Here are two stories in a series of articles on modern breakthroughs in science, commissioned by Sigma-Aldrich for an enewsletter. Target audience: cliients in academia and scientific research. I tried to speak in the language of the audience, but to employ a style warm and human.
Ginseng: “A Virtual Drugstore”
It has no lighted parking, no drive-through pharmacy and no giant displays of shampoo, but make no mistake: ginseng is a drugstore.
“A virtual drugstore,” clarifies Laura Murphy, PhD, Associate Professor of Physiology at Southern Illinois University Carbondale School of Medicine. Dr. Murphy’s research lab has released a series of groundbreaking findings relating ginseng to the slower growth of cancer cells.
“Ginseng has 30 different ginsenocides, supponent glycosides, polysaccharides, plus fiber and protein,” says Dr. Murphy. “There are 50 different compounds that affect the body, all through unique mechanisms. Working with ginseng is complex and challenging.”
Tan and gnarled, ginseng root has a forked shape, resembling human legs – hence its original Chinese name renshen, or “man root.” Central to Eastern medicine for 4,000 years for its many alleged healing properties, the chemically rich Panex quinquefolius is now under the microscope in labs throughout the world – notably in Dr. Murphy’s own.
But her recent news-making headlines about ginseng started years ago with another herb altogether. “In the 90s, we started doing research on the neuroendocrine effects of cannabinoids,” says Dr. Murphy, editor of a book on the subject. “We were treating animals with marijuana and looking at effects on male copulatory behavior.” (Side note: They have an inhibitory effect.)
“In putting together that cannabinoids paper, we saw that ginseng was anecdotally reported to stimulate libido. We extended the project to include it and I couldn’t believe the results. We did it two more times, same results.”
Newly intrigued by ginseng, Dr. Murphy tightened her focus on the science of the storied root. She learned Asian researchers were doing most of the recent clinical work, and most of that was about ginseng’s effectiveness in treating cancer cells. “It made me wonder if the discussed cancer-affecting qualities could be confirmed in the research lab.”
An endocrinologist, Dr. Murphy began her lab’s project with a supply of human breast cancer cells grown for researchers. When she and her students treated some of these cells with an American ginseng extract, they found this: the higher the doses, the slower the cancer cells grew. With a high enough dose, they could actually stop the cells from growing.
“It was consistent and repetitive,” says Dr. Murphy. “A very clean result.”
With similar findings came increased funding: from the university, the Department of Defense, the National Cancer Institute, the Penny Severns Fund, and the National Center for Complementary Alternative Medicine. The work expanded quickly.
“We wanted to see if we could get the same results in an animal as we got in a Petri dish, and we did. It was the first time an effect in animals has been document,” Dr. Murphy says.
Next up for her lab: studies on the relationship between ginseng and chemotherapy. “We submitted a grant proposal to the NCI that would involve us looking at ginseng’s chemo-preventive effects. Can ginsengs be used concurrent with chemotherapy drugs?”
In all her with with ginseng and cancer, Dr. Murphy cites a challenge within a challenge: molecular pathway management. “As the ginsenocides and polysaccharides act on the cancer cell, a lot of pathways are affected. We use Panorama arrays from Sigma-Aldrich. It provides a system which deals with signal transduction pathways, cell signaling and apotois. The Panorama arrays are quite specific to the pathways we’re looking for.”
As our interview was concluding, we just had to know: does Dr. Murphy herself take ginseng?
“Yes. I make a tea from the raw root,” she says, laughing. “I like the taste of it and believe in its restorative properties. I believe if you’re a healthy person, it’s good for you, and if you’re unhealthy, it will make you better.”
Ah. If only a real drugstore made it that easy.
DNA Breakthrough Over Dinner
“Would you people pleeeeeeeease quit talking about work?”
You can almost hear teenage Emily Nicolet of Davis, California, beseeching her parents across the dinner table.
Her mother, Peggy Farnham, PhD, Associate Director of Genomics at the University of California-Davis, says it’s not an uncommon plea. Dr. Farnham and her husband, Charles M. Nicolet, PhD, are also colleagues: Dr. Nicolet is Manger of the DNA Technologies and Gene Expression Core Facilities at UC-D, and both of Emily’s parents are distinguished for their groundbreaking work at the institution’s Genome Center. Conversations between them can quickly turn molecular.
At one such dinner in 2006, Dr. Farnham was the one complaining. She remembers criticizing the quality of data her lab was getting from the then-existing techniques of amplifying DNA from chromatin immunoprecipitation (ChIP) samples for hybridization to a genomic tiling array (ChIP-chip assays.) One technique – linker-mediated PCR (LMPCR) – was providing too great a signal-to-noise ratio. Another, pooling 50 replicated ChIP samples, was not feasible for multiple genome-wide analyses.
Between bites, her husband offered a suggestion. “Have you considered trying one of the WGA amplification methods they’re using in the lab performing Comparative Genomic Hybridizations? Somebody over there just gave me a pamphlet.” Dr. Nicolet handed it over.
Dr. Farnham saw the potential immediately. “Nobody’s tried this on ChIP-chip assays,” she recalls saying. “Let’s do it!”
It was probably about that time daughter Emily lobbed her mid-meal protest.
But the dinner dialogue proved an important catalyst.
Today the Farnham Laboratory at UC-D, a leader in genome-wide characterization of transcription factor binding sites and chromatin modifications, has abandoned the LMPCR and pooling methods and has completely switched over to the WGA technique for its research, getting what Dr. Farnham calls “really quite amazing” data from increasingly smaller cell samples.
“This level of amplification is critical to having enough material to put on the arrays,” Dr. Farnham says. “Using WGA, we just did a whole genome tiling of 38 arrays, going through every base in the genome, looking for a particular factor, and the data is really beautiful. We’ve done 200 arrays in the last six months and it works just as well for any of the factors we’ve tried.”
Miniaturization – getting more from less – is the trajectory of DNA research, Dr. Farnham says. The possible applications are many, but are particularly relevant to the future of medical science, where the ability to extract more sophisticated information on defects and disease from even the smallest biopsy could lead to more evolved diagnosis and cures.
It was in 2004 that Drs. Farnham and Nicolet and their daughter Emily moved to Davis from Madison, Wisconsin, where Dr. Farnham was professor of oncology at the University of Wisconsin. “We all had great friends and colleagues there, but this was a chance to do something new and different at the Genome Center. It’s exciting to be part of a group thinking on this scale. Everybody has these great, genome-wide assays to talk about. The energy is high and the opportunity for collaborations is fantastic.”
In fact, Dr. Farnham’s most recent scientific paper, the latest of many published findings released this year by the Farnham Laboratory, has a collaborative twist. One of the co-authors of Comparison of Sample Preparation Methods for ChIP-chip Assays is also her frequent dinner companion and husband, Dr. Nicolet. “This is our first paper together,” Dr. Farnham says of the work, which compares three ChIP sample preparation methods differing in background noise and reproducibility of binding site identification.
And to think: this influential Farnham/Nicolet collaboration crystallized with that seemingly innocuous “Have-you-considered?” conversation in their dining room months prior. The incident supports this simple, three-part conclusion:
Some scientific advances occur over years.
Some, over decades.
And some, over dinner.