Science & Technology

From left, Zachary Lippman and Dave Jackson, professors at CSHL who are working on ways to alter promoter regions of genes to control traits in tomato and corn. Photo by Ullas Pedmale

By Daniel Dunaief

He works with tomatoes, but what he’s discovered could have applications to food and fuel crops, including corn, rice and wheat.

Using the latest gene editing technique called CRISPR, Zachary Lippman, a professor at Cold Spring Harbor Laboratory, developed ways to fine-tune traits for fruit size, branching architecture and plant shape. Called quantitative variation, these genetic changes act as a dimmer switch, potentially increasing or decreasing specific traits. This could help meet specific agricultural needs. Looking at the so-called promoter region of genes, Lippman was able to “use those genes as proof of principal” for a technique that may enable the fine-tuning of several traits.

For decades, plant breeders have been looking for naturally occurring mutations that allow them to breed those desirable traits, such as a larger fruit on a tomato or more branches on a plant. In some cases, genetic mutations have occurred naturally, altering the cell’s directions. At other times, breeders have sought ways to encourage mutations by treating their seeds with a specific mutagenic agent, like a chemical.

In an article in the journal Cell, Lippman said the results reflect a road map that other researchers or agricultural companies can use to create desirable traits. This article provides a way to “create a new, raw material for breeders to have access to tools they never had before,” he said. Lippman has taken a chunk of the DNA in the promoter region, typically on the order of 2,000 to 4,000 base pairs, and let the CRISPR scissors alter this part of the genetic code. Then, he and his scientific team chose which cuts from the scissors and subsequent repairs by the cell’s machinery gave the desired modifications to the traits they were studying.

Invented only five years ago, CRISPR is a genetic editing technique that uses tools bacteria have developed to fight off viral infections. Once a bacteria is attacked by a virus, it inserts a small piece of the viral gene into its own sequence. If a similar virus attacks again, the bacteria immediately recognizes the invader and cuts the sequence away.

Scientists sometimes use these molecular scissors to trim specific gene sequences in a process called a deletion. They are also working toward ways to take another genetic code and insert a replacement. “Replacement technology is only now starting to become efficient,” Lippman said. Clinical researchers are especially excited about the potential for this technique in treating genetic conditions, potentially removing and replacing an ineffective sequence.

In Lippman’s case, he used the scissors to cut in several places in the promoter regions of the tomato plant. Rather than targeting specific genes, he directed those scissors to change the genome at several places. When he planted the new seeds, he explored their phenotype, or the physical manifestation of their genetic instructions. These phenotypes varied along a continuum, depending on the changes in their genes.

By going backward and then comparing the genes of the altered plants to the original, he could then hone in on the precise changes in the genetic code that enabled that variation. This technique allows for a finer manipulation than turning on or off specific genes in which an organism, in this case a plant, would either follow specific instructions or would go on a transcriptional break, halting production until it was turned on again.

At this point, Lippman has worked with each trait individually but hasn’t done quantitative variation for more than one at a time. “The next question,” he said, “is to do this multitargeting.” He will also use the tool to study how genes are instructed to turn on and off during growth, including exploring the levels and location of expression.

Lippman is talking with agricultural and scientific collaborators and hopes to go beyond the tomato to exploring the application of this approach to other crops. He is working with Dave Jackson, who is also a professor at Cold Spring Harbor Laboratory, on applying this model to corn.

The scientific duo has known each other for 20 years. Jackson taught his collaborator when Lippman was a graduate student at Cold Spring Harbor Laboratory and Jackson was chair of his thesis committee.

They have worked together on and off since Lippman became a faculty member about nine years ago. Last year, the two received a National Science Foundation genome grant to work on using CRISPR to study the effect of changes in promoter regions in their respective plant specialties.

“Unfortunately for us, tomato has a faster life cycle than corn, but we hope to have some results in corn this fall,” Jackson explained in an email. Lippman hopes to continue on the path toward understanding how regulatory DNA is controlling complex traits. “We can use this tool to dissect critical regulatory regions,” he said. “When we create this variation, we can look at how that translates to a phenotypic variation.”

Lippman said he is especially excited about the fundamental biological questions related to plant growth and development. When other scientists or agricultural companies attempt to use this approach, they may run into some challenges, he said. Some plants are “not transformable [genetically] easily.” These plants can be recalcitrant to plant transformation, a step sometimes needed for CRISPR gene editing. Still, it is “likely that CRISPR will work in all organisms,” he said.

Lippman hopes others discuss this technique and see the potential for a system that could help to customize plants. “My hope and my anticipation is that people all over the world will look at this paper and say, ‘Let’s start to try this out in our own systems.’ Hopefully, there will be a grass roots effort to import this tool.”

Anne Churchland. Photo from CSHL

By Daniel Dunaief

Someone is hungry and is walking through a familiar town. She smells pizza coming from the hot brick oven on her left, she watches someone leaving her favorite Chinese restaurant with the familiar takeout boxes, and she thinks about the fish restaurant with special catches of the day that she usually enjoys around this time of year. How does she make her decision?

While this scenario is a simplified one, it’s a window into the decision-making process people go through when their neurons work together. A team of 21 neuroscientists in Europe and the United States recently created a new collaboration called the International Brain Laboratory to explore how networks of brain cells support learning and decision-making.

“We understand the simple motor reflex,” such as when a doctor taps a knee and a foot kicks out, said Anne Churchland, an associate professor at Cold Spring Harbor Laboratory and the American spokesperson for this new effort. Scientists, however, have only a limited understanding of the cognitive processes that weigh sensory details and a recollection of the outcomes from various courses of action that lead to decision-making, Churchland said.

Scientists likened the structure of the new multilaboratory effort to the circuitry involved in the brain itself. The brain is “massively parallel,” said Alexandre Pouget, a professor at the University of Geneva and the spokesperson for the IBL. “We know it’s working on consensus building across areas so, in that respect, the IBL is similar.”

A greater awareness of the decision-making process could provide a step into understanding the brain network problems involved in mental health disorders.

Churchland’s lab is one of three facilities that will house a new behavioral apparatus to study decision-making in mice. The other sites will be in the United Kingdom and in Portugal. Eventually, other labs will use this same technique and house the same apparatus.

An ongoing challenge in this field of research, Churchland said, is that scientists sometimes create their own models to test the neurological basis of behavior. While these approaches may work in their own labs, they have created a reproducibility problem, making it difficult for others who don’t have expertise in their methods to duplicate the results.

Creating this behavioral apparatus will help ensure that the collaborators are approaching the research with a reliable model that they can repeat, with similar results, in other facilities.

While the scientists will all be exploring the brain, they will each be responsible for studying the activity of circuits in different parts. The researchers will collect a wealth of information and will share it through a developing computer system that allows them to maneuver through the mountains of data.

To address this challenge, the IBL is creating a data architecture working group. Kenneth Harris, a professor of quantitative neuroscience at the University College London, is the chair of the effort. He is currently looking to hire additional outside staff to help develop this process.

Harris suggested that the process of sharing data in neurophysiology has been challenging because of the complex and diverse data these scientists share. “In neuroscience, we have lots of different types of measurements, made simultaneously with lots of different experimental methods, that all have to be integrated together,” he explained in an email.

The IBL collaboration will make his job slightly easier than the generic problem of neurophysiology data sharing because “all the labs will be studying how the brain solves the same decision-making task,” he continued.

Harris is looking to hire a data coordinator, a senior scientific programmer and a scientific MATLAB programmer. He has a data management system already running with his lab that he plans to extend to the IBL.

Pouget said there are two milestones built into the funding from the Wellcome Trust and the Simons Foundation for this new collaboration. After two years, the researchers have to have a data sharing platform in place, which will allow them to share data live as they collect it.

Second, they plan to develop standardized behaviors in all 11 of the experimental labs, where the behavior has to be as indistinguishable from one lab to another as possible.

In addition to the experimentalists involved in this initiative, several theoretical neurobiologists will also contribute and will be critical to unraveling the enormous amounts of data, Pouget suggested. “If you’re going to tackle really hard computational problems, you better have people trained in that area,” he said, adding that he estimates that only about 5 percent of neuroscientists are involved in the theoretical side, which is considerably lower than the percent in an area like physics.

Researchers involved in this project will have the opportunity to move from one lab to another, conducting experiments and gaining expertise and insights. The principal investigators are also in the process of hiring 21 postdoctoral students.

Churchland said each scientist will continue to conduct his or her own research while also contributing to this effort. The IBL is consuming between a quarter and a third of her time.

Pouget suggested that Churchland was “instrumental in representing the International Brain Laboratory to the Simons Foundation,” where she is the principal investigator on that grant. “Her role has been critical to the organization,” he said.

Churchland said the effort is progressing rapidly. “It’s moving way faster” than expected. “This is the right moment, with an incredible team of people, to be working together. Everyone is dedicated to the science.”

Harris indicated that he believes this effort could be transformative for the field. “Neuroscience has lagged behind many other scientific domains” in creating large-scale collaborations, he explained. “If we can show it works, we will change the entire field for good.”

From left, Lisa Miller with her research team Andrew McGregor, Alvin Acerbo, Tiffany Victor, Randy Smith, Ruth Pietri, Ryan Tappero, Nadia Hameed, Tunisia Solomon, Paul Panica and Adam Lowery. Photo by Roger Stoutenburgh, BNL

By Daniel Dunaief

Most of the people at the building that cost near a billion dollars are pulled in different directions, often, seemingly, at the same time. They help others who, like them, have numerous questions about the world far smaller than the eye can see. They also have their own questions, partnering up with other researchers to divide the work.

Lisa Miller, a senior biophysical chemist at Brookhaven National Laboratory, lives just such a multidirectional and multidimensional life. The manager for user services, communications, education and outreach at the National Synchrotron Light Source II, Miller recently joined forces with other scientists to explore the potential impact of copper on a neurodegenerative disease called cerebral amyloid angiopathy (CAA).

Miller is collaborating with Steve Smith, the director of structural biology in the Department of Biochemistry and Cell Biology at Stony Brook University and William Van Nostrand, a professor in the Department of Neurosurgery at SBU who will be moving to the University of Rhode Island. The trio is in the second year of a five-year grant from the National Institutes of Health.

Miller’s role is to image the content, distribution and oxidation state of copper in the mouse brain and vessels. Van Nostrand, whom Smith described as the “glue” that holds the group together, does the cognitive studies and Smith explores the amyloid structure.

In an email, Smith explained that Van Nostrand’s primary area of research is in CAA, while he and Miller were originally focused elsewhere.

Potentially toxic on its own, copper is transported in the body attached to a protein. When copper is in a particular ionic state — when it has two extra protons and is looking for electrons with which to reduce its positive charge — it reacts with water and oxygen, producing hydrogen peroxide, which is toxic.

Miller and her colleagues are working on a technique that will enable them to freeze the tissue and image it. Seeing the oxidation state of the metal requires that it be hydrated, or wet. The X-rays, however, react with water, causing radiation damage to the tissue.

To minimize this damage, the researchers freeze the tissue. At NSLS-II, a team of scientists are working to develop X-ray-compatible cryostages that will allow them to freeze and image the tissue.

Miller is trying to figure out where and why the copper is binding to an amyloid beta protein. This is the same protein that’s involved in plaques prevalent in the brains of people with Alzheimer’s disease.

In Alzheimer’s patients, the plaques are found in the parenchyma, or the extracellular space around the brain cells. In CAA, the deposits are attached to the surface of the blood vessels on the brain side.

Lisa Miller and her dog Dora on a recent 100-mile trek from Hiawassee, Georgia, to Fontana Dam in North Carolina Photo from Lisa Miller

The current hypothesis about how copper becomes reactive in the brain originates from work Van Nostrand and Smith published recently. They suggested that the amyloid fibrils in CAA adopt an anti-parallel orientation and the fibrils in the plaques in Alzheimer’s are in a parallel orientation. The anti-parallel structure predicts that there is a binding site for copper that, if occupied, would stabilize the structure.

“We are currently working to establish if this idea is correct,” Smith explained in an email, suggesting that the NSLS-II provides a “unique resource for addressing the role of copper in CAA. The data [Miller] is collecting are essential, key components of the puzzle.”

The NSLS-II will provide the kind of spatial resolution that allows Miller to measure how much copper is in the deposits. Ideally, she’d like to see the oxidation state of the copper to see if a reaction that’s producing hydrogen peroxide is occurring.

A challenge with peroxide is that it’s hard to find in a living tissue. It is highly reactive, which means it does its damage and then reverts to water and oxygen.

As someone with considerable responsibilities outside her own scientific pursuits, Miller said she spends about a quarter of her time on her own research. One of Miller’s jobs during the summer is to host the open house for NSLS-II, which allows members of the community to visit the facility. This year, at the end of July, she “was thrilled” to host about 1,600 members of the community.

“Most of them wanted to go on the floor and meet the scientists and walk” around the three quarters of a mile circle, she said. While they are interested in the research, the surprising mode of transportation strikes their fancy when they trek around the site.

“The thing that fascinates them when they walk in the door is the tricycles,” she said. The NSLS-II can’t take credit for being the first facility to use these adult-sized tricycles, which number over 100 at the facility. “It’s a synchrotron thing.”

The previous NSLS at BNL was too compact and had too many turns, which made the three-wheeled vehicles, which, like a truck, need a wider turning radius to maneuver on a road, impractical.

Miller, who is a part of the trike-share program, is an avid hiker. This summer, she completed a 100-mile trek from Hiawassee, Georgia, to Fontana Dam in North Carolina. This section was located in the area of totality for the solar eclipse and Miller was able to witness the astronomical phenomenon at Siler Bald in North Carolina.

A resident of Wading River, Miller, who grew up in the similarly flat terrain of Cleveland, spends considerable time walking and running with her rescue mutt Dora, who accompanied her on her recent hike.

While Miller finds the research she does with copper rewarding, she said she also appreciates the opportunities NSLS-II affords her. “Every day is different and we never know what project will show up next,” she said.

Laurie Shroyer, center, with Gerald McDonald, left, who was chief of surgery survive at the VA Central Office and is now retired, and Fred Grover, right, a professor of cardiothoracic surgery in the Department of Surgery at the University of Colorado. Photo from Laurie Shroyer

By Daniel Dunaief

To use the pump or not to use the pump? That is the question heart surgeons face when they’re preparing to perform a surgery that occurs about 145,000 times a year in the United States.

Laurie Shroyer. Photo from SBU

Called coronary artery bypass graft, surgeons perform this procedure to improve blood flow to a heart that is often obstructed by plaque. Patients with severe coronary heart disease benefit from a technique in which an artery or vein from another part of the body is inserted into the heart, bypassing the blockage.

Doctors can perform the surgery with a heart-lung machine, which is called on pump, or without it, which is called off pump.

Recently, a team of researchers led by Laurie Shroyer, who is a professor of surgery and the vice chair for research at the Stony Brook University School of Medicine, published a study in the New England Journal of Medicine that compared the survival and health of 2,203 veterans five years after surgery, with or without the pump.

Contradicting some earlier research that showed no difference in the health and outcomes after the surgery, the study revealed that using the pump increased the survival rate and reduced the rate of other health problems.

Along with the other research articles in this area, this study “should help in deciding the relative value and risks of each technique,” Frederick Grover, a professor of cardiothoracic surgery in the Department of Surgery at the University of Colorado, explained in an email.

The study Shroyer led, which is known as the Rooby trial, showed that on-pump patients had a five-year mortality of 11.9 percent, compared with 15.2 percent for the off-pump patients, Shroyer explained.

The five-year rate of medical complications, including death, nonfatal heart attacks and revascularization procedures was also lower for the on-pump group than the off-pump group, at 27.1 percent compared to 31 percent, respectively.

Consistent with these findings, the overall use of off-pump procedures has declined, from a peak of 23 percent in 2002 to 17 percent in 2012, down to 13.1 percent in 2016, according to data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database Committee.

At one point, surgeons had considered an off-pump approach to be safer, but when other trials didn’t show a benefit and when the current Rooby trial demonstrated on pump had better outcomes, it “likely influenced many surgeons to use the off pump less often for specific reasons, considering it is a somewhat more difficult technique except in the most experienced hands,” Grover wrote.

The explanation for the difference five years after surgery are “not clear,” Shroyer explained in an email. The article suggests that the off-pump patients had less complete revascularization, which is known to decrease long-term survival.

Grover explained that the outcomes may have been better for the on-pump procedures in the Rooby trial for several reasons, including that the surgeons in the different trials had different levels of experience.

Leaders of the study suggested that patients and their surgeons needed to consider how to use the information to inform their medical decisions. Participants in the study were men who were veterans of the armed services.

“The data can likely be extrapolated to the general population since it is not an extremely high-risk population, but it is all male so would primarily extrapolate to males,” Grover suggested. Additionally, patients with specific conditions might still have better outcomes without the use of a pump.

“Our manuscript identifies an example for ‘patients with an extensively calcified aorta, in whom the off-pump technique may result in less manipulation of the aorta, potentially decreasing the risk of aortic emboli or stroke,’” Shroyer wrote in an email. Grover also suggested people with severe liver failure also might want to avoid the pump to prevent additional harm to the liver.

Shroyer and her team have already submitted a proposal to the VA Central Office Cooperative Studies Program. “Pending approval and funding, 10-year follow-ups will be coordinated appropriately,” Shroyer said.

Grover described Shroyer as a “spectacular investigator with a very high level of knowledge of clinical research” and, he added, a “perfectionist.” When he met Shroyer, Grover said he was “blown away by her intelligence, experience, background and energy.” He interviewed her many years ago to direct a major VA Cooperative Study. After the interview and before the next meeting, he called another interviewer and asked if he, too, agreed to hire her on the spot.

Grover recalled a trip back from Washington to Denver 15 years ago after they had been in a 10-hour meeting with no scheduled breaks. She took out her laptop on the airplane and asked him to write up results for a new grant.

“I was beat and finally said if she didn’t let up, I was going to jump out of the airplane just to get away from her,” he recalled. She shut her computer, ordered drinks and they enjoyed a peaceful flight back.

A resident of Setauket, Shroyer lives with her husband Ken, who is the chair of the Department of Pathology at Stony Brook School of Medicine. The professor said she loves the Staller Center, which she considers one of the greatest kept local secrets. She appreciates the opportunity to hear classical music performances by the Emerson String Quartet and by cellist Colin Carr.

When she entered biomedical research in 1992, it was unusual for women to rise to the level of full professor at an academic medical center. She strives to be an outstanding mentor to her trainees, including women and under-represented minorities, so that they can achieve their potential, too. As for her work, Shroyer’s hope is that the Rooby research “will provide useful information to guide future changes in clinical care practices” and, in the longer term “to improve the quality and outcomes for cardiac surgical care.”

Richard Moffitt, who joined Stony Brook University’s Biomedical Informatics and Pathology departments at the end of July, recently contributed to an extensive study of pancreatic cancer. Photo by Valerie Peterson

By Daniel Dunaief

It may take a village and then some to conquer pancreatic cancer, which is pretty close to what The Cancer Genome Atlas project assembled.

Pulling together over 200 researchers from facilities across the United States, the TCGA recently published an article in the journal Cancer Cell in which the scientists explored genetic, proteomic and clinical information from 150 pancreatic cancer patients.

Richard Moffitt, an assistant professor in the Departments of Biomedical Informatics and Pathology at Stony Brook University who joined the institution at the end of July, was the analysis coordinator for this extensive effort.

The results of this research, which worked with pancreatic ductal adenocarcinoma, the most common form of this cancer, offered a look at specific genetic changes involved in pancreatic cancer, which is the third leading cause of death from cancer.

“The study has several immediate clinical implications for patients facing the diagnosis of pancreatic cancer,” Ralph Hruban, one of the corresponding authors on the article and the director of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University School of Medicine, wrote in an email.

The work “provides hope for future clinical trials in that 42 percent of patients within this cohort had cancers with at least one genetic alteration that could potentially be therapeutically targetable, and 25 percent of the patients had cancers with two or more such events.”

These genetic findings suggest a potential basis for genetic change-driven therapy trials down the road, Hruban suggested. As the analysis coordinator, Moffitt “played a critical role” Hruban continued. “He brought hard work, amazing creativity and great scientific knowledge to the project.”

Moffitt joined this effort about four years ago, after the collaboration began. The assistant professor said he pulled together the various data sets and analysis results from different teams and helped turn that into a “coherent overall story.”

Moffitt was also in charge of the messenger RNA analysis. He had been at the University of North Carolina as a postdoctoral researcher in Vice Chair of Research Jen Jen Yeh’s lab for the last five years until his recent move to Stony Brook.

Benjamin Raphael, another corresponding author on the article and a professor in the Department of Computer Science at Princeton University, suggested Moffitt played a critical part in the recent work. “In any large-scale collaboration such as this one, there tend to be a smaller number of researchers who play an outsized role in the project,” Raphael explained in an email. Moffitt “played such an outsized role. Without his dedication to the project over the past few years, it is doubtful that our analysis” would have been as comprehensive.

Members of TCGA contacted Moffitt and Yeh because the tandem were working on a new approach to studying gene expression that would eventually be published in a 2015 Nature Genetics article.

Working with Yeh, Moffitt helped tease apart the genetic signature of pancreatic cancer cells from the different types of cells around it, which also includes healthy cells and a cluster of dense cells around the tumor called the stroma.

“The proportion of cancer cells in pancreatic cancer is low so if you imagine a mix of marbles of the same color on the outside but different on the inside and only having 10 in a bag of 100, figuring out what 10 [are] ‘tumor’ colors on the inside was very challenging,” Yeh explained in an email.

The TCGA study explains subtypes of cancer Moffitt didn’t know existed just a few years ago, while exploring the possible role that micro RNA and DNA methylation — the process of adding or taking away a methyl group from a genetic sequence to turn on and off genes — has in describing those subtypes.

Researchers “need projects like TCGA that are a really well-controlled way to study almost every molecule you want to study systematically for 150 cases to reveal these networks,” Moffitt said.

Moffitt has coupled his appreciation for algorithms and math with an interest in biology and engineering. His Ph.D. was done in a dry lab, which didn’t even have a sink. When he moved to UNC to conduct his postdoctoral work, he took a different approach and worked with surgical oncologists on tissue samples.

Moffitt plans to continue working with TCGA data and also to see how the subtypes can be used to predict responses to therapies. Some time in the future, researchers hope patients can get a diagnostic biopsy that will direct them to the specific therapy they receive, he said.

Moffitt grew up in Florida and earned his bachelor’s and doctoral degrees at Georgia Tech before completing his postdoctoral research at UNC. He has been gradually drifting north. Moffitt and his wife Andrea, who just started her postdoctoral work with Michael Wigler and Dan Levy at Cold Spring Harbor Laboratory, live in Stony Brook.

A competitive water skier during his youth in Florida, Richard Moffitt, dons two skis when he’s out with friends on Lake Oconee, Georgia in 2013. Photo by Andrea Moffitt

The water on Long Island is colder than it is in Florida, where Moffitt spent considerable time on a show skiing team. This was his version of a varsity sport, where he spent about six hours a day on Saturday and Sunday during the spring and about three hours a night before tournaments performing moving pyramids, among other tricks. When he was in high school, Moffitt wrote a computer program that automates the show skiing scoring process.

Moffitt processes the world through probabilities, which figured into the way he chose stocks in high school as a part of a stock picking competition and the way he approached his picks for March Madness. His basketball bracket won a competition for bragging rights among about a dozen entrants in 2016 and he was one game away from repeating in 2017 until UNC beat Gonzaga.

As for his Stony Brook effort, Moffitt plans to collaborate with members of the Cancer Center as well. “Being in demand is a good thing.”

By Elof Axel Carlson

Elof Axel Carlson

Why is the term race rarely used by geneticists? The term race is not a scientific one. It is largely cultural when applied to humans. It is too ambiguous a term for describing a population of any one species.

For example, suppose I were a breeder of dachshunds and I specialized in two varieties — one that had a black coat of fur and the other that had a tan coat of fur. I would not call them black or tan races. I would call them varieties of a specific breed called dachshunds of dogs who are described by biologists as the species Canis vulgaris.

The term race is vague. Is it the varietal difference? Is it the collection of traits that we use for dogs, cats, horses, cattle and other domesticated animals? If it is applied to the color of dachshunds, does that mean humans are divided into thousands of races if I were to use McKusick’s online reference work on Mendelian inheritance in humans?

That work describes thousands of genetic traits caused by single gene malfunctions. Geneticists use the term breed for genetically manipulated traits or collections of traits by human selection or breeding. They use the term varieties or naturally occurring variations in a population or for new varieties arising by mutation in a sperm or egg.

Racism is used to describe a social application of race to designate rights and to assign attributes to other races by members of a specific race. There is far more genetic variation within a single race than there is between any two races. The criteria for classifying human races are often arbitrary and are based on skin color, facial appearance, hair texture and other visually distinctive traits. Many of these traits involve quantitative factors (like skin color), and thus racial mixture quickly obliterates the sharp racial traits initially used to describe a person of a specific race.

Quite a few people who have considered themselves and their immediate family as white are surprised when they send off DNA to be analyzed and discover they have percentages of African, Asian, Hispanic, Native American or Jewish ancestry along with their majority Caucasian Western European ancestry.

Racism is particularly destructive in assigning behavioral traits (personality, intelligence and social failure or inadequacy) to race. Most of those traits are determined by how we are raised and not by a roll of genes in forming our parents’ sperm or eggs. If they were to follow their own criteria, racists would find that white Catholics and Protestants are inferior to Jews and Orientals in intelligence measured by intelligence tests or IQs.

The revival of racist ideology among groups like the KKK, neo-Nazis and white supremacy groups is not based on biology or genetics. It is based on prejudice passed down by people who feel victimized if people different from them are treated with justice, fairness and equal opportunity.

The Civil War was fought over slavery. Thousands of abolitionists participated to hide escaped slaves, write books and pamphlets denouncing slavery and demanded the freedom of all slaves. The Confederacy seceded from the U.S. and fought to keep its slaves, many slave owners justifying slavery on biblical grounds — that it was a divine punishment for the descendants of a son who laughed at his drunken naked father.

Most ministers and priests in the North denounced that interpretation. We are not born with a knowledge of our past history. It has to be learned and it has to be taught. It is easier to avoid talking about our past errors than to ignore them.

Germany made a special effort after World War II to teach the racism of its Nazi past to all its school children so that error would never again be repeated. Let us hope that we teach our youth that we are one living species, Homo sapiens, and in the Judeo-Christian tradition we all have one ancestor in common.

In the scientific tradition we also have one human species in recorded history and enormous genetic variation that is constantly changing as humans migrate around the world, settle down or move on to new areas of the Earth. Most of that variation is in Africa where our species first arose.

It is ironic that whites who enslaved or colonized Africa diminished, in their minds, this genetic variation and reduced it to racist formulas of a handful of physical or behavioral traits. I hope this revived racism will recede and our focus will shift to problems that can and should be solved by our elected representatives. Those problems are overwhelmingly caused by our social and economic conditions and not by our genes.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

Above, Ken Dill shows how molecules fold and bind together. Photo from SBU

By Daniel Dunaief

The raw materials were here. Somehow, billions of years ago, these materials followed patterns and repeated and revised the process, turning the parts into something more than a primordial soup.

Ken Dill, who is a distinguished professor and the director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University, took a methodical approach to this fundamental development. He wanted to understand the early statistical mechanics that would allow molecules to form long chains, called polymers, which contained information worthy of being passed along. The process of forming these chains had to be self-sustaining.

After all, Dill said, many activities reach an end point. Putting salt in water, for example, creates a mixture, until it stops. Dill, however, was looking for a way to understand auto-catalytic or runaway events. Lighting a forest fire, for example, is much more self sustaining, although even it eventually stops. Life has continued for over four billion years.

On Aug. 22, Dill, Elizaveta Guseva and Ronald Zuckermann, the facility director in biological nanostructures at the Lawrence Berkeley National Laboratory, published a paper in the journal Proceedings of the National Academy of Sciences (PNAS).

The researchers developed a fold and catalyze computational model that would explain how these long chains developed in a self-sustaining way, in which hydrophilic and hydrophobic polymers fold and bind together.

Random sequence chains of each type can collapse and fold into structures that expose their hydrophobic parts. Like a conga line at a wedding reception, the parts can then couple together to form longer chains.

These random chemical processes could lead to pre-proteins. Today’s proteins, Dill said, mostly fold into a very particular shape. Pre-proteins would have been looser, with more shape shifting.

The workhorses of the body, proteins perform thousands of biochemical reactions. Dill suggested that this model “rates high on the list” in terms of the findings he’s made over the course of his career.

Zuckermann described this work as significant because it lays out predictions that can be tested. It highlights the importance of chemical sequence information in polymer chains and “how certain sequences are more likely to fold into enzyme-like shapes and act as catalysts than others,” he explained in an email.

Zuckermann works with substances he figured out how to make in a lab that are called peptoids, which are non-natural polymers. These peptoids are a “good system to test the universality of [Dill’s] predictions,” he said.

The “beauty” of Dill’s work, Zuckermann suggested, is that “it should apply to most any kind of polymer system” where researchers control the monomer sequence and include hydrophobic and hydrophilic monomers in a particular order, putting Dill’s predictions to the test.

For her part, Guseva worked in Dill’s lab for her PhD thesis. She had started her research on something that was “more standard physical biology” Dill said, but it “was not turning out to be particularly interesting.”

The scientists had a discussion about trying to develop a chemical model related to the origins of life. While exciting for the scope of the question, the research could have come up empty.

“There was so much potential to fail,” Dill said. “I feel pretty uncomfortable in general about asking a graduate student to go in that direction, but she was fearless.”

Dill and Zuckermann, who have collaborated for over 25 years, are trying to move forward to the next set of questions.

Zuckermann’s efforts will focus on finding catalytic peptoid sequences, which are nonbiological polymers. He will synthesize tens of thousands of peptoid sequences and rank them on how enzyme-like they are. This, he explained, will lead to a better understanding of which monomer sequences encode for protein-like structure and function.

Zuckermann suggested that the process in this research could have the effect of transforming a soup of monomers into a soup of functional polymers. This, he said, might set the stage for the evolution of DNA and RNA.

Proteins could have been a first step towards a genetic code, although life, as currently defined, would not have blossomed until a genetic code occurred, too, Dill suggested.

The origins of DNA, however, remains an unanswered question. “We’re trying to think about where the genetic code comes from,” Dill said. “It’s not built into our model per se. Why would biology want to do a two polymer solution, which is messy and complicated and why are proteins the functional molecules? This paper doesn’t answer that question.”

Dill and Zuckermann are in the early stage of exploring that question and Dill is hopeful he can get to a new model, although he doesn’t have it yet.

Dill moved from the University of California at San Francisco to join the Laufer Center about seven years ago. He appreciates the freedom to ask “blue sky questions” that he couldn’t address as much in his previous work.

Wearing a hat from his native Oklahoma, Dill, in a photo from around 1997, tinkers with a toy boat he made with sons Tyler and Ryan. Photo by Jolanda Schreurs

A resident of Port Jefferson, Dill lives with his wife Jolanda Schreurs, who has a PhD in pharmacology. The couple has two sons, Tyler and Ryan.

Tyler graduated with a PhD from the University of California at San Diego and now works for Illumina, a company which which makes DNA sequencers. Ryan, meanwhile, is earning his PhD in chemistry from the University of Colorado and is working on lasers.

“We didn’t try to drag our sons into science,” Dill said. “With both kids, however, we had a workshop in the basement” where they often took anything that was within arm’s reach and nailed it to a board. One of the finished products was a remote-controlled and motorized boat.

As for his lab work, Dill is thrilled to have this model that he, Guseva and Zuckermann provided, while he recognizes the questions ahead. Scientists “see something puzzling and, rather than saying, ‘I need to avoid this, I don’t have an answer,’ we find it intriguing and these things lead from one step to the next. There tends to remain a huge number of super fascinating problems.”

Alex Orlov on the campus of the University of Cambridge. Photo by Nathan Pitt, University of Cambridge

By Daniel Dunaief

The Ukranian-born Alex Orlov, who is an associate professor of materials science and chemical engineering at Stony Brook University, helps officials in a delicate balancing act.

Orlov, who is a member of the US-EU working group on Risk Assessment of Nanomaterials, helps measure, monitor and understand the hazards associated with nanoparticles, which regulatory bodies then compare to the benefit these particles have in consumer products.

“My research, which is highlighted by the European Union Commission, demonstrated that under certain conditions, [specific] nanoparticles might not be safe,” Orlov said via Skype from Cambridge, England, where he has been a visiting professor for the past four summers. For carbon nanotubes, which are used in products ranging from sports equipment to vehicles and batteries, those conditions include exposure to humidity and sunlight.

“Instead of banning and restricting their production” they can be reformulated to make them safer, he said.

Orlov described how chemical companies are conducting research to enhance the safety of their products. Globally, nanotechnology has become a growing industry, as electronics and drug companies search for ways to benefit from different physical properties that exist on a small scale. Long Island has become a focal point for research in this arena, particularly at the Center for Functional Nanomaterials and the National Synchrotron Light Source II at Brookhaven National Laboratory.

Alex Orlov on the campus of the University of Cambridge. Photo by Nathan Pitt, University of Cambridge

Indeed, Orlov is working at the University of Cambridge to facilitate partnerships between researchers in the chemistry departments of the two universities, while benefiting from the facilities at BNL. “We exchange some new materials between Cambridge and Stony Brook,” he said. “We use BNL to test those materials.”

BNL is an “essential facility,” Orlov said, and is where the postdoctoral student in his lab and the five graduate students spend 30 to 60 percent of their time. The data he and his team collect can help reduce risks related to the release of nanomaterials and create safer products, he suggested.

“Most hazardous materials on Earth can be handled in a safe way,” Orlov said. “Most scientific progress and environmental protection can be merged together. Understanding the environmental impact of new technologies and reducing their risks to the environment should be at the core of scientific and technological progress.”

According to Orlov, the European Union spends more money on technological safety than the United States. European regulations, however, affect American companies, especially those that export products to companies in the European Union.

Orlov has studied how quickly toxic materials might be released in the environment under different conditions.

“What we do in our lab is put numbers” on the amount of a substance released, he said, which informs a more quantitative understanding of the risks posed by a product. Regulators seek a balance between scientific progress and industrial development in the face of uncertainty related to new technologies.

As policy makers consider the economics of regulations, they weigh the estimated cost against that value. For example, if the cost of implementing a water treatment measure is $3 million and the cost of a human life is $7 million, it’s more economical to create a water treatment plan.

Orlov teaches a course in environmental engineering. “These are the types of things I discuss with students,” he said. “For them, it’s eye opening. They are engineers. They don’t deal with economics.”

In his own research, Orlov recently published an article in which he analyzed the potential use of concrete to remove pollutants like sulfur dioxide from the air. While concrete is the biggest material people produce by weight and volume, most of it is wasted when a building gets demolished. “What we discovered,” said Orlov, who published his work in the Journal of Chemical Engineering, “is that if you take this concrete and expose new surfaces, it takes in pollutants again.”

Fotis Sotiropoulos, the dean of the College of Engineering and Applied Sciences at SBU, said Orlov has added to the understanding of the potential benefits of using concrete to remove pollutants.

Other researchers have worked only with carbon dioxide, and there is “incomplete and/or even nonexistent data for other pollutants,” Sotiropoulos explained in an email. Orlov’s research could be helpful for city planners especially for end-of-life building demolition, Sotiropoulous continued. Manufacturers could take concrete from an old, crushed building and pass waste through this concrete in smokestacks.

To be sure, the production of concrete itself is energy intensive and generates pollutants like carbon dioxide and nitrogen dioxide. “It’s not the case that concrete would take as much [pollutants] out of the air as was emitted during production,” Orlov said. On balance, however, recycled concrete could prove useful not only in reducing waste but also in removing pollutants from the air.

Orlov urged an increase in the recycling of concrete, which varies in the amount that’s recycled. He has collaborated on other projects, such as using small amounts of gold to separate water, producing hydrogen that could be used in fuel cells.

“The research showed a promising way to produce clean hydrogen from water,” Sotiropoulos said.

As for his work at Cambridge, Orlov appreciates the value the scientists in the United Kingdom place on their collaboration with their Long Island partners.

“Cambridge faculty from disciplines ranging from archeology to chemistry are aware of the SBU/BNL faculty members and their research,” Orlov said. A resident of Smithtown, Orlov has been on Long Island for eight years. In his spare time, he enjoys hiking and exploring new areas. As for his work, Orlov hopes his work helps regulators make informed decisions that protect consumers while making scientific and technological advances possible.

Hundreds of residents gather at the Ward Melville Heritage Organization’s Educational & Cultural Center to learn about Serbian inventor Nikola Tesla. Photo by Kevin Redding

By Kevin Redding

More than 100 years after his great-grandfather designed and oversaw the construction of Nikola Tesla’s Wardenclyffe laboratory in Shoreham, Sebastian White, a renowned physicist and St. James native, filled a local lecture hall to discuss all things surrounding the Serbian-American inventor.

White, whose famous ancestor Stanford White’s architectural achievements include Washington Square Arch, the original Madison Square Garden and what is now the Tesla Science Center, took time out of his busy schedule as a particle physicist for CERN — the European Organization for Nuclear Research — to engage a roomful of science lovers Aug. 27.

The presentation was in conjunction with the center’s summer-long Tesla exhibit in Stony Brook and ended with a screening of clips from “Tower to the People,” a documentary made by a local filmmaker about the laboratory.

The physicist, and chairman of the Tesla Science Center’s Science Advisory Board, examined the litany of Tesla influences in modern-day technology and the late-19th century culture that helped shape his genius.

Dr. Sebastian White, the great-grandson of Nikola Tesla’s architect Stanford White, discuss the importance of inventor Nikola Tesla and his work. Photo by Kevin Redding

“Today it’s very clear that Tesla is trending in much of the science that’s showing up, such as wireless transmission of energy, which is a new field, and the Tesla car, but I think we shouldn’t only remember him for what he did, but also the incredible time in America he became part of,” White told the 130 residents packed into the lecture hall on the top floor at The Ward Melville Heritage Organization’s Educational & Cultural Center. “I think the story of Tesla, who many of my colleagues don’t even know, is an important one as it tells us how we got to where we are.”

White explained how Tesla’s grand vision for wireless transmission of energy, which eventually culminated in a torn-down tower on the Shoreham site in 1917, remains a much-pursued concept.

“There’s a very lively industry happening today, mostly because people keep forgetting to charge their iPhones and they want to find a way to do it without needing cords,” he said.

Through a process called energy harvesting, industry scientists are actively working on ways to charge cellphones while they sit inside pockets by capturing energy just from the environment.

“It’s an enormous field now — new companies are very interested in it and a lot is happening,” White said, pointing out other examples of wireless power transmissions over the years. “In 1964, on the Walter Cronkite TV show, a guy named William C. Brown demonstrated a model of an electric helicopter powered by a microwave. The United States, Canada and Japan have experimented with airplanes powered by radio waves. I would say, probably, if Tesla were around today, he’d be more happy about all the things people are inventing with new techniques rather than always quoting him and saying, ‘Well, Tesla said this.’”

White said Tesla’s emergence as one of the most influential scientific minds of all time coincided with what he referred to as “an incredibly important time” in the late 1800s, a period referred to as the American Renaissance.

Among the prolific figures with whom Tesla interacted were writer Mark Twain, physicist Ernest Rutherford, American businessman John Jacob Astor IV, and, of course, Stanford White. The physicist said a huge year for Tesla was 1892, when he lectured and demonstrated his experiments at the Institution for Electrical Engineers at the Royal Institution in London.

Residents eagerly listen and learn about the life of invetntor Nikola Tesla during a lecture. Photo by Kevin Redding

Speaking on his great-grandfather and Tesla’s friendship, which proved itself through many projects prior to Wardenclyffe, White referred to one particular exchange.

“Stanford White [once] invited Tesla to join him for an outing with William Astor Chanler, an explorer,” he recounted. “Tesla said, ‘I’m busy in the lab.’ White kept pushing him and then wrote to him, ‘I’m so delighted that you decided to tear yourself away from your laboratory. I would sooner have you on board than the Emperor of Germany or the Queen of England.’”

David Madigan, a Tesla Science Center board member, said after the lecture that having White’s perspective on this near-and-dear subject was integral.

“It’s important having Dr. White give the talk, who’s a physicist himself and whose grandfather was Stanford White, who was intimately involved in Tesla’s advancement of his many ideas both as an investor and also as an architect,” Madigan said. “It’s a good triangulation of today’s event, the Tesla exhibit, and Dr. White bringing in the scientific and family history.”

White said he has always felt a strong connection with his great-grandfather, who had a home in Smithtown, since he was  young.

“He was part of our life for sure,” he said. “We all felt very close to him. My son is an architect, my aunt and uncle were architects, my grandfather was an architect, and even continued in the same firm.”

East Setauket resident Michael Lubinsky said he was drawn to the lecture through a lifelong interest in Tesla.

“I always felt that Tesla was not appreciated that much in his time,” Lubinsky said, laughing that much of the lecture went over his head with its scientific terms.

Paul Scala, a software engineer living in Centereach, said he too gravitated to the event to explore more of Tesla’s story.

“I think [Dr. White] did a very nice job,” he said. “It’s very cool seeing that in the tech world they’re still trying to harness wireless energy.”

From left, scientist Lin Yang at the LiX beamline demonstrates how the beam hits the sample to high school teachers James Ripka, Mary Kroll, Fred Feraco, Janet Kaczmarek and Jocelyn Handley-Pendleton. Photo from BNL

By Daniel Dunaief

He helped build it and now a range of researchers are coming.

Lin Yang helped create the LiX beamline at the National Synchrotron Light Source II at Brookhaven National Laboratory, which is attracting researchers eager to study the fine structure and function of everything from proteins to steel.

The lead scientist for the LiX beamline at the NSLS-II at BNL, Yang was the control account manager for the construction of the beamline and was the spokesperson for a team that wrote the original beamline development proposal.

“In our case, the scattering from the sample is sensitive to the underlying structure” of materials, Yang said. “That’s why people want to use scattering to study their samples.”

Like the other beamlines at the NSLS-II, the LiX enables scientists to use sophisticated equipment to search for links between structures and function. Each beamline has a three-letter acronym. In the case of LiX, the “Li” stands for life sciences, while the “X” represents X-ray scattering.

When they designed the beamline, LiX researchers were seeking optics that were capable of producing a beam to conform to the specifications required for different types of measurements. They then designed an experimental station that is suitable for handling biological samples. Specifically, that involved developing an automated sample handler for measurements on protein molecules in solution.

“With atomic resolution structures and functional assays, we do get new insights [about] important ions such as calcium,” which are involved in signaling and physiology, Qun Liu, a principal investigator in the Biology Department at BNL, described in an email. “LiX will be essential to allow us [to see] the transport process in real time and space.” Liu wrote that Yang is an “outstanding X-ray beamline scientist” who is also well known for his pioneering work on membrane diffraction.

The ability to perform measurements using a beam of a few microns is “pretty unique right now,” which also attracted researchers working with steel samples, Yang said. “When we designed the instrument, our focus [was] on the biological structure” but the beamline is “versatile enough” that it has found other uses, Yang said.

Researchers working with steel realized that the same diffraction-based approach to finding underlying structures in living tissue could also shed light on the structures of their samples.

In everyday life, diffraction is visible from the wavelengths of light that form the hologram on a credit card. Scientists working with steel have been applying for time on the LiX beamline, too, creating a competitive environment for researchers working in both fields.

Lynne Ecker, the deputy department chair in the Nuclear Science and Technology Department at Brookhaven National Laboratory, has used the beamline to study the effect of neutrons and ions on steel.

“Ions will only damage steel so far,” Ecker said. The LiX is “perfect” to study the degree of the damage. Ecker said she’s tried this kind of analysis in other places, but the LiX provides better spatial resolution. The LiX scientists are working on improving the degree of automation for sample handling and data processing.

“We are about to install a six-axis robot, which is typically seen in industrial automation, to help realize unattended overnight measurements on protein solution samples,” Yang said. The robot is already at the facility and Yang and his team will be installing the support structure to mount the robot in the experimental station this month. “The more challenging task is to put the software in place so that the beamline can control the robot,” he explained in an email.

The LiX beamline uses lenses made from beryllium, which are transparent to X-rays. For X-rays at the wavelength of about one angstrom, about 93 percent can pass through about a millimeter of beryllium. That compares favorably to aluminum, which allows about 2 percent to pass through at the same thickness.

The LiX beamline can run at 500 frames per second, which produces a wealth of data. In practice, it may take up to a second for the detector to accumulate enough signal from the sample. Still, the beamline can generate enough data that the experimenter may not be able to examine it frame by frame, which makes automated data processing more important.

Scientists have used the beamline to explore the structure of plants. These researchers mainly want to understand how materials like cellulose are organized within different parts of the plant and in different plants.

In bones, researchers can differentiate between organic matter like collagen and inorganic matter. Not only can they determine where they are, but they can also explore their orientation in a sample. Bones are easy samples since collagen and minerals in bone have distinctive scattering and diffraction patterns, Yang said. Researchers “like to look at how biological molecules change their shape as they interact with their functional partners,” Yang said.

A resident of East Setauket, Yang lives with his wife Mian Wang, who is an architect in Farmingdale, and their two daughters. A fan of tennis, Yang plays as often as he can during the summer at the Three Village Tennis Club.

Yang grew up in Yunnan province in the southwest of China. Trained as a physicist, Yang picked up knowledge of molecular biology from his years of working with other scientists. In his work, he gets to combine his talents in engineering, programming and molecular biology.

“We learn new things when we interact with our users/guest researchers since we first need to learn about their problems before we can help solve them,” he described in an email. Yang hopes the research he and the team at the LiX support will result in high-impact publications. “As more researchers know about us and our capabilities, I expect more people will want to perform experiments at our beamline,” he said.