Journal of Negative Results

Oops, Another Research Error

2012-02-08T11:10:00.000-08:00

For most of my life, I have heard all about how evil men are because we're polluting the planet. Ok, so many of us aren't very conscientious about where we put our waste, but then again neither are the Canadian geese that used to defecate EVERYWHERE at my alma mater. However, they talk about these doomsday prophecies and make movies about their predictions when many of their conclusions are founded in bad science.

At the beginning of each semester, I cover the Scientific Method with my students. I point out the pitfalls and problems in an effort to help them pay better attention to scientists, especially as they start prescribing pills produced by piss-poor projects. Lo and behold, today, an article appears less than a day after I discussed this with a colleague about how the polar ice is melting 30% less quickly than projected. The key phrase in this article is as follows:

previous teams had to measure ice loss at "a few easily accessible glaciers" and then extrapolate it to the 200,000 glaciers worldwide

They extrapolated a few to hundreds of thousands. A few technically means three, which is the equivalent of looking at everyone in the city of Linz Austria and saying they are representative of everyone currently living on the planet. This is why some people die from drugs, because everyone reacts differently.

What concerns me is whether the few they analyzed were truly representative of the whole. If they looked at a few outliers, then they will be way off. What made the other glaciers inaccessible? Weather? Money? Laziness of the researchers? Government policy that refused access? There are too many variables to even evaluate that well. They would have been best served to conclude that the data supported a certain level of ice loss in the area surveyed.

I may have mentioned this before, but we did a lot of work with students and standard curves. Intentionally, we gave them an unknown with a concentration outside the standard curve hoping that they would make an error and extrapolate. Outside the curve, you cannot be sure that the behavior remains the same. Even these researchers were smart enough to confess that "it's not clear how far into the future you can project" because too many things affect other things. I find it funny how they claim everything and everyone is related, that we should coexist, etc., and then they blame human activity with which they happen to disagree as a cause for everything. Who knows what the future will bring? Maybe it will bring meteors or Martians or more of the same. Who can say? They like to talk as if they know for sure, and I find that odd.

What 'Might' Be

2011-06-02T18:04:00.000-07:00

This is an article from another blogger I read, talking about the problem with conclusions that leads to bad science and worse journalism.

In case you live under a rock and missed it, the World Health Organization recently announced that cell phones "may possibly" cause cancer.

Now, I'm neither a researcher or statistician, and personally think the jury is still out on this one. I'm not going to take sides.

But here is what I am pissed off about: Notice that the story said "may possibly" cause cancer. But the way we think, it somehow becomes "does cause cancer", and so we panic, and hold our cell phones a yard from our head, and scream into them (that's gonna make driving while talking into one a helluva a lot safer, huh?).

"I can't hear you, Dave, but at least I may possibly not get cancer."

In my opinion a lot of the way this stuff gets played up as the top story on news outlets is just bullshit. It's no different than if I put "SEXXX" in screaming letters at the top of this post. It sure as hell would get your attention, and snag a few search engines, but the post has little, if anything, to do with sex (unless you're into setting the phone on vibrate and...)

This is the nightmare of medical research in the lay press. Let's say Dr. Hodgkin does some research on rat ovarian cells. He finds that in 25% of rats with ovarian cancer, there is a gene that may be able to stop cancer spread.

So he gets published in the journal Genetics Research and Lab Decor. A hungry reporter finds the article, and sees a great way to sell papers with a story on how ovarian cancer has been cured!

Now this isn't what Dr. Hodgkin said. His research had a 25% success rate in curing mice with a certain type of ovarian cancer. The most he might say is that someday this might lead to new methods of treating some types human ovarian cancer.

But, of course, nobody gives a shit about mice with cancer. A headline saying "25% Of Mice with Ovarian Cancer May Someday be Cured!" wouldn't get anyone's attention. But if you make a huge leap of illogic, extrapolate it to humans, and put up "CURE FOR OVARIAN CANCER NEAR!", it will sell newspapers and draw readers, no matter how far off from the truth it is.

For those of you who remember, in the mid-80's there was a HUGE media circus about how Interleukin-2 was THE cure for cancer (an absurdity, if you think about it, considering that cancer isn't even a single disease- it's hundreds). Major news magazines and TV networks ran stories about it. It made the front page... and that was about it. Not to take anything away from Interleukin-2. It eventually did settle down and find a place in malignancy treatment. But was it the miracle breakthrough that it got played up as? Not even close.

By the same token, in the 1970's EVERYONE knew Saccharin caused cancer. So it got a big black box on every product that contained it. And after several years it was quietly found that it DIDN'T. Of course, when the second story came out it was relegated to the back page, and people didn't notice when the warning labels disappeared. Because it's more interesting to scare people, or give them false hope, than to reassure them.

Certainly there are plenty of things that are clearly proven to cause cancer: cigarettes, for example. But hell, at this point we all know that. So it's not going to get attention. But put up a headline about something we believe is harmless (unless you're trying to pass a cell phone talker on the freeway) and it will get a lot of readers.

So let's get back to the cell phones.

What really grates my crank is the use of "may possibly" or "possibly" or "may be linked to..." that the articles about this are so full of. NOT "does" or "doesn't" but simply different variations on ambiguity which, while getting your attention, DON'T REALLY SAY A FUCKING THING!!!

Look at it this way. "Cell phone use may possibly cause cancer". How is that different from "cell phone use may or may not cause cancer"? But if the second sentence was used, you'd say "No shit, Sherlock" and skip the article.

To take it a step further, let's use the "may possibly" phrase in other circumstances, and see how definitive that sounds:

"Mrs. Smith, you may possibly be pregnant."

"Dave, you may possibly be fired."

"You're going to see Dr. Grumpy? I heard he may possibly be competent."

"The Grumpyville Faceplants may possibly win the Super Bowl."

"Congrats, Cindy. You may possibly be getting a promotion."

"Dude! There may possibly be beer and girls at the party!"

"OMG Buffy! Your new boyfriend may possibly be HAWT!"

"KIDS! You may possibly be punished if you don't clean up your damn rooms!"

Doesn't give you a lot of confidence, or clarity, does it?

So next time you see a medical research news story, think about how accurate it may possibly be.

PETPEAVES

2011-05-12T11:20:00.002-07:00

Every day during graduate school, I would park at the agriculture experiment station and walk the half mile or so to the Agriculture Building where I spent most of my days. Just across the street from the building where I worked was an attorney's office, and on the back of one of the cars was a bumper sticker I noticed every day and remember very vividly still now. It said, "Thou shalt not kill: go vegetarian".

I have often marveled on the irony of this statement. Here I was, a biochemistry major, studying in the agriculture college under the life sciences program, and this attorney thought plants weren't alive. Yes, I know plants don't seem to have feelings, but like I told some students a month or so ago, even they have blood. You just don't recognize it even though you lather your waffles in it at breakfast. It's called 'syrup'. The students were immediately grossed out by the notion.

For most of my life, I have been fully aware that plants are alive. If I am wrong, then everything I learned in college was a complete lie. I think what we really need in this nation is PETPEAVES: People for the Ethical Treatment of Plants Eaten After Violent Extraction from Soil. Plants cannot speak for themselves because they have no mouths or defend themselves because their weapons are not terribly useful against a predator with eyes (except for some cacti which are very good at dissauding any attempt at predation). Nobody represents their interests, and apparently some lawyers are active in the campaign against their rights. Without plants, all animal life on earth would cease.

Save the plants. Save yourselves. Join PETPEAVES.

**This post is mostly tongue in cheek, just for your information, but all the details are true as well as I understand truth**

Ripeness and Refractometers

2011-04-14T14:55:00.000-07:00

One of our anatomy professors just informed me that he passed on something I taught him. While testing the specific gravity of their urine, a student asked him if a refractometer was useful for anything else. He remembered a conversation we had and pulled up a picture of someone using one in the wine industry, which is basically what I did in graduate school.

Refractometers can be used to tell ripeness of fruit. Indeed, I sometimes will use one at the market to test produce. Where I live there are a lot of foreign markets with produce of initially dubious value. I don't really know why they are selling 5kg of limes for $1. Are they bad? Did they buy too many? If I ask them in Italian, will they be able to explain it to me in Spanish? I just trust the refractometer.

Now, imagine what they see. A bearded male of Saxon ancestry pulls a refractometer and some plastic pasteur pipettes from his jacket. He squirts some juice on this lightsaber-looking thing and looks into it as he points it towards the light. Some fruit, he takes. Others he passes. It must look like something out of science fiction to them.

Well, it certainly is science. Using a refractometer to measure the Brix ratio (one degree approximates 1% sugar content and is relatively reliable as an indicator of sweetness), and pH paper to measure acids, one can tell almost exactly when fruit is at the perfect ripeness. As fruits mature, the sugars cease to be reducing, and the total amount of acids diminishes while sugars accumulate in the fruit. At an optimum range of sugar to acid ratio, a fruit is ripe and ready not only for harvest but for consumption. Delicious!

As a practical matter, since you know I like practical science, this is a putative business model. You buy fruit if you live in the west hemisphere only once a week or more. You hope it will last on the counter until you need it and then only as much as you need to be ripe when you need it. With a refractometer, you could establish fruit in bins at various degrees of ripeness and classify fruit as 'ready now', 'ready within the week' and 'ready in more than a week' and thereby assist shoppers in planning their consumption without waste. Would it sell? I don't know. Could it? Most definitely. We have all seen people smelling mellons and scouring over berries, touching them all. No need for that. Science to the rescue!

You too could be like the wineries and know exactly when your fruits are ripe. Wouldn't that be nice?

For What Your Research Dollar Pays

2011-01-20T12:49:00.000-08:00

I try to keep abreast when time permits at work with advancements in medicine and research. Partly, this was spurred because one of our electricians came to ask me about some stuff I did in graduate school. I was kind of taken aback, but not as much as I was about how completely unnewsworthy this research was.

According to the Journal "Alcoholism: Clinical and Experimental Research" people who tailgate are more likely to get drunk than people who do not. Did they really need a study for that? Who got a PhD for this?

Don't even get me started on their 'scientific method'...

We conducted BAC tests of 362 adult attendees following 13 baseball games and three football games. We ran multivariate analyses to obtain factors associated with the risk of having a higher BAC.

Your tax dollars at work help some kid get an advanced degree. I could have told you this without collecting any data, but it's nice to know I'm right.

Bad Premise=Bad Science

2011-01-07T10:29:00.000-08:00

I am not honestly surprised to read that the study linking autism to MMR vaccines is a fraud. The assumption is often made that the subjects are 'normal' when that is either a complete fabrication or when what we assume normal to be is far from it. Face it, there are really no 'normal' people. They might be 'normal' for something, but that's not necessarily the case.

I have seen a lot of people exclude outliers because they're too far from the normal. They might be the most interesting subjects.

When I worked in industry briefly, we had this 'standard' that we used in our R&D work. This person was supposedly normal, but the sample was for Factor V bloodwork, not for Trisomy 21. We assumed that the person was normal, but we really don't know.

In this case, the authors of the study purposely deceived people and used subjects who were not 'normal'. Besides that, they only studied 12 children? Please.

Don't accept their premise. It is useless to theorize until you collect the facts. Otherwise, you start bending the facts to match the premise, which is basically the underlying fault of all scientific endeavors of which I am aware. They start with a premise and then look for evidence. Too bad. People plan their lives around these findings, many of which prove false, and so we alter things that were just fine before we began.

Conventional Wisdom

2011-01-04T14:16:00.000-08:00

I haven't written on here in a while, and it's really mostly a placeholder to prove that I came up with the idea first in case someone else tries to copy my idea.

However, I was reminded today of something from graduate school, and so I hearby invite you to join me as a member of the ASPCDSF: the American Society for Prevention of Cruelty to Dead Salad Fixings.

Across the street in graduate school was a small lawyers office. One of these lawyers had a bumper sticker on the back of his car that said, "Thou shalt not kill- go vegetarian."

If vegetables are not alive, then why are agriculture and plant physiology and similar majors considered part of Biology, the Life Science?

The lawyer probably saw himself as a crusader. I don't buy the premise. Lettuce is alive too, at least until I transfer it to the saline resistance chamber...

Marvel: Human Brains

2010-04-01T10:16:00.001-07:00

This is an original article today from a colleague that I wish to repost here.

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It ain't much to look at.

Two, maybe three pounds of grayish-white goop. It's not even solid in a living person. More like Jello that floats around in it's vault.

But it's amazing. From that sloppy goop has come remarkable stuff. It's sent a robot to land on a moon of Saturn. It's explored the bottom of our deepest oceans. Built the Taj Mahal. The Great Wall of China. Painted the Mona Lisa.

Go listen to the remarkable Bach's "Toccata and Fugue in D minor". Not just the famous opening 30 seconds or so, but the whole 9-10 minute thing. That all came from the goop, long before it was heard or played on an instrument, it was just a series of electric signals jumping from nerve to nerve. The piece is over 300 years old. The mind that created it has been dead for over 250 years. And humans will likely be listening to it long after my great-great-great-grandchildren are dust.

The soul is there. The heart is amazing, but for all our romantic beliefs about it, who we really are is floating around in the goop. It's where hate, love, and everything in between comes from.

It's capable of terrible evil, such as the Holocaust, and remarkable good. Look at the outpouring of altruism that follows disasters. I love my dogs, but if something bad happens to a dog on the next street, they're not going to care. Yet the goop wants to help people who we've never met and have no direct impact on our own lives

My regular readers know I'm interested in maritime history. Why? I have no idea. It's just been a subject I've loved as long as I can remember. I've never been in the navy, or lived near the ocean. The family military history consists of grandparents who served in the army, but never were sent overseas. I can only assume there is some particular molecular structure in my goop that makes me interested in it. Or that made me want to treat other people's goop for a living.

Twin and biological studies have shown that most of who we are is how we came here. Yes, life experiences and background count for something, but the goop is most of it. People with conservative beliefs raise kids who turn out to be liberals, and vice versa, now matter how hard they may try to pass on their beliefs.

Coke vs. Pepsi. Dogs vs. Cats. Mac vs. Windows. I suspect whatever makes us fall on one side or the other of these great philosophical issues is 95% or more in the goop, and we just come that way.

Everything you are, have been, and will be. Have desired, dreamed of, and done. Have felt. It all comes from a few pounds of goop.

And this fascinates me. Because, let's face it, we're just another part of the planet. A collection of complex molecules, electrical impulses, and chemical reactions. That's all people. Anatomically, all humans are pretty much the same. And we're not that different from other mammals. The difference in our genetic sequence vs. that of a mouse ain't much.

And yet that small amount of difference has led to amazing results. The ability to think beyond our own biological needs and to see the world around us for the beauty it contains. To watch a sunset and be in awe, even though we understand the science behind it. And to look up at the night sky, and wonder.

And that never bores me.

Coincidence and Causality

2009-04-15T09:17:00.000-07:00

In recent days, we've heard lots of editorials masquerading as news. They tell us that the economic rebound, the successful rescue of the captain of the Maersk Alabama, and housing starts are due to the president's economic plan, which hasn't even hit the ground yet. We hear from DHS that subversive militias are recruiting former members of the military in an attempt to overthrow the government. We hear that the world hates America because we are greedy.

What we don't hear should shock you. What we don't hear is that the pirates are attacking convoys of food and earning $150 million per year in ransom money. What we don't hear is that the Commander of the USS Bainbridge gave a split second decision command to fire that saved the captain of the Maersk Alabama. What we don't hear is that compared to last quarter, housing sales are actually down, but it seems up because fewer homes are going on the market so the percentage is down (my realtor gave me the stats herself on this).

Last night in class, we discussed one aspect of bad science- the ipso facto logical fallacy. They assume that because certain things are concurrent that one causes the other. You can't say that. At best, evidence suggests a link, but on further experimentation we can easily dispell this. One example in class deals with a woman whose flashlight doesn't work. She changes the batteries and it works. What if it hadn't? What other things could it be? We ignore so many things because we do not think of them. My students came up with some good ones: corroded connections, burnt out bulb, batteries inserted incorrectly, etc. Just because new batteries don't fix it doesn't mean they're bad either. Sometimes it's a matter of compounding variables.

Another powerful example, since I live in Nevada, is the roulette wheel. Many novice gamblers assume that because black has come up ten times in a row that it's red's "turn" to get a shot and they bet on red. Truth is that on the next spin, there are the exact same chances of black turning up again, and they don't have abetter chance of being right about red. Unless you remove a number when the ball falls on it, it doesn't change the chances of subsequent draws. It is mathematically possible on an unaltered roulette wheel for a ball to land on 17 black EVERY SINGLE TIME, however unlikely that might be.

See one other problem lies in differences between circumstances and operators. Every person performs experiments differently. A coworker called me yesterday to ask me how I innoculate a specific culture because it only works 50% of the time for her and it has so far always worked for me (most things don't work that frequently). Variations and variegations influence outcomes. We cannot predict the future because the circumstances are NEVER the same in subsequent trials. Things unseen and unknown change all the time, so no matter how well we try nothing is ever an exact replicate. Not even identical twins share everything.

I spent probably 75% of my time in laboratory troubleshooting to pin down unexpected outcomes and link them to unaccounted variables. About half of the rest of the time, I had to explain differences between trials to justify omission of results. Some scientists get excited apoplexy when they "discover" something new, when more often than not they are ghosts and not a result of our manipulations. Just because two things coincide does not mean they are linked. Just because they are linked doesn't mean one is causative. Sometimes things just happen and there is no real good reason.

Red Devil About Red Meat

2009-03-24T16:34:00.000-07:00

Meat makes man mortal. Ok, that's not so bad if, like I do, you also hope one day to die. The bad news is the way in which your mortality becomes more apparent through eating red meat.

Red meat consumption is linked to higher heart disease and cancer. Ok, are they causative? Not necessarily, but this is a problem with all science, which creates knee-jerk reactions of all kinds leading the banning of DDT, CO2, and now 2,2,4-trimethyl pentane and beef (which is also threatened by the Flattulence Tax).

Here's the codicil:

The study relied on people's memory of what they ate, which can be faulty.
In the analysis, the researchers took into account other risk factors such as smoking, family history of cancer and high body mass index.

Ok, now, I support this. Why? Scientifically, meat is high in nitrogenous waste, which must be purged immediately to keep the blood from being toxic. Secondly, most amino acids cannot be directly incorporated into proteins, so they must either be modified or metabolized. Third, animals do not eat the best foods- mad cow disease by way of example comes from feeding cows the ground up meat from other cows, and if that includes brain matter of a diseased cow the consuming cow will catch it. Even in Austria, which is a green and organic country, guess how they fertilize the fields of grass? They spray liquid cow dung on it. Gross.

Finally, meat must be cooked to be edible. Even if only one bacillus survives, E. coli doubles fast enough that one survivor can pollute you with millions in rapid succession. During cooking, the chemical structure, and therefore the utility, of components falls apart, making most of it of little use except as glucose substitutes. Also, if you cook it poorly, via charring, an innocuous enzyme in the liver can turn that harmless byproduct into a carcinogen.

Some people claim that you can't bulk up without meat, but cows just eat grass, and they bulk up just fine. Do you need meat? No. I love fish, and a really, really, really good steak tastes good now and then.

Math Conundrums

2009-02-17T15:24:00.000-08:00

If according to Dante 1+1=1 (one government plus one people to rule equals one society), then according to Tolkien, 3+7+9=1 (three rings for the elves, seven for the dwarves, and nin for men equal one master ring).

Also, 1 does not equal 1, else my one soldier could defeat your one army, or my one experiment should trump your one career.

Food for thought...

My Beef With Organics

2009-01-13T22:04:00.000-08:00

This past week, I butted heads with a good friend over the issue of organic foods. As soon as I explained why, she understood where I came from and seemed less adverse to my reasoning for opposing organics as presently constituted.

As a graduate student, I studied secondary metabolism deposition in plant tissues. We measured volatiles and terpenoids primarily in root, shoot, and berry throughout the vegetative process through to post-veraison. Results for Vitis vinifera varietals demonstrated how secondary metabolites are processed.

My problem with organics is how they come to market. We could track based on chemical properties to the exact day when fruit was ripe and ready for picking. Many organics are, like the foods they replace, picked before they are ripe for transport. Our research demonstrated that most of the chemoprotectants for which we consume plants (like tocopherols, resveratrol, etc.) remain in tissues we don't consume until the plant is absolutely certain the fruit will be set. A day or two prior to ripening, the plant starts shuttling these metabolites from leaves and stem to the fruit, and not before.

For this major reason, organic foods come to market as bereft of the nutrients for which we eat them as their inorganic counterparts, offering no added nutritional benefit, often at much higher cost. If you eat them because they come without hormones or inorganic phosphate, fine, but if you think you're getting better nutrition, consider from whence they come.

The best way to get pure unadulterated foods is to grow as many of them yourself as possible. That way you control the food you eat from seed to salad. You raise it without exogenous chemicals. You pick it at the height of ripeness. You consume food that you know meets all of your criteria. If you buy it because it says organic assuming it's better for you, it might be, but chances are it's just a more expensive fecal precursor than that which your neighbors buy and offers no more chemoprotectants to countermand assaults on your health than inorganics. Caveate empor.

Conditionalities of the Unseen

2008-12-04T15:01:00.000-08:00

I was just talking to a friend about how we're smack dab in the middle of cold and flu season. Some rather famous personages, including Rush Limbaugh, despite the medications and precautions they take, managed to catch flu, colds, or bronchitis so far this season. Not that I think colds are bad; by contrast, I think that periodic infections are good. Note that most of the major pandemics break out in civilized countries. Said virologist Gerald Lancz, we're scrubbing our kids down so much that we can't help but expect them to get sick.

By contrast, I cannot honestly remember the last time I "caught a cold". This might seem odd or perhaps by my own measurements alarming if you don't consider what I do for a living. As part of the microbiology lab in which I'm involved here, I obtain, maintain, and retain a series of strains of infectious microorganisms, including LVL2 Biohazard microbes (including E. coli, Diptheria, Cholera, and similar). The practical application of this I suppose is that periodic subclinical infections keep my immune system regularly challenged, such that it leaves little opportunity for opportunistic infections to take hold.

Without this information, it might seem that I'm more resilient against infection or that I'm "due" to catch something. Reality indicates however that I'm regularly and constantly under assault, but that my body is always ready to turn back the tide of invaders.

Some of the people I know who get flu shots complain that they don't work, and many people complain about responses of plants for which they care even after I dispense advice. What they do not realize is that that microbial world remains largely invisible to me. IN the first case, they probably catch the common cold, bronchitis, or even pneumonia after a flu shot and not the flu, such infections made possible by the fact that the body starts a primary response to influenza (which is a virus and MUST be fought by a secondary antibody-mediated immune response). In the second, they pretend that plants don't catch "colds" per se. Tobacco mosaic virus is basically akin to catching leprosy for a plant, but we don't pay it much mind.

Many things in science are not paid much mind. Touching plants induces genes. A failure in my building's climate control system shuts of laminar hood air flow (which was bad when I was mixing acetone and petroleum ether). However, I do not believe there are any coincidences. The problem for researchers is that when people discover unexpected things in science, they often don't provide public explanations if they come up with them at all. More often than not I observed scientists omit "anomalous" outliers in order to publish results when the outliers more accurately reflected the truth about that phenomenon.

When I studied diterpenes and volatiles in Vitis vinifera, we found, much to the chagrin of the funding agency that resveratrol increased only twofold in the berries but fiftyfold in the leaves under abiotic stress. That makes perfect sense biochemically now that I think about it, but if you're selling wine as an herbal supplement, that doesn't help your marketing. If you're making tea out of grape leaves, it's tantamount to a breakthrough. It wasn't what they wanted, but it was still useful.

One other thing that threw off our calculations was the alfalfa field adjacent to the vineyard. Overflow runoff from irrigation of that field influenced the grapes immediately antecedent, so once we were able to identify the source of the error, we omitted that one block out of the six total blocks of data available (a loss of 15 plants per subset out of 90 total biological replicates) until the situation rectified itself. Arbitrary omission or fanciful inclusion would have rendered our data irrelevant even if correct because it was founded on bad science.

Much goes on that we cannot see. The kind of scientific investigations in which I engaged as a graduate student involved ppb measurements, far below the detection levels of almost any human sense except taste/smell (which isn't quantitative). Just because we cannot see it doesn't mean it doesn't exist.

Yet my colleagues by and large also remain skeptics and atheists, except when they want me to buy their conclusions in peer review.

Consider Classic Experiments

2008-10-17T07:41:00.001-07:00

As part of the class I teach, the students get grades and complete some assignments on WebCT. One of them complained to me the other day about not being able to do something on the system and how much they loath it. I’m inclined to agree.

When I went to college, I didn’t actually want internet. I didn’t want to sit for hours at a time in front of the monitor surfing pointlessly, playing LAN games, or getting into trouble. Since I also know about Echelon, I also balked at the prospect of being tracked by the government whenever I opened a site, even if I ended up their accidentally. However, before too long, in one lab course I took in Biochemistry, we were required to, like my students are, complete assignments on WebCT.

If not for that, I probably would never have started a blog or wasted as much time as I have playing MMORPGs or in IM conversations. When it’s up to me, I prefer now to sit in my chair and read or play my guitar, now that it’s fixed. I find those things far more fulfilling, probably since I control them. You control very little on the internet.

Besides, old technology has its advantages. So many thieves have switched to online for easy money, that it’s almost become safe to send checks in the mail. Plus, they never steal a password for websites if I transact business via the USPS. It’s a lot of work to steal money through the mail, and you have to be physically there in order to do it. People can steal money from your account from the comfort of their home in Estonia while sitting nude smoking crack if they like.

Scientific technology likewise has come along so far that you can get publications for simpler things. For demonstrating that a gene has incomplete dominance or only a single allele (which is something they spend one whole lecture on in genetics classes), you can get into a journal because nobody does that anymore. A researcher in the lab I worked got his MS doing Chlorophyll fluorescence as a marker of stress. Nobody uses it, but it’s indisputable and very very easy, if only you own the equipment. Don’t ignore classics like Southern Blotting for ELISA or Y2H assays. Besides being simple and cheap, it leaves tangible results, not just readouts of electrons on a screen.

Federally Funded Fishing Expeditions

2008-10-14T07:48:00.001-07:00

As a biochemist by training, I grow increasingly tired at claims that scientific media “proves” environmental decay, a genetic basis for deviant behavior, evolution, or that medication causes disease states. What most people, including sadly many scientists, don’t realize is that much of science is no longer hypothesis-driven, leading to false presumptions and inconclusive conclusions from the data we collect. Rather, in order to maximize publications and fame, scientists sacrifice the quest to solve problems and embark on federally funded fishing expeditions in hopes of collecting mass amounts of data and finding something there from with which to wow the public. Nobody seems interested in following through on a project that has end user application, because those quests take a lifetime without promise of any return on the investment. Worse, nobody will fund those who maintain this ethical problem-solving strategy because society demands results.

Science doesn’t prove anything. Science disproves all other possibilities until only the truth presumably remains. In a hypothesis-driven endeavor, one collects data and tries to refute the hypothesis. Evidence either refutes the belief or proves insufficient to disprove the hypothesis. In this way, no matter how overwhelming the data, the truth is never really proved, we are merely unable to disprove it. This phenomenon is easily illustrated by physics, which is highly content-specific: all that we know about resistance, gravity and acceleration forces and “constants” applies only in the context of the earth. Although the principles remain the same, all the parameters change when we leave the planet, and some forces change depending on our latitude on this one.

Non-scientists refuse to accept this fundamental truth of science- that we cannot “prove” much by experimentation. Data at best provides evidence that A and B are related or that A and B may be causative agents of C. Alec Guinness had a good line in “The Empire Strikes Back”, when he said that much of what we hold to be true depends on our point of view. This is especially important to consider in light of rogue scientists who will obscure or fabricate data, ignore variables, or withhold information to prevent others from subverting their personal agendas. They cannot prove what they believe, so they fit the data to their preconceived notions.

Despite the deception and delusions, the truth is not offended. Some day, we may come to know it, and then those who sowed lies will be refuted and lose whatever glory they thought they had.

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2008-10-01T15:11:00.001-07:00

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Unaccounted Variables

2008-10-01T14:39:00.001-07:00

One of the first lab exercises I taught this semester dealt with simple use of the metric scale, but I found the opportunity to teach a much more powerful lesson in that part of our lab experience. When scientists plan experiments, we hope we take into account all the things that need to be controlled so that only one variable remains- the thing we intend to test. Due to ignorance, willful or innocent, however, sometimes things surprise us for which we do not account.

I asked the students to record the values on the board so that we could analyze the variance of data from person to person. I found another phenomenon that was easy to account for but not necessarily apparent. In the jar of pennies to weigh, there were pennies of different coinage. In 1981, the US Mint stopped coining pennies in pure copper and started wrapping copper around a zinc filler, changing the weight. Another student, unable to read apparently, weighed a 1000ml beaker instead of a 500ml one. This resulted in some widely varied numbers.

By and large, the students obtained weights where the only value that varied was in the last significant figure. That is common in science- it's the figure we're not EXACTLY certain of. For the different pennies (1997 and 1978), there was a 25% difference in weight (2.23 v. 3.41g). If you didn't know about the change in mintage and assumed that a penny was a penny, you might factor in both weights and have skewed data. Or you might throw out the one aberrant design because it was skew, but then you'd have to say "using pennies minted in the 1990s" in your description of the objects weighed. As for the beakers, it was easier to throw out the one value because he knew what he'd done wrong and could easily explain why it was okay to throw it out.

Outliers if not properly identified cannot be removed. That doesn't seem to stop many of my colleagues from deleting, losing or omitting data that counters the conclusion at which they wish to arrive. I have actually been TOLD by PhDs to omit data for various reasons. I must thank Genevieve Pont-Kingdon at ARUP for NEVER having given me the impression that so doing was acceptable.

In my last post, I mentioned briefly variegations across a species. Our lab studied 18 different cultivars of the species Vitis vinifera (wine grape), which isn't all of the cultivars available. There are at least seven members of the Vitis genus, and there are many other members of the fruiting vine family. To assume that Vitis vinifera cabernet sauvignon's behavior explains that of Vitis riparious (Norton- a North American native vine) or that of Watermelon would be silly, yet that's exactly what scientists try to tell us sometimes.

When I made conclusions, I said things like this:

For Vitis vinifera cultivar gewuertztraminer under water deficit stress in greenhouse conditions, we observed a 10-fold reduction of resveratrol in the leaves and a 2-fold reduction in the berries. A total of three biological samples were tested on three separate occasions to arrive at this figure.

I did not try to say that water deficit stress will affect other wine grapes grown in Africa or Iceland in the same way or that resveratrol was affected the same way systemically. You must restrict your conclusions to the limits you define or else you start running into other variables. Even then, sometimes they show up when you least expect it, even in something as simple as a penny.

Scale and Sample Size

2008-09-30T05:48:00.001-07:00

I made myself quite unpopular at conferences by asking questions as to statistical significance of findings. All scientists want to prove some sweeping new concept or cure a disease, but depending on the scale and sample size, their efforts may not be relevant or useful to the world at large. The vast array in possibilities of SNPs accounts by and large for the frequency with which pharmaceuticals seem prone to causing severe complications including death because they are designed for the many and do not often take into account minute aberrations from "normal".

Many researchers came equipped with graphs and charts in a vast array of data, meant presumably to awe us with the enormity of their conclusions. However, I noticed with alarming frequency an absence of statistics validating the fit of their conclusions (not that that's always a guarantee depending on the frequency and severity of outliers for which we cannot account. More on that later.) I used my time to ask them questions on statistical relevance in order to determine how useful their science might be to me. After all, if I intend to springboard from their conclusions, I want to make sure their claims that appeal to me stand on solid ground.

For my own research, we considered both biological and technical replicates. I learned that lesson in industry at ARUP Laboratories in Salt Lake City. I would sample at least three different biological samples three different times for a total of 9 samples before plotting the data. This tripartate replication in biological and technical capacity helped me determine a better normality of data and isolate aberrations, which were usually due to operator error (me).

After that, I performed ANOVA, X2, and other tests. Please note that the R2 value in the graph from last entry is 99%. You need not do that much. I was willing to accept a simple standard deviation bar set and an n number representing sample size.

If you test one plant and then tell me you were able to raise its resveratrol levels under enhanced CO2 concentrations to 50x the normal level and then ask me to believe that will be true for every individual grape of every cultivar of every species in the genus, I won't buy it. Congress might, or maybe ASEV, and they may give you money, but it won't be useful to anyone if it was a fluke. Utility is after all what we seek.

Anything worth doing at all is worth doing well. Plus, it would prevent FDA warnings, Pfizer settlements, GSK recalls, ad infinitum, if a few scientists took the time to test a few more samples, especially if their sample size was one. Come on people.

Projections and Prognostication

2008-09-25T05:47:00.001-07:00

While teaching undergraduate labs in graduate school, we reinforced the principle of being able to make a relevant comparison. The students were asked to analyze the protein content of tissues using various biochemical measurements in this particular example using an external standard.

After diluting a standard of 1mg/ml protein, they performed the analysis and calculations in order to produce a standard curve. The following represents a typical standard curve:

The students would then test their unknowns and compare them to this standard curve.

As luck would have it, the samples to be tested all had protein contents WAY outside the range of the curve they created. Some students foolishly extrapolated the data assuming it to be linear out to whatever value they obtained, ignoring the possibility that outside this range the curvealinear relationship observed might not hold true. We forced them to dilute their samples until the readings fell inside those covered by the standard curve and they could give an accurate number and then scale it back up using their dilution ratio.

When you project behavior beyond the measured realm, you lose all scientific credability. In economics, they continually remind you that "past performance does not guarantee future results", and in science we can only say what we have observed, not what we expect. That is a hypothesis, not data for a conclusion, so any projection represents what we THINK will be rather than what we know. This serves relevant point in politics I may address later on my other blog. It is not actually something we have measured, and represents not fact but conjecture and assumption.

Global warming advocates do this all the time. They project outside the range and extrapolate over a wide range of time and scale, the particulars of their experiment notwithstanding. Other scientists also like to apply measurements to things outside the scale and scope and make sweeping gestures which are not necessarily true.

When working on volatile compounds in grapes, the first thing I did was establish the linear detection limits for the GC/MS protocol I used. I was able for most compounds to detect them linearly to 4ppb, which is very important since the amount of volatile is not necessarily proportional to its importance or potency. Sometimes it is RELATIVE amount that makes all the difference. Even in a linear scale then, it might take 4000ppb to register a difference from 4ppb.

The proof is in the data. When scientists make broad sweeping claims across a vast array of possibilities in clime, scale, age, time, etc., I raise an eyebrow and my hand to inquire. More often than not, this error is also accompanied by another error and my next subject- economy of scale.

Why Start This Blog?

2008-09-21T22:28:00.000-07:00

Many years ago in graduate school, I wasted quite a few months pursuing a project that would never ever work. What was even more frustrating is that other labs knew it wouldn't work, but they didn't bother to share their findings with us because science journals don't publish things that don't work.

In his book Climate Confusion, climatologist Roy Spencer makes the following observations. In speaking about why global warming alarmists and their complicit media counterparts sensationalize the armageddon scenario of world destruction, he points out that:

In science, if you want to keep getting funded, you should find something earth-shaking.

This phenomenon provides most of the impetus for hastily and poorly-drawn conclusions in science. To get published in a prestigious journal many scientists will project their findings to astronomically irrational levels and claim that "Our research on abiotic stress in creosote will one day provide all the rubber the world needs without any cost because these bushes grow wild throughout Nevada, so everyone who owns any of these shrubs on barren lots will one day be multi-millionaires" as a crude example. The truth is that, much as I like the guy, Dr. David Shintani's lab isn't remotely close to bringing any kind of alternative rubber source to market, nor will his lab by itself in our lifetime without some kind of corporate sponsorship and investiture.

In their haste to publish, graduate, and tack on a series of unintelligible vowels and consenants to the end of their names (mine are incidentally MSBMB, SSRAII, APB- whatever the heck that means) colleagues of mine have falsified data, omitted or deleted information, thrown out abnormal results without good reason, and made inaccurate claims based on a statistically insignificant number of biological and technical replicates. If you then try to piggyback on their research, by and large you may find their data and their conclusions faulty, meaning that you waste a lot of time and resources duplicating their efforts. What consequences do they face? None. I don't personally know of anyone stripped of a MS or PhD for having had their thesis/dissertation disproven.

The true tragedy is in cost to you the taxpayer and consumer. How much duplicit effort in time and money exists because people are only able to/interested in publishing breakthroughs that will exalt their own personal self-interest? Scientific journals as presently constituted concern themselves only with publishing what did work, to the exclusion of everything else we tried that didn't work with its accompanying data and explanations.

Enter the Journal of Negative Results. Would you like to know if someone already thought about trying to solve a particular scientific question with a particular technique? How did they fare? Why did they fail? Why can't they get credit for all that hard work with a publication? I think such a Journal adds value to the system of science and may save people a lot of time.

Now I lack the fudiciary means to fund such an endeavor, but I do have this- a searchable blog dedicated to any and all who would like to let the rest of us know what they have been able to disprove by their work. I may not offer a prestigious journal in which to publish, but I offer you yet another chance to get yourself on the Google or Yahoo web results for work you did and give credit where credit is due. I ask no compensation for this, and I will publish any and all information on techniques, organisms, variegations, equipment, and personnel who netted you abnormal results and didn't get you what you were aiming at, because maybe someone can serendipitously segue from your efforts and get an idea they didn't think about before all while saving everyone else time and money.

Now accepting manuscripts.