Gaussling is a senior scientist in the chemical business. He occasionally breaks glassware, spreads confusion and has been known to generate new forms of hazardous waste. Gaussling also digs aerospace, geology, and community theatre.
As in the past, I will discuss some observations as a chemical scientist with cancer.
In 2013-4, I was treated for stage 4 squamous cell throat and separately, stage 4 prostate cancer and have been in remission since.
I picked up a new cancer as well as another precancer diagnosis a few weeks ago in late July, 2025. My very first colonoscopy (!!) identified several small precancerous polyps which were snipped out. The procedure was a breeze as was the much-derided colon-blow opening festivity. Propofol is amazing stuff.
Eleven days ago, I had my second partial glossectomy. The first in 2022 turned up a precancerous squamous cell lesion on the side of my tongue. The second, last week, removed a squamous cell tumor. A shallow, nickel-sized piece of tongue was removed along the middle-left edge. A skin graft from my arm was not performed, thankfully. Imagine having a hairy skin graft on your tongue!!
Prior to the surgery, I had to sanitize my arms, legs and torso with chlorhexidine (below as the gluconate), a common antiseptic. They even reamed out my nostrils with Povidone-Iodine. Incidentally Betadine is a trade name of Povidone-Iodine. First time for body-wide sanitization.
Graphic from chemical supplier TCI from Google images. This structure is the digluconate salt. Notice that the lower structure is a carboxylic acid and the chlorhexidine structure above is an is called a bibisquanide. Altogether there are 2 acid protons and 10 basic nitrogen atoms. The combination is actually an ammonium/iminium salt for water solubility.
Povidone is the polymer poly(N-vinylpyrrolidone). It is used in many medicaments and is regarded as relatively safe. The chemical structure is shown below.
Image from Wikipedia. Povidone Iodine is a broad spectrum bactericide useful against bacteria, protozoans, fungi and viruses. It is prepared by combining PVP with hydrogen iodide and iodine. It slowly releases iodine in situ.
/*begin anecdote*/
Of interest to me is the use of N-vinylpyrrolidone. In a previous life I had prepared poly-NVP by solution polymerization on many occasions as a base for experimental liquid ink charge carriers in xerographic imaging. Very simple to make. The point was to replace existing liquid inks that used flammable hydrocarbon solvents. The startup who recruited my small startup went under because the solvent they were banking on didn’t dry fast enough for their economic model. The whole thing rode on the use of low viscosity 0.5 centistoke silicon fluids.
The business plan was to provide the photocopiers at low cost and then rack in the profits on consumables- a common strategy in the printing business. The founders were all retired from the giants of the photocopier industry. They knew all about the technology except for this seemingly small ink modification.
Alas, the drying rate was far too low and the image transfer was of persistent low quality. The elderly and retired engineer behind this invention fell over dead in the middle of it. He provided the patents but never actually built a prototype or even physically investigated the suitability of silicone fluids and ink composition. It was a big handwaving exercise that the founders bought hook, line and sinker. In the end, the sinker took them to the bottom still grasping for that golden ring they so desired.
/*end anecdote*/
The ever-popular opioid fentanyl was part of the basket of anesthetics used in the partial glossectomy procedure. A little mentioned side effect of fentanyl is extreme itchiness, particularly of the face. In post-op I had this in spades and it was very uncomfortable for several hours. My interest in the chemistry of fentanyl had never fully ballooned to include side effects.
The tumor board at the university hospital I go to voted that I should undergo exploratory surgery to examine the many nearby neck lymph nodes for evidence of spread. This would point to further treatment. My throat cancer was discovered when a swollen sentinel lymph node fused to my carotid artery and decorated my neckline.
I’ll admit that a salad of pessimism and resignation with breadsticks of nihilism has arrived at my table at life’s Olive Garden. Much depends on how the upcoming lymph node surgery will come out. We’ll have to wait and see.
Summary: This essay addresses the important role the federal government has played in promoting the American march of progress. The old saying that “Necessity is the Mother of Invention” has a large element of truth to it. It is not enough to identify a problem or challenge. For a person, group or organization to solve a technological problem or challenge, the goal must be understood completely, resources acquired, a plan must be constructed and approved by those who control the purse strings, and skilled people must be organized and set to work on the matter at hand.
The federal government can provide the Necessity needed for attention and resources put to play in achieving a goal. For instance, NASA will set a goal and is able to open a project up for bid. The gov’t can provide seed money to the contractor for prototype equipment to present with their bid. Government grants provide the necessity to stimulate invention, hopefully on a competitive basis.
……………………
I have been a lifelong aerospace enthusiast from Project Mercury forward to the present day. What I’m realizing, however, is that I’m increasingly skeptical of the value of further manned space flight by NASA. Whatever the 6 successful manned Apollo landing missions on the moon may have found tramping around the regolith up there, evidently not enough value was found to compel the USA to go back. Obviously, the Apollo program was partially a geopolitical stunt to rival the USSR for prestige and by many measures the USA won. But what did we win? Prestige and a great many valuable technological spin-offs.
In the early 1960’s the US government financed and organized JFK’s challenge of landing a man on the moon and returning him safely to Earth by the end of the decade. Our government allocated considerable national treasure to the moon landing project and put lives on the line. Arguably, of greater importance than a round trip to the moon was the powerful boost to aerospace, computer, and other technologies. The technology-push advances funded by the government would soon become important economic drivers for industry.
In fulfilling Kennedy’s challenge there was both popular excitement about the space program and more than a little skepticism. The USA was increasingly bogged down with the Viet Nam war. Into the early 1970s, the western geopolitical argument about the advances of communism, the Domino Theory, was still cited, but it was gradually weakened by lack of popular support for the war and the loss of American blood and treasure invested in keeping communist influences out of southeast Asia. By the mid 1970’s, the US had pulled out of Viet Nam leaving behind millions of casualties and little to show for the effort. Added to Southeast Asia was the self-destructive meddling with the Cuban communist state. Castro died of old age in his communist bed.
There is an old saying that went “He’d complain if they hung him with a brand-new rope”. The suggestion was that some folks would complain about simply anything. Beyond the geopolitical and apparent military threat of the USSR beating the US into space were the much-ballyhooed technological benefits of the program. One of the oft-cited spin-offs was a Teflon coating for frying pans. It was an example that most citizens would understand and appreciate. Many incorrectly believed that NASA invented Teflon. Actually, Teflon was discovered unexpectedly in 1938 by the DuPont chemist Roy Plunkett.
Libertarians have argued (to my face) that if we wanted non-stick Teflon frying pans, why not just invent it? The introduction of any new and revolutionary product by a corporation carries financial risk and possible loss of reputation. The vaunted contribution of NASA to perfluorocarbon (PTFE) polymers was to push forward projects that required PTFE specifications. Industry did the rest by finely developing technology for PTFE production to meet the demand. Once there was an inkling of demand, industry kicked into gear. It was market-pull by that time.
NASA is very much in the technology-push world whereas many businesses are more safely oriented to market-pull. Technology-push is about invention of leading-edge vehicles, equipment, substances, instrumentation or services. Technology-push requires early adopters willing to wager that the new tech will give them a competitive edge. Government provides a ready-made early adopter.
Market-pull is where a manufacturer produces known or existing products and services. They compete by offering better availability, price and quality than their competitors.
Technology-push is the world of the tech startup. A start-up founder has a product or service that is sure to be a hit if only their products could get manufactured and pushed into the market. Tech investors will examine the startup’s business and financial plans and take a closer look at the technology or service to be offered. Is there a prototype? Is valuable intellectual property protected under patent? How stable is the supply chain or is there one? Will the company be sustained on the tech product only or will consumables be produced as well.
Importantly, is the technology-push startup looking to produce just a single product or is the technology expandible across a spectrum of applications? What if the product performs below acceptable tolerances or simply fails in the field? A startup with everything invested in a single product model is a “One-Act Pony”. Wonderful though the One-Act Pony may be, it can get sick and die in the marketplace. It can grow old and obsolete, giving way to falling sales and the mad scramble to develop a replacement product. I’ve been a part of 2 startups hoping to produce one-act ponies. The ponies died and we hit the streets.
Investors can analyze market-pull business plans by looking at the economics of demand as well as distribution of existing or similar products. Annual sales can be estimated, EBITDAs calculated, and profit margins uncovered. If the profit picture fits the general business model and timeline of the investors, they can release funding rounds to the startup with benchmarks to be met.
Necessity as the mother of invention?
In normal circumstances, industry operated by ambitious people may be motivated to advance their technology skillset to realize entry into new and promising markets. However, that said, an industry that only acts to match technological advances set by competitors is not showing the mettle required to launch a new paradigm in the technology-push manifold. Merely matching the competition does not quite describe a technology-pusher.
A technology-pusher is likely to find that they must walk the manufacturing highwire without a net and perhaps for a long time. Unless you are quite wealthy, launching a startup will likely hold personal financial risk. Commonly, external funding means that some percentage of ownership or shares will be given to the investors. By the time the product or service hits the market, the founders may find themselves as minority stockholders. Their dreams of grand wealth and influence is tempered by reality.
A naïve book-end view of technology pushers. Scientists are by nature more interested in phenomenology and naturally may see a two-dimensional universe of space and time. Scientists may gravitate to precision and accuracy while the engineer is also interested in not just precision and accuracy but also costs. When developing an engineering design, the engineers will constantly consider costs within the boundaries of space and time. Graphics by Arnold Ziffel.
A technology-push company is often started by engineers or scientists with experience in a particular subfield. Scientists commonly receive little or no business education as a degree requirement. Their role is the science guru. Engineers, on the other hand, fully understand the cost imperatives of a project and are able to design to remain within tight cost constraints.
In science, scientists are the main honchos. In business, engineers are the princes of the kingdom. They design projects, lead them, and come in on budget on time. A CEO with an engineering background is not at all unusual. They understand money part.
There are more than a few definitions of science out there. Every scientist you ask will give their favorite variation on a common theme. The whole business of science is built ideally around the concept of the scientific method. One of the better broad definitions of the scientific method is this-
The scientific method – the method wherein inquiry regards itself as fallible and purposely tests itself and criticizes, corrects, and improves itself.
Wikipedia as a Source of Authoritative Information
First, a homily on Wikipedia as a resource. It’s been my observation that in areas that I am familiar with, i.e., chemistry, aviation, the history of science and a few others, the content I’ve encountered comports well with my general knowledge. The more links and references, the better. And, more often than not, the links actually reflect the content that referenced it. What’s more, Wikipedia encourages input and corrections by the broader community and if you go into edit mode, you can see the list of edits over time. I’ve contributed to a few edits myself. Are there errors or just simple BS in Wikipedia? Well, of course. It’s been said that a camel is a horse designed by committee. While Wikipedia may reveal some of this camel design in places, basically most everything we read or hear is subject to this shortcoming. The freedom to edit a Wikipedia entry is a type of “peer review” but the qualifications of the peers is unknown. Believe me, in science publishing, anonymous peer reviewing is populated with more than a few sanctimonious jerks whose motivations may not be pure.
I’ve spent my career diving into the primary chemical literature via Chemical Abstracts. Primary literature is crucial, but it is usually very narrow in scope and often subject to later revision. This is why review articles, books and monographs are so important. Someone has combed through the primary literature and brought together some structure in an area of study. Wikipedia has become a third tier of scientific information and access for anyone. While it seems quite accurate, we should always be using our best judgement as we read the content. Do the links support the statements? Are there enough links, etc.?
A great deal has been written about the scientific method by those more capable than I so I won’t attempt to blather through it. Instead, I will share an example of how asking a very basic question led me to a treasure trove of information expanding my understanding of the universe.
Back to the definition of science. From a Google search of “Science”: ”Science is the pursuit and application of knowledge and understanding of the natural and social world following a systematic methodology based on evidence.” I’ve quoted it because I can’t improve on it.
Science is frequently regarded with excessive reverence, suggesting that it is solely the realm of “proper scientists” and embodies the ultimate truth. However, in reality, it is open to anyone armed with curiosity and resolve. Curiosity drives inquiry, but it is also enhanced by a prepared mind. Some questions illuminate, while others can deceive. A well-posed question can propel one towards the heart of a matter. A ready mind can recognize false trails early on and steer clear of them.
How or Why?
I favor “how” questions over “why” questions because they foster a more mechanistic inquiry into nature and adhere to established physical principles. “Why” questions often carry philosophical or religious connotations and can be laden with presupposed motives or assumptions. This doesn’t render “why” questions invalid; however, they may veer away from the realm of observable natural phenomena, the foundation of scientific inquiry. Asking “How did Stella move the lamp?” may differ from “Why did Stella move the lamp?”. The interchangeable use of ‘why’ and ‘how’ in everyday language can result in imprecise thinking and sloppy conclusions.
Obviously both how and why questions are useful is answering a question. Judicious use of ‘how’ and ‘why’ can lead to more focused thinking about either a mechanistic or motivational question. ‘How’ gets to physical causality whereas ‘why’ often seeks mechanist details but may also leave room for psychological motivation. Either entry into a question is valid depending on what a person wants to know: Physics or psychology.
Sharply pointed scientific inquiry requires the meticulous use of language to convey exact meanings. This scrupulous attention to language demands a precise vocabulary that narrows the scope of interpretation. While this may seem tedious, the benefit lies in getting quickly to the heart of a question. Similarly, lawyers have developed their specialized legalese for this very reason.
Being more precise in one’s use of language is very useful if you’re plagued with complex situations, incomplete information or the need to focus on a mechanistic pathway. ‘How‘ thinking helps with this.
>>>The best questions lead more directlyto the best answers. <<<
As one accumulates a greater vocabulary over time, the ability to apply nuances into your thinking and communication increases as well since even synonyms can differ a bit in their meaning. As you spend more time in scientific pursuits, you start to realize the value of having good questions to ask. In fact, the skill with which you formulate questions can drive your research further into the unknown, which is where everyone wants to go.
Assigning the stereochemical configuration of a cyclophane or a metallocene is a rare task out there for most chemists. Two classes of molecules, cyclophanes and metallocenes, have flat features that can be tough to assign priority numbers to.
I ran into an organic chemistry resource on LinkedIn that was worth zooming in on. It is a blog called MakingMolecules and it features graphics that give instruction and illustrate most aspects of sophomore organic chemistry. Having taught organic chemistry I know that nomenclature is a favorite topic among students (wink wink, nod nod), especially where stereochemical configurations are concerned. Ah …, if only the world had only chiral acyclic hydrocarbons to name. As we know, there is much, much more than that.
Finding a chiral carbon atom on most simple molecules isn’t that hard. Find a carbon atom with 4 different groups attached and then check for symmetry around it from every direction while you rotate the parts.
If it has rotational symmetry or a plane of symmetry including the atom of interest, then it may not be a chiral “center”. Molecules with a C2 symmetry axis but without a mirror plane can be chiral.
The more difficult molecules to characterize as chiral are those that have unusual rules necessary for an R or S configuration.
I subscribe to “Your Local Epidemiologist” by email. It’s written by a PhD epidemiologist on her substack and is quite informative. Below are some excerpts on people doing their own research-
“The beginner’s bubble. In early stages of learning, confidence tends to increase faster than skill, meaning people often overestimate their accuracy when they are first learning something new.
The quest to “do it all on your own” can backfire.“Epistemic superheroes” want to figure out everything on their own and distrust other people’s information. But their task is impossible—nature is too complex for us to solve by ourselves. When the “trust no one” mantra inevitably leads to “I must decide who to trust,” it is easy to gravitate towards other like-minded skeptics. This creates a highly biased information bubble, the exact opposite of the original goal.
Assuming “unbiased” knowledge will contradict consensus. For many, doing their own research began with doubting the consensus view. Challenging consensus is healthy when new data emerges, but assuming “real” truth always opposes the consensus creates bias, undermining the search for unbiased answers.
Hmmm. Confidence rising faster than accuracy. How interesting.
Kristen Panthagani, MD, PhD is an emergency medicine physician completing a combined residency and research fellowship focusing on health literacy and communication. She is the creator of the newsletter You Can Know Things and author of YLE’s section on Health (Mis)communication. Views expressed belong to KP, not her employer.
The very idea that a person like RFK, Jr, would land in Trump’s cabinet as the Secretary of Health and Human Services seemed so farfetched as to be bad pulp fiction. Yet there he is.
I have no special insights or knowledge on HHS other than what I read. Everything that could be said about the pathetic case of RFK, Jr, and his place in pseudoscientific madness has already been stated by better writers than I.
If you wanted to purposely obliterate certain patches of modern medical developments from the last 120 years, there are few better hatchet-men than RFK, Jr. RFK, Jr., is not without a certain charisma. His strength of conviction is taken as a measure of truth. He is a talented speaker despite his speech impediment and, like most popular speakers, is a performer playing to the entire USA. His compelling position on the stage lends a credibility to his assertions. His slashing of HHS funding and staff is jaw dropping in its extent and coverage.
The University-Government-Industry R&D Complex
Until Trump, the USA had accumulated considerable technological ‘soft power‘ internationally since WWII. An element of that soft power is the American University-Government-Industry research complex. The government funds basic university research across the spectrum of science and the universities provide basic research and training of scientists and engineers. Industry taps into this valuable technology resource for skilled technologists and develops applied science for their projects.
The USA has been a very productive engine of ingenuity, especially since the beginning of WWII. However, our dear leader’s administration has been deconstructing agencies in the name of rooting out the deep state. In reality he is busy putting in place his own deep state.
Project 2025, hosted by the Heritage Foundation, amounts to a libertarian coup backed by libertarian hardliners and supported by conservative protestant evangelical Christians. I’m trying to be fair to the evangelicals, but they have woven Trump into their Christian eschatology. They may still support #47, but many are holding their noses in doing so.
Why not remove the university research funding and leave it to industry? To our neoliberal friends that might sound appealing. Universities could continue to produce scientists and engineers but leave the R&D to industry. After all, letting the open market take care of R&D is one of the goals, right? Let industry produce and pay for their own R&D talent.
The problem will be that new R&D chemists hired into a company at the PhD level would have to be trained on how to execute chemical R&D. Normally this happens in graduate school and in a post doc appointment. But wouldn’t business prefer to hire walking, talking, trained, young and energetic chemistry researchers? I think so.
In #47’s administration, research efforts are being discontinued willy nilly by inexperienced and scientifically untrained actors whose only goal is to rack up dollar savings. Their amateur appraisal of what constitutes valuable scientific activity is cartoonish.
Having been in both academic and industrial R&D, my observation is that basic and commercial science can be quite different activities. Universities have a continuous stream of fresh students and post docs to do the actual work of research at a time period in their lives when they are the most productive and at a far lower labor cost than could industry. Benefits, if any, are quite modest.
The current approach simultaneously trains scientists and engineers while at the same time developing basic science and engineering for the price of a one or more grants. In the process, the advanced instrumentation and the many subject matter experts walking around in the building aid academic research greatly. If a transformation (i.e., a reaction) goes poorly, an academic lab may try to find a mechanism. A commercial R&D lab exists solely for the purpose of supporting profitable production. This means developing the best routes for the fastest conversion and highest yields of chemicals into money. Along the way, commercial chemists may discover new chemistries or have unexpected outcomes. If they are lucky, any given R&D ‘discovery’ may lead to a new product or better control of a reaction. The result of commercial R&D may be more profitable processing but also it may be of scientific interest.
The role of the university is quite different from the role of industry in our society. Universities are funded to provide leading edge research. Here, knowledge is acquired by exploring the boundaries of particular chemical transformations or in the realm of calculation. The driving force in academic R&D is funding and publication. Every scientist wants to be the first person to discover new processes and compositions. It is not uncommon in academics for a research program to finish with a sample of 2 milligrams of product for spectroscopic analysis. For a proof-of-concept result, a sample small enough to analyze and still get a mass for the yield closes the work.
The preferred role of industry is to take up where academia leaves off. If a known composition and/or process is commercially viable, the captains of industry would prefer not to fund enough basic R&D to get a product to market. Thirty minutes on SciFinder should provide an indication of the viability of a process to produce a given chemical substance. They would prefer their chemists work on scaleup to maximize the profit margin of a market pull product rather than wading into the murky waters of technology push.
You learn to do laboratory research by doing laboratory research. Reading about it is necessary but not enough. The success of much research requires broad and deep knowledge and specialized lab and instrument skills.
The industrial end is a bit different from academia. In applied science there are two bookends in business-to-business product development-
Market Pull is development to produce products that are already articles or processes of commerce or are analogs of existing solutions. At the commodity level, a producer must compete with existing suppliers. Market pull is the domain of producers who compete on price and service, offering products that may be substantially similar.
Technology Push is the development of new technologies (components and processes) awaiting first adopters. A customer must be convinced that a new technology is worth the risk of committing to it. Customers are generally aware that a new technology may develop teething pains leading to unanticipated expenses and disruption of the timeline.
In order for a company to allocate resources for an R&D project, sales projections, cost and margin studies must be performed to convince management to proceed. A great starting point is with a known substance and a good public domain procedure for it. This is where academia really shines. Industrial R&D will collect academic research papers on all aspects of the production of a new product.
One serious caveat for industrial R&D is the intellectual property (IP) status of all of the compositions of matter and the processes used therewith. In chemistry, IP is divided between the composition of matter and the method or process. Chemistry patents are often written with Markush claims that use variables to enrobe vast swaths of compositions of matter within patent coverage.
Some academics file for patents as inventors, leaving the ownership costs to the university assignees. The thinking has been that the university may someday collect license fees from the invention. The wild-eyed inventors may honestly believe that industry will beat a path to their door wanting licenses. More chemical patents of all kinds are allowed to quietly expire unlicensed than most realize.
Research Issue
University
Industry
Discovery of new chemistry
Built to excel in it
Can do but would much rather avoid the expense and time
Publication of results
Critical to career growth and scientific progress
Research developments are confidential
Patenting IP
Mixed views. Some patents may provide revenue to the university. Patents that are contested are very expensive to protect.
Patents enforce exclusivity for 20 years and cement competitiveness of the assignees.
R&D
Much time and care can be spent on the research. Research is distributed through publications and seminars.
Prefers that existing R&D be applied to scale-up and process improvements
Career growth
Students, post docs and professors can choose academics or industry
Scientists can take the business path or stay on the R&D path
Safe and smart technology
Academics have the ability to pursue environmental and safety matters with the chemistry.
Industry is a slave to quarterly growth. Changes that will increase the quarterly EBITDA are most favored by the C-suite and the board of directors.
“A patent is only as good as the latest attempt to invalidate it”. -Arnold Ziffel.
Some loose talk about patents
Many in academia view a patent as a publication that they can stuff into their vitae. While being awarded a patent is a validation of an idea, it also means that the examiner was unable to find a reason to deny the patent. Citizens are entitled to patents and the USPTO must find a reason to deny the application. The language in a patent application must be internally consistent, be written in the ‘patent dialect’ and provide a description for others to understand the claimed art enough to avoid infringement. The USPTO does not require that the reality of the claims be proven. (I’ve been involved in 2 technology startups based on patents that were not proven by prototyping because it was not required by the USPTO. Both were business disasters because the claimed art didn’t workwell enough).
Patents can induce a high credibility impression that may or may not be valid. Patents are commonly used to impress investors and are found stapled to a business plan. The startup may have an attorney on the board of directors who is supposed to serve as council. The attorney may or may not be a patent attorney. But if they do not possess patent and technical knowledge, they can only help with word smithing documents like NDAs, contracts, and sitting in on meetings to catch the odd procedural misstep. They can bring confidence and comfort to the startup founders with business structure, agreements, and negotiations etc., sorta like a big ole’ teddy bear for the CEO.
Summary
One of the purposes of government is to protect ourselves from each other. Another purpose that has worked well until now is that gov’t has been able to blunt many of the harsh and brutal forces of nature like disease, famine, drought, earthquakes and storms.
The USA has excelled in medical research for decades. The Food and Drug Administration (FDA) was begun to assure that food and drugs were safe for the public to consume. Every new drug developed in the USA has a paper storm trailing behind it. To be compliant with FDA generally, a sizeable amount of operational rigor must be demonstrated and practiced. Food safety in restaurants and in the food supply chain as well as drug development and testing are all subject to complacency or outright evasion without gov’t oversight. People and organizations will always drift away from safe practices if nobody is watching and auditing.
Organizations, like individuals, behave like a gas. They will expand to the space available. Retiring government regulations means that there will be a good deal of new space to expand into. Regulations were originally conceived to solve or prevent problems.
I have noticed that ChatGPT has been visiting this site more and more frequently. I can’t tell what posts they have been visiting. I do write the occasional humorous or lampoon style of post so I hope for the sake of mankind that ChatGPT can tell the difference.
We’ll see if my fictional Poltroon University gains wider recognition from AI.
It is amazing what you’ll find by just looking around. While reviewing recent blood test results it occurred to me that I didn’t know the first thing about albumin as a protein. A Google word search led to numerous links but provided many images as well. The crystal structure is below.
Source. The crystal structure of human albumin. The albumin was crystallized in the presence of excess palmitic acid for x-ray analysis. Front. Immunol., 25 January 2015, Sec. Vaccines and Molecular Therapeutics Volume 5 – 2014 | https://doi.org/10.3389/fimmu.2014.00682
It is not uncommon to describe the enzyme-substrate complex as a highly specific lock and key structure. In the earlier literature is was axiomatic that enzymes are described as being highly substrate specific and use a single binding site for a given substrate. This notion is not always correct as the above graphic shows. Albumin is produced in the liver and is sort of a molecular ox cart- it can transport many substrates in the blood.
The job of human albumin is to get various substrates mobilized in the bloodstream and offer them at a desirable location. With the high molecular weight of enzymes, and the consequent low molarity available, it is astonishing that the heat of binding of substrate to enzyme can be measured at all.
One way to determine binding enthalpy and stoichiometry of a substrate to enzyme is ITC- Isothermal Titration Calorimetry. These calorimeters are available from several manufacturers such as TA Instruments and Malvern. ITC is just a type of reaction calorimeter that allows for immediate access to the reaction mixture. It is a microscale RC1 in effect. An enzyme solution can be titrated with substrate allowing for a visual determination of an equivalence point where 1 eq of enzyme active sights just matches the titrant equivalents. From such an experiment both enthalpy and stoichiometry can be measured. The image below is from TA Instruments and nicely shows the graphic output of an ITC experiment.
Source: TA Instruments product brochure. Each peak is an aliquot of titrant. Note how cleanly the signal goes to baseline between aliquots.
This graphic shows the baseline signals from titrating directly into buffer. This is subtracted from an actual run. From TA Instruments sales brochure.
Above, the background signal from the buffer represents noise in the enthalpy signal.
TA Instruments also offer equipment for so-called nano scale experiments. See below.
The TA ITC specification table. Note the minimum heat in the low volume column: 0.04 to 0.05 microJoules with a 190-microliter sample cell size.
Albumin is endowed with binding sites open to a variety of substrates. It is like a wheelbarrow or an ox cart. It can ‘carry’ numerous substrates across several categories.
The downside of such low specificity is that albumin can bind many drug compounds at the expense of dose delivery to the desired site. Doses of drugs must be adjusted to account for drug lost to blood proteins like albumin.
Some folks have all the luck. America’s Orange Jesus has been (or will be) offered a Boeing 747 to use in place of the two presidential B747s which had developed an annoying rattle and had to be taken out of service. They are presently parked at Oskar’s Jet Shop and Grill somewhere in the Pacific Northwest. In sympathy to this niggling inconvenience to #47, an old man, the royal family of Qatar has generously stepped forward and offered a super luxury B747 for the Great One for his weekly trips to his many resorts. The B747 will transfer to #47’s Presidential Library foundation where it will remain. Some are saying that it will cost a gigabuck to upgrade it as necessary.
Keeping a third B747 ready to fly at any given moment will be expensive as are the 2 presidential jets now in the shop. In the new B747, the lavatories will have to be reduced in size for the media’s discomfort. Vending machines will be added for feeding the media but will be limited to exact change only. The machines will also offer #47’s trading cards which will include a 5 % discount coupon for his golden sneakers. As always, payment can be made with #47’s cryptocurrency plus a $50 service charge.
As the authoritarian regime of #47 continues to take hold, an increasing number of governments will express fealty and line up to offer something special, which #47 will gladly take and keep, the emoluments clause notwithstanding, found in Article I, Section 9, Clause 8 of the U.S. Constitution. It has already begun to turn stomachs worldwide but others will be attracted to the new ‘democratic dictatorship’ ramrodded by the GOP and led by the Orange Jesus himself. Many people around the world tolerate authoritarian leaders or see them as admirable strongmen. Kick ass and take names, some say. But too often the names aren’t taken or made available to anyone. There is just the ass kicking and transfer to a holding facility. Habeas Corpus? Gone! Evidence of a crime? Nah. Filing an appeal? What, are you being serious?
To the many readers outside the USA, know that a very large number of US citizens are horrified and in serious opposition to #47 and his MAGA movement. However, it seems that the Founders of this country failed to anticipate a situation where a single party rules both houses of Congress, the White House, the Supreme Court, and the governors and legislative bodies of many states. The Founders assumed that the checks and balances between the three co-equal branches of government and built into the government they designed would protect the democratic republic and keep essential government services working. They could not anticipate a simmering populist movement amplified by instantaneous social media. Whereas in times before the internet and smart phones, a large number of disaffected and under-educated citizens in America now have access to media of all kinds and can gravitate towards whatever populism that appeals to them. There seems to be little in the way of concern about truthfulness.
The single party dominance of MAGA in US government means that enforcement of federal laws or procedure will be ignored. The Department of Justice has been slow to enforce checks and balances or just ignore it altogether. MAGA GOP politicians know that endorsement by #47 ensures that they will get votes from MAGA block and assure their political careers.
Roughly 30 % of the voting population will support #47 until their dying day, regardless of his behavior. Resistant to the lessons of history and logic, they are essentially lost to modern times. They are angry from seeing and hearing the hype surrounding modernity and the corrosive conspiracy theories involved. Not having a college education, they missed out on opportunities that open up by living in a college environment. All of the job descriptions and opportunities requiring college education aren’t necessarily posted off-campus and are therefore missed.
Until I entered the university, I was completely unaware of a host of career choices available. I grew up in a rural midwestern blue collar environment and was completely unaware of the various futures available. Many have glorified our rural culture, but I found it quite boring in my years from birth to 14 years. Sure, there are wide open spaces and nature. But the fifth time you wander out into a large pasture you begin to realize that solitude is nice but quite boring.
I was introduced to science and technology by watching the progress of the Apollo moon mission in the 1960s. It was thrilling but there was no one around who could hold a decent conversation about it with me. Basically, if you were a kid into science at that time in my state, you were alone. Just knowing about sciency topics wasn’t enough. It is nice and necessary to have discussions to explore ideas and ask better questions. To share in the wonder and majesty of the universe. That’s not too much to ask, isn’t it?
Lamentations on Chemistry 