The urgent need to evaluate nature's repository of chemicals in plants, microbes, and marine organisms for their potential value in health care will be a major theme of a five-day scientific conference in New York that is expected to draw some 1,200 natural products researchers from around the world.
Organized and co-hosted by The New York Botanical Garden, the City University of New York, and other New York-area research institutions, the International Congress on Natural Products Research (ICNPR) will be held from July 28 to August 1 at the Grand Hyatt Hotel in New York City. The theme of the conference is "Global Change, Natural Products and Human Health."
Several scientists from the Botanical Garden will take part in ICNPR events at the Grand Hyatt, and on July 26, the Garden's Midtown Education Center, located on West 44th Street, will host a special presentation about the development of Taxol, the widely used chemotherapy drug first isolated from the bark of the Pacific yew tree.
Focusing on the study of medicines derived from natural sources, the ICNPR will feature sessions devoted to the traditional areas of natural products research—marine, microbial, and plant sources of medicinal chemicals—as well as the latest developments in analytical technologies, genomics, and many other areas of natural products work. Organizers expect it to be the largest U.S. gathering to date of natural products researchers.
From simple aspirin to sophisticated cancer-fighting drugs such as Taxol, the natural world has served as an important source of medically active compounds. That resource is under increasing strain from such global environmental problems as climate change and habitat destruction, yet only a fraction of the many thousands of plant, microbial, and marine species have been studied to determine if the chemicals they produce could be the basis of new pharmaceuticals to treat or prevent human illness.
This critical situation will be the subject of a July 29 symposium that will provide an overview of the current state of natural products research. Among the speakers will be James S. Miller, Ph.D., the Garden's Dean and Vice President for Science, who will review past efforts to find medically useful chemicals in plants, which proved disappointing, and recent technological developments that could improve the success rate of such efforts.
In a paper published last year in the journal Economic Botany, Dr. Miller calculated that there are probably at least 500 medically useful chemicals in plant species whose chemical constituents have not yet been evaluated for their potential to cure or prevent disease.
"Whether it's plants, microbes, or marine organisms, we've barely scratched the surface when it comes to screening programs for new pharmaceuticals," Dr. Miller said. "Why have we stopped looking?"
In a July 30 symposium on botanical supplements, the Garden's Damon Little, Ph.D., will review the use of DNA barcoding techniques to verify the ingredients in herbal dietary supplements. Black cohosh, for example, is commonly used for menopausal symptoms, but accidental misidentification or deliberate adulteration can result in impure supplements containing other related, but potentially harmful, species.
Despite grinding and drying during the manufacturing process, however, short portions of plant DNA can usually be sequenced and the results compared to a publicly available database of DNA barcode sequences. In a study of 36 samples that were marketed as black cohosh, Dr. Little and colleagues found that 25 percent contained three Asian plant species related to black cohosh. Dr. Little will also talk about his recent barcoding work on garlic and saw palmetto supplements.
On July 31, the Garden's Michael Balick, Ph.D.—co-organizer of a symposium on research and development based on ethnobotany, the study of how people use plants for food, medicine, fiber, and other necessities of life—will discuss how scientists and clinicians are learning about traditional uses of plants and evaluating their efficacy and potential for use in improving global primary health care.
Dr. Balick, who has spent more than 30 years studying the many ways in which indigenous people use plants in their everyday lives, will describe programs on remote tropical Pacific Islands in which a combination of traditional medicines and conventional Western therapies could result in improved public health and greater self-sufficiency.
On July 26, in an associated event prior to the conference, Susan Band Horwitz, Ph.D., who played a critical role in the development of Taxol, will recount the arduous, 20-year process that started with the discovery of a medically active compound in the bark of the Pacific yew (Taxus brevifolia) and eventually resulted in a drug that has been used to treat more than one million patients suffering from ovarian cancer, breast cancer and certain types of lung cancer. Dr. Horwitz, the Falkenstein Professor of Cancer Research at the Albert Einstein College of Medicine in the Bronx, will be joined by Mark O'Neil-Johnson, Ph.D., of Sequoia Sciences, Inc., a St. Louis natural products research company, to discuss the complexities of bringing a new drug based on a natural product to the market. They will speak at 7 p.m. at the Garden's Midtown Education Center, 20 W. 44th Street. (Admission is $13 for Garden Members, $15 for Non-Members.)
Intended to promote the interchange of the most current research among active investigators working in all aspects of natural products research, the ICNPR is a joint meeting of the American Society of Pharmacognosy and four European research societies: the Society for Medicinal Plant and Natural Product Research, the French-Speaking Society of Pharmacognosy, the Phytochemical Society of Europe, and the Italian Society for Phytochemistry.
Garden scientists have collaborated closely with researchers from other New York institutions, especially Lehman College of the City University of New York, in organizing the conference. Edward Kennelly, Ph.D., a Lehman biology professor, is the chair of the local organizing committee.
Underwater landslides can be far larger than any landslide seen on land. For example, the Storegga Slide that occurred 8,200 years ago offshore Norway is larger than Scotland. It contained over 3,000 cubic kilometres of material (300 times the amount of sediment carried each year by all of the world's rivers combined) and ran out for 800 kilometres into the deep ocean. This truly prodigious mega-landslide generated a tsunami that ran up to heights of three to six metres along northern parts of the UK coastline. A modern day event of a similar scale to the Storegga Slide would be likely to lead to significant loss of life and devastating damage to key infrastructure, and there are few other natural events that would have such a disastrous impact on the UK.
A team of scientists is embarking on a four–year investigation to assess the hazard that landslide-tsunamis in the Arctic could pose to the UK over the next 100 to 200 years. This team is led by the National Oceanography Centre and involves seven other UK institutions, together with international project partners. The other UK institutions include NERC's British Geological Survey, Imperial College London, and the Universities of Aberdeen, Cambridge, Dundee, Manchester, Southampton, and Ulster. The team will work alongside representatives from government bodies and the reinsurance industry, including the Willis Research Network. They will look at the likely impact on human society and infrastructure, the degree to which existing sea defences are effective, and how the threat of tsunamis can be incorporated into the UK's multi-hazard flood risk management.
Worldwide, most tsunamis - such as the 2004 Indian Ocean tsunami, and 2011 tsunami offshore Japan - are triggered by large earthquakes near plate boundaries. Tsunamis triggered by mega-landslides are far less frequent than those caused by earthquakes. However, landslide-tsunamis may represent a greater threat to the UK, which is located away from the plate boundaries that create large earthquakes.
In the past, submarine mega-landslides near to the UK have been very rare, and considerable uncertainty still surrounds the frequency of mega-landslides. The Storegga Slide was initially thought to be several events, some occurring more than 30,000 years ago. More detailed research was necessary to show it was a single and more recent event. The available sea floor mapping suggests that at least six mega-slides have occurred beneath the Norwegian and Greenland Seas during the last 20,000 years. It is not yet clear whether all of these mega-landslides generated large tsunamis, or whether they produced two recent tsunami deposits found in the Shetland Islands.
Importantly, it has been proposed that mega-landslides will become more frequent due to future ocean warming that causes melting of gas hydrate (crystalline solids resembling ice that contain methane) which weakens sea floor sediment. It has also been proposed that melting ice sheets will cause an increase in the frequency of large earthquakes, as the Earth's crust adjusts to the removal of the ice sheet's weight. Such earthquakes could potentially generate more frequent mega-slides and tsunamis. The project will test these hypotheses rigorously, to determine whether there is credible evidence that the frequency of mega-landslides and tsunamis will increase significantly in the near future.
A key point for hazard assessment is that submarine mega-landslides are much more poorly understood than almost all other types of natural hazard, such as river floods or storm surges. Submarine mega-landslides occur on sea floor slopes of just one or two degrees -similar to the gradient of a Premiership soccer pitch. Hillsides with such remarkably low gradients are almost always stable on land, and it is not yet clear why submarine landslides occur on such low gradients. A second major uncertainty is how submarine mega-landslides are set in motion - do they occur in one or multiple stages?
Scientists have so far been unable to monitor a mega-landslide in action. This is important because the way in which the landslide moves determines the size of the tsunami it produces. Landslides that occur in a series of stages produce much smaller tsunamis. The project will analyse sediment flow deposits generated by mega-landslides to help understand how the landslides moved.
The specific aims of the research project are four-fold: to clarify the frequency and timing of major Arctic submarine slides; to better understand trigger factors and assess whether the frequency of the slides is likely to increase as climate changes and oceans warm, and to assess the magnitude necessary for landslide-tsunamis to flood parts of the UK coast.
The fourth strand of the consortium's research will be an attempt to quantify the likely cost to the UK of different types of inundation triggered by different types of landslide occurring in different locations. The science team will work closely with stakeholders, including government bodies – notably the Scottish Government and Defra (the Department for Environment, Food and Rural Affairs) - the Environment Agency and the reinsurance industry and will try to quantify the risk to key UK infrastructure (including nuclear power stations) the likely costs of tsunami inundation, as well as measures that can be taken to offset its impact, such as improved flood defences.
The project will use a range of techniques, including shipboard expeditions that will map the Arctic seafloor and extract sediment cores from the seabed, fieldwork on land to identify and date coastal tsunami deposits, slope stability modelling, laboratory experiments showing how hydrate dissociation affects sediment strength, and modelling of future trends in seismicity. It will also include modelling of landslide motion, tsunami wave generation and propagation, and how tsunami waves would interact with existing UK coastal defence structures. A sensitivity analysis will aim to capture uncertainties, and the key factors that determine societal cost.
Project leader, Dr Peter Talling of the National Oceanography Centre, said: "This is the first extensive study to assess the probability and likely impact of a landslide-tsunami on the United Kingdom. It is timely as it has been proposed that climate change may be a factor that increases tsunami frequency significantly. This hypothesis is in need of careful testing. We have assembled a broad range of expertise to look at this issue and to produce findings which will have a significant influence on future decision-making on flood protection and resilience. We hope that the project will produce a step-change in scientific understanding about some of the most remarkable and largest natural events that occur on our planet."
Dr Phil Newton, the Natural Environment Research Council's Director of Science said: "NERC plays a leading role in the UK's research into natural hazards, such as tsunamis which, although extremely rare, would have a serious impact on our communities and economy. Working with government and a range of partners and stakeholders this project will add an important dimension to the assessment of flood risk by building tsunamis into the framework, while leaving a legacy of expertise in this area."
When Chris Melrose began his career at the Northeast Fisheries Science Center's Narragansett Laboratory, little did he realize where his work studying primary productivity and dissolved oxygen would lead. Now a member of the Center's Oceanography Branch, Melrose heads a long-term Ship of Opportunity Program (SOOP) that uses volunteer commercial cargo vessels as sampling platforms during their routine operations. Using an instrument, the Continuous Plankton Recorder (CPR), towed behind the ship, the SOOP program continues plankton surveys begun decades ago, but with a new global perspective and purpose.
In September 2011, Melrose represented NOAA and NEFSC at a meeting of the nine regional CPR surveys around the world to discuss the formation of a global program to routinely monitor changes in plankton patterns as an indication of the health of marine ecosystems.
The Global Alliance of Continuous Plankton Recorder Surveys, or GACS, was formed at that meeting in Plymouth, England: its primary goal to understand changes in plankton biodiversity at ocean basin scales through a global alliance of CPR surveys, like those done by NOAA and NEFSC.
"The idea is to work together to standardize our methods and contribute our data to a central repository or database that will make the data more accessible to potential users and more useful to the global scientific community," said Melrose. "Some of the participants already work together and share data, but having the global perspective will enable us to assess how changes and events at the local and regional level fit into the big picture, which is critical to understanding the impacts of climate change, ocean acidification and other phenomena that occur on a global scale."
GACS was formed during Plankton 2011, the celebration marking the 80th anniversary of the start of the North Sea CPR tows by Sir Alister Hardy, namesake of the instrument and the organization devoted to his vision, the Sir Alister Hardy Foundation for Ocean Science (SAHFOS). The GACS initiative was spearheaded by Peter Burkhill, the director of SAHFOS prior to his retirement in October of 2011. GACS is now chaired by Graham Hosie of the Australian Antarctic Division and includes member surveys from every continent except Antarctica.
Hardy, a fisheries biologist, designed the prototype CPR for use on a two-year expedition to Antarctica between 1925 and 1927 on the British research vessel Discovery. When he returned from that expedition, Hardy developed a smaller version for use on commercial ships. SAHFOS has been collecting data from the North Atlantic and North Sea since 1931, when the first tow of Hardy's mechanical Continuous Plankton Recorder (CPR) was made on a merchant vessel, the SS Albatross, traveling between Hull, England and Bremen, Germany. Since then the CPR survey has analyzed 250,000 samples, counted 500 taxa and towed some 5 million miles, making it "the longest, most geographically extensive biological survey in the world", according to GACS's first newsletter, issued in January 2012. At the end of April 2012 the CPR survey passed six million nautical miles towed.
Local and regional monitoring and observational programs established in the past have not had a global perspective on plankton biodiversity in response to global events like climate change and ocean acidification. GACS will provide that perspective using CPR data, which will also allow researchers to assess changes and events at a local or regional level in a world-wide context. Having so much data from around the world in a standardized format in one place, available to those who collect it as well as to potential users, will be invaluable, especially as the CPR surveys are developed in other parts of the world.
The second GACS Workshop will be held September 19-20, 2012 in Paris at the Intergovernmental Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization (UNESCO).
The Israel Center for Mediterranean Sea Research will investigate and research oil and gas extraction, desalination, infrastructure, and more. President of the University of Haifa, professor Aaron Ben-Ze'ev: "The sea is a strategic asset for Israel and by developing it the country will achieve economic independence." Photo courtesy of the University of Haifa.
Israel's Planning and Budgeting Committee (PBC; a sub-committee of the Council for Higher Education) adopted the recommendation of a special Israel Academy of Sciences committee and announced that a consortium headed by the University of Haifa has won a tender to establish Israel's national Center for Mediterranean Sea Research. The consortium consists of eight research institutions (six of which are universities): The University of Haifa; the Technion; the Hebrew University of Jerusalem; Bar-Ilan University; Ben-Gurion University of the Negev; the Weizmann Institute of Science; the Geological Survey of Israel; and the Israel Oceanographic and Limnological Research center. The cost of establishing the new Center for Mediterranean Sea Research is estimated at over 60 million shekels, or $15 million, for its first three years of activity, and it will focus on areas such as gas extraction, marine infrastructure, desalination, and more.
Heading the center will be Prof. Zvi Ben-Avraham, Founding Director of the University of Haifa's Leon H. Charney School of Marine Sciences, which was founded at the University five years ago, recognizing that Israel's primary field of research over the coming years will be focused on the sea. Recently discovered gas and other resources in the Mediterranean Sea off the coast of Haifa and Hadera reinforced the fact that Israel's academia requires skillfully trained researchers and scientists in the field to understand and guide the implications of such developments.
The initiative for a national Center for Mediterranean Sea Research was conceived in response to a special report presented by the Israel Academy of Sciences that revealed a worrying academic standard in terms of marine research in Israel. The PBC took action and drew up the tender that the University of Haifa-led consortium has now won.
President of the University of Haifa, Prof. Aaron Ben-Ze'ev: "I am proud of the PBC's choice. We already recognized the Mediterranean Sea's potential years earlier and invested extensive resources to establish our Leon H. Charney School of Marine Sciences. The new national Center for Mediterranean Sea Research will introduce the University of Haifa and Israel as a key partner and contributor to the international marine research arena. The Mediterranean Sea," Prof. Ben-Ze'ev added, "is a strategic asset for Israel and by developing it the country will achieve economic independence. Forming Israel's coastline to the west, the Mediterranean possesses magnificent resources, a developed infrastructure, economic promise, and international trade potential. The resources hidden beneath the surface can significantly strengthen Israel's energy economy, can contribute to closing social gaps, and can ultimately increase Israel's political strength at home and abroad."
This is a still of the artificial jellyfish. Credit: Harvard University and Caltech
The finding serves as a proof of concept for reverse engineering a variety of muscular organs and simple life forms. It also suggests a broader definition of what counts as synthetic life in an emerging field that has primarily focused on replicating life's building blocks.
The researchers' method for building the tissue-engineered jellyfish, dubbed "Medusoid," was published in a Nature Biotechnology paper on July 22.
An expert in cell- and tissue-powered actuators, coauthor Kevin Kit Parker has previously demonstrated bioengineered constructs that can grip, pump, and even walk. The inspiration to raise the bar and mimic a jellyfish came out of his own frustration with the state of the cardiac field.
Similar to the way a human heart moves blood throughout the body, jellyfish propel themselves through the water by pumping. In figuring out how to take apart and then rebuild the primary motor function of a jellyfish, the aim was to gain new insights into how such pumps really worked.
"It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps," says Parker, Tarr Family Professor of Bioengineering and Applied Physics at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard. "I started looking at marine organisms that pump to survive. Then I saw a jellyfish at the New England Aquarium and I immediately noted both similarities and differences between how the jellyfish and the human heart pump."
To build the Medusoid, Parker collaborated with Janna Nawroth, a doctoral student in biology at Caltech and lead author of the study, who performed the work as a visiting researcher in Parker's lab. They also worked with Nawroth's adviser, John Dabiri, a professor of aeronautics and bioengineering at Caltech, who is an expert in biological propulsion.
"A big goal of our study was to advance tissue engineering," says Nawroth. "In many ways, it is still a very qualitative art, with people trying to copy a tissue or organ just based on what they think is important or what they see as the major components—without necessarily understanding if those components are relevant to the desired function or without analyzing first how different materials could be used."
It turned out that jellyfish, believed to be the oldest multi-organ animals in the world, were an ideal subject, as they use muscles to pump their way through water, and their basic morphology is similar to that of a beating human heart.
To reverse engineer a medusa jellyfish, the investigators used analysis tools borrowed from the fields of law enforcement biometrics and crystallography to make maps of the alignment of subcellular protein networks within all of the muscle cells within the animal. They then conducted studies to understand the electrophysiological triggering of jellyfish propulsion and the biomechanics of the propulsive stroke itself.
Based on such understanding, it turned out that a sheet of cultured rat heart muscle tissue that would contract when electrically stimulated in a liquid environment was the perfect raw material to create an ersatz jellyfish. The team then incorporated a silicone polymer that fashions the body of the artificial creature into a thin membrane that resembles a small jellyfish, with eight arm-like appendages.
Using the same analysis tools, the investigators were able to quantitatively match the subcellular, cellular, and supracellular architecture of the jellyfish musculature with the rat heart muscle cells.
The artificial construct was placed in container of ocean-like salt water and shocked into swimming with synchronized muscle contractions that mimic those of real jellyfish. (In fact, the muscle cells started to contract a bit on their own even before the electrical current was applied.)
"I was surprised that with relatively few components—a silicone base and cells that we arranged—we were able to reproduce some pretty complex swimming and feeding behaviors that you see in biological jellyfish," says Dabiri.
Their design strategy, they say, will be broadly applicable to the reverse engineering of muscular organs in humans.
"As engineers, we are very comfortable with building things out of steel, copper, concrete," says Parker. "I think of cells as another kind of building substrate, but we need rigorous quantitative design specs to move tissue engineering to a reproducible type of engineering. The jellyfish provides a design algorithm for reverse engineering an organ's function and developing quantitative design and performance specifications. We can complete the full exercise of the engineer's design process: design, build, and test."
In addition to advancing the field of tissue engineering, Parker adds that he took on the challenge of building a creature to challenge the traditional view of synthetic biology which is "focused on genetic manipulations of cells." Instead of building just a cell, he sought to "build a beast."
Looking forward, the researchers aim to further evolve the artificial jellyfish, allowing it to turn and move in a particular direction, and even incorporating a simple "brain" so it can respond to its environment and replicate more advanced behaviors like heading toward a light source and seeking energy or food.
Along with Parker, Nawroth, and Dabiri, contributors to the study included Hyungsuk Lee, Adam W. Feinberg, Crystal M. Ripplinger, Megan L. McCain, and Anna Grosberg, all at Harvard.
Funding for the study included grants from the Wyss Institute for Biologically Inspired Engineering at Harvard, the National Science Foundation (NSF), the National Institutes of Health, the Office of Naval Research, and the NSF Program in Fluid Dynamics.