Chemistry – David Bradley

What are nitazenes? Benzimidazole opioids

Benzimidazole opioids, also commonly known as nitazenes, were first synthesised by CIBA Pharmaceuticals in the 1950s as putative alternatives to morphine and heroin for use as strong painkillers. They have never made it into use in clinical medicine because the risk of addiction, respiratory depression, and death in use is too high.

Etonitazene has hundreds of times the potency of morphine

The compounds are classified as opioid New Psychoactive Substances (opioid NPS). Their mode of action is to bind to the brain’s mu-opioid receptors, but their unique structure means that some examples are several hundred times more potent than morphine and stronger even than fentanyl.

The changing heroin market led to the emergence of nitazenes as drugs of abuse in the early 2020s if not earlier. They pose a major new problem for public health and law enforcement.

Nitazenes were first in the UK news in 2021, when an 18-year-old patient was treated for overdose. Since then, there has been a rise in nitazene abuse with more than fifty overdose deaths and perhaps many more that remain inconclusive. Several nitazenes are, as of this week, defined as Class A drugs in the UK.

On a point of chemical semantics, opiates are chemicals derived from opium or poppy straw. They are alkaloid compounds naturally found in the opium poppy plant, Papaver somniferum. The archetypal opiate is the compound morphine. The analgesic pro-drug codeine is converted in the body to morphine. Heroin (diamorphine) is extracted from the dried latex of the poppy and has a very similar chemical structure to morphine.

The term opioid is used to designate any substance, natural or synthetic, that binds to the opioid receptors in the brain. So, this includes morphine and heroin, but also compounds that are not chemically related to the opiates such as fentanyl, which is a piperidine, and the nitazenes, which are benzimidazoles. There are many different benzimidazoles used safely in pharmaceuticals for treating high blood pressure, fungal infections, parasitic worms etc.

Deathcap mushrooms – Amanita phalloides

What makes the death cap fungus (toadstool or mushroom), Amanita phalloides, so poisonous?

Well, the primary toxin present in this fungus is alpha-amanitin. This chemical goes by the following systematic name, although you’re unlikely to see it spelled out in full in the news about the ongoing murder trial that’s in the Australian news at the moment:

2-[(1R,4S,8R,10S,13S,16S,34S)-34-[(2S)-2-Butanyl]-13-[(2R,3R)-3,4-dihydroxy-2-butanyl]-8,22-dihydroxy-27-oxido-2,5,11,14,30,33,36,39-octaoxo-27-thia-3,6,12,15,25,29,32,35,38-nonaazapentacyclo[14.12.11 .0^6,10.0^18,26.0^19,24]nonatriaconta-18(26),19,21,23-tetraen-4-yl]acetamide.

The same toxin is also found in the Destroying Angel fungus, Amanita virosa.

The chemical is essentially a ring of eight amino acids. This structure fits easily into the active site of two enzymes, RNA polymerase II and III and blocks their activity in the body leading to liver and kidney failure. When ingested the toxin ultimately binds to the enzyme and kills liver cells, but symptoms often don’t appear for at least ten hours, sometimes a day. This period of time is way past the point at which stomach pumping to remove the fungus would help.

Diarrhoea and stomach cramps are the first symptoms. These subside after a day or so and gives the poisoned a false remission. By day four or five, the toxin starts to have severe effects on the liver and kidneys, leading to total system failure in both, coma and death ensue within a week.

A smelly boost for your mothing life

TL:DR – Recent research has demonstrated that adding the volatile organic compound amyl acetate to a scientific moth-trap can boost the number of moths attracted to the UV light by almost a third.

A social media discussion about UV light sources for scientific moth-trapping, the type of vanes on the trap, and the environment in which one traps brought up some interesting thoughts. Several moth-ers use double sources to give them a better chance of enticing numbers and diversity to their traps. Although moths have been shown almost always to simply opt for the most energetic (higher frequency, shorter wavelength) when given a choice. There is evidence that black lights (UV bulbs painted black) are not so effective for attracting those species that are drawn more to visible light.

Also, it seems that white plastic vanes seem to work better than other types of vane and certainly better than rain-shield supporting rods on the commonly used Robinson and Heath moth traps. It also seems that the specific terrain and vegetation can affect numbers and diversity in some ways more than light source or other factors. There was also some recent work on how low-wattage UV light sources have a very limited range of attraction, but also the range varies among macro moth families, some attracted from 30 metres others from just 10 metres.

Anyway, in the discussion, fellow moth-er Stephen Roughley mentioned a paper by Chris Tyler-Smith and Yali Xue in the journal Ent Rec, “Amyl acetate increases macromoth catches in light traps” 2021, 134(6), 315-321, that looked at how lepidopterists might boost their haul for scientific and citizen scientific purposes. They suggest the use of a simple organic molecule that smells of fruit, called amyl acetate, amyl is an alternative name for the five-carbon alkyl chemical group pentyl, to augment one’s trapping. They demonstrated that amyl acetate boosted the number of macro moths drawn to the UV trap by up to about a third. Strictly speaking, the product contains 3-methylbutyl acetate, so five-carbon group but not in a straight chain.

Chemical structure of the ester amyl acetate — The ester amyl acetate smells fruity

The molecule, sometimes known as pear oil, is used as a flavouring agent, as a paint solvent, and in the preparation of penicillin. It is also the fuel for Hefner lamps. But, it is also found naturally in the volatile organic compounds exuded by ripe pears and presumably other fruit and fermenting or decaying vegetable matter.

I asked author Xue about the work. “We only tried amyl acetate from Etsy, but suspect that moths would not care about the grade, and any that smells like pear drops to a human would be fine, they told me. “We used enough to moisten a cotton wool pad and placed this beside the trap in a metal bowl as the solvent dissolves plastics.”

Many species of moths are known to be attracted to the odours given off by ripe fruits and flowers. There is a suggestion that some female moths may well be particularly attracted to such odours, including amyl acetate, as they seek out ripe fruit in which to lay their eggs. Indeed, it’s worth noting that a lot of moths that are not necessarily interested in light can be drawn to a strong-smelling sugary solution made from molasses boiled with beer or wine and various other concoctions. Most moths use their olfactory senses to locate food, mates, and suitable habitats, so this is perhaps not surprising. It was the technique of sugaring to attract moths that inspired the team. (See also wine roping). Amyl acetate mimics fruit odours and so should attract moths. Indeed it has been used in the past as a sugaring ingredient.

The team suggest, however, that the chemical simply applied could substitute for sugaring concoctions and might boost moth trapping where scented flowers are not present at a site. It all adds to the useful data that might be gathered to feed back to moth recorders for scientific purposes and to show where and when various species appear around the country. I have previously discussed the pros and cons of moth-trapping on Sciencebase.

ChemistGPT

TL:DR – Recent experience with asking ChatGPT chemistry questions reveals the limitations of this language model, despite the claims and hype of an ignorant US politician speaking in March 2023.

There was lots of talk of ChatGPT apparently deciding to teach itself organic chemistry…now…ChatGPT is language model, it’s not really an artificial intelligence (AI) in the strict sense, all it really is is a sophisticated autocomplete that analyses your prompts and weighs up the most likely combination of words with which to reply. I wondered whether the only chemistry in all that hype was the chemistry between olfactory receptor and odourant molecules in bovine ordure. So, I set it a challenge, giving it the following prompt:

You are to act as an expert organic chemist. You need to devise a reaction scheme using retrosynthetic analysis for the drug molecule Taxol.

This is how it responded:

Taxol is a complex natural product that has antitumor activity and is used in the treatment of various cancers. The molecule contains a complex array of functional groups, including multiple stereocenters, which make its synthesis a significant challenge.

Here is a possible retrosynthetic analysis of taxol:

Step 1: The first step involves disconnection of the C13 side chain from the taxane core. This can be achieved using a standard acid-catalyzed esterification reaction between a carboxylic acid and an alcohol. This disconnection leads to the formation of the intermediate 10-deacetylbaccatin III.

Step 2: The second step involves disconnection of the A and B rings from the taxane core. This can be achieved using a retro-Diels-Alder reaction. The retro-Diels-Alder reaction involves breaking the six-membered ring formed in the Diels-Alder reaction between the A and B rings. This leads to the formation of the intermediate 9-dihydro-13-acetylbaccatin III.

Step 3: The third step involves disconnection of the C ring from the taxane core. This can be achieved using a ring-opening reaction. The ring-opening reaction involves breaking the bond between C9 and C10, leading to the formation of the intermediate 7,8-didehydro-10-deacetylbaccatin III.

Step 4: The fourth step involves disconnection of the D ring from the taxane core. This can be achieved using a ring-closing reaction. The ring-closing reaction involves forming a new bond between C1 and C14, leading to the formation of the intermediate 5-deoxy-4-O-methyltaxol.

Step 5: The final step involves disconnection of the C2 side chain from the taxane core. This can be achieved using a standard nucleophilic substitution reaction. This leads to the formation of the final product, taxol.

Overall, the retrosynthetic analysis of taxol involves a series of complex reactions, including esterification, retro-Diels-Alder reaction, ring-opening reaction, ring-closing reaction, and nucleophilic substitution reaction. These reactions can be challenging to carry out in practice, and developing efficient and practical synthetic routes to taxol remains an active area of research in organic chemistry.

Now, it’s a long time since I did any retrosynthetic analyses for organic chemistry and I was never any good at them when I was meant to be. So, I’ll put this to social media and see what some proper chemists think.

First comment in was from ChemJobber, who said “the first disconnection to start with 10-deacetylbaccatin is reasonable”

I wrote about the first total synthesis of Taxol back in the 90s, and recall that the overall reaction scheme had well over 20 steps…

Nessa Carson dissected it and found the ChatGPT scheme rather lacking – here. She also pointed out that in Step 5 it completes the retrosynthesis of Taxol by disconnecting it all the way back to… Taxol (lol)

Anti-covid, antiviral ensitrelvir

TL:DR – An antiviral drug called ensitrelvir could cut the time a person tests positive when they have COVID-19 by about a day. There is a controversial suggestion that it might also reduce the risk of developing long-covid.

An antiviral drug developed by Shionogi in partnership with Hokkaido University is an orally active 3C-like protease inhibitor, which can shorten the time between first testing positive after infection with SARS-CoV-2 and getting a negative test. Early signs are that it may well reduce the risk of developing long-covid, although that data is yet to be peer reviewed. There are some scientists sceptical of the claim having heared the results presented at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington, USA, in February. They suggest that more work in clinical trials is needed before the claim can be accepted. Mariana Lenharo has all the details in Nature.

Long-covid is also known as long-haul COVID, post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS). The term describes the long-term symptoms and effect on various body systems and organs following infection with SARS-CoV-2.

Currently, there are two orally active antivirals for treating COVID-19, Paxlovid (nirmatrelvir/ritonavir) and molnupiravir. The antiviral ensitrelvir has the brand name Xocova.

The controversy surrounding whether or not ensitrelvir can reduce the risk of a person developing long-covid is about whether or not the trials and the definitions offered by Shionogi on this point are valid. There had previously been a more general suggestion that shortening the time that a person tests positive for COVID-19 could be beneficial. That said, there is evidence that even those who only have mild symptoms of COVID-19 can still develop long-covid. It could be that long-covid is a side effect of the body’s immune response to infection rather than being due to residual virus. There is much we are yet to learn about this virus.

Whoops! AI might have invented 40000 new toxic nerve agents…but probably not

TL:DR – Software used to predict which chemicals in a database have potential as new medicines has been flipped as a warning demonstrating that the same system could be used to predict whether they are highly toxic.

Artificial intelligence, AI, machine learning, language models, neural networks, generative models, algorithms trained on big data. A lovely collection of buzzwords that have been littering grant proposals for years and are now emerging into the real world as apps and websites and citizen science projects. For chemists and pharmaceutical scientists, AI has been a tool to experiment with for a long time. Creating molecular diversity, simulating physiology and screening for drug-like activity have been high on the laboratory agenda for quite some time. They have also used it to test for toxicity in silico and so reduce animal testing and problems once a drug gets into early. clinical trials.

Scientists at Collaborations Pharmaceuticals Inc., which focuses on drug discovery for rare diseases, commonly use trained AI to help them determine the likely toxicity of various novel molecular structures. Molecules with physiological activity are a prerequisite for finding new pharmaceuticals but it is also necessary to avoid those compounds that have a toxic effect on the patient rather than the disease.

A thought experiment flipped this work for good on its head and had team leader Fabio Urbina and colleagues wondering about the implications of an AI that seeks out life-taking toxic compounds rather life-saving pharmaceuticals. The team was asked to carry out simulations and to present the findings and implications to an international security conference.

The Convergence Conference is convened every two years by the Swiss Federal Institute for NBC (nuclear, biological and chemical) Protection – Spiez Laboratory – on behalf of the Swiss government to identify developments in chemistry, biology and enabling technologies that could have implications for the Chemical and Biological Weapons Conventions. The conference seeks to spot the next VX or Novochok.

MidJourney AI generative image of people in hazmat suits

Urbina and his colleagues have been careful not to disclose the details of their simulations, but by setting their AI in reverse so that it seeks out structures that are likely to be toxic rather than safe pharmaceuticals they were able to generate a whole molecular library of potential toxic agents on a par with VX and Novochok. Indeed, six hours on the computer produced a database of 40000 such molecules any one of which might theoretically be synthesised in a rogue state laboratory and many of which were predicted to be more toxic than VX. Of course, it could be that the AI has got it wrong (it happens!) and that none of these compounds are at all toxic. The details the team provides were published in the journal Nature Machine Intelligence.

It is rather worrying. But perhaps also inevitable and better that we know this is now a possibility rather than our ignoring the risks. It’s worth remembering, that the invention of dynamite had a notable dual use, noble and not so noble, you might say. This is in some way just a modern take of how an invention for good might so easily be manipulated for bad.

To quote from the paper: “We can take inspiration from examples such as The Hague Ethical Guidelines, which promote a culture of responsible conduct in the chemical sciences and guard against the misuse of chemistry, in order to have AI-focused drug discovery, pharmaceutical and possibly other companies agree to a code of conduct to train employees, secure their technology, and prevent access and potential misuse.”

That is unlikely to be enough in the long-term and it is perhaps inevitable that some rogue team somewhere is already building its own database of toxic agents using AI. We just have to hope that the worst in any such database are false positives or that they all prove to be too to tough to crack even for the best, bad chemists. But, given that we already have AI tools for devising chemical reaction schemes and have done for many years, it feels unlikely that this particular toxic genie is going to stay in its reaction flask for long.

Meet GINA, Global INitiative for Asthma

TL:DR – Thanks to GINA I have not needed to use salbutamol to treat my asthma for three years at the time of writing.

It’s three years since my asthma nurse introduced me to GINA, the Global INitiative for Asthma. It was a phone consultation because the then new virus SARS-CoV-2, which causes what became known as COVID-19, was beginning to spread. At the time, I was very worried that it would be a killer for me given my asthma. Eventually, medical science learned that people with asthma were not necessarily at any greater risk of morbidity and mortality.

Anyway, it was nice to meet GINA. GINA contradicts some of what general practitioners (GPs) in the UK have been advising asthma patients for years, but supports what the medical evidence suggests one should do in terms of medication. The main thing is GINA told me to stop using Salbutamol (the reliever spray) and to use my Symbicort (combined preventer with reliever spray) instead. Salbutamol is an old, out-of-date drug with some unpleasant side effects in long-term use, partly because it can affect the heart but mainly because inappropriate use in the absence of proper control of the condition with a preventer can lead to scarring in the lungs.

Modern relievers are more targeted to the lungs rather than other organs. Moreover, using the preventer at a higher dose, which is what my nurse recommended, means you reduce inflammation and mucus production, which are the main issues with asthma in parallel with episodic bronchoconstriction.

For three years, I have been taking twice as much preventer each day as I was before, and only very occasionally need to take extra to get a dose of reliever. I have not used Salbutamol at all in those three years and don’t expect to have to ever again. I no longer carry Salbutamol with me.

A GP friend was concerned when I told him about GINA, he reasoned, quite sensibly that taking this approach would be increasing one’s exposure to the preventer drugs, which are corticosteroids. This is true. But asthma is mostly about inflammation and these drugs reduce inflammation and so should reduce asthma symptoms. They do. He discussed the issue with colleagues and is now persuaded that GINA is a more sensible approach to asthma control than the current NICE recommendations in the UK. Hopefully, someone will introduce NICE to GINA soon.

Dual antidote for cyanide and carbon monoxide poisoning

TL:DR – Scientists have developed a life-saving antidote for exposure to the deadly gases hydrogen cyanide and carbon monoxide.

Scientists have made a groundbreaking discovery in the field of antidote development by creating a synthetic heme-model compound that has the potential to save lives in the event of simultaneous poisoning by carbon monoxide and hydrogen cyanide, which are frequently encountered in building fires. The compound, which has been tested on mice, resulted in an impressive 85% survival rate and rapid recovery. The chemical group known as heme is at the heart of hemoglobin, the oxygen-carrying molecule in our blood, and various enzymes in our body.

The researchers, led by Qiyue Mao of Doshisha University in Kyotanabe, Kyoto, Japan, and her colleagues, have published their findings in the scientific paper “A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning.” The study shows that the antidote is highly effective and exhibits low toxicity. Moreover, the compound can be rapidly eliminated from the body through urinary excretion, making it an ideal antidote for emergency situations.

The fact that the synthetic heme-model compound is storable at room temperature is a significant advantage for emergency services, as it could be rapidly prepared and administered at the site of accidental exposure to fire-generated gases. The potential benefits of this discovery could be life-saving, and it represents a significant leap forward in the field of antidote development.

The compound was developed using porphyrin, a molecule that is known to bind to oxygen-carrying heme proteins in red blood cells. The synthetic heme-model compound mimics the structure of natural heme and binds to carbon monoxide and cyanide, preventing them from binding to the body’s own heme proteins. This mechanism of action makes the compound highly effective in treating poisoning by these deadly gases.

The findings of this study have significant implications for public health and emergency services. By providing a safe, effective, and easy-to-administer antidote, lives could be saved in emergency situations where carbon monoxide and hydrogen cyanide poisoning are a risk. The potential for this compound to be used in human patients is exciting and offers hope for those at risk of exposure to fire-generated gases.

Mao, Q. et al. Proc Natl Acad Sci, Feb 20, 2023

As an experiment, I used ChatGPT to edit the press release about this work from PNAS. The only changes I made were to add the sentence in italics at the end of the first paragraph, add the institution, and to change team to colleagues.

Supplementing physical and mental health

TL:DR – Anecdote is not evidence, but I feel like I gained some benefit from taking a multivitamin supplement, it probably compensated for poor absorption of iron and perhaps other vitamins caused by one of my prescription medicines.

I’ve always been wary of taking vitamins and other supplements. There are good reasons not to do so, if you have a reasonably balanced diet. Excesses of some vitamins and minerals can lead to problems like kidney and liver damage, kidney stones, and some can interfere with the absorption and activity of prescription medicines.

However.

I have been feeling rather tired in recent months, becoming unaccustomedly exhausted after even light activity. I’m talking after a short walk, but sometimes even just after a shower. Was it long-COVID, was it my medication, was it just me getting older?

Mrs Sciencebase had an iron and vitamin supplement for an unrelated reason and suggested I try it, see if it would help.

Well, I took the recommended dose for a few days, not expecting to experience much improvement. Amazingly though, I felt a remarkable change in what people commonly refer to as “energy levels”. Activities that had started to become a tiring chore became a lot easier, I hopped on my bike and did a decent half an hour’s cycling without breaking a sweat, a couple of days after that I did an hour, at speed, and aside from being thirsty when I got back to base, I was fine.

I know anecdote is not evidence, but honestly, it seems like too much of a coincidence that I felt like I had recovered from apparent chronic exhaustion within three days or so of taking the supplement. Moreover, when I look at the side effects of one of my medications, it does suggest that tiredness and various other side effects are associated with reduced absorption of micronutrients (vitamins and minerals). So, I’m sticking with the supplement for a while longer.

Intriguingly, the effects do not seem to have been wholly physical though. Most people have had a tough few years, but there has been significant family loss and stress here that happened in the middle of covid, is ongoing, and I have not been what you might call the happiest bunny in the warren, for a long tim, I must confess. Stuff that I usually really enjoy has not, on too many occasions, brought me much joy in recent months. I shrugged it off as being the grief and worry…but…a few days ago, I felt like the proverbial cloud had lifted, and even though it was a drizzly day, the sun seemed to be shining again.

Could this too have been a supplement fix? Well, there are many, many biochemical pathways that are linked to mental health, disturbance in some of those are known to be connected to depression. These various pathways need various micronutrients to work properly. Might I have been deficient in an essential biochemical component? Have I now replenished my supplies and rebooted those pathwats?

Perhaps the brain, when faced with deficiency, goes into some kind of lockdown to make you mope, reduce motivation, and so activity? And, when that lockdown is prolonged and deep, could it also begin to impinge on other pathways to the detriment of mental health. If so, I wonder if this is exacerbated in the wake of a double-dose of grief accompanied by a lot of not unwarranted stresses and anxieties.

I don’t know. Like I say, anecdote is not evidence. I’d rather not take the supplements for a prolonged period of time, so I will be having a chat with my doc at my annual review about my current medication. I will tell them that what I do know is that I’ve been taking a daily dose of micronutrients and feel physically much fitter than I have for a long time and mentally far brighter.

As a footnote, I shared this post on my Mastodon and a couple of people suggested that my experience may be due to my “taking control” or simply a placebo effect. Well, that is a possibility, of course. However, I’ve had symptoms for a long time that coincide with several mentioned on the documentation accompanying one of my medications and I feel that reversion to the mean/norm (basically, the placebo effect) was so sudden and coincided with taking the supplement that there must have been a physical effect of doing so rather than my spontaneously recovering…but, again, anecdote is not evidence, either way. One cannot do double-blind, placebo-controlled studies on oneself.

An old interview with one of this year’s Nobel Chemists – Carolyn Bertozzi

This was an interview for my Personal Reactions column on the old ChemWeb site from 1999 featuring Carolyn Bertozzi, who this week was announced as one of three recipients of the 2022 Nobel Prize in Chemistry.

Biography: Professor Carolyn Ruth Bertozzi, born 10th October 1966. Boston Massachusetts.

Position: Associate Professor of Chemistry, University of California at Berkeley

How did you get your current job?

The usual way. I applied for faculty positions in 1995 in response to advertisements in C&E News

What do you think clinched the deal?

Good fortune and a strong publication record from my graduate and postdoctoral labs

What do you enjoy about your work?

Everything. I love the variety, the interesting and brilliant people, the challenge of figuring out data and the thrill of new discoveries. Best of all is seeing how young people get turned on to research and develop into top-notch independent scientists. This must be the best job in the world.

What aspects would you change?

In the perfect world, there would be a more entrenched system to accommodate the demands of both work and family, and perhaps a better representation of women on the faculty. These are not out of the realm of possibility in my lifetime. Also, higher salaries to match the cost of living would help ease the burdens of everyday life

What was your first experiment? Ever?

I don’t remember it has been so long. My first research position was in the summer of 1986 and I performed experiments with lasers and cell membranes with the goal of understanding how photogenerated oxidants damage membranes

Did it work?

I don’t remember but I learned a lot and it was fun

Was your science teacher inspirational?

My high school biology teacher was a true inspiration. Then in college, I had several chemistry professors who inspired me to switch my major to that subject

What would the teenage you think of the present-day you?

Too serious

What is your greatest strength?

Versatility. I am reasonably competent at many things

Weakness?

Too quick to pass judgement. Perhaps also too limited attention span

What advice would you give a younger scientist?

Try to resist peer pressure and pursue those areas of science that you find truly fascinating

What would you rather be if not a scientist?

Nothing else compares but if forced out of science by factors beyond my control, I would pursue medicine or music

Which scientist from history would you like to meet?

Hermann Staudinger, the German Nobel prize-winning chemist who was far ahead of his time

What would you ask them?

How did you conceive of these reactions?

How has the Internet influenced what you do?

It has greatly facilitated our ability to understand genomic information, and to process literature in many areas of science. I am sure that the Internet has also provided information on my lab to others around the world, which helps us gain recognition, collaborations and new colleagues

In what ways can scientists improve their public image?

Participate in outreach programs so that young people can see the beauty and excitement of what we do

What might be the biggest achievements in science in the next century?

Complete sequencing of the human genome, structural elucidation of membrane proteins, real-time mapping of chemical transformations inside living animals. More globally, effective cures for cancer and microbial infections will affect millions of people.

What’s your favourite chemical reaction?

The Staudinger reaction between azides and phosphines

Which living scientist do you most admire?

My father William Bertozzi, a physicist at MIT. [Carolyn’ sister Andrea Bertozzi is a Professor of Math and Physics at Duke]