Tuesday, February 28, 2006

Epigenetics and Cancer

by Pharma Bawd

“Although individual genes vary in hypomethylation, all tumours examined so far, both benign and malignant, have shown global reduction of DNA methylation33, 34, 35. This is a striking feature of neoplasia.”

Nature Reviews Genetics had a good paper up about epigenetics and cancer in January. I planned to write about it, but..., life gets in the way. Not to mention reading blogs, and lately I’ve been reading Aetiology, specifically the threads about HIV/AIDS and then the new thread about viruses and cancer.

If you haven’t been reading these threads, you should. Tara has been visited by noted AIDS skeptic Harvey Bialy, a former editor of Nature Biotechnology. Although Dr. Bialy’s rhetorical style is offensive in the extreme, and many of his arguments about HIV/AIDS are really bad, he and the subject of his book, Peter Duesberg,


have an interesting point about cancer and aneuploidy.

The majority of cancers exhibit aneuploidy and it is Duesberg’s contention that aneuploidy itself is the proximal cause of cancer. This is very much a chicken and egg argument in my opinion, whether the genetic insults that lead to cancer lead to aneuploidy first and cancer later, or whether only once aneuploidy occurs does cancer arise doesn’t seem to be very clear nor very meaningful to me, especially if you can prevent the initial genetic insult that leads to either cancer, or to aneuploidy and then cancer. But Dr. Bialy has contended that there are two primary theories of how cancer arises:

1. The oncogene theory
2. The aneuploid theory

I “assert” that there is at least one other theory, the epigenetic theory of cancer. Now, Bialy may contend or assert, that epigenetic causes of cancer are just an extension of the oncogene theory of cancer. But in this he would be wrong. And therefore it is worthwhile to discuss exactly what “Epigenetics is and how it relates to cancer.

Nature Reviews Genetics 7, 21-33 (January 2006) | doi:10.1038/nrg1748
The epigenetic progenitor origin of human cancer
Andrew P. Feinberg1, Rolf Ohlsson2 and Steven Henikoff3 About the authors
Top of page
Abstract
Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.


So, if you’re like most people, you’re asking “What the heck is epigenetics?”
Epigenetics is a very important subject that most college genetics courses give short shrift, as in, it’s never mentioned. But it is arguably the most important part of gene regulation in development and the proper regulation of gene activity that when disrupted causes cancer to arise.

First, let’s talk about DNA for a moment. The genome of an organism is the string of chemical letters As, Ts, Gs, and Cs that make up its genes. Our genome consists of about 3 billion pairs of such chemical letters divided into 46 (23 pairs) individual molecules called chromosomes. If we were to stretch out this DNA to its full length and line it up end to end it would total about two meters in length, with a width across the DNA molecule of 2 nanometers. A nanometer is 1/1,000,000,000 of a meter. So if the DNA is two meters long it is one billion times longer than it is wide. For perspective, let’s say a human hair is about 50 Micrometers wide A hair that represents the same ratio of length to diameter as DNA would have to be 50,000 meters, that’s over 30 miles long! I know, I know! Rapunzel let down your DNA right?!

Well, that’s an awful long molecule with a heck of a lot of important information encoded on it that has to be available at any time for transcription as well as being available from time to time for DNA replication, so it has to be very well organized in order to fit the whole thing into the nucleus, about 5-10 micrometers in diameter, without the whole thing turning into a tangeled mess. So, for perspective again, imagine all the letters in The Bible, how many do you think that is?
3.5 million.

OK, so there’s 3 billion letters in the human genome so we need 857 Bible equivalents of text written on our 30 miles of hair, basically every hair on the head of a woman with .5 meter long hair. Then, all that hair needs to fit into a sphere something like the size of the woman’s head. And all of it needs to be organized so that any given sentence can be easily accessed and read, and all of the hair needs to be maintained in such a way that it can be replicated into two complete copies that are then able to divide into two daughter cells without any tangles or knots forming. In every single cell in the human body, around 70 trillion cells. It’s a pretty tall order and it requires a lot of organization. That organization is provided by proteins around which the DNA is wrapped in order to compact it so that it will fit into the small space of the nucleus. This complex of DNA and proteins is called chromatin and the major protein components of chromatin are the histone proteins. There are five histone proteins, each with specialized variants, histone H2A, H2B, H3 and H4 all occur in pairs that are bound together in a core particle around which the DNA is wrapped two times. Outside this core, sort of like a clip to keep the DNA in place on the core particle, is the linker histone H1. The whole complex eight core histones linker histone H1 and two loops of DNA wrapped around the histone core particle forms a structure called the nucleosome.

Picture of nucleosome.
As you can see from the figure all of this protein is roughly equivalent in volume to the total volume occupied by the DNA (hair) so the nucleus (head) is getting quite full just with the genome and associated histone proteins.

So that’s how cells cram all that DNA into the relatively small volume of the nucleus in such a way that it is still well organized and accessible. Now, on to the epigenetics. Epigenetics is basically the chemical modifications of chromatin (DNA and histones) that does not alter the nucleotide sequence of the DNA. These chemical modifications are primarily methylation of Cytosine residues in the DNA and acetylation of histones. Histones can also be methylated, phosphorylated, or ubiquitylated. All of these modifications contribute to the transcriptional activation or inactivation of gene sequences in the DNA.
This picture of methylated and nonmethylated DNA shows how a slight modification can alter the binding site for a protein on DNA.

These modifications to both DNA and to the histones are heritable through both mitosis (one cell divides into two) and in some cases meiosis (sperm and egg formation). (If the IDers are really looking for support for Lamarck, this is a much better area to look into than transfer of antibiotic resistance between bacterial species.) So this represents another level to the genome, an "epigenome" as it were, a collection of information present within our cells that is separate from the information contained within the DNA sequence itself. This epigenome is crucial to the regulation of gene expression by regulating which genes are able to be transcribed in certain cell types. In cells where certain genes are not transcribed they can be highly condensed as heterochromatin leaving room for the genes that are necessary in that cell type. And this is where it becomes important in cancer.

Old models of cancer such as the two hit model for knocking out both copies of a tumor suppressor gene suggest that cancer is selected clonally after a series of mutation events that knock out the various control mechanisms that regulate cell division. This process would require numerous sequential mutations to several different genes involved with regulating cell division.

Epigenetic modification of the genome is a much more dynamic and common process than mutation. Cells are constantly modifying the DNA and histones to regulate gene expression and for a variety of reasons they may perform these functions improperly. Epigenetic changes important to carcinogenesis include global hypomethylation across the geneome, site-specific hypomethylation and hypermethylation, and chromatin modification of gene promoters that control expression of oncogenes and/or tumor suppressor genes.

The authors’ model posits that epigenetic modifications of genes in stem cells lead to dysregulation of oncogenes or tumor-suppressor genes which leads to a gatekeeper mutation (basically a mutation in a gene that controls cell division, the gatekeeper mutation allows the precancerous cells to begin dividing, a critical step in cancer progression.), followed by further epigenetic and genetic instability.


This model is attractive in that certain stem/progenitor cells already have many of the features seen in late stage tumors, such as metastasis, and would not require precise genetic mutations in order to acquire these functions. It should also be noted that any of these three models: the genetic theory, the epigentic theory, or Duesberg's aneuploidy theory; would require Darwinian evolution and natural selection in order for tumore progression to occur.

I can see where Bialy or Duesberg may argue that the epigenetic modifications may be involved with the initial aneuploidization event in the cell. But I'm not sure I can buy the idea that it is the aneuploidy that is the cause of the cancer. I am more likely to agree that the upstream genetic and epigenetic events allow a cascade of events to occur, one of which is aneuploidization, that frequently leads to cancer. Their argument seems to be similar to saying: It's the driving that causes the accident when drinking and driving. The drinking may be an important factor in leading up to the driving, but the driving is what causes the accident. This may be true, but I don't think it makes the drinking any less necessary or important in causing the drunk driving accident.

(Will probably modify this when I have more time.)

Wednesday, February 22, 2006

Everybody's Talking About Herpes Viruses!

Tara's even got a picture up of her infection. I have a similar picture of myself, except every one of my pox was covered in pink Calamine lotion. It didn't do much to help the itching, but it sure made me look worse!

Meanwhile, a gang of HIV/AIDS deniers are pestering her to explain why certain groups of AIDS infected people suffer different diseases than others. At least one answer to their question is a herpes virus.

The herpes viruses are a large group of viruses with over one hundred members that infect a variety of animal species, at least eight herpes viruses call the human species home. These viruses include such "old family friends" as varicella-zoster virus (chicken pox, and shingles) and herpes labialis/HSV-1 (cold sores on the lips and mouth).

Alphaherpesvirinae:
Simplexvirus human herpesvirus 1, 2 (HSV-1, HSV-2)
Varicellovirus human herpesvirus 3 (VZV)

Betaherpesvirinae:
Cytomegalovirus human herpesvirus 5 (CMV)
Muromegalovirus mouse cytomegalovirus 1
Roseolovirus human herpesvirus 6, 7 (HHV-6, HHV-7)

Gammaherpesvirinae:
Lymphocryptovirus human herpesvirus 4 (EBV)
Rhadinovirus human herpesvirus 8 (HHV-8)

http://www.tulane.edu/~dmsander/WWW/335/Herpesviruses.html

The herpes viruses are large (150-250 nm in diameter) and all consist of an envelope, tegument, nucleocapsid and a core particle containing the viral genome of up to 235 kilobases of DNA in a linear double-stranded genome that encodes over 50 viral proteins (compared to 11 for adenovirus= the common cold).


herpes virus nucleocapsid:
162 protein capsomeres in an
icosahedral array with 5:3:2 symmetry







A herpes virus with the envelope, acquired by pinching off a portion of the cellular and nuclear membranes, glycoproteins are visible extending through the membrane.













All of the herpes viruses produce a life-long latent infection in their native hosts. That's right, you never really got rid of the chicken pox after you were infected with chicken pox as a child, the varicella zoster virus retreated to the trigeminal and spinal nerve ganglia at the base of your spine. There, the virus established a latent infection waiting until some time after you turn fifty, or your immune system is compromised, so that it can reemerge as a painful case of shingles (herpes zoster)! Don't you love viruses? (I have it from a good authority working in a herpes virus lab that the degree of painfulness of shingles in the elderly is directly correlated to how sympathetic they were to their own children while they had the chicken pox. So treat those kids nice! Or, better yet, get them vaccinated.)

The herpes viruses replicate through rolling circle replication. I could write a thousand words describing it to you, or you can click through this flash media presentation.

(Here's the thousand words version if you're interested.)

So, you see it's very easy for a latent virus to begin replicating many new viral particles to establish an active infection. (This is one of the false claims I called Coraphor on last week, they claimed that by killing herpes viruses on the skin, the store of latent virus could be reduced, decreaseing the number of viruses able to cause subsequent infections.)

Now, on to the HIV/AIDS denialists. One of the favorite points of Peter Duesberg is that different populations of AIDS diagnosed individuals suffer from different AIDS defining disorders. An excellent example of which is the high incidence of Kaposi's Sarcoma among male homosexuals with AIDS in the US:

"However, the plethora of AIDS diseases was not, and
still is not randomly distributed even among the different
risk groups (table 2). For example, Kaposi’s sarcoma
was exclusively diagnosed in male homosexual risk
groups using nitrite inhalants and other psychoactive
drugs as aphrodisiacs
"
"the predominant and most distinctive AIDS
diseases in the US and Europe, Pneumocystis carinii
pneumonia and Kaposi’s sarcoma, are almost never diagnosed
in Africa"
"Moreover, the findings that
specific drugs, as for example nitrite inhalants, correlated
with specific AIDS diseases, such as immune suppression
and Kaposi’s sarcoma, directly support the lifestyle hypothesis."
"In addition, a fast-rising epidemic of volatile nitrite
inhalants, primarily among male homosexuals, was identified
in the US by Newell et al, Lauritsen and Wilson,
and the National Institute on Drug Abuse (Lauritsen and
Wilson 1986; Haverkos and Dougherty 1988; Newell
et al 1988). It started in the late 1970s – immediately
preceding the male homosexual AIDS sub-epidemics of
Kaposi’s sarcomas and pneumonias..."

http://duesberg.com/papers/chemical-bases.html

"Kaposi's Sarcoma is at least 20 times more common among homosexual than among non-homosexual AIDS patients."
http://duesberg.com/papers/The%20AIDS%20Dilemma.pdf

So, homosexual AIDS patients in the US suffer from a rare form of cancer, Kaposi's Sarcoma, at a much higher rate than other groups of AIDS patients throughout the world. What could explain this discrepancy? Well, there is the possibility that the nitrite inhalants, "poppers", commonly used by homosexuals in the 80's to heighten orgasm could be weakening the immune system in some way that allows KS to occur, as Duesberg suggests. Or, it could be that a previously unknown herpes virus that can bring on Kaposi's Sarcoma, and is sexually transmitted, is being transmitted along with, before, or after transmission of HIV so that once HIV has weakened the immune system sufficiently, the herpes virus is now free to replicate at will producing Kaposi's Sarcoma. I know, it sounds like just as much hand-waving as Duesberg's doing, until the virus is actually discovered.
(Update: This link actually leads to the abstract for the Science paper where KSHV is first discovered. My apologies to Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS.) And it actually does correlate well with Kaposi's Sarcoma not only in AIDS patients, but in other populations as well.

In 2002 Osmond et al. went back and examined samples collected from homosexual men in the San Francisco area in 1978-79 when the AIDS epidemic began. They found infection rates for Kaposi's Sarcoma-associated herpes virus (KSHV/HHV-8) of 26.5% while HIV infection at the time was only 6.9%. In 1984-85 KSHV infection was relatively unchanged at 29.6%, while HIV infection had sky-rocketed to 49.5%! HIV infection dropped to 17.6% in 1992-93 while KSHV infection was 26.4% in 1995-96.

So, a herpes virus associated with the occurence of Kaposi's Sarcoma remained present at a fairly constant level in the male homosexual population of San Francisco at the same time that HIV went from a small number, to half the sample size and back down to less than the prevalence of KSHV. What could explain such a thing?

"The proportion of men practicing unprotected receptive anal intercourse with 1 or more partners declined from 54% to 11% during the 1984 through 1993 period (MHS) with similar though slightly higher values in the YMHS in 1992 and 1993; whereas for unprotected oral intercourse it ranged between 60% and 90% in the 1984 through 1996 period (MHS and YMHS). CONCLUSIONS: Infection with KSHV was already highly prevalent in homosexual men when the HIV epidemic began in San Francisco, and its prevalence has been maintained at a nearly constant level. Any declines in the incidence of Kaposi sarcoma do not appear to be caused by a decline in KSHV transmission."
Well, if both viruses HIV and KSHV are transmitted through different froms of sexual intercourse, HIV particularly through recpeptive anal intercourse, and KSHV particularly through receptive oral sex. (Yes, I do mean that the male recipient of oral sex is catching KSHV from the performing partner.) The static levels of KSHV infection, while HIV infection changed dramatically, can be explained by the differential use of condoms during anal and oral intercourse.

Thus, we have a test of the HIV as an infectious virus causes AIDS hypothesis, we also have a test of whether weakening of the immune system by HIV allows secondary infectious agents, that would normally be suppressed by a healthy immune system, to wreak havoc on the human body.

Score: Viruses (2), Duesberg and Denialists (0).

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Thursday, February 16, 2006

Genentech to Colon Cancer Patients: BOHICA!

Well really it’s not their colon cancer patients they’re telling to bend over but their new-found breast and lung cancer patients they want to grab their ankles.

Genentech had its drug Avastin (bevacizumab), a monoclonal antibody for Vascular Endothelial Growth Factor (VEGF) which prevents the growth of new blood vessels to cancerous tumors, approved for the treatment of colon cancer in 2004. Currently Genentech is selling $1 billion per year of Avastin and recent trials have shown that Avastin may also be effective at extending the lives of breast and lung cancer patients. To celebrate the good news Genentech announced it is doubling the price of Avastin for breast and lung cancer patients.

It seems that the smart guys and gals at Genentech and their partner Roche have found that when people's lives are at stake there is considerable price inelasticity of demand for the drugs needed to keep them alive.

"As we look at Avastin and Herceptin pricing, right now the health economics hold up, and therefore I don't see any reason to be touching them," said William M. Burns, the chief executive of Roche's pharmaceutical division and a member of Genentech's board. "The pressure on society to use strong and good products is there."

I see. The “pressure on society” is there, so it’s perfectly O.K. for you to charge whatever you like for your product. A product developed with significant expenditure of public research dollars. A product for which you hold a state enforced monopoly in the form of patents. A product that only extends cancer patients lives an average of 5 months. A product currently involved in 94 clinical trials for nearly two dozen different cancers. A product expected to reach $7 billion in sales by 2009. A product you set a price for in colon cancer patients that would recoup your R&D costs and earn you a hefty profit on your product. Why is it necessary to charge twice as much for the same product in breast and lung cancer patients?

Could it be because you’re greedy pigs?
















http://www.pigpalssanctuary.com/pictures/piggie.htm

I do have one question for you piggies: What makes you different than a hostage taker demanding a ransom?

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Tuesday, February 14, 2006

Miracle Cure for Herpes!

The Amazing Australian “silver bullet” that kills herpes I & II on contact
and rapidly removes
humiliating signs of breakouts

Welcome to Skeptical Pharmacy Friday!

I'll be your host, Pharma Bawd.

With 25 million Americans suffering from oral herpes (cold sores or fever blisters) and about 45 million suffering from genital herpes infections, herpes is the most widely spread sexually transmitted disease in the US. Between 500,000 and one million new cases of herpes occur each year and the rate of infection is on the rise. There is no cure for herpes and the infection is lifelong.

The huge number of people infected with herpes as well as the acute physical, emotional and psychosexual symptoms of the disease creates a tremendous demand for products that treat herpes. Big Pharma has responded by developing antiviral drugs that target the herpes simplex and related viruses. Unfortunately, this opportunity has also attracted less scrupulous operators who make bold claims and charge high prices for products of dubious efficacy.

One of these is Choraphor.

WARNING: Don’t spend another dime on herpes medications, lotions or potions no matter how slick their website or ads are until you read this life-changing message! What you’re about to discover is the closest thing there is on planet earth to becoming 100% absolutely free from herpes!

Besides noteing that there is currently no way to become 100% free from herpes, I think Choraphor's warning message is even better applied to this blog post.

Chorphor’s claims:

”Choraphor works by eliminating the virus on direct contact with the outbreak. It is an antiviral topical solution that helps to rapidly heal herpes lesions, blisters and sores rapidly, and then reduces any further recurrences.

This is a pretty direct claim, do you have any evidence? No? Well, lets continue.

P Choraphor is PROVEN to “eliminate” the herpes virus on contact

P Most users report their outbreaks have STOPPED completely and have --never come back!

P Users report if symptoms do reappear, they’re typically less frequent and less severe!

P PAIN and HUMILIATING LESIONS VANISH! Choraphor speeds up the recovery process from outbreaks so you can get on with your life

P Results seen almost IMMEDIATELY!

(That's why this product is unquestionably the closest thing there is to a cure.)

"Proven", "STOPPED", "never come back", "Results... IMMEDIATELY!", sounds like great stuff! Where's the proof? The evidence? The data? The independent testing? We already agreed there is no cure for herpes and Choraphor certainly isn't one either.

With the application of Choraphor you can expect:

1. A mild to strong stinging sensation as the Choraphor molecule eliminates the virus ...

When applied, a sharp tingling sensation is expected as the Choraphor travels down the peripheral nerves and begins to attack the herpes virus. ...

Choraphor will not sting when applied to normal, healthy skin, however, it must produce a stinging sensation when you apply it to the infection (this will be an indication that the application is working). ...

The solution will sting as the Choraphor eliminates the virus that it comes into contact with. This feeling is not always pleasant but it is short in duration and may result in a total end to the herpes outbreaks. ...


(All bold is mine for emphasis, words are all theirs.)

They seem to make a lot out of that stinging sensation don’t they?

"Stinging sensations are usually an indication that the application is working."

OK, just what the heck is in this stuff?

Choraphor is an sulfate based solution with copper as a trace metal in an aqueous herbal base. It is applied to the site of an active condition. Choraphorcontains the herb St. John's Wort (Hypericum perforatum), ammoniated acid in deionised water.

[Time out for a Moment of Science Laboratory Safety Advisory: Please watch this short educational film about combining acids and bases.

Carry on.]

The Choraphor molecule is an essential factor in the make-up of the product. It is this combined effect that causes the Choraphor to penetrate the membrane of the herpes virus, hence the destruction of the herpes virus on contact.

Oh, so now Choraphor is a molecule? I thought it was a solution. Do you want to know what I think it is? Let’s see, the St. John’s Wort and what-not are probably just that, marketing gimics. Then there’s copper, and sulfur, and the solution is blue. Could it be...

Copper Sulfate?

Copper sulfate is a fungicide used to control bacterial and fungal diseases of fruit, vegetable, nut and field crops. Some of the diseases that are controlled by this fungicide include mildew, leaf spots, blights and apple scab. It is used in combination with lime and water as a protective fungicide, referred to as Bordeaux mixture, for leaf application and seed treatment. It is also used as an algaecide, an herbicide in irrigation and municipal water treatment systems, and as a molluscicide, a material used to repel and kill slugs and snails.”

Many people who’ve used Choraphor say that it stings like the “dickens.”
Yeah, I'll bet it does!

Copper sulfate can be corrosive to the skin and eyes. It is readily absorbed through the skin and can produce a burning pain, along with the same severe symptoms of poisoning from ingestion.”

So, to the writers of the testimonials claiming Choraphor helped them, I suggest this experiment: The next time you have an abrasion similar in sensitivity and size to a herpetic lesion test Choraphor on it. Is the burning sensation the same/similar? Then it is unlikely that this sensation is do to Choraphor “destroying the herpes virus”. It is more likely destroying your nerves, or at least stimulating them to no good effect.

"The fact that the herpes virus will retreat into the nervous system makes it extremely difficult to eliminate completely. What can be done is to attack the virus each time that it surfaces, depleting it with every encounter and diminishing the amount of virus retreating back into the nervous system.

This can lower the virus levels in the body which helps your immune system have greater control over future outbreaks.

This is why some users of Choraphor have had no further outbreaks. Other users have reduced the severity of their monthly outbreaks down to mild, infrequent recurrences."

“. As well as speeding up the recovery time, Choraphor also reduce recurrences. if outbreaks return, the symptoms are typically smaller, less intense and happen less often.“Also, if you use Choraphor persistently (only once per outbreak) the symptoms tend to reduce with each application and it is reported in many cases that little to no further symptoms occur after treatment.”

This is all very deceptive, many people infected with the Herpes virus report a decrease in the number and severity of their outbreaks over time. So with or without Choraphor outbreaks are likely to lessen with time, and occur with less frequency. Also, the idea that destroying some virus depletes some reserve of viruses hiding out in the sacral nerve ganglion is ridiculous. The virus, like all viruses, replicates itself during an active infection. It doesn't matter if a product could destroy some virus in the body, a single virus can replicate millions or billions more at anytime.

Why does Choraphor seem expensive?

Choraphor is priced at US$93.00 per bottle plus delivery.

The product comes in a 12mL bottle of concentrated solution that only needs to be applied once per outbreak. Only a few drops of the formula are needed per application / outbreak.

At $93.00 for a 12 mL bottle Choraphor doesn't seem expensive it is outrageous! Right now I can buy 50 pounds of dry copper sulfate for $59.99 on E-bay.

OK so where is the Evidence of Choraphor’s effectiveness?

You see, Choraphor is so effective -- the manufacturer has a filing cabinet overflowing with testimonials from real people ecstatic how their lives have been changed dramatically for the better. (No other product on the market boasts this level of success.)

Wow a whole filing cabinet you say? Any clinical trials, or studies of any kind in that filing cabinet?

You see the reason I ask is because herpes is self limiting. The outbreak goes away after a short time on its own, so users of your product may attribute the healing of lesions to the effects of Choraphor when, in fact, the infection has simply run its course. This is called confirmation bias and is the reason we can't accept anecdotal evidence like testimonials.

And of course, what alternative medicine treatment would be complete without an endorsement by a doctor of naturopathy?

"I have been in full time professional practice since 1984 and during that time have treated the herpes lesions on many occasions. Choraphor is by far the best herpes treatment that I have come across to date." -- Dr John Spurge ND. B. Com. Doctor of Naturopathy ND (AAI) Bachelor of commerce B.Com. (UNSW)

The fact of the matter is, this product is a scam. Topical anti-herpes medications are largely ineffective. Yes, even the ones sold by large pharmaceutical companies with mountains of clinical trial data that prove their effectiveness. Just look at the package insert for Denavir, a topical product containing the antiviral compound penciclovir and sold by Novartis:

In both studies, the mean duration of lesions was approximately one-halfday

shorter in the subjects treated with Denavir (N=1,516) as compared to subjects treated

with placebo ( N=1,541) (approximately 4.5 days versus 5 days, respectively).”

½ a day. That’s all it gives you for putting the ointment on every two hours for four days. Yes, in certain cases, like on your wedding day, that ½ a day may be crucially important. But if a “proven” product like Denavir only provides this level of efficacy, how can a completely unproven product with a hodepodge of nonspecific chemicals do even this well at reducing the duration of an outbreak?

Answer: It can’t. Therefore, using Choraphor to treat a cold sore you can expect it to take much closer to five days for the lesion to heal, like exactly five days on average.

In my opinion, this product is targetting people who are having their first experience with genital and or oral herpes and are unwilling or embarrassed to visit their doctor for a prescription antiviral drug. This is unfortunate, not only because the product itself is highly unlikely to benefit the consumer, but because herpes is more than just an occasional physical disease, it is a psychosexual disease with occasional physical symptoms. Patients would be better served if both the psychological and the physical symptoms of herpes infection were monitored and treated appropriately by a physician.

Choraphor is available from these and other unscrupulous retailers:

http://www.choraphor-herpes-solution.com/index.html

http://www.choraphorlabs.com/

http://www.choraphor.com/

I would suggest either of these sites to learn about proven treatments for herpes:

http://www.famvir.com/info/living/with/life.jsp

http://herpeshelp.com/

Choraphor was not the worst sham herpes treatment that came up on Google but it was slick and the web site seemed professional enough that I’m sure many people desperate to do something about a herpes outbreak might be “willing to do anything” to make it go away. This includes spending their hard earned money on something that if they looked at it critically they would know better.

PhB.

choraphor hcoraphor cohraphor chroaphor choarphor chorpahor chorahpor chorapohr choraphro horaphor coraphor chraphor choaphor chorphor chorahor chorapor choraphr chorapho xhoraphor dhoraphor fhoraphor vhoraphor khoraphor cyoraphor cgoraphor cjoraphor cboraphor cnoraphor chiraphor chkraphor chlraphor chpraphor charaphor cheraphor churaphor choeaphor chodaphor chofaphor chotaphor chorqphor chorsphor chorzphor chorephor choriphor chorophor choruphor choraohor chorapyor chorapgor chorapjor chorapbor chorapnor choraphir choraphkr choraphlr choraphpr choraphar chorapher choraphur choraphoe choraphod choraphof choraphot

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Monday, February 13, 2006

Pure IDiocy!

I realize that there comes a point of diminishing returns when criticizing and making fun of the intellectually vacuous propaganda that is "Intelligent Design". But I just can't help myself.

Pharma Bawd made me go there to tell her what they were up to, and I saw this:



Aarrghh!!! Of course! Why didn't I notice that models of DNA are designed before now? It's so obvious now that I've had the blinders of Darwinian orthodoxy taken from my eyes...

Lets see what else may be an artifact of design.

I think we can all agree that a soccer ball is designed


But, what about a Bucky Ball?


Sure, this model is designed just like the model of the DNA in the ID throw pillow (really? a throw pillow?) but is the molecule itself designed? Of course not, it's formed as a by-product of burning carbon. There's nothing there but very cool chemistry. Where is the Intelligent Design vs. Valence Shell Electron Pair Repulsion theory of molecular structure? I mean it's just a theory afterall.

On a side note, I did learn that Bill DembskiDave Scot grows his own Japanese culinary mushrooms in semi-sterile conditions in his lab. That's a pretty cool "science" thing to do. I'm building a laminar flow hood in my shed so I can do sterile culture propagation of orchids myself. So, BillDave and I do share some common ground. We're both geeks.

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Thursday, February 09, 2006

I wonder what they'd do with the animals in a privatized National Park?


PZ Myers points out this post at Northstate Science which discusses the 24 year old college drop out who attempted to censor NASA scientists. (The News that George Deutsch had never finished college was brought to light by blogger Nick Anthis of Scientific Activist.) Deutsch was appointed to his post at NASA by the Bush administration for his efforts on the campaign trail. As Northstate Science points out there is a similar situation taking place in our national parks:

"...under the direction of Assistant Secretary of the Interior Paul Hoffman, the Park Service is re-writing its management policy guides. These reflect the larger vision expressed by the Park Service for management of our national parks and will guide the manner in which future policies and decisions are implemented."

"
The new guidelines would drop mention of evolution from National Park materials, they would drop scientific standards for manging the parks, and they would turn back policies aimed at the environmental protection of the parks. These rewrites come from a "former Cody, Wyoming Chamber of Commerce staffer with no National Parks experience"naturally.

This is a great blog and a great article about continued efforts to privatize our National Parks. It makes mention of these articles in the George Wright forum which discuss the prospects for privatizing various aspects of our National Parks.

Privatization: An Overview
Maurice H. Schwartz, guest editor

Privatization: An Overview—Introduction and Summary / Maurice H. Schwartz

From Public to Private: Five Concepts of Park Management and Their Consequences / Thomas A. More

The Greater Realities of Privatization: A Historian’s Perspective / Alfred Runte

Entrepreneurism in America’s State Parks / Ney C. Landrum

Beyond the Public Park Paradigm / Sylvia LeRoy

Competitive Sourcing in Our National Parks / Geoffrey F. Segal

The Effects of Neo-Conservatism on Park Science, Management, and Administration: Examples and a Discussion / John Shultis

Forces Underlying the Emergence of Privatization in Parks and Recreation
(Executive Summary) / John L. Crompton


A New Tragedy for the Commons: The Threat of Privatization to National Parks (and Other Public Lands) / Bill Wade

The Recreation Fee Demonstration Program and Beyond / Scott Silver

Everyone who wishes to pass the National Parks we inherited from our grandparents, on to our grandshildren should go here and get involved.

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Tuesday, February 07, 2006

My Dirty Little Secret, and Soil Microorganisms.


by Pharma Bawd

I have a dirty little secret. I’ve never told a soul, but Tara’s call for submissions has fond memories of my last encounter flooding over me, filling me with guilt.

I’m so embarrassed! What if my children found out? I can’t tell my husband, he wouldn’t understand. Hell, I don’t even understand why I do it. I just know I can’t stop.

I remember my first time like it was yesterday. It was a Friday, nobody was around, so I tried it. It was AMAZING! I’d never felt that way before, like I was Queen of the World! I was the expert. I had ALL the answers. Once, in grad school, I was teaching a biology class and I had a similar experience, but this... this was different. I was on a higher plane! It was incredible.

When I finished, I was glad I'd done it. It felt good! Hell, I went away from the experience feeling better about myself.

God, how I curse that day!

I thought I’d never do it again. I had my fun, nobody knew, I'll walk away like it never happened. Then, one day, I was feeling down, I was bored. So I did it again, and it was as good as the first time!

Hey! It’s not like you think. It’s not just a feel-good joy-ride, it’s frustrating too. Every time, the second I start, I can feel pressure growing inside me. Sometimes it builds slowly and I feel it rising through my body, my heart beats faster, the pressure on my lungs makes me labor for breath... Then, other times, it comes on me all of a sudden, but every time, it ends the same, a mad cathartic explosion: anger, joy, confusion, banging my keyboard, kicking my desk, shouting out expletives, I fall from my chair laughing, shouting, and crying out to Darwin!...

Every time I go away from that experience I’m certain that that time, that LAST time, was my absolute last.

But it isn’t. I did it again today, and I know in my heart, I’ll do it again tomorrow.

Once, when it looked like they were going to take it away from me for good....

I wept.

I know it’s wrong, I don’t need you to tell me that. I know it’s a false sense of security, that my conquests in that fantasy world are meaningless, masturbatory, and an utter waste of my time...

As Darwin’s my witness, I will never go to Uncommon Descent again!

And this time, I mean it!

Since they banned me and deleted my comments that first day, making going there an even bigger waste of time, I’ll post my last act of this particular intellectual Onanism here.

Dembski asks: Does Darwinian Evolution Explain Antibiotic Resistance? About this article in Science:

Sampling the Antibiotic Resistome

Vanessa M. D’Costa,1 Katherine M. McGrann,1 Donald W. Hughes,2 Gerard D. Wright1*

Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.

Wow! I can’t believe he’d ask a question like this so soon. You’d think these guys would have learned that soil microorganisms are not to be messed with.

To answer Dembski’s rhetorical question: No. Of course “Darwinian” evolution can’t explain all instances of antibiotic resistance. Although it can explain many, some of which are cited in the very article you offer your readers.

Forty percent of resistant isolates were capable of inactivating the drug, which is

intriguing because clinically, the most prevalent mechanism of rifampin resistance is through point mutations in the target: RNA polymerase_s b subunit.)

For Darwin’s sake! Billy Dembski, you know Darwin didn’t know about DNA, you silly boy. <\batting eyelashes >

However, if we incorporate the knowledge that DNA is the genetic material, as we do in modern theories of evolution, and we understand the very first experiments that proved that DNA is the genetic material, we can synthesize a modern theory of evolution that easily explains the phenomenon of antibiotic resistance among microorganisms. Additionally, we can explain how and why this antibiotic resistance, once arisen anywhere in the microbial world, can be expected to find its way into our hospitals.

Soil on earth is teeming with life. From Behe’s cross examination in Dover we learn that one ton of soil contains 10 to the 16th prokaryotic organisms. That’s 150,000,000,000,000,000 bugs in the top six inches of my backyard alone!

Excuse me a moment.

(calling out: Kids! Wash your hands before supper!)

Sorry about that, where was I? Oh, life in the soil is tough! There’s a whole lot of competition and the food, what there is of it, is not all that great. To survive in the soil you’ve got to live off the land, literally, you’ve got to stake your claim and then you have to defend it. Only then can you settle down with... uh... yourself, and raise a little family of a few hundred million children/siblings. So what’s the best way to accomplish this? First, you’ve got to be willing to eat anything! Second, once you find anything to eat you’ve got to eat it before your 10 to the 16th greedy neighbors come and eat it first. One way to keep the greedy neighbors away is to poison the food, this will usually kill their appetite for the succulent carbon source you’ve discovered. Thing is you don't want to kill yourself or your offspring/siblings.


If you choose this tactic you need to pick a poison that won’t kill you and the little ones. Having a unique enzyme that can break down the poison is a great way to do that. And since, even with all the unnecessary obstacles the Intelligent Design Creationists throw in your way, it will only take the organisms living in the backyards of the 1000 houses in my neighborhood 1 year to evolve such an enzyme from scratch, according to Behe’s calculations, that seems like a good way to go. According to the paper in Science, that's a very popular choice:

We uncovered a wealth of inactivating enzymes

produced by soil bacteria. Of the 11

antibiotics screened, bacterial isolates were

detected that putatively metabolized 6 drugs

(Table 1), including rifampicin and Synercid.

Alternatively you could export the toxin from your cell, leaving even more in the food to drive the neighbors away. But what if it’s the Fourth of July? And your cousins from out of town, who you haven’t seen in like 60,000 generations, show up. Well, they aren’t going to be able to eat that smorgasboard of cellulose you’ve found unless they can break down the poison you put in it to keep the neighbors at bay. There are three ways you can help your relatives out:

1. Conjugation

2. Transformation

3. Transduction

These three mechanisms allow antibiotic resistance and other beneficial genes to be passed from bacterium to bacterium. They can even be passed between different bacterial species, spreading a gene that will confer a tremendous selective advantage on any bacterium that finds itself in an environment that’s inundated with antibiotics, like a hospital. Once the genes for antibiotic resistance are present in a hospital, they are extremely difficult to get rid of because of the many ways that those DNA sequencees can be taken up and transferred by multiple bacterial species. Once present, these genes are maintained in the population by, you guessed it, natural selection.

Don’t miss the comments at Uncommon Descent. Dave Scot trumpets the vindication of Lamarck, and Salvador Cordova, (Oh Sal! I’m gonna miss you the most.) Is helpful as always.

They even go off on a paper in PLoS Biology that reports the researchers were able to STOP evolution of resistance to the DNA damaging antibiotic Ciprofloxacin in E coli by preventing activation of the SOS DNA repair pathway.

My God, what a discovery! These actual scientists were able to stop evolution in the lab, therefore, it can’t happen anywhere! I got news for the UD guys, if you kill the entire population it ain’t gonna evolve squat. Just ask the Dodoes.

Update: On second thought, don't go read the thread at uncommon descent. Just go over to Aetiology and read all the great articles Tara has collected for the inaugural edition of her new blog Carnival Animalcules.

"Bacteria acquiring resistance to antibiotics is an active response. It supports descent with modification and vindicates Lamarck." -- Dave Scot




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Monday, February 06, 2006

Let’s Talk About Herpes.

by Pharma Bawd

This is a very strange case of blog-imitating-life-anticipated-by-advertising. Maybe advertisers really have learned how to read our minds to target advertising based on our thoughts. To tell you the truth, I expected it to come from Google first.

It’s all my fault really, I suggested we drop the Google Adsense ads in protest of Google agreeing to censor its search results for the Chinese government. (The only reason we have the ads is in hopes of generating enough revenue to pay for a hosted domain instead of using blogspot.) So we signed up with Crispads

Join the CrispAds Blog Advertising Network!
(Yes, we may get $.50 if you ad CrispAds to your blog through that referral.)

We posted the code into the template and our new ad appeared. Now, don’t take this or any subsequent posts as a suggestion that you click on the ad. I mean, click on it if you want, or not, depending on your interest in the advertisement itself. Don’t interpret this as me encouraging you to click the ad. Do so if you want, but not because I said to. Because I didn’t. I just draw attention to it because it’s strange. No, not the subject of the ad itself, although it is a subject that rarely comes up in most people’s casual conversations or blog posts. The odd thing is I’ve been preparing to write about Herpes.



Orac seems to have a lot of fun debunking “alternative” medicine treatments like chelation therapy for autism and the like. These posts are a valuable public service frankly. Even a well-educated laymen can’t be expected to recognize every sham product, snake oil, and patent medicine offered on the internet at first glance. So, I thought maybe I would get in on the act talking about some “alternative medicines” and their pharmaceutical counterparts. But which one? I thought about writing about some of the most highly “Googled” pharmaceuticals but those turn out to be things like Oxycodone, Xanex, Viagra, etc. and although any traffic to the blog generated by Google would be great, I think most of those people wouldn’t be too happy with what they found here. So I started thinking what would be a “good” thing to write about? Something that would actually be helpful and appreciated by the random people who wound up here through a Google search for instance, something that not every blogger and skeptic is already talking about, something that attracts a lot of products of dubious efficacy, something that affects a lot of people who might not have access to good information or may, out of desperation, be “willing to try anything.”

That’s when I thought of the perfect topic: Herpes. Herpes is a great subject for such a project because there is a huge unmet medical need for treatment, there are several legitimate effective treatments to control the outbreaks of Herpes, and there are numerous products that make dubious claims as to efficacy. Many are sold at high cost right here on the internet.

When I saw the new ad I was like:

“Oh no. If this is one of those alternative medicine treatments I’m gonna slam them, and there goes our advertising empire.

Again!

I’ll just have to register a domain name myself and be done with the whole advertising thing.”

But it wasn’t. It’s a very legitimate company with a legitimate product with proven effectiveness in FDA evaluated clinical trials. What a relief.

Now, although I do work in the pharmaceutical industry, I do not work for the company advertising on this site. (Although I may have worked for them in the past. It’s tough to keep straight with all the mergers. I once worked for three different companies in one day all without getting up from my desk!) And as for advertising revenues from the ad, one of the reasons we chose to go with Crispads is that they’ll pay out your earnings when they reach $5.00 instead of waiting until you have $100.00 with adsense. I probably would have retired before we ever got out first check from adsense. Hopefully with Crispads we’ll be able to register a domain and move away from blogspot just like the big boys in the blogosphere do. So don’t think I’m some blog-whore pimping for my advertisers. That’s my day job, and I make a lot more there than I ever will on the internet!

So, I’ll be doing a series of articles about Herpes. They’ll probably go something like this:

1. Revolutionary Cure For Herpes!!! Not.
This will be a Skeptical Pharmacy Friday post (a planned regular irregular feature with the lofty goal of one article every two weeks on, of all days, Friday.) I’ll take a look at one “alternative” treatment for Herpes this week and evaluate whether it’s worth the money or should we just get a prescription.

2. Molecular Biology and Treatment of Herpes.
I’ll discuss how the virus is transmitted, what it does inside the cell, and how current legitimate treatments to control the symptoms of Herpes function.

3. Alternative Medicine and Herpes.
This will be about truly alternative Herpes medicine, in that I will be talking about uses of the Herpes virus to treat other diseases through gene therapy.

I may do a post before Friday on the Herpes viruses just to provide a little background information prior to discussing treatments.


PhB


Update: Oh well. Looks like the ad changes periodically. There was an advertisement for famvir earlier. I'm still going ahead with the series. What are the odds of something like that happening by chance? I feel that this was a sign from the internet gods, I must obey their calling.

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Sunday, February 05, 2006

Metabolism of Evolution Information in the Blogosphere.

A post-doc in the Moment of Science Laboratories has worked out the biochemical pathway by which evolution information is metabolized by the Blogosphere.

Click here for the clickable image.



Oh, just in case anyone hasn't taken biochemistry.
And, no. We don't plan on determining blogospheric metabolism of evolution information to this level of detail.

Apologies to all those other great enzymes who participate in both catabolic and anabolic processes, who were not included. Future research will focus on other biochemical pathways by which the Blogosphere processes information.

Please create links to this URL as the large image will probably be moved in the future.

With regards to the Commissar. Imitation is the sincerest form of flattery.

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Friday, February 03, 2006

What's a safe following distance...



for Bison?

Posted to the Friday Ark.
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