Exterminating the Parasitic CEO

Don’t be like these guys…

It is June and time for that twisted corporate introspective agony called the Annual Employee Performance Review. There is something slightly Maoist in the idea that, once every year, each employee-supervisor pair should turn on each other and start rank ordering their superlatives and deficiencies like some poor couple in marital therapy. It’s been my experience that more harm than good comes of this. Since I also do my own scathing self-review (Organization: Abysmal. It is demotivating to many of those who work around me to see to what degree my own work is in a shambles.), I had a chance to comment on my own compensation.

I make $300,000 per year running a company of about 300 people with global annual revenues of about $40 million. Fortunately, the New York Times recently reviewed CEO compensation in a piece that I picked up on Twitter, allowing me to make some comparisons and develop two simple guidelines for setting appropriate CEO pay.

  1. The CEO should never be paid more than 1% of gross revenue. At an astonishing 47% of gross revenue, the leader of the NYT survey is consuming his parent company feet first and his lips are slurping at his own ass.
  2. The CEO should never be paid more than 10 times the compensation of the lowest paid entry-level college graduate in that company. I don’t care how stuffed your Rolodex, how merrily you multitask, how bluetoothed your smartphone and laptop, how energized you emerge in the office at 5:00 am after leaving a mere 4 hours earlier—you don’t do the work of more than 10 people. No, you don’t.

Virtually all of the corporate CEOs compensating themselves at rates shooting past $100 million each year are doing so not because they have earned it or because they deserve it—they do it because they can. That is the same reason Viktor Yanukovych built himself a mansion containing a white Steinway piano modeled after the one presented to Yoko Ono by John Lennon. That is also why Muammar Gaddafi and Saddam Hussein [fill in any excess you find most grotesque].

The role model of the CEO should be that of a statesman, not a tyrant. His personal ambitions should be modest, while his ambitions for his staff and their enterprise should be unlimited. So if you want a raise, masters of the universe, add $5 million to your corporate sales, add $5,000 to the pay of your newest and brightest—and I’m sure you can do the math from there.

Yanukovych_piano

The piano of Viktor Yanukovych, President of Ukraine from 2010 to 2014.

Note added in proof: Application of these CEO rules to my own pay caps compensation at $340,000/yr. However, it was determined that my pay change will be 0.0%. The time being wasted writing and researching irrelevant topics for my personal blog as well as the time spent idly chatting on social media such as Twitter were duly noted. That is, performance issues have delayed the full actualization of my reward potential. Only HR could make it sound so positive.

Posted in Uncategorized | Tagged , | 7 Comments

Phenotyping and the Bucketmouth Beard

genome

genome

When the Personal Genome Project(PGP) launched and the first ten volunteers were inducted, it was clear that they were intent on more than just genomics. Most of us were photographed with a little 10cm ruler taped to the middle of our foreheads. This had the effect of making us all look (and feel) as if we were being hauled in for a DUI, but I think that was inadvertent. The only use that could arguably be made of that little bar grid was to phenotype us. That is, the PGP wanted to make an effort to describe and measure exactly the look, feel, shape and dimension of the protoplasmic projection of those genomes they were sequencing. That set the bar very high indeed.

As we have come to realize, phenotyping is easier said than done, and it doesn’t exactly roll off the tongue in the first place. I can extract at least a couple bits of crude phenotype from those early PGP photos. (For reference, see my earlier blog post Patients in Waiting) Interpupillary distance (how far apart are your eyes) is an important human metric. It undoubtedly follows a bell shaped Gaussian distribution, and a narrow one, because if it’s too short, you look cross eyed and stupid. If it’s too wide, you look bug eyed and alien. Two important points quickly emerge. There are numerous phenotypic designations already in common usage, and they are usually offensive. Scientists wanting to tease apart the many genetic and embryonic influences on craniofacial development that determine our interpupillary distance need to be able to talk about it without being hissed at by enforcers of the politically correct. Niceties aside, it’s pretty clear that Steve Pinker, PGP-6, and James Shirley, PGP-10, are the cross-eyed and bug-eyed outliers of our particular group.

Interpupillary outliers

Interpupillary Outliers

The author and his son share a SNP in intron 86 of the HERC2 gene, controlling expression of the adjacent OCA2 gene, and predicted to result in a blue colored iris.

My son and I share an SNP in intron 86 of the HERC2 gene, controlling expression of the adjacent OCA2 gene, and predicted to result in a blue colored iris.

You can also assess skin pigmentation, just based on whether you are whiter than your strip or your strip is whiter than you. James Shirley and Rosalyn Gill are probably our diversity winners, but melanization can be measured more precisely than this.

pigment

Melanization Outliers

All that is missing from this phenotypic analysis is precision, reproducibility, a common accepted semantics, and a testable underlying theory of genetic contribution. In addition, many people actively subvert accurate phenotyping by altering their appearance with cosmetics, surgery, prosthetics, dentistry and the coloring and shaving of hair. Only George Church of the original PGP-10 gave us a full view of his facial hair phenotype.

I was mildly curious about this, so I grew out my own beard. Nothing like a World Series on the line or anything – I just wanted to have an accurate phenotype. There’s been a lot of discussion around our labs about what a beard is for in the first place. Is it a microbiome warehouse of stray composting food particles  so you can mix probiotic bacterial spores into your mouth while you eat with your fingers? Is it the opposite of a love handle – a hate handle that you can grab and jerk on if you’re not receiving the full attention of the owner?

Imagine my surprise when mine grew out – the first time I had seen it since college – and it had bands in it. Seriously – from ear to chin, it goes dark-white-dark-white and then back up the other side in the same order. Not all people can grow a beard. Not all of them who do grow one have a striped one. WTF? I probably would have just left that thought to the dustbin of time and the ravages of senile dementia, but the next day on TV I saw an interview with Shane Smith, founder of Vice Media. It was an “I am your father Luke!” kind of moment.

shanekirk1_

So I took a few photographs and made some observations. I now think your beard is there to make you look authoritative and scary. If I open my mouth really wide and say something really mean, like “What the f*** is going on here??!!” the black bands make it look like my mouth is maybe 5 times bigger than it really is. I have a bucketmouth beard. Is this genetic? Looking back at the PGP, George Church kind of has one too. But I think both of us will recall that our beards were originally solid, not striped.

before and after

So here is my theory: Beards are secondary sexual characteristics of males that initially signal the onset of sexual maturity, the adequacy of whole body testosterone activity and the desire to advertise oneself as a suitable mate. Beards are initially solid in color, and the fullness and density of the beard can be used to advertise vigor, health and adequate strength and nutrition. As men age, those who are continuously in a position of authority as a group leader or chief undergo epigenetic changes that enhance the loss of  beard follicular melanin in a banded pattern. (George has been the head of Harvard’s Church lab since 1986; I have been CEO of Cayman for 35 years; Shane is a whippersnapper but he’s the founder of Vice) This banded, bucketmouth beard increases the intimidating appearance of facial gestures and reduces the physical effort required to maintain order among unruly subordinates. This is an easily testable hypothesis, although no biochemical basis is proposed. In short, you can’t be the boss until you’ve earned your stripes.

I’m really curious how common this sort of beard pattern is in the general population. Curious enough, that I’ll send a FREE Philips Norelco Vacuum Beard Trimmer to my favorite 5 photographic examples of a bucketmouth beard. Submit your beard one of the following ways:

Post the picture on Twitter and mention me, @KirkMMaxey

Email the picture to my address, KirkMike157@gmail.com

There was an elegant paper in Science recently that described precisely the underlying embryology and endocrine biochemistry leading to the stripes and bands on King Cheetahs and Mackerel Tabby cats. A single gene mutation distinguishes the cat on the left from the one on the right. However, at least four additional genes work in tandem to establish the striped pattern.  My wish for the Personal Genome Project is that it will someday let us know as much about ourselves as we do about our cats.

Posted in Short Stories | Tagged , , , , , , | Leave a comment

Winter of our Disrespect

lighthouseOn a cold February morning recently I checked the Great Lakes Environmental Research site and found that only one of the Great Lakes had any waves on it. Superior, Erie, Huron, and Ontario were frozen solid. A small peanut of Lake Michigan remained partially liquid and filled with floe ice. The same map also shows me that I could drive a snowmobile straight from St. Joseph, Michigan to Chicago, Illinois avoiding all the traffic on the interstate. On one hand I’m exhilarated, because I may personally witness in the winter of 2014 the first complete freeze of the Great Lakes in recorded history. Yet on the other hand, I’m disgusted by the chicanery, incompetence, self-righteousness and posturing of the so-called “climate scientists” who assured us that the opposite of this bitter weather would prevail in the 21st century. It is not so much that they made such a prediction and were wrong. My emotional overtone springs from the fact that, through politicization of their alarmism, they were just ginning up the funding mechanisms to allow them to spend poorly even larger sums of money in the service of predicting future climates badly.

Contempt is a poor prognostic indicator for any future reconciliation between disputing sides in a conflict. Upon reflection, it is surprising that I would find myself in such an intractable state of disagreement. I myself am a scientist. I’m naturally sympathetic towards other people who study things in detail and make discoveries about those systems or objects, even when those discoveries are counterintuitive or unexpected. I actually do read the peer reviewed literature that pertains to climate, and find many of the authors publishing there to be competent scientists making credible observations, carefully restricting their conclusions to those that are supported by their data. I also browse through news reports and social media, reading what various advocates and journalists say and write about climate. This led me to follow a recent Twitter post by Carl Zimmer, that took me to 173 pages of congressional testimony by Andrew E. Dessler,  that brought me to the crystalline, cathartic comprehension of the source of this winter’s ill will.

But first I want to point out the work, unnoticed in the press and generally unheralded, of some real climate scientists.

geomar

Professor Christian Berndt is a German scientist working at the GEOMAR Helmholtz Center for Ocean Research in Kiel, Germany. In January of this year, he and his group published a detailed study of the release of methane from submarine arctic sediments off Svalbard Island in the North Atlantic. In 2008, passing ships had noticed vigorous outgassing of methane in a narrow zone of water about 400 meters deep, and this was interpreted by some as the onset of catastrophic methane hydrate dissociation caused by global warming. Methane matters, because it is 30 times more opaque to infrared radiation as CO2 is. The GEOMAR team made several expeditions to the area, made parametric echosounder profiles of the area, photographed the bottom sediment features of the gas release sites, and made a continuous 21-month bottom water temperature observation at the site. They observed carbonate precipitate crusts up to 40cm thick indicating that methane had been oozing from these sediments for at least 3,000 years, and that it was being oxidized by benthic microbes. Based on the recorded temperature profile, the authors deduced that there is a seasonal growth and decay of methane hydrate deposits along the continental shelf that has been stable for many centuries. This work was characterized by the generation of much new data through direct observation, not by computer modelling of existing data. The conclusions were limited, in that the authors admit that we do not have any precise knowledge of the global methane budget. We do not know how much methane is released worldwide or where it comes from; we do not know why the atmospheric concentration of methane stopped increasing about 15 years ago, or why it began increasing again in the last few years. But we do know, thanks to their data, a lot more about this one source, and that it is not coupled in any way to global warming.

Andrew Dessler gave testimony in the US Senate with respect to President Obama’s Climate Action Plan on January 17, 2014, the same day that Professor Berndt’s paper published in Science. By way of background, Mr. Dessler’s previous employment experience was with First Boston Corp in the investment banking industry, and then as a senior policy analyst in the Clinton White House. That is to say, he has apprenticed in the two largest criminal con games operating in America – banking and politics. A review of his sparse peer reviewed publications reveals that he is a climate modeler. That is, he does not actually study climate, he takes the data generated by real scientists such as Dr. Berndt and plugs it into computer games that he programs using public funding, yielding improbable projections of future climate that are almost certainly incorrect. A summary of more than 100 of these contradictory computer climate models recently appeared on  Steve Goddard’s Twitter feed.

It may be of little consequence what I think of Andrew Dessler, but what is so telling is what he thinks of himself. On the third page of his Senate testimony, which reads very much like a political position paper, there is a little footnote 1 after the sentence “The actual amount of warming over the last century roughly matches what is predicted by the standard model of climate.” Then, at the bottom: “1. Following particle physics and cosmology, I’ll refer to the mainstream theory of climate science as the Standard Model. A climate model is a single computational realization of the physics embodied in this standard model.” So…Mr. Dessler thinks of himself and his faulty computer model as being on a par with the Standard Model of particle physics. Not only does he rub shoulders and share the stage with Einstein, Bohr, Schrodinger, and Feynman, but also more recent Nobel laureates Sheldon Glashow, Steven Weinberg, and Abdus Salam. With a pompous grandiosity that induces vomiting, Dessler tries to paper over the absurdity of his jury rigged algorithms with the wizardry and precision of physics. He’s nothing if not generous – every single climate model that runs and generates ‘roughly the same amount of global warming’ gets to be equivalent in importance with the foundations of particle physics and the fundamental properties of all matter.

I am driving my 4×4 pickup through 20 inch snow now on the weekends, to cut firewood that I could have cut a lot more easily in September. My mare is due to foal in 4 weeks, and I can hardly afford to heat her barn with propane now that the price has doubled. I could have bred her a month later, and filled the propane tank in August. Michigan is having one of the coldest winters ever recorded. This was not predicted six months ago by long term weather forecasters. But in the 1990s, the opposite of this was vigorously predicted by climate forecasters. They were wrong. Humans are currently unable to predict either seasonal weather or  long term climate with an accuracy that allows actionable steps to be made by ordinary people. This state of affairs will likely continue, because the likes of Mr. Dessler consume an inordinate amount of the scarce public funding available to actually study climate. Unnoticed and underappreciated, the true scientists in the field who make no alarmist statements and who generate real measurements and data find their support being parasitized by thinly-veiled con men who anoint themselves as a bunch of Einsteins. A validated climate model is one that has accurately predicted  100 year average precipitation and temperature anomalies, to within 5%, over the entire planet 25 years in advance, in 4 out of 5 iterations. We have no validated models. Even if one that’s up and running is valid, we won’t know that for 125 years.  For the present, it would help if those who wish to pontificate about  future climate preface their remarks with the sobering truth: Man does not yet understand how climate works.

Trilobyte_Single

Posted in Science | Tagged , , , , , , , , , | Leave a comment

Patients in Waiting

genome

The 10 high-profile volunteers currently having their genomes sequenced as part of the Personal Genome Project.

When people learn that I have been sequenced as part of George Church’s Personal Genome Project (PGP) they often say, “Wow- I’d like to be sequenced too!” My first response to them is, “Why – are you sick?” If the last decade has taught us anything, it’s that sequencing healthy people returns mainly raised eyebrows, but little more. Sequencing cancer patients and their tumors, on the other hand, can be life saving. Dr. Lukas Wartman probably saved himself from an early cancer death by being sequenced.

Genomic sequencing of children with unexplained illnesses also leads to heartwarming breakthroughs. The Beery brother and sister pair, Noah and Alexis, had severe dystonia from birth and could barely breathe or walk. Misdiagnosed and mistreated as having cerebral palsy, the medical and emotional cost of this failed diagnosis on the Beery family was huge.  Genomic sequencing revealed that they were complex heterozygotes for null mutations in the gene sepiapterin reductase, causing a known dopamine-linked dystonia that can be rescued by dietary supplementation. Properly treated, they now lead normal, healthy lives. Other similar pediatric miracles, such as solving a case of inflammatory bowel disease, come to mind.

The Beery Family

The Beery Family

Sequencing normal healthy people, in my experience, just tends to undermine the confidence one has in peer reviewed medical literature. I was on hand in Boston in 2008 when the first 10 completed sequences of the Personal Genome Project were rolled out. I had a special vested interest, in that mine was genome number 5. When the sequences were reported, we were all taken individually and counseled about a few of our “calls.” Remember – almost any genome will have something like 3 million SNP variants that differ with respect to the reference genome. So to say this was cherry picking, or barely skimming the surface, would both be understatements. Then they brought us back together to discuss the impact this had on us. John Halamka (PGP-2) was standing there looking sheepish because he was supposed to have an autosomal dominant neuropathy…but he didn’t. When I looked at my own data, I found mostly very vague GWAS associations. What does it really mean if you have a single nucleotide variant that is within an intron in a gene of unknown function, and that a GWAS study found it is associated with a 2.8% increase in the chance of rheumatoid arthritis, which I don’t have? Four of the first PGP-10 volunteers had mutations in the gene ELAC2 on chromosome 17, supposedly linked to prostate cancer. I was one of those – but I have a low PSA value and no history of any relative having prostate cancer for 4 generations. Fully 70% of the PGP-10 had mutations in the SP110 gene supposedly making us more susceptible to tuberculosis. Hmm. Lots of raised eyebrows and shrugged shoulders.

Looking deeper, I came across my KCNQ3 gene. The KCNQ genes are a family of voltage gated potassium channels, now numbering 1-5, working as heteromers with each other to generate the neuronal M-type current. I happen to have a single nucleotide mutation in one copy of KCNQ3, converting Arginine 777 to Glutamine. Scanning the literature, I found six other known human KCNQ3 mutants – Trp309Arg, Pro574Ser, Ala381Val, R330Cys, Gly311Val and Gly263Val – but not mine. All these other mutations lead to epileptic seizures, mostly BFNC or Benign Familial Neonatal Convulsions. They act as autosomal dominants, so only one bad copy of KCNQ3 is needed in order to have the seizure disorder. The only problem for me is…I’ve never had a seizure. What I’ve become is a “Patient in Waiting.” Otherwise called a hypochondriac made-to-order by too much genomic sequencing, or a person who is now startled by their smallest involuntary twitch.

The number of patients in waiting grows daily, as more humans are sequenced and more mutations are called…in healthy people who don’t have what the mutation is supposed to predict. I’ve included in this post the story of another such patient, a little girl named Laura Inestroza. Her story, and the fact that despite her genome, she does not have cystic fibrosis, were recently reported in The Wall Street Journal. So Laura, here’s to you, and to me, and to a long and healthy life for all of us who are proving that genes, for all that we know about them, are still keeping a lot of secrets.

Laura Inestroza, 4, was found at birth to have the genetic changes associated with cystic fibrosis, but she still has no symptoms. Michal Czerwonka for The Wall Street Journal By Amy Dockser Marcus

Laura Inestroza, 4, was found at birth to have the genetic changes associated with cystic fibrosis, but she still has no symptoms. Michal Czerwonka for The Wall Street Journal By Amy Dockser Marcus

To read the full WSJ article, Genetic Testing Leaves More Patients Living in Limbo, click here.

Posted in Genetics | Tagged , , , , , , , , | 1 Comment

Type I Diabetes – A Day in My Daughter’s Life

A parent easily falls into the trap of describing the most horrific of their adolescent children’s behaviors. There are always those loud and angry interactions of one brain soaked with testosterone interacting with another one soaking in 400 mg/dl glucose. That’s why it made me so proud when my sixteen year-old son, who loves photography, collaborated with his Type-I diabetic sister, and together they produced this video. It was a homework project that made all my years of parenting seem worthwhile. Please have a look, and pass this along to any kids you know who have recently been diagnosed with diabetes.

Trilobyte_Single

Posted in Short Stories, Uncategorized | Tagged , , , , , , , | Leave a comment

Lose Weight…and your poop will glow in the dark too!

laboratory ratSean Davies had a problem to solve: If you genetically modify enteric bacteria to make them more healthful, how can you quickly check to see if they’re happily growing away inside your experimental rat? The solution he chose could represent the pinnacle of scientific achievement in its own right – he incorporated bioluminescence into the same bacteria. Those rats that were successfully colonized by the modified E. coli could be detected at a glance – because their poop now glowed in the dark.

Sean did not start out to create the next GM novelty item. Working in the Vanderbilt Department of Pharmacology and with collaborators at Texas A&M and CNRS in France, he recognized that not all gut bacteria are created equal. Many recent studies have demonstrated that the gut microbiota can predispose an individual to metabolic disorders, including obesity. So why not engineer a gut microbe specifically to be a health-promoting bug?

Rat Diagram

Four weeks after ingesting a dose of these high-tech probiotic bacteria, lab rats on a high fat diet gained 20% less weight than their controls, who not only got fat, but also had boring bowel movements. Taking a cue from the field of endocannabinoids, the lipid substances that are your body’s own version of THC, the researchers surmised that a genetically modified gut microbe could be designed to produce a normal signal of satiety. The gene for N-Acylethanolamine (NAE) synthesis was transfected into the normal human commensal E. coli N1917, along with the luciferase gene so it was easy to check on how these new bugs were thriving. NAE works in the gut to induce a feeling of fullness and anorexia, normally in response to a high fat meal.

A preliminary report of the study was presented on November 4, 2013 in San Juan, Puerto Rico at the 13th International Conference on Bioactive Lipids. Sean hopes to publish a full description of these exciting results in the Journal of Clinical Investigation, no doubt to glowing reviews.

Cayman-official

Posted in Cayman Chemical, R&D, Science, Uncategorized | Tagged , , , , , , , , , , , , | 1 Comment

Jumping genes make fall come alive

I’m only two pages into the latest children’s book on learning one’s colors, and my 3-year old hits a snag. “Corn is NOT yellow!” he shouts indignantly. For several weeks now, he’s been going with me to the garden and bringing back armfuls of native corn, then sitting and husking them one leaf at a time until the kernels come into sight. Then, with “Oooohs!” and “Aaaahs!” worthy of a fireworks display, everyone admires the deep reds, purples, pinks, and greens that make up the true colors of maize.

Enough people have asked me about this recently that I thought I would take a stab at a topic so complicated that it won Barbara McClintock a Nobel prize. Maize is the ultimate transgenic exhibitionist, flagrantly moving bits of its genes around with each generation. This is not recombination – it is unguided transposition engineered by ancient parasitic bits of DNA that stick themselves in and out of the maize pigmentation genes at random. It made me smile when golden rice became all the buzz recently, as I’ve watched many generations of maize revert back and forth from white to golden without Greenpeace getting lathered up about it.New Corn Illustration - Looking Down-PART 2

That’s as good a place to start as any, because the carotenoids are expressed mainly in the endosperm, forming the base color of the kernel. See the illustration for the names and locations of the various seed layers. The endosperm forms the substance of the corn kernel, and it is the canvas, while the thinner pericarp and aleurone layers are like paint layered over this base color. Corn has a robust production of deep yellow carotenoids including zeaxanthin (Fig1), and these genes are either disabled by the insertion of transposons, giving a white background, or intact, giving yellow.

Continue reading

Aside | Posted on by | Tagged , , , , , , , | 8 Comments