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.

On Wednesday, Medtronic announced that the FDA has informed them that it has classified its communication to physicians related to inflammatory mass formation associated with intrathecal drug delivery as a Class I Recall.  On January 16, 2008, Medtronic sent a letter to inform clinicians worldwide of an increase in the rate of reported inflammatory mass cases in patients who have received intrathecal drug delivery through its implantable infusion systems. Even though Medtronic has issued communications regarding this issue since 2001 it was still deemed necessary by the FDA to issue a class I recall, something that Medtronic has downplayed. Physicians and patients will need to do nothing regarding this issue as it is Medtronic’s responsibility to follow the guidelines set by the FDA.

 Regarding FDA recalls, many people are confused when the FDA issues a recall, evident in this 2002 brochure released by the FDA to help explain its recall policies. Some interesting points, The FDA has a classification system regarding recalls which is as followed:

“The guidelines categorize all recalls into one of three classes according to the level of hazard involved.

• Class I recalls are for dangerous or defective products that predictably could cause serious health problems or death. Examples of products that could fall into this category are a food found to contain botulinal toxin, food with undeclared allergens, a label mix-up on a life saving drug, or a defective artificial heart valve.
• Class II recalls are for products that might cause a temporary health problem, or pose only a slight threat of a serious nature.  One example is a drug that is under-strength but that is not used to treat life-threatening situations.
• Class III recalls are for products that are unlikely to cause any adverse health reaction, but that violate FDA labeling or manufacturing regulations. Examples might be a container defect (plastic material delaminating or a lid that does not seal); off-taste, color, or leaks in a bottled drink, and lack of English labeling in a retail food.”

From this information we can see that even though Medtronic is issuing a press release saying that this recall is a non-issue, the fact that the FDA has classified this as class I would suggest otherwise.

A review published in Acta Paediatrica has found that from 1996 to 2002 only 2 percent of 739 children drug trials had independent safety monitoring. Independent safety monitoring gives an unbiased review of the drugs side affects and can determine if a drug trial should be stopped due to unwanted and harmful results. This is particularly important in children as they are more prone to issues than adults and could live with harmful effects for the rest of their lives.

When I read this earlier today I was shocked. I had always believed that compared to adult trials, children drug trials had higher standards and more emphasis on safety, however this report strongly shows my ignorance. The lead author Dr. Helen Sammons commented that “We were very surprised by the low level of trials that had independent safety monitoring committees and are urging pharmaceutical companies to include these in all future trials involving children.” Some surprising statistics come out of this report:

·     Seven out of ten trials reported adverse events and a fifth of the trials reported a serious adverse event, ie. an untoward medical occurrence, not necessarily related to a drug.

·     Adverse drug reactions were reported in just under 37 per cent of trials, with 11 per cent of trials reporting moderate or severe adverse drug reactions.

·     Six clinical trials — which all had safety monitoring committees — were terminated early because of significant drug toxicity.

·     Deaths were reported in 11 per cent of the trials, but the majority were thought to be unrelated to the drug use.

·     Death rates were highest in trials involving newborn babies, with 56 per cent of the 99 trials included reporting a death.

·     Other major specialities in which deaths were reported included infectious diseases, neurology, respiratory and kidney problems.

It should be noted that almost three fourths of the trials had safety monitoring but were not independent and could be considered unreliable. Finally it should be mentioned that in many respects these type of trials are needed if children’s health and conditions are to ever improve but it should be done in a manner that is responsible.

The main function of DNA is to encode the building blocks of proteins, and molecular biologists have become quite adept at cutting and pasting stretches of DNA to make nearly any protein they can envision. Unfortunately, small molecules, which are some of the most effective drugs, cannot usually be built so readily. Rather, synthetic organic chemists must use a bag of tricks and years of experience to synthesize compounds that on paper sometimes appear rather simple. However, several companies are taking advantage of a modular approach, programmed using DNA, for building diverse libraries of polyketides, naturally occurring small molecules with huge pharmaceutical promise. Two such companies include Biotica and Kosan Biosciences, which made Biotech Mashup’s list of the 15 companies with the potential to change medicine.

Polyketides, which are produced by diverse microorganisms found in places ranging from the soil to the oceans, are a structurally diverse family of natural products with an extremely broad range of biological activities and pharmacological properties. Numerous drugs spanning many therapeutic areas, such as antibiotics (e.g.erythromycin A), anti-cancer compounds and antifungals, have been derived from approximately 10,000 known polyketides. According to Biotica, polyketide natural products account for medicinal sales in excess of $20 billion per year.

The combinatorial potential of polyketide synthesis is what attracts the attention of scientists and pharmaceutical companies. Polyketide synthesis is performed by large modular multisubunit enzymes known as polyketide synthases (PKSs). The addition of each individual building block to a growing polyketide chain can be performed by a separate module of the PKS. These PKS mega-enzymes are composed of gene modules encoding the active sites for the successive activation, modification and elongation of carbon building blocks. By mixing and matching catalytic components, it is thus possible to genetically specify polyketide compounds using DNA and molecular biology. As described by Biotica, PKSs can be viewed as molecular assembly lines, in which every element of functionality of the polyketide product can be identified with a specific enzyme workstation.  It is estimated that a polyketide synthesis system with just 6 modules can theoretically produce over 100,000 compounds. Large polyketide libraries can be generated by assembling a gene with various combinations of altered DNA fragments. Novel compounds can also be produced using synthesized “starter units” that are fed to engineered microorganisms to be used as precursors.

Kosan is currently focusing on anti-cancer compounds, and has numerous drugs in its pipeline spanning the preclinical to Phase 2 development phases. Compounds currently in Phase 2 development target breast cancer, melanoma, and multiple myeloma. Biotica also has a portfolio of anti-cancer compounds, and is partnering with Wyeth on its mTOR inhibitor anti-cancer drugs. Importantly, both Biotica and Kosan are targeting Hsp90 (heat shock protein 90), a protein that interacts with several sets of signaling proteins and whose disruption leads to degradation of the interacting proteins that can promote cancer.

The ability to “program” small molecule synthesis in a combinatorial fashion is truly exciting. Given the proven utility of polyketides as drugs, we have good reason to believe there will be some great drugs coming from Biotica and Kosan.

If 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.

As reported on Biospace.com, PDL BioPharma announced that due to the inability to sell the company or a portion of the company’s biotechnology and discovery assets they will instead remain independent and downsize, cutting 260 jobs. PDL BioPharma owns proprietary antibody humanization technology that has been licensed to numerous companies, including Biogen Idec, Inc. They are a direct competitor with companies such as Medarex, as viewed by Medarex in their 10Q that “XOMA and PDL BioPharma both offer technologies to convert mouse antibodies into antibodies closely resembling human antibodies…( )PDL BioPharma,..( ) have generated therapeutic products that are currently in development or on the market and that are derived from recombinant DNA that comprise human antibody components.”

Spinning this downsize PDL BioPharma stated, “As a substantially more streamlined biotechnology organization, PDL will work to efficiently maximize the value of its core technical strengths and 21 years of antibody expertise, while successfully advancing its current portfolio and partnering, when appropriate, to maximize value, offset the costs and mitigate the risks of mid- to late-stage development,” said L. Patrick Gage, Ph.D., interim chief executive officer of PDL. “In addition to PDL’s technical competencies, our talented employees, who have continued to move our company forward during the strategic review, are a fundamental strength of our company, and I thank them for their ongoing dedication and hard work.”

At one time PDL BioPharma was considered an up and coming company with an exciting technology. However, the biotech company has wasted millions on research and development that lead no where and acquisitions that added little or no value to the company. PDL BioPharma’s products were acquired through the purchase of ESP Pharma. Of the three drugs ESP Pharma had on the market, the major revenue generating drug Cardene will be going generic in 2009. The biggest rung in PDL BioPharma’s ladder is Genentech. Genentech pays royalties to PDL for Avastin and Herceptin. Avastin has been and continues to be a very successful drug for Genentech and in proxy for PDL BioPharma. Even with the mismanagement of PDL it seems like they will continue to be a player in the humanized antibody market due to the coat tails of Genentech.

In 2007, fertilizer prices rose more than 200%, according to the International Center for Soil Fertility and Agricultural Development, IFDC. Doctor Balu Bomb of IFDC says “reasons include new demands for food crops, especially corn (or maize), for ethanol and other biofuels, increased energy and freight prices, higher demand for grain-fed meat in the emerging economies of China, India, and Brazil, and increased use of natural gas as liquefied natural gas.” Hardest hit by this increased cost are the poor farmers of Africa who use fertilizer to replenish the nutrients in the soil.

It is interesting that a large portion of the blame for this increased costs is placed on corn, due to the rise in price of corn bushels which farmers in the United States have noticed and are growing in place of other food commodities. In my opinion, if the government policy of mixing ethanol with gasoline had not been put in place, the cost of corn would not have increased and the substantial increase of fertilizer would have been averted. When the government regulates free markets, it negatively affects more than what was anticipated; food prices are increased as more farmers stop producing wheat, soy, and other commodities for corn. The icing on the cake against these types of regulations was announced last week when a study concluded that ethanol use could actually cause more harm than good due to land use changes caused by corn production.

At the 2008 Greener Gadgets Conference in New York, a conceptual design was released that could cool food or items while at the same time heating other items in a separate compartment. The design recieved a notable entry reward. The concept uses solar energy and converts it into electrical to run a compressor. The compressor can then cool or heat the items that have been placed in the compartments.

The original designers built the device with the intention of holding food. While I can imagine this would be a nice cooler to use for a picnic on a sunny day, it seems like it would have limited utility with the solar power requirement. However a great need exist in pharmaceuticals for an efficient and cheap way to ship new drugs or vaccines that require 4 degrees Celsius. With a slight modification to the device this could be a potential cheap and reusable shipper which could keep a constant temperature, a possible boon in the biotech and pharmaceutical industries.