From Nature, A Past And Future | August 10, 2009 Issue - Vol. 87 Issue 32 | Chemical & Engineering News
Volume 87 Issue 32 | pp. 32-35
Issue Date: August 10, 2009

From Nature, A Past And Future

Golden anniversary for natural products research society brings celebration, introspection
Department: Science & Technology
Keywords: Natural Products, Anniversary
[+]Enlarge
SCOURING THE SEAS
Fenical holds the "mud missile" aboard a boat.
Credit: Courtesy of William Fenical
8732sci1_opencxd1
 
SCOURING THE SEAS
Fenical holds the "mud missile" aboard a boat.
Credit: Courtesy of William Fenical
PAST AND PRESENT
In a 1960s photo, Varro Tyler, ASP's first president, holds a flask containing a fungal culture.
Credit: Courtesy of William Fenical
8732sci1_tylecxd
 
PAST AND PRESENT
In a 1960s photo, Varro Tyler, ASP's first president, holds a flask containing a fungal culture.
Credit: Courtesy of William Fenical
PAST AND PRESENT
Today, Fenical's team has coaxed several strains of deep-sea bacteria to grow in the lab.
Credit: Lloyd Library & Museum
8732sci1_fenicalcxd
 
PAST AND PRESENT
Today, Fenical's team has coaxed several strains of deep-sea bacteria to grow in the lab.
Credit: Lloyd Library & Museum
[+]Enlarge
ASP's 50th anniversary logo.
Credit: Courtesy of Barry O'Keefe and Roy Okuda
1
 
ASP's 50th anniversary logo.
Credit: Courtesy of Barry O'Keefe and Roy Okuda
[+]Enlarge
Attendees at ASP's first gathering, held at the University of Illinois, Chicago, in 1959.
Credit: Courtesy of Geoffrey Cordell
2
 
Attendees at ASP's first gathering, held at the University of Illinois, Chicago, in 1959.
Credit: Courtesy of Geoffrey Cordell
[+]Enlarge
This plaque stands in the Gifford Pinchot National Forest, a short way from where the Pacific yew tree from which the cancer drug Taxol was first isolated stood.
Credit: Courtesy of John Beutler and Nick Oberlies
3
 
This plaque stands in the Gifford Pinchot National Forest, a short way from where the Pacific yew tree from which the cancer drug Taxol was first isolated stood.
Credit: Courtesy of John Beutler and Nick Oberlies
[+]Enlarge
Mansukh C. Wani (left) and Monroe E. Wall of the Research Triangle Institute, in North Carolina, hold a sample of a yew tree, the natural source of Taxol, and a bottle of camptothecin, another natural product that inspired cancer therapies. Wall and Wani were key players in the isolation of both compounds.
Credit: RTI International/J. W. Crawford
4
 
Mansukh C. Wani (left) and Monroe E. Wall of the Research Triangle Institute, in North Carolina, hold a sample of a yew tree, the natural source of Taxol, and a bottle of camptothecin, another natural product that inspired cancer therapies. Wall and Wani were key players in the isolation of both compounds.
Credit: RTI International/J. W. Crawford
[+]Enlarge
Soil from Easter Island yielded the first samples of rapamycin, a natural product that has illuminated many biological pathways and is also given to transplant patients to prevent organ rejection.
Credit: Shutterstock
5
 
Soil from Easter Island yielded the first samples of rapamycin, a natural product that has illuminated many biological pathways and is also given to transplant patients to prevent organ rejection.
Credit: Shutterstock
[+]Enlarge
Scripps Institution of Oceanography researchers Christopher A. Kauffman (left) and Paul Jensen retrieve the "mud snapper," an ocean sediment sampling device.
Credit: Courtesy of William Fenical
6
 
Scripps Institution of Oceanography researchers Christopher A. Kauffman (left) and Paul Jensen retrieve the "mud snapper," an ocean sediment sampling device.
Credit: Courtesy of William Fenical
[+]Enlarge
This sediment-sampling device isn't tethered to a line. Instead, it's outfitted with weights and buoys so it can descend and return on its own.
Credit: Courtesy of William Fenical
7
 
This sediment-sampling device isn't tethered to a line. Instead, it's outfitted with weights and buoys so it can descend and return on its own.
Credit: Courtesy of William Fenical
[+]Enlarge
An adult southern pine beetle. Beetles' chemical relationships with bacteria and fungi are rich sources of natural products.
Credit: M. Cetin Yuceer/Mississippi State U
9
 
An adult southern pine beetle. Beetles' chemical relationships with bacteria and fungi are rich sources of natural products.
Credit: M. Cetin Yuceer/Mississippi State U

On the open ocean, a small fishing boat bobs on the rolling waves. The team of scientists on board has set out from a remote atoll in Fiji, and they are out to find new chemistry in the inky Pacific depths. That takes some specialized tools, including a 6-foot-long metal probe with a precisely calibrated system of weights and small buoys, not to mention a lot of patience. Devised by William Fenical and a team of engineers at Scripps Institution of Oceanography, the probe is designed to plunge to the ocean floor, pick up a sediment sample, and then drop its weights and float back to the surface. Fenical has a variety of such devices, each with its own nickname-the "mud snapper," for example, or the "mud missile."

Fenical's coworker, microbiologist Paul Jensen, is aboard the boat, and he knows it can take nearly half an hour for the probe to descend to the bottom, plus more time to grab some mud and come back up. So the team keeps waiting. But that day, the device never resurfaces. It seemed to have gotten stuck somewhere, perhaps with never-before-seen molecules trapped inside.

Thousands of scientists worldwide embark on similar pursuits to find bioactive chemicals in nature. Those chemicals, called natural products, have the potential to unlock new chemistry and biology and to become new drugs. Promoting these scientists' work is the job of the American Society of Pharmacognosy, a leading professional society for natural products researchers. This year, ASP, as it's known to its nearly 1,200 members, is celebrating its golden anniversary. This summer, the society held its 50th annual meeting in Honolulu, attended by an all-time high of more than 650 researchers, including heads of seven of the world's natural-product-related professional societies.

Although ASP's overall mission of promoting science and fostering community has stayed the same, today's ASP is a different group from the 88 scientists present at the society's founding in 1959 at the University of Illinois, Chicago. A theme throughout ASP's history has been bringing new groups of researchers into the fold and, through their ideas and tools, moving the science forward. Fenical's mud missile missions to the ocean floor, which have led to two molecules now in clinical trials, are only one such innovation. Researchers who spoke with C&EN say it is critical that natural products researchers embrace new technologies and explore new environments to propel the field into its next 50 years.

When ASP was founded, penicillin, a compound from a mold, had already ushered the world into the antibiotics age, and scores of folk medicines had already been extracted from plants. ASP began as a society of academic researchers studying plant natural products. Over the years, researchers looking at marine organisms and terrestrial and marine microbes joined ASP, along with industry researchers and scientists who study nutraceuticals, which are foods and food-derived products believed to provide health benefits, and traditional medicines. Despite the growth, ASP retains a tight-knit-family dynamic, says Ben Shen, who studies natural product biosynthesis at the University of Wisconsin, Madison. "Every time I go to an ASP meeting, I come back pumped. I get excited about research all over again because of all the enthusiasm and support there," he says.

ASP's broadening in both research and member makeup is evident in the pages of the society's flagship journal, the Journal of Natural Products, says JNP Editor-in-Chief A. Douglas Kinghorn of Ohio State University College of Pharmacy.

Since its 59th volume in 1996, JNP has been copublished with the American Chemical Society, in the start of a fruitful relationship between ASP and ACS, Kinghorn says. The journal was once copublished with the Cincinnati-based Lloyd Library & Museum and was called Lloydia. ASP recently reestablished a relationship with the Lloyd Library, which now maintains the society's archives.

Even as ASP celebrates the past, its members are looking toward the future. ASP "is constantly trying to renew the scientific establishment's view of natural product research," says Guy Carter, assistant vice president for chemical and screening sciences at Wyeth Research and immediate past-president of ASP. For the Honolulu meeting, each speaker was asked to speculate about future directions, says meeting coorganizer Roy K. Okuda of San José State University. "We want to be prospective as well as retrospective," he says.

The future was also on the minds of natural products researchers, including several past-presidents of ASP, who gathered last April at the National Institutes of Health, in Bethesda, Md., for a symposium and workshop organized by John M. Schwab, a program director at the National Institute of General Medical Sciences, and chemical biologist Jon Clardy of Harvard Medical School. The group advocated melding natural product science with the latest tools of other fields, such as genomics, genetic engineering, bioinformatics, and synthesis (Nat. Chem. 2009, 1, 261).

Interdisciplinarity is key, Fenical says. Traditional methods of isolation and chemical structure determination alone are no longer enough to be innovative. "If you use the same old tools without innovative methods, you're going to make the same old discoveries," he says.

Fenical's oceangoing probes don't usually get lost. When a new glop of seafloor arrives at the lab, his coworkers optimize culture conditions for the microbes they find within and set about sequencing genomes, analyzing biosynthetic pathways, and more. "Today, we're not just finding out that a natural product has anticancer activity; we may know a new natural product's biological target in a matter of days," he says.

Genomic tools also reveal "hidden" natural products, says Bradley S. Moore of the University of California, San Diego, a collaborator of Fenical's who studies natural product biosynthesis. With the right context, genetic sequence information can help scientists determine whether an organism has dormant biosynthesis pathways and figure out a way to get those pathways working as efficiently as possible. Molecular biology tools can also help researchers reengineer biosynthesis pathways to quickly study natural product analogs, he says.

Molecular biology can also help researchers obtain more of a scarce natural product, Shen adds. "If we understand biosynthetic pathways at a genetic level, we can go beyond what we learn from understanding them at a chemical level alone. We can manipulate these pathways and optimize them," he says.

Other researchers are using ecology to tease out small molecules' natural contexts in their native environments. They are then using that information to determine a natural product's bioactivity while also looking for new systems to study. For example, Julia Kubanek, a chemical ecologist at Georgia Institute of Technology, exposes seaweeds and other marine organisms to predators in order to turn on chemical defense systems, which can also flip on hidden biosynthetic pathways. "We're trying to be smarter about how we discover new chemistry," she says.

Clardy also finds new chemistry by exploring ecology. In collaboration with ecologist Cameron R. Currie at the University of Wisconsin, Madison, he explores the symbiotic relationships between insects, bacteria, and fungi and has uncovered new natural products by delving into the strange bedfellows' chemical communication (C&EN, April 13, page 5). "What's special about natural products is that they have an evolutionary history-that they've been selected to do something in biology," he says. Whether or not their application in the human world relates to their native function, it's undeniable that many natural products have had great success as drugs, he says.

Natural products continue to provide new drug candidates. However, in the decades since ASP's founding, many large pharmaceutical companies have moved away from dedicating significant resources to basic research on natural products.

The shift has to do with a decrease in infectious disease research, historically a fruitful area for natural-product-based drugs, and an increase in high-throughput screening technologies, which aren't readily compatible with natural product purification and identification processes (Science 2009, 325, 161). Today, Wyeth is the only U.S.-based company with a major presence in the natural products area. Some non-U.S.-based firms, such as Novartis, continue to have a strong presence in natural products research. New business models in this area are still emerging and are likely to involve the burgeoning community of biotech companies.

In the short term, this shift is leading to concerns about employment for scientists in the natural products area, Schwab says. But the long-term outlook is bright because new natural product discovery strategies are revealing heretofore unknown families of molecules with the prospect of unprecedented bioactivities, he adds. This might lead to brand-new therapeutic modalities, he says.

Pharmaceuticals aside, natural products can make their mark in many areas, notes Jef K. De Brabander, a synthetic organic chemist at the University of Texas Southwestern Medical Center. For instance, some natural products make great biochemical tools. The natural product leptomycin is too toxic to be useful as a drug, but because it blocks the export of proteins from the cell's nucleus, it's invaluable for researchers who study that process, he explains.

Natural products can also play a role in conservation efforts, says Mark Hay, a chemical ecologist at Georgia Tech. Humans are dependent on natural systems for cleaning air and water supplies, but the impact of rising populations and increased consumption is compromising how these delicate ecosystems work. "The language for understanding and mediating those processes is written in chemistry, and an understanding of how natural products work in the real world gives us insights into how we might fix things," he says.

A critical part of ASP's future, and of the field's future, lies in training young scientists worldwide in cutting-edge technology and giving them the support they need to succeed, Fenical says. "The strength of any society is in its young people," Moore agrees.

ASP isn't alone in embracing this mission. Programs including the NIH-led and interagency-funded International Cooperative Biodiversity Groups Program, which partners U.S. natural product researchers with scientists abroad, are as well. The program has a strong training component-it helps bring scientific infrastructure and the latest techniques to the resource-rich locales where natural products come from.

For his part, Fenical tries to imbue his young colleagues with enthusiasm for natural products research. "I tell my students, 'You're the only person in the world who's seen this compound, and you can be proud that you've made this discovery,' " he says. "In a way, it might be how the early explorers felt when they found new land that wasn't even on the charts. Natural products can give you that feeling."

Some time after the fruitless Fiji trip, one of the University of the South Pacific's Fiji campuses fielded a phone call from a local fisherman. He offered to return an unusual catch from a recent excursion back to the campus. Someone had printed a contact phone number on it, likely with a permanent marker, Jensen recalls. He was happy to have the probe back, although this time, it didn't snag a useful sample. Maybe next time.

Natural Products' Ongoing Story

[+]Enlarge
Cover for the Journal of Natural Products in 1996, the first year of copublication by ACS and ASP. The image shows the tree Camptotheca acuminata and the structure of the natural product camptothecin, which is isolated from the tree.
Credit: Courtesy of A. Douglas Kinghorn
8
 
Cover for the Journal of Natural Products in 1996, the first year of copublication by ACS and ASP. The image shows the tree Camptotheca acuminata and the structure of the natural product camptothecin, which is isolated from the tree.
Credit: Courtesy of A. Douglas Kinghorn

The American Society of Pharmacognosy's history spans 50 years, and it's been a stretch of time worth celebrating. In that time, natural products researchers discovered new drugs, new biological pathways, and more. This small selection of photos chronicles natural product research, past and present.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

Leave A Comment

*Required to comment