Treating Fat with Fat

Is brown fat ready for therapeutic prime time?

By | May 1, 2012

image: Treating Fat with Fat Istockphoto.com, Mik122

ISTOCKPHOTO.COM, MIK122

Nearly 500 million adults worldwide are obese—close to 10 percent of men and 14 percent of women, an incidence twice as high as in 1980, according to the World Health Organization. Obesity, defined as a body mass index of 30 or greater, has been linked with higher rates of serious illnesses such as cancer, heart disease, arthritis, and diabetes. But an obesity drug hasn’t been approved in the United States since 1999.

The regulatory environment for this class of drugs remains extremely tough following high-profile failures in the 1990s. For example, the infamous fen-phen drug combo caused life-threatening side effects and became one of a number of approved drugs removed from the market because of health concerns. “Obesity is the toughest market to get into,” says Praful Mehta, a senior analyst from IHS Global Ltd., a market research company. This is in part because obesity is not an immediately life-threatening disease, so side effects that are acceptable for the treatment of diseases like cancer are unacceptable when treating obesity.

Despite these odds, Lou Tartaglia decided that now was the perfect time to start a company to target obesity. A scientist turned venture capitalist, Tartaglia is betting on the newest science in this area: brown-fat biology. Unlike white fat cells, which get their name from the excess lipids they store and whose relatively few mitochondria transfer energy from the lipids and sugars to the energy-storing molecule ATP, brown fat cells’ many mitochondria contain an “uncoupling protein” that allows them instead to release the energy from sugars and lipids as heat—to warm hibernating animals, for example. Researchers think that by increasing the numbers of brown fat cells in adults, or by activating those that already exist, they will be able to help people burn calories, shedding extra pounds as a result. In contrast to previous efforts that tried to curb food cravings via compounds that acted on the central nervous system, brown-fat therapies would attack the problem by increasing energy expenditure, even while at rest. In addition, activating brown fat cells could help diabetic patients improve blood glucose control by increasing sensitivity to insulin.

Nearly 500 million adults worldwide are obese—an incidence twice as high as in 1980—yet an obesity drug hasn’t been approved in the United States since 1999.

With research findings continuing to endorse brown fat as a promising target for tackling obesity, Tartaglia and his colleagues decided to make the commercial leap. In December 2011, with $34 million in financing from Third Rock Ventures, where Tartaglia is a partner, they launched Ember Therapeutics in hopes of leveraging the work from the labs of its scientific founders and advisors, such as Bruce Spiegelman, whose lab at the Dana-Farber Cancer Institute discovered a hormone called irisin that appears to make white fat behave like its brown counterpart. “We’ve tied up the real A-team in brown fat in one company,” says Tartaglia.

And Ember isn’t the only company trying to capitalize on the growing promise of  brown-fat therapies. Several other companies—both large and small—have also jumped onto the brown-fat bandwagon over the last few years. Still, the obstacles in this area are many, from the scientific to the regulatory, and it remains to be seen whether this new target can deliver on the excitement that it has been generating.

Feel the burn

Brown fat, found only in mammals, has long been known to play a role in keeping hibernating animals and newborns warm by directing the conversion of calories into heat, rather than chemical energy, within the mitochondria. Three decades ago, however, researchers uncovered the tissue’s link to metabolism, revealing a whole new function for brown fat. In 1979, Michael Stock and Nancy Rothwell at St. George’s Hospital Medical School, University of London, fed rats a “cafeteria” diet—a choice of palatable foods, which tempts the rodents to overeat—and were surprised to find that the rodents’ weight gain, while substantial, was not proportionate to their calorie intake. On dissecting the gluttonous rats, they found that the mass of brown fat in their bodies had doubled, apparently increasing their metabolic rate to help them burn off the excess fuel. This pointed to brown fat as possible target to fight obesity. But in humans, investigators could only find definitive evidence of brown fat in babies and in adults who worked in cold temperatures, causing interest in the tissue to wane.

LOOKING AT FAT: Eric Ravussin (right) of Pennington Biomedical Research Center in Baton Rouge, Louisiana, and two of his mentees, Madlyn Frisard and Anthony Civitarese, read a Western blot to look at proteins important in the development of brown adipose tissue.
LOOKING AT FAT: Eric Ravussin (right) of Pennington Biomedical Research Center in Baton Rouge, Louisiana, and two of his mentees, Madlyn Frisard and Anthony Civitarese, read a Western blot to look at proteins important in the development of brown adipose tissue.
PENNINGTON BIOMEDICAL

Then, in the early 2000s, as radiologists were screening cancer patients using PET and CT scans to detect and identify tissues with rapid metabolism, such as tumors, they noticed several areas around the collarbone, neck, and upper back that also lit up. “They found lots of interesting spots that had nothing to do with the tumor,” says human physiologist Eric Ravussin of Pennington Biomedical Research Center in Baton Rouge, Louisiana. Then in 2009, three groups (including one led by a scientific founder of Ember Therapeutics and one led by a scientific advisor) published back-to-back papers in the New England Journal of Medicineshowing definitive evidence—including biopsy samples from patients undergoing surgery for other reasons—that brown fat does indeed exist in adult humans. And just as in rats and mice, lean people generally have more active brown fat than those who are obese.

By this time, researchers, including Spiegelman, had made substantial progress working out the molecular pathways involved in white and brown fat development. (Read Spiegelman’s article “The Skinny Fat,” The Scientist, January 2008.) In 2007, Spiegelman found a gene called PRDM-16 that appeared to turn on the expression of all of the other genes that guided the differentiation and function of brown fat, including the uncoupling protein that makes mitochondria burn hot by shifting cellular metabolism away from the production of ATP.

Most recently, in early January 2012, just a month or so after the launch of Ember, Spiegelman’s group published work on another molecule involved in the brown fat story, which they named irisin after the Greek messenger goddess Iris. The hormone, which appears to be produced by muscles during activity, helps to convert stores of white fat cells into energetically active brown fat cells. In addition, irisin appeared to stabilize blood glucose levels and increase sensitivity to insulin.

“When people talk about groundbreaking innovation [in this field], [irisin] is what they’re talking about at the moment,” says Mehta, who analyzes the health-care and pharma sectors for IHS. To fully capture the obesity and diabetes markets, drugs must focus on three areas, says Mehta: energy expenditure, glucose disposal, and insulin sensitivity. “A platform that can [increase] all three has a greater chance than anything” to make it in the marketplace, he says. The potential payoff is huge, ringing in at an estimated $1.1 billion a year for obesity and $16 billion annually for diabetes.

But there’s a long road ahead for irisin, says Ravussin, recalling the story of leptin, another hormone that just a few years ago had people extremely excited. (See “Hormones in Concert,” The Scientist, December 2009.) “When leptin was described, people thought it would cure obesity,” says Ravussin. But after promising results in mice, the hormone turned out to be a complete bust in the clinic. Humans who already expressed the hormone didn’t respond to greater amounts, and further studies revealed leptin’s role in regulating many other functions, such as immunity, bone health, and normal menstrual periods. “What are we going to find out about irisin in the next 2 years?” wonders Ravussin.

In the running

Irisin isn’t the only new target on the block. Preclinical data on brown fat’s effectiveness in fighting obesity and diabetes have been encouraging enough for several pharma companies to develop programs to target the tissue. Both Genentech, now backed by Roche, and Eli Lilly are focusing on another hormone that affects brown-fat biology: fibroblast growth factor 21 (FGF21). Genentech is developing an agonist antibody that mimics the action of FGF21 by binding to and activating its receptor, FGFR1, while Eli Lilly chose to focus just upstream, developing a small molecule that activated FGF21 production. And though Lilly has since dropped this particular effort, “we remain keenly interested in this new area of biology and continue our research and development efforts to further study its potential,” said David Moller, vice president of endocrine and cardiovascular research at Eli Lilly. Once again, however, the cautionary tale of leptin rears its ugly head: a study published in February showed that increased exposure to FGF21 may also change the biology of bone-making cells, and ultimately could make bones more fragile.

TARGETING STEM CELLS: The Energesis team, including senior scientist Scott Gullicksen (left), CSO and cofounder Olivier Boss (center), and COO and cofounder Brian Freeman, is targeting human brown adipocyte stem cells (bottom, after differentiation into brown adipocytes) to search for novel obesity drug targets.
TARGETING STEM CELLS: The Energesis team, including senior scientist Scott Gullicksen (left), CSO and cofounder Olivier Boss (center), and COO and cofounder Brian Freeman, is targeting human brown adipocyte stem cells (bottom, after differentiation into brown adipocytes) to search for novel obesity drug targets.
ENERGESIS PHARMACEUTICALS

Another brown-fat contender is peroxisome proliferation-activated receptor gamma, or PPAR-?, a nuclear receptor that activates FGF21 production and is also regulated by it, originally discovered by Spiegelman in 1994 as the master regulator of white-fat development. Researchers later learned that PPAR-? also decreases insulin resistance, while promoting brown fat growth—a win-win for diabetics. In fact, a class of antidiabetic compounds called thiazolidinediones (TZDs) or glitazones, introduced in the mid-1990s, appears to have unknowingly targeted PPAR-?, resulting in improved glucose uptake and insulin sensitivity. Retrospective studies showed that patients who took these drugs also suffered from increased weight gain, risk of cardiovascular events, and in some cases cancer, however, causing pharma and biotech companies to shy away from the molecule.

“PPAR-? is not our favorite target,” says Brian Freeman, CEO and cofounder of Energesis, a company founded in late 2009 that’s using brown fat “stem cells”—precursor cells found in skeletal muscle that can differentiate into either muscle or brown fat—to search for novel brown-fat targets. Energesis’s scientists are working on proprietary new target molecules that activate brown fat, as well experimenting with transplantations of the muscle precursor cells primed to differentiate into brown fat.

But Ember isn’t giving up on PPAR-? just yet, and it’s focusing on a new molecule that activates the positive antidiabetic effects of PPAR-? while bypassing some of the adverse effects associated with TZDs.  Ember is also looking more carefully at the PRDM-16 transcription factor that influences brown-fat function, continuing to pursue possibilities with irisin, and even investigating a fourth molecule called FoxC2, which appears to sensitize brown fat so that it converts energy into heat at room temperatures, rather than only in the cold. “We’re looking at quite a number of targets,” says Tartaglia.

While many challenges remain, including the regulatory hurdles of the obesity market and the fact that many countries don’t offer reimbursement for obesity treatments because it’s not usually considered a life-threatening disease, Ember and Energesis both have plans to start clinical trials for their brown fat therapies within 2 to 3 years. Despite the risks, “many companies do see brown fat as the best approach to combat these diseases safely,” says Tartaglia.

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Comments

May 8, 2012

It's funny.
Trying to invent a fat burning patentable molecule is just like bovine droppings.

Mother Nature has already crated a remedy for obesity. Just skip the carbohydrates and have animal fat instead. Then you'll decrease in weight if you are obese.
The old pig farmer knew precisely how to get a fat pig for Christmas. Let the pig eat lightly milled grain and boiled potatoe. The lightly milled grain is now renamed by the food industry to Extra Fiber Rich Pasta.

So by eating grain products and potatoes you will gain in weight, exactly the same food the pigs ate previously to gain weight.

The modern slim pig eats protein and a lot of fat to stay lean. We should do the same.

So Mother Nature is fixing the obesity epidemic if we listen to Mother Nature that created us carnivores, not herbivores.

Avatar of: yeruham

yeruham

Posts: 9

May 8, 2012

I've got something better than skipping the carbohydrates. Exercise a lot and eat all you want of anything you want.
Best to all,
Dr Frank J. Leavitt ("Yeruham")
Senior Lecturer Emeritus
Ben Gurion University

May 8, 2012


 
 It is  high time that we understand the wisdom behind our tradition and
culture including our food habits. The society we live in is influenced
by our health. We need to understand the impact and miscegenation of
habits like culture of other regions including food habits on our
society. Every region and race has evolved over the years adopting the
rightful mixture of food habits suited to the genetic constitution and
physical attributes of personality of the race. Take the example of a
camel which stores lipids both as a source of fuel and water derived
from metabolism. This holds good for humans also. Our physical
constitution has been tuned to the food habits and the environment we
live in. It is high time that we take serious stock of the situation the
world is facing due to this neglected aspect of human health.

'Gluttony is the culprit of adiposity and gourmet the panacea of health'- is it time for us to think more of habits than the science behind certain preventable causes of ill-health including obesity.
dhastagir sheriff
department of biochemistry
Faculty of Medicine
Benghazi University
Benghazi,Libya

Avatar of:

Posts: 0

May 8, 2012

It's funny.
Trying to invent a fat burning patentable molecule is just like bovine droppings.

Mother Nature has already crated a remedy for obesity. Just skip the carbohydrates and have animal fat instead. Then you'll decrease in weight if you are obese.
The old pig farmer knew precisely how to get a fat pig for Christmas. Let the pig eat lightly milled grain and boiled potatoe. The lightly milled grain is now renamed by the food industry to Extra Fiber Rich Pasta.

So by eating grain products and potatoes you will gain in weight, exactly the same food the pigs ate previously to gain weight.

The modern slim pig eats protein and a lot of fat to stay lean. We should do the same.

So Mother Nature is fixing the obesity epidemic if we listen to Mother Nature that created us carnivores, not herbivores.

Avatar of:

Posts: 0

May 8, 2012

I've got something better than skipping the carbohydrates. Exercise a lot and eat all you want of anything you want.
Best to all,
Dr Frank J. Leavitt ("Yeruham")
Senior Lecturer Emeritus
Ben Gurion University

Avatar of:

Posts: 0

May 8, 2012


 
 It is  high time that we understand the wisdom behind our tradition and
culture including our food habits. The society we live in is influenced
by our health. We need to understand the impact and miscegenation of
habits like culture of other regions including food habits on our
society. Every region and race has evolved over the years adopting the
rightful mixture of food habits suited to the genetic constitution and
physical attributes of personality of the race. Take the example of a
camel which stores lipids both as a source of fuel and water derived
from metabolism. This holds good for humans also. Our physical
constitution has been tuned to the food habits and the environment we
live in. It is high time that we take serious stock of the situation the
world is facing due to this neglected aspect of human health.

'Gluttony is the culprit of adiposity and gourmet the panacea of health'- is it time for us to think more of habits than the science behind certain preventable causes of ill-health including obesity.
dhastagir sheriff
department of biochemistry
Faculty of Medicine
Benghazi University
Benghazi,Libya

Avatar of:

Posts: 0

May 9, 2012

I dislike that this research doesn't address what activating brown fat may do to the rest of the body. A mitochondrial agonist was used for weight loss treatment in the 30's that switched activity from ATP production to heat generation. This ended up killing people though (for reference, http://news.sciencemag.org/sci...

Avatar of: Aaron Mercer

Aaron Mercer

Posts: 1457

May 9, 2012

I dislike that this research doesn't address what activating brown fat may do to the rest of the body. A mitochondrial agonist was used for weight loss treatment in the 30's that switched activity from ATP production to heat generation. This ended up killing people though (for reference, http://news.sciencemag.org/sci...

Avatar of: Daniel Ryder

Daniel Ryder

Posts: 1

May 18, 2012

Hi Aaron, I tried to find you reference but it was not working. Can you repost please.

May 18, 2012

Mastering the Zone. Dr Sears

Avatar of:

Posts: 0

May 18, 2012

Hi Aaron, I tried to find you reference but it was not working. Can you repost please.

Avatar of:

Posts: 0

May 18, 2012

Mastering the Zone. Dr Sears

Avatar of:

Posts: 0

May 19, 2012

Utilizing your conscious mind to learn a behavior that is based in modern day society to achieve an ideal weight ie: learning to eat for our modern rich environent instead of living in our subconscious fight or flight mode. It takes a month to learn a new habit... leanrn to work smart not hard and adapt to modern day America, it is not difficult just simple math and a little education.

Avatar of: Consciousthought

Consciousthought

Posts: 1

May 19, 2012

Utilizing your conscious mind to learn a behavior that is based in modern day society to achieve an ideal weight ie: learning to eat for our modern rich environent instead of living in our subconscious fight or flight mode. It takes a month to learn a new habit... leanrn to work smart not hard and adapt to modern day America, it is not difficult just simple math and a little education.

Avatar of: Luciana Gravotta

Luciana Gravotta

Posts: 1

May 29, 2012

It seems to me that the motivation behind these treatments is profit, not the desire to ease the obesity epidemic. The best solution to fighting obesity is policy. Schools need to educate students about diet and exercise. Governments need to bare down on fast-food chains and junk-food companies with stricter regulations (already nutrition fact labels on all foods is a step in the right direction). In poor neighborhoods, exercise facilities should be subsidized.

Right now, buying junk food and processed food is cheaper than buying fresh food. This does not leave poor families much of a choice and exacerbates the obesity problem.

According to Faulkner et al. (2011), "Based on empirical evidence and expert opinion, three recommendations
were supported. First, to create and implement an effective health
filter to review new and current agricultural polices to reduce the
possibility that such policies have a deleterious impact on population
rates of obesity. Second, to implement a caloric sweetened beverage tax.
Third, to examine how to implement fruit and vegetable subsidies
targeted at children and low income households."

(References: http://www.ncbi.nlm.nih.gov/pu... and http://www.nature.com/ejcn/jou....

Avatar of:

Posts: 0

May 29, 2012

It seems to me that the motivation behind these treatments is profit, not the desire to ease the obesity epidemic. The best solution to fighting obesity is policy. Schools need to educate students about diet and exercise. Governments need to bare down on fast-food chains and junk-food companies with stricter regulations (already nutrition fact labels on all foods is a step in the right direction). In poor neighborhoods, exercise facilities should be subsidized.

Right now, buying junk food and processed food is cheaper than buying fresh food. This does not leave poor families much of a choice and exacerbates the obesity problem.

According to Faulkner et al. (2011), "Based on empirical evidence and expert opinion, three recommendations
were supported. First, to create and implement an effective health
filter to review new and current agricultural polices to reduce the
possibility that such policies have a deleterious impact on population
rates of obesity. Second, to implement a caloric sweetened beverage tax.
Third, to examine how to implement fruit and vegetable subsidies
targeted at children and low income households."

(References: http://www.ncbi.nlm.nih.gov/pu... and http://www.nature.com/ejcn/jou....

Avatar of:

Posts: 0

May 30, 2012

Another fundamentally wrong way to address obesity.  What needs to be researched and fully understood is the real source of the rise in obesity.  It is not likely that "eating habits" are the cause.  Obesity can be seen as a hormone regulation disorder.  I think it would be more profitable to research all the industrial chemicals humanity is subjected to.  The hormone disrupting effects of food additives, pesticides, "fragrances", clothing additives, food container plastics... The ubiquity of exposure to these things is a more plausible and sensible avenue for research as the hormone disrupting effects of a few of them are known. Most have not been looked at for this purpose and we are stupid not to.

The approach of assuming one or a couple of stem cell metabolic adjustments will take care of the problem with no adverse side effects strikes me as willfully ignorant.  The whole system of hormonal balance, interaction, function and regulation needs to be understood before it can be imagined as safe to promote fundamentally modifying one part of it. And it is clearly not fully understood as a whole system.

This is the same problem as in industrial agriculture and they could be related problems.  Working against natural systems rather than fully understanding natural systems and working with them have in the short run made lots of cheap food available.  In the long run, we may be damaging our ecology in ways we don't yet understand that may be devastating to humanity in the future.  And even in the short run issues like multiple pesticide resistant superweeds and the fundamental issue of continued dependence on fossil fuels, threaten the industrial agriculture approach we subject ourselves to.  It is obviously not a sustainable model in the long term, and it is ridiculous not to be moving to a long term sustainable model of agriculture as national and international policy.

It is the drive for money that pressures us to be exposed to possible poisons and toxins and eat crap food.  So, obesity is a symptom of a much larger problem humanity faces.  Brown fat cells, while interesting as part of the whole metabolic system, are not the solution to obesity.  Better science and harmony with nature is the solution.  I propose that the US fund vastly more basic research in biology so we can work with nature and not against it.  I'm sure there will be other models for profit if we must have that. But the current monsanto, brown fat, ignoring the whole system approach should be abandoned with fuller, better science, and a long term perspective.

Avatar of:

Posts: 0

May 30, 2012

Google "dinitrophenol".

Avatar of:

Posts: 0

May 30, 2012

I agree completely.  Brown fat has been evolved into the physiological core of small mammals for millions of years.  One cannot simply think about throwing in stem cells or converting targets or enzymes or whatever without definitely knowing about the myriad of effects on many, many other physiological and metabolic systems.  "Two to three years" for clinical studies?  Forget that.  I'm sure the regulatory bodies are going to want to see several large animal pre-clinical safety and efficacy studies before anything is let out into the clinic, and none of that was even mentioned in the article.

Oh, and by the way, has anyone even thought about how people will feel with areas of their body constantly being on fire?  Animals turn on their brown fat when it's cold, and the thermoregulatory balance between the environment and metabolism makes their existence more comfortable.  With so much brown fat heat generation going on in our comfy, thermoneutral homes, workplaces, and automobile, people will be sweating, irritable blobs screaming to turn on the air conditioner.

Paul M. Stein

Avatar of: UpComing1

UpComing1

Posts: 1

May 30, 2012

Another fundamentally wrong way to address obesity.  What needs to be researched and fully understood is the real source of the rise in obesity.  It is not likely that "eating habits" are the cause.  Obesity can be seen as a hormone regulation disorder.  I think it would be more profitable to research all the industrial chemicals humanity is subjected to.  The hormone disrupting effects of food additives, pesticides, "fragrances", clothing additives, food container plastics... The ubiquity of exposure to these things is a more plausible and sensible avenue for research as the hormone disrupting effects of a few of them are known. Most have not been looked at for this purpose and we are stupid not to.

The approach of assuming one or a couple of stem cell metabolic adjustments will take care of the problem with no adverse side effects strikes me as willfully ignorant.  The whole system of hormonal balance, interaction, function and regulation needs to be understood before it can be imagined as safe to promote fundamentally modifying one part of it. And it is clearly not fully understood as a whole system.

This is the same problem as in industrial agriculture and they could be related problems.  Working against natural systems rather than fully understanding natural systems and working with them have in the short run made lots of cheap food available.  In the long run, we may be damaging our ecology in ways we don't yet understand that may be devastating to humanity in the future.  And even in the short run issues like multiple pesticide resistant superweeds and the fundamental issue of continued dependence on fossil fuels, threaten the industrial agriculture approach we subject ourselves to.  It is obviously not a sustainable model in the long term, and it is ridiculous not to be moving to a long term sustainable model of agriculture as national and international policy.

It is the drive for money that pressures us to be exposed to possible poisons and toxins and eat crap food.  So, obesity is a symptom of a much larger problem humanity faces.  Brown fat cells, while interesting as part of the whole metabolic system, are not the solution to obesity.  Better science and harmony with nature is the solution.  I propose that the US fund vastly more basic research in biology so we can work with nature and not against it.  I'm sure there will be other models for profit if we must have that. But the current monsanto, brown fat, ignoring the whole system approach should be abandoned with fuller, better science, and a long term perspective.

Avatar of: Paul M. Stein

Paul M. Stein

Posts: 1457

May 30, 2012

Google "dinitrophenol".

Avatar of: Paul M. Stein

Paul M. Stein

Posts: 1457

May 30, 2012

I agree completely.  Brown fat has been evolved into the physiological core of small mammals for millions of years.  One cannot simply think about throwing in stem cells or converting targets or enzymes or whatever without definitely knowing about the myriad of effects on many, many other physiological and metabolic systems.  "Two to three years" for clinical studies?  Forget that.  I'm sure the regulatory bodies are going to want to see several large animal pre-clinical safety and efficacy studies before anything is let out into the clinic, and none of that was even mentioned in the article.

Oh, and by the way, has anyone even thought about how people will feel with areas of their body constantly being on fire?  Animals turn on their brown fat when it's cold, and the thermoregulatory balance between the environment and metabolism makes their existence more comfortable.  With so much brown fat heat generation going on in our comfy, thermoneutral homes, workplaces, and automobile, people will be sweating, irritable blobs screaming to turn on the air conditioner.

Paul M. Stein

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
LI-COR Biosciences
LI-COR Biosciences
Advertisement
PITTCON
PITTCON
Life Technologies