April 13, 2021

I feel really bad for the young 5th year grad student whose presentation just crashed.

You could see how nervous she was, how hard she worked to put it all together, but she struggled with Powerpoint, and got just so far - English not being her first language and then the whole thing crashed.

The talk, if you got through all that was quite interesting, involving novel phosphoamidites and novel protecting groups for DNA synthesis, but it all just crashed...

She probably spent a long time preparing, and then this...

I hope she has a great career though, she's a smart kid doing good work.

April 11, 2021

Juke box fury

April 11, 2021

New Weekly Record Set at the Mauna Loa Observatory for CO2 Concentrations: 419.28 ppm.

As I've indicated several times I somewhat obsessively keep a spreadsheet of the weekly data at the Mauna Loa Carbon Dioxide Observatory, which I use to do calculations to record the dying of our atmosphere, a triumph of fear, dogma and ignorance that did not have to be, but nonetheless is.

This week's reading is the first in the history of weekly average readings, going back, to 1975 posted by the Mauna Loa is the highest ever recorded at the Mauna Loa carbon dioxide observatory, 419.28 ppm.

Generally, each year, these measurements peak in May or early June. I expect we will see 420 ppm, possibly more this year - the figure in the title is a weekly average but a daily reading this week exceeded 421 ppm - less than 10 years after we first saw 400 ppm.



The figures for this past week:

Up-to-date weekly average CO2 at Mauna Loa

The increase in carbon dioxide concentrations when compared to the same week in 2020 is "only" 2.64 ppm. (If one keeps track as I do, there is a fair amount of statistical noise in these measurements, but the trends are consistent.) The highest weekly increase over 2020 this year, 2021, was 3.90 ppm, observed in the week beginning February 28, 2021.

In my spreadsheet, I keep records of the increases over 10 year periods, in this case, a comparison of the reading this past week, with the last week of May in 2011. Using Excel functions, I can sort them by values high to low and do a lot of other things. The value for the 10 year increase is the highest ever recorded, 26.28 ppm.

The 12 month running average for increases over a ten year period, week to week, 2021 to 2011, is 24.27 ppm, 2.43 ppm per year.

If any of this troubles you, don't worry, be happy. You can always head over to the E&E forum and read that "renewable energy is growing 'exponentially.'" I've been hearing that, of course, my whole damned life and I'm not young, but again, don't worry, be happy.

But with respect to the most recent data point at the Mauna Loa observatory, so much for Bill McKibben's "350.org." Bill is another one of those putative "environmentalists" who has trouble mouthing the word "nuclear." He certainly wouldn't want to offend anyone by saying that word. Bill, of course, is a journalist, not a scientist. The job of journalist is to pay selective attention. Many of his supporters say things like: "Nuclear is 'too expensive,'" and "Nuclear is 'too dangerous,'" even while 18,000 to 19,000 people die every damned day - more than have died worldwide on Covid's worst day - from air pollution, precisely because we don't embrace nuclear energy.

By contrast, climate change is apparently not "too expensive." Climate change is also apparently not "too dangerous."

As for "too expensive:"

The earliest nuclear plant ever built in the Western World produced electricity for half a century. It was built on 1940's and early 1950's technology. Modern nuclear plants are designed to last 60 years or more. After they are amortized they are cash cows, they produce electricity only requiring trivial low fuel costs and maintenance costs.

By contrast, every damned piece of so called "renewable energy" on this planet will need replacement in 25 years or less - a few wind turbines, very few, as reported at the comprehensive Master Register of Wind Turbines from the Energy Agency of that off shore oil and gas drilling hellhole, Denmark, lasted 30 years; almost all of them were landfill in 25 years or less, with an average lifetime of under 20 years. Wind turbines will be greasy rotting hulks requiring diesel trucks to haul the blades to landfills before most babies born in 2021 graduate from college. Pretty much every damned solar cell now on this planet will all be more already intractable electronic waste in 25 years.

Nuclear energy is too expensive for whom? Certainly not for future generations, who might use nuclear plants, infrastructure, we build and for which we pay today, but we certainly don't give a rat's ass about their lives. When it comes to providing for them, we couldn't care less. We all turn into Ayn Rand when discussing nuclear energy; we only care for ourselves and those babies born today will have to deal with the shit we leave behind on a planet choking to death on dangerous fossil fuel waste, leaking fracking fields, destroyed ground water, abandoned depleted mines dug so we could be "green," all of the world's best ores completely depleted, hundreds of millions more tons of electronic waste, including spent solar cells, rotting and rusting wind farms, etc.

We couldn't care less.

History will not forgive us; nor should it.

I trust you are having a pleasant and safe Sunday.

April 11, 2021

My youngest son has a vaccine appointment!

I've been real worried about him; it's his first semester of graduate school. (He just turned 22.)

There are lots of frat nuts in his school; when we visiting last week, some of them burst out a nearby house, drinking, cheering, no masks.

My son assures me that these guys were not engineers.

Anyway, they had a few surges at the University, but this morning his girlfriend got her shot - J&J - and he has an appointment on Wednesday for a Pfizer shot.

My oldest, at 26, has had his first Pfizer, and is due for his second next Monday.

My wife and I are well past our two Modernas!

Thank you President Biden!

April 10, 2021

The 2nd worst year to year increase in CO2 concentrations over any March in 61 years was March 2021.

Here is the Mauna Loa CO2 observatory's data for the month of March 2012, Monthly Average Mauna Loa CO2

(Accessed April 10, 2021.)

I keep a sortable spreadsheet of the monthly data found here: Trends in Atmospheric Carbon Dioxide

Monthly data is available going back 61 years. The increase measured over 2020 is 3.14 ppm. It is the second worst March ever recorded, after March of 2016, when the increase was 3.31 ppm over March of 2015.

If any of this troubles you, don't worry, be happy. We've spent nearly three trillion dollars on solar and wind since 2004. It didn't work to address climate change, isn't working to address climate change, and won't work to address climate change, but it's not practical results that count, but the good intentions, the dream and the fantasy that count.

As for nuclear energy, which was calculated in 2013 by James Hansen and a colleague to have prevented the release of around 31 billion tons of carbon dioxide, this while being vilified by people who know very little about science and engineering, don't worry, be happy. Head on over to the E&E forum where you can hear that it's "too expensive" and "too dangerous."

Prevented Mortality and Greenhouse Gas Emissions from Historical and Projected Nuclear Power (Pushker A. Kharecha* and James E. Hansen Environ. Sci. Technol., 2013, 47 (9), pp 4889–4895)

By the way, nobody knows what to do with dangerous fossil fuel waste. It's just dumped, indiscriminately, at a rate of roughly 95 million to 100 million tons per day. We couldn't care less. Not even counting climate change, dangerous fossil fuel waste kills between six and seven million people a year, around 18,000 to 19,000 people a day, more than Covid-19 ever killed on its worst day.

Here is the most recent full report from the Global Burden of Disease Report, a survey of all causes of death and disability from environmental and lifestyle risks: Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 (Lancet 2016; 388: 1659–724) One can easily locate in this open sourced document compiled by an international consortium of medical and scientific professionals how many people die from causes related to air pollution, particulates, ozone, etc.

Climate change, according to what I hear, unlike nuclear energy, is decidedly not "too dangerous" nor, apparently, is it "too expensive."

Go figure.

In 2011, in coastal Japan, around 20,000 people were killed by seawater. We couldn't care less about them, but we hear all the time about nuclear reactors destroyed in the same event. How many people died from radiation again?

Go figure.

Have a pleasant Saturday evening.

April 10, 2021

There are some advantages to giant scientific meetings being conducted virtually.

This week the ACS (American Chemical Society) has been meeting virtually.

I can't always fit all of the ACS meetings into my schedule, but over the decades whenever I've been able to attend, I've been thrilled by the experience. The highlight for me among all of them was sitting next to Glenn Seaborg at the 1994 San Diego meeting during which the name Seaborgium was proposed for element 106 - during a talk attended by maybe 15 or 20 people. (The name "seaborgium" was accepted by IUPAC in 1997, after resolution of a controversy about naming an element after a living person.) The talk I attended, in a very small room in the nuclear section, was on the subject of the general chemistry of the heaviest element to have been isolated in visible quantities, Einsteinium. It's an event that stands out in my memory, only exceeded in scientific star watching by an afternoon spent in Freeman Dyson's office chatting with him.

For me, the ACS meetings have always been a physical challenge because my interests are broad and somewhat unfocused. Professionally I have focused on the medicinal chemistry sections, organic chemistry sections and sometimes the agrochemical sections; in recent years it's generally been about mass spectroscopy, but I always try to find time to sneak in environmental sessions, particularly with respect to carbon dioxide capture and reduction, as well as nuclear chemistry sections. (Nuclear chemistry sections are wonderful, because they are always small, and one can be in the presence of giants in the field, as was the case with Seaborg.)

Anyway the meetings always involves a lot of running, since these sessions tend to be in different parts of convention halls, and in many cases, in different nearby hotels - which sometimes involve a bus trip.

No one wants to speak in praise of Covid-19, a tragedy to be sure, but on the bright side, in this meeting I was able to fit in a few lectures on medicinal chemistry, including synthesis of two new drugs, talks on the vaccines, talks on the use of scientific databases, some of which are free and of which I was unaware, talks on the environmental chemistry of technetium, the chemistry of plutonium, several carbon dioxide talks organometallic talks, lots and lots and lots of high resolution mass spec, structure ID, glycans, proteomics and I got to chat with really really good, even great, scientists, all while sitting in my office, or in the late afternoon and early evening (East Coast Time) in my home office, no planes, trains, automobiles, no gasping for air after running from room to room, this while missing some talks because of transit time, no hotels, no need to join people for drinks, dinners, no need to be charming, since "charming" is hard for me.

You also get to see, if the cameras are on - and often they are - how other scientists live, to be a guest in their homes or in their labs.

It is also pleasing to understand that this was also a low carbon event, relatively.

There are some things that require face to face, and many face to face meetings are extremely pleasant - one can run into old friends and one can also see the mannerisms of people one has never met but about whom one has only heard or read - but for efficiency of information exchange, well, there are definitely some very large compensations.

Clichés become clichés by being true, and in this case, "Every dark cloud has a silver lining" is certainly true.

April 9, 2021

Wow. Carbon dioxide concentrations measured at Mauna Loa on April 3 were 421.21 ppm.

Accessed April 8: Recent Daily Average Mauna Loa CO2

I never saw a number like that before there, but I will for sure see many more such numbers in the future.

Heckuva job humanity, heckuvajob.

April 8, 2021

Tonights cool tip from the ACS for cancer patients being treated with checkpoint inhibitors.

For various reasons, I've decided to focus much of my attention during this ACS meeting (which is virtual, but pays some attention to the fact that it was supposed to be in San Antonio) on glycomics, mostly because it's a subject I about which I know next to nothing.

I just listened to a real cool lecture by Howard Hang which indicates that non-responders to checkpoint inhibitors, a group of immunostimulatory drugs that are designed, just like it sounds, stimulate the immune system to fight cancer, may fail to respond because they lack the proper bacteria in their microbiome.

Here's a paper in a prepub form: Enterococcus peptidoglycan remodeling promotes immune checkpoint inhibitor therapy.

Cool, I think.

April 6, 2021

Some news on the variants of SARS-CoV-2 and the effectiveness of the Pfizer vaccine, (good news)!

Today at the virtual ACS meeting I attended two lectures, one by Phil Dormitzer of Pfizer and one from Melissa Moore of Moderna.

I don't have much time to discuss the details, but during Dr. Dormitzer's fascinating lecture some cool things came up.

It appears that the variants are fairly well removed from the target areas of the vaccines, which a good thing. They have nonetheless been completely mapped, and work is underway to address them if needed. In Dr. Dormitzer's lecture he specified them, if my notes are correct as D614G (Aspartic Acid replaced at the 614th residue of the spike protein by glycine), N501Y, replacement of asparagine at the 501st residue by tyrosine, and E484K, replacement of glutamic acid at the 484th residue by lysine.

There are some genetic differences between races in diseases and response to diseases; for example, women of Chinese origins are much less likely than women of European extraction to get certain forms of breast cancer because of a variant in the COMT gene (catechol O methyl transferase). African American men and women are less likely to respond to certain blood pressure medicines, (which makes it regrettable that omipatrilat was not approved, since it treated this hole in medicine.)

It turns out that African Americans are winners in terms of the ethnic profile of the Pfizer vaccine effectiveness. For them, according to the data shown in the talk and them alone, the Pfizer vaccine is 100% effective in preventing Covid infections.

Dr. Moore's lecture made me realize something that had not occurred to me in the development of these novel RNA drugs and vaccines. (I'm not a nucleic acid kind of guy.) They are a lot more difficult to make than one might think niavely. This is because of the multiplicity of codons for several amino acids. One has to be very careful in considering the availability of transfer RNA's corresponding to these codons, since they are not necessarily available in the same concentrations in organisms in which they are generated. Dr. Moore pointed out that for the SARS-Cov-2 Moderna vaccine there were actually 10^201 choices that could have been made in the codon sequence, which is a number larger than all of the atoms in the known universe! She briefly described the statistical methods used to manage this chemical space and make wise choices.

Nevertheless, Moderna has spent years learning how to choose the particular sequences of codons, and they are also ready to make changes FAST! FAST! FAST! as necessary.

Another thing: Both vaccines incur, according to the existing clinical trial data, a higher level of immunity than one actually obtains by having Covid. This suggests that even people who have had Covid might want to consider vaccination.

Very cool, very cool.

April 6, 2021

Pfizer has developed a protease inhibitor for the treatment of infected CoV-Sars-2 patients.

I attended a lecture today at the ACS meeting by Dr. Daffyd Owen of Pfizer about which I will make a brief comment.

Years ago, when the protease inhibitors for HIV were being developed, one interesting thing about them was that they were designed to dock in a protease - a protein which cleaves larger proteins - at a specific sequence, bonds between the amino acid aspartic acid (ASP) and phenylalanine (Phe). Interestingly there are no mammalian enzymes that cleave at this sequence, making targeting much easier.

The SARS-CoV-2 RNA transcribes a protease also not found in mammalian species, which cleaves exclusively at residues of glutamine, (Gln). A widely used enzyme in analytical chemistry and mammalian stomachs is trypsin, which cleaves are arginine (ARG) and lysine Lys residues.

Dr. Owen walked us through the medicinal chemistry for the development of PF-7321332, which is designed to block the pocket of the unique SARS-CoV-2. It was simply beautiful. The work involved 210 Pfizer scientists working around the clock to produce a compound entering the clinic in 11 months, unprecedented speed!

The work built on work conducted at Agouron - a company acquired by Pfizer - to develop one of the protease inhibitors for HIV, nelfinavir. (I was involved in the scale up of this compound, peripherally.)

What is interesting is that the dose (tid, 3 times a day) is "only" on the order of 300 mg, making scale up somewhat simpler than it was for the HIV protease inhibitors which had higher doses.

Interestingly, to prevent CYP metabolism, the drug may be administered with ritinovir, a treatment for HIV, to saturate the CYP enzyme.

Cool.