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When Merck's AIDS vaccine candidate failed in clinical trials, the National Institute of Allergy and Infectious Diseases (NIAID), in the National Institutes of Health (NIH) called a summit. The drug candidate did not reduce HIV infections, in fact the adenovirus based vaccine seemed to increase the risk of infections.

The meeting of scientists on March 25th in Washington focussed on the future of HIV/AIDS research in light of the fallout of Merck vaccine trials. Scientists including Anthony Fauci, who heads the NIAID, agree that funding needs to be redirected towards a broader research agenda and ideas beyond drug development and vaccines. Science last week noted that the decision about whether to proceed with the large NIH clinical trial planned for its HIV vaccine is still pending. ("Review of Vaccine Failure Prompts a Return to Basics" DOI: 10.1126/science.320.5872.30)

Nature also reported on the summit last week, pointing out that these clinical AIDS trials went forward not necessarily based on the strength of the science -- one of the vaccine candidates had a unimpressive track record -- but because programs needed to "show the public that progress is being made, thereby justifying the millions of dollars from philanthropists and taxpayers". ("Broken Promises" doi:10.1038/452503a).

The Nature editorial offers analysis of this HIV-AIDS vaccine experience, noting that ambitious commitments made in a flush funding environment in the early part of this decade short-changed basic research. These choices to heavily fund drug development are regarded less forgivingly in light of the trial failures and the budget shortfalls of recent years, according to the journal. Nature warns other fields, for instance stem-cell research, autism, and Parkinson's disease, are repeating these same mistakes.

The business approach comes with a high stakes mentality and ample, vigorous marketing that can ratchet up expectations both within the organization, the field and the public arena. The business-oriented nature of many philanthropic organizations influences the focus on development and can distort public expectations. But investors can and do influence the direction of an entire field. When a field becomes dominated by a few foundations it can gather tremendous productive momentum, but it can also stampede so hard down a particular path with such strong momentum in a particular direction. If that direction proves to be less fruitful than hoped research cannot turn around on a dime.

Each high-funded disease has its own idiosyncratic pitfalls, but behind the good works and fine intentions of charities, but the science research rarely responds to pressure, unlike many entrepreneurial ventures. When scientists request research funding, the results don't always yield answers as quickly as businesses might hope -- research is the mythical man myth on steroids. Some people investing in biotech and international public health come from businesses very unlike public health with its vagaries of not only politics and human behavior, but biology.

In today's fast paced communications and computing climate, intense focus on "results" is inherent to our culture. Expectations carry over from the successful and extraordinarily speedy progress of the genome sequencing. Scientists and politicians built hopes during that time that drug development and an accelerated understanding of human disease would follow. It has, but did we expect more? TV drug advertising gives the impression that scientists are developing a pill for every insignificant hangnail, when many of these drugs aren't new, just the subjects of new marketing campaigns. Meanwhile tougher diseases and conditions remain elusive.

High profile funding can influence the research environment and lead to a very public dead end. In the larger picture, despite the wisdom that should be accruing from these experiences, politicians, technology leaders, and pundits sometimes wax-on about technology's potential to produce solutions not only for specific diseases but for extremely complicated social problems such as global warming and healthcare. But while science research may yield pharmaceuticals and oil extraction techniques but one cannot look to science or technology to solve the healthcare crisis in the United States. Science and technology contextualize these problems and are integral in our lives but despite heady declarations, they are not central to the solutions.

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Acronym Required has written previously about these subjects, AIDS and research directions, and vaccines. Here are a couple of our vaccine articles:

Vaccinations -- Why Worry?
Polio Vaccinations - The end of a scourge?
Group B Strep Vaccine Development
Vaccine Development For Infectious Diseases

BPA -- Here to Stay (In the Environment)

Bisphenol A (BPA) is a chemical used in plastic products we all use, everything from dental resins to household products, canned foods, plastic food containers, and baby bottles. Since the chemical gives plastic products useful properties, its ubiquity means that most of us have traces of it in our bodies -- 93% of populations tested have BPA in their blood. Chemists originally developed BPA as a possible synthetic estrogen so it binds to estrogen receptors, is potent at low doses, and as such it can cause deleterious health effects such as decreased sperm count, enlarged prostate, cancers, diabetes, early puberty, and immunological and developmental effects.

Legislators for the city of San Francisco recently proposed bans on bisphenol A and phthalates, however in the final bill, after the legislators had probably duly considered circumstances such as a lawsuit against the city by bisphenol A manufacturers and toy retailers, as well as sustained lobbying from chemical company lobbies, they removed bisphenol A from the bill. The states of California, Maryland and Minnesota all produced bisphenol A bills that died in process. The America Plastics Council rigorously lobbied against all these bills and is relentless in its efforts to convince the public that there's no scientific evidence to support the dangers of health effects of bisphenol A. In fact, there are hundreds of government sponsored research studies showing health effects of BPA.

Chem Link Love: BPA-->EPA--> FDA--> APC--> RTI--> PPG

Now Congress has taken interest in Bisphenol A. The U.S. House of Representatives and Committee on Energy and Commerce chaired by John D. Dingell (D-MI), and its Subcommittee on Oversight and Investigations, launched an investigation of Bisphenol-A in January. The subcommittee is focusing on BPA found in products made for infants and children like infant formula, where BPA is used in the epoxy liners of cans.

The subcommittee has sent out a series of letters requesting more information about the safety of BPA from the makers of infant formula, the EPA, the FDA, and others, including the consulting firm the Weinberg Group. The manufacturers of infant formulas responded variably that BPA was not found in formula, was found at levels considered safe, and/or BPA epoxy was the only option for lining cans*.

In a letter to the FDA the subcommittee questioned what evidence the FDA used to deem BPA safe, to which the FDA wrote back citing two studies both "sponsored by the American Plastics Council". Both of these studies were done by Research Technologies Inc. (RTI) and scientists have cited problems with at least one of the studies' methodology's. (The president and CEO of RTI Victoria Haynes coincidentally cut her teeth at Monsanto, rising to the post of director of their plastics division. In addition to her RTI post she was an adviser to the Homeland Security Advisory Committee and is a director at several companies, including PPG Industries, a company whose products include epoxy resins for cans as well as *'non-epoxy liners for the European market.')

Government and Industry Consulting, a Lucrative Formula Perhaps?

Last year Acronym Required wrote about Sciences International Inc. (SII), a small consulting firm that was fired for conflicts of interest from its contract running the NIH Center for the Evaluation of Risks to Human Reproduction's (CERHR) assessment of Bisphenol-A's safety for neonates and infants. We wrote that SI's mission included public education, such as publishing their own research on chemical safety in their own scientific journal headed by their own company executives. They cited this as "peer reviewed" research on their website and in white papers perhaps to increase their scientific credibility and assure people of chemicals' low safety risks.

The Sciences International website touted the company's abilities to leverage government contacts for corporate benefit, and their history of producing favorable regulatory outcomes and public opinion. For example SII described their risk analysis work used to influence lower regulatory standards for clean air for the EPA. On one version of their site, SII wrote: "Sciences' methods development work is often sponsored by public agencies, such as the U.S. EPA, while applications work is most often for the private sector where agents of particular concern need to be addressed."

In that post in 2007, Acronym Required wondered about the nature of regulation in Washington when the company NIH chose to assess the safety of BPA for neonates and infants that seemed to be more focused on industry objectives: "[Sciences International scientists]...have applied a biologically-based model approach to coke oven emissions for the industry and derived an alternative cancer potency factor which has been accepted by the EPA. We believe that our ability to utilize accurate dosimetry and pharmacodynamic models in tandem in risk assessments provides unique opportunities to the chemical industry",

Acronym Required is heartened to know Congress is paying attention. Similar to the SII example, the subcommittee explored the marketing website (since removed) of the chemical industry consulting company the Weinberg Group. As per the subcommittee's quotes in their request for more information, the Weinberg site was a virtual rodomontade of feats pulled off by Weinberg on behalf of chemical companies versus government regulatory agencies, all of which seemed to skew scientific integrity in favor of client "results".

The subcommittee sent a letter to the Weinberg Group asking about a series of case studies that included verbiage about various projects, such as swaying an FDA decision on a drug with "life-threatening adverse events", and being "at the forefront" of public relations addressing endocrine disrupting chemicals "leaching from food containers", and contained in "children's toys". (the latter sounding a lot like bisphenol A.)

The subcommittee requested information on details of another letter from the Weinberg Group to DuPont de Nemours referring to their work on the chemical perfluorooctanoic acid (PFOA), a carcinogenic chemical used to manufacture Teflon. Weinberg says they produced scientific papers on "PFOA, junk science and the limits of medical monitoring", handled scientific testimony and expert witnesses for court cases, and "[reshaped] 'the debate by....analyzing existing data, and/or constructing a study to establish not only that PFOA is safe over a range of serum concentration levels, but that it offers real health benefits.'" PFOA Dupont has been fined by the EPA and sued for its PFOA activities including suppression of safety information for 20 years.

The committee has now widened its scope beyond BPA. Their letter to the EPA's Stephen Johnson requested information about the dismissal of Dr. Deborah Rice as the chair of an external review panel that was investigating a type of polybrominated dephenyl ether (PBDE), decabromobiphenyl ether (deca) used as a flame retardant. Rice's sacking followed a letter the EPA received from the American Chemistry Council (ACC) complaining that she had testified for the State of Maine on the dangers of deca. The ACC called her expertise a "conflict of interest". The subcommittee's letter challenged the EPA's firing and included 9 incidences of people from industry who testified on various EPA chemical safety panels despite real conflicts with obvious pecuniary connections in the chemical industry.

It will be interesting to see where this goes beyond the obvious -- subcommittee members burnish their environmental credentials while giving companies serving both government and chemical industries another lesson on the pitfalls of producing zealous marketing material for the company websites. We remain optimistic that the inquiry will produce results and anyway, the public outing of information is always useful. Happy belated Sunshine Week.

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Acronym Required wrote about bisphenol A in the following posts:
"Phthalates and Bisphenol A: Media and Politics" (November, 2007)
Plastic Bottles- Protecting Your Baby, by the ACC (July, 2005)
"Bisphenol-A and Phthalates Bill in California" (January, 2006)
"San Francisco Bans Bisphenol A, Phthalates" (July, 2006)
"San Francisco Phthalates & Bisphenol A Ban" (November, 2006)
"Sports Retailers Stop Selling Polycarbonate Bottles" (December, 2007)
We wrote about PFOC in these posts:
"PFOC: Likely Carcinogen" (January, 2006)
"Dupont, The Teflon Company" (December, 2005)
"Slick Company Stands behind Teflon"(July, 2005)

My House or Yours?

One evening about 5 years ago I learned of "chicken pox parties". There on a news group, a dozen people chatted about sending their kids to a "party" with such nonchalance you'd have thought they were planning holiday shopping and $5.95 lunch special afterwards. Perhaps they'd spent hours thinking over the pros and cons. But on the public forum those do-it-yourself infectors didn't question the public health risks, the possible complications, or the ethics of purposefully exposing your kids and family to highly infectious diseases that fortunate people in western countries get immunized against. If they had doubts they masked them with derring-do.

I was taken aback by this parental concept of fun and thought it some new and bizarre fad. Naturally I was curious. How would it work? "OK kids, now we're going to pass the communal drink cup around, then we'll play the kissing game..."? (I also rethought my entire childhood in a positively idyllic way, though I never forgot the sting of merthiolate.¹)

These modern parental dalliances with infectious disease seem ironic. Public health's largest successes include the vaccination campaigns that eradicated or significantly reduced loathsome diseases such as smallpox, polio, yellow fever, measles, diphtheria, and tetanus. The UN reported last November that measles vaccination efforts, especially in Africa, have helped decrease measles deaths by two-thirds across the world since 2000.

Scientists and doctors toil to develop vaccines for ugly scourges like HIV and malaria, which are each responsible for mortally infecting up to 30% of some populations and when a recent AIDS vaccine trial failed, the collective global dismay was palpable. For diseases where vaccinations aren't available, citizens in developing countries latch on to promises from the public health community that millions of people's lives will someday be saved by immunization. Against this backdrop, suburban parents in western countries shun vaccinations, because in their country, in this day and age, the injections themselves seem more dangerous than the diseases.

It's tempting to think of these "chicken pox parties" as the privileged reserve of parents of a certain age who never saw the ravages of disease that previous generations knew intimately. Maybe if they saw a man crippled by polio; maybe if they had lived through the smallpox epidemics in New York at the end of the 18th century, where one in five victims died and in milder cases victims were left left blind. Maybe their mother or grandmother never described what it was like caring for a family during an outbreak of chicken pox as it swept through infecting each of six children.

But doubts about vaccines are perennial. Now parents air their vaccination suspicions via the web. Before the web, they talked on the phone, or at work, or in between hauling water from the well. This is not the fad of a select cohort of modern parents, convinced that a case of wild chicken pox is safer than a vaccine because they've never known anyone who died of the disease.

These unique "social events" seem shocking when they appear in your inbox. Go to any online article about any part of the whole wide topic of vaccination and peruse the comments section for horrifying rumors, misunderstandings, and cavalier-bordering-on-criminal pronouncements about never vaccinating kids. It's enough to make anyone shudder -- doctor, scientist, parent or casual reader. It's easy to see how those who claim that thimerosal is responsible for every imaginable childhood tic are dangerously misguided. It's less acceptable to question an authority who tags as crazy anyone who questions any aspect of vaccinations.

For Your Own Good -- Smallpox in New York

Naturally, vaccinations have an interesting and controversial history, like much of medicine. The tussle between public health campaigns and fearful citizens is part and parcel of that history. The first vaccinations introduced a wound with a sharp implement of some sort, then infected the area with a bit of virus from a sick neighbor or perhaps some pox in a jar. Vaccination became more sanitary, but the concerns about safety persist as with all cutting-edge medicine.

Along with the health worries, there has always been questions about the government's power to compel vaccination. When vaccinations arrived in the US from England in the early 1800's, people balked at what they saw as encroaching boundaries of government. At the time, American public health initiatives were more about trying to convince people not to do things, like "[let] their privy overflow into the street" says James Colgrove in "Between Persuasion and Compulsion:Smallpox Control in Brooklyn and New York, 1894-1902 (Bulletin of the History of Medicine 78.2 (2004)). As Colgrove's book title indicates, public health officials walked a fine line between persuading, cajoling and forcing public compliance, for many years without legal authority.

Health officials contained smallpox outbreaks by vaccinating households within a circumference of an infected household. If someone refused to receive the vaccine, authorities would station couple of policemen, the "Sanitary Police", to enforce a quarantine on the household. There are stories of people who made involved escapes from quarantined New York residences, only to be caught in New Jersey and hauled back for punishment.

While libertarians thought the government was overstepping, even when vaccinations became safer there were concerns about the deleterious effects of vaccinations. During several outbreaks of smallpox in New York in the late 18th century and early 19th century, rumors spread that the vaccine contained tetanus, despite significant efforts by health professionals to dispel such notions.

Arthur Allen writes in "Vaccine: The Controversial Story of Medicine's Greatest Lifesaver" that "Raggedy Ann", was named for a rag doll handed down from writer Johnny Gruelle's grandmother to his daughter Marcella and memorialized in Gruelle's books. Marcella died at 13 after receiving two smallpox vaccinations in school -- some fears were justified. According to Allen, the Raggedy Ann doll then became symbol for the anti-vaccination effort.

At the beginning of the 20th century, anti-vaccination advocates successfully brought two high profile cases to court to challenge the government's right to make vaccinations compulsory. In 1904, the New York state court decided in Viemeister v. White that the state could mandate laws curtailing individual liberties in order to protect public health. In 1905 the Supreme Court decided that all states have the right to legally enforce public health measures, in the infamous Jacobson v. Massachusetts precedent. This helped solidify government authority, and continued medical advances and quality control assured safety. However real and perceived hazards remain.

The same issues (legal, moral, individual liberty, public safety, medical safety) churn in the public arena today as during the smallpox vaccination campaigns of 100 years ago. People erroneously think modern issues are unique to our era but the underlying questions are the same. Is HepB really necessary for newborns they ask? Can I infect my own child with chickenpox? Can I skip vaccinations altogether and depend on herd immunity? States struggle with how to keep populations safe.

Additionally, people understand the profit incentives of pharmaceuticals and ask questions like: Is a cervical cancer vaccination really necessary for my 9 year old daughter? Since so many vaccinations are enforced by law there's an uncomfortable nexus of profit motives (pharmaceutical companies), individual health concerns (what are the risks of taking or not taking the vaccine), and public health concerns (how to prevent scourges and keep the public safe).

While vaccination is one of medicine's greatest coups there are still many issues and questions about vaccinating. Nevertheless among all the doctors, commentators and public health authorities who speak out, there's always one subset of the chorus who authoritatively treat all questions and concerns with the same universal knee-jerk dismissiveness. Is their approach the best public health strategy?

"Same, Same But Different" - Polio in Nigeria

Vaccination doubts are not the exclusive domain of "naive" westerners. Polio persists in countries like India, Afganistan, Pakistan and Nigeria where many people know first hand the crippling effects of the disease, yet still occasionally resist vaccination. In 2003, Nigerians in some northern states thought that polio vaccines contained HIV virus and/or sterility drugs, and began refusing vaccinations. Here's how the CDC described the problem (brackets mine):

False rumors about OPV [oral polio vaccine] safety adversely affected SNIDs [Subnational Immunization Days], with the greatest impact in Kano, where 25% of all Nigerian WPV [wild polio virus] cases occurred in 2003. Citing vaccine safety concerns, state authorities in Kano (which last conducted a SNID in April 2003) decided in August 2003 to suspend all SIAs [supplementary immunization activities]. Statewide suspension of SIAs at different times during 2003--2004 also occurred in Kaduna, Zamfara, and (to a limited extent) in Niger state. As a result of these rumors, public health managers and frontline health-care workers found it increasingly difficult to improve microplanning, training, and implementation of SIAs.

Unlike the New York Times, the CDC is not in the business of humanizing disease. The agency categorized the events but of course gave no hint as to where the false rumors may have come from. However it's worth looking at because Nigeria's history with vaccinations provides some insight into the quandary of public resistance to vaccination. For instance take these three recent events:

1) As Western AIDS denialists like Peter H. Duesberg influenced South Africa's Thabo Mbeki, some say a book by Edward Hooper published in 1999 called "The River: A Journey to the Source of HIV and AIDS" (Little, Brown) fed rumors throughout Africa that AIDS was spread to humans via a related simian virus contained in a oral polio vaccine (OPV) given to populations in the 1950's. Hooper theorized that OPV was developed when scientists used primary chimpanzee kidney cells as a substrate for the vaccine. The polio vaccine was tested in mass trials across Africa, Poland and Russia, but Hooper claimed that in Africa OPV led to HIV.

Hooper's book was well received. Reviewers from most major newspapers gave the book good reviews, and even more skeptical reviewers gave partial accolades. Robin Weiss of Science called the book "a towering achievement; right or wrong in its main conclusion, there is much to learn from Hooper's exposition" (Vol. 286. no. 5443, pp. 1305 - 1306). John Moore, in a Nature review called the book, "in many ways, superb. It is scholarly, thoroughly researched, well (if densely) written and deserves, indeed demands, to be taken seriously." ("Up The River Without a Paddle", 401, 325-326 (23 September 1999) | doi:10.1038/43778) However both journals disagreed with the central tenet of the book because Hooper based his conclusion on circumstantial evidence. Shortly thereafter no less than three research groups disproved Hooper's hypotheses in research that was published in Nature and Science. Nevertheless there's enough residual interest and belief in Hooper's book (and he continues to publicize and update his hypotheses), that the ideas he introduced persist today.

2) Africa has long been a place where clinical trials are conducted unlike the way they are in the US. When these trials don't work out the fallout hurts subsequent public health efforts. For instance take the recent example of Pfizer's Nigerian clinical trial of Trovan in 2006. Half the kids were given the antibiotic Trovan (Trovafloxacin) during a meningitis outbreak, and half were given ceftriaxone, the drug normally used to treat the disease. Kids from both groups died, but the focus was on the eleven of the kids in the trial on the test drug and others in the experimental cohort who remain permanently impaired.

The Washington Post covered the story in a series called the "The Body Hunters". Marcia Angell also outlined the trial in a New York Review of Books article, also called "The Body Hunters". Investigators who followed up on the clinical trials charged that the company breached medical ethics and said the trial wouldn't have been allowed in the US because it's unethical to do a trial of an unproven drug during an active epidemic. Among other issues, doctors gave inadequate or no informed consent to patients, and the dosage for the established (control) treatment was reportedly too low, which could have made the experimental drug (Trovan) look better.

National outrage over Pfizer's actions brought a group of Nigerian plaintiffs to New York where they unsuccessfully attempted to try the case in the US. Nigeria's suit against Pfizer continues to this day, and a lawyer for Nigeria recently testified about the US red tape complicating his attempts to summon to Pfizer executives.

3) In 2003 the idea that vaccine campaigns were nefarious sterilization efforts gained momentum after scientists reported that polio vaccines contained estrogen. A Muslim leader, Dr Ibrahim Datti Ahmed, secretary general of the Supreme Council for Sharia in Nigeria, claimed he had research proving western goals to "depopulate" Africa and introduce "adulterated" vaccines. Throughout history, the west has championed family planning, which has elicited abject suspicion, and led to occasional rumors about devious plots by western forces to decimate populations via birth control and vaccinations. Public health workers have diligently tried to solidify trust of vaccinations among Nigerians for decades.

But in 2003 the Nigerian polio vaccination program was forced to shut down so that politicians could test the vaccines suspected of being birth control agents and provide public proof of their safety. Such an interruption can have devastating health consequences. Vaccination rates fell to 30%. and the disease spread to Muslim communities around the world. Muslims tended to mount resistance to vaccinations people say, because they were wary of the war in Iraq and perceived animosity from the US to Muslims. Eighteen countries previously declared polio free incurred polio flare-ups and countries that hadn't seen polio since the 1980's had outbreaks.

Any of these incidents could have help spread fears about vaccinations. Hooper's ideas have been dispensed with and Trovan may have not have caused deaths, but the effect of these incidents has a far-reaching negative impact. Furthermore, when clinical trials are conducted in countries under circumstances that wouldn't be legal in the US, suspicion is not without foundation.

10 Billion Doses, 200 Side Effects.

During the interrupted 2003 polio vaccination effort, many Nigerians went unvaccinated, and the population became susceptible to another uncommon occurrence. The polio vaccine, made of attenuated virus, can occasionally mutate to a wild non-attenuated virus that causes infection. But the chance of this occurring increases when a large number of unvaccinated people give the virus more opportunity to replicate and mutate to the wild form.

The journal Nature reported that an outbreak of this type last fall ended up paralyzing 69 children. This is a rare occurrence -- the WHO expert interviewed by the journal pointed out that "10 billion doses of oral polio vaccine...administered worldwide were implicated in 9 outbreaks, accounting for fewer than 200 cases of disease" (Michael Hopkin, "Health officials fear Nigeria Polio setback" 12 October 2007 | Nature | doi:10.1038/news.2007.163). Despite how rare these occurrences, or the fact that they often occur when many people refuse to get vaccinated, the incidents feed suspicion.

Time reported that Nigeria's 2007 outbreak due to the wild-type virus was contained via collaborative public health messaging between religious, health and political leaders. However sometimes mischievous anti-immunization authors, politicians, organizations or religious leaders stir trouble by either malevolently or innocently blaming such an outbreak on vaccinations.

There are risks to vaccinations. There are risks to clinical trials. There are mistakes, and sometimes medical malfeasance. And there's a public disconnect when it comes to understanding risk, 200 side effects in 10 billion doses is very safe, but no one's content when their child has the adverse reaction. There's always the possibility that a few aberrant reactions to a vaccination can innervate fears in hundreds of people and derail a whole vaccination effort.

Some percentage of the population will always distrust vaccinations, no matter how good the messages. But another percentage of civilians have legitimate concerns. Public understanding of reasonable risks is further complicated by public health, pharmaceutical and political hesitation to admit errors for fear that people will shun vaccinations (or pursue litigation). So what do these suburban American families have to do with Nigerian villagers? People harbor distrust of government mandated vaccinations produced by for profit pharmaceutical companies. If all resistance, chicken-pox parties as well as questions about the necessity of cervical vaccines receive the same reception from authorities, as they do sometimes, this can lead citizens to distrust public health authorities and more vehemently shun vaccinations, ironically.

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¹ Merthiolate is a trade name for thimerosal and was widely used as a topical antiseptic for children. You'd fall down scrape your knee, and then into the wound mom would pour this reddish-orange-pink stuff, a toxin, as it turns out that really burned and smarted. Barbaric.

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You're so Sad, We're So Happy

Antidepressants have taken a beating over the past couple of years with a steady stream of difficult news, some of it contradictory -- about studies biased by doctors interests, potential dangers of the drugs for children, limited effectiveness as a result of selective reporting, and patients struggling to withdraw from the drugs. Regardless of the news, many patients critically depend on antidepressants and pharmaceutical companies invest heavily in their development.

Last week Wyeth announced the approval of Pristiq, an antidepressant they're marketing to succeed Effexor XR. Effexor was the first of the serotonin-norepinephrine reuptake inhibitors (SNRIs), followed by Eli Lilly's Cymbalta. Wyeth won FDA approval for the drug's use as an antidepressant and is hoping to get the drug approved for menopause. This is a savvy move. With the HRTs in decline because of cancer risks Pristiq is the first drug to be marketed as a non-hormonal option for menopause "symptoms".

Eating Your Own Dog Food?

Some doctors question whether "Pristiq", a metabolite of Effexor, is an improvement over any of the drugs currently on the market. Regardless of doubts, the drug is a lithe marketing confection, starting with the name, "Pristiq", which summons to mind "pristine", as in, that is the cleanest most crystal clear pristine lake you've ever seen, and "mystique", as in, wow, he/she has that certain je ne sais quois -- mystique. Ergo "Pristiq". Just saying it makes you want to hop out of the chair, dress well, smile brightly, finish a report, wrap up a business meeting, or throw a dinner party -- tonight, for 50 friends.

With Effexor coming off patent, Wyeth is happy to have Pristiq in the wings. As Gino Germano, Wyeth's president of pharmaceuticals told the New York Times, doctors and patients need to have options. The Times' print edition featured a photo of the beaming Germano, perhaps elated over the FDA approval news and definitely projecting a certain unique Pristiq mystique. Some analysts predict $1.5 billion in sales by 2012.

FDA Leader Criticized

We wrote the "State of the FDA" about a couple of reports documenting FDA management shortcomings compounded by budget shortfalls that compromise the health and safety of US citizens. Now Rep. Bart Stupak (D-MI), who heads the Subcommittee on Oversight and Investigations in the House Energy and Commerce Committee has called for FDA commissioner Andrew von Eschenbach to be replaced. Eschenbach has been in the post a little over a year.

In a press release Feb. 1, 2008 on the FDA, Stupak said the agency was no longer a "pending" crisis, but rife with problems and fresh off a formidable record of "378 recalls last year on everything from peanut butter to pet food to drugs". Stupak's goal "is to help identify what went wrong and implement changes to minimize negative health effects on the American people." Stupak even has a replacement candidate in mind according to the Wall Street Journal.

Firecracker Appointees

However some politicians see the Michigan Democrat as a little too aggressive. Rep. Joe Barton (R-TX) says that firing the commissioner is a bad idea and told the journal that Dr. von Eschenbach is a "dedicated public servant," who has "certainly not done anything unethical or illegal". (Gold Star commendable these days, but shouldn't we be throttling for a higher standard?)

Some news agencies scurvily suggest that the death of Stupak's son from suicide, a reaction to the acne drug Accutane, motivates his attention to the FDA's problems. However the congressman points out that while the incident gave him insight into the FDA, if people knew how little oversight the agency had on some products they'd be "marching in the streets." (like the Sixties?)

It's too bad Stupak wasn't in on the Senate confirmation hearings in August, 2006, since perhaps he could have guided the leadership choice at the beginning of the process. The Senate deliberated during von Eschenbach's confirmation hearings, voicing reservations about his suspected attention to politics over science. The commissioner is a family friend of President Bush's who had what Newsweek at the time called "a history of generating controversy".

Prior to his FDA tenure he worked at the National Cancer Institute (NCI), where he "introduced prayer to commission meetings", unrealistically set a goal of eliminating death from cancer by 2015, and was called a "disaster" by some staffers. Senators Murray and Clinton balked on his confirmation over the stance the FDA was taking on Plan B, the birth control pill. In what seemed like a sort of a quid pro quo deal, once Plan B got passed von Eschenbach got confirmed.

The interesting thing about Bush's political appointees to science agencies is that the lifecycles between Senate confirmation and given appointees' agencies' disasters has become quite short, in a way that nicely matches the current pace of news. The predictability and familiarity of it all gives us a sense of reassurance in a day when little else is predictable. Reporters aren't like - von Eschenbach who? It's just - oh yeah, that guy everyone worried about a year and a half ago.

But again, as with many of the science agencies it's not all about the commissioner. Stupak acknowledges that the FDA has entrenched problems that preceded Eschenbach's short tenure.

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Acronym Required wrote about von Eschenbach's confirmation hearings in "The FDA'S 'Medical Ideology'"

We wrote "Resuscitating The FDA", about the FDA in the wake of various fiascoes.

"FDA -- Calling Off The Dogs", is about Plan B and FDA staff turnover.

"Ethics- The NIH and FDA", discusses conflicts of interests among scientists in these two agencies.

Sciences International: Health and the Environment

It reads like the classic story of the fox guarding the hen house. Sciences International, (SI), a small company with clients like the American Chemistry Council, Dupont, WR Grace, and Exxon Mobil, also ran the Center for the Evaluation of Risks to Human Reproduction (CERHR), a project in the NIH's toxicology program (NTP) charged with deciding which environmental toxins pose health risks to reproduction and the development of unborn children.

Science International wrote a report last year on bisphenol A's (BPA) safety, which came to the attention of the public and congress when the Environmental Working Group (EWG) alleged that the conclusions were biased towards industry research studies in a Feb. 28th letter to the NIH hiring director.

Reproductive health and development, like children's health, is always a lightening rod for public attention, and increasingly, so is bisphenol A. Science International's review of the literature on bisphenol A caused enough concern among scientists, members of congress, and public health official that in the ensuing brouhaha, the NIH's National Institute of Environmental Health Sciences (NIEHS) terminated Science International's $5.24 million contract running CERHR. After the termination, Herman Gibb, the president of the approximately ten person company insisted to the Washington Post, "I don't ever believe in my heart of hearts there was a conflict of interest".

When the story made headlines last month it seemed to confirm our worst fears. NIEHS accepted a contract apparently written by Science's International to run CERHR without listing company's conflicts of interest, an arrangement that seems ripe for abuse. Acronym Required looked into the details of the story, which do little to allay those concerns. Had SI, working for the FDA, the NIH, and now CERHR, as well as significant numbers of chemical companies perhaps systematically watered down environmental safeguard regulations over the past decade to suit it's corporate clients? The Science International incident reveals the potential pitfalls of blending government and industry work, both for companies like SI and for public health and welfare.

Science International's Bisphenol A Study

Bisphenol A binds to estrogen receptors and can cause deleterious health effects such as decreased sperm count, enlarged prostate, cancers, diabetes, early puberty, and immunological and developmental effects. It's potent at very small doses and ubiquitous, found in everything from dental resins to household products like canned food, plastic food containers, and baby bottles. Today 95% of the population carries detectable levels of the chemical in their blood and hundreds of scientific research reports indicate BPA's toxicity to humans.

According to critics, Science International's first draft report on the health effects of BPA was biased. The report concluded the opposite of what hundreds of government funded BPA studies conclude. A survey of the research on bisphenol A effects shows that 92% over 100 (109/119) government studies on BPA found adverse health effects, whereas all 11 industry funded studies found that BPA caused no adverse health effects. Scientists critical of the Science's International report said that the review panel favored industry results while ignoring unreliable industry results base on unscientific methodologies like lab protocols that used no controls.The EWG also questioned whether SI's principal scientist could neutrally evaluate the dangers of bisphenol A (BPA) since he had worked with Dow Chemical and the European Chemical Industry Council -- entities with business interests in BPA.

Sciences International wrote the meta-study of the research studies, then chose the panel who reviewed their work. While SI said that the final conclusions as to the hazards of bisphenol A during reproduction and development were the panel's, when Acronym Required looked at the panel's edits of Science International's first draft they were stylistic, not scientific.

A New GovBiz Model?

Can a company consult to the chemistry industry and also evaluate the safety of that industry's products -- without bias? Can we trust government, industry partnerships to evaluate science when their contractual agreements cede the very principles we use to ensure integrity in research and in business, like peer review, conflict of interest statements, and competitive bidding processes? An older CERHR website described the partnership between SI and the CERHR:

"Under the direction of Michael Shelby, Ph.D., Director, CERHR at NIEHS, scientific and support staff at NIEHS and Sciences International, Inc. operate the Center for the Evaluation of Risks to Human Reproduction (CERHR). The Principal Investigator, Anthony Scialli, M.D., leads the scientific and support staff at Sciences International, Inc."

In addition to the BPA report, SI also produced reports profiling the safety of many other chemicals during their contract with CERHR. Sciences International consulted for 10 years with the FDA and the EPA, and worked with corporate clients like GE, Union Carbide, Hoechst Celanese, Otsuka Chemical, Cytek Industries, a plethora of law firms, and industry groups such as the American Chemical Council, Synthetic Organic Chemical, the Acrylonitrile Group, and the American Petroleum Institute. The EWG wrote in one letter to the director of the National Toxicology Program (NTP), about the "ethical concerns surrounding this contractor that involve apparent financial ties with the chemical industry..." Indeed, when we perused SI's older websites, they wrote clearly about the work they performed:

"Nowhere is Sciences' exposure assessment experience more evident than in EPA's new Clean Air Act residual risk program...[]...EPA generally applied, for the first time, this guidance in a recent residual risk case study of the secondary lead smelting industry. That guidance, or some variation of it, will be used to address residual risks for all remaining industrial categories with MACT standards. Working for a coalition of seven major trade associations (Chemical Manufacturers Association, American Petroleum Institute, American Coke and Coal Chemicals Institute, American Iron and Steel Institute, National Mining Association, American Forest and Paper Association, and Association of International Automobile Manufacturers), Sciences prepared detailed comments on the case study approach and results, and presented a report on March 1, 2000, to EPA's Science Advisory Board (SAB). The ensuing SAB draft meeting report clearly showed that Sciences' comments played a major role in their analysis, which included a recommendation to revise the case study and return it to the SAB for a second review.

Sciences also developed a vastly improved exposure and risk assessment method for evaluating coke oven residual risks and recently gathered residual risk data on the gasoline distribution industry for the American Petroleum Institute. Sciences' staff includes an ex-EPA manager who led for six years the hazardous air pollutant regulatory efforts for the Office of Air Quality Planning and Standards (OAQPS). In that position, he managed the initial development of the Human Exposure Model and was a member of the group that wrote the Agency's initial exposure and risk assessment guidelines. Earlier, he conceived of and managed the original 4-year study of the organic chemical manufacturing industry that ultimately formed the basis of the Hazardous Organic NESHAP (HON), he also..."

Naive marketing hype, or conflict of interest? If boasting to chemical companies about your company's power to have its way with government is inherently wrong, then for years Sciences International promiscuously flouted the rule in marketing material on their public website. Clearly, SI had strong ties to the chemical industry. But was it some especially insidious arrangement, a punishable offense? Or is this just how the U.S. government works?

Many companies who contract with the government also work for business clients who gain honest efficiencies and insights from consultants' familiarity with government rules and ruminations. In general, we wouldn't be shocked to find private contractors running public agencies, because privatization is a goal of recent governments -- both Democrat and Republican. The increasingly fuzzy demarcations between private and public entities constitute contracts in Iraq, New Orleans, U.S. National Parks and atmospheric weather monitoring operations. Overall, companies who mix business relationships with government work fare well these days. The Homeland Security Index, for instance, which includes SI's parent company Tetra Tech, rose 5.3% last quarter, whereas the S&P 500 posted -.86%, the DJIA; -1.70%, and Nasdaq; -1.57%. Are these corporate/public relationships the new normal, or something else, given that SI was summarily fired?

The Etiquette of Serving Two Masters

In one of two good pieces Nature wrote on the subject a couple of weeks ago, ("Regulators pull contract for chemical review" 446;958-959, Apr. 26), the author noted, "there's a legal grey area" that contractors navigate in dealing with clients. Nature makes a point. If you find SI's client mix disturbing, then the client list of most law firms or consulting companies might also disturb you. How are consulting companies supposed to separate the clients? Nature quoted one toxicologist who pointed out that the rules are unclear, even for companies like Sciences International, he said, who (as Nature summarized) "try to segregate industrial and government work to limit conflicts".

Contrary to what the consultant assumed, however, and perhaps leading to to its undoing, Science's International did not convincingly "segregate" it's constituencies. Here are some excerpts from their 2005 site.

"...EPA estimated very high cancer risks in one assessment of a regulated industry. Sciences developed a much more accurate exposure model and also reassessed the cancer unit risk estimate using much more recent worker epidemiology data and biologically-based modeling approaches, originally developed by Sciences' experts. Sciences' revised study showed that actual risk estimates were two to three orders of magnitude lower than EPA's earlier conservative estimates...."

"Sciences has unique experience in assessing health risks due to inhaled air toxicants. Sciences' experts were selected by the EPA, as sole source contractors, to work on the underlying methodology by which the EPA develops its safe levels of exposure to chemicals by the inhalation route..."

"...Through a contract with the EPA, Sciences carried out the quality assurance and validation of BMDS, making several critical recommendations that influenced its development. ...[]...Sciences is also currently involved in a similar effort for EPA's recently developed Categorical Regression (CatReg) software...[]...A 5-person Sciences International team is writing the EPA Benchmark Dose Guidelines. With all these considerations in mind, we are in an excellent position to apply the BMDS and CatReg methods to particular substances that would benefit from these approaches."

"[Sciences International scientists]...have applied a biologically-based model approach to coke oven emissions for the industry and derived an alternative cancer potency factor which has been accepted by the EPA. We believe that our ability to utilize accurate dosimetry and pharmacodynamic models in tandem in risk assessments provides unique opportunities to the chemical industry."

SI's statements seem clearly intended to sway a corporate audience. SI clearly tries to establish itself as an ally to the chemical industry, "working on underlying methodogies", a company who changed EPA estimates "two to three orders of magnitude lower", who made "critical recommendations" that "influenced" standards, and created "unique opportunities [for] the chemical industry". Under their "sole contractor" status, SI and its government clients had perhaps short-circuited the bidding process. EWG highlighted portions of a 1999 a letter from SI to RJ Reynolds, where the company wrote:

"Our experience in supporting these government agencies in the advancement of science gives Science a unique credibility to negotiate with regulators of behalf of our private sector clients, to speak authoritatively in the scientific community, and to be accepted in legal proceedings and by the public."

According to Sciences International's own self-promotion, it had broad influence in many agencies, which benefited chemical companies. But without knowledge about the specific science behind SI's marketing, it's difficult to discern what changes they made. It would require a research team to analyze whether those changes were indeed detrimental to health -- whether they are a sleight on behalf of industry, or whether SI simply refined the EPA's less accurate or outdated measurement techniques. Maybe the government standards for indoor and outdoor air, water, etc., did benefit from adjustments based on SI's expertise.

Toxic Puffery

Many big companies in Science International's position keep a more sanctified public front, a website splashed with value concoctions of their love for children, concern for animals and stewardship of the great outdoors. Naively or greedily, Sciences International tossed discretion to the wind and instead promoted their business, aggressively emphasizing the their influential role in government and their willingness to leverage that value proposition for corporate clients.

SI redesigned their website a couple of years ago, and seemingly came to its corporate senses, including a more publicly agreeable photo collage of children and trees, and a client list scrubbed of corporate entities. The new site brags less about the company's experience drafting "more accurate" measurements of exposure assessment and dose-response for the EPA. But sometimes information on the internet doesn't die as cleanly as people might wish. Occasionally ghosts of past lurk about to startle the unsuspecting with a bump in the night, a startling reminder of pasts long since banquished. SI's old website revealed SI's habit of not separating clients. The entire business model, in fact, leveraged conflicts of interest.

"...Sciences' methods development work is often sponsored by public agencies, such as the U.S. EPA, while applications work is most often for the private sector where agents of particular concern need to be addressed. Sciences' knowledge of the acceptable regulatory methods and practices can facilitate ultimate acceptance of these analyses for the private sector."

Dr. Gibb insisted that in cases where SI's government work with one chemical coincided with corporate work, consultants on one contract had no knowledge of what their cohorts were doing on another. How shall we interpret that? On one hand, consulting can be like that. On the other, this was a ten person company. The president doesn't know what people are working on? He complained to the journal Nature that the NIEHS action was unfair "with a capital U". Perhaps so, but then it would probably be fair to say that for whatever their intents and purposes, SI's record just happened to look fishy with a capital F.

Despite the challenge of sorting out what the company was really up to, SI's work is fraught with appearances of conflict of interest. As EWG pointed out, the NIH was remiss not to look at Sciences International's website years earlier. Even a half-hearted glance would have hinted at a slew of conflicts.

According to the Los Angeles Times, in response to NIH inquiries about their duel roles, Sciences International acknowledged that they had prepared Federal health reviews for styrene, ethylene glycol, and soy formula, while working for a styrene trade group, the American Chemistry Council, and the United Soybean Board. However, the president, Herman Gibb, told the Washington Post that he had only learned "last month", because of the NIH's information request request, that the company had worked for the chemical trade companies while simultaneously working to ascertain safe levels for those chemicals.

(Read the continuation of this story, starting with "Vanity Press and Educating the Layperson", in the next post)

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Acronym Required previously wrote about bisphenol A in the following articles:

Plastic Bottles- Protecting Your Baby, by the ACC (July, 2005)

Bisphenol-A and Phthalates Bill in California (January, 2006)

San Francisco Bans Bisphenol A, Phthalates (July, 2006)

San Francisco phthalates & Bisphenol A Ban (November, 2006)

The Wall Street Journal published a front page story today about Justen Deal, who last year confronted Kaiser Permanente management about a 4 billion dollar IT project he thought had gone awry, and a projected 7 billion dollar budget deficit at Kaiser. In "How an E-mail Jolted a Big HMO", (temporary link) the Wall Street Journal noted, "flicking away whistle-blowers isn't as easy as it once was".

Acronym Required wrote an account of the story, "Healthcare IT: The Perfect Storm", last November. Why this story bubbled up on the front page of WSJ now, (albeit in their middle, soft news, people focused column ), when there's not exactly a dearth of seemingly critical world news, we don't know. Local papers have pretty much spurned the story. The IT aspects have been mentioned sporadically in healthcare blogs, the IT media, and the LA Times. This is an interesting business case not only in terms of dealing with internal IT implementation strategy and PR, but also for corporate human resource teams, who in this case, perhaps anachronistically, underestimated his kamikaze-like persistence.

The Wall Street Journal posed a challenge to scientists in yesterday's paper: "Is an Economist Qualified To Solve Puzzle of Autism?" Author Mark Whitehouse looked at the controversy stirred up by Cornell economist Michael Waldman's study¹ last October that linked TV viewing to autism. In "Does Television Cause Autism?" Waldman used precipitation records and cable subscriptions as proxies for TV viewing, then performed statistical analysis to correlate television watching with incidence of autism.

Waldman was motivated to study autism by his family's experience with his young son, who was affected by Autism Spectrum Disorder. In response to his son's diagnosis, and in addition to doctor recommended therapies, he curtailed his son's television watching. To his surprise the child recovered completely. However he was unable to engage doctors to study whether TV caused autism, so he studied the connection himself. He found a causal effect in his study and recommended that parents not allow young children to watch TV. As the WSJ article recounts, many researchers don't agree with his conclusion. Scientists, autism researchers especially, were most critical, but economists also questioned his methods. Although his methods weren't unheard of, some economists said the "instrumental-variables technique" was imperfect and others said it tempted economists to study topics they're "not particularly well-trained" to study. Acronym Required wrote a satirical post on the study last October².

Despite the impression given by the Wall Street Journal, Waldman's self-reliant approach to setting a science research agenda is not unprecedented. Other people whose kids are afflicted by autism have also poured personal resources into autism research. A 2005 Wall Street Journal article, "A Hedge-fund Titan Stirs up Research into Autism", mathematician James Simons, who, motivated by his daughter's autism, founded an organization that plans to spend over 100 million dollars on autism research. The 2005 WSJ article noted the controversy over Simons' funding:

"When the Massachusetts Institute of Technology asked him for money for brain research, he demanded that the project focus on autism and include scientists he liked. He has provided his family's DNA for study, pitched in to help solve research problems and is pushing scientists to probe a genetically based explanation for the disease."

"Many are cheering this influx of cash, hoping Mr. Simons' riches can buy a breakthrough. Others complain that Mr. Simons isn't working with existing autism groups and that his focus on finding a genetic explanation could miss the disease's true cause."

Yesterday, two years later, the WSJ article cautions:

"by suggesting that something within parents' control could be triggering autism, Prof. Waldman has reopened old wounds in the realm of autism research, which is littered with debunked theories linking the disorder to the family environment."

The WSJ quoted senior vice president of Autism Speaks and mother of an autistic child, who said: "Autism is a genetic disorder. The only thing the parents do wrong is they have bad genes." Autism Speaks was founded by two years ago by Bob Wright, Vice Chairman and Executive Officer and GE Chairman of NBC Universal, whose grandson is autistic. However, if Waldman's research was solid, why shouldn't economists study autism? Wouldn't parents appreciate a solution in hand, as opposed to one that entails decades of research and development?

The connection between autism and TV would best be studied in controlled experiments between groups of children, but according to the WSJ, economists don't have the "money or the access to children" to perform this kind of research. The WSJ quoted "Ami Klin, director of the autism program at the Yale Child Study Center, [who] says Prof. Waldman needlessly wounded families by advertising an unpublished paper that lacks support from clinical studies of actual children." In other words, Klin said, Waldman's conclusions conflicted with results of clinical trials that were already done.

The genetic links to autism are currently being studied intensely and the effort is fruitful. Scientists have discovered genes that could account for one or more aspects of Autism Spectral Disorder. The Yale Child Study Center is partially funded by the Simon's Foundation.

The WSJ also quoted Klin sayng: "The moment you start to use economics to study the cause of autism, I think you've crossed a boundary." Yet is the question really about whether economists can study science problems? Economists contribute significantly to fields including psychology, ecology, and international development.

Scientists distort the issue by focusing on parental blame, or whether an economist can contribute to research. Shouldn't we just look at whether a specific paper more approximates rigorous research or Swiss cheese? Waldman's paper was criticized because it drew speculative conclusions and was advertised in a what amounted to a sensationalist press release as opposed to being published in a peer reviewed academic journal. While the researchers and authors may have been swayed by conviction, their resulting study didn't meet the standards of the autism community, psychologists or neurobiologists. As WSJ reported, Joseph Piven, director of Neurodevelopmental Disorders Research Center at the University of North Carolina, said of the confounding variables, "It is just too much of a stretch to tie this to television-watching...[W]hy not tie it to carrying umbrellas?"

Did the paper meet economist's standards, a skeptical reader's standards, or for that matter the own researcher's standards? Scientists ideally start from a neutral position then work to disprove their theories, in order to prove them to themselves, their peers, and the world. Social scientists approach problem solving similarly. If the paper was representative of the field of economics, we might look at economics and its influence with renewed skepticism.

Why not just conclude that this particular exploration, however well intended, wasn't that rigorous, and/or didn't seem to support the author's conclusions and final recommendations. Waldman perhaps used his reputation in another field to build media interest around this hypothesis. He's not the first researcher to flip the scientific process on its ear. Other scientists have announced "results" prior to publication, with various motives. Perhaps his move was strategic, but it remains to be seen whether this economist can circumvent the research process to successfully demand that the science community study his hypothesis.

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¹ The original paper "Does Television Cause Autism?", is posted online at NBER working papers and from the Cornell website. Read it for yourself. What do you think?

²Last October, Acronym Required wrote "Autism, TV, Precipitation: Dismal Science", a satirical 10 step research how-to for repeating the results of Waldman's original paper.

Last year, as avian bird flu H5N1 skipped around the world decimating bird populations and fatally infecting clusters of humans, governments near and far felt increasingly threatened by the possibility of a influenza pandemic. Tension and mistrust increased among countries at a time when full cooperation among them was essential to public health.

Countries promised $1.9 billion to a United Nations avian flu program but had yet to fulfill their pledges. The World Health Organization (WHO) established a repository for virus information from member countries at the Influenza Sequence Database (ISD) at Los Alamos National Laboratory in New Mexico in 2004, but the agency had a spotty history trying to deal effectively with infectious disease and was accused of beholden to the "gang of fifteen" labs given access to the data. The World Organization for Animal Health (OIE) and the United Nations' Food and Agriculture Organization (FAO) also committed to sharing data, but like the WHO, answered to their member states and could do little to compel countries to share resources. Private labs, the CDC, and individual countries like Russia, and China, had all been withholding data and biological samples, sometimes because of poor international relations, concern about intellectual property rights, or concern about credit for their contributions.

In response to the fragmentation in the research community, scientists, politicians and public health officials fulminated, concerned that hording virus and sequence samples would hobble effective responses to outbreaks. In February of 2006, Italian influenza scientist Ilaria Capua called on fellow scientists to promptly deposit their sequence data into gene banks."'Most of us are paid to protect human and animal health,' she said, 'If publishing one more paper becomes more important, we have our priorities messed up.'" ( Science 3 March 2006: Vol. 311. no. 5765, p. 1224)

By August she and about 70 influenza research allies, along with international consultant Peter Bogner, announced the establishment of a new, more open and collaborative system. Capua, Bogner, David Lipman, Nancy Cox and the others submitted a letter to the journal Nature announcing the Global Initiative on Sharing Avian Influenza Data (GISAID), a more collaborative and egalitarian effort to collect and share data in the scientific community.

The project is now set up and expected to begin accepting sequence data. Last week Science wrote that the database will live at the Swiss Institute of Bioinformatics (SIB) in Geneva. According to the article, access to the database will be free to people who register and accept the terms of use. Those who submit data have 6 months to take submit patents and scientific publications before their data becomes publicly available.

Last summer, people welcomed the initial announcement of GISAID and had high hopes for the collaborative approach. Yet some scientists are reserving their opinions until they know the exact terms of the agreement, still undisclosed. Others are openly skeptical of Bogner's motives, and wonder out loud why a media privatization mogel who is better known in skiing and sailing circles would pursue such a venture. For his part, he says he understands the issues scientists have with data rights from working with musicians. According to collaborators he has infused energy and financial backing to the project, and according to Science, might help bring future corporate funding .

Will sharing data help the frayed international relations? Emily Fitri of the Jakarta Post wrote her perception of the country's untenable situation in an article this week. Its unclear how well this represents the government's position in the wake of its agreement with Baxter. In summary she thought Indonesia and poor countries should be incensed for being used as "petri-dishes". While Indonesia struggled with geographical and informational challenges to containing bird flu she said, wealthier countries take cultures to study and make vaccines without offering assurance that whatever resulting remedy will shared with the country for an affordable cost. Indonesia has a right to be angry she says:

"There is a local saying cacing pun marah ketika diinjak, literally translated as even a worm gets upset when stepped upon. This must seriously be pondered upon by those with greater power to review their initial righteous intentions of creating a better world."

Indonesia said earlier this week that it would share data as soon as it is promised affordable vaccines. Perhaps GISAID will help promote the cooperation that is needed but it seems like a daunting challenge. Whatever relations are in place before a pandemic will be further tested in a crisis. Russia is in the midst of trying to control recent H5N1 outbreaks among birds in 8 villages around Moscow. The Moscow Times reported on the situation this week:

"A sign reading "Quarantine" welcomed a steady stream of vehicles passing through the checkpoint. The vehicles slowed down to drive over disinfectant-soaked sawdust intended to clean their tires. The traffic policemen took turns standing out in the icy wind and stopping drivers, ordering some to open the trunks of their cars and show their documents in a temporary cabin nearby."

The country is trying to vaccinate all birds and control the outbreak. One could imagine this scenario anywhere in the world. Some Russians interviewed for the Moscow Times article said that the control methods were arbitrary and that drivers circumvented the blockades by driving through surrounding villages. Others said it was a lot of hoopla for nothing. One veterinary worker who the Moscow Times interviewed commented: "Two chickens die and all this blows up. It's ridiculous."

Scientists agree that international cooperation is necessary to prevent infection and develop vaccines, and in the case of contagious human infection, to contain the disease and distribute medicines. Hopefully GISAID's accomplishment in meeting its six on-line month goal will reinforce the hope it engendered last August and help promote cooperation that citizens of the world are dependent on -- granted, a tall order.

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We also wrote about Avian Flu in these articles: Avian Flu v. Everyday Plagues, "Hopes For Avian Flu Vaccine"; "Modeling Epidemics", and "Avian Flu in China- Increasing Resistance", "Avian Flu Updates", and Avian Flu Pandemic -- Officials Save The Date"

In late December, Northfield Laboratories announced the results of Phase III clinical trials of Polyheme, a hemoglobin based oxygen carrier (HBOC), that ended last summer. The Wall Street Journal reported the negative results in "'Preliminary' Findings Of PolyHeme Death Rate Suggest Approval Setback"(12/20/06). We learned that 712 trauma patients with trauma and significant blood loss enrolled in the study. 46 patients treated with Polyheme died, versus 35 control patients who died from standard treatment. 13.2% of the Polyheme patients died versus 9.6% of the patients of standard treatment. The standard for care is to give saline to the patient during transport only until donor blood is available at the hospital.

The response to the negative news was immediate. Quite a few people suddenly distanced themselves from Northfield Labs. West Virginia University hospitals, who enrolled in the Northfield study and is listed on the clinicaltrials.gov site, issued a press release saying that even though ambulances were carrying Polyheme,"The drug, PolyHeme, was never used on any patients in West Virginia, according to Dr. Lawrence Roberts, director of WVU's John Michael Moore Trauma Center". (italics ours) The doctor defended the choice to participate in the study while dismissing the product: ''The data looks like the patients that got Polyheme had worse outcomes. That implies this stuff is no good and you can't use it."

Investors, brokers and some financial reporters, who had once rabidly attacked reporters and sites that brought up patient safety concerns, started echoing "I told you so" headlines back and forth to each other. The stock sunk from $17 to $4. Northfield Labs' CEO, Steven Gould presented to an investor teleconference last month and the WSJ noted his eternal optimism, saying he was

"'encouraged' and 'optimistic' that the company's blood substitute soon will become the first approved by the U.S. Food and Drug Administration to revive hemorrhaging patients." [WSJBurton, Thomas "Blood Substitutes Face Long Odds History, Scientific Concern Hamstring Sector" February 13, 2007].

None of this bodes well for patients. The negative results potentially impacted past patients who probably did not receive optimal care for their situation. Doctors, emergency workers and the military as well as future patients would benefit from a new product that delivers oxygen, survives storage and transport, and doesn't require blood matching.

In this clinical trial Polyheme's success is judged according to a simple but slightly unusual criteria. The goal was to show that the product "superior" to, "not inferior" to, or "inferior" to the standard treatment. The future of the product depends on how many people survived the Polyheme group as opposed to the control group. Northfield is now striving to get the FDA to label the Polyheme "not inferior".

The CEO called the shaky results "preliminary". He said that some of the data had errors because of "protocol violators", that is patients who were enrolled who for one reason or another should have been excluded. When these patients' data was removed from the analysis he said, then the results of the study looked better and would fair more favorably in an FDA review. True enough, the protocol violators died more frequently. Of the 126-patient "protocol violator" group that Northfield seeks to exclude, according to an analysis on Thestreet.com, by Adam Feuerstein, there was a large difference in death rate of patients getting Polyheme (17/70 or 23%), versus the controls (7/56 or 12.5%). However, since the trial was originally structured for patients with significant blood loss and trauma. Feurestein points out:

Northfield designed an ambulance trauma trial for Polyheme because it wanted to see how the blood substitute performed in the real world, where all kinds of patients are bleeding to death from all sorts of accidents. After the fact, when the results aren't to its liking, the company can't go back and argue that Polyheme works, but only when conditions are perfect.

Actually, Northfield also chose this particular patient cohort because previous trials of Polyheme (similar to other HBOCs) failed when the products were applied in routine surgery and non-trauma situations. These trials ended badly for patients, so the companies turned their attention to critical care scenarios where donor blood wasn't an option. Since we're at war (perpetually, now), there's a huge potential military market for these products which coincides with the uptick in FDA interest. But will the FDA will allow Northfield to meet the trial's patient quota with "protocol violators", then in retrospect exclude those patients? Some financial analysts like Feuerstein are doubtful. The FDA's actions will also be followed with interest by those in drug development, and those concerned with patient safety and clinical trials.

Northgate's Phase III trial attracted initial controversy because it necessarily waived patient consent in order to study severely injured trauma patients. The trial involved giving a blood substitute in lieu of saline during transport, and for 12 hours after the injury once donor blood was available. Doctors and people involved with patient ethics questioned whether communities were being educated adequately about the trials. People also probed why participating doctors and medical centers seemed unknowing about previous failures with the blood substitutes. Fortunately for Northfield, all of this controversy only heated up three years into the trial. Northfield stopped enrolling patients just a few weeks after a story about patient consent aired on 20/20.

However the next trial for an HBOC will be conducted differently. The FDA recently denied the company Biopure, Northfield's neck and neck competitor for over 20 years, latitude to conduct a Phase III trial with its competing product Hemopure. Instead it will conduct a Phase II trial with fewer patients and the use of Hemopure will only be allowed until donor blood is available.

Despite years of work and promises, some people doubt the HBOC's viability, due to decades of failures in clinical trials. The WSJ quoted a former medical director of Biopure Corp. in Cambridge, Massachusetts, a company that makes one of Polyheme's competing products Hemopure, who said that the '"totality of the data' on this class of products is that 'so much harm has been shown, without benefit, that the field should be stopped.'"

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Acronym Required previously wrote about Polyheme and Hemopure in Polyheme© and The Newest Plastic Bracelet. We looked at the history of the products, focusing on on Northfield and Biopure, in Polyheme& Hemopure: Life Savers? Products to Die For?

The Broad Institute announced the release of a genomic map based on sequence data of Type II diabetes afflicted individuals and controls yesterday. The group will make the information accessible to scientists worldwide via the internet. The Diabetes Genetics Initiative is a joint effort of the Broad Institute of MIT and Harvard, Novartis (NVS) and the Lund University in Sweden. In 2004 the Broad Institute and Lund University formed the collaboration with Novartis to utilize the unique resources and contributions of each organization in studying diabetes and metabolic diseases.

Type II diabetes, caused by a growing trend of unhealthy diet and lackadaisical exercise habits, is a public health health problem that affects about 180,000 million children and adults worldwide. In-patient health costs for diabetes patients were $3.8 billion in the U.S. in 2001. The goal of making the data public is to encourage researchers from around the world to contribute to the significant effort of developing knowledge and treatment of the metabolic diseases.

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Acronym Required previously wrote about diabetes in Diabetes. Heavy Living and Lite Reading, and Childhood Obesity, The American Way. We wrote about science data in the public domain in Accessible Research For All, By All- The Government, State, Universities and NGO's, and Dutch Research- Free!

Those Who Hold the Gold Make the Rules¹

In 2002-2003 The Los Angeles Times reported in a series of articles that senior NIH scientists were also industry consultants, paid in fees, stock, and options for their moonlighting. According to the series, the compensation was often permissible under lax agency regulations, however more often the scientists didn't disclose the income as required by the NIH. Congress followed the paper's reports with their own investigations. Then, an internal NIH review released in 2005 found that in 44 of 81 cases, NIH researchers who worked in industry did not follow the agencies' internal ethics rules.

The investigations triggered a debate over what industry activities should be allowed by public agency scientists, a debate that continues to roil today. Some of the NIH turmoil over ethics evolved naturally as a result of a changing research environment and changes in the nature of relationships between public and private research. The NIH tried to accommodate these change and ease concerns about the agency's ability to hire the most desirable candidates in 1995 under NIH head Harold Varmus. The organization loosened the rules, allowing employees to accept industry stock, options and consulting fees, but limiting the income to $25,000 and outside work to less than 500 hours per year. A mere seven years later the investigations revealed that certain scientists had pried open this chink of opportunity and defined their own, much more lucrative ethics boundaries, thus compromising an agency dedicated to deciding science objectives in the public interest.

In 2005, in the wake of the unfavorable media coverage and congressional investigations, the NIH proposed new rules to limit NIH scientists from any consulting engagements or stock ownership². However when the NIH announced the rules, some NIH scientists mounted a strong defense, hiring lawyers and lobbyists to fight the proposal and forming an inter-agency committee called the Assembly of Scientists to promote their own vision of ethical research. In what looked like a compromise to the lobbying efforts both inside and outside the agency, the NIH backed away from the most "draconian" limitations, but still barred certain consulting engagements and stock ownership.

The rules did not quell the concern over conflicts of interest. Today, some people say that the NIH rules are flagrantly ignored and that the agency fails to impose penalties on those who flout the limits. Congress held a panel discussion on the issue in September 2006, their 6th such meeting since the scientists activities were uncovered. Representative Joe Barton, Chairman of the House Energy and Commerce Committee noted that to date, none of "over 100 individuals identified by the NIH" for violating NIH policies had been terminated.

By the end of last year however, a couple of researchers had at least been reprimanded. One of those researchers was Pearson "Trey" Sunderland III, chief of the geriatric psychiatry branch of the National Institute of Mental Health and an Alzheimer's disease researcher, who was identified in the initial investigation. Sunderland had transferred spinal tissues stored at the NIH to Pfizer under a private contract he made with the company. Investigators never determined whether his consulting fees included payments for the "thousands" of NIH samples he gave to the company. But last month, he pled guilty to misdemeanor charges in federal court for failing to disclose payments of $285,000 that he had received for his consulting with Pfizer, although originally investigators alleged that he had accepted over $600,000 in payments. Sunderland was sentenced on December 22nd 2006 to two years of probation, 400 hours of community service and a restitution payment of $300,000. He could have been sentenced to a year in jail. He was never charged for transferring tissue samples. Some think that Mr. Sunderland was let off easily. Sunderland worked at the NIH throughout the investigation. He continued to benefit from agency perks and last year was offered a $16,000 retention bonus. However in his courtroom statement at the sentencing he said that he was "humbled".

Another publicized case was that of a pediatric oncology doctor, Dr. Thomas J. Walsh. The NIH found that Dr. Walsh had violated agency rules in at least 38 instances and had accepted over $100,000 in consulting fees from pharmaceutical companies. The doctor also promoted certain antifungal drugs for patients despite debatable evidence of efficacy, and industry affiliations that some scientists felt biased his recommendations . The LA Times delineated Dr. Walshes alleged offenses in July of last year in a damning article. The excorciation prompted a hearty rebuttal from many of Dr. Walsh's peers.

Both doctors are highly respected, have published widely, and have been with the NIH since the 1980s. They are also part of U.S. Public Health Service Commissioned Corps. The NIH has said that they have no authority over how discipline is meted out, however some members of Congress are incensed over the NIH's inaction. The September panel attempting to untangle the ethics mess was disheartened by the NIH's progress cleaning up its organization. Said Barton , "This is really an ethical Potemkin village, where a hollow system appears to provide the illusion of integrity, but transgressors never leave."

Four Out of Five Doctors Recommend Taking....

While the resolution of past conflicts of interest is murky, perhaps a change in political leadership in Washington will nudge the NIH in a more disciplined and transparent direction. A few days ago, the NIH canceled a meeting for February 23, scheduled for scientists to discuss policy for pregnant women for herpes.

The cancellation, that commentators uniformly characterized as "abrupt", followed a front page Wall Street Journal article on a nationwide education campaign that GlaxoSmithKline organized on pregnancy and herpes. GlaxoSmithKline markets Valacyclovir hydochloride, a patented oral anti-viral drug that is converted to internally converted to acyclovir. Acyclovir is an older antiviral which is also effective against the virus that came off patent in 1997. The company paid doctors to speak at conferences in hospitals across the US and advocate that all pregnant women be for herpes. Dr. Zane Brown, one member of the five person team chosen for the NIH herpes panel, is a University of Washington doctor who the company paid $1,000 to $2,500 per lecture, two or three times per week.

If testing were required it would naturally lead to more women being treated and more drug sales. But the studies have shown that the practice would be costly, with insufficient patient benefits. Furthermore the side effects and potential hazards for babies is unknown. The FDA hasn't approved the drug for use in neonatal herpes, however that doesn't prevent doctors from prescribing it, or giving lectures about the possible benefits.

According to Citizens for Science in the Public Interest, Four of the five panel members, including Dr. Zane, had financial ties to companies or organizations with interest in herpes drugs. A letter from 44 physicians and 16 health groups, including Lancet editor Richard Horton and two former New England Journal of Medicine editors, Marcia Angell and Jerome P. Kassirer, "called on director Elias A. Zerhouni to adopt an agency-wide rule prohibiting scientists with financial conflicts of interest from sitting on guideline-writing panels".So the NIH canceled the meeting following media coverage and public protest over what looked like an egregious effort by biased scientists to promote industry friendly policy.

It's not clear what lies ahead for herpes testing, but the increasingly pro-business environment in Washington perhaps coincides with an increase in pharma opportunities for NIH employees. As more and more doctors and researchers take advantage of lucrative opportunities to supplement their income working for pharmaceutical companies, government agencies have greater difficulty finding recognized experts who come without pharmaceutical associations -- or who even look like their unbiased enough to serve in policy decision making roles.

Medical research and treatment is certainly not the only area where colliding interests chafe along a hazy line between public interests and business interests, however in public health issues, the stakes are particularly high for both sides. But despite the consequences of appearing to let pharma have undue influence on public policy, it's unclear that the current paradigm will be changed.

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¹This article was edited and re-published January 30, 2006

²Acronym Required commented on the proposed rules here.

South Africa's Wealth/Health Paradox

South Africa, where approximately 1 in 9 people are afflicted with AIDS, has a paradoxical economic development profile. It is considered an upper middle income country based on its healthy Gross Domestic Product (GDP). The World Bank ranked South Africa's GDP 27th of 177 countries in 2005, putting it in about the 85th percentile for GDP. The International Marketing Council of South Africa, with the slogan "South Africa, Alive With Possibility", describes the country as the "economic powerhouse of Africa".

Yet about 800 people a day die from AIDS in this country. Life expectancy in South Africa has decreased by four years and deaths from AIDS continue to decimate populations of young women under age 35 and men in their 30's and 40's, people who are in their prime and who -- from an economic perspective -- are in the most productive years of their life.

Now more bad news. An alarming study from Statistics South Africa's shows yet another dramatic increase in deaths from AIDS in South Africa. The report analyzed death rates from unnatural and natural causes and found that the death rate from communicable diseases of South African women aged 30-45 had increased by about three times, from 500 per 100,000 to 1500 per 100,000 in the time period between 1997 and 2004. Male deaths from communicable diseases had also increased and had even doubled in some areas. Some of this bad news was predicted. Since there is a lag between infection and full blown AIDS, it was assumed that the death rates would not decrease until 2008. However the figures are still stunning - as they were last year, and the year before...

The expectations of economists and politicians was that post-apartheid Africa would rebound and that the health of South Africans would improve. Indeed according to economic measures Africa is doing better and foreign investment has skyrocketed. But even compared to Russia, where life expectancy decreased as a result of political upheaval and economic downturn, the current patterns in South Africa indicate a dire state of affairs. For scientists and doctors, the increases in deaths are distressing since there are few signs that action is being taken to stem the epidemic.

South Africa AIDS Policies

Public health officials, scientists and doctors are taking South Africa to task for its AIDS policy, and rightly so. Historically, the government has denied that the HIV virus caused AIDS, and it has been slow to implement treatment programs for AIDS afflicted patients. Despite pleading from world leaders, South Africa's AIDS policy remains one of obfuscation and denial. Health minister Dr Tshabalala-Msimang often insists that nutrition will beat AIDS, and regularly pushes garlic, beets and lemon, and African potatoes as effective cures.

Patient treatment via antiretrovirals now costs less that $130 dollars a year. South Africa's health policies are out of step with the modernity and prosperity that it claims.

The country was condemned at the AIDS conference in Montreal this year for displaying a basket of this produce in its booth, initially without antiretroviral drugs. Earlier this year it banned two Non-governmental organizations (NGO's) from a UN AIDS conference because they were particularly critical of its policies.

In the most recent international public plea for policy change, a group of 81 doctors wrote a letter to President Mbeki asking the president to replace the ineffectual health minister. In response to the recent letter, the health minister complained that the international community was undermining the country's efforts. She has long defended her nutrition advice as "the truth", and allegedly doesn't mind her moniker- Dr. Beetroot".

In response to the outcry, the president has assigned a new committee to oversee the AIDS program, according to an associated press article (South Africa Scales Back Health Minister's AIDS Role). But the health minister denies that she has been demoted, and in typical sidestepping form, a government spokesperson, Themba Maseko, said: we need to shift the focus from saying the problem is the minister of health".

Effective AIDS Policies

AIDS programs succeed in countries because many deliberate actions. It is imperative that there is strong leadership to combat AIDS at the very, very top levels of a government. If the problem is not with the minister of health then it is with the president.

People have said that effective AIDS policies will be pushed to the fore by governments who realize that deaths impede economic progress. It's hard to imagine that South Africa, where 1 in 9 people on average are affected by the deadly disease and only a small fraction receive drugs has not come to terms with this economic reality. How the government can still claim that beetroot is as effective as antiretrovirals is as Stephen Lewis said: "obtuse, dilatory and negligent."

Once it seemed intuitive that a higher GDP could be linked to greater general welfare of the country's citizens. Economists now recognize that GDP doesn't always correlate with overall broader measures of prosperity. South Africa is a telling example of this phenomenon.

The United Nations' Human Development Index (HDI) rates quality of life factors such as education, the status of women, morbidity, and mortality. South Africa's comes in at 121sh out of 178 countries. This puts it in about the 33rd percentile of all countries, in the company of many countries who have far fewer resources. Therefore in terms of HDI, as opposed to GDP, South Africa's is in the same band of countries that its pro-business groups lord over with their "economic powerhouse" status.

In this "post-apartheid" era, we would not expect this chasm between the HDI (where it lies in the 33rd percentile) and GDP (where it is the 85th percentile). We would not expect the travesty of preventable AIDS deaths. We only wish that such a sorry state of affairs would convince those at the top levels of the government that only an active AIDS program will assure that South Africa is "alive with possibility".

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Acronym Required previously wrote about AIDS in Not in Paradise Anymore - AIDS in Africa - Reason for Optimism?" - in response to a David Brooks column and optimistic prognosis for the AIDS epidemic in South Africa. We also wrote about AIDS in Zimbawe, in Burma, as well as in other articles.

The Food and Drug Administration had convened on the subject of silicone breast implant safety:

"But as the panel members spoke up one by one, it became clear that they were far from certain about the risks and benefits of the devices. The first scientist to speak quoted the prophet Isaiah and writers Ralph Waldo Emerson and Samuel Johnson before calling for more testing. The second said it was impossible for women to make an informed decision about whether to use implants because there was not enough information. The third complained that the issue should have been resolved years ago.

Unable to agree on how to interpret the jumble of opinion, fragmentary data and scientific speculation, the panel members finally threw up their hands in frustration."

So reported Malcom Gladwell for the Washington Post in March, 1992, perhaps before he reached a tipping point, blinked, and got off that beat. ( "Breast Implants; After a Decade of Controversy, Key Questions are Unanswered and the Future of the Device is Unresolved"). In the intervening fifteen years, scientists have continued to debate the safety of the implants. But doctors and patients say they prefer silicone over the currently available saline implants because "silicone implants feel more natural and look better". Is the time once again ripe for silicone implants?

Scary memories of silicone implants from Dow Corning, which the Economist said "earn[ed] a lifetime achievement award for the courting of controversy", in "America's Most-hated Companies: The Very Bottom Line" (Dec 20th 2005), have faded. The company once besieged and routed by the legal repercussions of leaking breast implants in the 1990's, has reorganized, emerged from bankruptcy, paid out at least 3.2 billion dollars to plaintiffs, and is once again courted as a Wall Street "darling". Although the scientific research on silicone implant safety is no less controversial then it was 15 years ago, the FDA is once again edging towards approving silicone implants.

Unfortunately, if silicone implants are approved, women will still be challenged in their quest to make informed decisions about implants. Who should they trust? Their surgeons? Scientific research in prominent journals? The FDA? If women turn to the internet for safety data, they will quickly find reassuring answers from sites like LookingYourBest.com, or CosmeticSurgeryTimes.com. The latter site features interviews with well-tanned, well-fed doctors who report that a women's safety is their primary concern. A more time consuming search might turn up more alarming news, such as the controversial paper in the journal Analytical Chemistry, widely covered in the national press.

The journal published a paper on silicone breast implants last May which provided evidence of platinum leakage from the implants. The authors proposed that the blood, urine and hair of 18 of 23 women who had implants contained higher levels of platinum then the controls. (Lykissa, ED and Maharaj, 2006. Total Platinum Concentration and Platinum Oxidation States in Body Fluids, Tissue, and Explants from Women Exposed to Silicone and Saline Breast Implants by IC-ICPMS. Anal. Chem. 78:2925-2933). Lykissa and Maharaj asserted that the platinum was found in oxidized reactive states, states that are associated with toxic physiological affects.

After that widely reported publication, Analytical Chemistry then published two articles that criticized the study. When the journal's editors quasi-retracted the paper, did that soothe readers, potential patients? It actually should have alarmed them. One was written by a chemist at Dow chemical, Thomas Lane. Lane has long been a supporter of silicone implants. He had testified about implants to the FDA, the National Institute of Cancer, and "other similar venues", but he had not been an expert witness, said the journal's disclaimer. Also, "Dow Corning Corporation has not manufactured silicone breast implants since 1992." Lane might be an unbiased scientist, yet he has long claimed that silicone implants are "harmless". Dow Corning might not currently manufacture implants, but that is irrelevant since as a corporation it is compelled to mount an active defense that 'the implants are and always were safe'. Michael Brooks, the other expert in the 'field' who wrote in to provide criticism of the paper was a 'neutral commenter' - according to Analytical Chemistry. However his background is not 'neutral'.

" ...he provided information on the chemical nature of the platinum in silicone breast implants at the FDA panel hearing on breast implants April 2005 on behalf of Inamed Corporation. He was also a member of Health Canada regulatory advisory panels considering applications by Mentor Corporation and Inamed Corporation for new breast implant models in March and September 2005."(Analytical Chem