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For the past decade or more multiple drug resistant strains of bacteria such as methicillin resistant Staphylococcus aureus (MRSA), enterococci and other Gram positive cocci have been highlighted and showcased in the medical and lay press. While the incidence of infections caused by MRSA and other Gram positive cocci has steadily risen, antibacterial drug discovery experts have long known that the greatest disease threat in the future will be from emerging multiple antibiotic resistant strains of Gram negative bacteria including Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa.

Last Spring, in an interview that I conducted with Barry Eisenstein, MD, Senior Vice President of Scientific Affairs at Cubist Pharmaceuticals and an antibacterial drug discovery expert, he indicated that there are currently no drugs in development to treat infections caused by antibiotic resistant Gram negative bacteria. He warned that this, coupled with the loss of interest in antibiotic development by large pharmaceutical companies, will cause infections caused by multiple drug resistant Gram negative bacteria to become a serious unmet medical need in the not so distant future. The appearance of an article in the New York Times this past Saturday chronicling the rise of infections caused by antibiotic resistant Gram negative bacterial suggests that the not so distant future may have already arrived! For the record: would newspaper and television reporters please refrain from identifying bacteria as “germs.” It is an anachronistic term which was coined in the 19^th century before bacteria and viruses were conclusively identified as the cause of most infectious diseases.

Despite the media hype about antibiotic resistant Gram positive bacteria, a variety of new drugs have been developed to treat infections caused by these bacteria. Interestingly, because of greater public awareness about MRSA infections and improved hospital infection control and surveillance programs, the incidence of disease caused by MRSA and other Gram positive bacteria is finally beginning to wane. Unfortunately, the same is not true for infections caused by antibiotic resistance Gram negative bacteria.

For those of you who may not know, the cell wall architecture of Gram negative bacteria (and a multitude of antibiotic resistance mechanisms) makes it much more difficult and costly to develop new antibiotics to treat Gram negative infections. Consequently, research in this area has been largely ignored for the past 15 years or so. This means that in the future the morbidity and mortality associated with infections caused by antibiotic resistant Gram negative bacteria is certain to rise. With this in mind, persons at the greatest risk of developing these infections include patients in hospitals and long term care facilities and individuals receiving implantable medical devices.

Because most large pharmaceutical companies abandoned antibiotic drug discovery in the mid to late 1990s, it is unlikely that new Gram negative antibiotics will come from the pharmaceutical sector. While there are several small biopharmaceutical start ups working on antibiotics for Gram negative bacteria (KaloBios Pharmaceuticals, Calixa Therapeutics and Novexel) the increasing regulatory scrutiny and rising development costs suggests that these companies may have trouble bringing new antibiotics to market. Sadly, this places the onus of new Gram negative antibiotic discovery squarely on the shoulders of the US government. To that end, as much as it pains me to say this, it will likely take the death of government official or family member before sufficient resources are allocated to address this rapidly growing unmet medical need. Maybe the Obama Administration ought to think about allocating stimulus monies to begin to address the problem!

Until next time...

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

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Amy Bishop, a tenure track faculty member of the Biology Department at the University of Alabama-Huntsville shot and killed three faculty members and wounded three others after learning that her appeal of a negative tenure decision was denied. While this incident doesn’t typify the response of faculty members who are denied tenure (subsequent reports suggest that she previously accidentally shot and killed her brother 20 years ago), it illustrates how high the stakes are or (may be perceived) by those aspiring to successful academic careers. 

Based my own experiences, being denied tenure is emotionally debilitating—mostly because of the public humiliation and stigma associated with it. Despite what your friends, loved ones or fellow faculty members say to you to ease the pain, being denied tenure suggests that you weren’t scientifically astute or “smart enough” to be guaranteed a job for life. It doesn’t matter whether or not the decision was fair or that there may have been extenuating personal or political circumstances, the bottom line is that you had your shot (no pun intended)and you simply didn’t have the right stuff to gain membership into the elite club populated by “outstanding scientists.” Put simply, your failure to win tenure has earned you the label of being a “failed scientist.” While nobody will ever utter those words, I can assure you, based on my own experiences that they think it no matter how successful you ultimately may become.

If I sound bitter...well....I am; but not for the reasons that you may suspect (being denied tenure was probably best career move that I was ever forced to make). While being denied tenure at institutions like Harvard, Stanford, Yale, Columbia or other elite universities doesn’t mean that you cannot have a successful academic career at lesser institutions, being denied tenure the University of Miami School of Medicine (or the University of Alabama-Huntsville for that matter) almost always means that your academic career is over. This means that after chasing an academic career for most of your professional life, you can longer do what you were trained to do and you must now do something else with your life Unfortunately, and not surprisingly, the vast majority of graduate students and postdocs that I have talked with over the past 15 years have given little thought to what that something else may be.

But, don’t be too hard yourself because you have no idea what you next career move may be after the academic career route path is no longer viable. The blame for this conundrum falls squarely on shoulders of the faculty members (mostly tenured) who train graduate students and postdoctoral fellows for careers in the life sciences. Despite the fact that only 10 percent of PhD-trained life scientists land tenure track positions after completing their training, graduate programs continue to exclusively focus on academic careers for their graduates and trainees. While I believe that this practice is ill-advised and clearly flies in the face of supply side economics, the steadfast refusal of life sciences graduate programs to develop alternative career tracts within their training programs to accommodate the career needs of a majority of their graduates is especially egregious and odious.

It is not difficult to understand why many tenured faculty members don’t give much thought about future employment prospects for their graduate students and postdocs. After all, they already have jobs that are guaranteed for life and it stands to reason that the careers and employment opportunities for others are not high on their priority lists.  Like it or not, when it comes to employment opportunities and career choices, most graduate students and postdocs are on their own!

It is extremely tragic that three people lost their lives and several others were wounded by a deeply troubled and misguided former tenure track faculty member. It won’t be surprising if certain faculty members dismiss the incident and attribute its horrific nature to a seriously disturbed and deranged person. After all, who in their right mind would do such an awful thing? However, I am certain that the humiliation, outrage and psychological pain experienced by Bishop are fairly common among individual who are denied tenure. Rather than turn her rage inward, she decided to take it out on the people who she thought had destroyed her life.  Maybe this incident will induce graduate programs to consider implementing career development programs that showcase alternate careers beyond the traditional tenure track career path.

Until next time...

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

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Mention the word “scientist” to most people and they will likely conjure up an image of a socially-inept, nerdy individual who cannot talk to “normal everyday folks” because they are either “too smart” or out of touch with the “real world.” I have been fighting that stereotype for as long as I can remember. I believe that, along the way, I have convinced a few people otherwise and hope that they have learned that “one size does not fit for all scientists”—or any other professional group for that matter. The public perception of scientists was improving until George W Bush, an inveterate anti-science and anti-intellectual advocate became President in 2001. I hope that America’s attitude toward science (and scientists) will change over the next four years as President Obama tries to “restore science to its rightful place.” Nevertheless, I felt compelled to write this post after reading a New York Times review of a television drama called “Breaking Bad” (AMC, Sundays, 10 EDT) which, in my opinion, reinforces the negative stereotypes of scientists held by many members of the lay public.

Breaking Bad centers on a former Caltech chemistry genius named Walt, who failed to live up to the legend of his graduate school days. At 50, he is teaching high school chemistry in Albuquerque, NM. Although he contributed to work of a Nobel-winning team, the teaching job in New Mexico is inexplicably the best that he can get. To make matters worse, his best friend at Cal Tech has amassed a fortune (based largely on Walt’s graduate school work) and is married to Walt’s beautiful ex-wife. Walt learns  after attending a lavish party thrown by his friend, that most of his graduate school classmates (unlike him) are famous world class scientists who live in big homes and make enough money to purchase guitars that previously belonged to Eric Clapton. On top of his devastating psychic and emotional pain, Walt is also suffering from stage 3A lung cancer—even though he never smoked! To save his life, Walt partners with one of his former high school students in the crystal methamphetamine business. Walt’s chemical genius allows him to synthesize the meth from scratch—unlike his scientifically-challenged competitors who must extract the starting materials from over the counter cold remedies—earning him the reputation as one of the best meth ‘cookers” in the US. Walt uses the drug money to pay for his chemotherapy to stay alive and care for 15 year old son with cerebral palsy.  

While the show sounds intriguing, and by all accounts is well acted and provides a glimpse into the lives of people struggling with chronic illness and unrealized career aspirations, it sends the wrong messages to the American public about scientists, their motivations and their lives. First, it portrays Walt’s classmates as wealthy, elitist dilettantes who live lavish lives and don’t think twice about flaunting their status and power as world class scientists. Aside from Craig Venter and several other high profile scientists who are sometimes featured on 60 Minutes, I don’t think that there are many scientists who enjoy the luxurious and opulent lifestyles depicted in Breaking Bad. To the contrary, I suspect that the vast majority of us are struggling, like others, to make ends meet to put food on the table. And, perhaps more importantly, I don’t think that money, fame and fortune induced most of us to become scientists in the first place. Portraying scientists as ego-maniacal, thoughtless, self-absorbed dilettantes sends the wrong message to an American public that is already suspicious and distrustful of science.

Second, Walt’ colleagues view him as a “failed scientist” who, despite his brilliance, has been humiliated and reduced to teaching chemistry (at a low wage) to high school students. Listen to an exchange between Walt and his oncologist “I am an extremely overqualified high school chemistry teacher. When I can work I make $43,700 per year. I have watched all of my colleagues and friends surpass me in every way imaginable....” Unfortunately, Walt’s view of himself—as a lowly, underpaid high school chemistry teacher —is consistent with the attitudes of many academicians who feel that teaching is far less important or valuable than laboratory research. In my previous life as a medical school faculty member, it wasn’t uncommon to see a prominent researcher cringe or shake his/her head in disbelief at the mere mention of a teaching career by a graduate student or postdoctoral fellow. I contend that we ought to encourage (and not dissuade) some of our best and brightest students to pursue teaching instead of research careers. Further, academic researchers must begin to recognize that PhDs who choose to pursue careers in teaching are not less competent or failed scientists—they are simply individuals who want to teach! Given the 20-year long decline in American science and technology preparedness, the scientific community can no longer afford to continue to exclusively promote research over careers in teaching and education.

Finally, the American public has long been suspicious and distrustful of science. In support of this, scientists are often portrayed in literature, movies and in the news as dark, and sometimes mad people who, when left unchecked, will unleash scientific “horrors” on the world.  I am old enough to remember the public fears about the secret bio-warfare programs in the Soviet Union and US during the cold war and more recently, the rumor that was circulating after the HIV/AIDS epidemic was disclosed, that the virus was created by the US government. The brouhaha that erupted over genetic engineering in the 1980s and continued suspicions surrounded genetically modified foods and human cloning are other examples of the public’s distrust of science. Sadly, the decision of the Breaking Bad’s creators to turn Walt, whose chemistry brilliance is unrivaled, into a crystal meth cooker perpetuates the myth about “evil misguided scientists” who are willing to jeopardize the safety of others for their own motives or self gain. The creators of Breaking Bad want us to believe that Walt is justified in turning to the dark side because his power hungry, egomaniacal, scientific colleagues have derailed his career and forced him to become an overqualified, underpaid chemistry teacher. In other words, he had no choice but to use his scientific talents to survive, and perhaps, more importantly, prove to his colleagues (and himself) that he truly is a gifted chemist and not a failed scientist.

Admittedly, while the plot line of Breaking Bad is a little over the top, it tends to reinforce the public’s negative perceptions of scientists and does little to assuage suspicions about the dark underside of modern science.  Like most other people, we scientists are human and have made our share of mistakes. Nevertheless, I think that we  must challenge ourselves to make an effort to educate the American public about who we are and what scientists do on a day to day basis.  If we fail to meet this challenge, I think that President Obama will continue to struggle to “restore science to its rightful place in America.”

Until next time...

Good Luck and Good Job Hunting (try public education-schools are hiring!)

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Novartis announced today that it intends to purchase Malvern, PA-based Protez Pharmaceuticals for $400 million. Protez is developing a novel spectrum carbapenem antibiotic that is active against variety drug-resistant Gram positive (most notably MRSA )and Gram negative bacterial pathogens. Its lead compound, PZ-601, is in Phase II human clinical testing. Protez acquired PZ-601 (formerly SMP-216601) in 2005 from Dainippon Sumitomo Pharmaceuticals.   

Novartis is buying Protez to sure up its antibacterial drug pipeline. Novartis already sells Cubicin, (manufactured by Massachusetts-based Cubist Pharmaceuticals Inc.,) in Europe and is developing other antimicrobials including Aurograb and Tifacogin to treat infections.

Like many of the newly marketed antibiotics, PZ-601 is injected and not orally bioavailable. Nevertheless, it is likely that PZ-601 will provide much needed help against the ever increasing number of drug resistant bacterial isolates. Swiss companies Basilea Pharmaceutica AG and Arpida Ltd. are also working on experimental medicines to treat MRSA.

It is not clear how the acquisition will affect Protez employees.  I suspect that most of the employees will keep their jobs except for Company officers.

Until next time…

Good Luck and Good Job Hunting!!!!!

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