How one family’s sustained philanthropy shaped groundbreaking
discoveries in chemical biology and cancer medicine
It is a typical weekly meeting at the Laboratory for Chemical Biology (LCB) at Stony Brook University and the topics under discussion have implications far beyond the campus. As the meeting begins, several team members, including past and present Zickler Scholars, share their new findings.
They examine how chemicals attach to the DNA double helix, causing faulty cell division. They share data from newly developed, noninvasive diagnostic methods called “liquid biopsies.” And they discuss a new, ambitious adductomics project linking DNA-damaging chemicals to the cancers they cause, an initiative so important that it received the highest priority score from a National Institute of Health grant review.
These extraordinary discoveries would never have happened without the dedicated support from the Zickler family, says Dr. Arthur Grollman, the Evelyn G. Glick Professor of Experimental Medicine and founder of the LCB. Over the past 35 years, the LCB researchers have made major breakthroughs in cancer biology and medicine—from identifying one of the world’s most potent carcinogens to uncovering chemical mechanisms of free radicals that damage DNA.
From building the LCB’s early infrastructure to enabling the Zickler Fellows’ current work, the family’s continuous patronage, over the last 35 years, made these groundbreaking advances possible. “Without their help, we wouldn’t have achieved what we did,” says Dr. Grollman.
Philanthropy Helped Burnish Pharmacology Department Reputation
In 1975, Arthur Grollman left his professorial position at the Albert Einstein College of Medicine, having been recruited to Stony Brook University as founding chair of the Department of Pharmacological Sciences. Trained as a chemist at the University of California, Berkeley, and as a physician at the Johns Hopkins University School of Medicine, he leveraged both disciplines to study the chemical biology of human health and disease. At the time, DNA was emerging as a major focus of NIH-funded scientific research. Grollman planned to investigate how various chemicals interacted with DNA and, in some cases, damage it. Simultaneously, he aimed to elevate Stony Brook University in the eyes of the scientific community. “We were a young university and I led a newly formed department – my hope was to put Stony Brook on the map by developing its reputation for groundbreaking chemical biology research,” he recalls.
Studying complex biological processes requires experience and sophisticated equipment. So, Grollman reached out to recruit some of the top researchers of the time—biochemist Seymour Cohen, toxicologist Adrian Albert from Australia, chemist Francis Johnson from Dow Chemical Company, and molecular biologist Edward Reich who earned his international reputation at Rockefeller University.
The laboratory setup, however, hit a snag. Stony Brook had ample state funding to support faculty salaries, but not enough to procure specialized instruments. However, the state was willing to provide matching funds if the school found donors willing to help. So Grollman reached out to Leo Zickler, a philanthropist who was interested in advancing medical research.
Zickler trusted Grollman’s choices in faculty recruitment. “Arthur served on review panels at NIH and received numerous rounds of federal funding, so I placed my faith in him,” Zickler says. Providing matching gifts fit the family’s philanthropic approach because it gave the project a start while encouraging institutions to look for other donors. “We want the institution to have some skin in the game, so it’s common for us to provide matching support,” Zickler notes. “My wife and I put up money designated as a matching grant for the lab’s equipment.” The funds were used to purchase highly specialized equipment that turned the laboratory into a state-of-the-art facility.
At the time, scientists were inserting genes into DNA and studying the consequences. It was a slow process and Zickler wanted to help speed up this important research. Zickler recalls: “We provided seed funding for two key pieces of equipment. One was a state-the-art microscope, and the other was a device that allowed researchers to target insertion of a gene into DNA, which increased the speed from approximately one procedure a day to one every hour.”
As a complement to the laboratory setup, the family at one point also endowed a visiting professorship that had allowed Dr. Grollman to invite distinguished scientists from around the world to visit Stony Brook, deliver lectures on cutting-edge research and share their scientific expertise. In addition to the intellectual exchange, the program drew attention to Stony Brook, helping to grow the reputation of Stony Brook’s Department of Pharmacological Sciences. Many of the visiting professors were Nobel Laureates, which helped to spread the word about the research ambitions of the University while elevating the Department’s visibility. As a result, Stony Brook gained recognition from scholars around the world, while researchers in Pharmacological Sciences were advancing their projects. “At the time, we were ranked in the top five pharmacology departments in the country, together with Harvard, Vanderbilt and Yale.”
Solving the “Poisoned Earth” Mystery
In the years that followed, the national scientific community faced new challenges. As government support for basic science waned, the NIH cut funding for fundamental science, favoring translational research. Using the “bench to bedside,” strategy, the NIH prioritized peer-reviewed research on medical issues that affected American taxpayers over fundamental scientific inquiries—despite the fact that translational medicine relies on basic scientific research. As a result, without governmental support, fundamental science became increasingly dependent on private philanthropy.
During this period, Grollman’s research branched out to encompass the actions of cancer-causing chemicals. “Many cancers are caused by chemicals,” he says, explaining why he studied DNA-damaging compounds and free radicals. “We could make significant headway in diagnosing and treating cancer if we could better understand these interactions from a molecular perspective.” With this approach, Dr. Grollman and his team set out to solve a long-standing medical mystery—what was causing a chronic kidney disease that selectively targeted residents of rural areas of the Balkan Peninsula.
Named Balkan Endemic Nephropathy (BEN) because of the affected region, the disease was associated with progressive kidney failure and, in its later stages, urothelial cancer. Mysteriously, it was endemic in hotspots along the Danube River while sparing other areas of the former Yugoslavia. For years, international agencies, medical researchers and toxicologists conducted tests of water, soil and air, but the causative culprit of BEN remained elusive, claiming hundreds of lives every year.
As research at Stony Brook got underway, Dr. Grollman read a New England Journal of Medicine report about a group of Belgian women who developed chronic kidney disease and urothelial cancers similar to BEN after visiting a fitness spa that provided to its clients an herbal mixture as part of its weight loss regimen. A link had been made between their illness and aristolochic acid, a toxic component of one of the herbs that attaches to human DNA. “When a chemical reacts with DNA it becomes a DNA adduct,” Grollman explains. Cells remove such adducts, but not before some of them cause mutations that lead to cancer. The Belgian women’s complex of symptoms suggested to Dr. Grollman that Balkan endemic nephropathy might be caused by aristolochic acid; but research would be needed to prove his hypothesis.
In 2003, Grollman visited the Balkans to investigate whether the natural source of aristolochic acid – a plant named Aristolochia clematitis, or European birthwort - was being used there for medicinal purposes. When herbal consumption was ruled out as a cause of BEN, he postulated that dietary exposure might be the culprit. Based on field research in Croatia, he discovered that Aristolochia often was found as a common weed growing in fields of wheat. As a result, when the villagers harvested the grain, Aristolochia seeds mixed with wheat grain, finding their way into local bread, which constituted half of the local diet. Thus, residents of the region unwittingly were poisoning themselves. Moreover, Dr. Grollman recognized that a threat to global public health loomed; namely that Aristolochia herbals also were a component of Traditional Chinese Medicine (TCM). If his theory regarding aristolochic acid toxicity in the Balkans proved correct, tens of millions of individuals throughout Asia could be at risk for kidney disease and cancer due to secondary exposure to the Aristolochia present in many herbal medicine formulations.
Dr. Grollman’s research team undertook the seminal studies that unequivocally established the link between aristolochic acid and mutations in DNA that had resulted in cancers of the kidneys, bladder, liver, and upper urinary tract. That discovery has led to life-saving changes in the use of herbal remedies containing Aristolochia.
Leo Zickler salutes this remarkable achievement. “I’ve been particularly impressed by the work Arthur has done on this kidney disease,” he says, noting it as an example of how basic and translational research are inseparable. “With modern day science it’s sometimes hard to pinpoint the impact of one’s giving,” Zickler points out. “That’s why philanthropy should support both types of scientific inquiry, fundamental and translational.” The Zickler family’s support provided the infrastructure needed for basic research, creating a resource-rich environment for Dr. Grollman and his team to explore the molecular interactions underlying cancer and kidney disease.
Importantly, the lab’s research on aristolochic acid toxicity proved to be a significant contribution to adductomics—the developing science of the DNA adducts that cells acquire over their lifetime. Adductomics research now receives high priority for funding from the NIH. With tremendous benefits for the American public, the novel findings of Dr. Grollman’s research team also were made possible by philanthropic support.
Sustained Philanthropic Support Bears Fruit over Time
The Zicklers remain involved in the LCB’s work. On several occasions, they have visited the campus and discussed recent developments with members of the lab. In the past, they also periodically attended lectures that were being held by Zickler Visiting Professors. These points of engagement have helped to keep the family apprised of the impact of their philanthropy and, indeed, have inspired them to do more.
In 2010, Leo Zickler made a gift to support the creation of the Zickler Translational Scholars in Biomedical Research. This program invests in early-career researchers whose focus is on chemical biology. The Zicklers have, to date, supported four Zickler Scholars — Kate Dickman, Thomas Rosenquist, Viktoriya Sidorenko and Masaaki Moriya — with plans to continue their support in the future.
Associate Professor Dickman, who received the first Zickler Scholar award, is working to develop UroSEEK, a novel, non-invasive method for detection of urothelial cancer—a project that evolved from Aristolochia research. “Upper urothelial cancers are unusual malignancies of the urinary tract,” Dickman says. “And unlike bladder cancers, they are often far advanced by the time symptoms appear.” Most cancers are found when they form a mass and typically require an invasive biopsy. Developed in collaboration with scientists at Johns Hopkins, UroSEEK detects cancer cell genes in the urine, which is why it is called a “liquid biopsy.”
Associate Professor Rosenquist, the second Zickler Scholar, initiated the adductomics project, focusing on adducts that generate mutational signatures. “A single cell acquires millions of adducts over its lifetime,” he explains. “It will repair most of them, but not all; some will remain. So, we sequence tumor DNA and characterize the relevant DNA adduct, so as to identify which chemicals cause mutations.”
Assistant Professor Sidorenko, the current Zickler Scholar, focuses on aristolochic acid’s interactions within the liver and kidneys. “I study molecular mechanisms underlying its toxicity,” she explains. “For example, only five to ten percent of people who are exposed will develop cancer, and we want to know which genes and enzymes are involved. The ultimate goal is to predict which individuals may develop adverse effects. We also wish to understand how aristolochic acid affects the kidney. We hypothesize it acts by interacting with proteins in the kidney, rather than with DNA.”
These research projects are complex and will take time to bear fruit. Understanding this, the Zickler family believes in sustained support. “Scientific knowledge doesn’t necessarily advance in a linear form—it hop-scotches around,” Zickler observes. Failures do not necessarily terminate scientific pursuits, but rather form new grounds for research, he adds. “It’s not uncommon for someone to make a breakthrough in 2021 based on a research ‘failure’ that took place 20 years earlier.”
That is where sustained support from patrons becomes especially important. It carries the research through the inevitable periodic setbacks—to the point when academics and their benefactors can reap the fruits of their dedication. While donors observe the impact of one-time gifts, a continuous relationship with an institution is more likely to produce major breakthroughs. It’s worth bringing this not-so-apparent fact to the attention of prospective philanthropists, Zickler thinks. “A little education in terms of why long-term philanthropic relationships are so important can go a long way.”
Philanthropy is a Critical Element
As government funding continues its downward trend, scientists based in the United States find it increasingly difficult to secure federal grants to support their research. In this tightened financial climate, sustained philanthropy plays a crucial role in scientific advancement. “Philanthropy is a critical element,” Zickler says, noting that his family favors matching gifts because it encourages philanthropy outreach. “The idea is to encourage the institution’s development office to focus on finding sources to augment existing support.”
To maximize the impact of their philanthropy, the Zicklers embrace several criteria. They choose their beneficiaries carefully, looking for talent and promising ideas, and “the whole package,” he says. “We bet on people who have a novel idea,” he explains. “But there has to be more than just a single brilliant scientist. There has to be a team with the infrastructure that allows them to develop that idea.”
Track record also is important, and funding the four Zickler Scholars was a logical progression of the family’s continued support. Seeing the remarkable scientific breakthroughs in the LCB, Zickler trusted Grollman’s selection of scholars and had no doubt in their abilities. “Our money has been well used here,” he says. At the same time, Zickler recognizes that not all ideas “take.” “Some people refer to [basic science funding] as venture capital philanthropy because you realize that not everything you support is going to work,” he explains. That’s why strategic, thoughtful funding that helps start several initiatives over time is more likely to eventually pay off. In this way, some of the many programs the Zicklers invested in are bearing fruit over time, with implications for the health of millions around the world.
Medieval Jewish philosopher and physician Moses Maimonides developed a rubric in which he described eight levels of philanthropic giving, starting with those who give reluctantly out of obligation and progressing to the “highest order,” those whose gifts enable the beneficiaries to become self-reliant. “The Zickler family’s philanthropy would be classified at that highest level,” Grollman notes, citing the initiatives facilitated by their giving—from the lab’s launch to the endowed lectures by Nobel Laureates, to the scholars whose research he helped advance.
The Zickler family’s generous and lasting support has become a model for others to follow.