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Bruce Stillman

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Dr. John Inglis Photo from CSHL

By Daniel Dunaief

Evolution doesn’t just favor species that have adaptive advantages in a changing environment. It’s also relevant for businesses, as they move into new markets, and even to scientific publishing.

A preprint scientific publishing effort that started in 2013 at Cold Spring Harbor Laboratory with bioRxiv and expanded in 2019 with medRxiv is making changes that its creators believe positions it to grow while continuing to serve the scientific community.

BioRxiv and medRxiv are becoming an independent nonprofit, called openRxiv. The new format, which takes the preprint offerings outside the home of Cold Spring Harbor Laboratory, will create a product that is outside the realm of a single institution and that has transparent governance.

“We had an independent needs assessment done by a consulting company,” said Dr. John Inglis, Chair of the openRxiv Scientific and Medical Advisory Board. The governance needed to be “more community-oriented, with not just funders, but committees of working scientists.”

The Chan Zuckerberg Initiative, which has been the major funder for the preprint services, understood the benefits of transitioning to an independent non profit. They also wanted to “see a diversification of funding” from other sources and contributors, Inglis said.

Up until co-founders Inglis and Dr. Richard Sever, Chief Science and Strategy Officer at openRxiv created these two preprint services, most biological and medical scientific discoveries progressed through the slower pace of peer review publishing that helps them advance their fields while sharing their results.

Preprints, however, greatly accelerated that process by allowing researchers to display their work before peer review. While scientists might need to amend their findings by adding further studies, these preprints enable researchers to do the equivalent of presenting their research to a worldwide audience, the way scientists do at meetings.

The preprint servers are “like the biggest conference you’ve ever seen, with millions of people,” said Inglis.

A growing market 

In each month of the last quarter of 2024, bioRxiv recorded between 8 million and 9.7 million page views, with between 4.7 million and 6.8 million downloads, Inglis said. MedRxiv, meanwhile, had between 1.8 million and 1.9 million page views with a million downloads per month.

With more than 110 new articles per day last year, bioRxiv added 11 percent more original preprints last year. MedRxiv grew by 12 percent, adding 12,863 preprints last year, or about 35 new articles per day.

MedRxiv launched the year before the pandemic and quickly became the major channel of communication for pandemic-related preprints.

In 2020, when pandemic related coverage accounted for 80 percent of everything posted, medRxiv shared a total of 14,070 research pieces.

At this point, contributing authors have come from 190 countries. The most prolific contributors are the United States and the United Kingdom. With readers coming from around the world, openRxiv’s primary task is to convert some of the readers from other countries into contributors, Inglis said.

Search for a CEO

OpenRxiv creates opportunities for several executives.

Sever, who had been CSHL Press Assistant Director, will leave the lab to become the chief scientific and strategy officer for openRxiv.

At the same time, openRxiv, which has an annual budget of $3 million, has hired a recruiting firm to lead the search for its first Chief Executive Officer.

The new CEO will need to “believe in the mission, promise, potential and ambition of openRxiv,” said Inglis, as the CEO will be the “principal ambassador” for the effort.

The new leader will also need experience running a complex organization with various stakeholders and that has community engagement.

Inglis described the current employees, which includes eight full time staff, as “fantastically motivated.” He anticipates the new leader could be announced as soon as three or four months from now.

Expanded opportunities

The preprint servers has appealed to academic institutions directly for ongoing repeated support, through a membership model.

Indeed, preprint managers reached out on the 10th anniversary of bioRxiv and received backing from institutions that are listed on every bioRxiv and medRxiv preprint.

“We want to build on that, to reach out to more institutions,” said Inglis. He wants to have a “real dialog with them about what these servers mean to their faculty and how we can be useful in terms of their operations.”

Some academic institutions don’t always know which research studies are appearing on these servers.

OpenRxiv can give universities information for researchers who are posting their studies.

Additionally, these servers have been offering authors the chance to transfer their manuscripts to particular journals. At this point, openRxiv has connections with 45 publishers who oversee 380 journals.

Inglis said they charge a small fee to set that up and described this effort as the “germ” of a business model. He anticipates that openRxiv could provide more of these connections.

Professional pathways

Authors have the ability to correct or amend their work on these servers. The preprints encourage people to explain the changes, while discouraging too many corrections or changes for grammatical reasons. The record for revisions on bioRxiv or medRxiv is seven.

Inglis has heard from numerous researchers who are grateful to increase the visibility of their work and their careers in a timely way.

These non peer reviewed studies can help scientists move up the ladder, getting job offers from other institutions while they await publication in a journal.

Ongoing support

CSHL, BMJ Group and Yale School of Medicine remain key supporters of openRxiv.

“OpenRxiv is the natural evolution and progression of free and open access to scientific information,” Bruce Stillman, President and CEO of CSHL said in a statement. “BioRxiv and medRxiv have revolutionized the field of science and scientific publishing. The establishment of openRxiv will allow for continued innovation in how the latest scientific results are communicated.”

In the last few weeks, openRxiv had the first in a series of webinars they are mounting on their own behalf. They plan to offer them to institutions across the world and believe they are an effective way to engage with the world of international science.

OpenRxiv is in conversation with faculty at an institution in Japan about organizing a webinar and will reach out to institutions in India. Staff at openRxiv plan to expand the scope of this process by contacting authors in potential locations who have multiple articles on the servers.

The response from students is an “encouragement to do more,” said Inglis. “Having more people and more resources will allow us to ramp up educational development of what we’re doing.”

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Bruce Stillman, CEO of Cold Spring Harbor Laboratory. Photo courtesy of CSHL

By Daniel Dunaief

The Oscars could learn a thing or two from Cold Spring Harbor Laboratory. The facility, which conducts research in cancer, neuroscience, genomics, quantitative biology and plant biology, hosted its 19th annual Double Helix Award Dinner on Nov. 14.

Front row from left, 2024 Double Helix Medals honorees Dr. Katalin Karikó, Daniel and Alisa Doctoroff.
Back row, from left, CSHL Chair Marilyn Simons, President & CEO Bruce Stillman, and Grace Stillman. Photo courtesy of Patrick McMullan Company

Held at the American Museum of Natural History in New York City and emceed by CBS journalist Lesley Stahl, the dinner, so named for the twisting ladder structure of the genetic material DNA, raised $7 million while honoring Nobel Prize winner Katalin Karikó, and Daniel and Alisa Doctoroff, a husband and wife team who are leaders of Target ALS.

Bruce Stillman, CEO of Cold Spring Harbor Laboratory, recently discussed the awards dinner, an innovative and potentially revolutionary study on aging, science funding, and a host of other topics in an exclusive interview.

The honorees at this year’s dinner were “really fantastic,” Stillman said.

Originally from Hungary, Karikó thrived in work that helped lead to BioNTech and Pfizer’s work using messenger RNA to create a vaccine for COVID-19 despite setbacks including four demotions while a scientist at the University of Pennsylvania.

Her experience shows how “a scientist can do Nobel prize winning research despite adversity,” Stillman said. She had an “idea she wanted to stick with.”

Through Target ALS, the Doctoroffs have helped generate progress in research on amyotrophic lateral sclerosis, or Lou Gehrig’s disease.

Daniel Doctoroff, who has ALS, had been Deputy Mayor for Economic Development and Rebuilding and CEO and president of Bloomberg LP.

The dinner has raised over $67 million since its inception and has honored scientists and public figures, including the late boxer and inaugural winner Muhammad Ali, baseball Hall of Fame right fielder Reggie Jackson and Nobel Prize winner and co-discoverer of gene editing tool CRISPR Jennifer Doudna.

As a part of the celebration, the lab produces videos of the honorees, who have made significant contributions to philanthropy or to research or who have been advocates for health.

A week after the dinner, Stillman had written a letter to potential honorees for next year.

“It’s a lot of work to do this properly,” said Stillman. “We have a time limit on the evening. We want everyone out by 9:30 p.m. We timed this whole thing down to the minute and it worked out very well.”

An important aging discovery

While the lab produced a large volume of research studies that could have implications in a range of fields during the year, Stillman highlighted the work of Corina Amor Vegas as being “probably the most impactful down the road.”

Corina Amor Vegas. Photo ourtesy of CSHL

Amor Vegas used a technology developed to treat cancer to address the effects of aging.

She produced chimeric antigen receptors on the surface of the immune system’s T cells to attack senescent cells, which have aged and are not functional but could otherwise cause aging related problems such as diseases.

In a mouse model, Amor Vegas found that treating these aging mice with modified forms of their own T cells, through car-T immunotherapy, improved metabolic dysfunction and exercise capacity. Indeed, even a single treatment was enough to provide long term benefits for these mice.

The work attracted considerable venture capital interest and the lab is in discussions about how to pursue a business approach that taps into the potential use of this discovery.

As for businesses, the lab has a number of companies that are “under the radar screen” but that will have an impact in their fields.

Professor Partha Mitra started a company called Clarapath that will make “a major splash” with its automatic slides for pathology, Stillman said. A machine can do the work automatically that is otherwise labor intensive.

Down the road, scientists could apply artificial intelligence to analyze the samples. The laboratory has several faculty that are doing machine learning or AI in their research in areas such as neuroscience or genetics.

Through a neuro-AI scholars program, CSHL brings in people who have had a high level of training in computer science related to machine learning. The scholars come to CSHL for one or two years, where they work in a neuroscience lab.

Meetings

Stillman was pleased with the meetings on site this year, including one on epigenetics and CRISPR.

At the end of May in 2025, CSHL plans to have a symposium called Senescence and Aging.

The lab has invited scientists to speak from Germany, Israel, Japan and the United Kingdom as well as from Harvard, Brown and Yale. Locally, Amor Vegas, Assistant Professor Semir Beyaz and Professor Lloyd Trotman have also received invitations to share their work.

Stillman anticipates the publication of compelling findings from CSHL next year, including in autism.

At the same time, the lab is building a new Neuroscience Research Complex that should be finished in 2026. The 36,347 square-foot facility will include three modern buildings that focus on neurodegenerative diseases, brain-body physiology and quantitative biology and NeuroAI.

The construction has been going “very well,” Stillman said.

Science and politics

Amid talk of a rationalization of the research budget next year when the former and future president Donald Trump takes office, Stillman cautioned against a heightened focus on translational studies.

“If we knew what basic science would be translational, we would be doing it,” Stillman said. “If you go back and look at fundamental discoveries of how a disease can be cured, like Spinraza, people would have said, ‘Don’t study this or that.’”

Professor Adrian Krainer developed the drug Spinraza at CSHL, which is an effective treatment for an otherwise debilitating childhood disease called spinal muscular atrophy.

The development of CRISPR came from a study of bacteria that grow in a marine environment.

If Trump’s administrators think they can predict that every dollar will be productive, “they are nuts,” Stillman said. “We should have a discussion before they start pronouncing what should be done.”

Converting the National Institutes of Health into a directed translational research institute will push down American competitiveness.

China is planning to spend large sums of money in basic research. If the United States cuts back in these areas, this is a “recipe for the country to become a second class citizen to those that are “investing in basic science.”

The Human Genome Project cost $3 billion over 25 years. The returns exceed $1 trillion, Stillman said.

“That’s an enormous payoff,” he added. 

Despite concerns and a watchful eye on research funding, Stillman shared a positive outlook.

“I’m not pessimistic about the future,” he said. “The United States economy is very strong.”

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Cold Spring Harbor Laboratory. Photo courtesy Cold Sping Harbor Laboratory website

By Daniel Dunaief

A stock fund is taking a page out of the Newman’s Own playbook.

The food company which was started by the late actor Paul Newman and author A.E. Hotchner donates its after tax profits to charity through the Newman’s Own Foundation, enabling consumers to feel that they aren’t just covering their salad with tasty dressing but are helping the world through their consumer choices.

Range Cancer Therapeutics, an exchange-traded fund that purchases a broad basket of cancer therapeutic stocks, created a new partnership with Cold Spring Harbor Laboratory to contribute to cancer research.

The fund, which was started in 2015, plans to contribute 23 percent of its revenues, reflecting the 23 pairs of chromosomes in the human genome, each quarter to Cold Spring Harbor Laboratory.

“The contribution from Range will directly benefit the research efforts at CSHL, underscoring our commitment to advancing scientific innovation in oncology therapeutics,” Range ETF’s founder and CSHL Association Board Member Tim Rotolo, said in a statement. The ETF provides “exposure to nearly the entire lifecycle of drug development and distribution, and this new collaboration with CSHL provides an opportunity for investors to also see their money go toward the earliest stages of cancer breakthroughs.”

Revenues collected by the fund are likely to vary by quarter, depending on the amount of money the fund manages. With an estimated $12.1 million in assets under management as of the end of September and an expense ratio of 0.79%, the fund could contribute about $21,850.

“Hopefully, people will feel when they’re buying the ETF that they are in some ways supporting cancer research,” said Charles Prizzi, Senior Vice President for Advancement & Special Advisor to CSHL President Bruce Stillman.

Prizzi anticipates that the funding could support the lab’s efforts to conduct a broad range of research as CSHL’s staff, who come to the site from all over the world, seek to address the kinds of questions that can lead to advancements in a basic understanding of processes as well as to translational breakthroughs that can help in the prevention, diagnosis and treatment of various diseases.

Prizzi hopes this partnership will attract attention and inspire other fund managers or businesses to contribute to the lab, particularly amid periods when the budgets for federal funding agencies that support research rise and fall.

Borrowing from the language of genetics, Prizzi hoped that this kind of arrangement will be “replicated” by others.

 NASDAQ event

The NASDAQ stock market, which is where the Range Cancer Therapeutics Fund trades under the ticker CNCR, will celebrate the partnership on November 14th in New York City.

The Nasdaq tower will feature a visual display, while Range ETFs and CSHL leadership and guests come together at the Nasdaq podium to mark the ongoing contribution.

Dave Tuveson, head of the Cancer Center, Professor Adrian Krainer, who developed an effective treatment for spinal muscular atrophy using antisense oligonucleotide to affect gene splicing, Vice Chair Howard Morgan, and Goldman Sachs’s Roy Zuckerberg, and others will attend the event.

d Spring Harbor Laboratory President Bruce Stillman. File photo

“Cold Spring Harbor Laboratory is one of only seven national basic biological research cancer centers designated by the National Cancer Institute in Washington, DC,” Bruce Stillman, CEO of the lab said in a statement. “The institution is investing heavily in the growth of our cancer program, specifically in multidisciplinary, collaborative ventures as part of our new brain-body physiology initiative.”

Prizzi is often searching for novel ways to support research and was pleased with the contribution and hopeful that it would spur other creative donations and support.

“I hope people will learn from it and copy it,” Prizzi said. “It will benefit the lab for many years to come.”

Rotolo joined the board at CSHL earlier this year and has supported the lab for about a decade.

Rotolo had approached the lab to establish this financial commitment.

The laboratory is a 501c3 nonprofit institution, which means that donations to the lab are tax deductible.

Prizzi suggested that interested donors often reach out to him towards the end of December.

“We would love to have more people support what we’re doing,” said Prizzi.

CSHL is home to eight Nobel Prize winners and employs 1,000 people, including 600 scientists, students and technicians.

The Meetings & Courses Program bring in more than 12,000 scientists from around the world each year, offering opportunities for researchers to meet and establish collaborations and to learn about the latest scientific breakthroughs.

CSHL is in the first phase of a Foundations for the Future project, which is a seven-acre expansion effort that will tackle research in neuroscience, neuro-AI and the brain-body. Scientists will pursue better patient outcomes by exploring cancer’s whole-body impacts.

In the second phase of the project, the lab will create a new conference center and collaborative research center.

As for the connection with Range, Prizzi added that CSHL is a “lab, we like experiments. This is like an experiment. I hope it goes well and other people build off of it.”

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Bruce Stillman. Photo from CSHL

The toxic talk and policies towards immigrants in the United States is hurting American science and could threaten the country’s ability to compete in technology, an important economic driver.

That’s one of several messages Bruce Stillman, Cold Spring Harbor Laboratory President and Chief Executive Officer, shared in an exclusive interview.

The attitude of some Americans towards immigrants, particularly amid the southern border issue, is “scaring a lot of people off, thinking about working in the United States,” said Stillman. Some of these talented immigrants are wondering why they would come to America. “The perception is that the US is not as welcoming as it used to be,” even for the immigration of highly skilled people, he added.

This hostility could have a detrimental top-down effect on science.

Indeed, immigrants have distinguished themselves, earning top prizes in science and accounting for 38 percent of the Nobel Prizes in physics, 34 percent in medicine and 37 percent in chemistry since 1901, according to Forbes.

“This is a very important economic and competitiveness issue,” said Stillman, who grew up in Australia.

It is increasingly difficult to recruit people from certain countries, particularly amid challenges getting visas, Stillman said.

Cold Spring Harbor Laboratory has an offer out to a “very talented scientist” who has been waiting for almost a year to receive a visa, he said.

Many people have an opinion on the way things ought to be, Stillman explained, including issues related to diversity, equity and inclusion.

“The dialog in the US is no longer civil, but now people are emboldened to attack those in leadership positions,” he explained in an email. “It is part of the wider adversarial dialog going on in America.”

Policies in some states like Florida create the impression, even to accomplished and dedicated workers, that the country does not want them to work here.

CSHL embraces “talented scientists who want to work in the US to come to CSHL,” he explained.

Major scientific recession

Apart from immigration policies that exclude a broad swath of people who might otherwise ensure American technological competitiveness, Stillman is also worried about how political logjams in Washington could limit future funding for science.

“The moderates on both sides of Congress need to come together to override those on the left wing of the Democratic party and those on the right wing in the Republican party,” he explained.

Stillman does not understand why most members of Congress don’t vote out the extremes. If everyone in the middle stood up, “they would be lauded by the general public,” Stillman wrote in an email.

Listening to the fringes of science on both sides who attack science raises the risk of maintaining a leadership position.

Still, he maintains that he is optimistic that the general public and the moderate majority will prevail.

Learning from history

As the leader of Cold Spring Harbor Laboratory for 29 years, Stillman recognizes his institution’s role in a dubious chapter in American history.

Indeed, a century ago, the United States passed the Johnson-Reed Act, or the Immigration Act of 1924, which provided a quota that limited the number of immigrants to two percent of the people of each nationality in the country as of the 1890 census. The law excluded immigrants from Asia.

After that law, Cold Spring Harbor Laboratory played a role in this policy by creating a eugenics record office.

CSHL put up a web site 18 years ago to chronicle the lab’s involvement in a period when science was used to justify discriminatory policies.

“We have highlighted on our web site about the eugenics movement so as to educate children and adults about how misunderstanding science, in this case genetics, can lead to dangerous public policy,” he explained in an email.

This year, on the 100th anniversary of the immigration law, the lab plans to highlight the 1924 Immigration Act as something that led to policies that are “not compatible with what the US is about,” he said.

Building for the future

Like other labs, CSHL is competing to earn federal grants from the National Institutes of Health and the National Science Foundation.

The lab needs to raise “considerable amounts of money each year to eep cutting edge science moving forward,” he wrote.

Indeed, CSHL recently started a major expansion on seven acres of land at the top of the campus to build four research buildings. The lab plans to hire about 14 to 16 new faculty to join the current staff of 56 investigators.

These buildings will expand on programs that explore brain-body physiology, which describes how organs such as the stomach and others interact with the brain.

Many diseases, including cancer, upset the normal brain body interactions, he added. Intervening in these circuits can lead to new therapeutics for cancer and for many neurological disorders.

Researchers at CSHL will publish several discoveries in the next few years in this field that represent “important breakthroughs,” Stillman said.

At the end of May and early June, CSHL will host an annual symposium on brain body physiology, which will include a lecture for the general public.

CSHL is pursuing the most ambitious capital campaign in the lab’s history, raising funds to support the construction of new research and education buildings and to increase the endowment to support the science.

The lab is also building another center called NeuroAI that integrates neuroscience, artificial intelligence and computer science. The computational AI effort has “taken on a life of its own,” he explained. “We plan a major effort to understand how our brain does normal computation and then use this knowledge to improve computer programs.”

In the realm of artificial intelligence, CSHL has used a program called alpha fold, which a unit of Google called Deep Mind developed.

This program predicts protein-protein interactions and protein-drug interactions, which helps “transform the way biology is done,” he said.

While the work “accelerates” the science, it doesn’t “replace doing real experiments,” he added.

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From left, CSHL President and CEO Bruce Stillman, CSHL Board of Trustees Chair Marilyn Simons, and 2022 Double Helix Medal recipients Albert Bourla and Jennifer A. Doudna. Photo by Sean Zanni / Patrick McMullan Company

By Daniel Dunaief

One of them helped tap into a process bacteria use to fight off viruses to develop a gene editing technique that has the potential to fight diseases and improve agriculture. The other oversaw the development of a vaccine at a record-breaking pace to combat Covid-19.

Cold Spring Harbor Laboratory honored both of them at its 17th annual Double Helix Medal Dinner at the American Museum of Natural History in NYC on Nov. 9.

The lab celebrated Dr. Jennifer Doudna, who won a Nobel Prize in Chemistry in 2020 for her co-discovery of the CRISPR-Cas9 gene editing system and Pfizer Chairman and CEO Dr. Albert Bourla, who helped spearhead the development of an RNA-based vaccine.

The black-tie optional award dinner, hosted by television journalist Lesley Stahl, raised a record $5.8 million for research at the famed lab.

“We are giving hope to people, hope for science — and that’s something that gives us a lot of pride,” Dr. Bourla said in a statement.

Dr. Doudna, who is Professor of Biochemistry, Biophysics and Structural Biology at the University of California at Berkeley, was encouraged by the transformative nature of gene editing.

“When I think about new therapeutics that are only possible using CRISPR technology, I’m thinking about ways that we can not just treat a genetic disorder chronically, but can provide a one-and-done cure,” she said in a statement.

The awards dinner has raised over $50 million since its inception. Pfizer underwrote the entire event last week.

Attendees included previous award winners Drs. Marilyn and James Simons, who founded Renaissance Technologies, actress Susan Lucci, who starred on All My Children for 41 years, Representative Tom Suozzi (D-NY3) and his wife Helene, David Boies, Chairman and Managing Partner of the law firm Boies, Schiller Flexner, and Jeanne Moutoussamy-Ashe, photographer and widow of tennis legend Arthur Ashe, among other business and philanthropic luminaries.

Cold Spring Harbor Laboratory will incorporate the funds raised through the dinner into its operating budget, which supports integrated research and education in fields including neuroscience, artificial intelligence, quantitative biology, plant biology, cancer, and neurodegenerative diseases like Alzheimer’s.

The funding from the dinner helps CSHL scientists engage in high-risk, high-reward research that can lead to important discoveries, CSHL said in a statement.

“Rather than relying entirely on the grant system, [scientists] are given the freedom to further explore the future implications of their work,” CSHL added.

Philanthropy also helps CSHL expand its Meetings & Courses program. The operating budget supports community engagement and environmental stewardship on Long Island.

Senior leadership at the lab chooses the honorees each year.

This year’s dinner surpassed the $5 million raised last year, which honored baseball Hall-of-Farmer Reggie Jackson, as well as Leonard Schleifer and George Yancopoulos, the founders of Regeneron, the pharmaceutical company that provided life-saving antibody treatment for Covid-19.

Other previous honorees included actor Michael J. Fox, basketball great Kareem Abdul-Jabbar, actor and science educator Alan Alda, and newscasters Tom Brokaw and Katie Couric.

The chairs of the Double Helix medal dinner included Jamie Nicholls and O. Francis Biondi, Barbara Amonson and Vincent Della Pietra, Drs. Pamela Hurst-Della Pietra and Stephen Della Pietra, Mr. and Mrs. John Desmarais, Elizabeth McCaul and Francis Ingrassia, Mr. and Mrs. Jeffrey Kelter, Dr. and Mrs. Tomislav Kundic, Mr. and Mrs. Robert Lindsay, Ivana Stolnik-Lourie and Dr. Robert Lourie, Dr. and Mrs. Howard Morgan, and Marilyn and James Simons.

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From left, CSHL’s Bruce Stillman, Double Helix Medal recipients Leonard Schleifer and Reggie Jackson, Chair of the CSHL Board of Trustees Marilyn Simons, and Double Helix Medal recipient George D. Yancopoulos. Photos by Constance Brukin
Above, NYC Mayor-elect Eric Adams speaks at the 16th Annual Double Helix Medals dinner with CSHL President and CEO Bruce Stillmanon and television journalist Lesley Stahl. Photos by Constance Brukin
The guests, including scientists from CSHL, and the honorees shared stories and hors d’oeuvres beneath the dinosaurs at the Museum of Natural History. Photo by Tobias Janowitz
Above, NYC Mayor-elect Eric Adams speaks at the 16th Annual Double Helix Medals dinner with CSHL President and CEO Bruce Stillmanon and television journalist Lesley Stahl. Photos by Constance Brukin
Double Helix Medal recipient George Yancopoulos takes a selfie with CSHL President and CEO Bruce Stillman, Regeneron Chairman of the Board P. Roy Vagelos, Double Helix Medal recipients Leonard Schleifer and Reggie Jackson, and Chair of the CSHL Board of Trustees Marilyn Simons. Photo by Constance Brukin
Dinner was served under the Blue Whale at the Natural History Museum. Photo by Sara Roncero-Menendez
CSHL Trustee Robert W. Lourie, CSHL President and CEO Bruce Stillman, and County Executive Steve Bellone. Photo by Constance Brukin
From left, Assistant Professor Tobias Janowitz, Professor Leemor Joshua-Tor, Assistant Professor Peter Koo, and Professor Linda Van Aelst. Photo by Constance Brukin
Dessert at the awards dinner was caramel tart dessert with chocolate ganache and vanilla ice cream. Photo by Sara Roncero-Menendez

By Daniel Dunaief

This November, Cold Spring Harbor Laboratory celebrated baseball’s Mr. October.

The research facility that specializes in studying cancer, neuroscience, quantitative and plant biology hosted its 16th annual Double Helix Medals dinner at the Museum of Natural History on Nov. 17.

The evening, which was emceed by television journalist Lesley Stahl, honored Hall-of-Famer Reggie Jackson, as well as Leonard Schleifer and George Yancopoulos, the founders of Regeneron, the pharmaceutical company that has provided a life-saving antibody treatment for COVID-19.

The evening, which featured a dinner beneath the blue whale at the museum, raised a record $5 million for research.

“When we were standing in the hall of dinosaurs at the museum, it was fantastic,” said CSHL President and CEO Bruce Stillman. “It was one of the first events where people went out like the old days” prior to the pandemic.

Stillman said guests had to have received their COVID vaccinations to attend the celebration.

In addition to establishing a career as a clutch hitter in the playoffs, Reggie Jackson has dedicated considerable energy through his Mr. October Foundation to improve education around the country.

“His Mr. October foundation complements and parallels the DNA Learning Center programs, particularly now that we’ve opened a large DNA Learning Center in downtown Brooklyn that is serving underserved students in lab-based science,” said Stillman.

In his acceptance speech, Jackson said he found it “significant” that he received an honor for his educational efforts off the baseball field.

Yancopoulos, meanwhile, described his roots as the son of first generation immigrant parents from Greece. Yancopoulos highlighted the need for more funding in research and suggested that science helped pull the world through the pandemic. Yancopoulos said the National Institutes of Health should increase its budget 10-fold to meet the research and clinical needs of the population.

“Biotechnology offers the promise of really solving some of the most difficult problems that we face if we want our citizens to live not only longer, but healthier lives,” Schleifer said in a statement.

Mayor-elect Eric Adams, meanwhile, gave a speech about his vision for the future of the city which included, after some prompting from Stillman, increasing science in the education system.

The Double Helix gala, which started in 2006 when the lab honored the late boxer Muhammed Ali, raises money that goes into CSHL’s operating budget to support research and education.

This year, the donations included a generous gift from Astros owner Jim Crane, who introduced his friend Jackson.

Stillman helps direct the funds raised through the dinner to support scientists who are making what he termed “breakthrough discoveries.”

Many of the most significant discoveries come through philanthropic support, Stillman said, which makes it possible for researchers to design high-risk, high-reward experiments.

CSHL Chair of the Board of Trustees Dr. Marilyn Simons, a previous winner, attended the festive evening.

Senior leadership at the lab chooses the honorees. Stillman said CSHL already has two honorees for the event next year.

Previous honorees include actor Michael J. Fox, basketball legend Kareem Abdul-Jabbar, actor and science educator Alan Alda, and newscasters including Tom Brokaw and Katie Couric.

“It is a really spectacular list,” Stillman said. The winners, who receive a medal, have all contributed in some significant way to science or to science education.

The dinner provides an opportunity for supporters of the mission of CSHL, which has had eight Nobel Prize winners work at the lab during their careers, to invite others to hear about research at the lab.

“It was a very inspiring evening,” Stillman said.

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Bruce Stillman. Photo from CSHL

By Daniel Dunaief

Bruce Stillman, the CEO of Cold Spring Harbor Laboratory, last week won the Dr. H.P. Heineken Prize for Biochemistry and Biophysics, which is considered the most distinguished scientific prize from the Netherlands.

The prize, which has been awarded to 13 researchers who have gone on to win Nobel Prizes, includes a $200,000 award and a crystal trophy.

Stillman earned the award, which began in 1964 and is given every two years in categories including Medicine, Environmental Sciences and History, for his decades of work on mechanisms involved in the replication, or copying, of eukaryotic DNA.

The understated Stillman, who was born and raised in Australia, expects he’ll put the prize money into a foundation, although he hasn’t thought much about it given the other concerns that dominate his time, including not only running his own lab amid the COVID-19 pandemic but also overseeing a facility where he has been the Director since 1994 and its CEO since 2003.

Stillman said the lab has had “extensive discussions” among the faculty about whether to pursue additional research fields on an ongoing basis to combat the current virus as well as any future public health threats.

While CSHL is not an infectious disease center, the facility does have a historical precedent for contributing to public health efforts during a crisis. Indeed, during World War II, the laboratory helped create a mutated strain of fungus that increased its yield of the drug penicillin.

At this point, CSHL does not have a high containment facility like Stony Brook University where it can handle highly infectious agents.

“We may have to have one here,” Stillman said. “The reality is there are tons of infectious diseases” and the lab might need to repurpose its scientific skills towards coming up with answers to difficult questions.

Even without such a Biosafety Level 3 designation, CSHL researchers have tackled ways to understand and conquer COVID-19. Associate Professor Mikala Egeblad has been exploring whether neutrophil extracellular traps, which are ways bodies fight off bacterial infections, are playing a role in blood clotting and severe respiratory distress.

These NETS may be “promoting severe symptoms in COVID,” Stillman said. Egeblad is working on a case study with several other collaborators who have focused on these traps. Egeblad is also studying the effectiveness of NETS as a biomarker for the most severe patients, Stillman said.

CSHL is also investigating a small molecule compound to see if it inhibits viral infection. Researchers including Assistant Professor Tobias Janowitz are about to participate in a combined Northwell Health-CSHL double blind study to determine the effectiveness of famotidine, which is the active ingredient in the ulcer-treating medication Pepcid.

The coronavirus treatment, which will include patients who don’t require hospitalization, would require a higher dose than for heartburn.

As a part of this study, the scientists will use a patient tracking system that has been used for cancer to determine the effectiveness of the treatment through patient reporting, without requiring laboratory tests.

Stillman is pleased with how CSHL has “repurposed ourselves quickly, as have many institutions around the world.” He highlighted the constructive interactions among scientists.

The public health crisis has “generated a different kind of behavior in science, where there’s a lot of interaction and cooperation,” Stillman said. The preprint journal BioRxiv, which CSHL operates, has had nearly 5,000 papers about COVID-19 since January. The preprints have “not only helped disseminate information rapidly [to the scientific community], but they are also “being used to determine policy by government leaders.”

Stillman urged scientists to apply the same analytical technique in reading preprinted research that they do with peer-reviewed studies, some of which have required corrections.

As for the government’s response, Stillman believes a retrospective analysis will provide opportunities to learn from mistakes. “I don’t think the [Centers for Disease Control and Prevention] has done a very good job,” he said. He suggested that the well-documented problems with the roll out of testing as community transmission was increasing, was a “disaster.”

The CSHL CEO also said the balkanized medical system, in which every state has a different system and even some local communities have their own processes, creates inefficiencies in responding to a fluid and dangerous public health crisis.

Coordinating those efforts “could have been done very, very rapidly to develop a modern, clear [polymerase chain reaction] test of this virus and yet states and federal agencies had regulations about how these tests can be approved and controlled and regulated that are far too bureaucratic and did not set a national standard quickly,” he said.

He hopes agencies like the CDC, FDA and the Biomedical Advanced Research and Development Authority have better coordination. The country needs a national response, like it had after the Homeland Security effort following 9/11.

Optimistically, Stillman expects a therapeutic antibody will be available by the end of the summer to treat COVID-19. The treatment, which will use monoclonal antibodies, will likely be injectable and will be able to prevent infection for a month or two. These treatments could also help limit the severity of symptoms for people who have been infected.

Regeneron has taken the same approach with Ebola effectively. Stillman doesn’t think such treatments can be used with everybody in the world, which increases the need to develop a vaccine. Creating a safe vaccine, which could be available as early as next year, is a “massive, under-recognized undertaking.”

Between now and next year, a second wave of the virus is certainly possible and may be likely, given that other coronaviruses have been seasonal. 

“This happened with the influenza pandemic a century ago, so we have to be careful about this,” Stillman said. He believes that the medical community has learned how to treat severe patients, which should help mitigate the effects of a second wave in the United States. 

That may not be the case in developing countries, which is a “concern,” he said.

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Photo by © Kevin P. Coughlin/Office of Governor Andrew M. Cuomo

After two years of extensive renovation and with generous support from New York State, Cold Spring Harbor Laboratory’s historic Demerec Laboratory was reborn as a state-of-the-art research facility. Governor Andrew Cuomo cut the ribbon for the building’s reopening on Oct. 30, celebrating how the state will benefit from this new chapter in CSHL research.

“It’s good for Long Island, it’s good for the economy, but also it is doing work that I believe will improve the quality of life for thousands and thousands of people. I believe this work will actually save lives and there is nothing more important than that,” Governor Cuomo said during his visit. “That is the work that the people in this facility are dedicated to and God bless them for that. The state is honored to be playing a small role today.”

The Demerec Laboratory, home to four Nobel laureates, has been both a bastion and compass point for genetics research in New York and the world. Its new research will focus on taking a more holistic approach to treating cancer and the disease’s impact on the entire body.

According to the CSHL’s website, the new center “will enable newly developed compounds to be refined by world-leading chemists to develop next-generation therapies. This research will form a basis for collaboration with private foundations and pharmaceutical companies, while advancing the development of new drugs. 

In addition, the center will support ongoing research activities aimed to develop therapeutics for breast cancer, leukemia, autism, obesity, diabetes and lung cancer. The primary goal of such research activities will include the development of advanced drug compounds targeting underlying biological pathways.” 

To prepare the Demerec building for 21st-century science, it had to be gutted, with extensive renovations of the basement and interior, while leaving the historic 1950s brutalist exterior largely unchanged.

“We really challenged ourselves to preserve the history of the building as much as possible,” said Centerbrook design firm architect Todd E. Andrews, who planned the renovation.

The result is a modern facility uniquely designed for a scientific approach that considers disease not as a stand-alone subject of study but as a complex system that focuses on the patient.

“Too often [scientists] are not looking at the patient and the system of the patient … even though there are obvious signs that we should be looking,” said Dr. Tobias Janowitz, one of the next generation of Demerec Lab scientists and research-clinicians dedicated to rethinking cancer medicine.

Other Demerec researchers will include Nicholas Tonks, who investigates relationships between diabetes, obesity and cancer, and Linda Van Aelst, a neuroscientist who is interested in how sleep and signals from the brain may be impacted by cancer. Semir Beyaz, who studies how a patient’s nutrition can affect cancer treatment, will also join the team.

While the Demerec Laboratory’s faculty hasn’t been finalized, the researchers will be working alongside the rest of the CSHL community — including 600 scientists, students and technicians — to create a distinctly collaborative and cross-disciplinary culture.

Governor Cuomo called the Demerec building and the larger CSHL campus “hallowed ground for scientific research,” after dedicating $25 million in 2017 toward the $75 million renovation and said he is confident the space and its scientists will deliver a new wave of scientific progress.

“We invested over $620 million statewide in life sciences with $250 million in Long Island alone in biotech. Why? Because we believe that is an economic cluster that is going to grow and that is going to create jobs and it already is,” the governor said. “I believe Long Island is going to be the next Research Triangle.“

Renovating a single research facility may seem like a small step toward the state’s goal, but this particular building has made Long Island a scientific hot spot once again.

“While the Demerec building is comparatively smaller than larger projects that the governor has initiated … it is arguably one of the most productive buildings in all of science,” said CSHL President and CEO Bruce Stillman. “This renovation allows us to really think about where the Lab will take things next. It will have, I hope, a global impact on the research community, especially in the biomedical sciences.

Pictured from left: Laurel Hollow Mayor Daniel DeVita, President of Long Island Association Kevin Law, Northwell Health CEO Michael Dowling, President of Empire State Development Eric Gertler, Commissioner of Health for NYS Dr. Howard Zucker, CSHL President and CEO Bruce Stillman, Governor Andrew M. Cuomo, CSHL Honorary Trustee Jim Simons, CSHL Chair of the Board of Trustees Marilyn Simons, Nassau County Supervisor Laura Curran, NYS State Assemblyman Chuck Lavine, NYS Assemblyman Steve Stern, NYS Senator Jim Gaughran and CSHL COO John Tuke.   Photo by © Kevin P. Coughlin/Office of Governor Andrew M. Cuomo

 

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Bruce Stillman. Photo courtesy of CSHL

By Daniel Dunaief

Bruce Stillman, the president and CEO of Cold Spring Harbor Laboratory, was recently awarded the prestigious Canada Gairdner International Award for his contributions to research about the way DNA copies itself. The 60-year-old prize, which Stillman will receive in a ceremony in October and that he shares with his former postdoctoral fellow John Diffley, includes a financial award of $100,000 Canadian dollars that he can spend however he’d like.

A native Australian, Stillman, who has been at Cold Spring Harbor Laboratory since 1979, recently shared his thoughts about the award, research at the lab and his concerns about science in society with Times Beacon Record News Media. 

How does it feel winning the Gairdner Award?

It’s one of the most prestigious awards in the life sciences in the world and it’s certainly a great honor to win it and to join the list of spectacular scientists in the history of the award. There are some really fantastic scientists who I very much admire who have received this award.

How does it relate to the research you’ve conducted?

The field of DNA replication and chromosome inheritance was recognized. It is something I’ve devoted my entire career to. There are a lot of people that have made important contributions to this field. I’m pleased to be recognized with [Diffley] who was my former postdoc. [It’s validating] that the field was recognized.

Has CSH Laboratory been at the cutting edge of discoveries using the gene-editing tool CRISPR?

Cold Spring Harbor didn’t discover CRISPR. Like many institutions, we’ve been at the forefront of applying CRISPR and gene editing. The most spectacular application of that has been in the plant field. Zachary Lippman, Dave Jackson and Rob Martienssen are using genetic engineering to understand plant morphogenesis and development, thereby increasing the yield of fruit. Hopefully, this will be expanded into grains and have another green revolution.

CSHL has also been making strides in cancer research, particularly in Dave Tuveson’s lab, with organoids.

Organoids came out of people studying development. Hans Clevers [developed organoids] in the Netherlands … Tuveson is at the forefront of that. The full promise hasn’t been realized yet. From what I’ve seen, we are quite excited about the possibility of using organoids as a tool to get real feedback to patients. It is rapidly moving forward with the Lustgarten Foundation and with Northwell Health.

What are some of the other major initiatives at CSHL?

The laboratory’s investment about 10 or 15 years ago in understanding cognition in the brain has paid off enormously. Neuroscientists here are at the forefront of understanding cognition and how the brain does computation in complicated decisions. [Scientists are also] mapping circuits in the brain. It took a lot of investment and kind of the belief that studying rodent cognition could have an impact on human cognition, which was controversial when we started it here, but has paid out quite well. At the same time, we are studying cognitive dysfunction particularly in autism. 

Any other technological advances?

There’s been a real revolution in the field of structural biology… [Researchers] have the ability to look at single biological molecules in the electron microscope. It shoots electrons through a grid that has individual biological molecules. The revolution, which was done elsewhere by many people actually, led to the ability to get atomic resolution structures of macro molecular complexes. 

Cold Spring Harbor invested a lot of money, well over $10 million to build a facility and staff a facility to operate this new technology. I’ve been working on this area for about 12, 13 years now … Our structural biologists here in neuroscience, including neuroscientists Hiro Furukawa and Leemor Joshua-Tor have really helped introduce a lot of new biology into CSHL.

What are some of the newer efforts at the lab?

One of the big new initiatives we started is in the field of cancer. As you know by looking around, there’s an obesity epidemic in the Western world. We started a fairly large initiative, understanding the relationship between obesity and cancer and nutrition, and we’re not unique in this. We’re going to have some significant contributions in this area. 

Cancer cells and the tumor affect the whole body physiology. The most severe [consequence] is that advanced cancer patients lose weight through a process called cachexia. We hired [new staff] in this new initiative, renovated a historic building, the Demerec building at a fairly substantial expense, which was supported by New York State. 

What will CSHL researchers study related to obesity?

We’re absolutely going to be focusing on understanding mostly how obesity impacts cancer and the immune system, then how cancer impacts the whole body physiology. Hopefully, once we start to understand the circuits, [we] will be able to intervene. If we can control obesity, we will by logic reduce cancer impact.

What worries you about society?

What worries me is that there is a tendency in this country to ignore science in policy decisions … The number of people not getting vaccinated for measles is ridiculous. There is this kind of pervasive anti-science, anti-technology view that a lot of Americans have. They want the benefits of science and everything that can profit for them. 

There are certain groups of people who misuse data, deliberately abuse misinformation on science to promote agendas that are completely irrational. One of the worst is anti-vaccination. … We should as a society have severe penalties for those who choose to go that route. They shouldn’t send their children to schools, participate in public areas where they could spread a disease that effectively was controlled. Imagine if polio or tuberculosis came back?

How is the lab contributing to education?

People need to act like scientists. It’s one of the reasons we have the DNA Learning Center, to teach people to think like scientists. If 99.99 percent of the evidence suggests [something specific] and 0.01 percent suggest something [else], you have to wonder whether those very small and vocal minority are correct.

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Adrian Krainer in his lab. Photo by ©Kathy Kmonicek, 2016/CSHL

By Daniel Dunaief

This Sunday, Adrian Krainer is traveling to California to visit with Emma Larson, a Middle Island girl whose life he helped save, and to see an actor who played the fictional super spy James Bond.

A professor at Cold Spring Harbor Laboratory, Krainer is the recipient of the Breakthrough Prize in Life Sciences, which noted Silicon Valley benefactors including Facebook’s Mark Zuckerberg and Google’s Sergey Brin financed seven years ago. Pierce Brosnan will host the event, which National Geographic will broadcast live starting at 10 p.m. Eastern time.

Dr. Adrian Krainer and Emma Larson. Photo from Diane Larson

Krainer will split the $3 million prize money with Frank Bennett, a senior vice president of research and a founding member of Ionis Pharmaceuticals. The duo helped develop the first treatment for spinal muscular atrophy, the leading genetic cause of death among infants, which affects 1 in 10,000 births.

Prior to the Food and Drug Administration’s approval of Ionis and Biogen’s treatment, which is called Spinraza, people with the most severe cases of this disease lost the ability to use their muscles and even to breathe or swallow. Many children born with the most severe symptoms died before they were 2 years old.

“No one deserves it more,” said Dianne Larson, whose 5-year-old daughter Emma has been in a trial for the drug Krainer helped develop since 2015. When Emma started the trial as a 2-year-old, she couldn’t crawl anymore. Now, she’s able to push herself in a wheelchair, stand and take steps while holding onto something. Emma refers to Krainer as the person who helped make “my magic medicine.”

People with medical needs “kind of take for granted that there’s a medicine out there,” Larson said. “You don’t think about the years of dedication and research and hours and hours and money it costs to do this.”

Bruce Stillman, president and chief executive officer at Cold Spring Harbor Laboratory, said that this award was well deserved and was rooted in basic science. Krainer’s “insights were substantial and he realized that he could apply this unique knowledge to tackle SMA,” Stillman wrote in an email. “He did this with spectacular results.”

Dr. Adrian Krainer with the Larson family, Matthew, Diane and Emma. Photo from Diane Larson

Children with the most severe case of this disease had faced a grim diagnosis. “Now those children have a treatment that will keep them alive and greatly improve the prospects for a normal life,” Stillman added.

New York recently added SMA to its newborn screening test.

Krainer, who specialized in a process called RNA splicing during his research training, began searching for ways to help people with spinal muscular atrophy in 2000.

SMA mostly originates when the gene SMN1 has a defect that prevents it from producing the SMN protein,  called survival of motor neuron. This protein is important for the motor neurons, the nerve cells that control voluntary muscles.

As it turns out, people have a backup gene, called SMN2, which produces that important protein. The problem with this backup gene, however, is that it produces the protein in lower amounts. Additionally, RNA gene splicing leaves out a segment that’s important for the stability of the protein.

Looking at the backup gene, Krainer began his SMA work by seeking to understand what caused this splicing inefficiency, hoping to find a way to fix the process so that more function protein could be made from the SMN2 gene.

Collaborating with Bennett since 2004, Krainer developed and tested an antisense olignucleotide, or ASO. This molecule effectively blocked the binding of a repressor protein to the SMN2 transcript. By blocking this repressor’s action, the ASO enabled the correct splicing of the survival of motor neuron protein.

Emma Larson standing during her Mandarin lesson at Middle Country Public Library. Photo from Diane Larson

At first, Krainer tested the cells in a test tube and then in culture cells. When that worked, he went on to try this molecule in an SMA mouse model. He then worked with Ionis Pharmaceuticals and Biogen to perform the tests with patients. These tests went through hundreds of patients in numerous countries, as diseases like SMA aren’t limited by geographic boundaries.

“Everything worked” in the drug process, which is why it took a “relatively short time” to bring the treatment to market, Krainer said.

People who have worked with Krainer for years admire his character and commitment to his work.

Joe and Martha Slay, who founded the nonprofit group FightSMA, helped recruit Krainer to join the search for a treatment.

Joe Slay recalls how Krainer made an effort to meet with children with SMA. He recalls seeing Krainer during a pickup football game, running alongside children in wheelchairs, handing them the ball and tossing it with them.

Krainer brought his family, including his three children, to meet with the SMA community. The trip had a positive effect on his daughter Emily, who said it “subliminally had an impact on wanting to work in this field.” 

Currently a third-year resident in a combined pediatric neurology residency and fellowship program, his daughter is “very excited for him and proud.” She recalls spending Christmas holidays and New Years celebrations at the lab, where she met with his friends and co-workers.

Emily Krainer said a few people in her residency know about the role her father played in developing a treatment the hospital is employing.

The treatment is the “talk of child neurology right now,” she said.

Researchers hope the recognition for the value of basic research that comes with the breakthrough prize will have an inspirational effect on the next generation.

“The idea of prizes like this is to highlight to the public that scientists spend many years working without public recognition but make really important contributions to society,” Stillman suggested.

For Larson, the research Krainer did was key to a life change.

“To me, science is hope,” Larson said. “If we didn’t have this science, we wouldn’t have any hope,” adding that she would like her daughter to become a scientist someday.

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