick breaths and high-pitched squeals kept him from speaking. The tale, however, became irrelevant as his performance more than compensated for the lack of a narrative, allowing the rest of the room, particularly those who knew him well, to share his laughter.

I can still hear the laughter from my late aunt, whose giggles would often end with joyous tears.

I recently spent a few days with my brothers to celebrate summer birthdays. We sailed, ate well and hit baseballs on a hot, airless field at Gelinas Junior High School.

I stood in right field, as one brother pitched and the other sent bombs deep into the outfield. My sister-in-law patrolled near second base, scooping up grounders and acting as a relay.

My brother crushed a hard grounder directly at his wife. I immediately shouted, “Field it to the side. Move out of the way.”

My brothers started laughing, slowly at first, at advice that was so contrary to the suggestions I had made when I coached baseball and softball over the last decade.

“Yes,” I acknowledged, “but I don’t want her to get hurt. I’d rather she missed a ball that hit a rock or took a crazy bounce than have it slam into her.”

“Sure, sure,” they teased. “You really don’t know anything about this game, do you?”

Then, it occurred to me to go with it.

“Well,” I shrugged, “I’m actually trying a new technique.”

“Oh yeah?” they asked dubiously.

“Yes, I’m going to tell the kids, ‘Take your eyes off the ball and make sure you have absolutely no idea what to do with the ball when it comes to you.’”

After a few snickers, the four of us shared the kinds of things you’d never tell kids on a baseball field, which ramped up the laughter. Things such as “Yes, it is all your fault” and “No, you’re not that good at this sport.”

The laughter somehow  made the heat of the afternoon more bearable.

Later, my younger brother was in the middle of a salad when he offered something so uproariously funny that his lips could barely contain the food, even as he couldn’t possibly swallow. With great effort, he slowed his laughter and swallowed.

I’m not sure what was so funny, but I know the value of laughter. Yes, of course, one movie after another tells us about the power of love, which drives people to incredible achievements and affirms the value of our connections.

Along the way, however, laughter helps fill our tank, soothes the frustrations of the day and puts a broad infectious smile on our faces that can spread, like a beneficial virus, delivering feelings of goodwill that can cascade through a crowd.

Alexander Krasnitz. Photo from CSHL

By Daniel Dunaief

If homeowners could find insects in their home, confirm that they were termites and locate nests before the termites damaged a house, they’d save themselves numerous problems. The same holds true for cancer.

Using the latest molecular biology techniques, researchers at Cold Spring Harbor Laboratory including Associate Professor Alexander Krasnitz and Professor Michael Wigler have explored ways to detect cancer earlier.

Unlike other scientists, who have created tests that reveal the genetic probability of developing cancer, Krasnitz and Wigler developed a blood test to reveal the presence of a tumor that might be hard to spot. Such a test could be particularly valuable for cancers such as ovarian and pancreatic cancer, which can be inoperable by the time they present clinical symptoms.

Urging what Wigler described as a “call to arms,” Krasnitz said they created a blood test, called copy number variation, that they hope will be economically feasible. In copy number variation, sections of genes are repeated. While healthy cells have copy number variation, cancer cells use them like a Jack Nicholson mantra in “The Shining,” where the repetition of “all work and no play makes Jack a dull boy” becomes a calling card for a killing spree.

In cancer, chromosomes or chromosome arms are duplicated or deleted. Sometimes, a narrow region of the genome undergoes amplification, creating multiple copies of the region. Other times, a region of the genome may be lost. Genome-wide copy number variation is a hallmark of cancer. Copy number variation occurs often amid the disruption of DNA repair mechanisms and the breakdown in the way DNA separates into daughter cells during division.

In a recent article in Trends in Molecular Medicine, Krasnitz, Jude Kendall, Joan Alexander, Dan Levy and Wigler — all scientists at CSHL — suggest the potential for single-cell genomic analysis that searches for the presence of copy number variations could raise the alert level for cancer, signaling the need to search more closely for developing tumors.

In most massive cancers in the population, including breast, ovarian and prostate cancer, copy number variation is “ubiquitous,” Krasnitz said. Screening for these changes could provide “evidence for the presence of something abnormal,” which can be validated through other tests, Krasnitz said.

Copy number variation, on its own, is not sufficient to detect cancer, Krasnitz said. Researchers need evidence of similar abnormal copy number profiles in multiple cells. For this test to have clinical relevance, it would need to minimize false positives, which could create alarm and lead to future tests that might not be warranted, while also avoiding false negatives, which would miss the presence of cancer.

The main sources of false positives could come from copy number variation that’s already in cells in the blood that randomly look like a tumor. Cells with partially degraded DNA can have high copy number variation, which the researchers have observed. These profiles, however, arise from random processes and typically look different from each other. Cells from a cancer clone, however, have similar copy number profile.

Cancers with low copy number variation were a minority among the 11 cancers the scientists studied and include a type of colorectal cancer called microsatellite-unstable. If these CSHL researchers developed a preclinical test, they would look for additional ways to detect such cancers.

While numerous technological innovations required for the test exist, including copy number profiling of single cells and methods to enrich specimens from blood for suspected tumors, Krasnitz explained that considerable work remains before its clinical use, including establishing tumor cell counts in the blood of early patients, making single-cell profiling cheaper and finding optimal ways to identify the tissue of origin.

They are planning to study newly diagnosed patients to observe the presence of circulating cells from tumors. Once the scientists prove that the test has some predictive value, they need to ensure that it is economical and that they can follow up with patients to find tumors.

At this point, it’s unclear what the presence of copy number variation might reveal about the type of tumor, which could be a slowly growing or an aggressive type. Additionally, an abnormal indication from this type of analysis wouldn’t reveal anything about the type of cancer. Further tests, including on RNA, would help direct doctors to a specific organ or system.

Apart from his work with Wigler, Krasnitz also has numerous collaborations, including one with CSHL Cancer Center Director David Tuveson.

In his work with Tuveson, Krasnitz is ensuring that the organoid models Tuveson’s lab creates, which are living replicas of tumors taken from patients, faithfully reflect the genetic make up of the tumors. That, Tuveson said, is a significant undertaking because it can validate the organoid model for exploring the biology of tumors.

“This is a deliverable that many people are waiting for,” Tuveson said. The researchers want to make sure “what we grew is what the patient had in the first place.” So far, Tuveson said, the data looks good and the scientists don’t have any examples of the genetics of the organoids differing from that of the tumor.

Krasnitz also attempts to predict an organoid’s response to drugs that haven’t been tested yet based on the organoid’s reaction to other drugs. Tuveson reached out to Krasnitz to work with his group. He said Krasnitz is “a major player” and is “very skilled” in the type of analysis of big data his group generates through the genome, the transcriptome and drug screens. “He’s able to look at those three types of information and make sense of it,” Tuveson said.

Krasnitz is grateful for the support of the Simons Foundation, the National Institutes of Health and the Breast Cancer Research Foundation for his work with Wigler. The most recent article with Wigler is an “invitation for the [research] community to join in the effort,” Krasnitz said. “We want collaborators and more competition in this area.”

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Before we race through August and land on September, I’d like to suggest that we stop and smell the roses, among many other scents of summer.

At the top of the list of smells, on an island where marine life is never far away, is the smell of the ocean. As we lounge on our soft towels, caressed by a gentle breeze, we can breathe in the reviving, sweet smell of salty seawater.

Go to any beach during a summer day and you’ll also find the odor of sunscreen filling the air, courtesy of those spray-on bottles that seem to miss their target and head for the nostrils of the nearest sunbather as often as they reach exposed skin. While you may not want to eat sunscreen in getting away from your office, the smell can help you appreciate your favorite season, as is the case for my wife.

When you’re driving around town, you might reach a stop light or stop sign adjacent to a freshly cut lawn. I’ve always connected that smell with baseball fields, primarily because people started trimming their lawns around the same time as I played my abbreviated baseball season. When I was younger, I had as many games on my schedule in a year as this next generation seems to play in a month.

The atmospheric conditions in this light-intensive time collaborate to liberate the smell of mouthwatering food. At night or on weekends, the smell of a cookout can often encourage us to make a U-turn back to the supermarket to pick up some burgers, hot dogs and chicken.

I can’t drive anywhere near The Good Steer in Lake Grove without my nose acting like a sensory GPS, taking me back to my childhood and the spectacular onion rings that filled my plate.

Stand near just about any bakery in town and you’ll often have the opportunity to enjoy the best form of marketing, as the scent of freshly baked breads and cakes drifts down the street, leading us by our noses to their glass-enclosed treats.

When we were younger, my mother used to get on a sailboat, unpack our pretzels, turkey sandwiches and cold waters, pick up her head as if an old friend had called to her from the middle of the Long Island Sound and proclaim, “Oh, smell.”

Now, I recognize that the world is filled with the kind of foul odors that can turn a subway ride into a trip to “Dante’s Inferno” and that a visit to a friend’s house can also bring the pungency of wet dog to our nostrils.

The heat and the humidity, after all, is an equal-opportunity odor elevator, bringing everything to our attention including an awareness that the guy in the car next to us had garlic at lunch or the woman in line at the deli fell into the marsh in the morning.

Still, I prefer to focus on the proverbial odor glass as being half-full, as did some of my friends, who shared their favorite summer scents.

One person’s favorite smell is that of rain after the first drops fall, while another enjoys honeysuckle and the smell of jasmine from her native Beirut. A third enjoys the scent of coconut with lime or pineapple, and a fourth sings the praises of pine trees, mushrooms and wildflowers that remind him of his youth.

When we breathe in deeply enough these moments of summer rain, honeysuckle, coconuts and wildflowers, we can slow down the treadmill of time.

Elizabeth Boon, back row, center, with graduate students from her lab at Stony Brook University. Photo from Elizabeth Boon

By Daniel Dunaief

It was in the back of Elizabeth Boon’s mind for the last decade. How, she wondered, could the switch that is so critical to life not be there and yet still allow for normal functioning? She suspected that there had to be another switch, so the associate professor in the Department of Chemistry at Stony Brook University, spent the last five years looking for it.

Sure enough, she and graduate students including Sajjad Hossain, found it.

Bacteria, like so many other living creatures, need to have a way of detecting nitric oxide gas. At a high enough concentration, this gas can kill them and, indeed, can kill other living creatures as well, including humans.

Nitric oxide is “toxic to any organism at a high enough concentration,” Boon said. “Most organisms have ways of detecting high concentrations … to avoid toxic consequences.” Other research had found a way other bacteria detect this toxic gas through a system called H-NOX, for heme nitric oxide/ oxygen binding protein.

When bacteria live together in colonies called biofilms, many of them typically rely on a signal about the presence of nitric oxide from the H-NOX protein. And yet, some bacteria survived without this seemingly critical protein. “We and others have shown that H-NOX detection of nitric oxide allows bacteria to regulate biofilm formation,” Boon explained.

Elizabeth Boon with her family, from left, Sheridan, 3, Cannon, 7, Beckett, 1, with her husband Isaac Carrico, who is also an Associate Professor in the Chemistry Department at Stony Brook University. Photo by Alfreda James

Named the nitric oxide sensing protein, or NosP, Boon and her team discovered this alternative signaling system that has some of the same functional group as the original mechanism. When activated in one bacteria, the Pseudomonas aeruginosa, this signaling mechanism causes biofilm bacteria to react in the same way as they would when an H-NOX system was alerted, by breaking up the colony into individuals. Using a flagella, an individual bacteria can move to try to escape from an environment containing the toxic gas.

Nicole Sampson, a professor of chemistry at Stony Brook University, suggested that this work was groundbreaking. While some biofilms are benign or even beneficial to humans, including a biofilm in the human gut, many of them, including those involved in hospital-borne infections, can cause illness or exacerbate diseases, particularly for people who are immunocompromised. Bacteria in biofilm are difficult to eradicate through drugs or antibiotics. When they are separated into individuals, however, they don’t have the same rigid defenses.

“They are resistant to most forms of treatment” when they are in biofilms, Boon said. “If we could get the bacteria to disperse, it’d be much easier to kill them. One of the hopes is that we could develop some sort of molecule that might loosen up the film and then we could come in with an antibiotic and kill the bacteria.”

Boon and her team published their results on the cover of the magazine ACS Infectious Disease, where they presented evidence of what they describe as a novel nitric oxide response pathway that regulates biofilm in the bacteria P. aeruginosa, which lack the H-NOX gene. The day the lab discovered this other protein, they celebrated with a trip for frozen yogurt at Sweet Frog.

In an email, Sampson said that finding the mechanism through which bacteria responds to nitric oxide “is important for developing therapies that target biofilms.”

While Boon is pleased that her lab found an alternative nitric oxide signaling system that answered a long-standing question about how some bacteria could respond to an environmental signal that suggested a threat to the biofilm, she said the answer to the question, as so many others do in the world of science, has led to numerous other questions.

For starters, the lab doesn’t yet know the structure of the NosP. “Not all proteins are immediately willing to crystallize,” Boon said. “We’re hopeful we’ll have a structure soon.” She knows it has a heme group, which includes an iron ion in the middle of an organic compound. That’s where the nitric oxide binds.

“We’d like to have the structure to piece together how that signal is relayed out to the end of the protein and how that gets transferred to other proteins that cause changes in behavior,” she said. The NosP is longer than the H-NOX protein, although they appear to have the same function.

Boon has also found that some bacteria have both the H-NOX and the NosP, which raises questions about why there might be an apparent redundancy. In organisms that have both proteins, it’s tempting to conclude that these bacteria live in a broader range of environments, which might suggest that the two systems react to the gas under different conditions. At this point, however, it’s too early to conclude that the additional sensing system developed to enable the bacteria to respond in a wider range of conditions.

Boon believes the nitric oxide system could be a master regulator of bacterial biofilms. “Detecting nitric oxide might be one of the first things that happen” to protect a bacteria, she said. The reason for that is that bacteria, like humans, use iron proteins in respiration. If those proteins are blocked by nitric oxide, any organism could suffocate.

Boon believes a multistep therapeutic approach might work down the road. She believes breaking up the biofilm would be an important first step in making the bacteria vulnerable to attack by antibiotics. She and her graduate students work with bacteria in the lab that generally only cause human disease in people who are already immunocompromised. Even so, her staff takes safety precautions, including working in a hood and wearing protective equipment.

Boon and her husband Isaac Carrico, who is an associate professor in the Department of Chemistry at Stony Brook University, have a 7-year-old son Cannon, a 3-year-old daughter Sheridan and a 1-year-old son Beckett. Boon said she and her husband are equal partners in raising their three children.

In her work, Boon is excited by the possibility of addressing new questions in this nitric oxide mechanism. “We’re trying to cover as much ground as fast as possible,” she said.