NIH has given us a $500K grant to further develop a whole genome amplification technology that we have been developing for some time. I am one of the inventors of the base technology, and over the past few years we have made a number of improvements to the technique. We wanted to try out these modifications on single cell sources of chromosomal DNA.

NHGRI, an institute of the NIH, is funding the human microbiome project. One of the issues microbiome researchers face when studying the mixture of microbes that grow on us and in us is that genetic characterization of the individual microbes is tough. Researchers really would like to sequence the entire genome of each microbe in the mixture, but sequencing requires a lot of DNA. Much more than is present in individual cells. And many of the microbes only grow in the mixture. They are unculturable as a pure strain. But if there were a method to amplify the DNA found in individual cells, all researchers would need to do is isolate individual cells, which is easy these days. We proposed to evaluate all of the improvements we have made to the amplification method on amplification of single cell isolates. Over the next 2 years we will be testing this and validating the methods by sequencing genomes of different bacteria found in the human gut.

You can read the full press release on this project here.

Hi all, I wanted to tell you about some of the interesting new work I’ve been doing with the Natural History Museum in London. This new project is really an extension of the studies I’ve been doing in DNA sequencing. My team at Global Research, along with GE Healthcare and the Museum, are now trying to improve methods of obtaining DNA from fresh and preserved historical samples of endangered species (like the giant squid you see below) in order to learn more about them. In the past the team has worked on methods to enzymatically amplify specimen DNA, long term preservation of samples, and the repair of specimen DNA that has been damaged by exposure to the environment (such as sunlight or oxygen). This work may seem very “Jurassic Park”-like and a bit far out, but if successful, the methods that we are researching will likely also help doctors obtain better genetic information from medical samples, as the methods of preservation for human biopsy samples are nearly identical to those used to preserve the museum samples.

I recently traveled to visit my collaborators and to attend a special symposium titled: “Sequencing the Red and the Dead” at The Linnean Society of London. The Linnean Society of London is the world’s premier society for the study and dissemination of taxonomy and natural history, and the symposium focused on new methods and issues associated with obtaining DNA from species that are extinct, or currently on the International Union for the Conservation of Nature and Natural Resources “Red List”. This Red List includes all species that are “Critically Endangered”. Critically endangered means that a species numbers have decreased, or will decrease, by 80% within three generations. After the symposium, there was a workshop where experts from across the field gathered to discuss how best to improve collection techniques and storage so that as new technology is developed, the historical samples will have as good a chance as possible of yielding more information about the different species. The presentations at the meeting discussed the various storage facilities at the San Diego Zoo, the Smithsonian Institute, and the Natural History Museum of London, along with the most recent methods being used to extract DNA from fresh and preserved specimens. Also, officials discussed government regulations on transport of samples from one research institute to another, and specialists discussed zoological and botanical issues with properly categorizing samples.

During the meeting I had the opportunity to tour the museum and once again visit the private “Tank Room”, where 250,000 different historical samples are stored in glass jars full of preservative. Particularly interesting is the 30 foot long giant squid, Architeuthis dux, and some of the samples obtained from the Galapagos Islands during Darwin’s development of the Theory of Evolution.

The original motivation of the GE Healthcare sponsored research collaboration was to explore the application of paper based sample storage using GE’s proprietary FTA products, towards further stabilizing samples that have been preserved using formaldehyde fixation. Dr. Michael Kenrick, who is based in Cardiff, Great Britain, is leading the GE Healthcare effort and Dr. Aidan Emery is leading the team out of the Natural History Museum.

The distinction between those two broad titles, “scientist” and “engineer”, is intuitively well understood by any stripe of technologist, yet still somehow resistant to a single, tidy, universally accepted definition. This fundamental question of what differentiates the two interested me enough to conduct an informal survey of my colleagues to see what they had to say. Here is a sampling of some of the more interesting and illuminating responses:

“A scientist develops concepts and principles about the natural world, while an engineer applies those validated concepts/principles toward making useful products.”

“Scientists answer the question ‘What is it?’ or ‘Is it possible?’ while engineers will then come in and answer the questions ‘What is it for?’ and ‘How do we make it better?’”

“The creative, disheveled, frustrating yet often brilliant ‘outside the box’ thinkers tend to be the scientists. The pragmatic, disciplined problem solvers, on the other hand, are the engineers. Really, you need both.”

“Basic research concerning the fundamental characteristics of nature is the realm of the scientist. Engineers are simply applied scientists who cover specific technologies. Descriptions for the scientist are pretty much limited to the basics: chemical, physical, biological. Engineers, on the other hand, are preceded by a much broader yet more specialized range of adjectives: electrical, software, chemical, genetic, civil.”

“Scientists will create some inefficient process which is still awesome because no one else thought of it before. Engineers will then come in and apply a bunch of math to improve that process.”

“Think Research & Development, R&D. Scientists are mostly responsible for the research part while engineers can take more of the credit for the subsequent development phase.”

“Just look at the word origins: science is Latin for ‘knowledge’ while the Latin translation for engineer is basically ‘one who operates a clever invention’. Scientists, then, accumulate knowledge, while engineers apply that knowledge toward ‘clever inventions’.”

Pretty fair descriptions, I would say. But regardless of exactly how you would define and distinguish the two, I think these comments all implicitly underscore the importance of both types for the creation of innovative new technology. If you can imagine (as I do!) modern research as a dynamic ballroom dance of disciplines and specializations, then scientists and engineers ultimately make not merely complementary—but pretty necessary—partners.

In  1900, life expectancy at birth in the United States was 47.3 years. In 2005, it was 77.8 years. This is a very good thing indeed, particularly when it corresponds with an increase in healthy years of life.

With longer life expectancy comes rising prevalence of chronic diseases associated with aging. One of these is Alzheimer’s disease.

The most common type of dementia, Alzheimer’s disease is a brain disorder that gradually destroys a person’s memory and ability to carry out daily activities. The greatest known risk factor is advancing age. Consider the following:

• One in 10 individuals over 65, and almost half over 85 are affected.
• It affects an estimated 5.3 million Americans
• Every 70 seconds, someone in America develops Alzheimer’s
• Because women live longer on average than men, women are more likely to have Alzheimer’s
• It costs our nation 172 billion dollars annually
• A rare, inherited form of the disease can strike individuals as early as in their 30’s or 40’s
• No “disease-modifying” treatment is currently available, although there are several drugs in clinical trials. Current FDA-approved drugs work by temporarily slowing down the worsening of symptoms.

Current diagnosis relies on clinical assessment of mental decline. The problem is by the time the patient shows these devastating symptoms; the brain has already undergone serious damage.

Our Healthcare and Biosciences groups at GE work very hard to develop ways to diagnose Alzheimer’s before the onset of these symptoms. This is particularly important because future disease-modifying treatment could then target the disease before irreversible brain damage has taken place.

One of the ways we can help overcome Alzheimer’s is to support the annual Memory Walk by the Alzheimer’s Association.  This is a nationwide event and you can find a walk in your local area. My colleague, Joanne Smith, has organized our Memory Walk team. The funds that we raise will help support research to treat and prevent Alzheimer’s, and programs and services to improve the lives of those afflicted with the disease and their families.

A passage in Mark Twain’s autobiography said that “There are three kinds of lies: lies, damn lies, and statistics”. Numbers certainly don’t tell the whole story. Participating in the walk has taught me a very valuable lesson: statistics are well and good, but nothing beats putting a face on Alzheimer’s.

As part of GE’s research program in molecular pathology, we have developed a breakthrough technology that enables us to identify and label multiple proteins, or disease markers, on a single slide. Basically, our technology is enabling pathologists to see more characteristics of a particular cancer than they could see before. The hope is that uncovering molecular information previously hidden from view will tell us more about cancer and how to treat it.

In the case of colon cancer, it’s well known that the risk of recurrence in stage 2 cases, can be difficult to predict . About one-fourth of these cases are higher risk than the rest. The hope is that new molecular insights gained from these studies will help to distinguish the high and low risk cases and ultimately, improve patient outcomes.

It’s exciting to be a part of this project and to work on a team with world class expertise in so many different areas. Recently, a Bloomberg News article highlighted GE’s increased commitment to R&D and our activity in the Life Sciences. Our work in molecular pathology and this project are great examples of how we are trying to make a difference in this space.

For all that we know about diseases such as cancer, much more is still unknown. With GE’s new cancer mapping technology, we’re working everyday to close this information gap.

BUT don’t be too sad…I am leaving you in good hands with Megan Rothney, a fellow member of Biosciences!  You may know her already because she has posted on Edison’s Desk before with articles, “Developing technology for health management” and “Battle of the bulge:  “Good fat” vs. “Bad fat”– and then of course, her campaign to have Barbie become the next computer engineer.  Megan has a Ph.D. in biomedical engineering from Vanderbilt, has a great sense of humor,  likes the Spice Girls and will you keep you up to date with all of the cutting edge research we’re doing here in Biosciences.

Thanks for letting me share our stories, it’s been fun!

Did you know…

• A sneeze can reach 100 miles per hour.
• Your heart pumps 8,000 gallons a day.
• Your circulatory system would wrap around the world twice.
• Your brain, while being only 3% of your weight uses 20% of your energy.
• The DNA in just your own body, if stretched out end-to-end would reach from Earth to Pluto and back again, 7 times.
• You are made up of 50 trillion cells, but you can carry 500 trillion microbes on and in you (you are more something else than you are “you”!)
• If all the elements contained in your body were removed and sold on the open market, you would be worth a little over a dollar.

Some of the parts he contains include speakers (a voice-box), a fish tank filter unit (his liver), a compact disk (his brain), some sections of wood held together end-to-end by rubber straps with sponge stuffing and bungie cords on either side (a knee joint with tendons, cartilage, and muscles), electric wiring (his nerves), rubber tubing (his circulatory system), and a complete life size intestinal tract. My presentation includes a slideshow that discusses some of the details related to each part. And of course, some of the different technologies that have been developed to examine each part (X-ray machines, MRI, CT, ultrasound, lateral flow test strips, DNA sequencing technology, microbial culturing tests). The presentation is targeted for 4th graders, but I have given the presentation to groups ranging from kindergarten up to high schoolers.

I recently developed a new presentation revolving around microbes that are found on and in people. I use the presentation as an opportunity to teach children about their own personal microbiome, and how they are really a collection of microbes. The presentation discusses microbes that grow on our bodies, which are responsible for all sorts of different bothersome observations. These include dandruff, body odor, colds and flu, athletes’ foot, and infections. I also include some clips of macrophage cells engulfing bacteria, and illustrations to give them an example of how small these things are. The presentation culminates in a hand-on demonstration in which the children have the opportunity to culture some of the microbes that are present on their body or on things they touch. They get petri dishes with standard bacterial growth media in them, and they can touch anything they want to the surface of the media.

Here is an image of a petri dish touched by a finger:

By the mouthpiece of a phone:

By a bathroom sink faucet:

By a kiss:

By a tongue:

They love this. They get to take the petri dishes home and watch them grow over the next week or so.

I really enjoy presenting to children. They tend to ask the most interesting questions, and they certainly remind us that science is indeed pretty cool. Putting these presentations together makes me sit back and think about the things that we sometimes take for granted, and how astounding they can be.

A skilled surgeon knows where the nerves are, but there are instances when precisely locating the nerves during surgery can be very challenging due to their small size, intricacy and variation in the anatomical location in each person.

That’s where we come in.  Our team comprising of chemists, biologists, and engineers has developed a group of fluorescent imaging agents to light up the nerves. Recently, we received a four-year,  ~4M grant from the National Institutes of Health to further improve the imaging agent and expand the capability of a compact imaging device that can be used in conjunction with the fluorescent agent (check out the story that Reuters put out this morning).  The goal is to provide surgical guidance safely and in real-time. Aside from prostate surgery, you can imagine that there are many more surgical procedures where nerve imaging could be used to improve the patient’s quality of life outcomes.

Following injection, the agent localizes to myelin, which is a layer of material that envelops the nerves.  It absorbs light from the imaging device then subsequently emits light at a longer wavelength, which is then captured and processed by the imaging device in real-time. In collaboration with Dr. John Frangioni’s lab at BIDMC, a peer-reviewed publication on some of the agents is in press. I’ll update this blog with a link once this work is published.

We believe this incredible technology, along with other fluorescent imaging agents such as one to light up the margin of a tumor, will one day make it possible for surgeons to better visualize parts of the anatomy, and improve patient outcomes while enhancing surgical efficiency.

The nerve glows reddish-orange with GE’s fluorescent labeling agent. The imaging agent exhibits some partitioning to fat tissue, where it glows with a greenish color. Note that the surrounding tissue, such as muscle, is dark. The image above is captured using a fluorescent imaging system with a colored camera.

Manager of IMILab in Biosciences, Kathy Bove, has sparked a competitive health challenge amongst her lab members.  Watch the video to learn what it’s all about.

The cool thing about this competition is that after performing the healthy tasks for one week, it almost becomes habit and easily fits into your schedule for the next week.  Take, flossing your teeth twice a day for example (Who does that?!?!) but when there are points and prizes involved it’s easy!  This week we are parking our cars by the helipad (trust me, it’s a looooong walk), no unhealthy snacks between meals, and performing one random act of kindness (for emotional health) to name a few.

If you work here, you should stop by the 5B hallway and see what we’re doing for next week.  If you don’t work here, download Morsel on your phones and keep track of your own points!

Though one can dig deeper into the medicine chest and discover alternatives, many of these drugs (such as the aminoglycosides) produce toxic side effects in addition to their seemingly inevitable induction of resistance.  In the last decade, there have even emerged strains resistant to vancomycin and other related glycopeptide antibiotics, the so-called “nuclear option” or last line of defense in the ongoing war against S. aureus.

At the risk of sounding like a hysterical doomsday prophet, this is only the beginning.  S. aureus is a Gram-positive bacteria.  Public health experts fear that Gram-negative pathogens may one day rival the deadly elusiveness of MRSA.  One such undesired candidate, Pseudomonas aeruginosa, has already given much of the public a vivid indication of its destructive potential.  Last year, it claimed the life of 20-year old Brazilian model Mariana Bridi Da Costa.  P. aeruginosa caused a urinary tract infection in Bridi which quickly spread throughout her body.  Septic shock soon followed.  In a desperate bid to save her life, doctors were forced to amputate her feet.  Her hands were next.  Eventually, her kidney and stomach were removed before she finally succumbed to the infection.

As tragic and gruesome as this death was, such infections from this bacterium are still rare.  The escalating indestructibility of another Gram-negative bacteria, Klebsiella pneumoniae, represents the bigger concern.  In 2003, K. pneumoniae resistant to carbapenems, a class of b-lactam antibiotics specific for Gram-negative bacteria, made a depressingly auspicious debut in the form of outbreaks at two separate New York City hospitals.  Sixty patients became infected.  Nearly half of them died within 2 weeks.  Since then, eight other states have reported the emergence of these strains.  And to come full circle, doctors have recently found strains of E. coli—and yes, P. aeruginosa—that possess a similarly deadly resistance to carbapenems.

All of this points to the diverse and effective array of means by which pathogens confer their antibiotic resistance to not only their neighbors and their progeny, but to those of other genera—or even other orders.  Intrinsic resistance, in which beneficial point mutations are passed on from one bad bacterial parent to its child, represents the classic evolutionary process.  It’s slow and rare, but still an important concern under the selective pressure of antibiotic treatment.  That is, the often-publicized/criticized tendency of individuals to not take their full prescription of antibiotics once they start to feel better is a recipe for encouraging intrinsic resistance in those lingering Darwinian survivor bugs.

A bigger concern, however, is the various mechanisms of acquired resistance by which bacteria horizontally transfer mobile resistance genes to each other.  Bacteria can, to put it crudely, have “sex” and thus transfer extrachromosomal plasmids to each other during a process known as conjugation.  Transduction, in which genes are transferred from one bacterium to another by way of bacteriophage middlemen, may also occur.  Finally, bacteria can soak up free DNA floating around in solution via transformation processes.  If you couple this with a fourth means of DNA transfer, transposition, by which mobile DNA can bounce back and forth between plasmids and the genome, then you have far too many options for moving around the genes of antibiotic resistance.  Keep in mind that there are over 2 quadrillion bacterial cells in the human body (that’s 20 times more than the number of human cells).  While most of these bugs are harmless—with many even being probiotic (i.e. healthy or beneficial like yogurt cultures)—this still represents an enormous, ever-present, ongoing swap meet of genetic information.  It is thus not surprising that a few destructive elements would emerge.

Though antibiotic resistance still pales next to heart disease and cancer in the rogue’s gallery of disease-related killers, it is nonetheless responsible for tens of thousands of deaths each year.  Thankfully, plenty of potential still exists for new therapeutic breakthroughs.  Alternative synthetic scaffolds, such as those derived from antimicrobial defensins, nisin peptides, or polyketide synthetase (PKS) modules, represent interesting bio-inspired alternatives to the traditional chemical classes of antibiotics.  Moving away from small molecules, additional genome sequencing of pathogens may reveal new antigens for vaccine development.  Also, new determinants derived from virulence factors may emerge.  Bacteriophage can potentially be hijacked and converted into delivery systems that combat antibiotic-resistant pathogenic strains.  Though the broad range of options available for genetic transfer clearly accounts for the rapid emergence of antibiotic resistance, they may also offer an equally broad range of new—and as yet undiscovered—therapeutic targets.  All in all, there is at least a fighting chance that the depressingly adaptable “superbugs” will someday meet an arch nemesis that they cannot evade.

A report from the Centers for Disease Control (CDC) on the growing trend of MRSA hospital infections:

http://www.cdc.gov/eid/content/13/12/pdfs/1840.pdf

The iconic former Chairman and CEO of GE, Jack Welch, has recently been added to the list of Staph infection victims . . . and survivors:

http://www.bloomberg.com/apps/news?pid=20601109&sid=ap3ENxAYX0Ng

The dangerous potential of Gram-negative bacteria:

http://www.cnn.com/2009/HEALTH/dailydose/02/20/gram.negative.bacteria/index.html

The tragic death of Mariana Bridi Da Costa:

http://www.huffingtonpost.com/2009/01/24/mariana-bridi-dies-miss-w_n_160551.html

The unfortunate emergence of antibiotic resistant K. pneumoniae:

http://knol.google.com/k/klebsiella-pneumoniae-carbapenemases-kpc

A general overview of just some of the strategies for overcoming antibiotic resistance:

http://www.ncbi.nlm.nih.gov/pubmed/10904248

The award is given to a promising young scientist in the molecular biology field at the onset of their career.  Grand prize includes: $25,000 cash, a trip to Stockholm, Sweden to accept the award

Entrants must submit a 1000 word essay describing their thesis work in molecular biology.  Visit www.gescienceprize.org for more details and submit an application.

Good Luck, and don’t forget who told you !

As I mentioned before, I recently earned my first patent while working on the Optical Tumor Margin Project (more on this project in a future post!). What made this achievement even greater was that my Great-Grandfather, Alton Foote, worked for GE and earned 14 patents developing filaments for lamp bulbs. He is the first from the left in this photo.

In 1953 he was the head of GE’s Large Lamp Department at Nela Park in Cleveland, Ohio and was responsible for the research and development of the Quartzline halogen lamps. Although I never knew my Great-Grandfather, I’ve learned about his life and accomplishments from my Grandfather who said he would’ve been proud! The picture below show our patent awards side by side (they were much heavier back in the ‘50’s!) and after that, a photo of us working side by side in the lab (in a manner of speaking).

To read more about my great grandfather’s invention and other historical breakthroughs, check out this Web site.

However, as you’ve made it this far, hope you enjoy the blog and leave any questions or comments behind!  Happy April!

Disclaimer:  Sorry for the wiggly camera.  I had been holding the FLIP for 30 minutes prior to this clip.  It’s a little difficult to hear if you don’t have speakers on your computer.  Here is the transcription below:

Audience member:“What are some things that would be important for young leaders, or the next generation of leaders to be exposed to early on?”

Tom Quick: “For me, it is what can we do for folks that are on the RELP program or anywhere, it is saying to yourself, “What triggers us thinking about: I going to do for someone to say, “That’s leadership.” I don’t think we do that enough.

Mark Little: “And to build on that, I see this in technology, but I think it pertains to anything.  Having a core to build on is really important.  You have to have a set of accomplishments or you have to be good in some area for someone to give you a chance at your first management job.  And I see this over and over again, getting that first management job is the toughest thing because you have to have domain expertise for someone to take a chance on you.  And they have to believe that you actually have potential.  But once you show you can be a leader, you can do almost anything.  People are much more ready to take a chance on you for other things. Demonstrate some skills, have some core expertise, build on that, land your first management job, and go from there.  And I really believe what you said Tom too, people get sometimes narrowly focused in their functional area and they’re not looking around.  If you build that core expertise that I was talking about, just be aware of other things going on.  Listen and learn and engage with other people outside your own area, definitely helps a lot.

Steve Bolze: “And the only thing that I’d add to that.  Let’s say you’re new to the facility here and let’s say you are in the engineering area, find a time to walk the factory.  Find a time to go see the remote diagnostics center.  Find a time to attend some of these other sections.  Branch out.  I think the sooner people branch out and understand what else is going on, it really helps you long term.

Check out the link below to read an article on the event.

The ACBJ used a diverse set of criteria ranging from environmental factors (such as traffic congestion, water quality, and carbon emissions) to support of energy efficient building projects.  They then determined their rankings by compiling an equally broad range of data originating from both government and independent research agencies.  Perhaps most impressively—and that which is most directly related to Global Research’s own ecomagination projects—is the fact that the capital district ranked No. 1 in green jobs per capita.

While Albany is not quite as impressive as west coast cities Portland and San Francisco (which took the top two spots), we at Global Research in Niskayuna can take more than a little pride in contributing to both the sustainability of, and technological innovations for, our surrounding community.  All in all, yet another reason to celebrate St. Patrick’s Day—just in case anyone really needed another reason to celebrate.

http://www.dailygazette.net/Default/Skins/SPE/Client.asp?Enter=true&skin=SPE&Daily=SPE&BaseHref=SPE/2010/02/20&AppName=1

You’ll see quotes from Senior Vice President Mark Little (whose blog entry on Huffington Post I linked to recently), Biosciences Global Techonolgy Leader Christoph Hergersberg, In Vivo Molecular Imaging Lab Manager, Kathy Bove, and fellow blogger Megan Rothney (talking about fat again!).   John Nelson, Bob Filkins, and John Burczak are also highlighted for their work on DNA Sequencing and Digital Pathology.

Megan’s entry last week on our project inspired me to voice my thoughts as well.  Many of them echo what Megan wrote. First, think back to the Superbowl.  How often during the football game were you surprised at how overweight some of the players seemed? Or have you ever wondered why all those 200 lbs plus Sumo wrestlers are not succumbing to obesity related diseases?

For years obesity has been defined using the Body Mass Index (BMI), a measure of a person’s overall weight to height ratio. A BMI of greater than 30 puts you in the obesity dungeon. The waist to hip ratio, which operates under the premise that abdominal fat is the most harmful of body fat, is another commonly used indicator of health. However, Megan pointed out in her entry that not all fat is created equal and that the fat around the abdomen can be especially misleading. In recent studies on adults in the United States 23.5% of normal-weight adults were metabolically abnormal while 51.3% of overweight adults had a healthy metabolism.

So, “visceral fat” or”bad fat” as Megan calls it, is what makes some slim people unhealthy.  Though it’ll keep you looking good in a bikini, visceral fat is more dangerous than the subcutaneous fat and has been linked to cardiovascular disease, diabetes and even some types of cancer.

I wanted to expand on Megan’s entry and explain that X-ray absorption is related to the subject’s bone density; the great the density the stronger the signal recorded by the scanner. GE’s Lunar iDXA scanner is a cheaper, low dose alternative to MR and CT, that allows direct measurement of fat and lean tissue distributions and is a gold standard for bone density measurement. Developing technology that enables the iDXA scanner to quantify levels of fat, lean and bone mass in the entire human body will allow a more accurate and reliable assessment of health and in turn, a better chance at diagnosis and preventive medicine.

‘So, the next time your skinny couch potato friend proclaims, “I don’t need exercise. I have higher metabolism!” Don’t fret, MRI data of those Sumo wrestlers show that their visceral fat deposits are negligible. Won’t you rather be an active fat-boy slim than a slim-boy fat?  Megan and I will be hitting the gym now… check back for more blog entries to come.