Oxford Martin School

Fabrication techniques are the foundation of physical technology, and are thus of fundamental interest. Physical principles indicate that nanoscale systems will be able to fabricate a wide range of structures, operating with high productivity and precise molecular control. Advanced systems of this kind will require intermediate generations of system development, but their components can be designed and modelled today.

Helical logic is a theoretical proposal for a future computing technology using the presence or absence of individual electrons (or holes) to encode 1s and 0s. The electrons are constrained to move along helical paths, driven by a rotating electric field in which the entire circuit is immersed. The electric field remains roughly orthogonal to the major axis of the helix and confines each charge carrier to a fraction of a turn of a single helical loop, moving it like water in an Archimedean screw. Each loop could in principle hold an independent carrier, permitting high information density. One computationally universal logic operation involves two helices, one of which splits into two "descendant" helices. At the point of divergence, differences in the electrostatic potential resulting from the presence or absence of a carrier in the adjacent helix controls the direction taken by a carrier in the splitting helix. The reverse of this sequence can be used to merge two initially distinct helical paths into a single outgoing helical path without forcing a dissipative transition. Because these operations are both logically and thermodynamically reversible, energy dissipation can be reduced to extremely low levels. This is the first proposal known to the authors that combines thermodynamic reversibility with the use of single charge carriers. It is important to note that this proposal permits a single electron to switch another single electron, and does not require that many electrons be used to switch one electron. The energy dissipated per logic operation can likely 4/30/96 2 be reduced to less than 10 -27 joules at a temperature of 1 Kelvin and a speed of 10 gigahertz, though further analysis is required to confirm this. Irreversible operations, when required, can be easily implemented and should have a dissipation approaching the fundamental limit of ln 2 x kT.

Development ofthe ability to design protein molecules will open a path to the fabrication of devices to complex atomic specifications, thus sidestepping obstacles facing. conventional microtechnology. This path will involve construction of molecular machinery able to position;reactive groups to atomic precision. It could lead to great advances in computational devices and in the ability to manipulate biological materials. The existence of this path has implications for the present. Feynman's .1959 talk entitled "There's Plenty of Room at the Bottom" (1) discussed microtechnology as a 'frontier to be pushed back, like the frontiers of high pressure, low temperature, or high vacuum. He suggested that ordinary machines could build smaller machines that could build still smaller machines, working step by step down toward the molecular level; he also suggested using particle beams to. define two-dimensional patterns. Present microtechnology (exemplified by integrated circuits) has realized some ofthe potential outlined by Feynman by following the same basic~approach: working down

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The revolutionary Feynman vision of a powerful and general nanotechnology, based on nanomachines that build with atom-by-atom control, promises great opportunities and, if abused, great dangers. This vision made nanotechnology a buzzword and launched the global nanotechnology race. Along the way, however, the meaning of the word has shifted. A vastly broadened definition of nanotechnology (including any technology with nanoscale features) enabled specialists from diverse fields to infuse unrelated research with the Feynman mystique. The resulting nanoscaletechnology funding coalition has obscured the Feynman vision by misunderstanding its basis, distrusting its promise, and fearing that public concern regarding its dangers might interfere with research funding. In response, leaders of a funding coalition have attempted to narrow nanotechnology to exclude one area of nanoscale technology-the Feynman vision itself. Their misdirected arguments against the Feynman vision have needlessly confused public discussion of the objectives and consequences of nanotechnology research.

Fabrication techniques are the foundation of physical technology, and are thus of fundamental interest. Physical principles indicate that nanoscale systems will be able to fabricate a wide range of structures, operating with high productivity and precise molecular control. Advanced systems of this kind will require intermediate generations of system development, but their components can be designed and modelled today.

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

It is unknown how abundant extraterrestrial life is, or whether such life might be complex or intelligent. On Earth, the emergence of complex intelligent life required a preceding series of evolutionary transitions such as abiogenesis, eukaryogenesis, and the evolution of sexual reproduction, multicellularity, and intelligence itself. Some of these transitions could have been extraordinarily improbable, even in conducive environments. The emergence of intelligent life late in Earth's lifetime is thought to be evidence for a handful of rare evolutionary transitions, but the timing of other evolutionary transitions in the fossil record is yet to be analyzed in a similar framework. Using a simplified Bayesian model that combines uninformative priors and the timing of evolutionary transitions, we demonstrate that expected evolutionary transition times likely exceed the lifetime of Earth, perhaps by many orders of magnitude. Our results corroborate the original argument suggested by Brandon Carter that intelligent life in the Universe is exceptionally rare, assuming that intelligent life elsewhere requires analogous evolutionary transitions. Arriving at the opposite conclusion would require exceptionally conservative priors, evidence for much earlier transitions, multiple instances of transitions, or an alternative model that can explain why evolutionary transitions took hundreds of millions of years without appealing to rare chance events. Although the model is simple, it provides an initial basis for evaluating how varying biological assumptions and fossil record data impact the probability of evolving intelligent life, and also provides a number of testable predictions, such as that some biological paradoxes will remain unresolved and that planets orbiting M dwarf stars are uninhabitable.

It is unknown how abundant extraterrestrial life is, or whether such life might be complex or intelligent. On Earth, the emergence of complex intelligent life required a preceding series of evolutionary transitions such as abiogenesis, eukaryogenesis, and the evolution of sexual reproduction, multicellularity, and intelligence itself. Some of these transitions could have been extraordinarily improbable, even in conducive environments. The emergence of intelligent life late in Earth's lifetime is thought to be evidence for a handful of rare evolutionary transitions, but the timing of other evolutionary transitions in the fossil record is yet to be analyzed in a similar framework. Using a simplified Bayesian model that combines uninformative priors and the timing of evolutionary transitions, we demonstrate that expected evolutionary transition times likely exceed the lifetime of Earth, perhaps by many orders of magnitude. Our results corroborate the original argument suggested by Brandon Carter that intelligent life in the Universe is exceptionally rare, assuming that intelligent life elsewhere requires analogous evolutionary transitions. Arriving at the opposite conclusion would require exceptionally conservative priors, evidence for much earlier transitions, multiple instances of transitions, or an alternative model that can explain why evolutionary transitions took hundreds of millions of years without appealing to rare chance events. Although the model is simple, it provides an initial basis for evaluating how varying biological assumptions and fossil record data impact the probability of evolving intelligent life, and also provides a number of testable predictions, such as that some biological paradoxes will remain unresolved and that planets orbiting M dwarf stars are uninhabitable.

Formal Methods for the Informal Engineer (FMIE) was a workshop held at the Broad Institute of MIT and Harvard in 2021 to explore the potential role of verified software in the biomedical software ecosystem. The motivation for organizing FMIE was the recognition that the life sciences and medicine are undergoing a transition from being passive consumers of software and AI/ML technologies to fundamental drivers of new platforms, including those which will need to be mission and safety-critical. Drawing on conversations leading up to and during the workshop, we make five concrete recommendations to help software leaders organically incorporate tools, techniques, and perspectives from formal methods into their project planning and development trajectories.

We consider the speculative prospect of superintelligent AI and its normative implications for governance and global policy. Machine superintelligence would be a transformative development that would present a host of political challenges and opportunities. This paper identifies a set of distinctive features of this hypothetical policy context, from which we derive a correlative set of policy desiderata-considerations that should be given extra weight in long-term AI policy compared to in other policy contexts. Our contribution describes a desiderata "vector field" showing the directional change from a variety of possible normative baselines or policy positions. The focus on directional normative change should make our findings relevant to a wide range of actors, although the development of concrete policy options that meet these abstractly formulated desiderata will require further work.

The Fermi paradox is the conflict between an expectation of a high ex ante probability of intelligent life elsewhere in the universe and the apparently lifeless universe we in fact observe. The expectation that the universe should be teeming with intelligent life is linked to models like the Drake equation, which suggest that even if the probability of intelligent life developing at a given site is small, the sheer multitude of possible sites should nonetheless yield a large number of potentially observable civilizations. We show that this conflict arises from the use of Drake-like equations, which implicitly assume certainty regarding highly uncertain parameters. We examine these parameters, incorporating models of chemical and genetic transitions on paths to the origin of life, and show that extant scientific knowledge corresponds to uncertainties that span multiple orders of magnitude. This makes a stark difference. When the model is recast to represent realistic distributions of...

The Fermi paradox is the conflict between an expectation of a high {\em ex ante} probability of intelligent life elsewhere in the universe and the apparently lifeless universe we in fact observe. The expectation that the universe should be teeming with intelligent life is linked to models like the Drake equation, which suggest that even if the probability of intelligent life developing at a given site is small, the sheer multitude of possible sites should nonetheless yield a large number of potentially observable civilizations. We show that this conflict arises from the use of Drake-like equations, which implicitly assume certainty regarding highly uncertain parameters. We examine these parameters, incorporating models of chemical and genetic transitions on paths to the origin of life, and show that extant scientific knowledge corresponds to uncertainties that span multiple orders of magnitude. This makes a stark difference. When the model is recast to represent realistic distributi...

In a neglected 2005 paper, Nobel Laureate Paul Lauterbur proposed that molecular imprinting in amorphous materials -- a phenomenon with an extensive experimental literature -- played a key role in abiogenesis. The present paper builds on Lauterbur's idea to propose imprint-mediated templating (IMT), a mechanism for prebiotic peptide replication that could potentially avoid a range of difficulties arising in classic gene-first and metabolism-first models of abiogenesis. Unlike models that propose prebiotic RNA synthesis, activation, and polymerization based on unknown chemistries, peptide/IMT models are compatible with demonstrably realistic prebiotic chemistries: synthesis of dilute mixtures of racemic amino acids from atmospheric gases, and polymerization of unactivated amino acids on hot, intermittently-wetted surfaces. Starting from a peptide/IMT-based genetics, plausible processes could support the elaboration of genetic and metabolic complexity in an early-Earth environment...

NOTES are short manuscripts describing new developments or important results of a preliminary nature. These Notes cannot exceed 6 manuscript pages and 3 figures; a page of text may be substituted for a figure and vice versa. After informal review by the editors, they may be published within a few months of the date of receipt. Style requirements are the same as for regular contributions (see inside back cover).