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The World of Silver Spoons and Golden Specks and All that Disinfects

Did you know that a Hong Kong company makes "Antibacterial Table Ware" that can "prevent people from the following diseases: duodenitis caused by spirillums, virosis hepatitis, dysentery caused by salmonella and food poisoning caused by golden staphylococcus"? Such wishful thinking is common in the product claims featured at the Project For Emerging Nanotechnologies' inventory of available nanotechnologies. (PEN is a collaboration of the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts.) "Antibacterial Table Ware's" antimicrobial power stems from the "nano silver coating" but the technology has some fine print limitations. During holiday dinner when you're sitting at the table laden with such utensils you would need to urge your mom to "please dawdle", as she ladles the gravy and potatoes onto your plate, so as to give the "Antimicrobial Table Ware" enough time to "kill the attached bacteria and microbial [sic] in ten minutes". (emphasis mine)

The company also makes hairdressing tools that "protect people" from diseases they would (never but for horrendous circumstances) pick up at the beauty parlor, "hairdressing-related infections such as trachoma, conjunctivitis, virosis hepatitis, dermatitis and AIDS." Nanotechnology claims by companies in the US tend to be slightly more responsible, but the precociously labeled products available as imports litter the internet, while regulation and oversight lags behind prolific headfirst investment in the new technologies.

In real life, nanotechnology is not as fantastical as some marketing boasts but is very impressive. Products incorporate elements that are 1-100 nanometers in length -- a nano being a billionth of a meter, and scientists can change the structure of an element in the lab to give it unique properties. So although Carbon nanotubules can be found in nature, in soot for example, one of the most common carbon nanotubules is produced when scientists vaporize carbon between two carbon electrodes. When you think of carbon you'd probably consider the soft form of it -- graphite, or the very hard form -- diamond; however, from carbon nanotubules, scientists now construct materials that are both very light and incredibly strong -- perhaps a hundred times stronger than steel. Carbon nanontubules are used to make electronic brushes used in engines and for future applications in optics, electronics and material science, .

Silver is a proven anti-microbial -- the FDA recently approved silver coated breathing tubes used in ventilators, that may help reduce the risk of pneumonia in hospital settings. Researchers use nanotechnology for drug development and are advancing sophisticated technology to accomplish feats such as delivering drugs to a specific location in the body or building scaffolding for the regeneration of bone, nerves and other body parts. Nanotechnology offers promising advances for almost every field, medicine is just one example. However before much of this promising research yields viable products, nanotechnology will also be relentlessly hyped for selling more mundane items with dubious benefits such as "antimicrobial" socks and refrigerators.

Gilded Age

Nanotechnology products tout anti-bacterial, anti-reflective or stain resistance properties, many of which are not yet proven. Just as flatware marketing preposterously proposes to protect you from infections like Hepatitis A, hundreds of other products collectively promise to erect a magical nanotechnology barrier, a personal missile shield between you and the millions of germs that threaten you.

When you're done sipping your silver nanoparticle preserved soup from your special silver spoon you might want to brush your teeth with "cutting edge toothpaste which innovative nanotechnology is applied", made from "pure nano-sized gold that is highly effective in disinfecting the bacteria in your mouth". And if that company went out of business (likely), you can find some Korean made silver nanotechnology toothpaste that will serve the purpose. The PEN inventory lists hundreds of products with these sorts of thrilling if unsettling properties.

More concerning than blatant labeling for the benefits of nanotechnology however, is the empty labeling from companies which choose not to advertise their nanotechnology because of federal regulations. For instance, the "FresherLonger Miracle Food Storage" containers used to be marketed as "infused with silver nanoparticles that will keep soups, sauces, meats and vegetables "fresher three or even four times longer". Now the same product doesn't mention the silver nanotechnology, only the "airtight silicone-gasket locking system" which helps "retard spoilage". The change in product literature was made to avoid the EPA's regulation of products claiming to be pesticides -- antimicrobials are considered by the EPA to be pesticides.

$50 billion dollars worth of goods incorporating nanotechnology were sold last year, and nanotechnology is entering the consumer marketplace at the rate of 3-4 products a week according to the Project on Emerging Technologies (PEN). There are over 600 consumer products currently on the market, everything from utensils to washing machines to teddy bears, camera lenses, make-up, hearing aids, suntan lotion,clothing, and waterless car washes.

NanoNannies?

Beyond the veracity of labeling, is consuming particles that can't even be seen under a microscope floating around in your body safe? One skin care product called "DNA Skin Optimizer" notes that "Nano technology was chosen because it makes it possible to place the sensitive ingredients in the form of tiny crystals directly into the cell nucleus" -- which, were it true, is certainly not a comforting prospect. Scientists don't know if how nanoparticles accumulate in the body and what interactions and effects they might have, since there are very few studies on the safety of these products.

Last week, however, Nature Nanotechnology published a pilot study suggesting that the safety of carbon nanotubes warrants further investigation. (Poland et al. "Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study"; doi:10.1038/nnano.2008.111) The researchers subjected the meseothelial lining of the body cavity of mice to carbon nanotubules of varying lengths. Like asbestos, the long fiber carbon nanotubules created an inflammatory response in the mesothelium and scarring, while shorter fibers did not, which indicates (at least) that people who work with carbon nanotubules in manufacturing might be at risk for the same types of problems seen with asbestos exposure.

The environmental risks of this new technology explosion are also unknown but disconcerting. Last month researchers from Arizona State University did some experiments on silver ion containing socks that were marketed for their ability to cut down on foot odor. The researchers washed several brands of socks, and the silver washed out of the socks at various rates. The study motivated concern that the inevitable increase and indiscriminate use of nanotechnology would cast silver into streams and run-off causing environmental damage and endangering the health of species that live in and depend on streams and rivers. Products like Samsung's EPA approved washing machine releases silver ions into every load of wash, a gimmick Samsung calls: "Silver Wash that sterilizes your clothes".

Nanotechnology has broad funding support from Congress and research in this area is flourishing. However scientists and some consumer groups are worried that there are too many unknowns about nanotechnology's safety and that more research should be aimed at investigating the potential hazards. Scientists from industry, environmental groups and academia acknowledge that not only are we producing products with unknown risks without regulation, but that the lack of regulation may cause consumers to become skittish about nanotechnology.

Earlier this month a group of consumer groups recently petitioned the EPA to take a stronger stance on nanotechnology, specifically on products that market silver as a pesticide (antimicrobial). Congress is currently considering legislation on nanotechnology but legislators pared funding for studies on the health and environmental risks of the technology.

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

A recent report by Marks & Clerk, "Biotechnology 2007" found that from 2002-2006, academia led corporations in the number of patents filed. Japan, the University of California, and the U.S. government were the top assignees.

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?

We're quite accustomed to lying. Some may feign shock - as they did when a slump-faced, shifty-eyed, quivery-lipped Frey confessed to Oprah, the arbiter of truth, that his book was a pack of lies. It seemed like more genuine disbelief when the stem-cell myth slowly unraveled and the legacy of Hwang did a landslide shift from "supreme scientist" to he who would have had a street named after him, could have had a museum named after him, or would have been forever revered by his countrymen. Really, all this shock can't be more than an act. Maybe all jurors should be chosen from Oprah audiences; but lets be honest about the pretend "surprise" of it all. The routine deceptions are no more surprising than Groundhog Day (the movie). With all the Enrons and WorldComs and Katrinas and Iraqs, isn't it just the same day all over again?

Cut to Bush's State of the Union address. People recoiled at his proclamation about banning any sort of cloning research, "human cloning in all its forms; creating or implanting embryos for experiments; creating human-animal hybrids; and buying, selling or patenting human embryos". It has been widely pointed out that animal-human chimeras are a not so very scary part of health research. What Bush proposes also pertains to infertility treatments used by thousands of couples today to have families. People speculate about what he really means.

On energy, Bush said we were "addicted to oil" and that we would reduce our dependence on mid-east oil by 75% -- "through technology". There were arguments about this out of the gate -- the reductions weren't realistic or feasible and only 20% percent of our oil comes from the mid-east anyway. Indeed, say Bush's aides according to the Philadelphia Inquirer today, the President did not mean any of this literally. "This was purely an example", Energy Secretary Samuel Bodman said.

So is the cloning rhetoric also just an "example"? If the administration knows what they say, perhaps they don't really mean it? Outside of the most obvious (and at the moment unfeasible) human cloning and therapeutic cloning "examples" that Bush wants banned, there are some technologies that are essential for the scientifically advanced, humane, non-isolationist nation he promotes. Unfortunately, since the administration has already gone to great lengths to curtail stem cell-like researh, indications are that they will be invigorated by their new court appointees and will continue down this path.

While the intention is certainly there, it seems ideologically distorted. The stated impetus of "a hopeful society...that recognizes the matchless value of every life", rings false. As a small example, why say "no cloning", then merrily "clone" these troops for speech props in this Photoshop picture. Isn't that disrespectful?

The good thing about Groundhog Day (the date) is that one way or another you know that the season or term or trend or silliness will eventually end.

The Seattle Times recently published an investigative report; "Drug Researchers Leak Secrets to Wall Street", alleging that doctors sell confidential drug information to investment firms who acquire the data for their "elite" clients. Apparently, the informational consultations are set up by "matchmakers", companies that pair Wall Street firms, especially hedge funds, with doctors involved in clinical trials. The article echoes some of the concerns of a recent article in the June issue of the Journal of the American Medical Association (JAMA), which warned that potential conflict of interest and ethical issues were bound to occur, either intentionally or unwittingly, when doctors engaged in such consulting.

The Seattle Times bested the JAMA article by adding journalistic flourish, and names, numbers, and drama to JAMA's account. Additionally, the authors claim to have found 26 cases of illicit liaisons between pharmas and investment banks. According to the account, "the largest matchmaker, the Gerson Lehrman Group "claimed to have 60,000 doctors available to speak to Wall Street, double the number from three years earlier." They conclude that the doctors, "violate confidentiality agreements they sign before drug companies allow the drug testing to begin".

Naturally, the Seattle Times article set off a flurry of concern and activity in the medical, journalism and political communities. This week UCLA announced an investigation of the doctor, Robert A. Figlin, MD, who was featured in the article. Representative Jay Inslee (D-WA) has asked the House Energy and Commerce Committee to hold hearings about the Seattle Times evidence. Also this week Chairman of the Senate Finance Committee, Senator Charles Grassley (R-Iowa), asked Attorney General Aberto R. Gonzales and Christopher Cox, chairman of the Securities and Exchange Commission (SEC) to investigate the claims, and as well the New York Times published its own investigative article.

The potential ethical issues pointed out by the article are legion. Premature drug information disclosure can potentially skew clinical trials and bias stock trading on Wall Street, not to mention enable short term speculation based on insider information. But while the potential for abuse obviously exists, not everyone agrees with the authors' suppositions. Mark Gerson of the Gerson Lehrman Group wrote a lengthy objection letter to the Seattle Times editor that was also published on his company's website. The response, though predictable, made a valid point:

"I was surprised that [one of the authors] ignored facts and arguments that were inconvenient to his story...most notably the value - to physicians, investors, even patients - of adding independent and objective perspectives to the investment decision-making process."

The Gerson letter explains in detail the benefits of expert science evaluations for potential drugs and fairly points out that doctors offer valuable insight into disease and treatments that is beneficial to the process because it enables people to evaluate a drug based on criteria other then how well it's marketed. Of course the letter is defensive, but consistent with Gerson's defense, it appears that the reporters repeatedly left information that would have provided readers with a more balanced view of the issues.

The journalists obtained a tape of a phone consultation between a doctor and some investors. The purpose of the consult was for the doctor to answer questions about "two potential new drugs for kidney cancer: Sutent, a Pfizer drug for which he was a principal researcher, and Sorafenib, a drug that he monitored the safety of for Onyx Pharmaceuticals.". The authors highlight selections from the exchange in their article and try to use this as evidence to bolster their allegations. However a more thorough look at what they present throws doubt on their story.

Although Seattle Times points out the doctor's associations with the two companies, they omit to mention his other significant credentials. He's an award winning UCLA professor, clinician and prolific researcher, who has authored over 150 research papers and 30 book chapters. His website mentions that he's listed in many *Who's Whos* - in "the West", "Science and Engineering", "Medicine and Healthcare", "America" and "the World" (who's lists, we don't know). He also co-authored a textbook; "Renal and Adrenal Tumors: Biology and Management". It seems that his credentials are relevant to the story, since he was consulting about angiogenesis inhibiting drugs that could protentially treat renal tumors, however they were ommitted from the article.

The authors report on an exchange from July 18 conference call related to the potential efficacy of the drugs and suggest illicit behavior:

"Figlin also was asked to "handicap" the results of one of the drug trials. In particular, one hedge-fund manager asked whether Onyx would be able to show that its kidney-cancer drug, Sorafenib, had a "survival benefit" — that patients taking Sorafenib were living longer. A survival benefit is the gold standard for a cancer drug's success."

The authors quote a part of the exchange:

QUESTION: "And your bet is ...that there will be a survival benefit?"

FIGLIN: "That's a good question. My bet - am I betting with your money or mine? - my bet is that there will be a survival benefit."

So according to the authors, the fact that Figlin "bet" that there would be a "survival benefit" suggests foul play. Smoking gun at hand, the The Seattle Times called Figlin and "quizzed" him about the information the transcript. Here's what they printed:

"In an interview with The Times after the call, Figlin...said he sees nothing wrong with talking to Wall Street investors as long as doctors discuss only publicly available information. "I don't think it's appropriate for the physician to ever discuss things that are unpublished, or anecdotal", including any prediction of a drug's survival benefit, he said."

The Seattle Times article alleges that the information was confidential and insinuates that Figlin was duplicitous in his answers.

"When asked about his prediction of a survival benefit during the July 18 call, Figlin said he was just expressing his hope for its success. "I take care of hundreds of kidney-cancer patients, and I'd like to finally have an agent that demonstrates a survival advantage. If they then take that information and decide, "Oh, Figlin thinks the trial is positive,' then they are extracting information and making conclusions on their own dime.""

Further background research showes that a lot of relevant information about both drugs is and always has been public. Whether the authors were aware of the information and ignored it, misunderstood the information, were not aware of it, or simply differ in their opinion is unknown. But data from clinical trials of both drugs was presented at the American Society for Clinical Oncology's (ASCO) annual meeting in San Francisco in May, 2005, several months before the conference call. Presentations and abstracts from both Pfizer and Onyx/Bayer are also available on the ASCO website. Finally, the ASCO meeting's "2005 Best of ASCO San Francisco" talk, was actually presented by Dr. Figlin, (20 minute talk linked above). He highlighted the two drug trials within the context of the unique biology of kidney angiogenesis, other available treatments, toxicity data, and relevant patient populations. He clearly outlined the results of the ongoing trials and the apparent pros and cons for both Sutent and Sorafenib. For the Onyx/Bayer Phase III Sorafenib trial results, he explicitly notes that the trial was "built as a survival trial". A slide states the primary objective, which was: "To compare the overall survival of patient treated with Sorafenib versus placebo".

The "target conclusions" were:

"Sorafenib significantly prolongs PFS [Progression-Free Survival Benefit] (24 weeks) compared with placeblo (12 weeks) in advanced RCC. PFS benefit is evident in all subsets of patients evaluated."

All of this information was summarized in several science publications as well as in general investor and biotechnology news. While these results don't predict "survival benefit", they should easily clue the astute investor in to the relative potential of both the drugs.

The authors emphasize that the doctor's associations with other doctors are questioned and portrayed as unscrupulous:

"[Figlin] said he had talked about "generally available" information but acknowledged he may have discussed information he heard from other doctors on the studies".

Figlin no doubt talked with the doctors because he presented their clinical trials' results at the meeting. The doctors were presumably present at the meeting, they are all in the same subspecialty, and one would assume that Figlin probably "discussed information" with them.

The Seattle Times also implied that Figlin's revelation about the schedule of Pfizer's FDA application to the investors at the meeting was secret information that benefited those in the conference call. They claim that when Onyx/Bayer filed for FDA approval, most investors, except those in the conference call, were in the dark about Pfizer's plans for FDA approval:

"The value of Figlin's information became obvious two days later (July 21), when Pfizer let slip that it had not yet filed with the FDA. Analysts who had not been on the call with Figlin put out research reports speculating that Pfizer was losing its cancer-drug race with Onyx. That day Onyx (Onxx) shares rose $2.94 — or 12 percent — on heavy volume."

However again, the authors overemphasize a view of the exchange that supports their story. Is it a biased view? As "The Street" wrote, in in an article about Pfizer and Onyx/Bayer after their ASCO presentations in May, "the companies plan to file for FDA approval of the treatment." Whether this was a rumor or not, in May, based on the ASCO data, some writer and editor capably predicted that both companies would file FDA applications.

Although the science (or the doctor's opinion of it) is important, it isn't the only thing that determines the stock price. Both companies had existing histories and reputations, and industry analysts issued strong opinions about both stocks continuously up to "the conference call". We should question the assumption that any one person, even an MD, has the information needed to predict drug efficacy at these stages of drug development. The business news available on the internet in May imediately following the ASCO conference, offered just as complete read of the tea leaves and each stock's potential fortune as the speculations of the doctor in the conference call on July 18th, months later.

The Seattle Times authors suggest that potential profits could be reaped from the information that the doctor provided, but their data is merely speculative at this point. While the stock did increase in price and volume Pfizer's (PFE) volume also doubled the same day. Bayer's (BAY) volume also increased. Short term profits could surely be gamed on this stock, but before judging this, there are questions outstanding. Perhaps one would ask: Did people profit from the trade through personal investments in the companies? What other variables were influencing the stock that day? What were other analysts saying? Was the conference all that relevant, and is a $2.94 (13% looks like alot when the price and volume are paltry to begin with) change truly significant in a volatile stock such as Onyx, compared to say 33%, or $13, which is how much the stock fell one day in October 2004?

No doubt the article reveals a regulatory weakness in the current system. Clearly, the Seattle Times authors stirred up an important issue. But with the incomplete set of facts they offer, one could make up several disparate stories that fit the data. For instance one could say that the doctor focused on these two new drugs at the meeting over existing or other emerging candidate drugs (which were also presented and available) and in doing so biased doctors opinions about both drugs, before they were even thoroughly proven in clinical trials. Furthermore, can the authors be so sure who was actually disadvantaged by the conference call? Are they sure the investors who didn't sit in on the conference call were really worse off? Perhaps it was the "elite" investors, who are paying hundreds or thousands of dollars for information that was largely available three months earlier who are being *scammed*, rather then the savvier investors who followed the news back in May and could adjust their portfolios accordingly.

While the probable abilities of a small group of people to profit greedily and unethically off market fluctuations is clear but unproven, it is more certain that the doctor was being frank when he asked who's money he was betting.

Science Magazine reports that a group of scientists at Chiron, the Institute for Genomic Research, University of Messina Medical School, and Brigham and Women's, have engineered potential vaccine candidates for Group B Streptococcus using genomic screening techniques or reverse vaccinology.

Group B Strep (GBS) is a leading cause of death in neonates. The bacteria resides in the mucosal tracts of adults, where it can cause infection but is generally not lethal. During birth women can pass the infection to babies, where it can cause sepsis, meningitis and sometimes death. In the U.S. a systematic testing and antibiotic administration program for women in the last weeks of pregnancy is used to prevent infection, however each year the infection causes hundreds of deaths worldwide.

Conventional vaccine development uses various methods, such as the attenuation of the virus advanced by Sabin to produce the polio vaccine, isolation of protein subunits, or recombinant methods to isolate candidate antigens from bacteria or viruses. These resulting proteins are then tested to see which ones if any stimulate immunity (without toxicity) in animals or humans.

Several vaccine strategies specific to GBS exist, such as isolating the polysaccharide capsule (that surrounds the bacteria) which is then conjugated with cholera or pertussis toxin subunits. In addition to the logistical and regulatory challenges of the clinical trials, however, one of the difficulties that these vaccines face is that there are many different serotypes of disease, so a vaccine that is developed for one population say in Europe, may not be suitable for another.

The Chiron group used reverse vaccinology, a technology it had previously investigated for other disease vaccine targets such as type C meningococcal disease, caused by Neisseria meningitidis for which they manufactured a vaccine called Menjugate, used abroad.

Reverse vaccinology uses the whole genome of an organism to isolate all possible antigens "in silico" by comparing the sequence with the sequences of known antigens and toxins, in order to identify likely vaccine antigens. Recombinant expression systems (where the gene is isolated and produced by another bacteria) were used to produce candidate antigens, then these were screened to discern which candidates produced protection against the virulent strains. This method of vaccine development, though not without limitations, has the potential to advance at a faster rate, because the availability of complete genome information accelerates the identification of protein candidates. Chiron explains the difference between conventional vaccine development and this new method here.

The researchers used multiple strains of Group B Streptococcus in their genomic analysis and screening. They ended up with 312 surface proteins that were then screened for protective activity. Four antigens were identified that when tested alone, had restricted activity. These were then combined and the result produced broad spectrum protection against multiple virulent strains of GBS.

In a recent article; "Brain Chips and Other Dreams of the Cyber-Evangelists", John Horgan dispatches a scathing critique of recent books that take up the topic of enhancement of human capabilities via technology. The article was published in the June 3, 2005 issue of The Chronicle of Higher Education, a weekly publication that can be found lying around campus offices or on-line, by subscription only.

He takes authors and texts to task, among them Digital People From Bionic Humans to Androids by Sidney Perkowitz, and Flesh and Machines: How Robots Will Change Us, by Rodney A. Brooks. This genre is entertaining but irrelevant fiction he argues, as he points to the limitations of bionic prosthetics. He cites evidence in the account in Rebuilt: How Becoming Part Computer Made Me More Human, by Michael Chorost, which describes the realities of prosthetic research.

Horgman also comments on "brain chips", the technology and ethics of which are discussed in "Citizen Cyborg", Why Democratic Societies Must Respond to the Redesigned Human of the Future", by James Hughes. Hughes suggests that the brain chips (which would store actionable information for the brain) could be provided to all and monitored for moral decency by a benign global government. As well, says Horgman:

"[Hughes] proposes equipping dolphins and monkeys with brain chips so that we can communicate with them. You would think someone who entertains such notions whould be a fun guy...But Citizen Cyborg has the deadly earnestness of an Al Gore white paper on toxic waste. Hughes wants us to take this cyborg stuff very, very seriously."

Of I, Cyborg, by Kevin Warwick, he says: "a masterpiece of naive, unwittingly comic narration", by a "flamboyant" and relentlessly self-aggrandizing- authorial persona"...who has "transformed himself into a kind of neurobionic performance artist".

"Warwick recounts how in 2002 he persuaded a surgeon to implant a chip in his forearm and another chip in the forearm of his hapless wife, Irena...who "remained brave", "shrieking on a couple of occasions when it was particularly painful."

"After the implantations, when Warwick made a fist, his chip picked up the minute electrical surge in his arm and sent a signal to his wife's chip, which buzzed her. She then flexed her hand, and he felt "a beautiful, sweet, deliciously sexy charge..""

"Warwick...calls his stunt, "the most incredible scientific project imaginable, one that is sure to change, incalculably, humankind and the future""

Horgman scoffs; "[T]he Warwicks could have achieved an equivalent intimacy with vibrating cellphones: the fact that the chips were embedded in their bodies made no functional difference.." He concludes that Warwick is either, in the words of another scientist, "a buffoon" or a "charlatan". He illustrates a point. Warwick does seem to have a knack for mixing tales of draconian torture with banal Harlequin romance dialogue with the egomanical rambles of a principle investigator, a delivery style that does little to inspire confidence in his vision for science.

Horgman also doubts the concepts of singularity, discussed by Ray Kurzweil (and many others) in a couple of books. Moreover he pans the solution offered in Kurzwel's most recent book; Fantastic Voyage: Live Long Enough to Live Forever". Not without reason. Could one really eat organic veggies and drink alkaline water long enough to extend ones life to experience "the singularity"- where ones neuronal code could be uploaded into a computer to allow one to live forever? Quite probably a preposterous proposition.

Horgman charges that such futuristic predictions fail to take into account the actual progress and limitations of scientific research. The authors take irrational leaps of faith about technology [not to mention politics and government] in order to construct their bionic worlds. Horgman correctly points out that in the past couple of decades research has made relatively small steps towards neural prostheses and artificial intelligence. Cochlear implants have made great advances, but as Chorost points out in Rebuilt, they still offer a rudimentary solution to hearing loss. Retinal implants allow patients to sense no more than random flashes of light.

Horgan is a science writer, a former editor of Scientific American and author of several books. In one of his previous books; "The End of Science" (1996) (some of the concepts are updated and reiterated here), he suggests that the major questions of science have been answered. Accordingly, there won't be any more major revolutions in scientific theory - discoveries in the realm of DNA comprising the coding blocks of life, Darwin's natural selection, or quantum mechanics.

That book drew hearty, biting criticism from various scientists as well as his fellow science authors/philosophers. Apparently at ease inciting controversy, he glibly reciprocated the heated points of his would be detractors. Interestingly, almost ten years later, in the light of notable scientific achievement, it appears that "Brain Chips and Other Dreams of the Cyber-Evangelists", reflects the same sentiments about the limited future of scientific research. Therefore however grounded Horgman's criticisms of these authors, his ideas seem bounded by his insistence in a sort of permanent scientific paradigm. His prognosis then, is predictable:

"[N]ow and for the foreseeable future, cyber-evangelism is best understood as an escapist, quasi-religious fantasy, which reflects an oddly dated, Jetxons-esque faith in scientific progress and it potential to cure all that ails us."

"Not only is each person's code [sic] probably idiosyncratic, the product of his or her unique biology, but our individual codes may also constantly evolve in response to new experiences. For all those reasons, some neuroscientists suspect that uploading, downloading, telepathic conversations, and other scenarios that involve precise reading and manipulation of thoughts may never be possible - no matter how far brain-chip technology advances."

His points are valid, but they are drawn from rigid thinking employed to assess an obviously changing physical world. This is ironic because he strongly reasons that it is the changing world of neurobiology that nimbly morphs, forever defying a scientific understanding that could lead to the actualization of some of the more edgy ideas posed by the authors. Horgman's blind spot may be that he refuses to imagine a world where the framework is vastly different from the current one, so in the end, the "end of science" suits only his "lack of imagination".

Man's history is miniscule relative to that of the universe and to many other organisms. So the idea that humans are capable of evolving indefinitely as suggested by cyborg theories is clearly debatable. But his is an imperfect lens. Many imaginative ideas are not scientifically tenable, but all discovery is fueled by a sense of possibility and imagination by those who dare to challenge current paradigms.

Genetically modified plants (and GMO's- genetically modified organisms) have long been controversial. Scientists use molecular biology to modify the genomes of plants in order to make them more hardy -- to give them resistance to pests or fungi for instance. Plasmids are developed and used to insert a desired resistance gene into the plant. When researchers attempt (sometimes it doesn't work) to insert fungicide or pesticide genes into plants via the plasmids, they add an antibiotic ("Ampicillin") gene on the plasmid along with the pest resistance genes. The Ampicillin gene is commonly used as a marker in these types of experiments because it allows scientists to identify the plants in which the experiment worked -- the plants that carry the desired gene.

However not only is the use of pest or fungus resistance genes controversial, the use of Ampicillin in the environment is also controversial because it potentially increases the risk of widespread antibiotic resistance. Some scientists defend the practice and argue that Ampicillin is no longer a relevant antibiotic for livestock and humans because it is now so prevalent in the intestinal flora of "untreated" humans and livestock. However other scientists disagree with this stance, and argue that the antibiotic should not be further dispersed in the environment via transgenic crops. They argue that Ampicillin is still effective against some species and that the antibiotic's effectiveness depends on conserving its use for therapy. Policy advocates and governments also disagree, with various parties taking different positions.

Europe and the U.K. (as well as Africa and Asia) have always been more squeamish than the U.S. about transgenic crops. The European Food Safety Authority has advised EU governments that Ampicillin containing strains should only be used in test fields. Other agencies and NGO's concur that Ampicillin should not be commonly used especially in the food system. Yet the journal Nature (subscription) uncovered a case of alarming and perhaps inadvertent Ampicillin carrying GMO seed propagation in its recent report: "Stray Seeds had Antibiotic-Resistance Genes" (Colin Macilwain: 434, p.548 March 31, 2005).

For the past 4 years the Swiss firm Syngenta sold corn seed that contained a gene that codes for antibiotic (Ampicillin) resistance. One strain of maize (Bt10) that contained the Ampicillin gene was sold instead of another (Bt11). Bt10 had originally been a control strain to show the lack of the Ampicillin gene in Bt11. "Hundreds of tonnes" of the seed were planted and farmed by American and European farmers from 2001-2004, years before the error was apparently noticed, the investigation reported.

The issue hasn't been resolved. In a June 2nd editorial; "Don't rely on Uncle Sam" (Nature 434, p. 807), the journal notes the lax regulatory agency response. Nature analyzed the responsibilities of three U.S. agencies who would be responsible for discovering and correcting the error. Why didn't the US Department of Agriculture (USDA), the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA), catch error for four years? Each had a media ready excuse:

• The FDA reasoned that since the intended pesticide gene was not a food safety issue, they weren't responsible.
• The USDA claimed that its "system was working"...despite the fact that it never caught the transgression. They gave a bureaucratic shrug (actually Nature suggested that it might have been more corporate dismissal) and fined the company $375,000. A very very soft slap on the wrist?
• The EPA claimed that it was short on resources, which prompted Nature to quote The Onion's satirical take, that the EPA had renamed itself "The Agency" -- since the "Environment" part of its title didn’t seem appropriate for its role of "not protecting anything"

In addition to collective shirking on the part of the U.S., Nature also commented on the rather limp European reaction. Back in April 2004, the European Food Safety Association (EFSA), published a directive on the use of antibiotic resistance marker genes in genetically modified plants, decreeing that genetically modified plants intended for food or feed should avoid genes that "confer resistance to antibiotics of clinical importance..." The authors at Nature wonder why European regulators haven't seemed to address Syngenta's 4 year oversight. After all, the editors reasoned, the company is a European one (even if Switzerland is not really in the EU). The Nature editorial concluded - "Thankfully, on this occasion we're not dealing with a threat to public health."

Most recently, in Nature's June 2, 2005 issue (435, 561: Correspondance), UK Scientist Gundula Azeez of the Soil Association responded to this Nature editorial:

"We are concerned by the suggestion, in your Editorial "Don't rely on Uncle Sam", that the US Food and Drug Administration does not consider the presence of the ampicillin-resistance gene in Syngenta's unapproved variety of genetically modified Bt10 maize to represent a safety problem.."

That's not exactly what the original editorial said, although government agencies across the board certainly did seem to support this opinion. The letter to Nature author takes a stance:

"This is not the view of the UK government's scientific advisers... The risk of horizontal gene transfer from genetically modified organisms genetically modified organisms (GMOs) is not a theoretical one."

The author cites a study that showed that the plasmids can survive certain conditions and go on to transform bacteria. He adds that not enough research has been done on the potential effects for horizontal gene transfer, as issue that pertains not only to Ampicillin resistance genes but to the toxin resistance genes in GMO's as well. The author also criticized the U.S. agencies' "case-by-case" approval mechanism for transgenic crops, saying that overall the technology hasn't been adequately researched.

While we can't comment on EU agencies' impetus, but the lack of vigorous U.S. response is not accidental. The U.S. has always supported and promoted the use of transgenic crops since the day when vice president Dan Quayle, in the name of business competitiveness, declared that GMO's and non-GMO's were the same.

Will there be more research and will it bridge the EU/US divide? For the U.S., it seems that when doing research would potentially protect public health would interrupt industry's speed in selling products research is eschewed. However when research could potentially show the detrimental affects of industry to public health and the environment, then the call is interminably for more research. Interestingly, while Europe and the U.S. continue to squabble over policies and science results; the potential effected customers are millions of farmers and consumers across the globe.

Codon Devices is a new biotechnology start-up that was recently profiled in Forbes Magazine. The company proposes to design bioengineering systems that will allow scientists to edit DNA sequences to create synthetic sequences for research and easier protein generation. Currently, molecular biology ressearch involves time consuming processes of cutting and ligating sequences together then transforming cells that will hopefully express the desired protein.

The founders recognize the challenge of their proposal but are optimistic about the potential of the technology, as are investors. One co-founder, Jay Keasling of the University of California, Berkeley, has recieved $42.6 million from the Bill & Melinda Gates Foundation via One World Health, to develop an anti-malarial medicine.

The Massachusetts Senate passed a bill on Wednesday that would allow human cells to be cultured for stem cell research. The bill passed by 10-2. On Thursday the House of Representatives version of the bill passed by 117 to 37, a vote wide enough to repel the Governor's veto of the bill, which requires 53 votes.

Mitt Romney, a Republican (as usual) governor in the largely Democratic state, vigorously lobbied against the bill, most recently in a radio campaign. Romney is against cloning embryonic stem cells via somatic cell nuclear transfer because that is for the creation of "new human life". However, in apparently nuanced and rather opaque position against embryonic stem cell research, he is not opposed to stem cells created from cells leftover from in-vitro fertilization. Romney conceded defeat on the Massachusetts measure, but added:

"I think you're going to see at the national level an interest in legislation which limits the creation of new embryos though cloning," Romney said. ''So I think you're going to see a national effort to define the boundaries of ethics, and I hope that proceeds."

There is speculation that Romney is polishing his resume for a prospective presidential run in 2008.