The vaccine is late, and in short supply—just at the US epidemic may be hitting its peak (see this ominous interactive map from the Wall Street Journal.)

But there is no shortage of blame: slow-growing viruses, chicken shortages, and, according to one opinion piece, higher doses of vaccine going to women than they may need. So, why not add another culprit to the mix: the lack of adjuvants. These are substances added to vaccines to increase their potency and decrease dosage.

The US is not using adjuvants in swine flu vaccines, whereas European regulators have approved them. As a consequence, each US citizen lucky enough to get a shot will be injected with 3 times as much vaccine material than people in Europe (15 vs. 3.75 micrograms).

But there are some subtleties. For instance, not all manufacturers in Europe are producing adjuvanted vaccines. Glaxo Smith Kline and Novartis, companies with large research enterprises devoted to adjuvants, have put them in their swine flu shots. But other companies, such as Baxter International, have not. European health authorities, it seems, have not figured out how to get adjuvants into the non-adjuvanted vaccine—something that can be done at the sight of administration. The US was prepared to spike its vaccines with adjuvant, ordering more than $500 million of the stuff from Novartis and GSK in case it was needed.

Another factor that could affect global supply is that European regulators this week recommended two shots of the vaccine, while most people in the US will get just one. It seems US authorities are content with the less-than-perfect protection afforded by one shot, while European regulators may be reaching for air-tight immunity.

Meanwhile, the US Food and Drug Administration has just approved a vaccine—cervarix, the shot against cervical cancer—with a new generation adjuvant. It’s the first adjuvant to hit US soil since alum, more than 60 years ago. The approval could signal a change in mindset at an agency with a reputation for extreme caution on vaccines—but it comes too late for the swine flu.

Some critics have charged the FDA with being asleep at the switch while European regulators developed plans over the last few years to put oil-in-water adjuvants into pandemic flu vaccine should they be needed. Europeans readied the safety data and set the stage for quick, systematic, approval (see my story on adjuvants in the September issue).

It’s not clear what factors went into the decision not to use adjuvants in the US. But the swine flu vaccine works fine without them, and when the decision was made, supply seemed assured. And just typing ‘vaccine adjuvants’ into Google will tell you how freaked out people can be about vaccine safety.

A few months ago, when swine flu vaccine manufacturing seemed on track, some health experts criticized the US for being a bad global citizen in deciding not to use adjuvants, because its extra needs could drain the world’s supply. But now the decision seems to be coming home to roost.

Blame the chicken

The woman on the line said that the agency was conducting the survey to find out more about attitudes towards vaccination, trying to find the demographic of people reluctant to vaccinate.

I could point them to one demographic: one of my local online parents' groups. “Don’t get your kids vaccinated!” warned one poster. “The risks outweigh the risks of the illness.” She said, citing unnamed ‘sources’ at NIH.

Apparently that mom is not alone in her safety concerns. A recent poll from Consumer Reports finds that just 35 percent of parents were sure they would get their children vaccinated, while 14 percent of parents would ‘definitely’ not. Even more disturbingly, a separate survey found that only 38 percent of health care workers were planning to get vaccinated. You can read more about the polls at the Los Angeles Times blog “booster shots.”

With the first swine flu shots coming on deck next week, the CDC does not have a lot of time to figure out how to get safety messages out to the public. Its website does a decent job, but it might be appropriate to link to a web page with a more detailed message outlining results of clinical trials with flu vaccines and explaining exactly how the vaccine is made. Or perhaps the agency has consciously chosen to go with a simple message.

My feeling is the agency might be facing some powerful anti-vaccine sentiment in the this country. I hope that the agency is ready with smart, detailed and to the point explanations. My phone call last night indicates they are at least thinking about how to craft their public health message on vaccine safety.

You can see the CDC website here. What do you think? Does it do a good job of explaining why the agency expects the vaccine to be safe?

That’s better news than expected—many experts had predicted two shots would be needed, putting pressure on tight supplies. But there clearly will still not be enough vaccine to go around, particularly in poor countries.

In the US, it is conceivable that high-risk populations like pregnant women might get vaccinated before the flu season hits full force, and most people could ultimately get the shot. That’s because the US has bought billions of dollars of vaccine--a price many countries cannot pay for such a limited commodity. Today the head of the World Health Organization, Margaret Chan, said she expected this “virus of extremes” to cause far more deaths in poor countries than in affluent ones.

The dosage in a single shot is 15 micrograms. But there is a way to bring down the dosage and further stretch the supply—using oil-in-water adjuvants, which have been approved for seasonal flu vaccines in Europe. Glaxo Smith Kline (GSK) recently showed that, with its AS03 adjuvant, a 5.25 microgram dose will protect 98 percent of adults (95 percent of the adults in its trials were protected with unadjuvanted vaccine at a 15 microgram dose). Stretching supplies further, GSK says it plans to sell shots with 3.75 microgram.

That’s a substantial reduction in dosage. But as I report in the latest issue of Nature Medicine, US regulatory authorities have not seemed eager to exercise their option to approve adjuvants in pandemic flu vaccine on an emergency basis—a decision that could have implications for global supply.

What do the recent data and vaccine approval mean for the prospects of using adjuvants in the US? I asked Amesh Adalja, a fellow at the Center for Biosecurity in Pittsburgh, Pennsylvania and a physician at the University of Pittsburgh Medical Center.

“I think the approval means that the pandemic vaccine will not be adjuvanted,” said Adalja.

Nonetheless, clinical trials are on deck at NIH to test adjuvanted vaccine. Adds Adalja: “I think that there is enough clamor about adjuvants that maybe we will see some trials using adjuvanted vaccine. The GSK adjuvant, AS03, can be mixed with some of the other manufacturers' vaccines after production and we might get enough data for an approval (but probably too late for this flu season)."

You can access a great rundown of the new vaccine data by Adalja in his blog posting. Despite the new findings, he is skeptical about whether enough vaccine will be ready, even in affluent countries, by the time the peak of the pandemic is expected to hit.

On Wednesday, an advisory committee to the US Food and Drug Administration recommended approval of the cervical cancer vaccine, Cervarix, which contains a new adjuvant-substances that give extra pep to vaccines.

If the agency follows through on the committee’s advice, Cervarix will be the first vaccine approved in the US with an adjuvant other than alum-an adjuvant based on aluminum salts used for more than 60 years. The agency is expected to issue a decision by the end of September.

But the big question is whether the US will consider using adjuvants in pandemic H1N1 flu vaccine, a decision that has serious potential to stretch a limited world-wide supply. A positive decision on Cervarix could change the way the agency perceives adjuvanted H1N1 pandemic flu vaccine, an option that does not seem to be its first-choice, as I report in a recent article on adjuvants in Nature Medicine.

Cervarix, made by Glaxo Smith Kline, has already been approved dozens of countries, as have other vaccines with next-generation adjuvants, including several vaccines for seasonal flu.

European regulators are poised to approve vaccines for pandemic H1N1 flu vaccine containing an oil-in-water adjuvant-the same adjuvant used in seasonal flu shots given safely to millions of people in Europe. But US regulators are widely perceived by public health researchers as much more cautious.

The agency, nonetheless, also gave the green light on Thursday to clinical trials of an adjuvanted hepatitis B vaccine, manufactured by the biotechnology company Dynavax. The FDA had put the trials on hold 18 months ago pending investigation into whether vaccination may have been linked to a rare autoimmune condition that had developed in a trial participant. Now the company can continue to test its vaccine in people with chronic kidney disease who do not respond well to the standard hepatitis B shot.

So, it’s been a good week for adjuvants at the US FDA. We will see what that means ultimately for pandemic flu shots.

Researchers at Novartis are still awaiting data on the degree to which adjuvants can cut down the dosage of pandemic H1N1 vaccine. Meanwhile, studies out Thursday in the New England Journal of Medicine suggest that one shot of vaccine may be sufficient. And this Friday the NIH will also discuss early results from its clinical trials. Stay tuned.

Today, a report published in Morbidity and Mortality Weekly Report gives another reason to keep sweets away from youngsters: inadvertent marijuana ingestion.

I think the journal's lay summary speaks for itself:

"It is beneficial for local health departments to establish good working relationships with law enforcement. In April, 2009, the Los Angeles Police Department and the Los Angeles County Department of Public Health launched a collaborative investigation concerning a group of preschool teachers with neurological and gastrointestinal symptoms after eating brownies purchased from a sidewalk vendor. This report summarizes the results of that investigation, which detected cannabinoids in a recovered sample of the brownies. Two patients sought medical treatment, and one patient’s urine and serum tested positive for marijuana metabolites. The findings demonstrate the utility of a collaborative investigation by public health and law enforcement and the importance of timely testing of clinical specimens after symptom onset. It also underscores the need to consider marijuana as a potential contaminant during foodborne illness investigations."

Image via Norwichnuts.

The US government is asking the public to vote on their favorite H1N1 public service announcement. And while some rappers might want you to throw your hands in the air and 'wave'em like you just don't care', at least one hopeful contestant, Dr. Clarke, is hoping to you'll throw your hands into the sink and start washing them. He already is gaining a bit of a following.

To see all the videos up for vote, click here.

Meanwhile, a cartoon aired at the Shanghai airport has also put the dangers of H1N1 into a rap. To see a capture of the video, click here.

Have you seen any other H1N1 flu raps out there that strike your fancy?

The place was packed with kids, whining to ride a pony and eat pink cupcakes. The adults were sweaty, distracted and grumpy. But at least they did not have my job!

I got to feed little children this:

I knew, in a vague way, that mass-produced popcorn wasn’t a great thing. But this was in another realm entirely: a 2:1 ratio of popcorn to coconut oil, tinged with some yellow substance. My job was to extrude the pure supersaturated ooze into the sizzling machine and joyfully dispense the popcorn product.

Apparently it’s not too different from what kids must be eating every day. According to a September 1 report from the Institute of Medicine (IOM), “Local actions to prevent childhood obesity,” 16.3 percent of children and adolescents in the US between the ages of two and 19 are obese.

People started flocking to my hot corner of the playground. Parents tactfully steered their children clear of the plastic-colored cake items and to what they might have thought, in their harried state, looked a little more like normal food. Admittedly, the popcorn people did a good job with the artificial butter, it had a certain chemotactic pull.

Holding back an urge to run home fast, I instead carefully placed an unopened plastic pod of kernels on the table. Surely, with the goop right in front of them, people would hesitate before grabbing a bag of popcorn.

No such luck. Cranky parents yanked at the cheerful striped bags, shoving quarters in my hand. Grubby 8 year olds came back for seconds. It was like some sort of food hell. When a pregnant woman came up my frozen smile cracked:

“You might not want to eat that,” I said, imagining what Yellow #6 Lake (E110) did to embryonic digits. She was unfazed by my meddling, “Oh! It’s not for me! It’s for my son!”

My only conclusion from the experience is that kids will eat whatever is in front of them and that harried parents will do little to stop it. Parents are a poor filter against the proliferation of junk food targeted to children (my favorite is this baby-bottle-shaped candy, marketed by teeny bopper band the Jonas Brothers, in a wildly popular YouTube video).

If the IOM had its way I’d be prosecuted. One of their recommendations: “Implement local ordinances to restrict mobile vending of calorie-dense, nutrient-poor foods near schools and public playgrounds.”

During my hours pouring grease and yellow stuff into a machine, and inserting it into the veins of my neighbors’ children, only one child paused. He looked at the package, turned it over gingerly, and walked away.

I had poisoned many, and saved one. I went home with my two-year old, face flecked with neon frosting, to contemplate my crime.

I am now a step closer to understanding the wonders of the pig uterus—which gestates an embryo that within a day goes from a 1 cm sphere to a 1 meter long thread (“Like dental floss,” explained one researcher.) I’m more wary than before of that uibiquitous stuff that lines food cans (bisphenol A; BPA). And I am threatening to turn into a scold against soy infant formula (studies at the meeting showed that estrogen-like compounds in the formula can shut down DNA in young animals in a process called methylation).

I’m late on the uptake blogging about the meeting—the usual excuses about trying to meet editing deadlines while attending the sessions, loose proofs, wayward authors. And I only went for two days—Monday, July 20 and Tuesday, July 21. But even belatedly, some of the highlights of the meeting, which took place in Pittsburgh, still seem worth touching on.

On Monday, researchers presented a cluster of studies where they attempted to freeze oocytes—the trendy way to promote fertility in countries such as Italy, where freezing of tiny embryos presents a legal quandary. No one has hit on the answer yet—upon thawing, the oocytes still seem to lose too many chromosomes. But some researchers are getting closer.

Theresa Woodruff, for instance, presented data on preserving fertility in women undergoing cancer treatment, showing how her group can culture human ovarian follicles that produce fully-sized oocytes. She hosted a conference on the subject in Chicago this July, the 'Oncofertility Reflections on the Humanities and Social Sciences ' bringing together religious and legal experts with ethicists and scientists to discuss the ramifications of the emerging technology. That seems like a smart thing to do for a researcher working a system that has the potential to bump up the upper age of female reproduction.

Much of the Pittsburgh meeting focused on reproductive toxins, not surprising given that chair of the meeting was Pat Hunt, known for her work suggesting that BPA may act through estrogen receptors to affect developmental processes such as the integrity of chromosomes in the oocyte.

She invited John Peterson, publisher of “Environmental Health News” to give a rundown of BPA research and government regulation. He pointed out that 90 percent of 232 animal studies funded by the government have found an effect of BPA at levels beneath that considered safe by the US Food and Drug Administration. He provided examples of industry influence at US regulatory agencies and argued they use outdated scientific standards to evaluate toxins. But I’m still not clear on why countries such as Canada have banned BPA in baby bottles while the FDA seems to be thinking about reviewing the data yet again.

That same evening organizers invited a firebrand who speaks up for animal research. Tom Holder, who founded the United-Kingdom-based group ‘Speaking of Research' looks about 18 and he speaks with the urgency of a politician gunning for office. He warned that the intimidation tactics of animal-rights groups in California threaten to turn the state ‘into the next Oxford’, known as a target of such groups. He showed how his organization is working to show the public in the UK how animal research help people, and directed scientists to his group’s website to learn of ways they can help.

To me, the poster sessions were the highlight. Along with the possum researchers, there were people working on fertility in elephants, cattle and manatees. "There is usually a bunchof panda people, but not this year," ’ lamented one researcher.

One poster caught my attention in particular. Swine researchers provide evidence that suckling pigs obtain a critical hormone, relaxin, through their mother’s milk—the hormone in turn seems to be required for the proper expression of developmental genes in the cervix. It may be a stretch, but perhaps the milk is helping to properly prepare the piglets to birth the next generation.

The Pew Charitable Trusts has initiated a campaign to limit the use of antibiotics in livestock. As the ads point out, routine use of antibiotics in farm animals can foster the development of antibiotic-resistance bacteria than can infect humans.

For years, microbiologists have raised their thin, meager voices against this practice. But now they seemed to be joined by some other voices that might carry wider impact. For instance, New York Times columnist Nicholas Kristof weighed in this March against rourtine use of antibiotics in agriculture. Last week Principal deputy FDA commissioner Joshua Sharfstein, testified before congress on the issue, saying:

"Purposes other than for the advancement of animal or human health should not be considered judicious use" says Sharfstein.

The problem is that many animals, raised in cramped quarters, receive antibiotics in their feed much of their lives. Cows that eat corn, instead of grass, are more susceptible to infection. Even the the family farm I took my kid to last month, the friendly one with the pettable happy cows, fed their chickens bags of “Medicated” feed.

Bills to restrict the practice have been kicking around the US Congress for years now, but agriculture interests have kept them from going anywhere. It’s conceivable this year’s version might have a better chance.

But advocates for reform may have been missing an easy target: Pharmaceutical companies receive tax deductions for such advertisements. This week, congressman Charles Rangel proposed dropping this deduction, which could raise as much as $37 billion over 10 years--money he says could be put towards overhauling health care. The big four television networks oppose this idea, noting that advertising employs millions of people in the United States.

What do you think? Is this a worthy tax deduction, or is Rangel right to call for its elimination?

One finding getting a lot of press has its origins in a pair of studies in Nature in 2005. The studies showed how to selectively kill cancer cells deficient in BRCA1 and BRCA2, genes that are mutated in some of the deadliest breast and ovarian cancers.

The agent that does the killing is called a PARP inhibitor. And trial results released last week show some pretty promising results.

Olaparib, a PARP inhibitor under development by AstraZeneca PLC, shrank tumors in more than a third of women whose breast cancers had BRCA mutations. The trial did not have a control arm, but the data look encouraging, considering the agent was given alone, without other drugs, and that the subjects had already had an average of 3 chemotherapy regimens. A similar trial showed that the drug could also shrink advanced ovarian tumors in subjects with BRCA1 or BRCA2 mutations.

A truer test of whether a drug is likely to help patients is whether it can prolong survival. A randomized, controlled trial of BS1-201, under development by Sanofi-Aventis SA, examined this question in 116 women with some pretty nasty tumors: their breast cancer had metastasized to other parts of their body and was ‘triple negative’, meaning it lacked receptors on their tumors for estrogen, progesterone and HER2, each of which are targets for current therapies. The drug prolonged survival by three and a half months, to 9.2 months, when added to a standard chemotherapy regimen.

Bigger studies are needed, but the findings so far validate a concept with deep origins in basic research. BRCA1 and BRCA2 facilitate DNA repair, a function that emerged after years of painstaking research. PARP (poly(ADP)-ribose polymerase) mediates DNA repair also, but in a distinct way. The Nature studies exposed cells lacking BRCA1 or BRCA2 to PARP inhibitors and showed that these cells get nailed: their DNA is such a fragmented mess that they die.

Mice deficient in PARP are viable, fertile and tumor-free, which bodes well for the side effect profile of these drugs. Subjects who received the drugs reported only mild side effects, including nausea and fatigue.

Other highlights at ASCO include promising findings with multikinase inhibitors, which can block several types of proteins that go astray in tumor cells. Cancer vaccine approaches also got a boost with positive findings from trials in melanoma and non-Hodgkin’s lymphoma.

Flu viruses circulate year-round in tropical regions, where they can mix with each other, mutate and spawn new strains. Two studies published last year outlined this process, showing how seasonal flu strains in the temperate regions originate in tropical regions.

Unfortunately, as Declan Butler at Nature reports, surveillance networks are often weak in tropical countries, so it may be difficult to monitor the evolutionary trajectory of the new H1N1 virus.

Vaccine experts breathed a sigh of relief when the first sequences of the new H1N1 virus revealed relatively little variability among isolates. That makes it easier for manufacturers to produce a vaccine that could work against all forms of the virus. But the virus may surprise us in the fall, popping up as a different sort of beast—or beasts.

There are also fears that the virus will wreak havoc in sub-Saharan Africa, where there are many people living with HIV, weakening their immune system and possibly increasing their vulnerability to swine flu.

But finally someone has made the subect readable--that expert at medical prose, Atul Gawande. His article in the latest issue of the New Yorker is an insightful read.

He takes us on a tour of McAllen, Texas, the town with the most expensive health care system in the country. Here, it seems, doctors routinely send patients to surgery who might not need it. Doctors have financial relationships, some legal, some apparently not, with hospitals and other institutions that do surgery, imaging and testing. It all has the effect of funneling money into doctors' wallets and ramping up the costs for Medicare, the primary payer in the county.

In contrast, he notes that the famous Mayo Clinic provides much less expensive care. The incentives in this system, and others like it, are set up so that doctors focus more on the patient; they spend more time with them, they consult more with specialists in other fields, and perform fewer unecessary procedures. The result is not only less expense, but radically better patient care.

As the debate on health care ramps up this summer, I'm happy that there are some people out there who devour policy papers on health care like it's candy. For them, this might be old news. For the rest of us, Gawande makes it come alive.

Last Friday, President Obama chose a firebrand to head the US Centers for Disease Control.

Thomas Frieden is known for pushing through a ban on smoking in public spaces in New York City, where he has served as health commissioner since 2002. He refused to take that position until the mayor promised to back his plan. After that he took aim at artificial trans fats in restaurants, instituting a ban that inspired other communities to do the same.

He’s likely to put the CDC’s focus back on tobacco, the nation’s number one killer. But he’s also got the creds on infectious disease—having bolstered needle exchange and condom distribution programs in New York, along with supporting a controversial program to increase HIV testing. In the early 1990’s, he ran the city’s tuberculosis program, putting the kibosh on an illness that had taken hold in the city’s vulnerable populations.

Not all of his ideas have been conventional, and some are unpopular. To get an idea of how he gets things done, see this profile by our former news editor, Apoorva Mandavilli.

“If I’d known you were going to ask me to sign so many forms, I wouldn’t have said yes to commenting! ”

Ok, so we felt like a faceless, inflexible bureaucracy. And, our staff duly explained --in the bureaucratic monotone of an email correspondence–why we need so many %##** forms!

One of those—the conflict of interest form—has become a familiar staple at biomedical journals, conferences, and just about every where else physician-scientists set foot. Except in their own home: Too many research institutions still have weak conflict of interest policies.

The Institute of Medicine has now joined a host of other organizations weighing in on the issue. This week they released their report on financial conflict of interest, outlining a series of recommendations for institutions, including medical colleges.

The report weighs about as much as ‘Molecular Biology of the Cell’—and its contributors seem themselves to have been thoroughly vetted for conflict of interest. Overall, its recommendations, though thorough, are perhaps not surprising. For instance, the report said that, with certain well-vetted exceptions, physicians should not participate in clinical trials in which they have a financial interest in the outcome , and professional societies should not accept direct industry funding for developing clinical guidelines.

The report also recommends that Congress pass legislation—which is being considered--that would require medical device and pharmaceutical companies to disclose publicly all payments they make to physicians. With such a database, medical colleges could make sure researchers—even ones who claim they are next to God—are being straight with them.

All of this sounds good to me. But there’s one recommendation I particularly agree with: get all the conflict of interest scolds—that includes us—on the same boat. Essentially, the report called for more uniformity in policies.

At the press conference announcing the report, committee chair Bernard Lo mused that some software developer (presumably someone ‘detail oriented’) could make filling out the forms, with all their various formats, easier.

Here—fighting sheaves of paper, irritated authors and corrupted pdf files—that’s a reform I could get behind!