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.

 The era of personalized medicine is fast approaching. Having your genome sequenced rapidly and cheaply will be key to this fundamental change in the way medicine is practiced and drugs are developed. Several companies are working toward the $1,000 genome, including Pacific Biosciences, one of Biotech Mashup’s top 15 picks for companies that have the potential to change medicine.

The motto of Pacific Biosciences is “Single molecule, real time,” which promises cheap, long reads. In fact, the company last month announced amidst a fireworks display that within five years they will be able to sequence at high quality an entire human genome in just 15 minutes and obtain raw sequence in under an amazing three minutes. The company’s first commercial instrument will be ready by 2010, at the earliest.

“PacBio” was founded in 2004 based upon technology reported in a 2003 Science publication. The sequencing technology essentially makes use of two key techniques. The first is the ability to “focus” a light beam into a tight area using a zero mode waveguide. The waveguide does not actually focus light, but rather restricts the area that is illuminated to a small portion at the bottom of a nanofabricated well, where a single DNA polymerase molecule is anchored. The second technique is the use of fluorescently labeled nucleotides. As a fluorescent nucleotide is added to a growing DNA chain, it spends enough time illuminated in the light beam that its fluorescence can be detected. Each base is labeled with a unique fluorophore that is cleaved off as the base is added to the growing DNA chain, and the color of emitted light reveals which base was added. Nucleotides floating in solution do not contribute to the signal or a significant background because they are not illuminated long enough. The polymerization process occurs in real time at about 10 bases per second, a speed which is expected to increase since polymerases can operate 50-75 times faster. Since the micro-wells can be arrayed, many polymerases can be monitored in parallel using a CCD camera. The company has already demonstrated 1,000 polymerases sequencing DNA in unison, and aims to increase that number to 1 million. In fact, the wells are so small at just 20 zeptoliters that the company claims they are the world’s smallest reaction volumes.

The company predicts that 100 gigabase-per-hour read rates in real time can be achieved. According to the company, their technology is “disruptively faster than current next-generation technologies.” We will be anxiously watching Pacific Biosciences as they disrupt their way to sequencing our genomes.

Researchers at Purdue University, have published in Nature, a new technology for detection of toxins and food-borne pathogens. The research group claims the technology is able to detect several pathogens in thousands of food and water samples in a couple of hours. Interestingly, it can also estimate the number of microbes present in a sample and determine whether that amount poses an active health hazard.

The technology uses live mammalian cells, B-cell hybridoma, PED-2E9, in a type I collagen matrix, that release a chemical, alkaline phosphatase, when harmed. This chemical can be detected uses optical equipment, such as laser scanning cytometry or cryo-nano scanning electron microscopy. The group developed software which can then analyze the signal and determine the quantity of harmful microbes present. Since the bio-sensor uses live cells it only detects actively harmful pathogens and ignores those that are inactive and harmless. Most test on the market currently detect dead or alive microbes and are prone to high false alarm rates or use a lengthy incubation periods, up to 20 hours or more, to grow only living microbes for detection.

This is an interesting application for live cells but is not novel. BAE systems has had this algae detector on the market for some time now. Even with this being said, the food market is lacking a fast, relatively speaking, detection method for Listeria monocytogenes. We at Biotech Mashup will follow this group to see if they are able to spin this out of the laboratory.

Julie Steenhuysen (Reuters) reported on a recent study published in PLoS Genetics which found that genes that helped early humans adapt to cold climates may be driving metabolism-related diseases such as obesity or diabetes. U.S. researchers at the University of Chicago found a strong correlation between climate and genetic adaptations that influence the risk of metabolic syndrome, a group of related disorders such as obesity, high cholesterol, heart disease and diabetes. “Climate over a long period of time has shaped the distribution of genetic variants that may be associated with the risk of these common metabolic disorders,” said Anna Di Rienzo, a professor of human genetics at the University of Chicago. Anthropologists have long argued that differences in skin pigmentation, for instance, are related to early human migration. “There are all of these traits, body mass or skin pigmentation, that we know are strongly correlated with environmental variables,” Di Rienzo said. Di Rienzo and colleagues wanted to see if genes that were once useful for tolerating cold climates were playing a role in metabolic diseases. “To survive in these climates, they had to adapt,” said Di Rienzo.

To test the hypothesis that climate shaped variation in metabolism genes in humans, the team used a bioinformatics approach to select 82 candidate genes for common metabolic disorders. They then genotyped 873 tag SNPs in the genes in 1,034 people from 54 populations. They saw several clusters of different genetic variations related to metabolic syndrome in colder climates. Interestingly, one haplotype was associated with higher body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin, suggesting that it conferred a selective advantage on energy metabolism. Biotech Mashup thinks that we might be able to use some of the SNPs from this study to better understand our hunger pains. Furthermore, the SNP tests offered by companies such as 23andme and Navigenics might be more insightful in light of these studies.

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.