Tuesday, September 25, 2012

Hospital Births: Are they safe?


Exploding the Myth of Hospital Birth for Low Risk Women
Since the beginning of hospital birth, research supporting its use for low risk women has been lacking. The last 15 years has produced 17 studies all supporting attended planned homebirth as safer for low risk women. 
Research reveals that there are only 2 acute conditions that might occur at homebirth in which the mother or baby may have a better outcome had they planned a hospital birth, namely: Cord prolapse and Amniotic Fluid Embolism (AFE). Although tragic, cord prolapse and AFE occur rarely at homebirth, 1/5000 and 1/500,000 respectively, when balanced with the dozens of acute emergency conditions endangering the health of mother and baby that occur at planned hospital birth caused by intervening in the birth process, the scales tip easily in favor of planned attended homebirth for low risk women.  Acute conditions caused by hospital birth are discussed here, to allow low risk women to make informed choices as to place of birth.

Is Hospital birth ever safer than homebirth for low risk women?

The answer is an unequivocal 'no’.
There are 12 high quality studies since 1995 (1-12) from Canada, Switzerland, Sweden, Holland, US, UK, New Zealand and Israel, which all show planned attended homebirth to have either lower or similar rates of perinatal mortality and very significantly lower rates of maternal morbidity, such as cesareans, hemorrhage, and third and fourth degree tears compared to matched groups of low risk women who plan to deliver in hospital.
Another 5 studies (13-17) claim homebirth to have a higher perinatal mortality rate compared to hospital birth but they all include high risk births in the planned homebirth group.  Instead of excluding the high risk births from both groups, they include the homebirth outcomes of premature births at 34-37 weeks gestation (13-17) breech and twins (13,14) lethal anomalies incompatible with life(13,14) unattended homebirths (15,16) unplanned homebirths(15,16) or women who became risked out of homebirth by becoming high risk at the end of pregnancy, had hospital births, but are included in the homebirth group. (17)
These 5 studies conclude that homebirth is less safe than hospital birth, when what these papers actually found is that low risk births are safer at home but premature births have better outcomes in hospital.  Possible explanations for the false conclusion of these studies could be paternalistic power games over women or hospital birth being not only the most common but also the most profitable reason for hospitalization.  Remove the high risk births from those studies and they also confirm that homebirth is safer for low risk women than hospital birth.
Margaret Tew, a statistician, pointed out as early as 1977 (18) that hospital birth was never researched for safety before it was instituted.  She analyzed whatever data she could find from the years in which birth transitioned to hospital 1920-1950, searching for evidence of improved outcomes of hospital birth, but did not find any.  She found great resistance to publishing her findings in peer reviewed journals, with only the one scholarly reference in a journal(18) and the rest of her findings published in a chapter of a book and her own book. (19,20)
Dr Shearer 1985: "When I started in general practice in 1954 about a third of all babies were born at home, and only women with problems and a few primiparas were able to book a bed in the local hospital, St John’s Chelmsford.  By the early 1970s this had changed greatly, and it was possible to book all mothers who wished for or needed a bed in the consultant unit. Although my partners and I continued to look after home deliveries, we were often asked about the risk of a home birth, and in the past decade the usual reason given by low risk mothers for a request for a hospital delivery was 'because it is safer.’  There appears to be no firm evidence for this view." (21)
Hospital Birth Realities


Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

Saturday, September 22, 2012

Drug's Don't Work: A Scandal


The drugs don't work: a modern medical scandal

The doctors prescribing the drugs don't know they don't do what they're meant to. Nor do their patients. The manufacturers know full well, but they're not telling.
For the full article:
a0158-000112View larger picture
Drugs are tested by their manufacturers, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that exaggerate the benefits. Photograph: Photograph: Getty Images. Digital manipulation: Phil Partridge for GNL Imaging
Reboxetine is a drug I have prescribed. Other drugs had done nothing for my patient, so we wanted to try something new. I'd read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It's approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.
  1. Bad Pharma: How drug companies mislead doctors and harm patients
  2. by Ben Goldacre
  3. Buy it from the Guardian bookshop
  1. Tell us what you think:Star-rate and review this book
But we had both been misled. In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal, for doctorsand researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.
It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients' worth of data was left unpublished, and this unpublished data showed that patients on reboxetine did worse than those on other drugs. If all this wasn't bad enough, there was also the side-effects data. The drug looked fine in the trials that appeared in the academic literature; but when we saw the unpublished studies, it turned out that patients were more likely to have side-effects, more likely to drop out of taking the drug and more likely to withdraw from the trial because of side-effects, if they were taking reboxetine rather than one of its competitors.
I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.
Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us. These problems have been protected from public scrutiny because they're too complex to capture in a soundbite. This is why they've gone unfixed by politicians, at least to some extent; but it's also why it takes detail to explain. The people you should have been able to trust to fix these problems have failed you, and because you have to understand a problem properly in order to fix it, there are some things you need to know.
Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.
For the full article:

PLOS: Medical Journals Extension Arms of Big Pharma


Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies


“Journals have devolved into information laundering operations for the pharmaceutical industry”, wrote Richard Horton, editor of the Lancet, in March 2004 [1]. In the same year, Marcia Angell, former editor of the New England Journal of Medicine, lambasted the industry for becoming “primarily a marketing machine” and co-opting “every institution that might stand in its way” [2]. Medical journals were conspicuously absent from her list of co-opted institutions, but she and Horton are not the only editors who have become increasingly queasy about the power and influence of the industry. Jerry Kassirer, another former editor of the New England Journal of Medicine, argues that the industry has deflected the moral compasses of many physicians [3], and the editors of PLoS Medicine have declared that they will not become “part of the cycle of dependency…between journals and the pharmaceutical industry” [4]. Something is clearly up.

For the full article

"Journal editors are becoming increasingly aware of how they are being manipulated and are fighting back [17,18], but I must confess that it took me almost a quarter of a century editing for the BMJ to wake up to what was happening. Editors work by considering the studies submitted to them. They ask the authors to send them any related studies, but editors have no other mechanism to know what other unpublished studies exist. It's hard even to know about related studies that are published, and it may be impossible to tell that studies are describing results from some of the same patients. Editors may thus be peer reviewing one piece of a gigantic and clever marketing jigsaw—and the piece they have is likely to be of high technical quality. It will probably pass peer review, a process that research has anyway shown to be an ineffective lottery prone to bias and abuse [19].

Furthermore, the editors are likely to favour randomised trials. Many journals publish few such trials and would like to publish more: they are, as I've said, a superior form of evidence. The trials are also likely to be clinically interesting. Other reasons for publishing are less worthy. Publishers know that pharmaceutical companies will often purchase thousands of dollars' worth of reprints, and the profit margin on reprints is likely to be 70%. Editors, too, know that publishing such studies is highly profitable, and editors are increasingly responsible for the budgets of their journals and for producing a profit for the owners. Many owners—including academic societies—depend on profits from their journals. An editor may thus face a frighteningly stark conflict of interest: publish a trial that will bring US$100 000 of profit or meet the end-of-year budget by firing an editor."

Examples of Methods for Pharmaceutical Companies to Get the Results They Want from Clinical Trials

  • Conduct a trial of your drug against a treatment known to be inferior.
  • Trial your drugs against too low a dose of a competitor drug.
  • Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
  • Conduct trials that are too small to show differences from competitor drugs.
  • Use multiple endpoints in the trial and select for publication those that give favourable results.
  • Do multicentre trials and select for publication results from centres that are favourable.
  • Conduct subgroup analyses and select for publication those that are favourable.
  • Present results that are most likely to impress—for example, reduction in relative rather than absolute risk.

Tuesday, September 18, 2012

In India: Drug Makers Woo Doctors With Gifts.


Insight: In India, gift-giving drives drug makers' marketing


MUMBAI | Mon Sep 17, 2012 7:38am EDT
                                                                                                   A medical representative (C) with Abbott talks to a chemist at a market in Pune August 27, 2012. Picture taken August 27, 2012. To match Insight INDIA-PHARMA-KICKBACKS REUTERS-Danish Siddiqui
(Reuters) - Sales representatives for Abbott Laboratories Inc's Indian subsidiaries know what it takes to get a doctor to prescribe the drugs they market: a coffee maker, perhaps, or some cookware, or maybe a vacuum cleaner.
These are among the many gifts for doctors listed in an Abbott sales-strategy guide for the second quarter of 2011, a copy of which was reviewed by Reuters. As laid out explicitly in the guide, doctors who pledge to prescribe Abbott's branded drugs, or who've already prescribed certain amounts, can expect some of these items in return.
Consider the guide's entry for Nupod, an Abbott antibiotic generically known as cefpodoxime. It lists a medical textbook, a mosquito repellant and a coffee maker as incentives for doctors.
It also provides a script of the social niceties for clinching the quid pro quo: "Dr presenting you advanced coffee maker from Philips which will make coffee within three minutes … Dr in the box we have made advancement easy for you by giving the ideal usage guidelines of the coffee maker … Dr I look forward for advancement in action i.e. our Nupod brand … Dr can get just 3 Rx per day for Nupod."
Especially in India's poorer areas, says one Abbott rep, "if you give them a small gift, they are happy."
A LARGER PROBLEM
The Abbott guide -- reps say the company produces them regularly -- is evidence of a larger problem in India. In interviews with Reuters, dozens of doctors, drug reps and other healthcare insiders said domestic and multinational drug makers routinely shower Indian doctors with gifts, posh junkets abroad, and cash payments disguised as consultancy or other types of fees.
"Indian CRM," or customer-relationship management, is what industry insiders call this system of inducements. None of the doctors or reps who described their participation in this trade would speak on the record. Under Indian law, doctors are prohibited from accepting cash, gifts or travel from drug companies. Still, enforcement is rare, and drug makers may lavish gifts on doctors with impunity, though their home countries may punish the practice.
In a country where doctors often make less than $10,000 a year, it can be an effective strategy.
"Somebody is doing something for you," says a Delhi-based cardiologist. "Obviously you will want to return the favor." He says he prescribes more drugs from companies that provide gifts and send him on paid vacations to Thailand, Hong Kong and elsewhere. One of those companies, he says, is the India-based Ranbaxy unit of Japan's Daiichi Sankyo Co.
"We do not sponsor vacations for doctors," a Ranbaxy spokesperson said. "We are viewed as a scientifically and academically orientated company and our promotional activities are built around academics and science."
In response to questions from Reuters, Chicago-based Abbott said that it complies with local laws and regulations in India. It added that company policy forbids employees to "offer or give a sponsorship, gift, meal or entertainment in exchange for an explicit or implicit agreement that Abbott Products will be used, purchased, ordered, recommended or prescribed or that Abbott or any Abbott products will receive any favorable treatment."
SO MANY CHOICES
The Indian market is particularly vulnerable to corruption because of the intense competition here. Until 2005, India flouted drug patents, refusing to rein in domestic copycats of Big Pharma's blockbusters. Brands proliferated. Today, an Indian doctor can choose from among 224 registered brands of the cholesterol-lowering drug atorvastatin, sold by Pfizer Inc as Lipitor in the U.S. and elsewhere.
Foreign companies that want a piece of this crowded market "have to adapt, or they are not going to survive," says an executive with Biocon, a leading Indian biotech company. The executive says Biocon routinely gives doctors iPads, iPods, mobile phones, "you name it."
A Biocon spokesperson said the executive's statements are "incorrect and absolutely untrue" and added that the company operates "in strict compliance" with the law.
Public health experts and some Indian doctors say that as a result of drug companies' tactics, drugs are dangerously overprescribed and expensive brands are prescribed instead of cheap ones. That can be devastating for patients -- physically and financially -- in a country where health care is mostly private and unsubsidized and 400 million people live on less than $1.25 a day.
At the Amrita Clinic, a private practice in Pune, Maharashtra State, physician Vinay Kulkarni says he refuses to accept gifts from reps, in part because he believes drug makers overcharge for their products to recoup marketing expenses. "Ultimately," he says, "everything is being paid by the patient."
As Big Pharma has pushed into emerging markets like India in recent years, companies have been running into trouble with their home-market overseers. Many of the world's top drug makers have warned in recent regulatory filings of potential costs related to charges of corruption in foreign markets.
TEA SETS IN CHINA
Last year, Johnson & Johnson agreed to pay $70 million to settle U.S. charges that it paid bribes and kickbacks to win business in Greece, Iraq, Poland and Romania. Pfizer Inc recently agreed to pay $60.2 million to settle a U.S. government probe of the drug maker's use of illegal payments to win business overseas, including gifts such as cellphones and tea sets to doctors in China who prescribed the company's products.
Abbott became the No. 1 pharmaceuticals company in India in 2010, when it paid $3.7 billion for the branded generics business of Mumbai-based Piramal Healthcare. Its thousands-strong Indian sales force has helped buoy the parent, as sales in emerging markets rose 23 percent to $2.59 billion in the second quarter of 2011 -- more than twice Abbott's global growth rate.
Reps from Abbott True Care, Abbott Healthcare and Abbott Primary Care - all formerly part of Piramal and now subsidiaries of Abbott -- say sales plans are revealed to them at "cyclical sales meetings" every three or four months. These meetings, they say, sometimes include studying printed strategy guides like the one for second-quarter 2011 that Reuters reviewed.
That guide offers no clarity on why particular gifts are paired with particular drugs. None of the items that come with Nupod, the antibiotic, go to doctors who prescribe Pantagon IT. That drug - a combination of itopride, for bloating and indigestion, and the antacid pantoprazole - comes with a stapler, a set of six glasses and a jar from Luminarc, and a Forbes Trendy Nano vacuum cleaner.
"THE PANTA REWARDS INPUTS MUST ONLY BE PRESENTED AT THE DRS HOME," the guide tells reps. When delivering the glassware, reps are instructed to say, "Thus Dr requesting your continuous prescription support for Pantagon IT."
Prescriptions for Paraxin, a drug for typhoid fever, are rewarded with a hand sanitizer and an antique pen. Prescriptions for Lysupra, a multivitamin supplement, could earn a beaded car-seat cover "for the relaxation when you are traveling."
Depending on the drug, a doctor might find himself the owner of a Kiwi shoeshine kit, an Ambi Pur car air freshener, a Birla steam iron, or a Pure Relaxation CD series. And if that's not enough, participation in a "Doctor Talent Contest" judged by Bollywood actor Boman Irani might seal the deal.
SCANNERS AND STEAM IRONS
Abbott reps say that so far this year, they have doled out, among other things, scanners, steam irons, shoes, stethoscopes and gift vouchers worth more than $100 to doctors - both private and government-employed.
Amitava Guha, a member of the national working committee of the Federation of Medical and Sales Representatives' Associations of India, worked as a rep for decades, including for Piramal from 1997 to 2008, when he retired. "Everybody is doing it," he says. "I was doing it when I was in service.... They said that it is your job to go and give to the doctors."
He says he resisted giving anything but the smallest gifts, like pens. Today, he says, he receives frequent complaints from reps across the country about the practice. It taints their professional image, he says. Also, it's hard work toting around all those gifts. "They have been given huge extra bags to carry," he says. "One on the shoulders and two others in the hands."
The managing director of a large diabetes clinic in Calcutta says he sees as many as 25 reps a day. "Whatever you like, they can provide you," this doctor says.
His interview with Reuters was interrupted when a man squeezed into his office and placed a big yellow box on the table. "Sir, this is an exquisite casserole set," the visitor said, slipping the doctor a note bearing the brand name Rostar, a cholesterol-lowering medicine from Mumbai-based Unichem Laboratories Ltd.
Unichem did not respond to requests for comment.
Guha, the union federation official, says that reps have begun reporting a shift in emphasis away from the types of gifts listed in Abbott's guide toward free "foreign tours" and outright cash payments, often made under the guise of public health initiatives or research.
Every year, Abbott, collaborating with doctors and other groups, conducts hundreds of "health camps" across India to raise awareness about conditions such as diabetes, high cholesterol, anemia, breast cancer, sleep problems and thyroid disease.
Abbott says these programs "generally incorporate diagnosis, prevention and education. … The focus of these camps is around disease and not products."
IN THE NAME OF SCIENCE
Reps say public health isn't always the point. "This is a business transaction," says one. This rep says that at a diabetes camp he worked on, patients were given random blood-sugar tests - not a valid means of diagnosing diabetes - and based on the result, were prescribed Abbott oral diabetes medications by the participating doctor.
Similarly, reps and doctors say companies try to boost sales through so-called non-interventional post-marketing studies, commonly used around the world to monitor the safety and efficacy of drugs after they have been approved for sale.
Doctors and reps say that often, companies use these studies as cover for paying doctors to prescribe the drugs under study. According to one Abbott rep, the company doesn't pay doctors if sales at nearby pharmacies don't increase.
A doctor who has done post-marketing studies in India says the companies rarely monitor the studies or check the data. "We all understand that post-marketing studies are not really true studies," says the doctor, a diabetes specialist at a Calcutta hospital. They're "just a way to offer an honorarium. So we also don't take them seriously."
(Editing by John Blanton)

Wednesday, September 12, 2012

DNA Contamination in HPV vaccines


ISIS Report 12/09/12

DNA Contamination in HPV vaccines

A serious safety issue that should not be swept under the regulatory carpet Professor Joe Cummins
Please circulate widely and repost, but you must give the URL of the original and preserve all the links back to articles on our website. If you find this report useful, please support ISIS by subscribing to our magazine Science in Society, and encourage your friends to do so. Or have a look at the ISIS bookstore for other publications
When the Human Papilloma Virus (HPV) vaccine Gardasil was recently found to be contaminated with DNA, the US Food and Drug Administration (FDA) lost no time in declaring that the DNA was not a contaminant but a harmless by-product of vaccine production. I disagree; that extraneous DNA is potentially harmful. It should also be noted that the safety and efficacy of HPV vaccines have been controversial from the start (see [1] The HPV Vaccine Controversy and other articles in the series, SiS 41).

The virus

HPV establishes productive infections only in keratinocytes of the skin or mucous membranes. While the majority of the known HPV types cause no symptoms in most people, some types can cause warts (verrucae), while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus.
Recently, HPV has been linked to an increased risk of cardiovascular disease. In addition, HPV 16 and 18 infections are strongly associated with an increased risk of developing throat cancer. Worldwide in 2002, an estimated 561 200 new cancer cases (5.2 %) were attributable to HPV, making HPV one of the most important infectious causes of cancer, and cervical cancer is the second most common cancer in women worldwide. In 2008, there were an estimated 529 000 new cases of cervical cancer and 274 000 deaths; more than 85 % of the deaths in developing countries, where it accounts for 13 % of all female cancers [2]. 

The viral genome

The HPV genome consists of 8 genes coding for proteins and a non-protein-coding region with regulatory genes. The genes are distinguished as early and late functioning in virus development. The early genes include those involved in virus replication and transcription along with the oncogenes for cancer development. The late genes encode the two structural proteins L1 and L2 of the virus capsid. HPV infects the basal cells of the cervical epithelium when it is damaged in some way. The viral genome becomes established in the basal cells as an episome (an independently replicating nuclear micro-chromosome). The episome replicates in tandem with the chromosomes of the cell and forms virus particles. The complete virus particles are in the outermost cells of the epithelium and the viruses are spread as the cells slough off from the epithelium. Some virus proteins function as oncoproteins, transforming the epithelial cells to a precancerous state. HPV infection is necessary but not sufficient for cancer formation, however. In high grade lesions and cancer, an episome is integrated into the cell chromosome. Integration disrupts a viral transcription regulatory protein that controls the production of the cancer proteins, leading to their continual and enhanced production [3] (Recombinant Cervical Cancer VaccinesSiS 29). HPV integration into human chromosomes is non-random; with integration hot spots in chromosome regions homologous to the oncogene E5 of HPV or the structural protein L2 [4]. Women with cervical cancer have been found with viral chromosomes integrated completely or partially as chromosome fragments, or as independent episomes. Partially integrated HPV was most prevalent in women with cancer while complete virus integration was about half as frequent and the episomal form rare. The cancer- causing integration breaks the HPV chromosome at the E1/E2 region, causing a loss of that region.  This in turn results in loss of control of the cancer genes E6 and E7. The E7 cancer gene produces a protein that inactivates the retinoblastoma gene – a cancer suppressor gene - of the host cell, thereby promoting cancer [5]. (Retinoblastoma is an inherited cancer of the eye caused by loss of the retinoblastoma gene.)  The main lesson is that fragmentation  or breakage of the  HPV DNA is an important factor in cancer progression of the host cell.

Gene transcription

The viral genes have a complex transcription pattern. There is a single promoter for all of the early genes. The early promoter initiates production of a large pre-messenger RNA from which messages containing exons and introns are then spliced to generate each of the early proteins. The other viral promoter initiates production of pre-messenger for structural proteins L1 and L2, which also contain exons and introns, and are similarly spliced prior to translation of the messenger RNA into protein.  There are early and late polyadenylation (poly A) signals for the large pre-messenger RNA transcripts. Gene expression of HPV is tightly coupled to the developmental status of the host cells [6].
Micro RNAs are very small (around 22 nucleotides in chains) non-coding regulatory gene products of cells. Micro RNAs are altered in a number of human cancers and one is significantly elevated in HPV anal cancer [7]. A cluster of micro RNAs was found associated with HPV head and neck cancers [8]. The natural history of HPV cancers shows a complex pattern of gene transcription and micro RNAs are implicated in the development of HPV cancers.

HPV vaccines

HPV vaccines have been deployed worldwide since 2006. Two vaccines have been commercialized: Gardasil, manufactured by Merck and Cervarix, manufactured by GlaxoSmithKline. They are prophylactic, that is, they prevent cervical cancer but do not cure existing infections, and are based on the L1 virus-like particles to achieve immunity against HPV. The L1 protein is capable of self-assembly to form empty virus like particles that activate the human immune system to form antibodies. The HPVs targeted by the vaccines are “high risk” types 16 and 18 and “low risk” types 6 and 11. The two commercial HPV vaccines are both made using genetically modified (GM) microbes in a laboratory. Gardasil protects against all four HPV types because it contains virus like particles with mixtures of the four subunit proteins, and is called a tetravalent vaccine. The four L1 proteins are manufactured using GM baker’s yeast. Cervarix protects against the HPV types 16 and 18, and is a bivalent vaccine, and is manufactured using GM baculovirus (a soil-born insect virus) in cultured insect cells [9].

Gardasil

The vaccine consists of the four Monovalent Bulk Adsorbed Products (MBAPs), one for each of the four human papillomavirus (HPV) types. The active components in each MBAP are virus-like particles (VLPs) made up of the recombinant major capsid (L1) protein for that HPV type, produced in recombinant S. cerevisiae. The pGAL110 yeast expression vector was used for all four HPVL1 proteins. The L1 genes were derived by a direct cloning protocol. However, the coding sequence for HPV11L1 was synthetically rebuilt based on HPV6L1 nucleotide sequences that supported good VLP expression in yeast. Polymerase chain reaction (PCR) was used to subclone the L1 genes into the yeast expression vector pGAL110, which contains the yeast GAL1-GAL10 promoter and the yeast ADH1 terminator (ADH1t) for transcription termination and polyadenylation. The pGAL110-related yeast expression vectors for each of the four HPV types were used to transform the recombinant S. cerevisiae [10].

Gardasil DNA contamination

In 2011, Gardasil was found to be contaminated with recombinant HPV DNA in all of the lots of vaccine marketed in the United States, Australia, New Zealand, Spain, France and Poland. One of the DNA fragments identified was a gene fragment from the HPV capsid protein L1 [11]. Sane Vax, a girl age 13, was found to have blood containing HPV DNA two years after Gardasil inoculation [12].  Other DNA contaminants were not specifically identified in the many contaminated vaccine samples but are presumably DNA fragments from the genetically modified yeast used to produce the vaccine protein. Even though the FDA and the vaccine manufacturer had earlier claimed that Gardasil contained no DNA they later changed their tune, and are now claiming that DNA HPV L1 gene in the vaccine is not a contaminant but it is a normal consequence of vaccine production. The remaining DNA fragments are presumed to be safe [13].  The World Health Organization (WHO) had earlier claimed that DNA fragments shorter than 200 base pairs should be presumed safe [14]. It appears that the Merck Corporation, FDA and WHO are closing ranks to claim that the DNA contaminant in vaccines should be presumed safe without any evidence.
The DNA contaminants in Gardasil such as L1 gene fragments and the probable yeast DNA fragments such as the GAL1-GAL10 promoter and the ADH1 terminator flanking the synthetic L1 gene used to produce the vaccine, may pose no threat to the victims of Gardasil vaccination. But it is totally unacceptable to presume that they are safe for human vaccination without experimental evidence or evaluation. Indeed, short DNA fragments can be incorporated into the human genome. Although the yeast used to produce the vaccine does not have the small regulatory RNA employed by most organisms from bacteria to humans, it does contain 247 small open reading frames including 22 short DNA sequences specifying peptides involved in cell growth or damage and growth in the presence of DNA damage and  replication arrest. At least one yeast gene product inactivates the cancer suppressor gene p53 and in that way promotes cancer in multicellular organisms [15]. The integration of the L1 and/or yeast genes may enhance the chances of acquiring cancer in numerous tissues of the body. It has been known for many years that ingested DNA may be covalently linked to mammalian DNA in blood cells, liver cells, spleen macrophages and T cells [16], and horizontal gene transfer and recombination via circulating nucleic acids is now well known [17] (Intercommunication via Circulating Nucleic AcidsSiS 42) .

Cervarix

Cervarix contains recombinant C-terminally truncated (shortened) major capsid L1 proteins of HPV types 16 and 18 as active ingredients. The L1 proteins of HPV-16 and HPV-18 are separately produced using a recombinant baculovirus expression system and the insect cell line Hi-5 Rix4446 derived from Trichoplusia. After extracting the L1 proteins and further purification, they are assembled separately as VLPs. The VLPs of each HPV type are formulated with the AS04 adjuvant system composed of aluminium hydroxide and 3-O-desacyl-4.-monophosphoryl lipid A (MPL). The MPL immunostimulant is a detoxified derivative of the lipopolysaccharide of the gram negative bacterium Salmonella minnesota R595 strain. Host cell proteins (HCP), DNA, and infectious recombinant baculovirus DNA are potential impurities removed in the preparation process. Other impurities such as lipids or carbohydrates are present only in negligible trace amounts [18].

Cervarix DNA contamination?

Cervarix’s manufacturer maintains that the vaccine is not contaminated with DNA or other products from the baculovirus vector or the insect cells.  The baculovirus, Autographa californica nucleopolyhedrovirus (AcMNPV) for which the complete genome sequence has been determined, has a circular, double-stranded, super-coiled DNA genome of approximately 130 kilobases packaged in a rod-shaped nucleocapsid. These nucleocapsids can be extended lengthways and thus the virus genome can effectively accommodate large insertions of foreign DNA. Such insertions of foreign genes into the AcMNPV genome has resulted in production of baculovirus expression vectors; recombinant viruses genetically modified to contain a foreign gene of interest, which can be expressed in insect cells under the control of a baculovirus gene promoter [19]. Baculovirus infects and is viable in human cells. Baculoviruses mediate gene expression in a wide array of vertebrate cells including those of humans [20] and numerous baculovirus genes are expressed in human cells [21, 22]. Baculoviruses contain two genes that prevent apoptosis and in that way facilitate progress of cancer cells [23]. Baculoviruses contain small DNA genes coding for micro RNAs with 8 viral and 64 cellular targets including interference with the host immune defence machinery [24].  There is clear evidence that the baculovirus vector DNA harbours genes detrimental to humans. It is imperative that DNA and RNA along with proteins from baculovirus and insect cells should not contaminate Cervarix vaccine.

To Conclude

DNA contamination of HPV vaccines is a serious problem, and not a normal or acceptable consequence of recombinant vaccine production as claimed by FDA. The false claims of FDA put into serious question not only Gardasil but also Cervarix.  A truly independent agency is urgently required to undertake studies on the content of contaminating DNA and of RNA in the two vaccines.

References

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We eat by Nature's Grace, Not Monsanto's


We Eat by the Grace of Nature, Not by the Grace of Monsanto

“Organic, schmorganic,” fumes New York Times columnist Roger Cohen sarcastically in an article entitled “The Organic Fable.”
He bases his sweeping dismissal of the organic foods movement on a new Stanford University study claiming that “fruits and vegetables labeled organic are, on average, no more nutritious than their cheaper conventional counterparts.”
Cohen does grant that “organic farming is probably better for the environment because less soil, flora and fauna are contaminated by chemicals…. So this is food that is better ecologically even if it is not better nutritionally.”
But he goes on to smear the organic movement as an elitist, pseudoscientific indulgence shot through with hype.
“To feed a planet of 9 billion people,” he says, “we are going to need high yields not low yields; we are going to need genetically modified crops; we are going to need pesticides and fertilizers and other elements of the industrialized food processes that have led mankind to be better fed and live longer than at any time in history.
“I’d rather be against nature and have more people better fed. I’d rather be serious about the world’s needs. And I trust the monitoring agencies that ensure pesticides are used at safe levels — a trust the Stanford study found to be justified.”
Cohen ends by calling the organic movement “a fable of the pampered parts of the planet — romantic and comforting.”
But the truth is that his own, science-driven Industrial Agriculture mythology is far more delusional.
Let me count the ways that his take on the organic foods movement is off the mark:
Organic food may not be more “nutritious,” but it is healthier because it is not saturated with pesticides, herbicides, fungicides and preservatives, not to mention antibiotics, growth hormones and who knows what other chemicals.
There are obvious “health advantages” in this, since we know—though Cohen doesn’t mention—that synthetic chemicals and poor health, from asthma to cancer, go hand in hand.
Organic food is only elitist if it comes from Whole Foods—the one source Cohen mentions. I grow organic vegetables in my backyard, and they save me money every summer. We don’t need the corporatization of organic foods, we need local cooperatives (like the CSAs in my region) to provide affordable organic produce that doesn’t require expensive and wasteful transport thousands of miles from field to table.
About feeding 9 billion people: first of all, we should be working hard to curb population growth, for all kinds of good reasons. We know we’ve gone beyond the carrying capacity of our planet, and we shouldn’t be deluding ourselves that we can techno-fix our way out of the problem. Industrial agriculture is a big part of the problem. It will never be part of the solution. Agriculture must be relocalized and brought back into harmony with the natural, organic cycles of the planet. If this doesn’t happen, and soon, all the GMO seed and fertilizers in the world won’t help us survive the climate cataclysm that awaits.
Mankind is better fed and longer lived now than any time in history? Here Cohen reveals his own elitist, Whole-Foods myopia. Surely he must know that some billion people go to bed hungry every night, with no relief in sight? Mortality statistics are also skewed heavily in favor of wealthy countries. So yes, those of us in the industrialized nations are—again, depending on our class standing—living longer and eating better than in the past, but only at the cost of tremendous draining of resources from other parts of the world, and at increasing costs in terms of our own health.
Just as HIV/AIDS is the scourge of the less developed world, cancer, asthma, heart disease and diabetes are the bane of the developed world, and all are related to the toxic chemicals we ingest, along with too much highly processed, sugary, fatty foods.
For someone who is calling the organic movement “romantic,” Cohen seems to have an almost childlike confidence in authority figures. He says he trusts “the monitoring agencies that ensure pesticides are used at safe levels — a trust the Stanford study found to be justified.” And I suppose he also still believes in Santa Claus? We cannot trust that the “safe levels” established by the EPA or FDA are in fact safe, given the fact that we in an environment where thousands of chemicals enter the market without sufficient testing, presumed innocent unless proven guilty—but to win the case against them, first people must get sick and die.
Cohen’s concluding zinger, “I’d rather be against nature and have more people better fed,” displays his own breathtaking blind spot as regards the human relation to the natural world.
Human beings cannot be “against nature” without being “against ourselves.” We are a part of the natural world just like every other life form on this planet. Our fantasy that we can use our technological prowess to completely divorce ourselves from our material, physical reality is just that—a fantasy. We eat by the grace of nature, not by the grace of Monsanto.
For the entire history of homo sapiens, we have always eaten organic. It’s only been in the last 50-odd years, post World War II, that wartime chemicals and technologies have found new uses in agriculture.
The result has been the rapid and wholesale devastation of vast swaths of our planet—biodiversity giving way to monoculture, killer weeds and pesticide-resistant superbugs going wild, the weakening and sickening of every strand of the ecological web of our planet.
The relevant fable to invoke might be the tale of Jack and the Beanstalk. We might be able to grow a fantastically huge beanstalk if we fed it with enough chemical fertilizers, and we might even be able to climb it and bring back a goose that lays golden eggs.
But in the end, that beanstalk will prove to be more dangerous to us than it’s worth—we’ll have to chop it down, and go back to the slow but solid organic way of life that has sustained us unfailingly for thousands of years.