Saturday, September 20, 2014

The $30 Billion Ice Bucket Challenge

This past summer 3 million people spontaneously dumped buckets of ice water on their heads and/or donated their hard earned cash to the ALS Association to support research.  What on earth would provoke this synchronized advent of charity, without warning?  The answer to that question is far beyond the scope of this blog and lies somewhere wrapped up in the mysteries of human behavior, perhaps beyond human explanation.  But it certainly had a lot to do with social media. 

And it’s a good thing. 

Although the origins of the ice bucket challenge phenomenon are mysterious, the outcome so far has been an additional $100 million dollars raised to fund efforts to counter Lou Gehrig’s disease (ALS).  Faith in humanity?  Restored.

Mysteries aside, I was really excited to see so many people taking an interest in supporting medical research, and recognizing it as a valuable cause worthy of uniting us.  ALS is a terrible disease without a cure, and those who are trying to understand it and treat it need all the help they can get.  But, it is only one of many problems that medical researchers are working on, and incidentally funding for research must be spread around far and wide.

So, where does funding for research on diseases like Lou Gehrig’s come from when people aren’t turning buckets of ice water upon themselves and posting the video on youtube?  Well, in the United States most of the money comes from the National Institutes of Health (NIH), which is part of the Department of Health and Human Services.  The NIH is actually the “largest source of funding for medical research in the world”. 

And where does the NIH get the money from?  It comes from YOU (assuming you are a tax-paying U.S. citizen, of course). 

This year, the NIH was given a budget of $30,151,000,000 (that’s 30 bilion).  For 2015, NIH Director Francis Collins has requested from congress a 0.7% increase (the current inflation rate is 1.7%, FYI).  To put this in perspective, the budget for the Department of Defense in 2014 was 526 billion, and the budget for the Department of Labor was 12 billion. 

30 billion dollars is a lot of lettuce – for one person.  But for the NIH, this money gets sliced and diced many ways.  At least 237 ways, to be precise.  That is the number of disease research categories where the money is distributed.  You can see the full list here, but these are the most salient targets of funding: 

1.       Clinical Research: $10,928,000,000 (10.9 billion)
2.       Genetics: $7,330,000,000 (7.3 billion)
3.       Prevention: $6,853,000,000 (6.8 billion)
4.       Biotechnology: $5,845,000,000 (5.8 billion)
5.       Neurosciences: $5,477,000,000 (5.4 billion)
6.       Cancer: $5,418,000,000 (5.4 billion)
7.       Infectious Diseases: $5,015,000,000 (5.0 billion)

And somewhere much further down the list, you would find Lou Gehrig’s Disease (ALS), which received a $40,000,000 (40 million) slice of the pie.  Note that many of these categories overlap, so the sum is well above 30 billion.

The actual ‘research’ is for the most part done by thousands of grad students and post-docs who are holed up in labs with pipettes away at universities and research institutes across the country.  These are people who work hard, many are passionate about what they do, and most are obviously not in it for the money.

But over the years, federal spending on medical research has not increased at the same rate as inflation.  This makes it harder and harder to be a research scientist in the United States.

As a scientist, in order to receive any of this funding in the form of a grant, you must first write up a long and detailed grant proposal that explains exactly how much you need, how it will be spent, and how long you will need it for.  After going through a very competitive review process, only about 17% of the proposals will currently get the stamp of approval from the NIH.  The other 83% go in the rejected bin. 

It was not always so competitive.  The success rate was once as high as 45% in the mid-1970’s, and even 30% at the turn of the millennium.  This is illustrated in the chart here below, that I made from data posted on the NIH website.

The Center for American Progress has produced two graphical illustrations of the decline of NIH funding: one as a percentage of GDP, and one with values adjusted for inflation.  You can see them here.

Diminishing budget or not, research and development is by nature not a financially profitable venture.  But perhaps the payoff can be measured in terms of life expectancy rather than dollars.  Consider that the average American lifespan from birth is currently about 78.5 years, an increase of 8.4 years from 1966 in spite of the introduction of HIV, the increasing ubiquity of cancer, and the rise of fast food during the meantime.

In conclusion, the most important thing to understand from all of this is that medical research is important, it is difficult to do, it is expensive, it is not usually financially profitable, but it is all for your benefit.  The research that results from it will hopefully someday find its way back to you down the road when you need it.  It is a tremendous resource to us, one that perhaps we take for granted too often.

And so next time you file your federal income taxes, feel free to at least splash a few drops of cold water on your face.  Our 30 billion dollar ice bucket challenge has collectively been accepted.

Wednesday, August 20, 2014

Blog Updates: From Antarctica to Dr. Oz

Although my posts are less frequent these days, I do intend to keep this blog going when I’m not otherwise occupied in the lab. In the last few months I have noticed some new research developments related to things I have posted on previously.   And so here are some updates on past blog articles, beginning with my very first post about the MERS virus: the topic nearest and dearest to my own research.

Back in September 2012, the World Health Organization (WHO) announced the emergence of what is now known as the MERS virus (or, Middle Eastern Respiratory Syndrome virus).  Two years have now passed, and the MERS virus has spread from the Arabian Peninsula to a short list of countries.  It has even found its way as far as the U.S., as reported this past May.

In the media, the MERS virus is sometimes referred to as the ‘SARS-like virus’.  This is because the MERS and SARS virus are both classified in a virus family called coronaviruses – a group of about 30 related viruses with genetic and physical commonalities that infect various mammals and birds.  As with the SARS virus of a decade ago, there has been some discussion about which animal the newly identified MERS virus originated from before it leaped into the human population.  A study was just recently published that pins the blame for MERS on camels (I’m sure they didn’t mean to do it).

The study looked at a group of camels infected with the MERS virus and their caretaker, who also had MERS.  Tests showed that the MERS virus found in the camels was genetically identical to the MERS virus found in the person taking care of them.  Also, the virus tested positive in samples of air taken from the barn where the camels and the owner resided.  And so the implications of this study are that:

1.       The virus can be transmitted to humans from camels, and
2.      The transmission can potentially occur without physical contact (although like a cold or flu virus, it’s always easier to get if someone is sneezing or slobbering on you).

Previous observations also supported this hypothesis that camels may be transmitting the virus to humans. So how many cases of MERS have there been so far?

The most recent report from the WHO is that in 2 years there have been 837 laboratory confirmed cases of MERS, with 291 deaths resulting (35% death rate, yikes!).  So, how does this compare to SARS – the cousin of MERS that showed up 10 years ago that we never hear from anymore? 

SARS by comparison had at least 8096 cases confirmed by the WHO, with 774 deaths (close to 10% death rate).  Unlike MERS, most SARS cases occurred soon after it was first identified in February of 2003.  Within a year after the initial outbreak, it was essentially gone.  Two years later now with the MERS virus on the other hand, and we continue to see a slow trickle of new cases.

Most of these cases seem to be restricted to Arabian Penninsula – kind of like how SARS transmission was mostly restricted to China

So in a nutshell, SARS was more widespread, but MERS so far has a higher fatality rate.  Fortunately, there is much we learned about quarantine, containment, and communication from the SARS epidemic that helped prepare us to deal with MERS.  Hopefully, it will soon go the way of SARS.
A notice I came across at an airport during international travel in 2013.

In January 2013 a team of mostly US scientists reported that they had drilled into a sub-glacial lake in Antarctica, and found signs of life.

Now, in a follow up report published in an August 2014 issue of the journal Nature, the scientists report more specifically on what that life is.  This team drilled through 800 meters of glacier ice to get into Lake Whillans and collect a sample of the water trapped beneath.  They reported finding 130,000 cells of bacteria or archaea per 1 milliliter (or, 1 cubic centimeter) of lake water.  And in these samples, there appears to be about 4,000 different species represented.

This is interesting to scientists because Lake Whillans has been completely sealed under ice for an estimated 120,000 years (perhaps up to 1 million years).  That means no sunlight, and so there is no photosynthesis going on down there to drive the food chain like it does on the rest of the planet.

This discovery at Lake Whillans will open up a lot of discussion about how those microorganisms got there to begin with, what they are feeding on, and what life might be like if it exists on other frozen planets or moons in our solar system with conditions similar to Antarctica.

In March of 2013, an announcement was made that a Mississippi baby who contracted HIV through birth, appeared to no longer carry the infection after an unorthodox aggressive early treatment.  Although researchers were cautious not to overplay what was then an early observation, it appears now unfortunately that we hoped too soon. 

The child, now 4 years of age, has once again tested positive for the virus following a 27-month hiatus from treatments.  This June 2014 announcement was discussed the following month at the 20th International AIDS Conference in Melbourne, Australia (the same conference that a plane full of AIDS researchers on Malaysian Airlines flight MH17 was en route to before tragic circumstances dictated otherwise).

This finding is obviously a disappointment on a rational and emotional level for those involved in the trials.  Disappointment is common in research, but it is not necessarily synonymous with discouragement. 

Often, negative results can be viewed as part of the feedback loop that shapes the direction of future experiments and studies, which ultimately bring you closer to the desired outcome.  In this case, it is likely that future research will look more closely at where in the body of this child the HIV virus was able to hide and evade treatment, and why it apparently waited 27 months to continue its life cycle.

In recent months it seems that there has been somewhat of a public backlash against the idea that vaccines cause autism (at least in my facebook newsfeed, anyways).  Unfortunately, a change in current beliefs will not immediately undo the consequences of misinformed decisions of the past.  And so it follows that there has been a recent resurgence in vaccine preventable diseases. 

Whooping cough has seen a steady rise in cases.  California has particularly been affected and has already dealt with a handful of infant deaths in recent years as the number of cases reported approaches pre-vaccine levels.  2014 has so far also seen a huge spike in the number of measles cases, as reported by the CDC.  This is reportedly caused in large part by a few Americans choosing not to vaccinate.

Meanwhile, studies continue to show that there is no cause/effect relationship between vaccines and autism.  In June of this year, a meta-analysis of 10 separate peer-reviewed studies reported in various journals between 2002 and 2012 was published in the journal Vaccine.  The total number of children included in all the studies was 1,266,407 (compared to the 12 in Wakefield’s infamous 1998 report).  Researchers summarized data from all studies, averaged it, and concluded the following:

No relationship between vaccination and autism or autism spectrum disorders (ASD).
No relationship between MMR vaccine and autism or ASD.
No relationship between mercury and autism or ASD.
No relationship between thimerosal and autism or ASD.

So let it be written, so let it be done.

In 2013 researchers reported the discovery of what they called Pandoravirus (Don’t worry, it infects amoebas and not people).  Although it is a virus, it is comparable to smaller bacteria both in terms of genetic complexity as well as size.  It was the largerst virus known to man….until this year.

The same researchers reported in March the discovery of another ginormous virus, now even bigger than that freakish Pandoravirus.  They call it ‘Pithovirus’.  While this Pithovirus is 1.5 micrometers in diameter compared to 1.0 micrometers for Pandoravirus, it has far fewer genes (only 467 compared to 2556 in Pandoravirus). 

Unlike other large viruses discovered in the past decade, Pithovirus was not extracted from a living water or sediment sample.  Instead, it was resurrected from a soil sample that had been frozen in Siberia for the last 30,000 years until scientists extracted it for study.  This discovery adds to the debates about whether or not viruses are ‘living’ or at least undead; and which came first, the virus or the cell?

As noted, the dietary supplement industry is at liberty to make claims that their products can perform great miracles and magic wonders.  Such supernatural product testimonials are also a regular occurrence on Dr. Oz’s daytime show, in spite of the dearth of scientific evidence to support even modest assertions. 

In June this year, Dr. Mehmet Oz appeared before U.S. Senate to be questioned by Senator Claire McCaskill (D-Missouri), who chairs the senate consumer protection sub-committee.  The issue at hand was weight loss supplements that may have the side effects of false hope and throwing your money away.  While the use of “flowery or passionate” rhetoric (as described by Dr. Oz) may boost ratings in the world of daytime television, it will also likely invite criticism and mockery everywhere else.

Wednesday, February 26, 2014

Of Supplements, Vitamins, Placebos, and Kale

The 32 billion dollar vitamin and supplement industry has been booming during the last decade.  Financial prospects continue to look bright, as manufacturers bank on the axiom that “prevention is the best medicine”.  However, recently published scientific research has not been as kind to the industry as profits were.

Herbal Supplements
Herbal supplements are usually some form of isolated plant extract in a pill.  But an October 2013 study published by the journal BioMed Central Medicine revealed that what is inside the pill is not always the same as what is written on the outside label.

The method of analysis used for this study is known as DNA barcoding, which involves sequencing a certain fraction of a genome from an unknown biological sample that is unique for every organism.  Like a UPC symbol on a given product, a species can be identified by this small segment of its genome once the DNA sequence is determined.

In the 2013 study, 44 different samples of herbal supplements were tested, from 12 different manufacturers.  Only 48% of the supplements tested were proven to contain the herb that was listed on the label.  Obviously, a consumer would expect their odds of getting what they pay for to be better than the average coin toss. 

Furthermore, the analysis identified plant species that were not listed on the product label in 59% of the supplements.  Finding unlisted filler or contamination in a product is sloppy at best, and harmful at worst – and the latter was more than just hypothetical in several cases. 

Of the 12 manufacturers included in the study, only 2 were found to be innocent of mislabeling any of their products.  These study results were noted in the New York Times, among other mainstream news outlets.

Vitamin Supplements
From Fred Flinstone to Centrum Silver, we are told that we need to take our daily vitamins.  But the December 17 2013 issue of the highly regarded journal, Annals of Internal Medicine was not compliant.  Three separate publications in this issue challenged the expectations of the 10 million strong that have now grown, and continue to take their vitamins.

The first article was a summarization of the results from several studies released between 2005 and 2013 that examined the health effects of vitamin supplements on older individuals with normal diets.  With regards to cancer, cardiovascular disease, and mortality, no significant benefit could be observed among those who took vitamin supplements.  The total sample size of participants numbered tens of thousands of people in the sum of all the studies. 

The second study included a group of 5,947 men over the age of 65, and was aimed at determining if multivitamins boost cognitive abilities.  In standard form, the group was split, half were given a multivitamin, and the other half was given a placebo in a double-blind fashion.   No significant difference was noted between the two groups over the 12 year period of the study. 

The third study examined 1,708 individuals over the age of 50 who had previously suffered a heart attack.  Again the group was divided into one half that received placebos, and one half that received a multivitamin; administered in the standard double-blind format.  No significant reduction in cardiovascular dysfunction could be observed in the multivitamin group compared to the placebo group over the remaining life years of the participants.  This conclusion supported the findings of several earlier studies that were reviewed in the same journal earlier in the year. 

A panel of doctors and scientists including the editorial staff of the journal made special note of these three studies in an accompanying editorial.  In summary, they stated:

“Although available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population, we believe that the case is closed— supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful. These vitamins should not be used for chronic disease prevention. Enough is enough.”

The U.S. Department of Agriculture has previously made a similar assertion.  In the USDA’s 2010 Dietary Guidelines Advisory Committee Report, the following conclusion was stated:

“A daily multivitamin/mineral supplement does not offer health benefits to healthy Americans. Individual mineral/vitamin supplements can benefit some population groups with known deficiencies, such as calcium and vitamin D supplements to reduce risk of osteoporosis or iron supplements among those with deficient iron intakes. However, in some settings, mineral/vitamin supplements have been associated with harmful effects and should be pursued cautiously.” (A5 – A6)

And most recently the U.S. Preventive Services Task Force (USPSTF) published their two cents:

“The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (except β-carotene and vitamin E) for the prevention of cardiovascular disease or cancer.  The USPSTF recommends against the use of β-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer.”

(β-carotene is metabolized in the body to form Vitamin A.)

This February 25, 2014 USPSTF report also pointed out that their recommendations are supported by independent studies conducted by the National Institutes of Health, The Academy of Nutrition and Dietetics, The American Cancer Society, and the The American Heart Association.

In spite of these studies, some people of course do remain unconvinced.  In fact, if the great biochemist Linus Pauling were alive today, it is probable that he would be numbered among them.

The Placebo
Although supplements that have been substituted with filler are nothing more than placebos at best, it is possible that those who take them can still see a benefit.  This is important to the manufacturers, because product sales are very dependent on testimonials.

In reality, the ‘placebo effect’ is not entirely an imaginary thing.  Psychology is often a component of, or at least an influence in physiology.  For instance, one study published in the journal Science showed decreased brain activity in regions of the brain where pain is registered when placebos were administered to treat a controlled pain stimulus.  Follow up studies revealed a physiological explanation: opioid production. 

In other words, the brain can be persuaded make its own feel-good medicine with the right stimulus.  The results were surprising, even to those conducting the studies.  The caveat is that such placebo effects cannot be sustained over a long period of time.

Hence, the inclusion of placebos in clinical trials – the kind that pharmaceuticals must undergo before being approved by the Food and Drug Administration.  FDA approval ensures that products are not only effective, but also safe to a determined limit and properly labeled.  Incidentally, because pharmaceuticals have been scientifically proven to induce a physiological response beyond the placebo effect, they also require a prescription.

According to the Dietary Supplement Health and Education Act of 1994, products advertised as supplements do not require this FDA approval in order to be marketed.  And so although nutritional supplement manufacturers will be held accountable if product quality is lacking in integrity, there is no mechanism of regulation to stop them from manufacturing and marketing a compromised product until and unless they get caught.  And in the meantime, they are at liberty to make unsubstantiated claims regarding the effectiveness of their products as long as they add the following asterisk:

 “*This statement has not been evaluated by FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.” 

Nature’s Vitamins and Supplements
Becoming reliant on taking pills to supplement nutrients that you assume are missing from your diet is perhaps indicative of a deeper concern: your diet.  And whether you realize it or not, some of your diet is probably already “fortified” with vitamins and minerals if you are eating processed foods (note the side of a box of Lucky Charms, for instance).

Perhaps it would be prudent to skip the supplements and go straight to the foods that will give you those important nutrients, along with natural combinations of fiber, protein, fats, and starches in proportions that the human body has been accustomed to digesting for thousands of years. 

Since you won’t see advertisements on TV or in magazines for carrots and spinach with superlative claims, here is a table of real data instead.  The data is taken from the USDA National Nutrient Database, where you can find similar numbers for over 8000 other food items.

The table here shows how much of each nutrient you will find in a 100 gram sample of the following common produce items:

Although some items may be more or less likely to be consumed in 100 gram quantities, this is the arbitrary value I chose for the sake of comparison because it is a realistic serving size for most items.  A small banana, for instance, is about 100 grams.  Among other things, you’ll note that Kale really is highly nutritious – even if some people think that it is trendy and tastes like bug spray.

On the top is shown the U.S. Recommended Dietary Allowances for men and women of a variety of nutrients – an estimation of the average daily amount required to maintain health.  It will be obvious that man should not live on bananas alone, or any other food item.  Variety is important here.  And plant life alone may not sufficiently provide what can be more easily obtained from meats, such as iron and vitamin B12.

It is worth noting that there are also maximum recommended amounts for some nutrients.  Consider that your body can quickly expel excess amounts of water-soluble vitamins when you pee, but the fat-soluble vitamins are stored away in tissue for future use.  And so consuming an unnatural amount of the fat-soluble vitamins (A, D, E, and K) can lead to a toxic buildup because your body has no quick way to clear them out.

Until the nutritional supplement industry is held to a higher standard, the consumer is left with the responsibility to follow current research from legitimate sources if they want quality assurance with their product purchases.  And although there is a mix of evidence beyond the realm of pseudoscience that shows the benefits of certain nutritional supplements, the consumer is also left with the responsibility to sort this out on their own. 

Alternatively, if you are an otherwise healthy adult and choose to follow Michael Pollan’s mantra ‘Eat Food. Not too much. Mostly plants.’, and go for a jog occasionally, then the only thing you probably need to swallow is a chill pill.