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A MICROSCOPIC MATTER OF PERSPECTIVE: Researchers at the University of Aberdeen Marine Biodiscovery Center encountered a chemical compound they were unable identify until they teamed with IBM and the company's modified atomic force microscope (AFM).
Image: IMAGE COURTESY OF IBM
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Chemists at times look to plants, sea life and other natural sources for the basic ingredients needed to develop the next breakthrough medicine. Unfortunately, nature is not always willing to easily part with its secrets, forcing scientists to rely on sophisticated imaging technology—nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry, for example—to decipher the molecular formula of newly discovered organic compounds so they can be replicated in the lab.
Sometimes these new compounds defy even the most powerful lab equipment. Researchers at the University of Aberdeen Marine Biodiscovery Center (MBC) in Scotland found this to be the case last year when studying a bacterial species—Dermacoccus abyssi sp. nov. —found in a mud sample harvested via robotic submarine from the Pacific Ocean's Mariana Trench, the deepest place on Earth, at about 11,000 meters. When the sample produced a chemical compound they were not able to identify, the researchers tried high-resolution mass spectrometry to determine the chemical compound's components but were unable to figure out its exact molecular structure.
The Aberdeen scientists are studying the potential of marine organisms as a source for new chemical compounds, which could be used to develop novel treatments for cancer, inflammation, infection and parasitic diseases. The search for new natural compounds is necessary because nature provides much greater chemical diversity than researchers can come up with, says Rainer Ebel, an Aberdeen lecturer working at the Marine Biodiscovery Center. "Nature is a far more creative chemist," he adds. "We keep finding new templates from nature that synthetic chemicals try to improve upon."
When promising candidates are discovered, the scientists must identify the structure of these compounds in order to determine whether they are viable for use in drug development. This approach has been successful, in particular when researchers in the late 1960s and early 1970s extracted a then-unknown compound from the stem bark of the Pacific yew tree that would turn out to be a key ingredient of the anticancer drug Taxol (pdf).
Each carbon and hydrogen atom in a molecule has a defined frequency in the NMR spectrum that scientists use determine how hydrogen and carbon atoms are connected together. The D. abyssi sp. nov. sample's dearth of hydrogen atoms, however, meant that NMR could not provide Aberdeen researchers with enough information to solve the mystery. Instead, the scientists' efforts left them with four potential structures, none of which could be ruled out by the NMR data alone. The only remaining possibility to find the correct structure would have been to take a chemical synthesis of the proposed structures, a very complex task that can take several months.
"We knew basically what was in the lower left and upper right of the molecule, but we couldn't connect the two sides," Ebel says. It was like solving a jigsaw puzzle without the benefit of a photo of the finished product.
The researchers caught a break late last year when the wife of MBC Director Marcel Jaspars recalled an August 2009 article she had read in the London's Daily Mail about a team of IBM Research—Zurich scientists who had used a modified atomic force microscope (AFM) to create an image revealing all the bonds in an individual molecule. One of the pictures accompanying the Daily Mail article showed the hexagonal shapes of five carbon rings as well as the positions of the hydrogen atoms around these rings. Jaspars got his hands on the IBM scientists' study the following day and soon contacted lead researcher Leo Gross. Jaspars sent Gross a sample of Aberdeen's mystery compound, which IBM started examining in January.
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17 Comments
Add CommentI can't help but wonder why the person who recalled the prior use of AFM, and offered the idea of using it in the current context, wasn't mentioned by name, being referred to only as the researcher's wife? Surely she should get more credit.
Reply | Report Abuse | Link to thisI'm also curious how the identified molecule was found both in a Thai orchid and deep in the Mariana Trench, two widely different settings.
quincykim - If she had been the wife of a lab assistant you'd have never known of her suggestion. Her relationship with the MBC Director was the critical factor producing this non-discovery, for which no real credit is deserved.
Reply | Report Abuse | Link to thisIMO, this is just a nice story promoting the (very useful) capabilities of IBM's AFM technology. You know - kinda like a commercial.
Regarding the commonality of molecules, humans and sea slugs share a large number of molecules and, I guess, even produce some of the same. I suspect that organisms adapted to extreme environments or conditions of extreme biodiversity are more likely to produce more unusual and complex compounds.
I am immediately reminded of Paul Davies(and company) research and his current book "The Eerie Silence" and " Shadow Biospheres" which he delves into (which ironically I'm just finishing now.) Certainly worthy of further investigations. Is it possible this could be a chemical signature from a yet unknown form of "life"???
Reply | Report Abuse | Link to thisjtdwyer - I agree, if her husband were further down the totem pole it wouldn't have been mentioned at all. I also agree that this is not a particularly newsworthy item, which, considering it's SA, means there's a hidden motive for posting it. I'm betting on "commercial".
Reply | Report Abuse | Link to thisquincykim - I do agree that if there had been any real justification for accreditation, based on the story, anyway, the wife deserved the recognition... Her husband probably has the MBC contract authority, though.
Reply | Report Abuse | Link to thisRegarding the comments about the wife of the Marcel Jaspars , the professor, his wife and family are currently on vacation and in respect for her privacy we didn't release her name without her permission.
Reply | Report Abuse | Link to thisAs for the "commercial aspects" the article is based on the peer-reviewed journal Nature Chemistry, which doesn't take ads and is very particular about the content that it accepts. So as experts in this field if they think its news worthy, then we should probably agree with them.
Additional photos are here: http://www.flickr.com/photos/ibm_research_zurich/sets/72157624273503313/
Regarding the comments about the wife of the Marcel Jaspars , the professor, his wife and family are currently on vacation and in respect for her privacy we didn't release her name without her permission.
Reply | Report Abuse | Link to thisAs for the "commercial aspects" the article is based on the peer-reviewed journal Nature Chemistry, which doesn't take ads and is very particular about the content that it accepts. So as experts in this field if they think its news worthy, then we should probably agree with them.
Additional photos are here: http://www.flickr.com/photos/ibm_research_zurich/sets/72157624273503313/
Regarding the comments about the wife of the Marcel Jaspars , the professor, his wife and family are currently on vacation and in respect for her privacy we didn't release her name without her permission.
Reply | Report Abuse | Link to thisRegarding the comments about the wife of the Marcel Jaspars , the professor, his wife and family are currently on vacation and in respect for her privacy we didn't release her name without her permission.
Reply | Report Abuse | Link to thisIBMZRL - No, I agree the AFM technology is quite impressive and useful... Say, you don't happen to be an IBM representative, do you?
Reply | Report Abuse | Link to thisBack in the mid-80s one of my young colleagues gave a lunch seminar on his new GC-FtIR. He was enthusiastic and even went so far as to suggest that an FTIR spectrum in argon frost was about as good as it could get. He even teased some of us older guys about catching samples from a GC effluent in chilled KBr in a test tube and making pellets to identify an unknown peak. I was more often a user of analytical services than an analytical chemist but I piped up in their/our defense and suggested that one day maybe we could just look at a molecule under a microscope and sketch out its structure, therby rendering his new toy obsolete. Scanning tunneling microscopy had just been announced (by IBM) but AFM had not been invented or announced yet. So Thanks IBM for making one possible view of the future a reality. So is this as good as it gets? Maybe not - I can imagine using those surface plasmon waves which were undiscovered or at least not well known to allow us to lay a new molecule on a surface and interpret the wave changes at even higher resolution. Nice work !
Reply | Report Abuse | Link to thisYes, I am. With a user name of IBMZRL (Zurich Research Lab) I wasn't trying to hide it.
Reply | Report Abuse | Link to thisIBMZRL - Sorry, I was just trying to be funny.
Reply | Report Abuse | Link to thisSeriously, the AFM capabilities are amazing, and should contribute to many meaningful discoveries in the future. Congratulations and best of wishes to ZRL and IBM.
By the way, I never accept an expert's opinion at face value but always determine my own.
There is little or no attempt at understanding how the body works. Instead, Novartis and others keep trying these 'chemicals' on known 'conditions', like erection-dysfunction or some other discomfort, and see if it allevieates things. The result is money making 'convenience' chemicals for these companies, but no science.
Reply | Report Abuse | Link to thisThe root of the problem is our health insurance laws. Bob Dole got lots of money from Pfizer and helped invent a 'disease' for erctile dysfunction, so that health-insurance money could be justified for this 'disease' (which is, at best, tough luck! rather than a disease).
We need to change our health insurance laws so that we only pay for drugs that are based on science and actually cure something. Until then, the drug companies are just going to keep looking for comfort chemicals.
In the mean time, who has the generosity and financial resources to fund such applications? Cheap drugs (relatively speaking) and the research costs associated with them trump expensive, time consuming, and obscure treatments any day of the of the week. No one is going to gamble their finances away for something that has a low potential for success.
Reply | Report Abuse | Link to thisYes, I am an IBMer. Sorry, I thought IBMZRL (Zurich Research Lab) made that clear. Thanks for your comments.
Reply | Report Abuse | Link to thisEinsteins wife did not get a mention for her important work on relativity, its the human condition I'm afraid! aquaponics.me.uk
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