On this Independence Day in one country in North America a few notes on life outside current politics, scientific and otherwise.<\/p>\n
Part the First: The Archaeology of Food Is Fascinating.<\/strong>\u00a0 Having read about Roman eating habits over the years I have wondered about two things, fish sauce and the dormouse.\u00a0 Now we know which fish were in the Roman fish sauce courtesy of DNA analysis: Sardina pilchardus<\/em>: Ancient DNA helps trace stinky Roman fish sauce to its source.<\/a>\u00a0 The link to the article in Antiquity<\/em> (Cambridge) is here<\/a>:<\/p>\n The Romans were among the first societies to extensively exploit fish resources, establishing large-scale salting and preservation plants where small pelagic fish were fermented to produce sauces such as garum. \u00a0Here, the authors demonstrate that, despite being crushed and exposed to acidic conditions, usable DNA can be recovered from ichthyological residues at the bottom of fish-salting vats. \u00a0At third-century AD Adro Vello (O Grove), Galicia, they confirm the use of European sardines (Sardina pilchardus<\/em>) and move beyond morphology to explore population range and admixture and reveal the potential of this overlooked archaeological resource.<\/p>\n<\/blockquote>\n My palate is regrettably underdeveloped, so I can\u2019t say the fish sauce sounds all that appetizing.\u00a0 These sardines on the other hand?\u00a0 I grew up with the children of Portuguese fishermen, but their prime catch was the white shrimp<\/a>, which I never liked very much despite local pressure and now have a late-onset allergy to them.\u00a0 And sardines were little smelly things from a small tin opened with a key. \u00a0I have never eaten one of those, on a cracker or otherwise, as far as I remember.\u00a0 But next time you are in New Bedford, after visiting the Whaling Museum<\/a> stop by Antonio\u2019s<\/a>, where the Sardinhas Assadas is the dish to order along with a Portuguese wine.\u00a0 Don\u2019t forget the flan for dessert.\u00a0 I am now officially hungry in the middle of the afternoon.<\/p>\n And the edible dormouse<\/a>, Glis glis,<\/em> is still eaten in a few places coterminous with parts of the Roman world.\u00a0 They are said to be delectable, and I am sure someone in the international NC community can attest to this.<\/p>\n Part the Second: The Prospects for Cancer \u201cVaccines\u201d Are Improving. <\/strong>\u00a0Cancer chemotherapy famously kills normal cells while targeting cancer cells. \u00a0Sometimes the race is won by the drug but by a small margin.\u00a0 Sometimes the race is lost.\u00a0 Either result leads to poor outcomes. \u00a0The goal of cancer therapy for the past fifty years has been to find a \u201cmagic bullet\u201d that kills cancer cells while sparing normal cells. \u00a0In my former laboratory life, I helped develop a magic bullet that would work by conjugating the toxic castor bean protein ricin<\/a> to an antibody that binds to cancer cells and kills them when the complex is taken up by the cell.<\/p>\n Those of us of a certain age will remember that ricin was probably used in the murder of the Bulgarian dissident Georgi Markov<\/a> in London in 1978.\u00a0 I am living proof that it can be purified from castor beans without any danger.\u00a0 The ricin-antibody conjugate worked, very slightly, in cultured cells but translation to the oncology clinic was problematic as we say in the lab.\u00a0 Another good theory killed by a plain fact.\u00a0 A much better magic bullet is required.<\/p>\n We have discussed pancreatic cancer \u201cvaccines\u201d here before.\u00a0 Vaccine is a term of convenience in this context.\u00a0 A cancer vaccine is a preparation that elicits a specific immune response to a patient\u2019s own cancer, which expresses novel non-self antigens, and destroys it.\u00a0 This article, Individualized mRNA cancer vaccines make strides<\/a>, <\/strong>from Nature<\/em> is an update on these interventions that are in clinical trials for melanoma, bladder, pancreatic, kidney, bladder, colorectal, stomach, esophageal liver cancer, and others listed in this table<\/a>.<\/p>\n Many of these cancers are generally intractable to current therapies.\u00a0 This work-in-progress is the culmination of long-term research in basic immunology and cancer biology that was supported by public entities such as the National Institutes of Health<\/a> and other agencies including the American Cancer Society<\/a> and Cancer Research UK<\/a>, which was the Imperial Cancer Research Fund when I almost got a postdoctoral position there. \u00a0My intuition tells me these interventions will be the magic bullet that actually cures an individual\u2019s cancer.\u00a0 And just so we remember, the scientific foundations of these therapies were financed by everyone!\u00a0 They will be expensive but we can afford them.\u00a0 The question is whether we will.<\/p>\n Part the Third: Consciousness, What Is It?<\/strong>\u00a0 Philosophers and neuroscientists have been trying to explain the nature of consciousness for a very long time. \u00a0Recent progress is in the eye of the beholder<\/a>:<\/p>\n Where in the brain does consciousness<\/a> originate? \u00a0Theories abound, but neuroscientists still haven\u2019t coalesced around one explanation, largely because it\u2019s such a hard question to probe<\/a> with the scientific method. \u00a0Unlike other phenomena studied by science, consciousness cannot be observed externally. \u00a0\u201cI observe your behavior. \u00a0I observe your brain, if I do an intracranial EEG [electroencephalography] study. \u00a0But I don\u2019t ever observe your experience,\u201d says Robert Chis-Ciure, a postdoctoral researcher studying consciousness at the University of Sussex in England.<\/p>\n Scientists have landed on two leading theories to explain how consciousness emerges: integrated information theory, or IIT, and global neuronal workspace theory<\/a>, or GNWT. \u00a0These frameworks couldn\u2019t be more different\u2014they rest on different assumptions, draw from different fields of science and may even define consciousness in different ways, explains Anil K. Seth, a consciousness researcher at the University of Sussex.<\/p>\n The Cogitate Consortium project, which began in 2018, set out to pit the predictions against each other at multiple labs run by theory-neutral teams. \u00a0\u201cThese were people that did not have skin in the game,\u201d explains Chis-Ciure. \u00a0They used three different brain-imaging techniques to observe the brains of 256 participants\u2014a very large sample size for a neuroscience study\u2014while those participants completed the same visual tasks, which involved rotating faces and letters. \u00a0These types of tasks require conscious experience.<\/p>\n The results challenge both theories because neither\u2019s predictions were fully borne out by the data. \u00a0For instance, GNWT predicted that electrodes in the prefrontal cortex would detect a signal when a stimulus disappeared and was removed from the mental stage of consciousness, but that was largely absent in the findings. \u00a0\u201cThe fact that you didn\u2019t see that\u2026is something that I think is a significant challenge,\u201d says Seth, who wasn\u2019t involved in the new study. \u00a0IIT, on the other hand, predicted that a sustained synchrony of networks of neurons would occur at the back of the brain, which also wasn\u2019t observed.<\/p>\n<\/blockquote>\n This is all well and good and no doubt progress is being made.\u00a0 However, I tend to believe Iain McGilchrist<\/a> has the better handle on what is at stake in this research and what it means.\u00a0 But I freely admit that \u201cbelieve\u201d may be the operative word in his context.\u00a0 It also seems that Hegel\u2019s hypothesis (and Engels\u2019s more accessible version from Dialectics of Nature<\/a>) that an \u201cincrease in quantity eventually results in a change in quality\u201d will remain essential in the study of consciousness.\u00a0 We know the neural circuitry of the sea hare<\/a>, Aplysia californica<\/em>.\u00a0 This organism is sentient, but does it have a consciousness similar to that of a human?\u00a0 Good question.<\/p>\n This principle of \u201cquantity-to-quality\u201d is the first principle underlying all multicellular life, even if this is not explicitly recognized by the general run of biologists (including by one of my grant reviewers back in the day who strenuously objected to a reference to integrative levels that was too old to be \u201crelevant\u201d).\u00a0 Whatever, but a hallmark of cancer is that cancer cells forget their place in the organism and cause all sorts of trouble.\u00a0 And whatever the outcomes of this research, room will remain for philosophers, poets, psychiatrists, neuroscientists, and social scientists<\/a> (open access, interesting) in this never-ending discussion.\u00a0 The one thing I do know is that when the brain dies, so does its conscious mind, despite a persistent and puerile resistance to the reality of death<\/a> among some, discussed here<\/a> last February.<\/p>\n Part the Fourth: The Remediation of Pollution on the Back End, Literally.<\/strong>\u00a0 A long time ago when I was a chemical worker in a unionized plant, I had the title \u201cMercury Handler\u201d for one long, hot summer.\u00a0 My employer (a large transnational corporation) operated a chlor-alkali plant<\/a> and the electrolysis cells used a layer of metallic mercury at the bottom (the cell room in the photograph did not change much in the 50+ years between the photograph and my time). \u00a0The things I remember most as an 18-year-old is that a steel flask of mercury about the size of a quart bottle weighs 92 pounds (it was easier to carry two at a time instead of one, for balance) and that I had to give a urine sample to the analytical chemist once a week.\u00a0 I never saw the results of the urinalysis and in retrospect it would not surprise me if the samples were poured down the drain.<\/p>\n Mercury inevitably escaped into the environment and my former workplace is now a Superfund site.\u00a0 As explained by Erik Loomis<\/a> in Out of Sight<\/a>, the Global North has fixed its problem by exporting such manufacturing to the Global South.<\/p>\n Thus, global mercury pollution endures.\u00a0 And while this has remained out of sight, it is still a problem in the Global North, especially for those who eat both saltwater and freshwater from, from the top of their food chains.\u00a0 These include tuna, salmon, and swordfish from the oceans and various varieties of bass and other large predators (e.g., pike and trout) from freshwater rivers, lakes, and reservoirs near coal-fired power plants and other sources or mercury.\u00a0 The sardines mentioned above are at the bottom of their food chain and do not present a risk of mercury ingestion!<\/p>\n A research group at UCLA has developed a strain of common gut bacterium and probiotic, Bacteroides thetaiotaomicron<\/em><\/a>,<\/em> that detoxifies methyl mercury, which has been recognized as the severely toxic form of mercury at least since the Minimata disaster<\/a> in Japan, which I read about in National Geographic.\u00a0 Some things stick:<\/p>\n Mercury resistance (mer<\/em>) genes are largely absent from the microbes present in the human and mouse gut microbiota. \u00a0Because of this, the researchers turned to gene sequences merA <\/em>and merB<\/em> from a mercury-resistant strain of Pseudomonas aeruginosa<\/em>. \u00a0These genes demethylate and reduce MeHg. \u00a0This process generates less harmful compounds like inorganic mercury (the mercury I handled), which is less readily absorbed and more easily excreted from the body. \u00a0They integrated both sequences into Bacteroides thetaiotaomicron<\/em>, a highly prevalent commensal gut bacterium that has proven to be safe as a probiotic.<\/p>\n To test this engineered strain called Bt(merAB)<\/em>, the researchers grew the bacterium in media supplemented with either pure MeHg or a bluefin tuna-derived form of MeHg. \u00a0In both conditions, Bt(merAB)\u00a0 <\/em>exhibited MeHg demethylation activity while strains lacking the genes could not reduce MeHg.<\/p>\n Then, the researchers colonized germ-free mice with either wild type B. thetaiotaomicron<\/em> or Bt(merAB)<\/em> \u00a0followed by a high oral dose of pure MeHg, since oral ingestion is the main route of exposure. \u00a0Mice with the engineered bacterium only broke down MeHg in the gut, measured through fecal content; however, the researchers still saw MeHg in other tissues such as the liver or brain.<\/p>\n \u201cWe thought that we were overloading them with too much methylmercury because it was still able to get into the bloodstream,\u201d explained Hsiao. \u00a0Instead, the researchers opted to study its effects through chronic dietary intake. \u00a0Indeed, mice colonized with the engineered microbe and fed a diet high in bluefin tuna had much lower MeHg levels than expected in the colon and brain. \u00a0The researchers also saw similar effects when they gave the bacterium as a probiotic to mice with normal microbiomes.<\/p>\n Next, the researchers investigated whether this pattern would also occur in pregnant mice. \u201cThis is kind of the most vulnerable population to methylmercury,\u201d said Hsiao. \u00a0The team examined the effects of toxin exposure to MeHg-rich (tuna), MeHg-modest (salmon), and no MeHg diets during gestation. \u00a0They found that mice with Bt(merAB)\u00a0 <\/em>successfully decreased levels of MeHg in both maternal and fetal tissues, and the mice had lowered signs of mercury toxicity in the fetal brain.<\/p>\n<\/blockquote>\n These convincing experiments were done using mice.\u00a0 Will this be transferrable to humans, with Bt(merAB)<\/em> \u00a0included as a probiotic in the human diet? \u00a0This seems very possible.\u00a0 There is no obvious mechanism by which the modified B. thetaiotaomicron<\/em> could cause trouble.\u00a0 But this work as a long way to get to the clinic.\u00a0 Still, this is one example of biohacking that might be useful.<\/p>\n In the meantime, it is a good idea to avoid eating too many fish likely to have concentrated mercury in their bodies because they are at the top of their food chain. \u00a0People on my home ground have learned where to catch fish, crabs, and shrimp.\u00a0 No one goes near the two Superfund sites, one with mercury and other heavy metals and the other with persistent pesticide residues, that drain into the marsh.\u00a0 If not for the Clean Water Act signed by our last liberal President Richard Nixon\u2026Anyway, planet Earth needs a Clean Water Act in force everywhere.<\/p>\n Part the Fifth: <\/strong>The unanimous Declaration of the Thirteen united States of America.<\/strong><\/a>\u00a0 Although the author will undoubtedly be cancelled one of these days, if this has not already happened and I missed it, he had a way with words:<\/p>\n We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.\u2013That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed, \u2013That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness.<\/p>\n<\/blockquote>\n Eleven years later Benjamin Franklin<\/a> replied to his high-society interlocutor<\/a> that he and his like-minded cohort had created for her and everyone else \u201ca republic,<\/strong> if you can keep it.<\/strong>\u201d\u00a0 There is work to do yet!\u00a0 And always.<\/p>\n To members of our American community, Happy Independence Day!\u00a0 And remember, this is our only Earth and we should treat it as our only home everywhere we live.<\/p>\n To all, see you next week!<\/p>\n\n
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