Abstract: Paul Greengard was found unresponsive on the floor of his home on East 63rd Street in Manhattan early in the morning of April 13, 2019, by his housekeeper who was arriving to begin her day. Emergency services were summoned and transported Greengard to the NewYork-Presbyterian/Weill Cornell Medical Center at the 68th Street and York Avenue in Manhattan, but he never regained consciousness, spontaneous respirations, or cardiac rhythm. At the time of his passing, Paul was aged 93 years, and every day, he enjoyed the richness that was his life devoted to his science and to his wife, sculptor Ursula von Rydingsvard, who survives him. Paul's favorite name for Ursula was “Dolly”, and he was as smitten with and enchanted by her as was humanly possible. Over the past decades, the originality and soulfulness of Ursula's work had grown rapidly, garnering her a well-deserved international reputation as a singular talent. Paul was her biggest fan and cheerleader. Back at the laboratory and for most of the past 30 years, at any one time, Paul oversaw graduate students and fellows who totaled between 30 and 50 in number. His brilliance was often breathtaking as he personally ran weekly laboratory meetings, with each week's session of one or two hours devoted to the progress of a single student. The student was expected to project well-labeled images of his or her primary data, perform a careful recitation of each and every step of the protocol, and then share with Paul and the laboratory whatever tentative conclusions he or she had drawn. Typically, the student's version of this narrative was followed by comments from Paul who spoke the definitive interpretation, often in a semimonotone aimed at elucidation but not humiliation. Paul often broke up these moments with his levity, and after the room chuckled and the tension had been dispersed, the speaker would go on to the next experiment, autoradiogram, or micrograph. The successful Greengard trainee would typically learn to coauthor papers under Paul's personal tutelage in extended one-on-one sessions. In its most straightforward incarnation, such a paper would begin with a few rounds of drafting and editing by the first author and the middle authors. When that group pronounced the paper ready, the draft would be shared with Paul who would review and annotate with what would often look like a manageable volume of revisions. However, anyone familiar with the process would realize that Paul's markup did not indicate near completion but rather evidence that the maestro was ready to begin in earnest. The serious work was performed in the one-on-one sessions with Paul (Fig. 1). These sessions usually began with a multistack spread of pages across the writing table—usually, from left to right, the tentative figures, their legends, and the corresponding results sections—so that it was obvious to Paul and to the student exactly which images the reader would see and in which sequence. Paul carefully cross-compared each of the three components. He (or the student) would read every word aloud, first those in the legend and then those in the text. If this sounds excruciating, that's because it was clear that these papers were being written as a part of the permanent scientific record with a level of rigor and accuracy that would stand the test of time. Paul Greengard was a connoisseur of anecdotes and malapropisms, many of which were sidesplittingly hilarious. He so enjoyed some favorites that he would ask to be told and retold these jokes for decades. Moreover, he enjoyed both the hearing and the telling, and he would typically ask to hear the story first and then he would retell the story himself, laughingly heartily at both the hearing and the telling. From Nestler EJ, Huganir, Cell 177, 1365-1366, 2019. The student had better have arrived with the patience of Job because writing with Paul involved careful and deliberate selection of each word and phrase followed by testing sentence structures until one sounded the most euphonious as judged by Paul. He was a better grammarian and editor than one might imagine, and—to the end—for the fortunate students whose data were moving into the manuscript form, evenings and weekends were often reserved for one-on-one writing sessions with Paul. These sessions were the moments and hours when Paul got to know his students and vice versa, not simply as mentor and mentee, but as friends. These sessions may sound dry, but they were not so at all. There were breaks for dog walking, snacking, and chatting, and there was always time for gossip including at least a few minutes of schadenfreude when either Paul or the student would contemplate a competitor's misfortune or their hope that the paper that they were writing would be a major scoop, major breakthrough, or both. There was also an extended period of misery when Paul's name was mentioned among—but ultimately not included among—those of the recipients of the 1994 Nobel Prize in Physiology or Medicine shared by Alfred Gilman and Martin Rodbell. Paul's disappointment was well known and luckily short-lived because soon thereafter, he shared the 2000 Prize with Arvid Carlsson and Eric Kandel. Although this gap sounds brief, the 2000 Prize could not come soon enough for Paul and for those of us who were aware of his 1994 disappointment and for those years when he and we worried that the Prize would never come his way. But it did. Paul arrived at The Rockefeller University from Yale at the age of 60 years, bringing along senior Greengard laboratory family members who composed his “kitchen cabinet” of consiglieri. Joshua Sanes [1] and Pietro de Camilli [2] have covered in their articles Paul's early career and the major achievements described in the recitation accompanying the 2000 Nobel Prize. In brief, in the years following the discovery of the adenylyl cyclase signaling system in the hepatocyte by Edwin Krebs and Edmond Fischer, Paul envisioned that there must be a similar system in the brain and in neurons. The figure below from the Science magazine archive reproduces the masthead and cover art from the July 4, 1969, issue of that magazine, wherein Paul reported his success at purification and characterization of brain adenylyl cyclase (Fig. 2) [3]. The masthead from the issue of Science in 1969 when Greengard reported the successful purification of cyclic AMP-dependent protein kinase (also known as protein kinase A) from brain. This was the beginning of Greengard's 50 year narrative about the importance of protein phosphorylation in signal transduction in the brain, for which he was shared The 2000 Nobel Prize in Physiology or Medicine. From Science 165, 63-65, 1969. Paul was in a hurry to understand the brain, so he rushed on past first and second messengers to the physiological effectors that he envisioned as downstream third and fourth messengers. Much of his attention focused on the steps by which the second messenger controlled reversible posttranslational modification by addition (or removal) of a phosphate moiety (i.e., “phosphorylation”). Synapsins I and II and the dopamine and cyclic adenosine monophosphate–regulated phosphoprotein of 32 kDa were among the most famous and important substrates to undergo reversible phosphorylation discovered and popularized by Greengard [4]. One of us (S.G.) first collided with Paul and his laboratory and body of work while evolving from being an M.D., Ph.D. neurologist into a molecular neurologist investigator. As Sam's neurology residency was entering its penultimate year, he began to apply and interview for basic postdoctoral fellowships, mostly in laboratories focusing on molecular neurobiology and especially in those focusing on the molecular neuropathogenesis of dementia. This was subconsciously but undoubtedly influenced by the fact that Sam was raised in a family where he was exposed everyday to Alzheimer's disease, first in a paternal grandmother, eventually in a maternal aunt, a maternal uncle, and eventually in his own mother, mother-in-law, and father-in-law. Sam's chairmen and program directors, Fred Plum, M.D., and Jerry Posner, M.D., (Chairs of Neurology and Neuro-Oncology at the New York Cornell and Memorial-Sloan Kettering, respectively) were two key referees for his fellowship applications, so both were aware of the several laboratories in the Northeast, Midwest, and West Coast US regions where he had applied. One day, Fred called Sam into his office and, without looking up from his keyboard, pronounced in his usual curt manner, “Sam: you should go to Greengard. He has the best track record of anyone in the world in training new neuroscience laboratory heads who can compete and succeed at the National Institutes of Health and at the best journals.” Fred resumed his typing, and once Jerry weighed in, the decision was essentially a fait accompli. Although Fred had had a career in the laboratory several decades earlier, Jerry's input was especially timely because, at that same moment, his career in unraveling the molecular mechanisms underlying paraneoplastic disorders was gaining momentum, as was his close, enthusiastic, and still-ongoing collaboration with Robert Darnell, M.D., Ph.D., also a product of The New York Hospital-Cornell-Memorial-Sloan-Kettering Cancer Center Neurology Residency Program who went on to become the Robert and Harriet Heilbrunn Professor of Cancer Biology at The Rockefeller University, an investigator of the Howard Hughes Medical Institute, and the Founding Director and CEO of the New York Genome Center. Soon after accepting the position with Paul, as Sam was finishing his chief residency year, Paul paged him and asked him to meet not at Paul's Rockefeller laboratory but in a hospital room at the New York hospital where Paul was preparing to undergo biopsy of a group of “hot spots” on his spine and ribs that were suspicious for cancer or tuberculosis. This was the first of several health scares that Paul would face and defeat over the ensuing decades; myocardial infarction, dengue fever, transthyretin amyloidosis peripheral neuropathy, traumatic brain injury, and a surgically evacuated subdural hematoma are the first to come to mind. Each time, as he entered his 70s, 80s, then 90s, we feared that one of these events would set off some important decline in Paul's intellect and cognitive skills, but to the end, he remained intact, with a sparkle in his eyes and the hyperverbal childlike affect that is so often displayed by the best scientists. When Sam joined Paul's laboratory in the summer of 1986, both were keen to move in more clinically relevant directions than where Paul's science had focused up to then. Although Sam had wanted, from the beginning, to contribute to a redirection of Paul's effort in a more translational direction, when Sam arrived at the Rockefeller University, Paul assigned him to a project already in progress, aimed at purifying a “180-kD” calcium-/calmodulin-dependent protein kinase substrate highly enriched in postsynaptic densities. At that moment in the Alzheimer's area, there was much interest directed toward a protein called Alz50, discovered by Ben Wolozin, M.D., Ph.D., (now a Professor of Neuroscience at the Boston University, but then a graduate student at the Albert Einstein School of Medicine at the Yeshiva University with Peter Davies, Ph.D., who was then a Professor of Biochemistry at Einstein and is now the Director of the Litwin-Zucker Alzheimer's Center at the Hofstra-Northwell Hospital Medical School). Ben and Peter had some early intriguing evidence that Alz50 was associated with protein kinase catalytic activity, and Paul and Sam had approached them about a collaboration wherein Sam would work with Ben in Peter's laboratory and the four would conduct further characterization of Alz50. The catalytic activity that Ben was observing in his Alz50 preparations turned out to be a contaminating protein kinase, dissociable from Alz50 using standard protein chromatography methods. That was a disappointing dead end, but within weeks, there appeared an even stronger lead that would consume 3 decades of the careers of all four men. At the Annual Meeting of the Society for Neuroscience in the fall of 1986, the audience was listening to the opening moments of an Alzheimer's slide session when the chair announced that a special additional slide talk had been added so that the session would run 15 minutes late to accommodate this emergency add-on. The speaker was to be Dmitry Goldgaber, Ph.D., then a fellow with the senior author of the abstract, D. Carleton Gajdusek, M.D., then the head of a major neurodegenerative disease unit at the National Institute of Neurological Disorders and Stroke and already a winner of the Nobel Prize for his work on kuru transmissibility. The room was abuzz with anticipation, and when Dmitry spoke, he revealed that he and his team in Gajdusek's laboratory had succeeded in the molecular cloning of the Alzheimer's amyloid precursor protein (APP) and its assignment to chromosome 21, the significance of which was lost on no one in the room [5]. Dmitry strongly implied that persons with the known predisposition to Alzheimer's pathology as a late complication of trisomy 21 (Down syndrome) almost certainly were suffering in this way because they harbored an extra copy of the APP gene (a “genetic overdose”). As luck would have it, Dmitry included a transcript of his APP amino acid sequence in a Christmas card that he sent to Peter, who shared the sequence with Sam, whereupon Peter and Sam immediately spied potential phosphoacceptor serine, threonine, and tyrosine sites, and using the battery of purified protein kinases accumulated in Paul's laboratory, they were able to rapidly demonstrate that these potential phosphoacceptor sites could function at highly favorable catalytic efficiencies. In 1988, Paul and Sam reported in proceedings of the National Academy of Sciences evidence for direct phosphorylation of those APP cytoplasmic tail sequences that had arrived in that 1986 Christmas card from Dmitry to Peter [6]. The PNAS article by Gandy et al. (1988) served as a definite declaration of the trajectory that Paul had in mind, but it was only with contributions from Axel Unterbeck, Ph.D., a molecular biologist who had moved from Benno Muller-Hill's laboratory in Germany to Molecular Therapeutics, Inc., on the Bayer campus in West Haven, that the research was able to take flight. Back in Germany, Axel had been the supervisor for a graduate student Jie Kang, whose name was associated with the “Kang sequence”, the first full-length APP clone and the sequence that had appeared in Nature in 1987 in an article coauthored by Kang, Unterbeck, Muller-Hill, and their collaborators Colin Masters, M.D., of The University of Melbourne and Konrad Beyreuther, Ph.D., from The University of Heidelberg [7]. Now, armed with the complete amino acid sequence of APP and with a bit of “Kang sequence”, APP cDNA was brought by Unterbeck to West Haven, Sam, Paul, and their colleagues set out to develop antibodies that would enable them (and others) to ask and answer the most burning cell biological questions posed by the cloning and chromosomal localization of APP. Soon that literature devolved into an undecipherable mess with no two laboratories making any consistent claims for having demonstrated endogenous human APP at the protein level. One of those who helped overcome this problem was Michelle Ehrlich, M.D., a Greengard laboratory postdoctoral researcher who was the first to clone dopamine and cyclic adenosine monophosphate–regulated phosphoprotein of 32 kDa and designed, for the APP project, a highly labor-intensive but ultimately successful strategy for screening for what has remained since 1990 as one of the best antibodies that reacts with high avidity and high affinity for both human APP and APP-like protein-2. Ehrlich used Unterbeck's human APP cDNA to develop an in vitro transcription/translation assay that generated [35S]methionine-labeled, authentic human APP that Sam and his team used to screen sera from dozens of rabbits vaccinated with peptides based again on that Goldgaber/Davies 1986 Christmas card. Out of this heroic (and somewhat frantic) effort that was being conducted in Paul's laboratory at the Rockefeller University, there emerged a single useful antibody named “369” that had the “secret sauce” necessary to become the first useful precipitating antibody against the APP cytoplasmic tail [8] (“369” was the rabbit's cage number). The need for exactly such a reagent became acutely clear when Andreas Weidemann, Colin Masters, and Konrad Beyreuther reported in Cell that they had developed useful antibodies against the human APP extracellular domain and that they had gone on to discover apparently that a large ectodomain was being excised and released into bodily fluids. Initially, Andreas, Colin, Konrad, and colleagues were somewhat stymied in describing APP metabolism completely because they could not detect and determine the cleavage sites of the cytoplasmic stubs left behind after the APP ectodomain was released in a process later dubbed as “shedding” because the proteolytic event is a local plasma membrane–localized event attributable to the a disintegrin and metalloproteinase (ADAM)10 protease. The identification of ADAM10 as what is now known as the basal APP α-secretase was made by Joseph Buxbaum, a former Greengard postdoctoral researcher who, by this time, was the new laboratory head at Mount Sinai. At about the same time, Joan Massague, Ph.D., a Professor of Cell Biology at Memorial-Sloan Kettering, and Marcus Bosenberg, his M.D., Ph.D. student, asked Sam to chair Bosenberg's thesis defense in which ADAM17 was identified as the protein kinase C (PKC)-regulated α-secretase or “sheddase” for protransforming growth factor-alpha (pro-TGFα). This regulated “sheddase” of TGFα turned out to be identical to the regulated APP α-secretase [9]. “Regulated,” in the case of TGFα shedding, turned out to mean “regulated by PKC,” which resonated with us on the Greengard APP team as our report in the 1988 PNAS article had implicated PKC [6], [8]. Along this same line, one of us (T.S.) went on to discover the efficient phosphorylation of the APP cytoplasmic tail, not only by PKC but also by cyclin-dependent protein kinases (cdc2 and cdk5) [10], [11]. So to recap the early contributions of the authors of this comment, S.G. had predicted the involvement of PKC (on Ser655) based on short peptide model substrates, and T.S. confirmed this event in a permeabilized cell model incubated with [35S]methionine, lysed and immunoprecipitated with the 369 anti-APP cytoplasmic tail antibody. In T.S.'s hands, as one would expect, only fully mature APP was an apparent substrate for phosphorylation by PKC on Ser655 [12]. cdk5 was in the early days of characterization and had not been part of the original protein kinase panel tested by S.G., but when that enzyme had been purified, T.S. demonstrated its ability to efficiently phosphorylate Thr668. That project was spun off by T.S. and his M.D., Ph.D. student, Masaki Oishi [10]. While the direct phosphorylation of APP was being elucidated by Suzuki, Gandy, Czernik, Nairn, and Greengard, the 369 anti-APP cytoplasmic tail antibody generated by Ehrlich, Unterbeck, Ramabhdran, Greengard, and Gandy was being used for metabolic labeling and molecular vesicle transport biology not only by Joseph Buxbaum, Ph.D., but also by an M.D., Ph.D. student named Gregg Caporaso whose thesis research was cosupervized by S.G. and Greengard. Both Joseph and Gregg used the 369 antibody in a protocol of pulse-chase [35S] metabolic labeling after pretreatment using standard signal transduction and vesicle biology reagents such as phorbol esters, okadaic acid, chloroquine, brefeldin A, and monensin [6], [8], [13]. Soon thereafter, a novel [35S]O4-labeling trans-Golgi network (TGN) vesicle budding assay was brought to the Gandy-Greengard group (now spread between Gandy's independent laboratory at Cornell and Greengard's laboratory at the Rockefeller University) through the recruitment of Huaxi Xu, Ph.D. [14]. In various combinations of authors, four PNAS articles and two JBC articles emerged over the period from 1988 to 1992, wherein was defined what is now considered the standard canonical fate of APP: APP is synthesized and inserted across the endoplasmic reticulum membrane cotranslationally, matures in the Golgi where the ectodomain undergoes N- and O-glycosylation and tyrosyl sulfation. Fully mature APP heads toward making its exit from the TGN mostly intact and toward its entrance into the endocytic system where it encounters the β-APP-site–cleaving enzyme (BACE1). The pathogenic mutations in the Swedish mutant APP (APPK670N/M671L) enable its cleavage by BACE1 to be a mostly TGN-localized event, while wild-type APP is most cleaved by BACE1 in the endocytic system [15]. Buxbaum, Gandy, and Greengard showed that the metabolic consequence of activation of PKC with phorbol esters or of inactivation of protein phosphatases 1 and 2A (PP1 and PP2A) with Okadaic acid was enhancement of transport of intact APP holoprotein from the TGN to the plasma membrane where the amyloid-β (Aβ) domain is destroyed via activated α-secretase cleavage by ADAM17 when PKC is stimulated or when PP1 and PP2A are inactivated. Cleavage at the identical intra-Aβ site between lysine 16 and leucine 17 of Aβ is made by ADAM10 under basal conditions when PKC, PP1, and PP2A are not stimulated. The first messengers linked to these APP processing events included acetylcholine (discovered concurrently by Buxbaum, Gandy, and Greengard. [16] and by Nitsch and Wurtman [17] and 17-beta-estradiol (described first in a team led by M.D., Ph.D. student Ari Jaffe, Greengard, and Gandy, in a collaboration with Dominque Toran-Allerand, Ph.D., Professor of Anatomy and Neuroscience at the Columbia University College of Physicians and Surgeons, and in greatest detail by Xu, Greengard, and Gandy in a Nature Medicine article in 1995 [18]). Buxbaum and Greengard [19] (and in an independent concurrent study, Christian Haass, Ph.D., then a postdoctoral researcher with Dennis Selkoe, M.D., at the Brigham and Women's Hospital in Boston [20]) showed that acute hyperactivation of PKC can apparently lead to enhanced relocation of APP to the plasma membrane and cleavage by ADAM17 such that ectodomain shedding is dramatically enhanced and, in that acute setting, Aβ generation is reduced. This looked like the beginning of a strategy for reducing Aβ generation even without having identified the proteases responsible for its generation. However, Dmitry Goldgaber, Ph.D., by then a professor of psychiatry at the Stony Brook University, showed that PKC activates APP transcription [21], raising the question of which wins out over the long haul: PKC reduction of Aβ generation or PKC activation of APP transcription. This issue was solved in Portugal when Odete and Edgar da Cruz e Silva (former postdoctoral researchers in the Greengard laboratory, but by this time, professors at the University of Aveiro) worked with Gandy to show that while acute short-term PKC activation reduced Aβ generation, as had been feared, long-term PKC activation or PP1/PP2A inactivation causes the effect of PKC on APP transcription to overtake its effect on α-secretase cleavage such that with chronic PKC activation, Aβ generation increases enormously [22]. This has turned out to be an especially important point because some investigators have proposed that PKC modulatory drugs such as bryostatin might be useful for as therapeutic modulation of Aβ generation. As of this writing, bryostatin has shown no meaningful benefit in human clinical trials. Two of the “open loops” on the PKC and ADAM10 α-secretase stories have been closed over the past 5 yrs by Rudolph E. Tanzi, Ph.D., Joseph P., and Rose F. Kennedy, Professor of Neurology at the Harvard University and Vice-Chair of Neurology, Director of the Genetics and Aging Research Unit, and Co-Director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital. In one study, “Rudy” and his colleagues reported the first pathogenic mutation in ADAM10 [23], indicating that impaired α-secretase activity could foster amyloidosis and enhance susceptibility to Alzheimer's disease. In a separate study, Rudy and collaborator Alexandra Newton, Ph.D., at the University of California, San Diego, described association of a mutation in PKCα [24] with increased risk for Alzheimer's disease. These discoveries cement the importance of the breakthrough discovery of the role of PKC in APP cleavage by α-secretase now associated with Greengard, Gandy, Suzuki, Buxbaum, and the da Cruz e Silvas. In addition to his identification as the quintessential scientist, Paul was both a perpetuator and a consumer of wit. He loved to laugh, and he loved to make others laugh. The writing sessions would often be brought to abrupt conclusions when the student-orator reading aloud each sentence became too weary and tongue-tied to avoid making hilarious misspeaks that would eventually break up the skills of concentration of both authors. Paul was especially amused by a particular malapropism delivered by a minister from the pulpit which had been witnessed by Sam Gandy and his mother and then related to Paul by Sam's mother over a Thanksgiving dinner when they joined Paul, Ursula, and their extended families over 20 years ago. Paul enjoyed this story so thoroughly that he was still recalling and retelling it two weeks before his death and still laughing heartily for several minutes. Moreover, after he told the story, he usually asked that it be related back to him so that he could enjoy alternatively being a joker and a joke consumer. Not all was sweetness and light. The bete noir of Paul's lighter side was his ruthlessly competitive alter ego. He always wanted to win when priorities were at stake, and he pulled out all the stops, all the time. This meant making some enemies (or, quite a few enemies, in fact), but he considered this as part of the cost of working in important areas. Back in the present—in the late summer toward early fall of 2019—many of us in the neuroscience community still mourn the loss of this singular intellect that functioned at the uppermost margins of productivity until well past the age when most would consider retirement. Voluntary retirement was never on Paul's mind. Although his most recognized work emerged when he was in midlife and recognized when he was in his 70s, he continued to break new and clinically important ground well past the age of 90 years and was still productive at the time of his sudden demise. Space precludes description of Paul's recent discovery of p65 (a major novel protein implicated in the etiology and pharmacotherapy of mood disorders) and his founding of the biotechnology company Intra-Cellular Therapies Inc. (whose drug ITI-007 is almost certainly destined for the Food and Drug Administration approval for use in psychotic disorders). As if the breadth and depth already mentioned here were not sufficiently awe-inspiring, I refer you a June 2019 issue of Neuron that hit the newsstands the week after Paul's death. In that article, together with Jeffrey Friedman, M.D., Professor and Head of Laboratory at The Rockefeller University, Paul, Jeff, and their team describe a major breakthrough in elucidating novel pathways linking dopamine, satiety, and obesity. In every direction of his gaze, Paul's genius was evident and piercing. He is sorely missed, especially as our first 40 yrs in the “molecular era of dementia” come to a close without clinically meaningful disease-modifying interventions in hand or even in sight. The need for critical thinking from scientists such as Paul is even more acute in the realm of strategic planning and/or policy formulation in the Alzheimer's field regarding future directions for research. Specifically, 40 years of R&D for Alzheimer's therapy based on prevailing ideas or theories have failed us. There is strong evidence that amyloidosis is a frequent instigator, but there is no evidence that we will be able to exploit that observation as a meaningful intervention. The discovery of the Icelandic APP mutation shows that reduction of whole body and brain Aβ levels by about 50% from the moment of conception apparently prevents Alzheimer's disease [25]. This has fueled prevention strategies using enzyme inhibitors or antiamyloid antibodies. The former have had the unfortunate effect of accelerating cognitive decline, while the latter have succeeded in purging all detectable Aβ from the brain, but this Aβ-free brain continues to fail on schedule. There is a major unmet need for novel conceptual models, theories, and out-of-the-box thinking about interventions for complex chronic brain disorders. But yet, policy and decision-makers in government, academia, financial institutions, R&D underwriters, and pharmaceutical companies fail to access the impartial critical analytical reports that might guide them in important productive directions. Paul has left us with big shoes to fill and only ambiguous clues as to the best way forward. We now must ask ourselves the difficult questions and set aside the long-held dogmas if we are to realize the important breakthroughs that are required if we are to mitigate the economic and emotional devastation that are currently on track to decimate the world's Western economies.