Bio Job Blog : Bio Jobs : Biotechnology Jobs : Biopharmaceutical Jobs : Bioscience, Biotech Jobs : Bio Job Blog : Biocareer : Bio-Business Training, Biotechnology Training : Jobs in Biology : Internships in Biology : Internships in Biotechnology

Vincent, Michael, and Stanley recorded episode #8 of the podcast This Week in Microbiology live at the 2011 ASM General Meeting in New Orleans, with guests Andreas Baümler, Nicole Dubilier, and Paul Rainey. 

They spoke about how pathogens benefit from disease, symbioses between chemosynthetic bacteria and marine invertebrates, and repetitive sequences in bacteria.

Hosts: Vincent Racaniello, Michael Schmidt, Stan Maloy, Andreas Baümler, Nicole Dubilier, and Paul Rainey.

Right click download TWiM #8  (60 MB, .mp3, 86.5 minutes).

Links for this episode:

• Salmonella invasion from the gut lumen into tissues (PLoS Pathogens)
• Symbiotic diversity in marine animals (Nature Rev Micro)
• REPINs, a new family of mobile DNA bacteria (PLoS Genetics, In Press)
• Letters read on TWiM #8

Subscribe to TWiM (free) on iTunes, Zune Marketplace, via RSS feed, by email or listen on your mobile device with the Microbeworld app.

Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv , or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

 Until next time...

Good Luck and Good Listening!!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

On episode #4 of the podcast This Week in Microbiology, Vincent, Cliff, Margaret, and Michael review foodborne bacterial illness in the context of outbreaks associated with cantaloupes and Lebanon bologna.

Right click to download TWiM #4 (51 MB .mp3, 75 minutes).

Links for this episode:

• CDC statement on Salmonella outbreak
• CDC statement on E. coli outbreak
• CIDRAP summaries of cantaloupe and bologna associated outbreaks
• ProMedMail summary of Salmonella outbreak
• Summary of food related illness in US (pdf)
• Food safety and irradiation (CDC)
• Geosmin (thanks, Atila!)
• Letters read on TWiM #4

Subscribe to TWiM (free) on iTunes,  Zune Marketplace, via RSS feed, by email or listen on your mobile device with the Microbeworld app.

• Email This
• Print
• Comments
• Trackbacks
• Share Link

The almost two-year manufacturing woes of orphan drug manufacturer Genzyme have been well documented and publicized. Despite these problems and an FDA consent decreed, it was not enough to stop Sanofi-Aventis from doggedly pursuing Genzyme as a take over target for the past year.

As you may recall, production shortages of several of Genyzme’s key products, most notably Fabrazyme, a treatment for Fabry disease (a rare genetically inherited lysosomal enzyme storage disease) forced Genzyme to ration Fabrazyme to patients. Fabrazyme is the only approved treatment for Fabry disease and the rationing plan called for patients already taking Fabrazyme to receive half the approved dosage while newly diagnosed patients were prevented from receiving the drug at all!

A post on the Pharmalot blog last week revealed that at least half a dozen patients with Fabry disease who were taking Fabrazyme filed a lawsuit against Genzyme and New York’s Mt. Sinai Medical School for the ongoing shortages and the ill-conceived rationing plan. According to the lawsuit, as many as three patients with Fabry disease have died as a result of the Genzyme rationing plan. Mt. Sinai was named as a co-defendant in the case because it licensed Fabrazyme to Genzyme and went along with the company’s rationing program. Further, the lawsuit contends that neither Genzyme nor Mt. Sinai had adequately tested whether or not the reduced dosage was effective as a treatment for Fabry disease. Obviously, the FDA approved Fabrazyme as a treatment for Fabry disease based on the dosage information that Genzyme determined to be optimal in it BLA.

The lawsuit will likely never make it to trial (Genzyme will undoubtedly settle) and therefore have little or no impact on the impending acquisition of Genzyme by Sanofi-Aventis. Companies that are being acquired or merging don’t like it much when there is outstanding litigation that may interfere with the transaction.

Nevertheless, Genzyme’s manufacturing problems highlights one of the weaknesses of the US Orphan Drug Act. For those of you who may not know companies granted approval of drugs for orphan indications (< 200,000 patients) are guaranteed seven years of market exclusively (along with tax credits, grants and less onerous clinical trials). This means that no other company (aside from the innovator company) will be granted regulatory approval for a similar orphan product for seven years from the approval date of the first product. Not surprisingly, this forces patients with orphan diseases to exclusively rely on a single drug that is manufactured by a single company i.e. there is no backup. And, if an orphan drug manufacturer has regulatory compliance issues or goes out of business etc the patients that rely on the drug are SOL (as it is said in the vernacular). Unfortunately, this was exactly what happen with Fabrazyme when Genzyme’s chronic manufacturing problems resulted in shortages of the drug.

While many people take drug companies to task for developing so-called “me too” drugs there is a reason why FDA and other regulatory agencies approve them. That is: when there is more than one manufacturer of drugs that treat a particular indication then there will be alternate treatments available to patients if something goes awry with one or another of the products. Although I am a strong proponent of the Orphan Drug Act, the recent entry of several major pharmaceutical companies like Pfizer, GlaxoSmithKline and others into the orphan drug development space suggests that the seven years of market exclusivity offered by the Act may no longer be necessary. Further, shortening or eliminated the market exclusivity term would like help to increase competition among orphan drug developers. Increased competition would, in turn, and then help to drive down the price of orphan drugs which are currently exorbitantly expensive and sometimes not covered by insurers. Changing the orphan drug act would primarily benefit patients with rare diseases and not drug makers. And, in the end, helping patients is admittedly all that matters!

Until next time...

Good Luck and Good Job Hunting!!!!!!!!

• Email This
• Print
• Comments (1)
• Trackbacks
• Share Link

On episode #2 of the podcast This Week in Microbiology, Vincent, Cliff, and Michael review a fatal laboratory acquired Yersinia pestis infection, and how gut bacteria which are part of the normal flora of all animals control body weight and metabolic activity.

For those of you who may not know, bubonic plague—which killed thousands of people during outbreaks in the Middle Ages —still occurs at a low level in many places through out the world including sporadic cases in the Western US! About 10 to 20 Americans catch plague each year, and 1 to 3 die of it, according to the Centers for Disease Control and Prevention. Nowadays, most cases are in the Four Corners area, where Utah, Arizona, New Mexico and Colorado meet, and most victims live in rodent-infested rural housing. Despite the fear that the word plague induces in most people, the infection is easily treated with antibiotics if caught earlier enough (modern antibiotics were discovered in the 1940s starting with penicillin).

"Bring out your dead"from Monty Python and The Holy Grail

Y. pestis, the bacterium that causes bubonic plague, lives in the blood of infected prairie dogs and ferrets and other rodents and can be transmitted to human via bites from infected fleas (which are commonly found in wild rodent populations) that have previously had a blood meal on -infected animals. Interestingly, an article appeared in the NY Times last Fall, which linked climate change (aka global warning) to a reduction in the incidence Y. pestis infections in the Western US.

The article cited a study in the American Journal of Tropical Medicine and Hygiene, which  tracked climatic conditions in 195 counties in 13 Western states, from Washington to Texas, that reported even one plague case since 1950.

Cases of plague have dropped over time, and authors of the study concluded that rising nighttime temperatures since 1990 may have helped to reduce the incidence of plague. They suggested that warmer nights melt winter snow packs earlier than in the past, leading to drier soil in rodent burrows. When the soil gets too dry, fleas die and plague can no longer be transmitted from infected rodents to human hosts. Talk about an upside for global warming!!!!!!

While this may be good news for potential plague victims, the incidence of plague in the US is so low that the public health benefits offered by climate change may be nominal as compared with the damage that global warming will cause if continues unchecked. That said, who knew that climate change and bacterial pathogenesis were interconnected?

To learn more about the less well known interrelationships between bacteria, animals and the planet we invite you to continue to listen to TWiM. You can subscribe to TWiM (free) at the Zune Marketplace, via RSS feed, by email or listen on your mobile device with the Microbeworld app.

Until next time...

Good Luck and Good Listening!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

Previously, BioJobBlog reported on the race between two groups led by the Mars and Hersey companies to sequence and decode the cacao (chocolate) tree genome. It should come as no surprise that the world’s two largest chocolate companies have pitted themselves against one another to decode the wonders of the cacao bean. After all, chocolate is big business and learning how to maximize yields, improve flavors and optimize the levels of cacao bean chemical components would be a boon to the company that was able to obtain the genetic information first!

Currently, most cacao farmers earn about $2 per day, but producers of fine cacao earn more. Increasing the productivity and ease of growing cacao can help to develop a sustainable cacao economy. The trees are now also seen as an environmentally beneficial crop because they grow best under forest shade, allowing for land rehabilitation and enriched biodiversity. Today, many growers prefer to grow hybrid cacao trees—rather than the original variety Theobroma cacao, Criollo)—that produce chocolate of lower quality but are more resistant to disease. Roughly five percent of the world’s current cocoa production is derived from Criollo cacao beans because of increased susceptibility to fungal diseases which results in higher costs and lower yields.

At the last installment of this ongoing saga, the Mars group, September 2010, released a statement that that they had beat the Hershey group and unraveled DNA sequence of the most common cacao bean variety that is used to manufacture most commercial chocolate.

The Mars researchers constructed a preliminary genomic map that covered over 70 per cent of the total cacao bean DNA sequence which is distributed over 10 chromosomes. These data were uploaded to The Cacao Genome Database which is publicly available as long as persons who access the data sign an agreement that stipulates that they “will not seek any intellectual property protection over the data, including gene sequences contained in the database. The Information Access Agreement allows any cacao breeders and other researchers to freely use the genome information to develop new cacao varieties.”

While the Mars group may have beat the Hersey group to the popular press, their research has not yet appeared in an academic journal for scientific scrutiny. Interestingly, the Hersey group yesterday announced that their version of the cacao genome was published in the most recent edition of Nature Genetics. According to the authors,

We sequenced and assembled the draft genome of Theobroma cacao (Criollo), an economically important tropical-fruit tree crop that is the source of chocolate. This assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of these genes anchored on the 10 T. cacao chromosomes.

Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example, flavonoid-related genes. It also provides a major source of candidate genes for T. cacao improvement.

While Theobroma is often used to manufacture gourmet chocolates that particular variety of cacao tree often remains vulnerable to disease. Information gleaned from this study could be used to breed bioresistant varieties of Theobroma.

Further the authors noted:

Our analysis of the Criollo genome has uncovered the genetic basis of pathways leading to the most important quality traits of chocolate--oil, flavonoids and terpene biosynthesis […] It has also led to the discovery of hundreds of genes potentially involved in pathogen resistance, all of which can be used to accelerate the development of elite varieties of cacao in the future.”

Other genes that were identified include those for the production of cocoa butter, natural antioxidants, hormones, pigments, and aromas. BTW, for those of you who may be interested, cocoa was thought to be domesticated about 3,000 years ago in Central America; making it one of the world’s oldest domesticated tree crops.

It isn’t clear yet how the cacao genomes deciphered by the Mars and Hersey groups match up against one another. Regardless, the big winners here are chocolate lovers. What to you think the world stance will be on genetically engineered chocolate? 

Oy!

Until next time...

Good Luck and Good Eating!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

I previously blogged about honey bee colony collapse disorder (CCD) a disease that is destroying honey bee hives all over the world. While the incidence of the disease has been subsiding over the last year or so, it is still ravaging many hives. 

In the Wednesday edition of the online research journal PLOS a group of researchers from the University of Montana and the Army’s Edgewood Chemical Biological Center at Aberdeen Proving Grounds in Maryland suggested that CCD may be caused by two infectious agents; a virus and a fungus. 

Previously, many entomologists and apiary experts believed that CCD was possibly caused by multiple RNA viruses or the effect of certain pesticides. However, samples collected hives affected by CCD contained both a virus and a fungus whereas both agents were absent in unaffected hives. 

The new study said the suspect virus is insect iridescent virus (IIV) (Iridoviridae), which is similar to a virus first reported in India 20 years ago, as well as a virus found in moths. The virus infects the insect digestive system and the abdomen of infected insects takes on a bluish-green or purplish hue. The fungus, Nosema ceranae, can infect insects following ingested of its spores. Laboratory cage trials with a strain of IIV type 6 and Nosema ceranae confirmed that co-infection with these two pathogens was more lethal to bees than either pathogen alone.

Authors of the study speculate that initial infection of bee with one of the two agents makes infected bees more susceptible to infection by the second agent. In other words, primary infection by one agent followed by secondary infection may be responsible for the devastating effects of CCD. Further research will be necessary to confirm that both agents are responsible for CCD.

Until next time.....

Good Luck and Do Good Science!!!!!!

• Email This
• Print
• Comments (1)
• Trackbacks
• Share Link

Despite a court ruling last week that dismissed the bogus link between vaccination and autism, I continue to receive comments from so-called “non-vaccinators” about a post that I published last week about New Jersey’s dismal vaccinations rates. Most of the comments are anecdotal and suggest that childhood vaccination was the likely culprit for their children’s autism, brain damage or other ailments. While I feel their pain, the notion that children should not continue to be vaccinated is misguided and has serious negative public health implications.

There is ample public health and scientific information that suggests that childhood vaccination has worked well to reduce the incidence of morbidity and mortality in Western nations. Ironically, if it wasn’t for mandatory childhood vaccinations, the death and lasting physical or neurological damage caused by many preventable diseases like smallpox, measles, mumps, diphtheria and whooping cough would be much higher. Unfortunately, we Americans have been lead to believe —intentionally or not—that there should be no side effects associated with drugs, vaccines and other medicines. The bottom line is that all drugs, vaccines and medicines have side effects; some more serious or noticeable than others! Further, the decision to develop new drugs and vaccines is always based on a risk to benefit ratio. Pharmaceutical and biotechnology companies will only develop products to address unmet medical needs when the benefits of these products clearly outweigh the potential risks. However, in some cases, most notably cancer drugs, the risk to benefit ratio becomes less obvious. There is no question that most cancer drugs have serious and potential life threatening side effects. Nevertheless, the benefit—survival and not death—far outweighs potential downstream risks!

Like it or not, the medical benefits of vaccination far outweigh the risks associated with them. As many of you may know, there is currently a whooping cough epidemic in California. California health officials assert that the epidemic likely started among unvaccinated individuals and then spread to the larger population. The observation that many of the patients with whooping cough were previously vaccinated against the disease in childhood suggests that either their immunity to whooping has declined over the years or that the causative bacterium, Bordetella pertussis has become more virulent. 

The former hypothesis is more likely than the later mainly because Bordetella infections were almost non-existent until increased immigration and the non-vaccination movement began in earnest about 15 years ago! Students of infectious diseases will tell you that virulence of infectious agents tends to increase as they are passed from one infected individual to the next. Consequently, the lack of any significant B pertussis outbreaks (until very recently) suggests that changes in the underlying virulence mechanism of the bacterium are not responsible for the current outbreaks.

Again, as a parent, I understand the pain and suffering of those whose children may have experienced debilitating effects coincident with childhood vaccination regimens. However, as more parents continue to eschew vaccination against childhood disease, the incidence of death and children with serious life long debilitating effects associated with many common childhood diseases is certain to rise. With this in mind, I will continue to write and post articles that support childhood vaccinations. I will gladly stop posting these articles when someone can provide me with scientifically accurate and valid data that suggest that vaccination does more harm than good!

Until next time...

Good Luck and Good Job Hunting!!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

Can things get any worse at Genzyme? First there were the manufacturing problems that result in plummeting stock share prices and a proxy battle by Carl Icahn and company. Next up was a $175 million consent decree judgment levied by the US Food and Drug Administration for the manufacturing problems. Then came the $18 billion takeover bid from Sanofi Aventis. Now, patients affected by shortages of the drugs Fabrazyme three patients have petitioned the US Department of Health and Human Services (HHS) to disregard Genzyme’s patent for the medicine to overcome the drug shortages.

Because of the manufacturing problems, Genzyme rationed its supplies of Fabrazyme to one-third of the normal dose for Fabry disease patients. Some of these patients reported increased pain and no newly diagnosed patients could receive the drug. Meanwhile, Shire Pharmaceuticals has been trying to obtain FDA approval of its Fabry disease treatment, Replagal which is approved in Europe.

The patients who petitioned HHS contend that HHS can override the patents because the National Institutes of Health paid for research at the Mount Sinai School of Medicine, which exclusively licensed Fabrazyme to Genzyme. The goal of the action is to induce another company to produce the drug in case Genzyme is unable to deliver adequate quantities to new and existing patients. Provisions in the Bayh-Dole Act suggest that this action may not be unreasonable if ‘a licensee cannot reasonably meet the public health and safety needs of the American public.’

Stay tuned for the next installment of the continuing Genzyme saga!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

Genzyme announced yesterday that it expects to be fined roughly $175 million in fines and penalties related to the manufacturing troubles at its Allston Landing, MA manufacturing plant that resulted in severe shortages of two of its best selling products, Cerezyme (Gaucher disease) and Fabrazyme (Fabry disease) 

The fines and penalties are part of a consent decree that the US Food and Drug Administration (FDA) intends to levy against the company for the manufacturing infractions. A substantial portion of the penalties included a disgorgement settlement, a process that allows FDA to collect a certain percentage of the sales of products made at the troubled Genzyme production facility.

According to an article in today’s New York Times business section, Genzyme representatives said that patients using Cerezyme would continue getting half a dose for two or three more months. It previously said full supplies would be restored May.

Patients who use Fabrazyme would continue to be allocated a third of their usual dose at least through the third quarter. The company had previously hoped to resolve the Fabrazyme shortage in the third quarter.

The highly publicized manufacturing problems at Genzyme, has shaken both physician and patient confidence in the company’s ability to safely manufacture and supply sufficient quantities of Cerezyme and Fabrazyme; two orphan drugs designed to treat patients with debilitating genetically-inherited diseases. 

Several physicians and patients who were previously loyal and ardent supporters of Genzyme, have indicated that they may switch to recently approved and new treatments being developed by Genzyme’s competitors that include Shire.

The lack of commitment to quality manufacturing by Genzyme executives has seriously tarnished the image of a once highly respected and reputable orphan drug developer.

Until next time…

Good Luck and Good Job Hunting!!!!!

Until next time…

Good Luck and Good Job Hunting!!!!!!!   

• Email This
• Print
• Comments
• Trackbacks
• Share Link

A rare or orphan disease is defined in the US as one that affects fewer than 200,000 at any given time. It is estimated that there are 6000 to 8000 rare diseases in the world today. Because the number of patients afflicted with orphan diseases is so small, drug companies have historically been reluctant to invest money to discover and develop new treatments for them. The dearth of treatments for rare diseases induced Congress to pass the Orphan Drug Act in 1983 which provided market exclusivity, tax breaks and incentives and regulatory help for companies to development new drugs for orphan disease indications.

While many current blockbuster drugs including recombinant human insulin, growth hormone and erythropoietin originally garnered regulatory approval after receiving orphan status in the late 1980s, most big pharma and biotechnology companies (except Genzyme) largely abandoned orphan drug development until recently. The renewed interest in orphan drug development has been primarily driven by the demise of big pharma’s blockbuster business model that began in the early 2000s. The search for new, non-blockbuster drugs and fresh markets is what induced Pfizer, the world’s largest pharmaceutical company, to recently inked a multimillion dollar deal with Protalix Biotherapeutics, a small biopharmaceutical company developing a new treatment for Gaucher disease—an orphan indication.

Because of renewed interest and the ever increasing need for new orphan drugs, the FDA’s Office of Orphan Products Development is offering an Orphan Drug Designation Workshop that will provide a unique opportunity for all potential drug sponsors—including biotechnology companies, pharmaceutical firms and academic institutions—to learn about the application process for orphan drug designation.

The National Organization for Rare Disorders (NORD) is a co-sponsor of the workshops, which will take place on February 25-26 at Keck Graduate Institute and August 3-4 at the University of Minnesota.

Participants are encouraged to bring specific product proposals for at least one candidate orphan drug that holds promise for the treatment of a rare disease. A significant portion of the workshop will be dedicated to preparing applications, including one-on-one guidance sessions with FDA staff members. FDA will keep product and disease information confidential.

Final applications can be submitted to the FDA at the close of each workshop. For information or to register:

FDA Workshop Brochure
Registration for the February Workshop

Finally, February 28^th is Rare Disease Day. The event is sponsored by the EURODIS a European advocacy group that promotes awareness and research for rare diseases. NORD and Discovery Health are also sponsoring the day.

Until next time....

Good Luck and Good Job Hunting!!!!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

Harrison Ford’s new movie “Extraordinary Measures” (also starring Brendan Fraser) is loosely based on John Crowley’s ongoing crusade to find a cure for Pompe Disease a genetically inherited illness that afflicts two of his three children.The film chronicles the 'extraordinary measures' taken by Crowley to find a treatment for the so-called orphan disease that affects the lives of about 40,000 persons worldwide. While I haven’t seen the film, it bears a striking resemble to the 1992 film “Lorenzo’s Oil” which chronicled the struggles of two parents to find a “cure” for their son’s adrenoleukodystrophy an another orphan disease.

Crowley’s story began about 12 years ago when his oldest child was diagnosed with Pompe Disease. For those of you who may not know, Pompe Disease is a progressive, multisystemic, debilitating, and often fatal neuromuscular disorder. The disease is linked to an inherited deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), which is responsible for the breakdown of glycogen inside the cells. The result is intralysosomal accumulation of glycogen, primarily in muscle cells, that leads to a progressive loss of muscle function and ultimately death. At the time of the diagnosis, Crowley, a Princeton, NJ resident, was working as a marketer for Bristol Myers Squibb. He quickly learned that there was no effective treatment for Pompe Disease and that his daughter may not live beyond early childhood. Further, because the disease afflicted so few individuals, no pharmaceutical or biotechnology companies were working on treatments for Pompe Disease. 

To stave off the likelihood of his daughter’s death, in 2000, Crowley raided his 401k plan and mortgaged his home to start a company called Novazyme that focused exclusively on developing treatments for Pompe Disease. Having no time to waste, Crowley and the Novazyme team worked feverishly to develop an alglucosidase alfa enzyme replacement therapy for Pompe. By 2001, the Novazyme team had identified a likely treatment and Crowley sold his company to Genzyme. As a senior vice president at Genzyme, he oversaw clinical development of the product which is now called Myozyme and is the first FDA-approved treatment for Pompe Disease. Crowley left Genzyme in 2004 and is currently CEO of Amicus Therapeutics a 100 person company focused on developing new treatments for Pompe Disease and other orphan indications.

At present, there are no other treatments besides Myozyme for Pompe Disease. This is because Pompe Disease is designated as an orphan indication and Genzyme received seven years of market exclusivity for Myozyme as stipulated in the Orphan Drug Act. Myozyme received FDA approval in 2006.

While Genzyme has been the only player in the Pompe Disease market for the past four years, manufacturing and scale up problems threaten to jeopardize the Myozyme franchise. Genzyme’s highly publicized problems at its Allston, MA-manufacturing facility have been well documented and Genzyme’s management team is taking bold steps to correct them (including hiring a new senior vice president for global product quality) and entering into an agreement with Hospira Worldwide Inc to provide fill and finish manufacturing services.

But perhaps more troubling, were the problems that the company experienced when attempting to scale up Myozyme production from the 160L to 200L bioreactor scale to meet growing demand for the drug.  FDA informed Genzyme that that Myozyme® (alglucosidase alfa) produced at the 160L bioreactor scale and Myozyme produced at the 2000L scale should be classified as two different products because of differences in the carbohydrate structures of the molecules. And, the company would have to file a new biologics application (BLA) for the 2000L product to garner regulatory approval.

Currently, Genzyme has U.S. approval to sell Myozyme manufactured at the 160L scale, and the company has been seeking clearance from the FDA for Myozyme produced at the 2000L scale (now marketed as Lumizyme). Lumizyme has already been approved in more than 40 countries. However, manufacturing problems and violations at the Allston facility forced FDA to delay a decision on the approvability of Lumizyme this past March. Earlier this week, Genzyme announced that FDA will issue a new decision on Lumizyme in June.

While originally spurned by large drug companies, orphan drug development is becoming much more attractive because of the lack of new blockbuster drugs in most company’s development pipeline. According to a recent report, the number of orphan product designations in the US more than doubled in the last decade rising from 208 in the 2000-02 periods to 425 in 2006-08. More recently, Pfizer, the world’s largest pharmaceutical company announced that it agreed to pay at least $60 million for rights to Protalix Biotherapeutics Inc.'s new treatment (taliglucerase alfa) for Gaucher’s Disease another orphan indication. This suggests that Pfizer has made a decision to directly compete with Genzyme, the world leader in orphan drug development.

Don’t be surprised when other large pharmaceutical and biotechnology companies announce plans to compete in the orphan drug market...there is money to be made!

Until next time...

Good Luck and Good Job Hunting!!!

• Email This
• Print
• Comments (1)
• Trackbacks
• Share Link

The media frenzy surrounding the impending H1N1 swine flu pandemic has spawned a recent spate of articles and television news segments on “germs.” In the last 48 hours, articles on germs have appeared in the New York Times, my local paper (The Trenton Times via the Chicago Tribune), on news channels and most recently this morning on the Today Show on MSNBC. Most of these have focused on where “germs” are found, how they are spread and ways to minimize or prevent their transmission. For those of you who may be interested, the word germ was first coined in 1664 and is defined as a “small mass of living substance capable of developing into an organism or one of its parts” or more conventionally, as a “microorganism that causes disease.” While these media pieces are intended to inform the public about infectious agents and their transmission, most people who read or see these reports don’t understand that the word germ can encompass viruses, bacteria and fungi. And, to make matters worse, most Americans don’t know that viruses, bacteria and fungi are different microorganisms.

Unfortunately, after reading newspaper articles and seeing reports on television about so-called germs, many consumers rush out to their local groceries and purchase a variety of antibacterial soaps and detergents—erroneously believing that these products will protect their families from infection by the dreaded H1N1 virus and other pathogens. Although frequent hand washing and the appropriate use of viricidal disinfectants can help to reduce transmission of H1N1 and other viruses, antibacterial products are generally less effective (or ineffective) against viruses and overuse can result in emergence of multi-drug resistant bacteria.

To that end, I think it is high time that the news media eschew the use of the anachronistic term germ in favor of bacteria, virus or fungi when referring to causative agents of infectious diseases. Promulgating the use of the word germ will continue to keep the lay public in the dark about infectious agents and the diseases they cause and hinder people from making informed decisions about treatment and preventing their transmission.

Until next time...

Good Luck and Good Job Hunting!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

On several occasions while driving in upstate New York, I noticed an exit sign on the NY State Thruway for Coxsackie, NY. And, not surprisingly, I began to wonder whether or not the Coxsackie virus was named after this obscure upstate NY town.

I first learned about coxsackie viruses as a graduate student while taking a medical virology course at the University of Wisconsin taught by the late noble laureate Howard Temin. However, despite a thirty year friendship with Vincent Racaniello, a BioCrowd co-founder and virologist extraordinaire, I never asked him about the origin of the coxsackie virus name. Much to my surprise, he had recently taken a trip to upstate NY and noticed the Coxsackie NY exit sign while driving on the thruway. This prompted him to blog about the coxsackie virus isolation, its pathogenic properties and of course, the origin of its name!

Coxsackie NY and the virus named after it 

by Vincent Racaniello,PhD

Recently while driving north on the New York State Thruway I passed the exit for the town of Coxsackie, NY (population 8,884). I grabbed my camera and photographed the exit sign, and reminded myself to write about the virus named after this small town.

In the summer of 1947 there were several small outbreaks of poliomyelitis in upstate New York. Gilbert Dalldorf, the director of the Wadsworth Laboratory in Albany, NY, and his associate Grace M. Sickles investigated this outbreak. In particular they sought polioviruses that could replicate in mice. This search was motivated by the fact that research on poliovirus required the use of monkeys which were extremely expensive. Dalldorf had attended the Fourth International Congress for Microbiology in 1947 where he heard that very young mice – suckling mice – could readily be infected with Theiler’s virus.

Dalldorf and Sickles made fecal suspensions from two children suspected of having poliomyelitis, and inoculated these into adult and suckling mice. Only the suckling mice (1 – 7 days old) developed paralysis; animals more than one week old were resistant to infection. The damage responsible for limb paralysis was widespread lesions in skeletal muscles, not in the central nervous system as occurs with poliovirus. Further study revealed that the viruses could be distinguished serologically from poliovirus.

Not only had Dalldorf and Sickles identified the first members of a very large group of human viruses, but they also introduced and popularized a new and inexpensive animal into the virology laboratory – the suckling mouse. In 1949 Dalldorf suggested that the new viruses be called Coxsackie viruses, because the first recognized human cases were residents of that New York village. This unique name is of native North American origin.

Over ten years later the importance of this work was recognized by Dr. Max Finland of Boston City Hospital:

The isolation by Dalldorf and Sickles of viruses which produced paralysis with destructive lesions of muscle in sucking mice and hamsters, from the stools of two children with signs of paralytic poliomyelitis was an achievement that may rank in importance with Landsteiner and Popper’s production of human poliomyelitis in monkeys.

In subsequent years many different Coxsackie viruses were isolated that cause a variety of clinical syndromes. Today at least 30 serotypes of Coxsackie viruses are classified in the enterovirus genus of the Picornaviridae. The viruses are classified into groups A or B depending upon the pathological effect in suckling mice.

Not every locale is pleased to have a virus named after it. In May 1993, an outbreak of an unexplained pulmonary illness occurred in the southwestern United States, in an area shared by Arizona, New Mexico, Colorado and Utah called “The Four Corners.” Muerto Canyon was proposed as the name for the etiologic agent of the disease, because the virus was first isolated from a rodent near the canyon. However after residents objected, the name Sin nombre virus was given to the agent of hantavirus pulmonary syndrome.

Dalldorf G, & Sickles GM (1948). An Unidentified, Filtrable Agent Isolated From the Feces of Children With Paralysis. Science (New York, N.Y.), 108 (2794), 61-62 PMID: 17777513

• Email This
• Print
• Comments (1)
• Trackbacks
• Share Link

Several weeks ago, I blogged about a growing need to improve the American public’s perception and understanding of the life sciences if the US wants to remain competitive in science and technology. Much to my delight, there was an article this Sunday’s NY Times entitled “Microbes R Us” which explores the evolutionary relationship with bacteria and humans. It was written by Dr. Olivia Judson an evolutionary biologist and author of “Dr. Tatiana’s Sex Advice to All Creation: The Definitive Guide to the Evolutionary Biology of Sex,” which was made into a three part television program.

While the evolutionary relationship between bacteria and humans isn’t as titillating as the biology of sex, the article sheds light on the importance of bacteria and how genetic changes in bacteria that normally inhabit the human intestinal track can have a positive impact on human nutrition and health. Many lay people believe that bacteria are “bad” because certain species can cause serious and potentially life threatening diseases. However, the benefits, advantages and uses of bacteria e.g., to make food, antibiotics and other medicines, far outweigh their negative impact on society. 

Articles like the one written by Ms. Judson, offer the public unqique insights into  the amazing and often fascinating world of microbiology. I hope that a few aspiring young scientists read the article and tell all their friends about it!

Until next time....

Good Luck and Good Reading!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

The long sought after cow genome has been sequenced. Heralded as a milestone in animal genetics, unraveling the cow genome will provide scientists with “tantalizing clues to explain the essence of bovinity.” Two papers describing the results of the project will appear in today's issue of the journal Science. 

The cow who donated its DNA for sequencing was a Hereford named LI Dominette 01449 and is one of the estimated 94 million bovines in the US. The project, led by researchers at National Institutes of Health and the U.S. Department of Agriculture, was a gargantuan effort that spanned six years and involved more than 300 scientists from 25 countries and cost only $53 million. Based on sequence analyses, cows haver 22,000 genes as compared with 20,000 to 25,000 for humans. Some of the other findings include: 

• Cattle and humans have about 80 percent of their genes in common

• The organization of human chromosomes is closer to that of domestic cattle than to those of rats or mice, which are often used in lab tests of drugs intended for people.

• Cattle chromosomes, like those of humans and other mammals, contain segmental duplications, which are large, almost identical copies of DNA present in at least two locations in a genome.

• In domestic cattle, there are duplications related to immunity, metabolism, digestion, reproduction and lactation. Such duplications in humans have been related to a variety of disorders.

Researchers hope that elucidating the bovine genome will help them find ways to improve milk and meat production, develop new strategies to treat and prevent diseases and to reduce the carbon foot print of cows that release large amounts of greenhouse gases that contribute to global warming.

Great news to receive on National DNA Day! 

Science rocks.

Until next time...

Good Luck and Good Job Hunting!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

Colony Collapse Disorder (CDD) a mysterious syndrome that kills adult worker bees outside of the hive has been plaguing Europe and the US in recent years. The US Department of Agriculture (USDA) reports that American beekeepers have lost 37% of their hives to CCD in 2008 after losing 31% the year before. The government estimates that a third of the US food supply may be at risk--$15 billion annually in vegetables, nuts and fruits from plants that depend on bee pollination. The cause of CDD is still hotly debated but many scientists believe that it is caused by a virus

A start up company in Miami FL (my old stomping grounds) called Beeologics is developing a vaccine against all of the apiary viruses that could be responsible for CDD. The company was started by two Israelis, Eyal Ben-Chanoch at tech entrepreneur who helped design the first Intel Pentium chip and Ilan Sela a bee genomics expert. 

The vaccine is pending FDA approval and Beeologics expects it to hit the US market this summer and sell it for $2 per dose. A hive will need one dose per month and current estimates suggest that there are 2.5 million hives in the US. Not a bad revenue stream!

For those of you who may not know, bee keeping is big business and can be lucrative for beekeepers. I learned everything I know about bee keeping as an undergraduate at Cornell when I took Introduction to Beekeeping in my senior year. It was one of the best courses that I ever took at Cornell because it was taught by an entomologist who was also a commercial beekeeper!   Since then, I have always been extremely fond of honey bees—they are fascinating creatures.

Until next time…

Good Luck and Good Job Hunting!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

A European friend of mine sent me a link to a video of Sarah Palin espousing her understanding of the relationship between basic research and it application to solving human disease. Along with the video (see below) she sent the message "Please ,please don't tell me they (McCain and Palin) are going to win..."  I hope for science's sake they don't....

Until next time...

Good Luck and Good Job Hunting!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

After beating Wall Street expectations and disclosing positive results from an osteoporosis (densomab) clinical trial, Amgen was ordered by the US Food and Drug Administration (FDA) yesterday to change the labels for its EPO drugs (Epogen and Aranesp) that will likely further restrict their use in treating patients with cancer.

The label changes ordered by FDA represent the first time that the agency has invoked its power to change prescribing information for drugs that it previously approved. In the past, FDA could only negotiate with drug manufacturers about changes to labels and prescribing information. In my opinion, it’s about time that FDA has been empowered to unilaterally order these types of changes. I have long contended that negotiations between the agency and drug makers about labeling and prescribing information is not in the best interests of Americans who use prescription drugs. To that end, it was negotiations between FDA and Merck about whether the serious cardiovascular risks associated Vioxx should appear on the Vioxx label (they didn’t) that lead to the misuse, safety problems and ultimate recall of the drug.

While the ordered label changes are not good news for Amgen and its partner Johnson and Johnson which sells Procrit (EPO manufactured by Amgen and sold by J&J), they are in the best interests of all Americans who use these drugs to treat anemia caused by cancer chemotherapy and kidney disease.

Until next time….

Good Luck and Good Job Hunting (avoid A Thousand Oaks, CA)!!!!!!!!!!

• Email This
• Print
• Comments (1)
• Trackbacks
• Share Link

Somebody once said “Jews know two things—suffering and where to find good Chinese food”. Since I am Jewish, it is not surprising that I have experienced a fair amount of suffering throughout my life and, wherever I go, I seem to know where to find “good” Chinese food.  That said, my interest was piqued when I found a post in Yahoo Science News entitled “Study finds Chinese food good for your heart”. Given my lifelong fondness and penchant for Chinese cuisine, I thought that all of that eating that I had done had finally paid off. Unfortunately, after reading the subtitle of the article; “Chinese red yeast rice reduces repeat heart attacks/mortality rates” I realized that my joy and optimism were somewhat premature.

According to the report, researchers at Jefferson Medical College found that a partially purified extract of Chinese red yeast rice, Xuezhikang (XZK), reduced the risk of repeat heart attacks by 45%, revascularization (bypass surgery/angioplasty), cardiovascular mortality and total mortality by one-third and cancer mortality by two-thirds. The multicenter, randomized, double-blind clinical study was conducted on about 5,000 heart attack patients, ranging in age from 18-70 during a five-year period at over 60 hospitals in the People's Republic of China. Study participants were given 300-milligram XZK capsules or a placebo and tracked over a five-year period. The XZK extract used in the study contained a combination of lovastatin, lovastatin hydroxyl acid, ergosterol and several uncharacterized components.

Based on study results, the study’s authors believe that XZK may offer therapeutic benefits to people at risk of heart attack and cardiovascular disease. However, they cautioned that the active pharmacologic ingredient (API) of the red yeast rice is unknown and it isn’t clear how XZK works to fight cardiovascular disease.

Chinese medicine practitioners have long touted the benefits of red yeast rice for heart patients. Nevertheless, this is the first controlled clinical study of red yeast rice that tends to substantiate these claims. According to the study authors it is important to note that “the commercially available over-the-counter supplement found in your average health food store is not what was studied here. Those over-the-counter supplements are not regulated (by the US Food and Drug Administration), so exact amounts of active ingredient are unknown and their efficacy has not been studied yet.”

It is unfortunate that I didn’t know about the benefits of red yeast rice during my recent trip to China. I certainly would have gone out of my way to try some. That said, given the plethora of exotic foods that I tasted in China, maybe I ate some XZK without knowing it!

Until next time

Good Luck and Good Eating (Chinese of course)……

• Email This
• Print
• Comments (3)
• Trackbacks
• Share Link

Metals like copper and silver have long been known to possess antibacterial properties. I learned this as an undergraduate microbiology major circa 1972. That said, I didn’t know whether to laugh or cry when I read an article in today’s NY Times entitled "Regulators Stamp Copper as a Germ Killer". According to the article, the Copper Development Association (CDA), a NY-based trade group for copper companies, announced that federal regulators at the US Environmental Protection Agency (EPA) approved its application to market copper, bronze and brass-containing products as antibacterials that are effective enough to protect against bacterial infection. Apparently, what made this newsworthy is that this is the first time that EPA has allowed health claims to be attached to a solid antimicrobial material (rather than an aerosol or liquid disinfectant). For those of you who may not know, EPA (not FDA) regulates antimicrobial agents like disinfectants and air fresheners that are not directly applied to the human body.

Not surprisingly, there are many consumer products already on the market which are impregnated with silver and some other antimicrobial substances that claim to reduce the risk of infection.  Some of the more creative and pricey ones include silver-coated computer keyboards and mice manufactured by Iogear. However, none of the companies that manufacture these products can legally claim that the impregnated metals in them kill bacteria or provide a health benefit because they never thought to submit data to  EPA regulators to substantiate these claims. This is marked contrast with the CDA which smartly and painstakingly performed “clinical studies” for the past 4 years with copper and its alloys (mostly door knobs) to gain regulatory approval to claim that these metals have bona fide antibacterial properties. According to a CDA spokesperson, additional “clinical trials are underway to test how copper bed rails, arm rests and other hospital fixtures can reduce the numbers of bacteria in hospitals.”

Don’t get me wrong–you gotta love the creativity of the CDA for developing an innovative business strategy to help maintain the price of copper and bolster the sales of copper-based products. As you may know, the advent of fiber optics and silicon chips has been steadily pushing the price of copper down for the past few years–something that the CDA is keenly aware of.  Unfortunately, in contrast with CDA’s new vision, I believe that the only way to effectively reduce the high bacterial loads in our hospitals is through vigorous enforcement of hospital sanitation and hygiene programs, regular screening of hospital personnel and routine environmental monitoring.  Based on over 30 of experience with food borne and nosocomial bacterial diseases, I firmly believe that improperly sterilized equipment and instruments and people who are either unsuspecting carriers or fail to maintain good sanitation and hygiene practices are the main causes of bacterial contamination and transmission in hospital settings. I don’t think that inanimate metal objects (which have long been known to have inherent antimicrobial properties) contribute to the high levels of bacteria that are commonly found in today’s hospitals. Nor do I think that replacing existing hospital fixtures with copper, brass or bronze ones will do much to reduce bacteria levels in most hospitals.  Nice try CDA–but no cigar this time (at least not from me)!

Until next time….

Good Luck and Good Job Hunting!!!!!!!

• Email This
• Print
• Comments
• Trackbacks
• Share Link

For the past 30 years or so, the Unites States government has been looking for any reason what so ever to argue against the legalization of marijuana. This is despite a growing body of evidence that marijuana use provides documented, palliative and therapeutic benefits to people who suffer from serious illness like glaucoma, chronic pain and the side effects of cancer chemotherapy. Although marijuana use for medicinal purposes is illegal at the federal level, some Western States, most notably California, have legalized its use —it can now be purchased by people who have valid prescriptions from specially-designed .

From time to time, papers have appeared in the literatures which suggest that marijuana use has deleterious effects on mental acuity, emotional stability, breathing and sperm production. A  recent report  from New Zealand (which was published in the Journal of the American Medical Association) suggests that chronic marijuana use can increase the likelihood of periodontal disease in young adults.

C’mon, gum disease….are you kidding me? Don’t get me wrong, untreated periodontal disease is a serous medical issue. That said,  I suspect that more people are likely to develop periodontal disease from poor dental hygiene and a lack of dental insurance than from smoking a joint from time to time. The fact that the American Medical Association is subliminally try to turn marijuana-induced periodontal disease into an American public health crisis signals to me that government officials are running out of credible arguments to prevent the legalization of marijuana in this country.

Growing up in the 60s, I am very familiar with the consequences and negative outcomes of drug misuse and abuse. While I don’t advocate the use of marijuana and other psychotropic drugs for recreational use, I do believe that patients with serious medical illnesses ought to have legal access to drugs that are safe and offer therapeutic benefits. Further, I think that many drugs that are currently illegal in America ought to be legalized. In my opinion, the legalization of drugs in America will help to reduce crime, allow monies currently allocated to combat illegal drug trafficking to be used for struggling social programs and to demystify the use of illegal drugs American children and young adults. Ironically, illegal drug use by  American children and young adults has been declining over the last few years whereas abuse of  legal, prescription drugs has been skyrocketing out of control. Maybe it is time for America to re-think its drug polices and craft new ones that do a better job of safeguarding America’s youth.

Until next time….happy trails to you! And as always…..

Good Luck and Good Job Hunting!!!!!!!!

• Email This
• Print
• Comments (2)
• Trackbacks
• Share Link

Unraveling the Cholesterol Conundrum

By now, I am sure that everyone is sick of hearing about Zetia, Vytorin, cholesterol levels and heart disease. Whether you like it or not, results from the now infamous Enhance study have certainly caused many scientists and physicians to rethink the relationship between cholesterol levels and heart disease and stroke. Conventional wisdom (and current medical dogma) holds that low LDL cholesterol levels reduce the risk and incidence of heart disease and stroke. This belief is now so widespread and entrenched in that the medical community that FDA now approves drugs to prevent heart disease, as it did with Zetia and Vytorin, solely on the evidence that they lower LDL cholesterol levels. Unfortunately, Enhance study results indicate that lowering LDL cholesterol levels alone are not sufficient to reduce the incidence of heart disease or stroke. 

Zetia, one of the active ingredients of Vytorin, lowers blood LDL cholesterol levels by reducing absorption of cholesterol in the gut (from foods that we eat). In contrast, the other ingredient in Vytorin, Zocor, is a statin that acts to lower LDL cholesterol by interfering with its production in the body. The results of the Enhance study, which showed that Vytorin doesn’t reduce the risk of heart disease or stroke any better than Zocor itself, suggest that the only way to prevent heart disease and stroke (by lowering LDL cholesterol) is through statin use. This assertion is supported by results from clinical trials involving Lipitor and Zocor (both statins), which showed that lowering LDL cholesterol also resulted in a lower incidence of heart disease and stroke. This suggests that statins may act to reduce heart disease and stroke by mechanisms other than their LDL cholesterol-lowering properties. Indeed, statins have also been found to reduce inflammation, keep artery walls flexible and healthy and help to maintain LDL and HDL cholesterol balance in the blood.

There were hints along the way which suggested that the relationship between LDL cholesterol and heart disease and stroke were not as straightforward as it seemed. For example, torcetrapib, a Pfizer drug that lowers LDL and raises HDL cholesterol, was being evaluated in clinical studies that were subsequently halted because it increased the risks of heart attack and stroke rather than prevent them. Another example is estrogen replacement therapy which is known to lower LDL cholesterol levels but failed to reduce the incidence of heart attack and stroke in clinical studies. Nevertheless, it did not take much to convince FDA that lowering LDL cholesterol levels alone was sufficient to prevent or reduce the incidence heart disease a stroke. This notion was strongly substantiated by results from clinical studies with Lipitor and Zocor which showed a strong relationship between lowering LDL cholesterol and reducing the risk and incidence of heart disease and stroke. Unfortunately, it now appears likely that the ability of statin drugs to reduce the incidence of heart disease and stroke is related to other mechanisms besides lowering LDL cholesterol. For an excellent historical review and recap of the cholesterol story, I suggest reading an article is this Sunday’s NY Times by Gary Taubes.

So what are the lessons learned from this story? First, I think that it is unwise to make assumptions about cause and effect relationships until all of the data is carefully analyzed and vetted. Second, it is our obligation as scientists, whether we are company employees or not, to point out inconsistencies or problems with prevailing theories regardless of personal or professional consequences. Finally, and perhaps most importantly, FDA must not allow drug companies to influence or affect the type or amount of data that it requires to approve new drugs.

Until next time…

Good Luck and Good Job Hunting!!!!!!

• Email This
• Print
• Comments
• Trackbacks (1)
• Share Link