Chemistry


See No Evil, Hear No Evil, Speak No Evil…Researchers from George Washington University have published in Animal Cognition that monkeys make character judgments based on reputation. In the past research has suggested that primates use eavesdropping and third-party interactions to help judge character, now Dr. Francy’s Subiaul believes that his work provides further evidence that a primate system exist similar to human social skills. Dr. Subiaul performed three experiments which showed that chimpanzee’s demonstrate judgment of reputation of individuals through observational interactions with strangers.

This further brings to light questions regarding our use of animals for pharmaceutical testing. Clearly more evidence is suggesting social interactions of many animals that we use in vivariums. Anyone in science realizes the benefits these test bring to the table but we should recognize, at the minimum, the intelligence of these animals.

 
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Blood Drive SignResearchers at Rockefeller University have published in Science the first chemical mechanism on how DEET, mosquito repellent, works on mosquito’s preventing them from biting humans. According to the paper DEET inhibits signals from the olfactory co-receptor  OR83b. This receptor responds to 1-octen-3-ol, a chemical secreted by humans. When DEET is sprayed on human skin it competitively binds to OR83b preventing the mosquito from detecting 1-octen-3-ol.

According to the Department of Health and Human Services DEET has a range of side effects on humans, from skin rashes and seizures to eight reported deaths since 1961. Due to these effects many people do not use DEET, even though mosquitoes carry a multitude of diseases which can be passed to humans. With this recent research, many home remedies such as Citronella, lemongrass, peppermint, eucalyptus, cedarwood, and garlic, can be tested and compared to DEET to see if they behave similarly and can be made into a commercial product. Biotech Mashup can not wait for the day that everyone is spreading peppermint garlic butter on their skins to prevent mosquito bites.

 
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HemCon LogoTen years ago if you had a car wreck and suffered deep lacerations the standard treatment would have been a tourniquet to prevent bleed out. While waiting to reach a hospital, the result of this treatment could have been loss of a limb or death. Now, it is the year 2008, and treatment procedures have slowly been changing to use a new revolutionary product to greatly reduce these incidents, the HemCon Bandage. The HemCon Bandage provides an instant antibacterial barrier to control bleeding, replacing the need for traditional gauze bandages or tourniquets. This innovative new treatment for hemostatic control is the reason that HemCon Medical Technologies is on Biotech Mashup’s list of 15 companies that have the potential to change medicine.

HemCon Medical Technologies launched in 2001 under the auspice of grants provided by the united states ARMY with additional capital from the two founders, Dr. Bill Wiesmann and Dr. Kenton Gregory. Doing a lot of hard work and having a little bit of luck, the doctors, have turned a small startup into what HemCon Medical is today. The company before last week had three products on the market; HemCon Bandage, ChitoFlex, and HemCon Dental Dressing. Using these products HemCon’s technology was only available to the military, hospitals, and emergency responders until now. This last week HemCon announced a new product, KytoStat, bringing the company’s technology from the hospital and military battlefield to your backyard. The KytoStat is the next generation band-aid, providing instant wound care.

The HemCon bandage contains chitosan, an organic substance found in crustacean shells. In 1984, scientists published in Neurosurgery the use of chitosan to stop bleeding in cats. Since then numerous journal articles have been published describing this new hemostatic agent but it was not until the doctors Wiesmann and Gregory founded HemCon did someone develop a chitosan bandage. As described by HemCon’s website the process starts with chitosan processed in Iceland from shrimp shells. After mixing it with acetic acid and turning it into a gel, the material is cast into square tiles. The squares are then freeze-dried in a vacuum chamber, compressed to about half their original thickness, and backed with a thin sheet of brown plastic. This completes the manufacturing of what is now a HemCon bandage, each bandage is then sealed in foil and sterilized by gamma radiation.

The benefits of a chitosan bandages are two fold; first when it is placed on a wound the chitosan has been found to have antimicrobial properties, second the bandage promotes clotting because blood cells and platelets carry a negative electrical charge and are attracted to chitosan, which bears a positive charge. The bandage has stopped or slowed down severe bleeding from combat wounds in 97 percent of the cases according to this special report in 2006. Hemcon’s media department responded to our inquiries with some interesting additional information, such as “are the HemCon dressings kosher? Hemcon dressings are made from shellfish, a creature that is considered forbidden from consumption by some religious groups. Although the dressing is not technically consumed, it is not considered kosher.” An interesting ethical dilemma may occur if a patient who must follow kosher laws is or could be saved by HemCon bandages.

HemCon may have a presence in the market, a new product that is direct to consumers and an exclusive license agreement with Cardinal Health but, a large number of challenges are still ahead. Two other companies offering next generation hemostatic control technologies are in the market, Celox Medical and Z-Medica. Celox Medical has a granule hemostatic agent which was tested by the United States Marine Corps and obtained 100 percent survival rates. Celox however, still does not have a product for sale. Z-Medica on the other hand sells the QuikClot, which is currently being used by the military, hospitals, and first responders. As well the company has multiple product offerings. In a recent study done by the Naval Medical Center, they compared all three hemostatic methods and found that all substantially improved outcomes verses traditional dressings but, Celox technology appeared to show the greatest improvement for control and survival. It should be noted this was a very small study with only 12 animals in each group and should be taken only lightly until larger studies can be carried out. This study points out that HemCon has some tough competition in the near future. Even with this competition Biotech Mashup feels that with the benefits of chitosan and the current leverage that HemCon has in the market, they stand a very good chance of greatly impacting the medical community and the standard of care for the foreseeable future.

 
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dna_strand_gaub.jpgWhen in 1990 IBM arranged 35 individual xenon atoms to spell out “IBM,” the feat heralded a new era of nanofabrication. And it was so totally cool. But there’s not much you can really do with xenon atoms, and the process had to be performed under a near vacuum at close to absolute zero. A new technique that is much more flexible was recently reported by a group in Munich.

The Munich team manipulated individual DNA molecules into position using an atomic force microscope as a cantilever. The process was performed at room temperature and in solution, making it relatively accessible to a wide range of labs. But the quantum leap forward achieved by using DNA is that it can be readily functionalized. For example, the Munich group attached both a fluorophore and a biotin group to their DNA. Furthermore, DNA can act as a template or “seed” for self assembly of larger structures, such as those demonstrated using DNA staples to create nanoscale shapes and patterns. The Munich team attached a piece of DNA to the microscope tip and picked up from a “depot” pieces of DNA with complementary stretches to the tip-bound DNA. The cantilever then moved the DNA to the assembly area. The assembly area had an anchored DNA molecule that also was partially complementary to the moved piece of DNA, so the moved piece could be immobilized at the destination. The tip-bound piece of DNA was re-used thousands of times without loss of fidelity.  I’ve actually oversimplified the binding/unbinding process a bit, and in actuality the group makes ingenious use of the orientation of hybridized DNA molecules to take advantage of either “shear” or “zipper” binding/unbinding geometries to aid their efforts. You can find more details about that in their Science article.

While it’s unlikely that you will be buying any mass-produced products manufactured with these new techniques, the ability for researchers to construct objects to exact specifications may greatly aid materials and life-science research.

 
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Menssana Website CloudIf I told you in the future you will be able breath into a device and know if you have cancer, would you believe me or would you ask me what new science fiction book I was talking about? Menssana Research would tell you that the future is now. They have developed and tested a new device that requires you to only breathe and then it can determine if you have cancer or other common ailments such as Tuberculosis. If successful in this endeavor, this will be a revolution in diagnostic testing and is the reason that Menssana Research has made Biotech Mashup’s top 15 picks for companies that have the potential to change medicine.

Diagnostic test using your breath is not a new idea. Spirometry, pulmonary lung function testing, is believed to date back as early as sometime between 129-200 A.D. when Galen did volumetric testing on a boy. In 1852, John Hutchinson, developed a water spirometer which is still in use today. Spirometry testing can be used to help determine a number of ailments such as, chronic bronchitis, pulmonary fibrosis, chronic obstructive pulmonary disease, asthma, and emphysema. Similar to volumetric testing but distinct in that biomarkers can be used for disease determination is the analysis of volatile compounds in breath. Many credit the technology basis of volatile diagnostic testing to Linus Pauling, who in 1971 found that normal breath contains volatile organic compounds. However, some argue that this credit should be given to Robert Borkenstein, who in 1954, developed the breathalyzer to measure the amount of blood alcohol in an individual. Regardless of who is to be given credit little else has advanced this form of diagnostic testing for the last 35 years.

Menssana Research Incorporated, founded by Doctor Michael Phillips, believes it is time for a leap forward. The Breathscanner is the first clinical device offered by Menssana. The concept behind the Breathscanner seems simple; collect a person’s breath and analyze the unique volatile organic compounds, VOCs, which can be indicative of disease. The reality though is different as the typical concentration of VOCs in a breath is very low and nobody knows what VOC profiles indicate disease. To address these problems Menssana put to use two analytical techniques known to have very good sensitivity, gas chromatography and mass spectroscopy. Using these instruments to analyze the VOCs in someone’s breath they have been able to put together what they have coined “breath methylated alkane contour, BMAC.” A person’s BMAC is a unique profile which can be used to determine someone’s risk for numerous diseases such as, heart transplant rejection, lung cancer, breast cancer, pulmonary tuberculosis, and other diseases. The Breathscanner was recently shown at DARPA Tech 2007, and was a big hit.

In 2004, the FDA gave Humanitarian Device Exemption status to Menssana for a heart transplant rejection breath test. Even though HUD is intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year, this was a huge step for Menssana. Moving forward Menssana is well funded and pushing for commercialization of numerous new diagnostic tests. Speaking via email with Dr. Michael Phillips he was kind enough to respond to our request for information letting us know, “The next big things in breath testing will be:

The Lungscreen breath test for lung cancer: This has been validated in three published multicenter studies(…)It has a CE Mark that approves it for marketing in Europe. NIH has awarded us a $3M grant to perform a multicenter validation study in the USA in order to obtain FDA approval.

Breath test for breast cancer:  NIH funded us to perform a pilot study that demonstrated breath biomarkers of breast cancer (publications on our website). We are now evaluating a point-of-care breath test for breast cancer that will deliver results in minutes. No radiation, no breast compression, no pain - it is completely safe.

Breath test for pulmonary tuberculosis: NIH funded us to perform a pilot study that demonstrated breath biomarkers of pulmonary TB. We are currently analyzing the data from a large multicenter international validation study. Results soon, we hope.”

Biotech Mashup is very impressed with the work done by Menssana Research and how far they have come in developing this technology. However, we recognize that with the use of mass spectrometry and gas chromatography equipment for analysis, these types of test will still be required to be sent to a diagnostic laboratory thus taking days for the patient to know the test results. The diagnostics field is having a big push for results to be available in the office while you visit your doctor. We know Menssana may be addressing this as they are currently in development of a next generation system. We are eager for the day that we can walk into our doctor’s office and do a quick breath test to let us know if we are healthy or if we need immediate treatment.

 
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Green Fluorescent Protein Transgenic MouseResearchers from China reported, in Acta Biochimica et Biophysica Sinica, a way to improve antibody production. Traditionally, antibody production uses recombinant fusion protein as an antigen to raise antibodies against the epitope, part of the molecule recognized by the immune system, of a target protein. At noted by the authors however is the issue that “the concomitant anticarrier antibody in resulting antiserum reduces the production of the desired antibody and brings about unwanted non-specific immune reactions.” To alleviate these issues the authors used a green fluorescent protein transgenic mouse. The carrier protein mouse produced a higher concentration of antibodies against the desired target protein compared to control mice.

This is an interesting but already developed way to use transgenic animals.  Medarex has been using transgenic mice since 2001 to make 100% human protein antibodies for use in therapeutics. The more pressing question is the application of this technology. For years Medarex has been promising that they would have a product out with one of their partners; a long list including Bristol-Myers Squibb, Pfizer, Amgen, Roche, Genmab, and Eli Lilly. However this promise is still on the back burner. The closest they have come to being on the market is the work they have done with Centocor. This product, CNTO 1275, is in the process of getting Biologica License Approval. Hopefully Medarex will finally perform as stated but, if I was an investor I would be concerned as the stock has taken a dive in the last six months from above $17/share to the current price of $8.77/share.

 
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plankton.jpgAbout 70% of the world’s surface is covered in oceans which are filled with plankton. Plankton that generate calcium or silica carbonate skeletons account for most direct carbon sequestration. To increase this carbon sequestration, iron can be used as a “fertilizer.” Iron fertilization is the intentional introduction of iron to the upper ocean to increase the marine food chain with the hope of fostering the sequestration of carbon dioxide from the atmosphere. Last year, two companies entered the space, Planktos and Climos. Although Planktos folded, Climos has received $4 million in venture funding. This highlights efforts to commercialize iron fertilization by selling carbon offset credits in exchange for the company fertilizing the oceans with iron sulfate in 60 mile by 60 mile swaths. As Wired Blog reported, leading iron fertilization scientists are not sure how much of the consumed carbon ends up sequestered and therefore “don’t have enough confidence to say that ocean iron fertilization could have any real impact on stopping or even slowing climate change.” It sounds to Biotech Mashup like potentially polluting the oceans with iron sulfate could be an environmental disaster in the making. More studies are required, and perhaps regulatory oversight, before we go dumping more chemicals into the ocean. “There are much safer and proven ways of preventing or lowering carbon dioxide levels than dumping iron in the ocean,” said Lara Hansen, chief scientist with the WWF International Climate Change Program. “This kind of experimentation with disregard for marine life and the lives of people who rely on the sea is unacceptable.

 
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Protien Memory MethodResearchers at Osaka University in Japan have found that proteins can store data. Professor Tetsuro Majima has developed a new method for spatiotemporally regulating fluorescent proteins. He can array a pattern of proteins using a photochemical technique, read the pattern and then erase the surface using photoirradiation. This process is useful for holding information. such as binary code for storage of data.

Memory devices based on biological building blocks have numerous advantages verses traditional magnetic devices. Protein devices should be immune to magnetic interference and thus the danger of a rogue magnet erasing your memory will be obsolete.  Another advantage is it is believed memory capacities will be larger with a protein hard drive.

A lot of hard work is still left before this is a commercially viable technology. Currently the protein memory has the greatest stability at 4 degrees Celsius.  However, this is not an acceptable temperature for a consumer computer product.  Furthermore, the protein patterns take about one minute to write, a time far too long for traditional memory.

 
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