Varney--What an idiot :)

Not only did ACAD execute a private placement at a premium to the previous closing price, but their share price was up ~40% today in response to the deal. Does anyone have any idea how they orchestrated this, and is it possible for Corx to achieve the same feat?:

ACADIA Pharmaceuticals Announces $15 Million Private Placement
--Proceeds to Support Advancement of Pimavanserin Phase III Program--

Press Release Source: ACADIA Pharmaceuticals Inc. On Monday January 10, 2011, 8:30 am EST

SAN DIEGO--(BUSINESS WIRE)-- ACADIA Pharmaceuticals Inc. (NASDAQ:ACAD - News), a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders, today announced that it has entered into a securities purchase agreement for a private placement financing with a select group of institutional investors, including New Enterprise Associates and Venrock. Upon the closing of the transaction, ACADIA will receive gross proceeds of $15.0 million from the sale of approximately 12.57 million units at a price of $1.19375 per unit. Each unit consists of one share of ACADIA's common stock and a warrant to purchase 0.35 shares of common stock. The private placement is expected to close on January 12, 2011 and is subject to the satisfaction of customary closing conditions.

The anticipated proceeds from the private placement will provide ACADIA with additional resources to advance its Phase III pimavanserin program, including the ongoing Phase III trials in Parkinson’s disease psychosis, and is expected to extend ACADIA’s cash runway into 2013.

JMP Securities LLC acted as lead placement agent and MTS Securities, LLC, an affiliate of MTS Health Partners, acted as co-placement agent in the transaction.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

The securities sold in the private placement have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission (“SEC”) or an applicable exemption from such registration requirements. ACADIA has agreed to file a registration statement with the SEC covering the resale of the shares of common stock, including the shares of common stock issuable upon exercise of the warrants, sold in the private placement.

We regret to inform shareholders that there was a catastrophic collapse in the Cortex data mine 101 days ago (end of Sept.) and, with the exception of Pierre Tran, we don't believe there were any survivors.

We would have publicly released the information in a timely fashion, however, we were deeply involved in negotiations (from day one) with a private party for the book and movie rights. Please find it in your hearts to understand. There will be a token compensation arrangement (ie., a pittance) for shareholders on record. We hope this will suffice as our sincere consideration for your contributions and encouragement. For those doubters out there--Take that you bloody whiners! You deserve it, fools!

-sadly (pronounced 'SA-delay' to you bitches!)
mgmnt

My money is on the belief that there is no way they are sitting on SA results that the market could/should construe as positive. My only caveat being that the public dissemination would only be the most logical choice for a competent mgmnt team. There is only a small chance they are making effective moves behind the scenes--the evidence is too strong to the contrary.

4 months earlier:

(from NI July/August 2010)

The first half of 2010 has set the stage for Cortex Pharmaceuticals to resurrect itself from its near-death experience of 2009. Following a relatively benign financing courtesy of Korea's Samyang, Cortex consummated a deal with Biovail for the Ampakine/Respiratory depression program. Needing as much upfront cash as possible, they sold the program outright, along with two related compounds, and thus have no royalty rights, only the potential for $15 million in milestone payments. But the $10 million they received upfront will allow them to run the long-awaited Phase II ADHD trial with CX-1739. That trial should begin late 3Q:10, and will take up to a year to complete. The wild card for Cortex is the completion of the seemingly interminable sleep apnea trial, where it has required approximately 20 patients entering screening to produce each trial completer. They have been stuck at fifteen patients for some time, hopefully they will wrap up and unblind the trial in September, regardless of whether they have reached the goal of twenty. Our hope has been that Cortex has stubbornly stayed with its trial this long because of some anecdotal evidence of clinical impact, but that is a hypothesis only. Positive findings--and all they need is a trend with safety, would add an entirely new dimension to the partnering prospects for Cortex.

19 years earlier:

Talking Deals; Small Companies Try a Partnership
By Lawrence M. Fisher
Published: January 9, 1992

SAN FRANCISCO— WHEN science-rich but cash-poor biotechnology companies go looking for a savior with deep pockets, they usually turn to one of the giant drug concerns. Cortex Pharmaceuticals Inc., a start-up company focusing on products for treating brain diseases, tried that route at first, but found a better match with a company its own size.

This week Cortex, based in Irvine, Calif., announced a collaborative agreement with Alkermes Inc., a four-year-old company in Cambridge, Mass., that is developing technology to enable drugs to enter the brain more easily. The two companies will co-develop compounds that Cortex is now working on that are believed to counteract the destruction of nerve cells that accompanies strokes. Alkermes will also make a series of investments in Cortex, which could ultimately total as much as $26.5 million.

Cortex's management knew it could not afford to develop the compounds into drug form and bring the drug to market alone, and began looking for possible partners among the large pharmaceutical companies. But after nine months of meetings with several candidates, none of which they would name, they became discouraged with the slow pace and bureaucracy of those concerns. In contrast, the deal with Alkermes came together in just one month.

"I think we fell in love with each other very quickly, began dating intensely and were married soon after," said Raymond T. Bartus, Cortex's executive vice president for research and development and chief operating officer. "Alkermes is very aggressive," he said, noting the rapid progress Alkermes has made moving its own product into human clinical trials.

Another attraction is that a single successful drug will have the same relative importance to both companies. "Having spent 15 years in large pharmaceuticals companies, I greatly appreciate the net value of working with another small company," Dr. Bartus said. "The net value of a success here is not diluted for either of us. The worst thing we could have done is to do a deal where our first-born wasn't treated with the utmost importance."

For Alkermes, which is developing drug-delivery technologies rather than drugs, Cortex presented an opportunity to acquire a drug candidate at an early stage to which that technology can be applied. Although itself a young company, Alkermes has both more capital, as the result of two successful public offerings last year, and more experience taking a product through development into clinical trials.

"If you think of us as being a company building a significant development capability, the smart thing to do is to pump products through it," said Richard F. Pops, president and chief executive of Alkermes. "It is a huge commitment for a company to make, to take a drug from a bench-level lead to a drug in a vial that you can actually inject in a patient."

The collaboration will focus on three classes of enzyme inhibitors discovered by Cortex. They block the action of calpain, an enzyme that appears to be responsible for the destruction of nerve cells after the brain is temporarily deprived of blood, as during a stroke or heart attack. The action of calpain follows the stroke by several hours, providing an opportunity to administer a drug that blocks it.

Under the terms of the agreement, Alkermes will provide $2 million to Cortex in research and development funds this year and an additional $2.5 million in 1993. As products of the collaboration proceed through clinical trials, Cortex will receive up to $10 million in payments tied to passing various hurdles in testing and regulatory review. The agreement gives Alkermes worldwide, exclusive rights to make and market any products resulting from the collaboration; Cortex will receive royalties on sales.

In a related transaction, Alkermes purchased 750,000 newly issued shares of Cortex's common stock for $1.5 million, and warrants to purchase an additional two million shares of common stock -- one million shares at $3 each and another million at $7.50 each. Cortex shares closed yesterday at $3.75, up $1.5625 a share, in over-the-counter trading; Alkermes shares closed at $27, up $4.75 a share.

One reason Cortex decided on the partnership was that its relatively low stock price precluded doing a secondary public offering during the bull market for biotechnology stocks in recent months. Cortex went public several years ago, at a relatively early point in its history, which has limited its subsequent ability to raise capital. Alkermes waited longer, and was able to go public last year at a more favorable stock valuation.

"The check that we write today is very, very manageable, given our balance sheet," Mr. Pops said, noting that Alkermes has about $56 million.

I think most of the criticisms on this board are harmless, and the speculations into mgmnt strategizing are meaningless (albeit entertaining). The real harm is perpetrated by the over thinking and under delivering squad at the helm. Their non-existent sense of urgency has, in itself, produced our greatest enemy: Time. Not until the bleeding stops, will time work to our advantage.

It's a relief to know that they are interested in digging themselves out of the rubble created from their self-implosion. I suppose they don't have much choice--they are forced to act at this dreadful point in time, or be deadmeat. They must be liquidating their remaining self-esteem, that which was generated from their stand-out year in 2010. Some entity has the opportunity to steal this one from under the shareholders, as the desperation is quite obvious.

The whining I brought to you came from Varney. What other whining did I "come along with" in my prior post that proved your expectation?

Ps. Look up the word hypocrisy and ruminate over your last few posts.

As far as answering your question: They should have sold the company or stepped aside to allow more capable leadership when they had more value, more credibility, and more scientific momentum. Oh well, money ain't nothin' but a thing...

While inching the science forward over the course of many years, they've effectively destroyed the value. What we have here is a babyload. Maybe a growth spurt lies ahead, but you can probably eliminate any hopes of a motherload.

...or a 1:300000 reverse split. Like everything else, they will have no problem developing an ulterior reason which sounds rational and believable to lowly individual shareholders like us (or if they don't, some apologists or tools will). The reason: Denial of near total incompetence. It's odd, that in the 3 or so years I've had concerns over their abilities as leaders, and their delusional sense of financial entitlement (ie., bonuses and options awards), they've only stepped up their dismal performance and pace of nearly impenetrable failings. These gross underachievers defy logic...they shouldn't be alive (figuratively of course).

The Metal Marvel That Has Mended Brains for 50 Years

Lithium—a simple metal and the oldest drug in psychiatry—might protect the brain against mental illness, Alzheimer’s, and other diseases. One problem: There’s no profit in it.

by Paul Raeburn; additional reporting by Monica Heger
From the Brain special issue; published online December 27, 2010

http://discovermagazine.com/2010/the-brain-2/27-metal-marvel-mended-brains-50-years-lithium/article_view?b_start:int=0&-C=

Lithium is as puzzling as it is potent. It was the first drug used to treat mental illness, and more than 50 years later, it is still one of the most widely used psychiatric medications. But the doctors who prescribe lithium to their patients still do not know how it works or even why it works. “It is the most mysterious drug in psychiatry,” says De-Maw Chuang, a biologist at the National Institute of Mental Health. “It’s so small, but it is so powerful.”

Unlike other psychoactive chemicals—large, complex molecules like Prozac (fluoxetine) or Abilify (aripiprazole)—lithium is extremely simple. It is an element, the lightest of the metals, and its chemical properties are similar to those of the sodium in table salt. Nonetheless, researchers have recently found that lithium could be something close to a psychiatric wonder drug. It has two remarkable powers in the brains of mentally ill patients: protecting neurons from damage and death and alleviating existing damage by spurring new nerve cell growth. Far beyond its current application as a mood stabilizer, lithium could be helpful in treating or preventing Alzheimer’s disease, schizophrenia, stroke, glaucoma, Lou Gehrig’s disease (amyotrophic lateral sclerosis), and Huntington’s disease—an impressive tally that earned it the nickname “the aspirin of the brain” in the journal Nature.

The mood-stabilizing powers of lithium were discovered by accident in the 1940s by John F. J. Cade, a lone psychiatrist working in Melbourne, Australia. Cade had noticed that some substance in the urine of patients with mania was particularly toxic and was investigating uric acid as the potential culprit. He added lithium to the uric acid so it would dissolve more easily in water and injected it into mice. The lithium appeared to have a protective effect against the uric acid. Cade also noticed that the injections made the animals extremely lethargic and unresponsive. That response made him wonder: Might lithium also neutralize his patients’ mania?

After giving himself a shot of lithium to be sure it was safe, Cade injected it into 10 patients with manic depression, the roller-coaster psychiatric condition (also known as bipolar disorder) in which people experience bleak depression alternating with agitated, frenzied highs. The results were spectacular: All 10 improved. One man, who had been in “a state of chronic manic excitement for five years, restless, dirty, destructive, mischievous, and interfering,” improved in three weeks. He left the hospital and resumed his job.

In the United States, lithium is now the first-line treatment for bipolar disorder, a dangerous condition with the highest suicide rate of any psychiatric illness. Lithium compounds, usually given as lithium carbonate or lithium citrate, have three beneficial effects on bipolar patients: preventing mania, easing acute manic episodes, and, to a lesser extent, lifting depression.
Picking up Cade’s work decades later, Chuang has found that lithium protects neurons from damage. In one of his first experiments, he and a colleague treated nerve cells in a test tube with glutamate, which stimulates neurons to fire off an electric signal. Glutamate is a natural brain chemical, and we could not survive without it. But it has a dark side: When the brain is injured by trauma or stroke, cells die and release a massive amount of glutamate, which then excites other cells to death. An excess of glutamate is also found in patients with Huntington’s disease, the incurable degenerative condition that killed the folksinger Woody Guthrie.

When Chuang added glutamate to his laboratory cultures of nerve cells, the cells were wiped out. The story was very different when he put lithium in the dishes before adding the glutamate. “The neurons were almost completely protected,” he says. Even better, the protective effect occurred at low concentrations, similar to the doses already being used in psychiatric patients. Chuang repeated the experiment using Prozac and other anti­depressants to see if they had the same protective effect. None of them did. The mysterious little lithium ion was unique.

Next Chuang wanted to know if the compound could protect cells in an actual living brain. So he gave rats lithium for a couple of weeks, then artificially triggered strokes by blocking a brain artery. Lithium reduced the resulting brain damage by half compared with other rats in a control group. It even helped prevent damage when given after an artificial stroke, suggesting an important new medical application. The lithium had to be given quickly after the stroke to save brain cells—probably within a few hours—but hospital emergency room staff could easily be trained to do that.

Chuang has found that the compound has other powers that may make it useful in Huntington’s disease, a genetic illness that causes cell death in a part of the brain called the striatum. By injecting an excitotoxin—a chemical that destroys neurons by overstimulating them—into the striatum of rats, he was able to cause effects similar to those seen in Huntington’s: jerky movements and cognitive problems. When Chuang first administered lithium to the rats, however, the damage caused by the toxin was sharply reduced. He is now studying the effects of lithium in genetically altered mouse models of Huntington’s disease to see whether the drug might be beneficial.

A research group at the Eve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research in Haifa, Israel, found in 2004 that lithium has a similar protective effect in mouse models of Parkinson’s disease. Chuang thinks that the metal might also prevent neuron death in other diseases in which the brain gradually loses function, such as Lou Gehrig’s disease.

If this were all lithium did, it would be impressive. But it also seems to promote cell growth, according to studies by Husseini Manji, a psychiatrist previously at the National Institute of Mental Health and now at Johnson & Johnson. Manji, who has long been interested in bipolar disorder, was studying lithium compounds to gain fresh insights into the cause of the illness. “We thought these drugs were probably working by turning on or off certain genes,” Manji says. His hunch was correct, but he and his colleagues were surprised to learn which genes were involved: Lithium seemed to be affecting the behavior of a so-called cancer gene, BCl-2, which is mutated in certain kinds of leukemia.
Other researchers had found that mutations in the BCl-2 gene were related to the excessive cell growth of leukemia. Manji decided to investigate whether BCl-2 could also be altering the growth of brain cells in bipolar disorder. He collected a group of volunteers with bipolar disorder who were not doing well on medication, and he took them off their drugs completely. He then scanned their brains with magnetic resonance imaging (MRI), which depicts brain anatomy, put them on lithium for four weeks, and scanned them again.

Postmortem studies of bipolar brains have shown that patients’ frontal lobes, regions that control higher cognitive functions, are smaller than normal. The disease causes nerve cells in the frontal lobes to shrivel, their branches and limbs withering like dried flowers. But Manji’s second round of scans—done after the patients had been put on lithium—were remarkable. “We were astounded to see increases in gray matter,” Manji says. In normal volunteers, the drug did not produce any nerve cell growth. “It’s not causing brain cells to grow unregulated, but it’s correcting damage,” Manji says.

These findings point to a deeper understanding of bipolar disorder: They imply that the disorder may arise when nerve cells shrink to the point at which they can no longer communicate effectively with one another, although it’s not clear whether the shrinkage is a cause or a symptom of the condition. Lithium may act like a natural nerve-growth factor, helping the damaged cells reestablish connections and restore the circuits, Manji theorizes. Other drugs, including SSRIs—the class of antidepressants that includes Prozac and Zoloft—also prompt brain-cell growth, which might partly explain how they work.

Manji’s findings about cell regrowth suggest that lithium treatment might be able to prevent or treat other diseases that involve the ongoing death of brain cells. The BCl-2 gene has also been shown to affect the growth of cells in the optic nerve, the bundle of fibers leading from the eyeball to the brain. Glaucoma damages the end of the optic nerve that connects to the retina, causing a gradual loss of vision. Laboratory experiments conducted by Dong Feng Chen at Harvard suggest that lithium, by boosting the expression of BCl-2, might not only prevent glaucoma damage but also aid the regeneration of damaged nerve cells, restoring vision. Chen’s experiments show that when mice with damaged optic nerves are given lithium in conjunction with a drug that reduces scarring, they will regenerate some cells.

The resurgent excitement about lithium has prompted researchers in Melbourne—the site of John Cade’s pioneering experiments—to test it to see if it might prevent schizophrenia, another disease marked by the withering and death of brain cells. “This is not a treatment for schizophrenia,” cautions one of the researchers, Gregor Berger, a psychiatrist now with Integrated Psychiatry Winterthur in Zurich, Switzerland, but formerly at the University of Melbourne. (His office was just a few hundred yards from Cade’s laboratory, which has since been torn down.) “We want to use lithium in the same way as cholesterol-lowering drugs—as a prevention.”

The symptoms of schizophrenia (hallucinations, delusions, apathy, and cognitive problems) usually appear in late adolescence or early adulthood. So Berger and his colleagues aimed young, identifying teenagers who were at risk because they had schizophrenia in their families or had mild symptoms of psychosis, such as imagining they heard their names being called. He performed proton magnetic resonance spectroscopy scans of these at-risk young people before any of them developed schizophrenia, and again after some of them did. His studies documented a clear decrease in brain volume, probably due to a loss of neurons. The question then became this: Could lithium prevent that cell death, and in doing so prevent the illness?

So far, Berger and his colleagues have given lithium to 30 teenagers and young adults at high risk for schizophrenia. “They have fewer symptoms and feel better with lithium, but it is too early to draw any conclusions,” he says. If his study succeeds, it still will not offer help to patients who already have the disorder. But preventing even a small percentage of cases would be a major achievement against a devastating, lifelong disease that is difficult to treat.

In the process of exploring what lithium does, Peter Klein, a developmental biologist at the University of Pennsylvania, identified another promising application. He noticed that lithium blocked the action of a protein called GSK-3. That discovery immediately suggested a link with Alzheimer’s disease. The brains of people with Alzheimer’s disease contain two kinds of abnormal structures: braided fibers known as neurofibrillary tangles and hard, flat growths called amyloid plaques. The two abnormalities are formed in different ways, but GSK-3 is implicated in both processes and both are suppressed by the application of lithium. Klein believes that lithium’s neuroprotective effects could also reduce the loss of neurons seen in Alzheimer’s disease. Only a few trials have tested the compound in Alzheimer’s patients, and results have been mixed so far. Some researchers think it would be more likely to prevent Alzheimer’s rather than improve the cognitive abilities of those who already have the disease.
Lithium is not a perfect drug. In its early years, while researchers and clinicians were still figuring it out, they discovered that the dosage window was extremely narrow. “With many medications you can take four times the normal dose and you’d have some side effects, but nothing that bad,” Manji says. “With lithium, even just 30 percent more can cause serious problems.” People who take it develop a slight shaking of the hands and fingers. It can affect the kidneys and the thyroid gland, and an overdose can be lethal. Most of these side effects can be managed reasonably well by capable doctors who know enough to carefully adjust the dose, however.

Perhaps a bigger obstacle is lithium’s status as intellectual property. Nobody has a patent on the drug. It’s freely available to anyone. If Merck or Pfizer spent millions to prove that lithium protects against schizophrenia or prevents the worst symptoms of Alzheimer’s disease, any other company could sell the drug, profiting from the research done by its competitor. “This is a huge problem,” Manji says. “It’s very difficult to do these clinical studies without a lot of money. The NIH can provide some of that money, but it’s the pharmaceutical industry that must spend the millions of dollars. And they aren’t going to fund it.” Human studies of lithium are stalled out for the most part, he says, because the costs are so high.

As a result, some scientists have had to turn to natural experiments to gain a better understanding of lithium’s potential. Roughly 20 years ago, researchers at the University of California, San Diego, found that the counties in Texas with the highest levels of lithium in the water had the lowest rates of mental hospital admissions for psychosis, neurosis, and personality disorders. Other studies suggested that crime rates were lower in areas where lithium was present in drinking water. In Japan, researchers at Oita University found a correlation between the levels of lithium in drinking water and rates of suicide.
Nobody is yet suggesting that we start dumping the mineral into our water supply. But if the brain-protecting promise of lithium truly pans out, this humble element might become something close to a modern panacea.

The rut is relative to Cortex, not me. The figure possibly lurking in wait--the smart money--is not MJFF. At least that is not what I was suggesting. Lurking implies being outside or on the edge of. MJFF is actually involved with Cortex. Let us not also overstate the impact of what MJFF contributed to us: Your numbers, ie., MJFF contributions to date ($221m) and Sergey Brinn's personal investment in PD ($50m), seem to be sensationalizing the relationship to a down-and-out Cortex team. This was charity by its very creation and definition. Where does a $300+K investment fit in overall (the generous gift to Cortex), both in terms of Corx shareholder's future, and from the vantage point of MJFF, who probably deal with several hundred organizations/institutions on a regular basis. I'm not diminishing the efforts of MJFF at all, whose scope goes far beyond even that of a typical charity, I'm putting it into a more balanced perspective for shareholders, posters, and lurkers.

Much praise should be given to Michael J. Fox, who I always liked as an actor and who I truly admire as a PD research pioneer, but I would not categorize his foundation as smart money. Fortunately for society, they are in a position (Brinn included) to throw a plethora of investment monies at the PD wall and hope some of it sticks. Their purpose is far greater than that of smart money: They are not investing in research to make money, they are making money to give to research to advance science and medicine.

Given that clarification, with what do you disagree?

Stoll talked a lot of bullshit in those days--he knew the formula which would allow him to walk away a very wealthy person. But like many others, he lacked the ethics to deserve it. Now Stoll himself is the artifact. Ironic sort of, isn't it?

Big Pharma's small voice

Out of fear of federal regulation, drug companies shun social media

http://www.delawareonline.com/article/20101219/BUSINESS/12190312

BY JONATHAN STARKEY • THE NEWS JOURNAL • DECEMBER 19, 2010

It's all too common these days to wake up in the morning, fire off a tweet about some piece of news, then log onto Facebook to drone on about one thing or another.

For most, it's all pretty simple, and safe.

Not for Big Pharma.

Executives at pharmaceutical companies are all tied in knots about what they can and can't say through social media sites like Twitter, Facebook and other popular Web forums where patients and doctors congregate.

They worry that one wrong move will land them in the penalty box with the U.S. Food and Drug Administration, their federal regulator.

A recent survey from audit and consulting firm Deloitte found that 35 percent of companies surveyed had no interest in social media, a striking number given that the general public seems enamored with such 21st century pleasures as Tweeting on Twitter and Friending on Facebook. Many firms see the new media as a gold mine for customer engagement.

But more than half of firms surveyed by Deloitte said confusion about what regulators believe is appropriate communication over social networks gives them heartburn about participating.

Promoting a branded drug over Twitter, for example, is virtually unheard of. Even observing conversations at more private forums like Sermo.com, a professional networking site for doctors, has its dangers.

"Our concern is particularly around what the FDA is going to think about social media and the fact that you're really at times limited in what you can communicate," said Fritz Bittenbender, a spokesman for Frazer, Pa.-based Cephalon, which makes the sleep-disorder drug Provigil.

Cephalon recently issued a set of new media guidelines to its employees that cautioned them against promoting products through their personal accounts.

"The FDA could see that as an official corporate message," Bittenbender warned.

Pharmaceutical companies have become masters at pitching their products in old media outlets. Think of those fancy Viagra ads on TV. Or full-page spreads in mass-market magazines hawking the latest and greatest cholesterol pill.

In 1997, the FDA issued rules allowing those direct-to-consumer ads, so long as the drugmaker also discussed the corresponding risks and side effects of the medicines.

It's the lack of similar rules for social media -- where room for messaging is often more limited -- that has made big pharmaceutical players sheepish about entering the space.

Many in the industry believe the Food and Drug Administration is dragging its feet on issuing guidelines for social media use, according to consultants who coach pharma types on using new media tools.

Regulators held a two-day meeting on the topic last November, but have remained mostly silent about guidelines since.

FDA spokeswoman Shelly Burgess said the agency still plans to issue a set of social media guidelines before year's end.

"I think there's a lot of pessimism because it's taken them a year to do something," said Phil Charron, a senior director at Conshohocken, Pa.-based Think Brownstone, which consults with pharma companies.

Meanwhile, the regulator's delay in issuing guidance hasn't kept it from reacting strongly to pharmaceutical companies it believes are using social media networks inappropriately.

In a letter sent in August, and posted to its website, the FDA dinged Swiss drug giant Novartis for its use of a Facebook-sharing widget on a website for its leukemia drug Tasigna.

The widget was a button that allowed the site's visitors to share the drug's information with their friends on Facebook.

Problem was, the FDA, said, the information that carried over to Facebook -- descriptive metadata stored in the page's code -- didn't contain any mention of the drug's risks.

"The shared content is misleading because it makes representations about the efficacy of Tasigna but fails to communicate any risk information associated with the use of this drug," the FDA wrote in its letter, ordering the company to "immediately cease the dissemination of violative promotional materials."

Consultants say this presents one of the most perplexing issues for pharmaceutical companies looking to engage on social networks: How do you communicate risk in limited space, like the 140 characters allowed by Twitter for a single message?

Charron said most hope the FDA will allow companies to place the risk warnings "one click away." But the default position for now, without that guidance? Companies avoid promoting branded products through new media.

Representatives of pharma companies also are often advised to steer clear of doctor and patient forums like Sermo.com, where their participation may be helpful, but raises the risk of regulatory run-ins, consultants say.

"At what point does something that's said around the performance of a product suddenly become a reportable event," said Terry Hisey, head of the U.S. life sciences practice at Deloitte. Hisey said companies remain uncertain about the answer to that question.

Charron, from Think Brownstone, says all of this means less information on the Web. And that's a big deal, considering that 61 percent of American adults look online for information about health care topics, according to a 2009 study from the Pew Research Center.

British drugmaker AstraZeneca, which has its U.S. headquarters and 4,000 employees in Delaware, has a strong presence on networking sites like Twitter, but keeps its accounts mostly focused on industry trends, or news that's non-controversial by any measure.

AstraZeneca's U.S. tweeters -- @AstraZenecaUS -- recently told their 4,134 followers that the company had received a "Community Partner of the Year," award, for example. It ignored news that the company's most important new drug, the blood thinner Brilinta, had failed to win regulatory approval.

In a memo to the FDA in February-- when the regulator was publicly studying the social media issue -- AstraZeneca said its participation on social networking sites was "intentionally quite limited."

"Without guidance, our activities are limited in a manner that we believe is not in the best interests of informed health care decision making," the drugmaker said. "In our absence, consumers will turn to information sources that are not regulated and not always well-informed."

The Switches That Can Turn Mental Illness On and Off

The difference between one personality and another is not determined by genes alone. Love’s got something to do with it too.

by Carl Zimmer
From the June 2010 issue; published online June 16, 2010

http://discovermagazine.com/2010/jun/15-brain-switches-that-can-turn-mental-illness-on-off/article_view?b_start:int=0&-C=

This month’s column is a tale of two rats. One rat got lots of attention from its mother when it was young; she licked its fur many times a day. The other rat had a different experience. Its mother hardly licked its fur at all. The two rats grew up and turned out to be very different. The neglected rat was easily startled by noises. It was reluctant to explore new places. When it experienced stress, it churned out lots of hormones. Meanwhile, the rat that had gotten more attention from its mother was not so easily startled, was more curious, and did not suffer surges of stress hormones.
The same basic tale has repeated itself hundreds of times in a number of labs. The experiences rats had when they were young altered their behavior as adults. We all intuit that this holds true for people, too, if you replace fur-licking with school, television, family troubles, and all the other experiences that children have. But there’s a major puzzle lurking underneath this seemingly obvious fact of life. Our brains develop according to a recipe encoded in our genes. Each of our brain cells contains the same set of genes we were born with and uses those genes to build proteins and other molecules throughout its life. The sequence of DNA in those genes is pretty much fixed. For experiences to produce long-term changes in how we behave, they must be somehow able to reach into our brains and alter how those genes work.

Neuroscientists are now mapping that mechanism. Our experiences don’t actually rewrite the genes in our brains, it seems, but they can do something almost as powerful. Glued to our DNA are thousands of molecules that shut some genes off and allow other genes to be active. Our experiences can physically rearrange the pattern of those switches and, in the process, change the way our brain cells work. This research has a truly exciting implication: It may be possible to rearrange that pattern ourselves and thereby relieve people of psychiatric disorders like severe anxiety and depression. In fact, scientists are already easing those symptoms in mice.
Two families of molecules perform that kind of genetic regulation. One family consists of methyl groups, molecular caps made of carbon and hydrogen. A string of methyl groups attached to a gene can prevent a cell from reading its DNA sequence. As a result, the cell can’t produce proteins or other molecules from that particular gene. The other family is made up of coiling proteins, molecules that wrap DNA into spools. By tightening the spools, these proteins can hide certain genes; by relaxing the spools, they can allow genes to become active.
Together the methyl groups and coiling proteins—what scientists call the epigenome—are essential for the brain to become a brain in the first place. An embryo starts out as a tiny clump of identical stem cells. As the cells divide, they all inherit the same genes but their epigenetic marks change. As division continues, the cells pass down not only their genes but their epigenetic marks on those genes. Each cell’s particular combination of active and silent genes helps determine what kind of tissue it will give rise to—liver, heart, brain, and so on. Epigenetic marks are remarkably durable, which is why you don’t wake up to find that your brain has started to turn into a pancreas.
Our experiences can rewrite the epigenetic code, however, and these experiences can start even before we’re born. In order to lay down the proper pattern of epigenetic marks, for example, embryos need to get the raw ingredients from their mothers. One crucial ingredient is a nutrient called folate, found in many foods. If mothers don’t get enough folate, their unborn children may lay down an impaired pattern of epigenetic marks that causes their genes to malfunction. These mistaken marks might lead to spina bifida, a disease in which the spinal column fails to form completely.
Other chemicals can interfere with epigenetic marks in embryos. Last year, Feng C. Zhou of Indiana University found that when pregnant lab rats consumed a lot of alcohol, the epigenetic marks on their embryos changed dramatically. As a result, genes in their brains switched on and off in an abnormal pattern. Zhou suspects that this rewriting of the epigenetic code is what causes the devastating symptoms of fetal alcohol syndrome, which is associated with low IQ and behavioral problems.
Even after birth the epigenetic marks in the brain can change. Over the past decade, Michael Meaney, a neurobiologist at McGill University, and his colleagues have been producing one of the most detailed studies of how experience can reprogram the brain’s genes. They are discovering the molecular basis for the tale of the two rats.
The differences between rats that got licked a lot and those that got licked only a little do not emerge from differences in their genes. Meaney found that out in an experiment involving newborn rat pups. He took pups whose mothers who didn’t lick much and placed them with foster mothers who licked a lot, and vice versa. The pups’ experience with their foster mothers—not the genes they inherited from their biological mothers—determined their personality as adults.
To figure out how licking had altered the rats, Meaney and his colleagues looked closely at the animals’ brains. They discovered major differences in the rats’ hippocampus, a part of the brain that helps organize memories. Neurons in the hippocampus regulate the response to stress hormones by making special receptors. When the receptors grab a hormone, the neurons respond by pumping out proteins that trigger a cascade of reactions. These reactions ripple through the brain and reach the adrenal glands, putting a brake on the production of stress hormones.
In order to make the hormone receptors, though, the hippocampus must first receive signals. Those signals switch on a series of genes, which finally cause neurons in the hippocampus to build the receptors. Meaney and his colleagues discovered something unusual in one of these genes, known as the glucocorticoid receptor gene: The stretch of DNA that serves as the switch for this gene was different in the rats that got a lot of licks, compared with the ones that did not. In the rats without much licking, the switch for the glucocorticoid receptor gene was capped by methyl groups, and the neurons in the underlicked rats did not produce as many receptors. The hippocampus neurons therefore were less sensitive to stress hormones and were less able to tamp down the animal’s stress response. As a result, the underlicked rats were permanently stressed out.

These studies hint at how experiences in youth can rewrite the epigenetic marks in our brains, altering our behavior as adults. Meaney and his colleagues cannot test this hypothesis by running similar experiments on humans, of course, but last year they published a study that came pretty close.
Meaney’s team examined 36 human brains taken from cadavers. Twelve of the brains came from people who had committed suicide and had a history of abuse as children. Another 12 had committed suicide without any such history. The final 12 had died of natural causes. The scientists zeroed in on the cells from the hippocampi of the cadavers, examining the switch for the stress hormone gene they had studied in rats. Meaney and his colleagues found that the brains of people who had experienced child abuse had relatively more methyl groups capping the switch, just as the researchers had seen in rats that had not been licked much as pups. And just as those rats produced fewer receptors for stress hormones, the neurons of the people who had suffered child abuse had fewer receptors as well.
Child abuse may leave a mark on its victims in much the same way that parental neglect affects rat pups. Abuse seems to have altered the epigenetic marks in their hippocampi. As a result, they made fewer stress receptors on their neurons, which left them unable to regulate their stress hormones, leading to a life of anxiety. That extra stress may have played a part in their committing suicide.

The hippocampus is probably not the only place where experiences rewrite epigenetic marks in the brain. An international group of researchers recently compared the brains of 44 people who had committed suicide with those of 33 people who died of natural causes. The scientists looked at a gene that produces the protein BDNF, which promotes hormone receptors, in a part of the brain called the Wernicke area. That area, located behind the left ear in most people, helps us interpret the meanings of words. In March the researchers reported that the BDNF switch had more methyl groups attached to it in the Wernicke area of suicide victims than in other people.
And the influence of environment doesn’t end with childhood. Recent work indicates that adult experiences can also rearrange epigenetic marks in the brain and thereby change our behavior. Depression, for example, may be in many ways an epigenetic disease. Several groups of scientists have mimicked human depression in mice by pitting the animals against each other. If a mouse loses a series of fights against dominant rivals, its personality shifts. It shies away from contact with other mice and moves around less. When the mice are given access to a machine that lets them administer cocaine to themselves, the defeated mice take more of it.
Eric Nestler, a neuroscientist at Mount Sinai School of Medicine in New York City, wondered what the brains of these depressed mice looked like. Last fall he reported discovering an important difference in a region of the brain called the nucleus accumbens. It was probably no coincidence that depression altered this region, since the nucleus accumbens plays an important role in the brain’s reward system, helping to set the value we put on things and the pleasure we get from them.
The change Nestler and his colleagues discovered in the nucleus accumbens was epigenetic: Some of the DNA in the neurons in that region became more tightly or less tightly wound in depressed mice. Such an epigenetic change might permanently alter which genes are active in the brains of those mice. The same may hold true for humans. Nestler’s team looked at cadaver brains from people who had been diagnosed with depression in life. They discovered the same epigenetic changes in the human nucleus accumbens.
If scientists can pinpoint the epigenetic changes that our experiences impart, it may be possible to reverse those changes. Nestler and his colleagues pumped drugs known as HDAC inhibitors into the nucleus accumbens of their depressed mice. These drugs can loosen tight spools of DNA, making it possible for cells to gain access to genes again. Ten days after treatment, the mice were more willing to approach other mice. The drug also erased many other symptoms of depression in the animals.
The possibility that we can rewrite the epigenetic code in our brains may be exciting, but it is also daunting. Modifying epigenetic markers is not easy—and that’s a good thing. After all, if our methyl groups and coiling proteins were constantly shifting, depression would be the least of our problems. Nothing ruins your day like finding that your brain has turned into a pancreas.

A Sleepy Secret

A healthy young man falls into a coma, but there are few other signs that anything else is wrong. Then comes the real surprise.

by Tony Dajer
From the September 2010 issue; published online December 11, 2010

http://discovermagazine.com/2010/sep/17-vital-signs-a-sleepy-secret

The woman burst through the emergency room doors shouting: “Where’s my son?”
“Over here,” I blurted, startled by her entrance. Short and wiry, she flew past the paramedics to her motionless, well-built 25-year-old. Then, turning to me, she rose on the balls of her feet and hissed, “I told those doctors he needed an MRI!”
“Does he have epilepsy, ma’am?” I asked carefully. “Any type of seizure disorder?”
“He did this once before,” she continued, as if not listening. “Those idiots upstate couldn’t tell me what was wrong. Three months ago he had this…event. Same as today. They told us to see a neurologist. But the damn insurance company wouldn’t approve the MRI.”
Trying to take control of the situation, I pulled aside the lead paramedic. “Tell me again—why did you intubate him?”

“He was comatose,” the burly man in the blue uniform said. “Didn’t respond to Narcan,” an antidote to overdoses of opiates, like heroin. “Then he started seizing.”
“Full-blown seizures?” I asked.
“Hard to tell,” the paramedic replied, wiping his forehead. “Jerking his arms back and forth, not breathing well. We decided not to wait, so we sedated him—that stopped the seizures—and then we put the tube in.”
Comatose patients have a tendency to vomit stomach contents into their lungs. A cuffed breathing tube prevents that. “Sounds reasonable,” I said. “And when the family called 911, what exactly did they say?”
“Mom found him in bed, couldn’t wake him up.”
The young man on the gurney looked utterly peaceful—except for the plastic breathing tube arcing out of his mouth. I turned back to the mother and asked, “Did he have a CAT scan that first time?”
She smirked. “It came out normal.”
A young woman came over to where we were standing. “I’m the sister,” she said.
Seeing a new opportunity for information, I asked, “Any drugs that you know of? Medications?”
Mother and daughter’s heads both shook an emphatic no. “He’s a good boy. No drinking, no craziness,” Mom cut in.
“He had some friends over last night. They hung out upstairs,” the sister added. “Maybe a few beers. Nothing more.”
The young man’s physical exam offered no clues. His vital signs were perfect; his pupils were small but reacted well to light; his arms and legs barely moved when pinched, but they had good tone, not the flaccid splay of paralysis. I went down the differential diagnosis. Drug overdose? That would have been detected three months earlier, the first time this happened. Brain bleed or meningitis? Obviously these were the nastiest contenders, but my alarm bells weren’t going off; coma aside, Doug looked too good. Persistent seizures? He lay inert as a statue (although it is possible for a brain to have epileptic electrical activity yet cause no visible muscle contractions).
The best clue I had was that this event was a repeat. But a repeat of what? Relapsing encephalitis? Narcolepsy? A degenerative neuronal disorder? A new form of mad cow disease? I envisioned the answer buried in some thick tome titled Neurological Disorders You Can’t Even Imagine.

Doug’s mother grabbed my arm. “What is wrong with him?” she pleaded, tears now welling up.
“Don’t worry. We’ll do the tests he needs.”
A CAT scan showed nothing (again). Minutes later, Doug started thrashing and breathing quickly, as if the breathing tube were gagging him. Good sign. Was he waking up? I deflated the cuff and pulled the tube. Coughing until he turned red, he tried to sit up, popped his eyes open, then fell back. Abruptly he resumed breathing very quickly, stopped for a full minute, then revved up again.
“Is that Cheyne-Stokes breathing?” the nurse asked me. This ragged, stop-and-start breathing pattern—so distinctive it has its own eponym—indicates a malfunction in the brain stem’s breathing center. I had seen it most recently in a patient with lupus-induced brain inflammation. He had died.

The toxicology screen came back clean: No alcohol, no Valium, no cocaine. And the rest of Doug’s blood work was stone-cold normal. Stumped, I phoned a member of the intensive care team. “Twenty-five-year-old man,” I began. “Unexplained coma, maybe seizures. Might need a spinal tap. On the positive side, neck’s supple, no fever, no white count. Either way, he needs to be in the ICU.”
“OK,” the junior resident said. “But please call our attending. She has to approve.”
Two minutes later I had the attending on the phone. “Sara here.”
“Sorry to sound so vague,” I said, then recapped the story.
Silence on the other end. Finally she asked, “Is this kid on GHB?”
“Family denies drugs,” I said, instantly hearing how weak that sounded. “Idiot!” I thought to myself. “I’ll call you back,” I answered aloud. I wanted to slam down the receiver.
I cornered mom and sister. “Sorry, but we have to know this: Did Doug do GHB last night?”
Mom did a double take: “What?” But a look flitted across the sister’s face.
“Please ask his friends specifically. Tell them it’s life-or-death.”
Gamma hydroxybutyrate (commonly called G, liquid ecstasy, Georgia home boy, or cherry meth) is to rave parties of the new millennium what cocaine was to Wall Street of the 1980s. A natural brain neurotransmitter, GHB is a stimulant in small doses. Take an extra hit and it is said to bring on a warm, dreamy feeling, with some sexual arousal thrown in for good measure. As a recreational drug, it enhances the hypnotic, techno-music-driven, quivering state that defines rave parties.
The catch? At higher concentrations GHB binds to the GABA brain receptors, just as Valium does. This interaction produces GHB’s signature effect: lights out, like walking into a Mike Tyson uppercut. Worse, GHB’s dose effect is wildly unpredictable. A tad too much and you can go from life of the party to 911 emergency. (GHB was used as an anesthetic in the 1960s but was discontinued precisely because dosing was so touchy.) Little wonder that it has become a leading cause of drug-induced coma and ranks second among all illegal drugs in requiring emergency consultations. Throw in alcohol—which competes for the same liver enzymes that metabolize GHB—and the duration and severity of the drug’s effects zoom off the charts.
Side effects of GHB overdose run the gamut from vomiting, muscle spasms, and seizures to slow heart rate and cardiac arrest. Since its rise in popularity in the 1990s, GHB has killed hundreds. And it is highly addictive: Some abusers need a hit every two hours. Withdrawal after chronic use is particularly nasty. Delirium and life-threatening agitation can flare for weeks after GHB is stopped.
GHB has also gained notoriety as the “date-rape drug.” An odorless, colorless liquid easily masked by a cocktail, it is quickly metabolized and not detectable in routine blood and urine tests. A specialized lab might pick it up, but only by analyzing an immediately obtained urine sample. GHB doesn’t even have to knock a victim out. At a sub-KO dose it can induce amnesia, arousal, and a passive, compliant state of mind.
The sister returned. “The friends fessed up,” she said with a brisk, grim nod. “They did some GHB last night.”
Mom just stared. Then her shoulders sagged.
I called Sara back. “Bingo. And thanks for turning my brain back on. That ‘second episode’ malarkey had me going.”
“You’re welcome,” she replied graciously. “My husband’s a cop. He’s seen a lot of it lately.”
I turned back to the family. The fight with the insurance company over getting an MRI? The kid watching his mom go to the mat for him—for a lie? Then doing it all over again?
I raised my eyebrows at the sister. Her gaze went opaque. Who knew what went on here? I wondered.
The good news was that Doug didn’t display any signs of chronic GHB use, and once this dose of the drug was out of his system, he would be none the worse for wear.
“He should wake up in a few hours,” I reassured his mother. “He’ll be OK.”
“No he won’t,” she muttered, her voice fierce again.

Why Scientific Studies Are So Often Wrong: The Streetlight Effect

Researchers tend to look for answers where the looking is good, rather than where the answers are likely to be hiding.

by David H. Freedman
From the July-August special issue; published online December 10, 2010

A bolt of excitement ran through the field of cardiology in the early 1980s when anti-arrhythmia drugs burst onto the scene. Researchers knew that heart-attack victims with steady heartbeats had the best odds of survival, so a medication that could tamp down irregularities seemed like a no-brainer. The drugs became the standard of care for heart-attack patients and were soon smoothing out heartbeats in intensive care wards across the United States.

But in the early 1990s, cardiologists realized that the drugs were also doing something else: killing about 56,000 heart-attack patients a year. Yes, hearts were beating more regularly on the drugs than off, but their owners were, on average, one-third as likely to pull through. Cardiologists had been so focused on immediately measurable arrhythmias that they had overlooked the longer-term but far more important variable of death.

The fundamental error here is summed up in an old joke scientists love to tell. Late at night, a police officer finds a drunk man crawling around on his hands and knees under a streetlight. The drunk man tells the officer he’s looking for his wallet. When the officer asks if he’s sure this is where he dropped the wallet, the man replies that he thinks he more likely dropped it across the street. Then why are you looking over here? the befuddled officer asks. Because the light’s better here, explains the drunk man.

That fellow is in good company. Many, and possibly most, scientists spend their careers looking for answers where the light is better rather than where the truth is more likely to lie. They don’t always have much choice. It is often extremely difficult or even impossible to cleanly measure what is really important, so scientists instead cleanly measure what they can, hoping it turns out to be relevant. After all, we expect scientists to quantify their observations precisely. As Lord Kelvin put it more than a century ago, “When you can measure what you are speaking about, and express it in numbers, you know something about it.”

There is just one little problem. While these surrogate measurements yield clean numbers, they frequently throw off the results, sometimes dramatically so. This “streetlight effect,” as I call it in my new book, Wrong (Little, Brown), turns up in every field of science, filling research journals with experiments and studies that directly contradict previously published work. It is a tradition that was already well established back in 1915 when an important experiment led by a rather prominent young physicist named Albert Einstein was published. To discover the ratio of magnetic forces to gyroscopic forces on an electron, Einstein had to infer what the electrons in an iron bar were up to based on a minuscule rotation their activity caused the bar to make. His answer was off by a factor of two, as corrected by more careful, but similarly inferential, experiments three years later. (What a loser!)

Physicists have a good excuse for huddling under the streetlight when they are pushing at the limits of human understanding. But the effect also vexes medical research, where you might think great patient data is there for the tabulating. The story of the anti-arrhythmia drugs only hints at the extent of the problem. In 2005, John Ioannidis of the University of Ioannina in Greece examined the 45 most prominent studies published since 1990 in the top medical journals and found that about one-third of them were ultimately refuted. If one were to look at all medical studies, it would be more like two-thirds, he says. And for some kinds of leading-edge studies, like those linking a disease to a specific gene, wrongness infects 90 percent or more.

We should fully expect scientific theories to frequently butt heads and to wind up being disproved sometimes as researchers grope their way toward the truth. That is the scientific process: Generate ideas, test them, discard the flimsy, repeat. In fact, testing ideas is supposed to be the core competence of most scientists. But if tests of the exact same idea routinely generate differing, even opposite, results, then what are we humble nonscientists supposed to believe?

I have spent the past three years examining why expert pronouncements so often turn out to be exaggerated, misleading, or flat-out wrong. There are several very good reasons why that happens, and one of them is that scientists are not as good at making trustworthy measurements as we give them credit for. It’s not that they are mostly incompetents and cheats. Well, some of them are: In several confidential surveys spanning different fields, anywhere from 10 to 50 percent of scientists have confessed to perpetrating or being aware of some sort of research misbehavior. And numerous studies have highlighted remarkably lax supervision of research assistants and technicians. A bigger obstacle to reliable research, though, is that scientists often simply cannot get at the things they need to measure.

Examples of how the streetlight effect sends studies off track are ubiquitous. In many cases it is painfully obvious that scientists are stuck with surrogate measures in place of what they really want to quantify. After decades of dueling studies about whether it was an asteroid or volcanic eruptions that did in the dinosaurs, it is apparent that the mineral-deposit evidence is indirect and open to interpretation, even if the scientists advancing the various claims sound pretty sure of themselves. Astronomers enlist surrogate measures all the time, since there is no way to stick thermometers in stars or to unreel tape measures to other galaxies. Likewise, economists cannot track the individual behaviors of billions of consumers and investors, so they rely on economic indicators and extracts of data.

How reliable are the results? In 1992 a now-classic study by researchers at Harvard and the National Bureau of Economic Research examined papers from a range of economics journals and determined that approximately none of them had conclusively proved anything one way or the other. Given that dismal assessment—and given the great influence of economists on financial institutions and regulation—it’s a wonder the global economic infrastructure is not in far worse shape. (Of course, scientific findings that point out the problems with scientific findings are fair game for reanalysis too.)

By far the most familiar and vexing consequences of the streetlight effect show up in those ever-shifting medical findings. Take this straightforward and critical question: Can vitamin D supplements lower the risk of breast, colon, and other cancers? Yes, by as much as 75 percent, several well-publicized studies have concluded over the past decade. No, not at all, several other equally well-publicized studies have concluded. In 2008 alone, around 380 published research articles addressed the link between vitamin D and cancer in one way or another. The ocean of data on the topic is vast, swelling, and teeming with sharp contradictions.

One likely confounding factor is the different ways in which the studies assessed the intake of vitamin D. In fact, some of the studies did not measure intake at all. Researchers simply looked at levels of the vitamin in subjects’ blood without tracking whether supplements affected those levels, assuming that both artificially and naturally high levels have the same effect on cancer risk. In some cases researchers looked at blood levels of the vitamin only after a cancer had been diagnosed, instead of measuring the levels before and after. In other cases scientists asked subjects how many vitamin D pills they took but did not look at blood levels. The investigators in at least one widely reported study did not look at vitamin D blood levels or supplement intake at all. They merely estimated blood levels based on the sunniness of the subjects’ geographical locations, since sunlight spurs the body to produce vitamin D.

The point is not that the scientists running these studies screwed up. They were probably doing the best they could with the data they had. We would certainly be a lot more likely to get a straight answer if someone would carefully track pill intake, blood levels, and cancer outcomes in a large population for many years. But such large, clean studies can take years of planning, fund-raising, and lining up patients, plus a decade or more to execute. That is why we first get bombarded by years of weaker studies plagued by the streetlight effect. It sure would be nice if someone would point that out to us when one of those studies makes headlines.

Maybe while we are waiting for that to happen we should pop vitamin D pills just in case, as physicians now commonly recommend. Chances are, that is good advice—unless, of course, the wisdom on vitamin D ends up following the same path as the consensus on aspirin. That consensus long insisted that most people with risk factors for heart disease ought to take a low dose of aspirin every day. But now the prevailing view maintains that unless you have a worrisome history of heart problems, an aspirin regimen is about as likely to hurt you as help you. Oops.

Posted on Sat, Dec. 18, 2010

Frank Baldino Jr., 57, founder and chief of biotech firm Cephalon

By Linda Loyd
Inquirer Staff Writer
Frank Baldino Jr. was a biotech survivor. He started Cephalon Inc. in 1987 and developed it from zero to an expected $2.7 billion in annual revenue. He was still running the company after 23 years.

Mr. Baldino, 57, who had been on medical leave from Cephalon since August, lost his battle Thursday evening with leukemia. He died at the Hospital of the University of Pennsylvania.

The charismatic founder and chief executive of the region's largest independent biotechnology company was remembered by colleagues, university leaders, and the philanthropic world as a great guy, bigger than life, and extremely generous.

Many consider the Dutch-born biochemist Hubert J.P. Schoemaker to be the father of the local biotechnology industry. With three colleagues, he started the Philadelphia region's first biotech company, Centocor Inc., in 1979.

Frank Baldino was a close second.

"This is a guy who started in a cubicle in an incubator with a book of how to write a business plan and took the company to a multibillion-dollar organization," said Bruce Peacock, who worked for Mr. Baldino from 1988 to 1996, when Peacock left to head Orthovita Inc. in Malvern.

"Across the nation, he's one of the very few guys who has done it from scratch to a commercial, large, successful company," said Peacock, now a venture partner in SV Life Sciences in Boston and chief business officer of Ophthotech Corp. in Princeton.

"He helped dozens of other entrepreneurs get companies started. Frank was just a force," Peacock said. "He was a scientist by training, but developed an acumen in finance, sales, and marketing as well. It's a sad day."

Brenda D. Gavin, managing partner of Quaker Bio Ventures in Philadelphia, said she personally has known "fewer than a handful of people" who took a company from the science, through venture funding, public financing, and product approval to profitability.

"Believe me, they are so rare," Gavin said. "Typically what happens, the guy who's the founder is not the same person who can go forward and take it all the way.

"The great thing about Frank," Gavin said, "after he had the personal success with his company, he was instrumental in getting the life-sciences greenhouses started and funded in Pennsylvania, particularly the local one. He's on the board there. He really tried to give back to the community."

The "greenhouses" in Philadelphia, Harrisburg, and Pittsburgh are economic-development incubators for life-sciences jobs and businesses.

Although friends and colleagues knew he was ill, "everybody thought he'd be back. This is Frank!" Gavin said. "He's indomitable and would beat this and be back."

At age 33, while a research biologist at DuPont Co., Mr. Baldino was approached by two venture capitalists and asked to start a company to treat neurological diseases. He jumped at the chance and took with him two other DuPont scientists.

He built Cephalon, in Frazer, from no products in the late 1990s to eight sold now in the United States and more than 150 products sold in 80 countries. The company, whose net income was $342.6 million in 2009, employs about 4,000.

Cephalon has grown by looking for drugs and businesses to buy and, in the last decade, acquired 16 products or companies.

Cephalon's first experimental drug, Myotrophin - for amyotrophic lateral sclerosis, or Lou Gehrig's disease - was rejected by the Food and Drug Administration. Even while working on Myotrophin in the early 1990s, Cephalon looked to diversify, and it licensed modafinil, sold under the brand name Provigil. It was that treatment for narcolepsy that became its first big seller.

Mr. Baldino, one of the longest-serving CEOs in biotech who has a doctorate in pharmacology from Temple University, ran one of the nation's few profitable biotechnology companies.

He had been a Temple trustee since December 2001. "We were repeatedly impressed with Frank's energy and enthusiasm for Temple, particularly his passion for enhancing Temple's reputation in the medical and business communities," board chairman Patrick J. O'Connor and university president Ann Weaver Hart said in a prepared statement.

Mr. Baldino also was a board member of the Franklin Institute, where he brought the perspective of scientist, businessman, and entrepreneur. "Frank's entrepreneurial spirit was really matched by his strong philanthropic drive," said institute president and CEO Dennis Wint. "His enduring legacy is one of creativity, generosity, leadership, and a passionate belief in the transformative powers of science to make the world a better place."

Out of respect for Mr. Baldino, the company was not discussing a succession plan Friday.

Cephalon chief operating officer J. Kevin Buchi has been handling Mr. Baldino's duties since August.

"He's a very capable guy," Gavin said, referring to Buchi. "I'm not privy to their plans. It will be the board's decision. The company, in this interim, has been functioning very well. The company will be fine. But still, it's a real blow."

Cephalon shares closed up $2.13, or 3.38 percent, at $65.24 on Wall Street speculation that the company might now be sold.

Cephalon vice president of public affairs Fritz Bittenbender said, "The short term is, we are not talking about a transition out of deference to Frank and his family." Buchi has been a strong leader during Mr. Baldino's medical leave, Bittenbender said, "and he will remain so in the near term."

Mr. Baldino is survived by his wife, Sandra; their two sons, Douglas, 6, and Harris, 1; and two sons, Jeff, 28, and James, 21, and daughter Leslie, 26, from a previous marriage.

In lieu of flowers, those wishing to honor Dr. Baldino and his family may make a contribution to:

Bone Marrow Transplant Research Fund
University of Pennsylvania
Attn: Elda Ford
3400 Civic Center Boulevard
PCAM 2 West Pavilion
Philadelphia, PA 19104

Let's just say I hope you are right--I'm sick and tired of being this malcontent and bitter. I would like a decent outcome of course, and I'm just too damn stubborn to give up on the science...

Frank Baldino Jr., 57, founder and chief of biotech firm Cephalon

By Linda Loyd
Inquirer Staff Writer
Frank Baldino Jr. was a biotech survivor. He started Cephalon Inc. in 1987 and developed it from zero to an expected $2.7 billion in annual revenue. He was still running the company after 23 years.

Mr. Baldino, 57, who had been on medical leave from Cephalon since August, lost his battle Thursday evening with leukemia. He died at the Hospital of the University of Pennsylvania.

The charismatic founder and chief executive of the region's largest independent biotechnology company was remembered by colleagues, university leaders, and the philanthropic world as a great guy, bigger than life, and extremely generous.

Many consider the Dutch-born biochemist Hubert J.P. Schoemaker to be the father of the local biotechnology industry. With three colleagues, he started the Philadelphia region's first biotech company, Centocor Inc., in 1979.

Frank Baldino was a close second.

"This is a guy who started in a cubicle in an incubator with a book of how to write a business plan and took the company to a multibillion-dollar organization," said Bruce Peacock, who worked for Mr. Baldino from 1988 to 1996, when Peacock left to head Orthovita Inc. in Malvern.

"Across the nation, he's one of the very few guys who has done it from scratch to a commercial, large, successful company," said Peacock, now a venture partner in SV Life Sciences in Boston and chief business officer of Ophthotech Corp. in Princeton.

"He helped dozens of other entrepreneurs get companies started. Frank was just a force," Peacock said. "He was a scientist by training, but developed an acumen in finance, sales, and marketing as well. It's a sad day."

Brenda D. Gavin, managing partner of Quaker Bio Ventures in Philadelphia, said she personally has known "fewer than a handful of people" who took a company from the science, through venture funding, public financing, and product approval to profitability.

"Believe me, they are so rare," Gavin said. "Typically what happens, the guy who's the founder is not the same person who can go forward and take it all the way.

"The great thing about Frank," Gavin said, "after he had the personal success with his company, he was instrumental in getting the life-sciences greenhouses started and funded in Pennsylvania, particularly the local one. He's on the board there. He really tried to give back to the community."

The "greenhouses" in Philadelphia, Harrisburg, and Pittsburgh are economic-development incubators for life-sciences jobs and businesses.

Although friends and colleagues knew he was ill, "everybody thought he'd be back. This is Frank!" Gavin said. "He's indomitable and would beat this and be back."

At age 33, while a research biologist at DuPont Co., Mr. Baldino was approached by two venture capitalists and asked to start a company to treat neurological diseases. He jumped at the chance and took with him two other DuPont scientists.

He built Cephalon, in Frazer, from no products in the late 1990s to eight sold now in the United States and more than 150 products sold in 80 countries. The company, whose net income was $342.6 million in 2009, employs about 4,000.

Cephalon has grown by looking for drugs and businesses to buy and, in the last decade, acquired 16 products or companies.

Cephalon's first experimental drug, Myotrophin - for amyotrophic lateral sclerosis, or Lou Gehrig's disease - was rejected by the Food and Drug Administration. Even while working on Myotrophin in the early 1990s, Cephalon looked to diversify, and it licensed modafinil, sold under the brand name Provigil. It was that treatment for narcolepsy that became its first big seller.

Mr. Baldino, one of the longest-serving CEOs in biotech who has a doctorate in pharmacology from Temple University, ran one of the nation's few profitable biotechnology companies.

He had been a Temple trustee since December 2001. "We were repeatedly impressed with Frank's energy and enthusiasm for Temple, particularly his passion for enhancing Temple's reputation in the medical and business communities," board chairman Patrick J. O'Connor and university president Ann Weaver Hart said in a prepared statement.

Mr. Baldino also was a board member of the Franklin Institute, where he brought the perspective of scientist, businessman, and entrepreneur. "Frank's entrepreneurial spirit was really matched by his strong philanthropic drive," said institute president and CEO Dennis Wint. "His enduring legacy is one of creativity, generosity, leadership, and a passionate belief in the transformative powers of science to make the world a better place."

Out of respect for Mr. Baldino, the company was not discussing a succession plan Friday.

Cephalon chief operating officer J. Kevin Buchi has been handling Mr. Baldino's duties since August.

"He's a very capable guy," Gavin said, referring to Buchi. "I'm not privy to their plans. It will be the board's decision. The company, in this interim, has been functioning very well. The company will be fine. But still, it's a real blow."

Cephalon shares closed up $2.13, or 3.38 percent, at $65.24 on Wall Street speculation that the company might now be sold.

Cephalon vice president of public affairs Fritz Bittenbender said, "The short term is, we are not talking about a transition out of deference to Frank and his family." Buchi has been a strong leader during Mr. Baldino's medical leave, Bittenbender said, "and he will remain so in the near term."

The funeral will be private for family, with a public memorial service later.

Mr. Baldino is survived by his wife, Sandra; their two sons, Douglas, 6, and Harris, 1; and two sons, Jeff, 28, and James, 21, and daughter Leslie, 26, from a previous marriage.

In lieu of flowers, those wishing to honor Dr. Baldino and his family may make a contribution to:

Bone Marrow Transplant Research Fund
University of Pennsylvania
Attn: Elda Ford
3400 Civic Center Boulevard
PCAM 2 West Pavilion
Philadelphia, PA 19104

I think if they have to spend this much time fine-tuning the data on a tiny little study that took nearly two years (and at the rate of 1 enrollee per month, mind you), on the contrary, it looks weak and pathetic. But that is just par for the course when summing up this perpetual disappointment.

Early Holiday Gift?—Alzheimer’s Act Goes to President’s Desk



16 December 2010. The National Alzheimer’s Project Act could be signed into law just in time for Christmas. On 8 December 2010, the U.S. Senate passed their version of the bipartisan Act (S.3036), originally coauthored by Representatives Edward J. Markey of Massachusetts and Chris Smith, New Jersey, and championed in the Senate by Evan Bayh from Indiana and Susan Collins of Maine. Early yesterday, the House of Representatives overwhelmingly gave the Act their approval. President Obama now has 10 days to sign the Act into law or reject it.
The National Alzheimer’s Project Act (NAPA) mandates the establishment of an office within the Department of Health and Human Services to devise a national plan for tackling Alzheimer’s disease, including coordination of efforts for research, treatment, and education. The Office will be aided by an Advisory Council. NAPA was one of the recommendations of the Alzheimer’s Study Group (see ARF related news story). To stay with the gift metaphor for a moment, however, NAPA is mostly a token of recognition, as it comes without appropriation of actual funds for research or care.

“This is a significant, but first step in devising a national strategy for dealing with Alzheimer’s disease,” said Bruce Lamb, Cleveland Clinic, Ohio. “Ultimately, increased funding for research will be required to devise effective treatments and therapies for those suffering with the disease.” Lamb chaired the Alzheimer’s Breakthrough Ride, which recently rolled into Washington in support of NAPA and the Alzheimer’s Breakthrough Act, which languishes in Congress. The Alzheimer’s Breakthrough Act would appropriate an extra $2 billion a year to fund research on AD. This infusion would address a looming funding crisis at the National Institute on Aging (see ARF related conference story).

NAPA’s passage came after a flurry of intense activity in the national media and before Congress on the part of numerous advocacy groups in the past few weeks. For example, the Alzheimer’s Foundation of America ran a telethon on NBC stations on 4 December, the Geoffrey Beene Foundation organized a letter campaign, and the Alzheimer’s Association lobbied intensely. On 9 December, experts from the NIA, AD organizations, and a public-private partnership called the Coalition Against Major Diseases testified before the Subcommittee on Health for the Committee on Energy and Commerce of the U.S. House of Representatives. See their freely downloadable statements to the nation’s representatives.—Tom Fagan and Gabrielle Strobel.

Neuro-Do you have any idea on the nature of Baldino's ailment?:

Cephalon CEO dies at 57 after medical leave

Dec 17 (Reuters) - Frank Baldino Jr., chief executive and founder of biotechnology company Cephalon Inc (CEPH.O), died Thursday night at the age of 57, the company said. The cause of death was not disclosed.

Cephalon announced in August that Baldino would take a temporary medical leave and said the company, which makes the sleep disorder drugs Provigil and Nuvigil, would be run in his absence by Kevin Buchi, its chief operating officer.

On Dec. 6 the company said Baldino would be on medical leave indefinitely and that Buchi would continue to perform his duties.

Announcing his death, Fritz Bittenbender, vice president of public affairs, said that "in deference to Frank and his leadership, we are not going to make any announcements about the transition in the near future."

Baldino, who received a Ph.D. in pharmacology from Temple University, founded Cephalon roughly 20 years ago and built it on the back of Provigil, a drug for a rare sleep disorder called narcolepsy. Provigil was subsequently approved in other indications.

The company now focuses on central nervous system disorders such as pain, and cancer. Cephalon has a market value of $4.7 billion.

From 1981 to 1987, Baldino served as senior research biologist in the medical products department at DuPont Co (DD.N), where he was responsible for developing research strategies for identifying novel neuropharmaceutical agents.

Among many other positions, Baldino chaired the Executive Council of the Harvard Division of Sleep Medicine and was a member of the boards of Temple University, the University of the Sciences in Philadelphia, and the Franklin Institute. (Reporting by Toni Clarke, editing by Gerald E. McCormick and John Wallace)

Cephalon Mourns the Passing of Founder, Chairman and CEO, Frank Baldino Jr., Ph.D.

Press Release Source: Cephalon, Inc. On Friday December 17, 2010, 8:05 am EST

FRAZER, Pa., Dec. 17, 2010 /PRNewswire/ -- Cephalon, Inc. (Nasdaq:CEPH - News) is sad to announce today that its founder, Chairman and Chief Executive Officer, Frank Baldino, Jr., Ph.D. passed away Thursday evening, December 16, 2010. A pioneer in the biotechnology industry, he was an inspirational leader who will be sorely missed. The Cephalon organization mourns his passing and extends its sympathies to the entire Baldino family.

Really ombow, this is what you're pegging your confidence on...the 'tone' of his formal response? Y'all need to find a new method of searching for clues. Between you and Jerry, there is no need for a blind man to [mis]lead this investment path into a black hole. I would, however, choose a blind man to run this company, any day, over the insane clown posse we've been graced with--those with physical disabilities tend to have a heightened/exceptional ability with other senses...

I believe your cup runneth over. May I suggest a Pythagorean cup--I think ombow has one that he isn't using.

Not exactly a bold prediction. Now, if you would just have left [the speculation] at an ADHD partnership by the end of the year, then you would have really dropped my jaw...

Jerry--They haven't had a real partnership during my humble time here, commencing some 6 years ago. Now you want to throw a sizable partnership in the mix for year end? Dude, you lost your marbles...

With fuzzy mgmnt comes fuzzy math. eom

Your hunch, or something similar to it, is the only thing of investment value which can be derived from that article (ie. reading the tea leaves). The content itself is complete trash. Most disconcerting is the focus on children's ADHD, as that is likely the longest shot on goal (ie. the furthest carrot).