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Cold Spring Harbor Laboratory

Chemist John Moses on the campus of Cold Spring Harbor Laboratory. Photo from CSHL

By Daniel Dunaief

If you build it, he will come.

That’s an iconic line from the movie “Field of Dreams,” starring Kevin Costner, in which a mythical voice calls to the Iowa farmer, encouraging him to plow through his corn to build a baseball field so the ghosts of past baseball players can entertain a modern audience.

It seems only fitting that this year, in which Major League Baseball hosted its first professional game in Iowa near the set of the popular movie, chemists have built something they hope brings together numerous other chemicals to produce products with various applications, from drug discovery to materials science.

About 120 years ago, researchers in France discovered a highly reactive gas called thionyl tetrafluoride, whose chemical symbol is SOF4.

The gas has numerous potential applications because researchers can control its reactions and derivatives. Scientists can swap each sulfur-fluorine bond with a bond between sulfur and something with desirable properties or applications.

While the gas serves as a potential building block, it is scarce and is not commercially available.

Thionyl tetrafluoride is “very reactive,” said chemist and Cold Spring Harbor Laboratory Professor John Moses. “It’s not something the Average Joe wants. It’s dangerous chemistry.” It was largely overlooked until the 1960’s, when chemists at DuPont reinvestigated it.

Once Suhua Li, the lead author of a recent paper in Nature Chemistry and a former post doctoral researcher in Nobel-prize winner K. Barry Sharpless’s lab at Scripps Research Institute in La Jolla, California, generated more of this gas, the team could work together to determine the types of connections that might be possible. 

While the research was a group effort in terms of planning and ideas, Li, who did the vast majority of the synthesis of the gas, is “the hero,” Moses said. “The gas itself, and reagents used to make the gas, are potentially very dangerous, and it takes courage and confidence to attempt such chemistry. ([Li] even had a bit of a mishap, to say the least, but still went ahead and tried again.”

Moses also appreciates how “ideas are just ideas until somebody takes the initiative to put them into practice.”

Moses, Sharpless, and Scripps Research Institute Associate Professor Peng Wu developed the polymer chemistry, while Hans Zuilhof of Wageningen University in the Netherlands helped elucidate the helical structure of the polymers.

The team used a technique Sharpless calls “click chemistry” to explore the substances they could create with this gas.

Thionyl tetrafluoride acts like a lego building block that can be connected with other building blocks in several dimensions.

Click reactions create defined products with absolute reliability, Moses explained. Scientists get what they expect, which is not always true in chemistry.

“In some reactions, you take A and B and you don’t always get C,” Moses said. “You get C as a major product, but you also get D, E and F.”

In click chemistry, however, the combination of A and B is guaranteed to produce C.

Some click reactions run better in water, or at least when water is present. Water is non-toxic, inflammable, inexpensive and a good heat sink.

Click philosophy is about using reliable reactions for the purpose of function discovery.

With thionyl tetrafluoride, Li and the other researchers made about 30 polymers, each of which had original structures using different fragments.

The group managed to attach antibiotics to a thionyl tetrafluoride-derived polymer and demonstrated that it retains antibacterial function.

As long as the module has a handle to exchange with the sulfur-fluorine bond, the gas has a broad range of potential applications.

With thionyl tetrafluoride as his inspiration, Moses coined the term multidimensional click chemistry, which identifies the gas a multi dimensional hub.

The chemists used a regular party balloon to transfer the gas, which is connected to a syringe and a needle. They inserted the needle through a rubber septum into a sealed flask. The reaction with reagents in the flask is straightforward to perform once the gas is available, Moses said.

Born and raised in Wrexham, North Wales, a town aglow after actors Ryan Reynolds and Rob McElhenney last year bought a 156-year-old local soccer team, Moses had no interest in science when he was young, although he was curious about life in general.

He left school to work in a factory that made life rafts and buoyancy jackets when he was 16.

The factory had a distinct odor of toluene and glue.

“It was dreadful,” he recalls. “I was lucky to escape that life.”

He eventually landed an apprenticeship at a company called App-Chem, that allowed him to study physics and chemistry in college one day per week. 

Michelle and Paul Paternoster

By Daniel Dunaief

Part 2

Three families and their foundations jump-started a research mission on Long Island that offers a chance for change. Their stories reflect a desire to remember their family members and a need to offer hope and help to others.

Christina Renna

Christina Renna with sister Rae Marie Renna

Phil Renna waited while his 16-year old daughter Christina spoke with her doctor. He and his wife Rene had decided to allow their daughter, who was battling a form of connective tissue cancer called rhabdomyosarcoma (RMS), to be involved in decisions about her treatment.

When Christina came out of the room, Phil, director of operations in the communications department at Cold Spring Harbor Laboratory, asked if he should also speak with the doctor. Christina said it wasn’t necessary. On the way home, she told him it had to be a “really good Christmas.”

He knew what that meant, although she also asked him not to tell anyone how close she was to the end of her life.

Renna and parents throughout the country have had to cope with the agony of rhabdomyosarcoma, which mostly affects children. People battling this cancer have turned to medicine for help, only to find that the treatment options are limited.

That, Renna and others say, was as unacceptable to them when their children were battling cancer as it is now, when the next generation is struggling with this illness.

RMS doesn’t receive the same level of funding nationally as cancers that affect more people, such as breast, lung and prostate cancer, but the agony and suffering are just as significant.

Amid their battles with the disease, families have turned to their support groups, including friends, extended family, and community members to raise funds for basic research, hoping grass roots efforts allow future generations to have longer, healthier lives.

Supported by these funds and a willingness to fill a research gap, Cold Spring Harbor Laboratory CEO Bruce Stillman has backed efforts to gather information and to support research that may also help people with other forms of cancer.

Renna, who lives in Lindenhurst, struggled with his role as father and protector when Christina developed rhabdomyosarcoma.

“I’m supposed to protect my kids,” Renna said. “I should be able to tell them, ‘It’s going to be okay.’”

Renna went to Stillman to ask whether Christina, who was a patient at Memorial Sloan Kettering, might get better care somewhere else.

After conducting some research, Stillman told his colleague about the lack of basic research and other treatment options.

“That was a crushing moment for me,” Renna said.

During treatment, Christina had to be at Memorial Sloan Kettering at 7 a.m., which meant he and Christina’s mother Rene got in the car at 5 a.m. with their daughter.

Renna dropped them off, drove back to work, where he’d put in a full day, drive back to the hospital and return home at 10:30 p.m.

“That was every night, five days a week,” Renna recalled. While those were tough days, Renna said he and his wife did what they needed to do for their daughter.

Five years after his daughter died at the age of 16, Renna drove home from work one day to find his shirt was wet. It took him a while to realize the moisture came from the tears, as he cried his way back to his house. At one point, he thought he had post-traumatic stress disorder.

Renna continues to raise money to support research into this disease, while also helping people create and develop their own foundations, often after enduring similar pain.

“Every single foundation that has come and given money to the lab, I have personally met with,” he said. “I helped our advancement team onboard them.”

As someone who has lost a child and understands what a parent can be feeling, Renna is committed to helping others cope with their grief. 

“For me, it is about helping the lab, but also about helping families honor the memory of their child in a meaningful way and what better way than to help another family and perhaps find a cure,” he wrote in an email.

Renna believes investments in research will pay off, helping to answer basic questions that will lead to better treatments down the road.

So far, the foundation has given $387,300 to Cold Spring Harbor Laboratory for research. They also gave $50,000 to Make-a-Wish in Suffolk, and $25,000 to local scholarships. The foundation supported Memorial Sloan Kettering with an iPad program. Ultimately, Renna believes in the ongoing return from research investments.

“Everybody wants to find and fund the silver bullet,” he said. “Everybody wants to give money to fund a clinical trial. Basic research is where the discoveries are made.”

Renna urged people creating foundations to have a strong board that included business people and that might also have a scientific or medical advisory element. He also suggested funding foundations a year ahead of time. That helped his foundation in 2020, when finding donors became more challenging during the pandemic.

Being at Cold Spring Harbor Laboratory and helping others get through darker days that are all too familiar to him gives Renna comfort. “I know, in some way, every single day, I’m making an impact,” he said. “How measurable it is, I don’t know. There are days when I’m pretty proud.”

As far as he feels they have come, Renna said it’s not the time to look back, but to press ahead.

T.J. Arcati

A former summer intern in Bruce Stillman’s lab when he attended Notre Dame, T.J. Arcati was married and had two children when he succumbed to sarcoma.

“We know what we went through,” said his father, Tom Arcati, an oral and maxillofacial surgeon in Huntington. “He left a son and a daughter without a dad.”

Tom and his wife Nancy, who raised T.J. in Lloyd Harbor and live in Huntington, were with their son for his treatments and therapies.

Tom and Nancy Arcati are determined to extend people’s lives by more than a year or two and are actively engaged with other families who are coping in the midst of the cancer storm. “I’m talking to people now that unfortunately are going through what we did seven years ago,” Tom Arcati said.

While the Arcatis support other families, their empathy “brings you back to a place you never really leave,” Nancy Arcati said. These interactions “keeps T.J.’s life on people’s minds and in their hearts.”

Tom Arcati tries to be a source of solace to people who are trying to gather information.

In the aftermath of TJ’s death at the age of 34, Arcati reached out to Stillman to see if the lab could work towards better treatments.

One Saturday, Arcati and his son Matthew went to Stillman’s house, where they sat in his living room, with Stillman drinking tea and Arcati having coffee.“What do you think?” Arcati recalled asking. “Are you going to do sarcoma research?” Stillman looked back at his guest and mentioned that he was thinking about it. Stillman called Arcati a few days later.

“When he called me, he said, ‘We’re a cancer institute. We should be doing sarcomas.’ That’s how I remember this whole thing going down. It was pretty heart warming.”

The first step for CSHL was to host a Banbury conference. The site of international meetings on a range of scientific topics since 1978, the Banbury center brings together experts in various fields. The meetings provide a forum for scientific advances and result in various publications. By holding a Banbury Center meeting, CSHL helped advance research into sarcomas.

The Arcatis have remained active in the Friends of T.J. Foundation, which TJ and several college friends founded in 2009 after T.J. was diagnosed with sarcoma. They have stayed in close contact with CSHL Professor Chris Vakoc and his PhD student Martyna Sroka, who regularly keeps him informed of her progress. Sroka has spoken at some of the outings for the Friends of TJ Foundation. This year, Stillman will speak at the September 13th fundraiser at the Huntington Country Club.

“It’s really imperative that people who are supporting us know what their dollars are being spent on,” Arcati said.

The Friends of TJ Foundation has raised about $50,000 each year, bringing their total fundraising to about $400,000.

Arcati hopes something positive can come out of the losses the families who are funding Vakoc’s research suffered.

“If we can save one kid’s life somewhere by doing what we’re doing, then this whole process is worth it,” Arcati said.

Michelle Paternoster

Michelle Paternoster of Lindenhurst developed sarcoma in her sinuses. Her husband Paul Paternoster helped her through 38 surgeries, over 90 radiation treatments and several rounds of chemotherapy.

Michelle and Paul Paternoster

The couple tried immune therapy in the Bahamas in the fall of 2008 and went to New York in 2011 for treatment.

“We drove [to the city] for 90 days” excluding weekends, Paternoster recalled. The treatments seemed to have a positive effect during the trial, but shortly afterward, the cancer continued growing.

After Michelle died in 2013 at the age of 34, Paternoster was determined to help others, initially asking supporters to contribute to the fundraising effort from the Arcatis.

Donations to the Friends of T.J. Foundation reached $30,000, which helped underwrite the Banbury conference at Cold Spring Harbor Laboratory. Michelle and T.J. had seen each other in the radiation suite in the halls of Memorial Sloan Kettering.

Paternoster then started the Michelle Paternoster Foundation for Sarcoma Research. The President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, Paternoster wanted to help people at a clinical level.

Through Michelle’s Clubhouse, he partnered with the Children’s Hospital of Pittsburgh, paying for hotels of pediatric cancer patients when the Ronald McDonald house is full. The clubhouse also provides gift cards to help pay for gas, tolls and copays on prescriptions.

“Knowing how difficult it is to go through this, I can’t imagine what it’s like to not have that capability” to pay for basic needs during treatment, Paternoster said. “That is why it is so important for our board to do something at the clinical level to support families in this battle.”

Paternoster said the relatively small but growing size of the group dedicated to helping each other makes each person’s contribution that much more important.

“Normally, when you’re doing any kind of charity work, you feel like you’re a tiny part of this project, especially when it comes to [diseases like] breast cancer and things that impact millions of people,” Paternoster said. When he attended the Banbury conference that launched the research effort at Cold Spring Harbor Laboratory, he said “you felt you could make a difference. You’re sitting in a room with 25, 30 people max. That was the entire effort to eradicate this disease.”

Paternoster, who lives in Cold Spring Harbor, called the collaboration that came out of the meeting “astounding.”

The Michelle Paternoster Foundation has raised $500,000, with about $350,000 of that supporting the work at Cold Spring Harbor Laboratory.

Ultimately, like the other families who raise funds, stay informed and offer help to strangers battling an all-too-familiar disease, Paternoster feels that the opportunity to make a meaningful contribution inspires him.

“That’s our dream,” he said, “to find a cure, so other people don’t have to feel what we felt.”

To read Part 1 of the article click here.

Martyna Sroka. Photo by Sofya Polyanskaya

By Daniel Dunaief

Part 1:

A group of people may prove to be the guardian angels for the children of couples who haven’t even met yet.

After suffering unimaginable losses to a form of cancer that can claim the lives of children, several families, their foundations, and passionate scientists have teamed up to find weaknesses and vulnerabilities in cancers including rhabdomyosarcoma and Ewing sarcoma.

Rhabdomyosarcoma affects about 400 to 500 people each year in the United States, with more than half of those patients receiving the diagnosis before their 10th birthday. Patients who receive diagnoses for these cancers typically receive medicines designed to combat other diseases.

 

Christopher Vakoc. Photo from CSHL

A group of passionate people banded together using a different approach to funding and research to develop tools for a different outcome. Six years after the Christina Renna Foundation and others funded a Banbury meeting at Cold Spring Harbor Laboratory, the grass roots funders and dedicated scientists are finding reasons for optimism.

“I wish I could run up to the top of a hill and scream it out: ‘I’m more hopeful than I’ve ever been,’” said Phil Renna, director of operations, communications department at CSHL and the co-founder of the Christina Renna Foundation. “I’m really excited” about the progress the foundation and the aligned group supporting the Sarcoma Initiative at the lab has made.

Renna and his wife Rene started the foundation after their daughter Christina died at the age of 16 in 2007 from rhabdomyosarcoma. Renna’s optimism stems from work Cold Spring Harbor Laboratory’s Christopher Vakoc, a professor and Cancer Center co-director and his research team, including PhD candidate Martyna Sroka have performed.

The cause for optimism comes from the approach Vakoc has taken to cancers, including leukemia.

Vakoc has developed a way to screen the effects of genetic changes on the course of cancer.

“Usually, when you hear about a CRISPR screen, you think of taking out a function and the cell either dies or doesn’t care,” Sroka said, referring to the tool of genetic editing. Sroka is not asking whether the cell dies, but whether the genetic change nudges the cellular processes in a different direction.

“We are asking whether a loss of a gene changes the biology of a cell to undergo a fate change; in our case, whether cancer cells stop growing and differentiate down the muscle lineage,” she explained.

In the case of sarcoma, researchers believe immature muscle cells continue to grow and divide, turning into cancer, rather than differentiating to a final stage in which they function as normal cells.

Through genetic changes, however, Sroka and Vakoc’s lab are hoping to restore the cell to its non cancerous state.

Cold Spring Harbor Laboratory has had success with other diseases and other types of cancer, which is where the optimism comes from, explained Paul Paternoster, President of Selectrode Industries, Inc. and the founder of the Michelle Paternoster Foundation for Cancer Research.

As a part of her doctoral research which she’s been conducting for four years, Sroka is also working with Switzerland-based pharmaceutical company Novartis AG to test the effect of using approved and experimental drugs that can coax cells back into their muscular, non-cancerous condition.

The work Sroka and Vakoc have been doing and the approach they are taking could have applications in other cancers.

“The technology that we’ve developed to look at myodifferentiation in rhabdomyosarcoma can be used to study other cancers (in fact, we are currently applying it to ask similar questions in other cancer contexts),” said Sroka. “In addition, our findings in RMS might also shed light on normal muscle development, regeneration and the biology of other diseases that impact myodifferentiation, e.g. muscular dystrophy.”

Martyna Sroka’s journey

Described by Vakoc as a key part of the sarcoma research effort in his lab, Martyna Sroka, who was born and raised in Gdańsk, Poland, came to Long Island after a series of eye-opening medical experiences.

In Poland, when she was around 16, she shadowed a pediatric oncology doctor who was visiting patients. After she heard the patient’s history, she and the doctor left the room and convened in the hallway.

Martyna Sroka. Photo by Sofya Polyanskaya

“He turned to me and said, ‘Yeah, this child has about a month or two tops.’ We moved on to the next case. I couldn’t wrap my head around it. That’s as far as we could go. There’s nothing we could do to help the child and the family,” said Sroka.

Even after she started medical school, she struggled with the limited ammunition modern medicine provided in the fight against childhood cancer.

She quit in her first year, disappointed that “for a lot of patients diagnosed with certain rare types of tumors, the diagnosis is as far as the work goes. I found that so frustrating. I decided maybe my efforts will be better placed doing the science that goes into the development of novel therapies.”

Sroka applied to several PhD programs in the United Kingdom and only one in the United States, at Cold Spring Harbor Laboratory, where she hoped to team up with Vakoc.

Sroka appreciated Vakoc’s approach to the research and his interest in hearing about her interests.

“I knew that we could carve out an exciting scientific research project that tries to tackle important questions in the field of pediatric oncology, [the] results of which could potentially benefit patients in the future,” she explained in an email.

The two of them looked at where they could make a difference and focused on rhabdomyosarcoma.

Sroka has “set up a platform by which advances” in rhabdomyosarcoma medicines will be possible, Vakoc said. “From the moment she joined the sarcoma project, she rose to the challenge” of conducting and helping to lead this research.

While Sroka is “happy” with what she has achieved so far, she finds it difficult at times to think about how the standard of care for patients hasn’t changed much in the last few decades.

“Working closely with foundations and having met a number of rhabdomyosarcoma patients, I do feel an intense sense of urgency,” she wrote.

Read Part 2 here.

 

Attendees at a conference at CSHL, an in-person tradition started in 1933. These conferences were suspended from 1943 to 1945 during WWII and were virtual during the pandemic in 2020 and for most of 2021. Photo by Miriam Chuai/CSHL

By Daniel Dunaief

For scientists, meetings and conferences aren’t just a chance to catch up on the latest research, gossip and see old friends: they can also provide an intellectual spark that enhances their careers and leads to new collaborations.

Amid the pandemic, almost all of those in-person conferences stopped, including the annual courses and meetings that Cold Spring Harbor Laboratory hosts. The internationally renowned lab has run meetings since 1933, with a few years off between 1943 and 1945 during World War II.

CSHL’s David Stewart. Photo by Gina Motisi/CSHL

While scientists made progress on everything from basic to translational research, including in laboratories that pivoted towards work on the SARS-CoV-2 virus, which causes COVID-19, they missed out on the kinds of opportunities that come from in-person interactions.

Assuming COVID infection rates are low enough this fall, CSHL is hoping to restart in-person conferences and courses, with the first conference that will address fifty years of the enzyme reverse transcriptase scheduled for Oct. 20th through the 23rd. That event was originally scheduled for October of 2020.

One of the planned guest speakers for that conference, David Baltimore, who discovered the enzyme that enables RNA to transfer information to DNA and is involved in retroviruses like HIV, won the Nobel Prize.

“I am hoping that there will be significant participation by many eminent scientists, so that is in itself somewhat [of] a ceremonial start,” wrote David Stewart, Executive Director of meetings and courses at Cold Spring Harbor Laboratory.

To attend any of the seven in-person meetings on the calendar before the end of the year, participants need to have vaccinations from either Pfizer, Moderna, Johnson & Johnson or AstraZeneca.

Attendees will have to complete an online form and bring a vaccination card or certificate. Scientists who don’t provide that information “will not be admitted and will not get a key to their room or be able to attend the event,” Stewart said.

CSHL also plans to maintain the thorough and deep cleaning procedures the lab developed. 

Stewart hopes that 75 to 80 percent or more of the talks presented will be live, with a virtual audience that could be larger than the in-person attendance.

“It is important to have a critical mass of presenters and audience in-person, but there’s no real limit on how large the virtual audience could be,” he explained.

Typically, the courses attract participants from over 50 countries. Even this year, especially with travel restrictions for some countries still in place, Stewart expects that the majority of participants will travel from locations within the United States.

The Executive Director explained that CSHL was planning to introduce a carbon offset program for all travel to conferences and courses that the facility reimburses starting in 2020. After evaluating several options, they plan to purchase carbon offsets from Cool Effect and will encourage participants paying their own way to do the same or through a similar program.

The courses, meanwhile, will begin on October 4th, with macromolecular crystallography and programming for biology. CSHL hopes to run six of these courses before the end of the year, including a scientific writing retreat.

“We are looking to 100 percent enrollment for our courses, so likely this year that will largely be domestic,” Stewart explained.

The courses, which normally have 16 participants, may have 12 students, as the lab tries to run these training opportunities safely without masks or social distancing.

From March of 2020 through the end of last year, the lab had planned 25 meetings and 25 courses. As the pandemic spread, the lab pivoted to virtual meetings. “I felt like a car salesman trying to sell virtual conferences,” Stewart recalled. For the most part, the lab was able to keep to its original schedule of conferences, albeit through a virtual format.

In addition to the scheduled meetings, CSHL decided to add meetings to discuss the latest scientific information related to COVID research. 

Stewart approached Hung Fan, a retired virologist at the University of California at Irvine, to help put together these COVID exchanges. Those meetings occurred in June, July, August, October, and January. The sixth one recently concluded.

The meetings addressed “everything around the science of the virus,” Stewart said, which included the biology, the origin, the genomics, the immune response, vaccines, therapeutics and diagnostics, among other scientific issues.

“There was a lot of excellent work being done around SARS-CoV-2,” Stewart said. “We were trying to identify that early on. It was helpful to have people who knew the field well.”

Fan said he combed through preprints like the CSHL-based bioRxiv and related medRxiv every day for important updates on the disease.

Fan described the scientific focus and effort of the research community as being akin to the Manhattan Project which built the atomic bomb during World War II, where “everybody said, ‘We have a common enemy and we want to apply all our capabilities to combating that.”

While Fan is pleased with the productive and valuable exchanges that occurred amid the virtual conferences, he recognized the benefit of sharing a room and a drink with scientific colleagues.

“A lot of the productive interactions at meetings take place in a social setting, at the bar, over dinner” and in other unstructured gatherings, he said. “People are relaxed and can share their scientific thoughts.”

After presentations, Fan described how researchers discuss the work presented and compare that to their own efforts. It’s easier to talk with people in person “as opposed to making a formalized approach through letters and emails.”

A western view of Cold Spring Harbor, above. The seawall is visible along the shoreline beneath the buildings. Photo from Cold Spring Harbor Laboratory

Over a decade before the Civil War, brothers John, Walter and Townsend Jones recognized that they needed to protect the land at Cold Spring Harbor from the effects of storms that flooded and eroded the shoreline.

The view circa 1910. Cold Spring Harbor Laboratory Archives

In 1850, they built a seawall using stones transported in three schooners from a Connecticut quarry to block water from coming ashore in what is now the picturesque coast of the Cold Spring Harbor Laboratory, according to the booklet “Cold Spring Harbor Rediscovering history in street and shores by Terry Walton.

Time and powerful storms, including Hurricane Sandy in 2012, have taken their toll on the protective seawall, causing weaknesses that might allow future storms or water surges to damage the internationally renowned lab and the surrounding area.

Cold Spring Harbor Laboratory will soon start an effort to rebuild and refurbish the seawall, preserving some of its historical value by reusing original stones. The refurbishing effort, which will cost $14 million and includes $500,000 from New York State, will take 10 to 11 months to complete.

The state funds have been appropriated and are in the process of being released from the New York State Department of Budget, according to State Senator James Gaughran (D-Northport). Gaughran said he helped secure the funds and is pleased with their design.

“I applaud Cold Spring Harbor [Laboratory] for incorporating the original stones in the seawall’s restoration, which will preserve the beauty of the historic seawall,” Gaughran explained in an email.

“It’s really a feat that it lasted as long as it has,” said Stephen Monez, facilities manager at CSHL. The designers originally built the wall by stacking stones on top of each other.

“We’re starting to lose elevation of our ground,” Monez said. Utility lines for a lab where four Nobel prize winners have conducted some of their research over the years and where numerous faculty continue to conduct basic and translational research run behind the seawall, increasing the importance of the effort.

The seawall, which the Jones brothers and their Cold Spring Harbor Whaling Company built, has failed in two places, according to Errol Kitt, vice president, principal and Long Island branch manager for GEI Consultants Inc, PC. Kitt, who runs the Huntington Station office of GEI, leads the team that developed design plans for the new seawall.

A national company, GEI has worked in other areas of historical significance, including Boston Harbor.

The Cold Spring Harbor seawall is an “interesting one, with reusing the stones,” Kitt said. “That’s the new twist to this.”

The original seawall. Photo from Cold Spring Harbor Whaling Museum

Kitt helped ensure that the plans would be consistent with the concerns of regulatory agencies.

“We came up with a preliminary design that we sought buy-in from the regulatory agencies early on,” Kitt said. “That helped move the project along.”

Skanska, a Swedish-based construction and engineering group, will oversee the work, while Triumph Construction will do the construction. Kitt said the team has permits in place to start construction and is awaiting the U.S. Army Corps of Engineers to finalize their permit.

The seawall had been protecting the area for four decades in the 19th century when the Biological Laboratory of the Brooklyn Institute of Arts and Sciences, a predecessor to CSHL, was established in 1890.

State and local authorities, including the New York State Historic Preservation Office, the U.S. Army Corps of Engineers and the Village of Laurel Hollow, have approved the plans to rebuild the wall.

Skanska, a Swedish-based construction and engineering group, will oversee the project, while Triumph Construction, of the Bronx, will do the building work. The Huntington Station office of GEI Consultants provided the design and engineering plans.

Triumph will use concrete and rebar to rebuild a seawall that will be 2 feet higher than the original. That is the maximum additional height the lab could add. The company will clean the original and historic stones, which they will then use to reface the seawall to retain its original look.

The New York State Historic Preservation wanted to ensure that the wall “would look as original as it was before we did this project,” Monez said.

In 2014, the lab started putting money aside to rebuild the seawall. In the last 18 months, the weather has caused erosion.

“Once a wall starts to go, it doesn’t take [long] for the rest of it” to weaken, Monez said.

The facilities team at CSHL recently closed the road along the shoreline.

The seawall will be longer than the original, with the team adding more to the structure on the landward side.

CSHL has put up a 10-foot high safety fence, has added warning signs to the area and mandated a hardhat area.

Members of the facilities staff are also receiving 10 hours of training from the Occupational Safety and Health Administration, a regulatory agency of the U.S. Department of Labor, in case they need to enter the area.

The construction team is putting in sheet piling prior to rebuilding the seawall to protect the land while they do the work. This will prevent any damage from tidal or storm surge over the next year until the project is complete.

The first two months of the work is likely to be the loudest part of the construction process.

“We met with scientists in adjacent buildings,” Monez said.

He said the effort will provide protection for the area amid storms and any rise in the sea level.

“We are installing our insurance policy for the future,” Monez said.

Photo courtesy of CSHL

By Daniel Dunaief

Cold Spring Harbor Laboratory’s DNA Learning Center and the Red Cloud Indian School recently launched a program called Students Talk Science in which high school students could ask questions from several senior scientists about the vaccine for COVID-19 and healthcare disparities in minority communities.

Dr. Eliseo Pérez-Stable

 

The talks are a component of a program called STARS, for Science, Technology & Research Scholars, an effort the group started in 2019 to build interest and experience in STEM for minority students. The Students Talk Science program engaged the STARS participants and students from the Red Cloud Indian School on the Pine Ridge Indian Reservation.

Jason Williams, Assistant Director of Inclusion and Research Readiness at the DNA Learning at CSHL; Brittany Johnson, an educator at the DNA Learning Center; Katie Montez, a teacher at the Red Cloud Indian School ;and Carol Carter, Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, wanted to connect minority students with practicing physicians and scientists in leadership positions at the National Institutes of Health to allow them to ask questions of concern regarding the vaccines.

Dr. Monica Webb-Hooper

“We did this to empower them to function as trusted resources for their families, friends and network,” Carter, who participated as an individual rather than as a formal representative of Stony Brook University, explained in an email.

The conversations included interactions with Dr. Eliseo Pérez-Stable, Director of the National Institute on Minority Health and Health Disparities, or NIMHD at the National Institutes of Health; Dr. Monica Webb Hooper, Deputy Director of the NIMHD; Dr. Gary Gibbons, Director of the National Heat, Lung and Blood Institute; and Dr. Eugenia South, Assistant Professor in Emergency Medicine at the Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia.

The high school students prepared informed questions.

Dr. Gary Gibbons

“The students were encouraged to do their own research” on the interview subjects, Williams explained. “We asked students not to look just at [each] interviewee’s science work, but also any personal background/ biography they could find. Students had multiple opportunities for follow up and were largely independent on their choices of questions.”

Samantha Gonzalez, a student at Walter G. O’Connell Copiague High School, asked South about her initial skepticism for the vaccine.

South acknowledged that she had no interest in taking the vaccine when she first learned she was eligible. “I almost surprised myself with the fierceness with which I said, ‘No,’” South said. “I had to step back and say, ‘Why did I have this reaction?’”

Some of the reasons had to do with mistrust, which includes her own experiences and the experiences of her patients, whom she said have had to confront racism in health care. In addition, she was unsure of the speed at which the vaccine was developed. She had never heard of the mRNA technology that made the vaccines from Moderna and Pfizer/ BioNTech possible.

“I had to do my own research to understand that this wasn’t a new technology,” she said.

Dr. Eugenia South

South went through a learning process, in which she read information and talked to experts. After she received answers to her questions and with the urging of her mother, she decided to get the vaccine.

“I’m so thankful that I was able to do that,” South said.

The team behind Students Talk Science not only wanted to empower students to make informed decisions, but also wanted to give them the opportunity to interact with scientists who might serve as personal and professional role models, providing a pathway of information and access that developed amid an extraordinary period.

“We wanted to engage high school students in something unique going on in their lifetime,” Carter said.

To be sure, Carter and Williams said the scientific interactions weren’t designed to convince students to take the vaccine or to urge their parents or families to get a shot. Rather, they wanted to provide an opportunity for students to ask questions and gather information.

“We purposely did not participate in the discussions because our goal was not to convince or ‘preach,’ but to enable students and their networks to make informed decisions,” Carter said.

Parents had to read and sign off on the process for students to participate. The organizers didn’t want a situation where they were doing something that conflicts with a parents’ decisions or views.

Williams added that the purpose of the conversations was never to say, “you must get the vaccine. Our purpose is to talk about information.”

The objective of these interactions is to help minority students find a track for a productive career in ten years.

In addition to questions about hesitancy, Williams said some of the high school students expressed concerns about access to vaccines. He is pleased with the result of this effort to connect students with scientists and doctors.

The group was “able to get some of the most important scientists in the country to sit with high school students,” he said. “It was very powerful to give students access to these role models.”

The goal is to stay with these students, mentor them and stay in touch with them until they graduate from college and, perhaps, return as research scientists.

Even for students who do not return, this type of interaction could provide an “impactful experience that prepares them for other opportunities,” Williams explained, adding that the STARS program would incorporate the Students Talk Science Series into the program more formally in the future, with new students and topics most likely during the school year.

The interviews are available at the following website: https://dnalc.cshl.edu/resources/students-talk-science/.

From left, John Inglis and Richard Sever. Photo from CSHL

By Daniel Dunaief

Scientists rarely have people standing at their lab door, waiting eagerly for the results of their studies the way the public awaits high-profile verdicts.

That, however, changed over the last 16 months, as researchers, public health officials, school administrators and a host of others struggled to understand every aspect of the basic and translational science involved in the Sars-Cov2 virus, which caused the COVID-19 pandemic.

With people becoming infected, hospitalized and dying at an alarming rate, businesses closing and travel, entertainment and sporting events grinding to a halt, society looked to scientists for quick answers. One challenge, particularly in the world of scientific publishing, is that quick and answers don’t often mesh well in the deliberate, careful and complicated world of scientific publishing.

The scientific method involves considerable checking, rechecking and careful statistically relevant analysis, which is not typically designed for the sharing of information until other researchers have reviewed it and questioned the approach, methodology and interpretation.

The pandemic changed that last year, increasing the importance of preprint servers like bioRxiv and medRxiv at Cold Spring Harbor Laboratory, which provide a way for researchers to share unfiltered and unchecked information quicker than a scientific review and publishing process that can take months or even years.

The pandemic increased the importance of these preprint servers, enabling scientists from all over the world to exchange updated research with each other, in the hopes of leading to better basic understanding, diagnosis, treatment and prevention of the spread of the deadly virus.

The importance of these servers left those running them in a bind, as they wanted to balance between honoring their mission of sharing information quickly and remaining responsible about the kinds of information, speculation or data that might prove dangerous to the public.

Richard Sever and John Inglis, Assistant Director and Executive Director of Cold Spring Harbor Laboratory Press, created pandemic-specific criteria for work reporting potential Covid-19 therapies.

“Manuscripts making computational predictions of COVID-19 therapies are accepted only if they also include in vitro [studies in test tubes or with live cells] or in vivo [studies in live subjects] work,” the preprint directors wrote in a recent blog. “This restriction does not apply to non-covid-19 work.”

Inglis and Sever continue to decline research papers that might cause people to behave in ways that compromise public health.

“We are simply doing our best to tread carefully in the early days of clinical preprints, as we gain experience and bias our actions toward doing no harm” the authors wrote in their blog.

In the first few months after the pandemic hit the United States, the pace at which scientists, many of whom pivoted from their primary work to direct their expertise to the public health threat, was the highest bioRxiv, which was founded in November of 2013, and medRxiv, which was started in June of 2019, had ever experienced.

These preprint servers published papers that wound up leading to standards of care for COVID-19, including a June research report that appeared on June 22nd in medRxiv on the use of the steroid dexamethasone, which was one of the treatments former President Donald Trump received when he contracted the virus.

The rush to publish information related to the virus has slowed, although researchers have still posted over 16,000 papers related to the virus through the two pre-print servers. MedRxiv published 12,400 pandemic-related papers since January of 2020, while bioRxiv published over 3,600.

At its peak in late March of 2020, medRxiv’s abstract views reached 10.9 million, while downloads of the articles were close to five million.

Currently, bioRxiv is publishing about 3,500 papers a month, while medRxiv put up about 1,300 during a month. Close to 60 percent of the medRxiv papers continue to cover medical issues related to the pandemic.

The numbers of page views are “not anywhere near the frenzy of last year,” Inglis said in an interview. 

With the volume of papers still high, people can receive alerts from the preprint servers using parameters like their field of interest or word searches.

“The real question is how to sort out the gold from the dross,” Inglis said. While some people have suggested a star system akin to the one shopping services use, Inglis remained skeptical about the benefit of a scientific popularity contest.

“Have you looked at the stuff [with four or five stars] on Amazon? It’s one thing if you’re buying a widget, but it’s different if you’re trying to figure out what’s worthwhile science,” he said.

Other organizations have reviewed preprints, including the Bloomberg School of Public Health at Johns Hopkins.

“By sheer diligence, the [Johns Hopkins team] go into medRxiv mostly and simply pick out things they think are striking,” Inglis said. 

At the same time, a team of researchers led by Nicolas Vabret, Robert Samstein, Nicolas Fernandez, and Miriam Merad created the Sinai Immunology Review Project, which provides critical reviews of articles from the Cold Spring Harbor Laboratory preprint sites. The effort ranks COVID-related preprints according to their immunological relevance. Fernandez created a dedicated website to host and integrate the reviews. The group also worked with Nature Reviews Immunology to publish short weekly summaries of preprints, according to a comment piece in that journal.

BioRxiv and medRxiv were founded on the belief that early sharing of results as preprints would speed progress in biomedical research, better equipping scientists to build on each other’s work.

“My team is proud to have contributed to the response to this worldwide human tragedy,” Inglis said. “We’re also glad we made the decision to set up a separate server for health science, in which the screening requirements are different and more stringent.”

Inglis explained that the pre-print servers have “learned a lot in the past year” about providing information during a crisis like the pandemic. “If another pandemic arose, we’d apply these learnings and respond immediately in the same way.”

Linda Van Aelst. Photo from CSHL

By Daniel Dunaief

Different people respond to the same level of stress in a variety of ways. For some, a rainy Tuesday that cancels a picnic can be a minor inconvenience that interrupts a plan, while others might find such a disruption almost completely intolerable, developing a feeling of helplessness.

Scientists and clinicians have been working from a variety of perspectives to determine the cause of these different responses to stress.

From left, graduate student Nick Gallo, Linda Van Aelst and Postdoctoral Researcher Minghui Wang. Photo by Shanu George

Cold Spring Harbor Laboratory Professor Linda Van Aelst and a post doctoral researcher in her lab, Minghui Wang, recently published a collaborative work that also included graduate student Nicholas Gallo, postdoctoral researcher Yilin Tai and Professor Bo Li in the journal Neuron that focused on the gene Oligophrenin-1, which is also implicated in intellectual disability.

As with most X-linked diseases, the OPHN1 mutation primarily affects boys, who have a single X chromosome and a Y chromosome. Girls have two X chromosomes, giving them a backup gene to overcome the effect of an X-linked mutation.

In addition to cognitive difficulties, people with a mutation in this gene also develop behavioral challenges, including difficulty responding to stress.

In a mouse model, Wang and Van Aelst showed that the effect of mutations in this gene mirrored the stress response for humans. Additionally, they showed that rescuing the phenotype enabled the mouse to respond more effectively to stress.

“For me and [Wang], it’s very exciting,” Van Aelst said. “We came up with this mouse model” and with ways to counteract the effect of this mutated analogous gene.

As with many other neurological and biological systems, Oligophrenin1 is involved in a balancing act in the brain, creating the right mix of excitation and inhibition.

When oligophrenin1 was removed from the prelimbic region of the medical prefrontal cortex, a specific brain area that influences behavioral responses and emotion, mice expressed depression-like helpless behaviors in response to stress. They then uncovered two brain cell types critical for such behavior: the inhibitory neurons and excitatory pyramidal neurons. The excitatory neurons integrate many signals to determine the activity levels in the medial prefrontal cortex.

The inhibitory neurons, meanwhile, dampen the excitatory signal so they don’t fire too much. Deleting oligophrenin1 leads to a decrease in these inhibitory neurons, which Van Aelst found resulted from elevated activity of a protein called Rho kinase.

“The inhibitor keeps the excitatory neurons in check,” Van Aelst said. “If you have a silencing of the inhibitory neurons, you’re going to have too much excitatory response. We know that contributes to this maladaptive behavior.”

Indeed, Wang and Van Aelst can put their metaphorical finger on the scale, restoring the balance between excitation and inhibition with three different techniques.

The scientists used an inhibitor specific for a RhoA kinase, which mimicked the effect of the missing Oligophrenin1. They also used a drug that had the same effect as oligophrenin1, reducing excess pyramidal neuron activity. A third drug activated interneurons that inhibited pyramidal neurons, which also restored the missing inhibitory signal. All three agents reversed the helpless phenotype completely.

Japanese doctors have used the Rho-kinase inhibitor fasudil to treat cerebral vasospasm. which Van Aelst said does not appear to produce major adverse side effects. It could be a “promising drug for the stress-related behavioral problems” of oligophrenin1 patients, Van Aelst explained in an email. “It has not been described for people with intellectual disabilities and who also suffer from high levels of stress.”

From left, graduate student Nick Gallo, Linda Van Aelst and Postdoctoral Researcher Minghui Wang. Photo by Shanu George

Van Aelst said she has been studying this gene for several years. Initially, she found that it is a regulator of rho proteins and has linked it to a form of intellectual disability. People with a mutation in this gene had a deficit in cognitive function that affected learning and memory.

From other studies, scientists learned that people who had this mutation also had behavioral problems, such as struggling with stressful situations.

People with intellectual difficulties have a range of stressors that include issues related to controlling their environment, such as making decisions about the clothing they wear or the food they eat.

“People underestimate how many [others] with intellectual disabilities suffer with behavioral problems in response to stress,” Van Aelst said. “They are way more exposed to stress than the general population.”

Van Aelst said she and Wang focused on this gene in connection with a stress response.

Van Aelst wanted to study the underlying cellular and molecular mechanism that might link the loss of function of oligophrenin1 with the behavioral response to stress.

At this point, Van Aelst hasn’t yet studied how the mutation in this gene might affect stress hormones, like cortisol, which typically increase when people or mice are experiencing discomfort related to stress. She plans to explore that linkage in future studies.

Van Aelst also plans to look at some other genes that have shown mutations in people who battle depression or other stress-related conditions. She hopes to explore a genetic link in the brain’s circuitry to see if they can “extend the findings.” She would also like to connect with clinicians who are studying depression among the population with intellectual disabilities. Prevalence studies estimate that 10 to 50 percent of individuals with intellectual disability have some level of behavioral problems and/or mood disorders.

Reflecting the reality of the modern world, in which people with various conditions or diseases can sequence the genes of their relatives, Van Aelst said some families have contacted her because their children have mutations in oligophrenin1.

“It’s always a bit tricky,” she said. “I don’t want to advise them yet” without any clinical studies.

A resident of Huntington, Van Aelst arrived at CSHL in the summer of 1993 as a post doctoral researcher in the lab of Michael Wigler. She met Wigler when he was giving a talk in Spain.

After her post doctoral research ended, she had planned to return to her native Belgium, but James Watson, who was then the president of the lab, convinced her to stay.

Outside of work, Van Aelst enjoys hiking, swimming and running. Van Aelst speaks Flemish, which is the same as Dutch, French, English and a “bit of German.” 

She is hopeful that this work may eventually lead to ways to provide a clinical benefit to those people with intellectual disabilities who might be suffering from stress disorders.

Peter Koo Photo from CSHL

By Daniel Dunaief

The goal sounds like a dystopian version of a future in which computers make critical decisions that may or may not help humanity.

Peter Koo, Assistant Professor and Cancer Center Member at Cold Spring Harbor Laboratory, would like to learn how to design neural networks so they are more interpretable, which will help build trust in the networks.

The neural networks he’s describing are artificial intelligence programs designed to link a molecular function to DNA sequences, which can then inform how mutations to the DNA sequences alter the molecular function. This can help “propose a potential mechanism that plays a causal role” for a mutation in a given disease, he explained in an email.

Researchers have created numerous programs that learn a range of tasks. Indeed, scientists can and have developed neural networks in computer vision that can perform a range of tasks, including object recognition that might differentiate between a wolf and a dog.

Koo when he received a COVID vaccination.

With the pictures, people can double check the accuracy of these programs by comparing the program’s results to their own observations about different objects they see.

While the artificial intelligence might get most or even all of the head-to-head comparisons between dogs and wolves correct, the program might arrive at the right answer for the wrong reason. The pictures of wolves, for example, might have all been taken during the winter, with snow in the background The photos of dogs, on the other hand, might have cues that include green grass.

The neural network program can arrive at the right answer for the wrong reason if it is focused on snow and grass rather than on the features of the animal in a picture.

Extending this example to the world of disease, researchers would like computer programs to process information at a pace far quicker than the human brain as it looks for mutations or genetic variability that suggests a predisposition for a disease.

The problem is that the programs are learning in the same way as their programmers, developing an understanding of patterns based on so-called black box thinking. Even when people have designed the programs, they don’t necessarily know how the machine learned to emphasize one alteration over another, which might mean that the machine is focused on the snow instead of the wolf.

Koo, however, would like to understand the artificial intelligence processes that lead to these conclusions.

In research presented in the journal Nature Machine Intelligence, Koo provides a way to access one level of information learned by the network, particularly DNA patterns called motifs, which are sites associated with proteins. It also makes the current tools that look inside black boxes more reliable.

“My research shows that just because the model’s predictions are good doesn’t mean that you should trust the network,” Koo said. “When you start adding mutations, it can give you wildly different results, even though its predictions were good on some benchmark test set.”

Indeed, a performance benchmark is usually how scientists evaluate networks. Some of the data is held out so the network has never seen these during training. This allows researchers to evaluate how well the network can generalize to data it’s never seen before.

When Koo tests how well the predictions do with mutations, they can “vary significantly,” he said. They are “given arbitrary DNA positions important scores, but those aren’t [necessarily] important. They are just really noisy.”

Through something Koo calls an “exponential activation trick,” he reduces the network’s false positive predictions, cutting back the noise dramatically.

“What it’s showing you is that you can’t only use performance metrics like how accurate you are on examples that you’ve never seen before as a way to evaluate the model’s ability to predict the importance of mutations,” he explained.

Like using the snow to choose between a wolf and a dog, some models are using shortcuts to make predictions.

“While these shortcuts can help them make predictions that [seem more] accurate, like with the data you trained it on, it may not necessarily have learned the true essence of what the underlying biology is,” Koo said.

By learning the essence of the underlying biology, the predictions become more reliable, which means that the neural networks will be making predictions for the right reason.

The exponential activation is a noise suppressor, allowing the artificial intelligence program to focus on the biological signal.

The data Koo trains the program on come from ENCODE, which is the ENCyclopedia Of DNA Elements.

“In my lab, we want to use these deep neural networks on cancer,” Koo said. “This is one of the major goals of my lab’s research at the early stages: to develop methods to interpret these things to trust their predictions so we can apply them in a cancer setting.”

At this point, the work he’s doing is more theoretical than practical.

“We’re still looking at developing further tools to help us interpret these networks down the road so there are additional ways we can perform quality control checks,” he said.

Koo feels well-supported by others who want to understand what these networks are learning and why they are making a prediction.

From here, Koo would like to move to the next stage of looking into specific human diseases, such as breast cancer and autism spectrum disorder, using techniques his lab has developed.

He hopes to link disease-associated variance with a molecular function, which can help understand the disease and provide potential therapeutic targets.

While he’s not a doctor and doesn’t conduct clinical experiments, Koo hopes his impact will involve enabling more trustworthy and useful artificial intelligence programs.

Artificial intelligence is “becoming bigger and it’s undoubtedly impactful already,” he said. “Moving forward, we want to have transparent artificial intelligence we can trust. That’s what my research is working towards.”

He hopes the methods he develops in making the models for artificial intelligence more interpretable and trustworthy will help doctors learn more about diseases.

Koo has increased the size and scope of his lab amid the pandemic. He current has eight people in his lab who are postdoctoral students, graduate students, undergraduates and a master’s candidate.

Some people in his lab have never met in person, Koo said. “I am definitely looking forward to a normal life.”

Stem cell growth, required for kernel development, is controlled in corn by a set of genes called CLEs. But how these genes change the corn is complicated. Using CRISPR genome editing, CSHL researchers found they could change kernel yield and ear size by fine-tuning the activity of one of the CLE genes, ZmCLE7. In the image: an unmodified corn cob with normal ZmCLE7 gene activity (1) is packed with regular rows of kernels. Shutting off ZmCLE7 (2) shortened the cob, disrupted row patterns, and lowered kernel yield. However, decreasing the same gene’s activity (3) led to an increase in kernel yield, while increasing the gene’s activity (4) decreased the kernel yield. Jackson Lab/CSHL 2021

By Daniel Dunaief

The current signal works, but not as well as it might. No signal makes everything worse. Something in the middle, with a weak signal, is just right.

By using the gene-editing tool CRISPR, Cold Spring Harbor Laboratory Professor Dave Jackson has fine-tuned a developmental signal for maize, or corn, producing ears that have 15 to 26 percent more kernels. 

Dave Jackson. Photo from CSHL

Working with postdoctoral fellow Lei Liu in his lab, and Madelaine Bartlett, who is an Associate Professor at the University of Massachusetts Amherst, Jackson and his collaborators published their work earlier this week in the prestigious journal Nature Plants.

Jackson calls the ideal weakening of the CLE7 gene in the maize genome the “Goldilocks spot.” He also created a null allele (a nonfunctional variant of a gene caused by a genetic mutation) of a newly identified, partially redundant compensating CLE gene.

Indeed, the CLE7 gene is involved in a process that slows the growth of stem cells, which, in development, are cells that can become any type of cell. Jackson also mutated another CLE gene, CLE1E5.

Several members of the plant community praised the work, suggesting that it could lead to important advances with corn and other crops and might provide the kind of agricultural and technological tools that, down the road, reduce food shortages, particularly in developing nations.

“This paper provides the first example of using CRISPR to alter promoters in cereal crops,” Cristobal Uauy, Professor and Group Leader at the John Innes Centre in the United Kingdom, explained in an email. “The research is really fascinating and will be very impactful.”

While using CRISPR (whose co-creators won the Nobel Prize in Chemistry in October) has worked with tomatoes, the fact that it is possible and successful in cereal “means that it opens a new approach for the crops that provide over 60% of the world’s calories,” Uauy continued.

Uauy said he is following a similar approach in wheat, although for different target genes.

Recognizing the need to provide a subtle tweaking of the genes involved in the growth of corn that enabled this result, Uauy explained that the variation in these crops does not come from an on/off switch or a black and white trait, but rather from a gradient.

In Jackson’s research, turning off the CLE7 gene reduced the size of the cob and the overall amount of corn. Similarly, increasing the activity of that gene also reduced the yield. By lowering the gene’s activity, Jackson and his colleagues generated more kernels that were less rounded, narrower and deeper.

Uauy said that the plant genetics community will likely be intrigued by the methods, the biology uncovered and the possibility to use this approach to improve yield in cereals.

“I expect many researchers and breeders will be excited to read this paper,” he wrote.

In potentially extending this approach to other desirable characteristics, Uauy cautioned that multiple genes control traits such as drought, flood or disease resistance, which would mean that changes in the promoter of a few genes would likely improve these other traits.

“This approach will definitely have a huge role to play going forward, but it is important to state that some traits will still remain difficult to improve,” Uauy explained.

Jackson believes gene editing has considerable agricultural potential.

“The prospect of using CRISPR to improve agriculture will be a revolution,” Jackson said.

Other scientists recognized the benefits of fine-tuning gene expression.

“The most used type/ thought of mutation is deletion and therefore applied for gene knockout,” Kate Creasey Krainer, president and founder of Grow More Foundation, explained in an email. “Gene modulation is not what you expect.”

While Jackson said he was pleased with the results this time, he plans to continue to refine this technique, looking for smaller regions in the promoters of this gene as well as in other genes.

“The approach we used so far is a little like a hammer,” Jackson said. “We hope to go in with more of a scalpel to mutate specific regions of the promoters.”

Creasey Krainer, whose foundation hopes to develop capacity-building scientific resources in developing countries, believes this approach could save decades in creating viable crops to enhance food yield.

She wrote that this is “amazing and could be the green revolution for orphan staple crops.”

In the United States, the Food and Drug Administration is currently debating whether to classify food as a genetically modified organism, or GMO, if a food producer used CRISPR to alter one or more of its ingredients, rather than using genes from other species to enhance a particular trait.

To be sure, the corn Jackson used as a part of his research isn’t the same line as the elite breeding stock that the major agricultural businesses use to produce food and feedstock. In fact, the varieties they used were a part of breeding programs 20 or more years ago. It’s unclear what effect, if any, such gene editing changes might have on those crops, which companies have maximized for yield.

Nonetheless, as a proof of concept, the research Jackson’s team conducted will open the door to additional scientific efforts and, down the road, to agricultural opportunities.

“There will undoubtedly be equivalent regions which can be engineered in a whole set of crops,” Uauy wrote. “We are pursuing other genes using this methodology and are very excited by the prospect it holds to improve crop yields across diverse environments.”