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Do Allergy-Induced Endogenous Blood Histamine Fluctuations in Humans Modulate Blood-Brain Barrier Permeability and Psychotropic Drug Efficacy?

December 10, 2015 Leave a comment

Content Moved here

[Draft of December 10, 2015]

Abstract

Simple seasonal allergies, or other allergies, may impact the efficacy of psychotropic drugs in some people, because:

  1. Histamine modulates blood-brain barrier permeability (BBBp) ([5] and refs., [9]).
  2. Psychotropic drug efficacy is determined in part by BBBp.
  3. Human blood-histamine levels vary idiosyncratically as part of the allergic response.
  4. A normal human allergic response can elevate blood histamine levels to 10(-8) M.
  5. Histamine levels of 10(-9) M are sufficient to open the BBB significantly in cats.

That is, allergies cause histamine level fluctuations, which cause BBBp fluctuations, so constant extracranial drug levels may correspond to varying intracranial levels, with widespread clinical implications.

Details

Wide agreement in the literature, going back to the 1990s, supports the observation that endogenous histamine mediates BBBp — e.g., [8] from 1992, [6] from 2000 (authorship overlapping with [8]), and [2], also from 1992.

Schilling and Wahl [7] show that an in vivo blood histamine concentration in cats of 10(-9) M is sufficient to let Na(+)-fluorescein (mw 376 g/mol) through the BBB.

In humans, non-acute histamine concentrations range up to 10(-8) M ([3]; [1], from 1976; and [4]).

The molecular weights of common psychotropics fall within the range that may be impacted by histamine-induced changes in the BBBp: Diazepam (Valium) [285 g/mol], Fluoxetine (Prozac) [309 g/mol], Lorazepam (Ativan) [321 g/mol], Quetiapine (Seroquel) [384 g/mol], Haloperidol (Haldol) [376 g/mol], Sertraline (Zoloft) [306 g/mol], Carbamazepine (Tegretol) [236 g/mol], Paroxetine (Paxil) [329 g/mol], etc.

Case Study

Patient S, suffering from intractable epilepsy and seasonal allergies, was hospitalized 31 times before age 25 for either uncontrolled seizures or intolerable adverse reactions to various AEDs. None of her hospitalizations occurred in May, June, July, or August. (The statistical likelihood of 31 events occurring at random during the same 2/3 of the year is about 5 in a million.)

My hypothesis is that seasonal allergies give S constant histamine levels during the summer but, during the rest of the year, varying histamine levels, and thus varying intracranial AED levels.

Ramifications

Therapeutic dosing for psychotropics may depend on the presence of serum histamine, and may be impacted by allergies, including seasonal allergies.

Therapeutic AED levels, in particular, are often expressed in extracranial blood concentrations. This approach may need to be modified.

Research Suggestions

  • Retroactive patient intake review: Do other epileptics demonstrate seasonal hospital admission patterns?
  • Retroactive patient intake review: Do other patients taking psychotropic drugs demonstrate seasonal hospital admission patterns?
  • Patient study: Measure histamine levels as part of routine AED monitoring.
  • Patient study: Measure histamine levels as part of other psychotropic-drug efficacy monitoring.
  • Basic research: Study BBBp with regard to AEDs/other psychotropics in other mammals, to see if Schilling and Wahl’s results hold for these compounds.

References

[1] Bruce C, R. Weatherstone, A. Seaton, and W. H. Taylor. Histamine levels in plasma, blood, and urine in severe asthma, and the effect of corticosteroid treatment. Thorax. 1976.

[2] Butt AM, Jones HC. Effect of histamine and antagonists on electrical resistance across the blood-brain barrier in rat brain-surface microvessels. Brain Res. 1992 Jan 8;569(1):100-5.

[3] Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, Tenenbaum C, Westfal RE. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):65-71.

[4] De Marchi, Sergio M.D., Emanuela Cecchin, M.D., Danilo Villalta, M.D., Grazia Sepiacci, M.D., Gianfranco Santini, M.D., and Ettore Bartoli, M.D. Relief of Pruritus and Decreases in Plasma Histamine Concentrations during Erythropoietin Therapy in Patients with Uremia. N Engl J Med 1992; 326:969-974 April 9, 1992.

[5] Mayhan, WG. Role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier. Brain Res 1996 Dec 16;734(1-2)70-6, pubmed ID 9017232.

[6] Patnaik R, Mohanty S, Sharma HS. Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat. Acta Neurochir Suppl. 2000;76:535-9.

[7] Schilling L, Wahl M. Opening of the blood-brain barrier during cortical superfusion with histamine. Brain Res. 1994 Aug 8;653(1-2):289-96.

[8] Sharma HS, Nyberg F, Cervos-Navarro J, Dey PK. Histamine modulates heat stress-induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: an experimental study in conscious young rats. Neuroscience. 1992 Sep;50(2):445-54.

[9] Varon, David. Personal Communication: “Of course” histamine modulates BBBp.

Categories: other

Twenty-four hours with 5,000 Jews

November 8, 2015 Leave a comment

Dinner with Sonja, my father, and his wife.

Dinner with Sonja, my father, and his wife.

It was a really quick trip, with just barely 24 hours in the Orlando hotel that housed the 5,000 Jews at the URJ Biennial. But it was worth it.

I managed to squeeze in time with good friends and colleagues, dinner with my father, a book signing, a panel presentation, and a pre-announcement announcement. (Look for more on that here soon.)

The Jewish Book Council had brought me down, as part of their partnership with the URJ, for a panel discussion along with Aviya Kushner and Michal Lemberger on “Rereading the Bible: Text, Subtext, and Filling in the Gaps in Between.”

Signing Books for the JBC at the URJ Biennial

Signing Books for the JBC at the URJ Biennial

Joe Biden was scheduled for Saturday evening, by which time I was already en route back to New York. At first I didn’t care that I was missing his address and the inconvenient security that it necessitated. But apparently it was quite an event, with the vice president praising the Jewish commitment to social justice and thanking the Jews for never remaining silent.

We got the idea, of course, from the prophets of the first millennium BCE, whose vision for a better world lives on a hundred generations later.

Fittingly, the taxi driver to the airport had foreshadowed the acknowledgment of that achievement. A woman from Haiti, she heard us talking about this and that, and in response told us how much she admired the Jews and the way they kept their heritage alive.

What a thing to be a part of.

Categories: other

The Heartbleed Bug Explained in Non-Technical Language

April 11, 2014 Leave a comment

Heartbleed Bug ExplainedI’ve been asked by a lot of people to explain the “heartbleed” bug in non-technical terms. It’s really not complicated.

There are two parts to understanding what’s going on.

The first part is how computer memory works.

Computer memory is like a book of pages made from magic slates or mini whiteboards. Anything can be written on any page, and every page can be erased and overwritten with something new. The pages go in order, but the information doesn’t have to, which is why the computer constantly updates a changing table of contents to keep things straight.

For example, when you connect to, say, one of your bank’s computers to pay your bills online, that computer has to keep track of your name, your account number, your password, etc. So it puts all of that on whichever page is convenient — call it page 99 — and also makes a note in the table of contents so it knows where your information is.

The second part of understanding the heartbleed bug is knowing about an obscure part of the way computer connections work.

When your computer (or phone, or whatever) connects to your bank’s computer, you want to make sure that no one except you and your bank have access to the information you’re sending back and forth, like your password or your account balance. To make this possible, your computer and the bank’s computer work out what is essentially a brand new secret code, and use that to create what’s called a “secure connection.”

This process of negotiating a code is slow, so if you’re sending a lot of information back and forth (which you almost always are), you want a way of indicating that whatever you’re sending is part of an ongoing conversation. In other words, instead of creating a new code each time you type something or click on something on your bank’s website, you want some way of indicating that you want to keep using the code you have.

The mechanism for keeping a code active is called a “heartbeat,” and it’s pretty simple. You send an encoded message, and the other side decodes it and sends it back. It’s like you keep saying, “prove that you understand our secret code.” Because this is a code that you and your bank just created, no one else has it, so this is a pretty reliable system.

Of course, your bank’s computer has to write down your message on one of its pages. Let’s say it picks page 101. It writes down the message, then sends you page 101.

To make things even more secure, you get to choose how long your heartbeat message is. It might be one page. Or it might be 64 pages. If it’s 64 pages, the bank’s computer writes the whole thing down and sends back all 64 pages.

And here we come to the heartbleed bug: The way they programmed this thing, the computer at the other end doesn’t check if you sent as much as you said you did.

So if you say you’re sending 64 pages and only send one page, the computer will write down your message on page 101, but send you back pages 101-164. This means that you’ll get 63 pages of other people’s stuff!

And this could be anything. It could be someone else’s account balance. It could be someone else’s password. It could be someone else’s PIN number for their ATM.

But none of those are the worst case scenario. The secret codes that make secure communication possible all depend on keeping special keys (as they’re called) secret. Here the details really are complicated, but the bottom line is that the security of the Internet depends on the secrecy of these keys

Your bank — and only your bank — has one of the keys, which is why you can trust your on-line banking. But if that key just happens to be on page 102-164, which you just stole, you can pretend to be your bank!

This means that even once the bug is fixed on your bank’s computer, you can’t know for sure if you’re sending your information to your bank, or to a guy in Africa who’s robbing you blind.

In short, because the heartbleed bug reveals random pages in otherwise-secure computers, it’s not hard for malicious computer users to grab your private information and to grab the secret keys that will let them masquerade as a site you trust.

Categories: current events, other

The Surprising Value of Downtime at Work

February 10, 2014 2 comments

To many outside observers, it’s a waste to have employees sitting around and doing nothing more than chat. But the outside observers are wrong, we learn from MIT’s renowned Dr. Alex Pentland, who has studied how to increase productivity and creativity at work.

Among his conclusions are that interaction among workers is one of the best predictors of overall work productivity.1

For example, he studied a call center at Bank of America. Call centers are interesting because they have exact data on productivity. They know how much each person gets done per hour. Call centers are also interesting because, at first glance, it seems that any time an employee is not working is time wasted.

But it turns out to be just the opposite. By increasing the time employees spent together on coffee breaks, Dr. Pentland increased each worker’s productivity.

To be clear, in this case he didn’t give the workers more downtime. He rescheduled their downtime so that they would have breaks together.

I think the lesson for organizations that value productivity is to make sure their employees get to spend unstructured time together at work.

Dr. Pentland didn’t just study call centers, and he didn’t just study productivity. For instance, he also looked at an IT support department, one which — like the call center — has clear records on productivity. He found the same thing: he could predict the employees’ productivity by looking at how much they talked to each other.

Dr. Pentland investigated creativity, as well, and found, again, that interaction was crucial: “the difference between low-creative groups and high-creative groups is their pattern of face-to-face exploration outside the group.”

All of this (massive) research points in a single direction: Giving people time at work to talk to each other is good policy all around.




1. Social Physics: How Good Ideas Spread — The Lessons from a New Science by Alex Pentland. Penguin Press HC, 2014. Pp 93-97.

Categories: other

Just Because You’re Right Doesn’t Mean the Other Guy is Wrong

October 10, 2013 1 comment

Sometimes the opposite of the right answer is another right answer.

It’s counter-intuitive, but it’s true. And I think it’s important.

Noble Prize-winning economist Thomas Schelling gives us a helpful example. Tying together sports and animal science the way only he can, he starts by quoting the first paragraph of a book by Leonard Koppett about baseball: “Fear.” That’s the whole paragraph, and it’s a good one. Then on the theme of fear, Schelling reminds us that dogs can actually smell fear, and their reaction to fear is aggression. This means that it makes perfect sense to be afraid of dogs. At least, it’s the experience of someone who’s afraid of dogs that there’s every reason to be afraid of them.

But the catch is that people who aren’t afraid of dogs find that it makes just as good sense not to be afraid of dogs. That is, it’s the experience of someone who’s not afraid of dogs that there’s no reason to be afraid of them.

Two people. Two different answers to the same question, both of them rational. But just because they’re both right doesn’t mean that they are both just as good.

Precisely because they are both right, we have a choice — in this case a choice between living in justified fear, or justifiably living free of fear. It seems to me that the better path is the one without fear and without dog bites.

But I can only imagine how hard it would be to convince someone who’s already been bitten a few times. In fact, if such a person and I tried to find the fearless path together without the proper preamble, the fearful person would join me, express entirely rational fear, cause the dog to get aggressive, and then the dog, seeing me as the easier target, would attack me.

The fearful person would leave vindicated (if unscathed). But my perception would be that the fearful person ruined my previously good relationship with dogs. We would never see eye to eye, and might never understand why the other one can’t grasp our own eminently sensible and correct position.

The truth is, I don’t know if dogs actually do smell fear. (Schelling’s other example is bomb diffusion officers, whose fingers tremble if they think the task is dangerous, but the task is only dangerous if their fingers tremble.) I only bring it up because there are usually lots of right ways to do something, with various combinations of freedom, constraint, trust, skepticism, praise, discouragement, encouragement, holiness, and banality.

Just for example, in an environment based on distrust, people will quickly find that they are right not to trust their fellow. But people who trust each other can be just as right to do so.

The more general point is that it might be helpful, the next time we think we know that other people are wrong, to ask if maybe all we really know is that we are right. Because if so, maybe they’re right, too.

Finally, returning to the dogs and the lessons we learn from them, a question presents itself: Which one do we want to be? The one who spreads fear or the one who spreads calm?

We get to choose.

Categories: other

“The Warwick Files: Checkpoint” is Now Available

December 5, 2012 Leave a comment

The Warwick Files:  Checkpoint

The Warwick Files: Checkpoint

I’m pleased to announce the publication of “Checkpoint,” the first story in my new thriller series: The Warwick Files.

The stories feature Police Chief Coyote “Kai” Goodman, whose past is so secret that even his cover story is classified. The setting is Warwick, NY, where, according to the official count, there are no spies.

In the inaugural story, “Checkpoint,” a man evades a police checkpoint and unknowingly triggers his own murder. Police Chief Kai Goodman knows why. Do you?

The story is available in soft cover for $3.95, and, like most short stories, for only $0.99 on Kindle. Take a look, or start with the official trailer.

I wrote this to be a fun diversion from my research (even though I try to have fun with that, too). I hope you enjoy reading it as much as I enjoyed writing it.

Categories: other

Who is Your Chief Impression Officer?

September 12, 2012 Leave a comment

Everyone knows the value of first impressions.

The ancient Romans had a saying: vestibulum domus ornamentum est (“the entrance hall is a house’s jewel”), by which they meant that people judge a house on what they first see. The Roman rhetorician Quintilian added that the worst impressions are also the most lasting (haec ipsa magis pertinaciter haerent quo deteriora sunt). The English playwright William Congreve agreed (“There is a great deal in the first impression”), and so did Dickens (“First impressions, you know, often go a long way”).

And our modern proverb that “you never get a second chance to make a first impression” is so common that it’s attributed to a variety of people.

Yet for all of this, at most not-for-profits and small businesses no one is responsible for first impressions. Frequently, the job of first impressions is left as an afterthought, relegated to someone with another job (a secretary, say) or to whoever happens to answer the phone. Other times, the people in charge of different kinds of first impressions — the website (on-line), office (phone), and physical space (in-person) — never talk to each other. Or just anyone is allowed to place a hastily written hand-scrawled notice on the front door. Sometimes the people in charge don’t even know how the phone is answered, let alone whether the entrance hall and website are coordinated to give the same first impression.

So here are my questions:

1. What kind of a first impression do you want to give people?

2. Do your entrance hall, website, and phone personas convey that impression?

3. Who is your Chief Impression Officer?

Categories: other

We Have Sinned: Sin and Confession in Judaism

August 29, 2012 1 comment

We Have Sinned:  Sin and Confession in Judaism by Rabbi Lawrence A. Hoffman

We Have Sinned: Sin and Confession in Judaism, by Rabbi Lawrence A. Hoffman, PhD

Just in time for the High-Holidays, a book about sin and confession in Judaism: We Have Sinned.

The third entry in the “Prayers of Awe” series, and the 15th volume my father and I have worked on together, the book offers in-depth essays on the themes of sin, penitence, confession, and the High-Holiday prayers that deal with them; my translations of those prayers, along with detailed notes; and over two dozen shorter essays expanding on the themes of the prayers.

I had a great time preparing my contributions to this volume. I hope you enjoy it, too.

(The book is available in print as well as the major e-formats: Kindle [Amazon.com], Nook [B&N], and iBooks [Apple].)

Categories: other

A Tale of Customer Service and Customer Disservice

July 20, 2012 1 comment

Help/Blame GraphicA curious thing happened to me on the way home from a conference in Detroit: Delta Airlines gave me a hotel voucher for the Westin in the airport, and the Westin refused to honor it.

What’s really interesting is the difference between the follow-up response from Delta and from Westin and its parent company, Starwood Hotels. Delta tried to help and Starwood tried to cast blame.

The background is this: Weather was creating havoc across the eastern seaboard with practically no flights landing anywhere from Washington to New York, so my 5:30pm flight from Detroit to LaGuardia was delayed. By 6:30pm, the 3:30 to New York hadn’t left yet, the 5:30 (my flight) was tentatively scheduled for 7:45, and the 8:15 flight had an estimated departure time of 10:30. It was a mess.

I explained to Delta that I had been at a five-day conference and I was exhausted. If I landed in New York at 9:30, I thought I’d still be able to drive home safely. But if I landed at, say, 11:00, or (as was predicted for the 8:15-revised-to-10:30 flight) around midnight, I’d be too tired to drive. Could they help?

It was a gray area. On the one hand, the delays were weather related, and the airlines don’t usually take any responsibility for anything that might even rhyme with weather. On the other hand, I expressed my concern that Delta couldn’t give me solid information, and I had to make a decision. A supervisor agreed to put me up in a hotel, and then a desk agent started phoning around to find out where there was space. Fifteen minutes later, she told me that the Westin, actually in the airport, had a room for me. (Delta also gave me a $6 voucher for dinner, which is fine if all you want is a chocolate-chip cookie and a bottle of water to wash it down — but that’s for another day.)

Ten minutes later I handed the hotel voucher to an immaculately-dressed and hyper-polite desk agent at the Westin. After scrutinizing the document, he seemed concerned, though he didn’t tell me why. “Let me make a phone call,” he said and disappeared into the office behind the check-in desk. I thought he was new and didn’t know what a voucher was, or perhaps didn’t know how to process it. I was sure that some better-trained employee would set him straight.

But when he came back he told me simply, “I won’t accept this.”

“May I please speak to a manager?” I asked.

“I am the manager.”

Oh.

It took a few minutes for me to learn that he didn’t have any rooms for voucher customers. That didn’t seem fair, and I told him so.

The manager agreed to make a few more phone calls. Some twenty minutes later I learned that, in fact, he didn’t have any rooms at all. His phone calls had been to try and find out who had made the mistake.

“I don’t care who’s at fault,” I told him — though my suspicion was and still is that the Westin gave my room to a VIP Westin customer even though they’d already promised it to Delta. “All I need is a hotel room, here or somewhere else. Can you help me? Do you have provisions for this sort of thing?”

He wouldn’t help me.

At this point I was balancing a few competing factors: I needed a hotel room. I also had to pick up my checked bag from baggage claim, and I was worried that if I waited too long they’d put it somewhere where it could be retrieved only after a lengthy wait in line. My cell phone didn’t have reception in the Westin lobby, so I couldn’t make any arrangements for myself from there. But the manager had left a voice message (or so he said) at Delta and they were on their way to help.

I decided to leave my carry-on at the Westin, run to baggage claim, get my bag, and run back as fast as possible, hoping not to miss Delta.

As it happened, I wasn’t late to baggage claim but early, a fact I learned when I didn’t see my bag and had to wait in (a mercifully short) line after all. There a Delta agent helped me track down my bag. I mentioned something like “at least one thing is going right,” and when she asked what I meant, I told her about the hotel. “Well let’s find you another hotel,” she said. And she did.

I went back to the Westin, got my carry-on, and took a shuttle to the Best Western, where a room key was waiting for me. Having just joined Twitter a little while ago, I tweeted a question to @DeltaAssist, copying @StarwoodBuzz and @Delta.

And this is where things really get interesting. Apparently from my tweet it wasn’t clear that I had found a replacement hotel.

Delta replied immediately offering to help.

Starwood also replied, publicly blaming Delta: “This seems to be an error on Delta’s end.”

My point here is not who made the initial mistake. I really don’t care. I have the manager’s name from the Westin, for example, but I’m not publishing it.

Rather, I think this is an example of two kinds of cultures: helping and blaming.

I’ve written before about the value of customer service (“For $12.17 you can have the best school in the country“), in the context of TD Bank helping me with a mistake that was my own fault.

It seems to me that helping a person no matter who is at fault, and whether or not the person is a current customer, is both kind and good business sense. Yet remarkably few businesses will spend money/time/energy/resources to help a person when they don’t think there’s any immediate financial gain in doing so.

I spend most of my professional life with faith-based not-for-profits, and, perhaps surprisingly, it’s been my experience that they tend not to do any better. They’ll often help a person only when it’s specifically part of their mission — because the person is a member, say, or a grant recipient.

What are the policies and culture where you work? Do you help or do you blame?

Categories: other

How Maximizing Profits is Making Life Worse for Everyone

April 9, 2012 2 comments

“we end up with schools that don’t work, planes that only young children fit comfortably in, hotels that are too dark to see if your clothes match, phone menus from hell, long lines to buy food, burdensome workweeks, and so forth”

It is well known that people are generally sensitive only to big relative changes, and tend not to care about, or even notice, small ones. This is why three shots of vodka is much more than one, but if you add two shots of milk to a gallon of milk, you still have about a gallon. They’re both a 3-ounce addition, but the vodka increased 200%, the milk only about 2.5%, and we notice the percentage, not the absolute amount. Similarly, a fifteen minute car ride feels longer than a five minute one, but seven hours and 15 minutes on a flight doesn’t seem different than only seven hours and five minutes. A child who grows from four feet to five has shot up, while a mountain in the Rockies that goes from 8,200 feet to 8,300 looks the same.

“maximizing profits is a bad idea in the long run”

This can be a problem when small changes yield big profits. If, for example, you could earn a million dollars by making your house only 5% darker, you’d do it. You wouldn’t even notice the 5% reduction in light. But here’s the rub. If you’d do it once, you’d do it again and again. Pretty soon you’ll end up rich but living in the dark.

Worse, you won’t even know what went wrong. You’ll try in vain to isolate which 5% decrease did you in, and you’ll conclude that every step of the way seemed like a good one. Each time you got a lot of money for a difference you couldn’t even notice.

This dilemma is especially pronounced when big organizations get involved. Most of us can’t earn a million dollars by making changes to the lighting, but hotel chains can, and they do, which is why hotel rooms are so dark. Of course, it’s not just lighting. That same chain makes the soap bars just a little smaller, and gathers up the tiny profit from each bar of soap for a huge increase in the bottom line. Airlines put the seats in their planes just a little closer together to augment revenue. Oil companies raise the price of fuel by just a cent or two every so often. Call-center managers reduce staff just a tad. Supermarkets provide slightly fewer cashiers. Managers demand just five more minutes out of each employee’s workweek.

And it’s not just the corporate world. Municipalities suffer the same kind of fate when they cut the number of police just a bit. So do school districts that reduce each teacher’s training only a little. And at the federal level, a decision is made from time to time to spend just 1% less on some important program.

What we end up with, though, is schools that don’t work, planes that only young children fit comfortably in, hotels that are too dark to see if your clothes match, phone menus from hell, long lines to buy food, burdensome workweeks, and so forth.

The problem comes from the seemingly desirable goal of maximizing profits combined with the human tendency not to notice small changes.

The only solution I can think of is to agree that maximizing profits is a bad idea in the long run.

To look at another example, imagine a swimming pool. With so much water, it’s hard to imagine that giving away a single cup could make any difference. Yet a pool can be emptied one cup at a time. If you think you can sell one cup and not impact the pool, you’ll end up with lots of money and nowhere to swim.

At first glance, it might seem as though the same mechanism that prevents us from noticing slightly darker rooms also means that a huge hotel chain won’t care about slightly higher earnings. For example, Marriott International had gross revenue of over 12 billion dollars in 2011. That’s over 12,000 million dollars. Does it really matter if it’s 12,321 million or 12,322? Sometimes, maybe not, though other things being equal any CEO or board member will opt for more money instead of less, no matter how small the difference. But other times, even a tiny amount can make a huge difference: if saving just a thousand dollars means not going over budget, even a huge hotel chain might need that $1,000. Or if a bonus for some employee is tied to meeting a certain goal, that $1,000 might be the final step toward getting the bonus.

The overhead cost of making any change might also seem important. Even if smaller bars of soap are cheaper, for example, the one or two cents saved on each bar is offset by the costs of putting someone in charge, of changing the specs, etc. But even though this may mitigate the tendency for our lives to get worse, it doesn’t eliminate it. Furthermore, as companies grow larger, the overhead costs become less significant compared to the potential savings.

Similarly, eventually the soap will be so small, the lighting so dark, the teachers so poorly trained, that a 5% reduction doesn’t net much profit. For example, if a bar of soap weighs 3.5 ounces, cutting 5% means not having to pay for 1/6 of an ounce of soap. Multiplied by over half a million Marriott rooms and 365 days/year (potentially over 180 million guests, but probably closer to 100 million), that’s up to almost 1,000 tons of soap each year saved by that 5% cut. But once the bar is whittled down to only 1 ounce, the same 5% cut saves less than 200 tons. It might not be worth it. Unfortunately, this pattern just means that there might be a lower limit to how bad things can get. Even more unfortunately, as companies grow larger, this limit goes down.

So, again, the only solution I can think of is to agree that maximizing profits is a bad idea in the long run.

Categories: other