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.

Many of the drugs we use to fight cancer or ward off pain aim to inhibit the activity of proteins that the body naturally produces. Instead of inhibiting the activity of a protein, what if you could just instruct your body to stop making it altogether? Or instead of getting injected with a lab-produced protein that your body isn’t making enough of, wouldn’t it be more convenient to just tell your body to use the instructions in its own DNA to make more? Sangamo Biosciences is pursuing these exact approaches to gene regulation using an engineered class of proteins called transcription factors. These so-called “designer” proteins promise to change the way medicine is practiced, and that’s why Sangamo is one of Biotech Mashup’s top 15 picks for companies that have the potential to change medicine.

The instructions for making proteins reside in DNA. For a protein to be produced, the DNA must be copied into an intermediate molecule, RNA, and then translated into protein. The first step of copying DNA to RNA relies on a large class of proteins termed transcription factors. Transcription factors can recognize and bind to a specific DNA sequence. Whence bound, they can either repress or stimulate the copying of DNA into the RNA that is required for protein production. Sangamo’s technology is based upon a class of transcription factors termed zinc finger transcription factors, or ZF-TFs. ZF-TFs are especially useful because their DNA binding domains and functional domains can be assembled as modules. It is thus possible to attach a transcriptional repressor or activator to the same DNA binding sequence. In this manner, it is possible to increase or decrease the expression of any gene depending upon the choice of functional domain. Transcriptional activators and repressors are not the only functional domains that can be attached to ZF proteins. It is also possible to attach nucleases, proteins that cut DNA, to a ZF protein. Nucleases can be used for targeted repair of a defective gene, or gene disruption to completely knock-out the gene.

The technology gets even better. The DNA binding domain of ZF-TFs is also modular. So it is possible to pick individual protein fragments that are known to bind to 3-base stretches of DNA and string the protein pieces together so that they collectively recognize larger stretches. Stringing just six such protein fragments together permits the unique targeting of almost any 18-base pair DNA sequence. Sequences as short as 18 bases have so many possible combinations that they are almost guaranteed to be unique within the entire human genome.

According to Sangamo, an advantage of activating an endogenous gene, rather than supplying the lab-generated protein product, is that activation of the endogenous gene results “In the production of all of the normal splice variants and thus the natural protein isoforms in the ratios normally observed in nature.” For VEGF-A, a vascular endothelial growth factor, this is especially important. “VEGF A, in its natural state, has multiple splice variants that are involved in the normal physiologic response and appear to be required for the generation of normal, functional vasculature,” according to Sangamo.

Sangamo, located in Richmond, California,  has a large pipeline of therapeutic ZF-TFs aimed at diseases including diabetic neuropathy, HIV, congestive heart failure, cancer, and cardiovascular disease. The technology has its technical limitations, however. For instance, delivering protein therapeutics to the nucleus of a cell, where this class of compounds must function, is not straightforward. Viruses carrying DNA that encodes the ZF-TFs are one approach, but they carry their own set of risks. As with most technologies, when there is a will, there is a way. We believe that ZF-TFs hold such promise as therapeutics that delivery obstacles will be overcome.

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.

 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.

In upcoming posts, we will be discussing what we believe is so exciting and revolutionary about each of these 15 companies that Biotech Mashup believes will change medicine:

NanoBio Corporation

            -New Vaccines using Nanotechnology

23andMe

            -Personalized Genomics

Cryoport Inc.

            -New Cold Shipper Technology

OrphageniX Inc.

            -Targeted Gene Alteration     

Robotic Systems & Technologies

            -Surgical Robot, Part of the Traumapod Team

HemCon Medical Technologies Inc.

            -Instant Wound Care

Halozyme Therapeutics

            -Novel Drug Delivery

Menssana Research

            -Breath Analyzer Technology, Possible Early Cancer Test

Vocera Communications Inc

            -Instant Two Way Wireless Communication for Hospitals

Amyris Biotechnologies, Inc.

            -Synthetic Biology to Create Cheaper Drugs

Kosan Biosciences

            -Combinatorial Polyketide Biosynthesis for Cancer Therapeutics

Regulus Therapeutics

            -Develops microRNA Therapeutics

Sangamo Biosciences

-Designer Transcription Factors That Directly Regulate Gene Expression

Advanced Cell Technology

            -Stem Cell Company Which Can Harvest Stem Cells without Damaging Embryos

Pacific Biosciences

            -Sequence Entire Human Genomes from a Single Molecule

Next time you go to put a handful of fresh, fluffy, white snow into your mouth, think bacteria. A recent report in Science Magazine found that bacteria often function as nuclei in forming snowflakes, a surprisingly common side job for them. Snowflake formation requires the presence of some particulate matter in order to condense around. Atmospheric dust would be the obvious contender. Snow samples were taken from widely dispersed areas including Antarctica, France, Montana and the Yukon, although most bacteria were found in French snow (for whatever that tidbit is worth). In some samples, bacteria comprised up to 85% of snowflake nuclei.

Since cloud seeding is an important way for humans to influence precipitation, this research begs the question of how we can put this knowledge to use to increase snow fall in otherwise lacking areas (ski resorts and drought areas, for instance). Blowing bacteria into the sky may not be the best solution, but by studying what makes bacteria one of nature’s first choices for snow formation, we might be able to come up with something that is both eco-friendly and equally as efficient.  

-Canola oil was derived from the rapeseed through conventional breeding.
-The word “rape” in rapeseed comes from the Latin word “rapum,” meaning turnip.
-Turnip and many other vegetables are related to the two canola species commonly grown.
-Negative connotations with the word “rape” in North America resulted in the marketing-friendly name of “Canola.”
-Genetically modified canola, which is resistant to herbicide, was first introduced to Canada in 1995.
-Today 80% of the acreage of canola is sown with genetically modified canola.
-In 2004, North Dakota produced 91% of the Canola in the United States.
-Canola oil is a promising source for manufacturing biodiesel, a renewable alternative to fossil fuels.
-Europeans used rapeseed oil in lamps hundreds of years ago.

What will we use it for next??

Here’s what happened this week on Biotech Mashup:

Monday, February 25th, 2008

Researchers “filmed” for the first time an electron in motion around a nucleus.

Bullfrogs may produce an anti-aging compound.

Tuesday, February 26th, 2008

Your next computer may use a protein hard drive.

Robots can be powered by rat heart muscles.

Wednesday, February 27th, 2008

Nanotechnology is improving medicine with better vaccines.

Wired Blog reported on a controversial iron fertilization scheme.

Thursday, February 28th, 2008

Human Primate genes may be driving the obesity epidemic.

New antibiotics are made from battling bacteria.

Friday, February 29th, 2008

Pollution causes songbirds to sing better.

The doomsday vault opens, but should be only the first step.

By now, you’ve probably heard of the doomsday vault that opened in Norway last Tuesday. It is a facility built to safely hold and protect the world’s supply of seeds. The vault was carved 364 feet deep into sandstone and limestone under the permafrost of a remote Arctic mountain only 620 miles from the North Pole, where, ironically, nothing grows. The vault is comprised of three spacious cold chambers, each measuring 89 x 33 feet. It has the capacity to hold up to 4.5 million batches of seeds from all known varieties of the planet’s main food crops, making it possible to re-establish plants if they disappear from their natural environment or are obliterated by major disasters. Samples will remain the property of their countries of origin. The vault is protected by high walls of fortified concrete and an armored door, as well as its 425-ft altitude above sea-level, in the event that the polar ice sheets melt due to global warming. At least if that happens,there will be no shortage of fresh water to germinate the seeds. Fortunately, the vault can also withstand a nuclear attack (which could also be expected to melt some ice).

I really commend Norway for undertaking the expense and effort to build this vault. It is an acknowledgement of the difficult times we live in and the uncertainty of the future. Instead of sugar coating the planet’s situation, the Norwegian government has forked out nearly $5 million to build the vault at a time when the U.S. seems interested in only military conquests and the immediate threat of terrorists. The construction of this vault also highlights the need for vaults to store cells from all living creatures and at diverse locations. Someday, cloning technology will likely permit extinct animals to be re-created, although they may not be able to survive in the wild without training from their parents. We should also store along with the cells as much information about the species as possible (habitat, food preferences, etc). I think that this seed vault is fantastic, but it is really only a first step for our planet.

-China produces more cotton than any other country.
-Texas grows the most cotton of any state in the U.S.
-A bale of cotton weights about 500 pounds.
-Each bale is subjected to more than 800,000 pounds of force during wrapping.
-One bale can produce:
  1,217 men’s T-shirts
  313,600 $100 bills
  215 pairs of jeans
  3,085 diapers
  1,256 pillow cases
-There are about 35,000 cotton farms in the U.S.
-The U.S. produced 23.89 million bales of cotton in the year 2005.
-This is enough cotton to print nearly 7.5 trillion $100 bills.

(Some facts courtesy of the National Cotton Council)