Form and Function

I'm not very in tune with what's going on right now in the world of A&P, but I do know that in March of this year a whole bunch of Fort Collins residents were getting down to the business of making babies, because the birth situation for my doula partner and I for the end of December is starting to look really hairy.

You'll probably get other journal entries on this, but Time magazine announced a retail DNA test as its "Invention of the Year". The test, developed by a company called 23 and Me, is a personal DNA analysis that can give its purchasers information on the link between their genes and 90 traits and diseases. While affordable, personalized, genetic information may well be the wave of the future (this home saliva test costs $399), the 23 and Me test has its share of controversy, the most valid of which in my opinion is the quality of the information gained. Only 23 of the 90 traits or diseases tested for have enough science behind them to allow the company to develop "quantitative estimates and definitive explanations" of the results to their customers. Quite a few of these 23 conditions are medically significant (e.g. Parkinson's, Type II Diabetes) but the possibility of finding out whether I am likely to produce an excess of ear wax is not going to have me running for the checkbook. The remaining 68 genetic components tested for do not have enough scientific evidence behind them to confidently link the genetics to the potential resulting diseases or traits.

My assessment is that this type of test is the first step towards broadly used, highly personalized health care based on individual genetics but that we have a long way to go to bring the scientific basis for this kind of testing up to par.

I just cannot get on the bandwagon that says that we know what's going on with the relationship between diet, cholesterol, and heart disease to a level that allows us to dramatically reduce the rate of cardiac disease and resulting death in our population as a whole. The "Homeostatic Imbalance" entry on cholesterol levels on page 981 of the text seems like a good representation of how little we know. To rephrase its content:

1. We used the think that high total cholesterol levels and LDL to HDL ratios were the predictors of heart disease but now we think only LDL levels and other risk factors are better predictors.

2. Half of people with heart disease have "normal" (as defined by the AHA or whoever) cholesterol levels.

3. Many people with "bad" cholesterol levels do not have heart disease.

4. Still, statins are prescribed (supposedly only) to those people who a) are cardiac patients and b) have LDL levels over 130.

5. The number of people who meet those 2 criteria apparently number 10 million, because that's the number of people taking statins.

6. Everyone should change their diet, regardless of total cholesterol or HDL levels, despite the fact that only 15% of cholesterol in the body comes from diet, and that dietary restriction of cholesterol may result in deficiencies of other essential nutrients found in cholesterol-containing foods.

Good grief.

Because my husband and I are apparently old and boring liberals, or something of the sort, we listen to a lot of public radio podcasts and a couple weeks ago we caught a really interesting segment from Canadian public radio on the history of the HIV virus. The researcher, Dr. Michael Worobey, had come across two tissue samples from the Congo, circa 1960, with different strains of HIV. Based on the the amount of difference between the two strains and the known rate of mutation in the HIV virus, he was able to estimate that the two strains had differentiated from a single strain beginning around the year 1900. 1900! About 70 to 80 years before any knowledge of the virus really hit the worldwide scene.

Dr. Worobey believes that that virus was present (but still lethal) in widely dispersed populations in Africa for many decades before being recognized as a unique condition because those who succumb to the HIV virus die of opportunistic infections, primarily tuberculosis in many non-industrialized countries, and therefore deaths from HIV were not unlike the many other TB-related deaths. He also believes that the virus would not have grown to epidemic proportions had Africa's population remained dispersed in small tribes, but that the growth of city populations in the 1900s allowed HIV to spread very quickly, becoming the worldwide epidemic it is today.

The .mp3 of the interview with Dr. Worobey can be downloaded here.

Well I just realized that my last two entries are about TV. How scholarly of me. So here's a meatier one on the use of aluminum in vaccines.

Aluminum salts (aluminum hydroxide and aluminum phosphate, collectively called alum) are used in many vaccines as adjuvants - components that increase the vaccine's effectiveness when combined with other vaccine ingredients but do not independently create a targeted immune response to any particular disease. The use of adjuvants creates a stronger and longer-lasting vaccine-induced immune response for a given amount of antigen, thereby requiring less antigen per dose and decreasing production costs.

The modes by which aluminum enhances the immune response occur at the level of macrophage and T-cell function and include (not necessarily an exhaustive list, just what I could find online without feeling like I was researching a dissertation):
1. Increased uptake of antigen by the antigen-presenting cell¹.
2. Increase in antigen-induced T-cell proliferation¹.
3. Increased ability of macrophages to induce a antigen-specific memory response².

Questions arise over safety of aluminum use in vaccinations as excess levels of aluminum in the tissues can result if the kidneys are unable to secrete any excess, potentially resulting in impaired bone formation and impaired neurologic function. The FDA limits intravenous aluminum to no more than 4 to 5 micrograms per kilogram of body weight per day³ based on a 1997 study⁴ of premature infants indicating that these low levels are safe. Full-term infants and older children with good kidney function, receiving the aluminum intramuscularly, are likely able to tolerate greater amounts, but no studies meeting these criteria seem to exist⁵. Safe levels in vaccines are therefore not established, but current levels are very high in relation to the 4 to 5 micrograms per kilogram of body weight recommendation for IV medications.

For the sake of an example, amounts for the vaccines on the AAP schedule for the 2 month visit are given here⁵ (by brand, aluminum amount in micrograms):


HIB
- PedVaxHIB 225
- all other 0

Pc
- Prevnar 125

DTaP
- Tripedia 170
- Daptacel 330
- Infanrix 625

Rotovirus
- all brands 0

Polio
- Ipol 0

So an average infant at 2 months old, weighing about 4.5 kilos, could receive no more than 22.5 micrograms of aluminum intravenously as per the FDA (based on the AAP study), but would receive between 295 and 975 micrograms at their well-baby visit assuming all AAP-recommended vaccines are given.

Resources

1. Mannhalter, J. W., H. O. Neychev, G. J. Zlabinger, R. Ahmad, and M. M. Eibl. 1985. Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation. Clin. Exp. Immunol. 61:143-151.

2. Romaniol, A.C., et al. Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine. 2004 Aug 13;22(23-24):3127-35.

3. http://www.fda.gov/ohrms/dockets/98fr/03-6227.html

4. Aluminum toxicity in infants and children, Committee on Nutrition, American Academy of Pediatrics, Pediatrics 1996; 97:413-416.

5. Sears, Robert W. The Vaccine Book. New York: Little, Brown and Company, 2007.

HBO has a new series out called True Blood about vampires able to make themselves public after a synthetic blood is developed by the Japanese that the vampires can consume in lieu of human blood. The plot revolves around Sookie, a human telepath, and her developing relationship with a vampire named Bill. When Sookie demands Bill tell her how he can be literally dead but seemingly alive, he tells her it's magic. When she scoffs he goes on to say:

"You think it's not magic that keeps you alive? Just 'cause you understand the mechanics of how something works doesn't make it any less of a miracle. Which is just another word for magic."

That's kind of how I've felt about taking A&P. No matter how much we know there will always be more that we have yet to lean. And the more we know the more we can wonder at the staggering complexity of what is.

There's a new show on TV called "The Drs." and the image above is from their set. I only watched a few minutes before being annoyed enough by several things to turn it off, but one of the most annoying is their set. There are some major problems with that attempt at an EKG reading along the front of the desk. That's one jacked-up P-wave and I bet it's hard to live without ventricular repolarization, eh?